Molds, Mushrooms, and Medicines

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 Molds, Mushrooms, and
Medicines
Our Lifelong Relationship with Fungi

Nicholas P. Money

PRINCETON UNIVERSITY PRESS

PRINCETON & OXFORD

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Copyright © 2024 by Nicholas P. Money
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Library of Congress Cataloging-in-Publication Data
Names: Money, Nicholas P., author.
Title: Molds, mushrooms, and medicines : our lifelong relationship with fungi / Nicholas P. Money.
Description: Princeton : Princeton University Press, [2024] | Includes bibliographical references and index.
Identifiers: LCCN 2023030612 (print) | LCCN 2023030613 (ebook) | ISBN 9780691236308 (hardback) | ISBN
9780691236315 (ebook)
Subjects: LCSH: Fungi. | Materia medica, Vegetable. | Molds (Fungi). | BISAC: SCIENCE / Life Sciences / Mycology |
NATURE / Plants / Mushrooms
Classification: LCC QK603 .M58 2024 (print) | LCC QK603 (ebook) | DDC 579.5—dc23/eng/20230908
LC record available at https://lccn.loc.gov/2023030612
LC ebook record available at https://lccn.loc.gov/2023030613
Version 1.0
British Library Cataloging-in-Publication Data is available
Editorial: Alison Kalett, Hallie Schaeffer
Jacket: Heather Hansen
Production: Jacqueline Poirier
Publicity: Matthew Taylor (US), Kate Farquhar-Thomson (UK)
Copyeditor: Susan Campbell
Jacket Credit: Jacket images (clockwise): Nataliya Hora / Alamy Stock Photo; Eye of Science / Science Source;
BSIP SA / Alamy Stock Photo; Guido Blokker / Unsplash

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 Contents

Acknowledgments vii
1 Interacting: Encounters with Fungi from Birth to Death 1

Part I Inward

2 Touching: Fungi on the Skin 23

3 Breathing: Spores in the Lungs 40
4 Spreading: Opportunists in the Brain 57
5 Digestion: Yeasts in the Gut 73

Part II Outward

6 Nourishing: Molds and Mushrooms in Our Diets 93

7 Treating: Medicines from Fungi 110
8 Poisoning: Toxins in Mushrooms and Molds 125
9 Dreaming: Using Mushrooms to Treat Depression 142
10 Recycling: The Global Mycobiome 159

Appendix: Ghost Gut Fungi 175

Notes 179
List of Illustrations 225
Index 227

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 Acknowledgments

I WOULD LIKE to thank my agent, Deborah Grosvenor, and my editor, Alison

Kalett, for making this book happen. Andor Kiss helped me to untangle the
studies on ghost gut fungi, Michael Klabunde assisted with Latinisms, and
my wife, Diana Davis, proofread the developing manuscript.

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 1
Interacting
ENCOUNTERS WITH FUNGI FROM
BIRTH TO DEATH

Sing, heavenly Muse …

 What in them is dark
Illumine, what is low raise and support;
That to the height of this great argument
I may assert eternal providence,
And justify the ways of mushrooms to men.
—JOHN MILTON, PARADISE LOST (1667), BOOK I, LINES 6, 22–26, AMENDED

FUNGAL SPORES cast a shadow over my childhood and almost killed me. One
day in 1967, my five-year-old body began to run out of oxygen as my lungs
shut down with inflammation, turning my skin blue before the ambulance
arrived. I was born in the Thames Valley of southern England, which is a
lovely place unless you are an asthmatic. Tree pollen and fungal spores fill
the Oxfordshire air in summer and turn paradise into hell. There had been a
thunderstorm that afternoon, which whipped clouds of these noxious
particles into the sky. They filtered into my chest with each breath, causing
my little airways to narrow and flood with mucus. A severe asthma attack
feels like death. The nurses put me in an oxygen tent and gave me big orange
tablets that were difficult to swallow, but after a day or two these antibiotics
combined with a steroidal medicine reopened my lungs. More than fifty
years later I can still see myself struggling to breathe under that clear plastic
canopy, and I wonder how much this trauma led to my career as a
mycologist and immersion in research on the spores of the fungi that put me
there.
The fact that a boy plagued by spores became a scientist who has spent
his adult life studying fungi, teaching students about their biology, and
serving as an expert witness in lawsuits related to mold exposure is one of
those serendipitous outcomes that define so many lives. The connections
between my childhood and my profession did not occur to me until my brief
experience as the patient of a therapist. He was a gentle, bearded man who
asked insightful questions as he sought to help me understand why I was
wrestling with thanatophobia, or death anxiety, which was distracting me
from enjoying not being dead. Early in our conversations, I told him that I
was an expert on fungi, a mycologist, then explained a little about what a
fungus is and what a fungus does. We talked about many other things—my
health, marriage, and the challenges of parenting teenagers—before he
circled back one day and asked: “Have you ever wondered why you are
obsessed with death and with the microbes that you have described as the
great decomposers?” We both laughed. It seems plausible that my asthma
attacks were the foundation of it all: thanatophobia and what some would
view as a morbid fascination with fungi that may have developed as a
subliminal attempt at therapy, like the hypochondriac who becomes a doctor.
On the other hand, maybe I just liked mushrooms.
What intrigues me now, and is the subject of this book, is the science of
the human-fungus symbiosis, both the intimate and the extended relationship
between fungi and our species. This relationship runs all the way from yeasts
that grow on the skin and inside the gut to our uses of fungi as food and
sources of medicines and, ultimately, to the mushroom colonies in soil that
make life on land possible. Our closest physical ties with the fungi are
invisible because the ones that live on the body are microscopic. These
species grow amid the more numerous bacteria and viruses and are critical
players in human health. Together, these microbes form the human
microbiome, and we identify the fungal part of this intimate ecosystem as
the mycobiome. (The prefix, myco-, from the Greek mykes, refers to all
things fungal.)
The growth of immense numbers of fungi on the skin and inside the body
is an unexpected and startling fact of science. Fungi are a vital part of the
immense ecosystem of the human body, which operates as a partnership
between trillions of human and microbial cells. We cannot live without these
fungi. Touch the creased skin behind one of your ears or run your hands
through your hair. You will not see them, of course, but fungal cells will
cling to your fingertips afterward and every other time you rub, scratch,
pick, or caress. They are essential partners, lodgers on all of us. Most of the
fungi of the mycobiome are helpful, but some can turn on us when our
immune defenses are weakened and cause terrifically damaging infections.
Fungi that normally grow on plants, rotting wood, compost heaps, and bird
droppings can also settle on the body and attack our tissues if we are
vulnerable. Human diseases caused by fungi are called mycoses, and these
range from the irritation of athlete’s foot to life-threatening brain infections.
But our relationship with fungi does not end with the species found on the
body. It widens to our conscious interactions with these microbes through
their roles in our diet and as a source of powerful medicines. Science has
been advancing in all of these areas of mycological inquiry, from studies that
reveal the diversity of yeasts that grow on the skin to research on the use of
psychedelic mushrooms in the treatment of depression. Once we expand our
view of the give-and-take between humans and fungi to these deliberate uses
of fungi, we discover a broader relationship, a human-fungus symbiosis that
is a defining feature of our biology and culture. The term “symbiosis” is
used in its original and most liberal sense in this book to describe helpful and
harmful relationships between species. This is a perfect reflection of the
incredible range of interactions between humans and fungi.

WHAT IS A FUNGUS?
Not plant, not animal, more animal than plant, and treated as the most
mysterious kingdom of life in popular culture, fungi come in many shapes
and sizes.1 The fungi we see most often seem too big to be categorized as
microbes. These are mushrooms, which include the fairy-tale fly agaric, with
its red cap spotted with white scales; shelf fungi, as big as dinner plates, that
grow on decomposing logs; and slices of white button mushrooms on pizzas.
The reason we call these species microorganisms is that the fungus that
forms the mushroom is microscopic. For almost all of their lives, these
organisms exist as spidery colonies of tiny threads called hyphae. Each
thread, or hypha, is ten times thinner than a human hair. These filaments
elongate and branch as they feed in soil and go about the process of rotting
wood. The colony of branching hyphae is a mycelium. When this mycelium
has grown over a large area and absorbed enough food, it reverses direction
and flows to the surface, where the threads merge to form mushrooms.
Mushrooms with gills are the fruit bodies or sex organs of fungi that mist the
air with spores. As the urge to reproduce becomes an imperative, the fungus
moves from belowground to aboveground, changing its role from feeding to
fruiting in the wondrous cycle of its life.
But most fungi never form a mushroom and are microscopic throughout
their feeding and reproductive stages. These include aquatic fungi that swim
in ponds, with tailed cells that resemble animal sperm; molds with stalks
hung with sparkling spores that look like miniature chandeliers; and 1,500
species of yeasts. Yeasts include the species used in brewing and baking,
whose Latin name is Saccharomyces cerevisiae, and another fungus, called
Candida albicans, that lives on everyone and is best known, unfortunately,
for its irritating nature as the vaginal yeast.2 (Latin names are kept to a bare
minimum in this book, but some of the fungi are best known through their
Latin names, and others are so obscure that they have never been given a
common name.) Unlike fungi that grow as thin threads, which we call
molds, yeasts develop as single rounded cells and produce buds, or daughter
cells, on their surface.

MAKING SENSE OF THE MYCOBIOME

The entire human body is affected by fungi. Yeasts populate the skin and
crowd around the hair follicles on the scalp; other species live in the ear
canals, nasal passages, and mouth; and fungi swarm in the digestive and
reproductive systems. The fungi are as small as the cells of our tissues and
only become visible when they grow in such profusion that they form
patches and pastes on the surface of the skin. But at this moment, and
throughout our lives, fungal cells are feeding on the scalp and growing in the
gut, consuming the mucus and dead cells that we discharge every day, and
helping to control the bacteria. This microbial community is in constant flux
—and so much of it was completely unknown until recently.
Fungi have been sidelined at meetings of microbiologists by studies on
bacteria and viruses during my career and have been an afterthought in
medicine. Earlier generations of mycologists misunderstood the fungi that
they found on the body, regarding most of them as germs that damaged
hospital patients and overlooking the significance of the yeasts growing
peacefully on everyone else. Even when molecular genetic techniques began
to reveal the incredible diversity and number of microbes in the gut, the
fungi were missed because the methods were limited to identifying the DNA
sequences of bacteria. This picture is changing at last, and new investigative
methods are exposing the yeasts and molds—the blobs and filaments—
multiplying from scalp to toes on the outside of the body and from mouth to
anus on the inside. As this examination of the fungi has proceeded, the
vision of the microbiome as a mostly bacterial territory has shifted to an
appreciation of the diverse communities of fungi that fight and cooperate
with bacteria through webs of chemical interactions to make a living on the
body.3 Through these innovations we are beginning to fathom the
extraordinary influence of the mycobiome on our health and well-being.
Even with this knowledge, the invisibility of the human mycobiome
makes it difficult to comprehend. This is life-changing science in the sense
that it permits a new view of the body, but it takes some imagination too.
There is nothing cellular and microbiological about the way we look and
feel. We picture ourselves as semisolid individuals, singular beings
constructed with varying degrees of smoothness and raggedness, pert here,
drooping there, and hanging together across the decades, but this half-truth
belies our biological nature. For a more enlightened sense of self, we have to
close our eyes to picture the body as a galaxy of cells, to say, and to believe,
“I am a trinity, born from one cell, copied in trillions, and filled with other
forms of life.”
Microbes that grow naturally on the body belong to the healthy
microbiome. Different microbes populate different locations on the body,
including the skin, ear canals, nasal passages, lungs, teeth, digestive tract,
and reproductive system. In each place, the body supports intermingled
communities of bacteria, viruses, and fungi that form the bacteriome,
virome, and mycobiome. The term mycobiome was used first to describe the
fungi associated with plants in a salt marsh on the Eastern Shore of Virginia
and now applies to the communities of fungi found in any location.4 For
example, cultivated pineapples harbor forty-nine species of fungi, tropical
corals host a jumble of marine fungi, and the gut of the largest living lemur,
called the indri, is heaving with microbes acquired from its vegan diet and
supplemented with fungi from the soil.5 Every animal, plant, and seaweed is
crawling with fungi.
We see hints of the ancestral human mycobiome in monkeys and other
apes, whose gut fungi vary among species.6 The community of fungi that is
distinctively human has been remodeled from earlier mixtures of the fungi
that grew on our hominid ancestors. This has involved losses and
replacements of fungi as the mycobiome has adapted to changes in our diet
and behavior. These evolutionary modifications have unfolded over the
course of millions of years, but fungi have also come and gone on much
shorter historical timescales. The communities of fungi on the body were
rejiggered when we emigrated from our birthplace in Africa to other climatic
zones and began fabricating clothing and footwear. Clothes and shoes
affected the fungi on the skin, and the gut fungi were modified as we
exchanged hunting and gathering for life in agricultural settlements.

WHAT THE FUNGI ARE DOING ON THE BODY

Fungi grow on humans because fungi grow everywhere they find food, and
we are stuffed with energy. A pound of flesh has the same number of calories
as a pound of ice cream, for an average of more than one hundred thousand
calories per body.7 Colonies of yeasts consume a snippet of this when they
digest the natural oils on the scalp. Other fungi live by breaking down
bacteria and food particles as they are squeezed along the 1.5-meter-long
tube of the colon. We are the unconscious hosts of a 24/7 buffet.
Although we are unaware of these fungi unless they cause inflammation
and tissue damage, the immune system is policing them throughout the day.
This defense mechanism is a marvel of natural engineering. White blood
cells are the biggest players in immunology. These colorless cells flow in the
blood alongside the more plentiful red blood cells. Red blood cells
outnumber white blood cells by six hundred to one, and all of these red
blood cells do exactly the same thing: they pick up oxygen from the fresh air
entering the lungs when we inhale and carry it around the body; on the return
path, the red blood cells release the carbon dioxide that we exhale. White
blood cells have nothing to do with this import and export of gases and are
more diverse in their roles. Following their own genetic programming, white
blood cells called phagocytes move around the body, stretching themselves
forward and retracting behind, just like amoebas that live in soil and water.
Some of them spread from the bloodstream into the surrounding tissues and
crawl into the linings of the lungs and the outer layers of the skin. Wherever
they encounter microorganisms, they decide whether to kill them or give
them a pass. White blood cells also rid the body of human cells that are
damaged or start to grow in a way that can lead to the development of
tumors. We would not last for very long at all without these defenders of the
immune system.
The immune system manages the whole ecosystem of human tissues and
embedded microorganisms. It allows specialized fungi to feed on the dead
cells on the skin surface and the fatty secretions on the scalp and other fungi
to multiply in the mucus linings of the digestive and respiratory systems.
Turning to its more aggressive role, the immune system works continuously
to eliminate insurgents, including the fungal pathogens that threaten to choke
the whole enterprise. The resulting mixtures of fungi that live on an
individual body are unique.8 The types of fungi differ in each location, and
their numbers change as some grow and reproduce and others deteriorate
and die. Our age and gender affect the numbers and kinds of microbes on the
body too, and there is some evidence that hormonal differences between the
sexes may stimulate the growth of distinctive groups of fungi. Sweating
stimulates the skin residents to proliferate, sun exposure kills others;
gardeners pick up fungi from the soil and from plants; children transfer fungi
to their parents and vice versa; and lovers swap fungi in bed. The number
and identity of the spores flowing through the nose and into the lungs vary as
we breathe, and the fungi in the mouth and digestive system are agitated
with each meal.
Geography is another variable, because fungi are not distributed evenly
across the planet. This means that there is a regional character to the
mycobiome, with people in Africa partnering with different fungi than Asian
populations. Diet has a dominating effect on the kinds of fungi and their
abundance in the gut, with major differences between vegetarians, meat
eaters, and consumers of lots of processed foods.9 Many illnesses affect the
types and abundance of fungi, especially those in the gut, and traumatic
injuries including severe skin burns enable fungi to penetrate deep into our
tissues. The catalog of these sundry influences on the composition of the
fungal communities on the body is endless.
The significance of human-fungal interactions is surprising, at first, when
we consider the scarcity of the fungi compared with the bacteria in the
microbiome. There are only 40 billion fungal cells in the human gut,
compared with 40 trillion bacterial cells, a thousand bacteria to each
fungus.10 Heaped together, the bacteria weigh as much as a cup of sugar, and
spread in a single line, they would encircle Earth. The less numerous but far
larger fungal cells weigh no more than a raisin, but their combined surface
area is impressive—equivalent to an eight-person dining table. The interior
lining of the large intestine covers a similar area, and even though many of
the fungi are buried in the dissolving food and developing feces, these
calculations reveal that the fungi offer a lot of real estate for chemical
interactions with the body. The molecule-by-molecule transactions between
the immense surface presented by the fungi and the immune system go a
long way toward explaining how such tiny organisms can have such a
profound effect on our health.
The impact of the fungi on the health of the gut is a controversial subject
among microbiome experts. Some view the fungi as critical players in the
internal ecosystem, while others believe that their activities are eclipsed by
the overwhelming number of bacteria.11 These differing viewpoints have
arisen because the science of the mycobiome is moving at lightning speed,
and conclusions about the influence of the fungi on some health conditions
swerve from study to study. But the truth is unfolding, and this book will
share consensus views when they are available and highlight other areas of
mycobiome research where we remain puzzled.
Uncertainties come from many sources. The first and most formidable of
these is the question of cause versus effect.12 If we find differences in the
abundance of fungi in people suffering from a particular illness, it can be
very difficult to determine whether the fungi are responsible for the illness or
whether the change in their number is a consequence of another issue with
the patient’s health. Either way, treating the fungus may be effective at
alleviating some of the most distressing symptoms of the complaint.
Examples of these conditions that do not seem to be caused by fungi but are
associated with shifts in the onboard populations of fungi are explored in the
chapters that follow. The second diagnostic problem comes from the
awesome power of the modern genetic techniques that allow us to detect the
dead cells of fungi that are passing through the intestine and may have
entered the body in our food. This makes it difficult to identify the living
species that are long-term residents in the gut, which are more important in
the health of the digestive system than the remains of dietary migrants.
While the relevance of the fungi in understanding some aspects of healthy
gut function is debatable, a substantial body of research has proven that
fungi belong to communities of microorganisms in other parts of the body
where they are crucial in health and disease. There is no question about the
importance of the fungi on the body surface, where they support skin health
and can also cause allergic responses and unsightly infections. Similarly, we
know that fungal spores are powerful triggers of asthma and other allergic
illnesses in the respiratory system. Lastly, it is important to recognize the
connections between the mycobiome in different parts of the body. The
effects of the gut fungi on the immune system can influence the development
of health conditions elsewhere, and fungi can also move physically from one
location to another—from skin to gut and vice versa. With so much attention
to the effects of fungi on human health, this is the perfect time to explore this
phenomenal symbiosis.

WHEN THINGS GO WRONG

Everyone is damaged by fungi at some time in their lives. Hundreds of
millions of people suffer from allergies caused by fungal spores, and fungal
infections range from skin irritation and toenail disintegration to the foulest
flesh-melting diseases ever pictured in a pathology textbook. The World
Health Organization (WHO) prioritized the surveillance of serious fungal
infections in 2022 with the publication of a list of nineteen species that pose
the greatest threat to public health.13 This was in response to the rising
numbers of fungal infections and difficulties in diagnosing and treating these
serious illnesses. Mycoses kill 1.5 million people every year, and the threat
of the severest infections is growing with the emergence of strains of yeasts
that are resistant to antifungal medicines. The burden of these illnesses is
heightened in the developing world, where access to adequate medical care
is limited, and in more affluent countries with aging populations that are
more vulnerable to infection. Poisoning is another hazard of our relationship
with the fungi, resulting from the mistaken identification of wild mushrooms
by foragers and by consuming the toxins produced by molds that grow on
harvested grain. These harmful interactions complete the picture of our
relationship with the fungi, which runs from beauty to the beast, the yin and
the yang of the human-fungus symbiosis.
It is easy to disregard the fungi that support our health because they are
invisible, and we can live in blissful ignorance of the dark side of mycology
if we are fortunate to avoid infections. But wisdom comes from familiarity
with this subject. The types of fungi that live on the body and their levels of
activity vary according to where we live, what we eat, and whether we work
indoors or outdoors. Changes in our health, drugs that we are prescribed, and
the use of consumer products including toothpaste, shampoos, and body
lotions modify our closest relationship with fungi too. No amount of
grooming will leave us unfungal, which is a good thing because we would be
in bad shape if we abolished our partners. A body without fungi would be as
barren as a forest without mushrooms. Equipped with this self-knowledge,
we can seek opportunities for correcting imbalances in this intimate
relationship.

BEYOND THE BODY: THE EXTENDED SYMBIOSIS

Beyond the body, fungi inhabit our pets, are active in damp places in our
homes, and flourish on fruits and vegetables in the kitchen. Pet dogs and cats
are covered with yeasts, bathrooms are mycological playgrounds, and we
consume fungi clinging to salad ingredients without giving them a thought—
until the tomatoes sprout hairs. Physical contact with these fungi is certain,
continuous, and consequential. There is a historical character to these
passive interactions with the fungi in the environment, which has changed
over thousands of years and continues to shift in the modern world. The
transition from hunter-gatherer and nomadic lifestyles to agricultural
settlements around ten thousand years ago had a profound effect on our
interactions with fungi, by exposing us to masses of fungal spores emanating
from moldy grain stores and to toxins in food made from these spoiled
cereals. Asthma and other allergies to fungal spores were born from changes
in farming over the millennia, and the crowding of populations in cities
promoted the spread of skin infections by ringworm fungi. The human-
fungus relationship has also operated on a more conscious level with the
incorporation of fungi into our diet, from foraging for wild mushrooms and
cultivating an increasing selection of species, to the growing popularity of
nuggets of fungal protein or mycoprotein manufactured in bioreactors. The
uses of fungi for food have also multiplied through cheesemaking, leavening
bread, brewing beer, and making wine. By domesticating the fungi that
enrich our diet, we have folded the natural environmental actions of these
microbes into human culture and driven changes in civilization over
thousands of years. All of the uses of the microscopic yeasts and molds for
food are extensions of the human-fungus symbiosis.
Human interactions with fungi reach further through the biotechnological
manipulation of fungi in drug manufacture. Fungal medicines include
antibiotics to treat bacterial infections; cyclosporin, which prevents the
rejection of transplanted organs; and “human” insulin and vaccines produced
by genetically modified yeast. On the subject of fungal medicines, there is a
lucrative global market for medicinal mushrooms with reputed life-
enhancing and lifesaving benefits. Consumers spend tens of billions of
dollars per year on mushroom extracts in the belief that they are effective at
treating illnesses through their effects on the immune system. Few of the
claims made by marketers have been tested, yet there is some hopeful news
on this front with investments in clinical trials on mushroom products as
anticancer agents. Drawing on stronger scientific evidence, “magic”
mushrooms have outgrown their countercultural associations to be embraced
as a promising treatment for clinical depression and post-traumatic stress.
Through these ancient and modern cultural practices, we have amplified the
positive influence of the fungi on our lives.

FROM WOMB TO TOMB: THE FUNGUS IS WITH YOU

Some years ago, when I gave seminars on the so-called toxic molds found in
buildings, I would say, “We inhale their spores from first breath to last
gasp.” This was true, but more recent findings show that the phrase provides
an incomplete picture of our interactions with fungi, which begin before
birth and extend into the grave. The bookends must be extended because the
fungi are with us from womb to tomb.
 The view of the womb as a perfectly sterile incubator for the fetus has
been consigned to medical history today.14 Our interaction with bacteria and
fungi before birth is evident from genetic analysis of the meconium, which is
the tarry liquid expelled by the newborn that develops in the fetal bowel. It is
the initial deposit that comes to light in the first few days after birth and
presages a lifetime per capita unloading of twelve tons of feces. Fungi that
live within the mother’s vagina, particularly the Candida yeasts, are the
commonest species detected in the meconium, which suggests that they
colonize the amniotic fluid that surrounds the fetus and make their way into
the gut of the baby when it swallows a little of the fluid before birth.15
Whether the traces of fungi found in the meconium affect the developing
fetus is unclear, although we do know that the risk of premature birth
increases as the number of microbes within the amniotic sac rises.16 Fungi
may also spread all the way from the mother’s skin to the fetus through her
bloodstream. Microbes are normally excluded from the blood, but when the
tissue barriers are weakened, and leakage occurs, the bloodstream becomes a
distribution system for bacteria and fungi. Inflammation of the gums or
gingivitis, which develops into more serious forms of gum disease, or
periodontitis, is one way that this can happen, raising the importance of oral
hygiene and dental care for pregnant mothers.
Birth propels the baby into the microbial world, where it will be coated
with fungi, filled with bacteria, infected by viruses, and breathe air brimming
with all manner of irritating particles. As a fetus we receive sips of foreign
proteins through the placenta and encounter the tiny populations of microbes
in the amniotic fluid. Outside the womb we are deluged with microbes.
Natural selection shaped Earth as a jungle of hospitable and hostile microbes
over billions of years and each of us is forced to adjust to this carnival. The
only possibility for survival resides with our guardian angel—the immune
system—which allows us to explore this melee safely, cultivating microbes
on the body that keep us healthy and warding off the germs that are more
likely to kill us.
The deeper relationship with the microscopic starts after birth and
depends on how we are born. If we surface via the natural route, the rupture
of the amniotic sac leaves us squeezing through the vagina, where we
receive a coating of bacteria and fungi from our mothers. The elastic fit of
the birth canal around the baby ensures that the whole surface of the
newborn receives this treatment. This is why the same strains of Candida
yeast that grow in the mother’s vagina are found on the skin of infants born
in this manner. Babies born by C-section become colonized by Candida
from their mothers too, but by different strains of the yeasts that are more
abundant on the surface of the mother’s skin. Difficulties in identifying
fungal species make these studies challenging, but the overall pattern of
vaginal microbes for vaginal deliveries and skin microbes for the C-section
babies seems to be true. Our birthday is the first day of intensive schooling
for the immune system that has been preparing for a microbiological
hurricane for nine months.
Fungi are also conveyed through intimate contact with the mother and
handling by others after delivery, and breastfeeding furnishes the infant with
a different mix of species. According to recent experiments that took
precautions to avoid contamination from the nipple surface, there are a lot of
fungi in breastmilk. These studies show that a slurping infant absorbs more
than two hundred million fungal cells a day, along with a similar number of
bacteria.17 The majority of the fungi are yeasts, although there are traces of
molds whose spores drift in from the air. It seems likely that fungi found in
the milk get there through the bloodstream, like the ones that cross the
placenta. Cells in the immune system may also pick up fungi from the nasal
passages, lungs, and gut and carry them to the breast tissue where they are
released into the milk. The couriers that perform this proposed role are the
dendritic cells that prowl the body looking for microorganisms.
The transmission of microorganisms from mothers to their offspring is a
widespread phenomenon in nature.18 The ubiquity of this seemingly
deliberate donation of foreign organisms from mother to child suggests that
some of them are critical for the vitality of the newborns of all animals. Most
of these microbes appear to be beneficial, although some pathogens can also
be relayed in this manner. Harmful microbes that pass from the human
mother to child include the parasite that causes toxoplasmosis, the syphilis
bacterium, and the human immunodeficiency virus (HIV). The fact that
some pathogens take advantage of this intimacy is an inevitable drawback to
the elementary processes that support the next generation. Natural selection
has fostered microbe transfer because the advantages of readying the
immune system for the outside world outweigh the disadvantages. The proof
is evident in the success of the human reproductive mechanism and the fact
that most infants do not succumb to microbial infection. Evolution is blind to
a small proportion of casualties.
The split personality of the fungi as beauty and beast is exactly what we
would predict from nature. The idea of some grand harmony among
organisms is pure fantasy. Like every other scrap of life, fungi are engaged
in a continuous struggle for existence. They collaborate with other organisms
when there is mutual benefit, fight when their partners act too aggressively,
and set up shop elsewhere by dispersing spores. Others have no time for
collaboration and live by damaging host tissues from the moment they
arrive. When we think about the beneficial fungi on the body and inside the
gut, there is a tendency to ascribe intention to the relationship. This is
wishful thinking. The fungi that grow on us fulfill a role that they have
crafted, occupying a niche on the body—the scalp for example—where no
other microbes do it better. During their evolutionary history, these fungi
have developed the mechanisms for living on the dryness of the head,
feeding on fats, and keeping the bacteria in check. As long as they do not
irritate the skin, they are left in peace. When the environment between the
hairs becomes unbalanced in some way, the fungi get unruly, and accumulate
in unusual numbers. This causes the skin to flake, and the immune system is
alerted that something is amiss. Swings and roundabouts, day in and day out,
ups and downs, and the same goes for the digestive system, vagina, and
everywhere else that the fungi blossom on the body.
Fungi that adapt themselves to living in these different locations in the
human ecosystem are the ones that need to be recognized as partners by the
immune system and left alone. Much about this process of acceptance
remains unknown, but the immune system of the baby seems to be tutored
inside the uterus, during birth, and via breastfeeding, priming the newborn
for a lifetime of encounters with microbes. Learning to work with some of
the commonest kinds of fungi on the skin seems like a very good lesson. By
acknowledging these harmless species and avoiding conflict, their growth
may limit the ability of bacteria to coat the skin. We know that yeasts engage
in chemical warfare with bacteria, and as long as these fungi do not
proliferate to the point of becoming a nuisance themselves, they remain part
of the healthy microbiome.
The newborn immune system is very fragile, with a small population of
mobile cells to police the lungs and other tissues, but the number of these
caretaker cells skyrockets to adult levels within the first days of life. This
period of vulnerability to infection is one of the characteristics of infants that
resulted in such a high level of historical mortality. Before the twentieth
century, more than 25 percent of babies died in the first year of life, and half
of all children died before they reached the end of puberty. Oral Candida
infections, or thrush, which spread to other parts of the body were a
significant cause of infant deaths.19 A combination of better nutrition and
hygiene, and the development of vaccines, antibiotics, and other drugs in the
twentieth century transformed this picture, and today’s infant mortality rates
range from 5 percent in some African countries to less than 1 percent in
Europe.
Considering these statistics, it is difficult to find fault with modern
medical practices, but we have introduced new hazards by increasing the
number of births by C-section and avoiding breastfeeding.20 Breastfeeding
follows a disturbing pattern, with few countries meeting the WHO and
UNICEF targets for infants.21 These regional differences are affected by
ethnicity and culture as much as economic prosperity. They are alarming
from a mycological perspective because the use of milk formula is linked to
a greater risk of asthma and other allergies to fungi. The immune system
needs to be introduced to grubbiness of the natural world from the get-go,
and if this lesson fails, we may face a lifetime of struggle, responding to
each fleck of fungus as if we are under attack. There is some evidence that
this poor formatting of the immune system in childhood can also lead to
autoimmune diseases later in life.22
The drama of the mycobiome does not end with infancy, and our
interactions with fungi change as the years pass. The mycobiome in the
digestive system is adjusted in response to the shift to solid food and later as
we pursue more omnivorous, carnivorous, or vegetarian diets. The
mycobiome is modified in adulthood, wobbling this way and that as we gain
and lose weight, become pregnant, undergo cosmetic surgery and dental
procedures, take antibiotics, are injured, and develop short-term (acute) or
long-term (chronic) illnesses. We can pick up fungal infections at any time,
although the likelihood of developing these mycoses increases among the
elderly. Fungal infections increase with age as we develop illnesses that
damage the immune system or require us to undergo therapies that lower
these defenses to maintain transplanted organs or to treat cancer.
Moving to the tomb, we are the latest additions to the menu of meat
dishes available to fungi that have been in the recycling business for
hundreds of millions of years. Bacteria take care of a lot of the soft tissues in
the human cadaver, leaving the keratin protein in hair and nails for a variety
of specialized molds.23 Bones are infiltrated by fungal hyphae too, assisting
their disintegration. These are the slowest processes of decomposition, but
the disappearance of the hair, nails, hooves, horns, and antlers of dead
animals in nature demonstrates the power of the fungi. We are sustained by
this planetary-scale nutrient cycling, together with the breakdown of plant
debris, because we rely on the forests, grasslands, and agricultural
ecosystems fertilized by the fungi. We would not be here without them.
Mycorrhizal partnerships with living plants are another essential part of this
broader relationship. We need fungi to work with plants as much as we need
fungi to work with our bodies.

THE PAGES AHEAD

In the chapters that follow, we will explore the communities of fungi that
live in every place on the body, pursue the historical and contemporary uses
of fungi as food and medicine, and look at the ecological roles of the fungi
beyond the body that function as an invisible life-support system. This book
is a revelation of the human relationship with the fungi, the human-fungus
symbiosis, from the fungi growing around the roots of our hairs to the
colonies of mushrooms wrapped around the roots of forest trees. The
chapters are organized into two sections that speak to the direction of the
inquiry: part I, “Inward,” and part II, “Outward.”
 Part I, Inward. Starting with the fungi on the skin surface (chapter 2), we
slip inside the body with the spores that enter the lungs (chapter 3), and dive
deeper with the yeasts and filaments that infect our internal organs (chapter
4). All tissues in the body can become colonized by fungi, which expands
the activities of the restless mycobiome to the lungs, liver, kidneys, brain,
and gut. Fungi in the gut are also part of the healthy digestive system, until
this part of the mycobiome is disrupted and a whole range of illnesses
related to immune dysfunction develop (chapter 5).
Part II, Outward. In the second set of chapters, we look at our interactions
with fungi that grow outside the body, beginning with their importance in
our diet, both as wild and cultivated mushrooms, and in the development of
mycoprotein meat substitutes that are energizing the food industry (chapter
6). This concept of the extended symbiosis incorporates the modern use of
drugs produced by genetically modified fungi in conventional medicine and
the controversial marketing of mushroom extracts in alternative or
naturopathic medicine (chapter 7). From medicines we move to poisons and
the dangers of consuming the wrong mushrooms and the spoilage of grains
by molds that produce mycotoxins (chapter 8). Magic mushrooms and their
use in the treatment of clinical depression and other serious mental health
issues follows (chapter 9). Proposed links between the use of magic
mushrooms and the origins of Christianity and other religions have been
dismissed by theologists, but there is room to reconcile these viewpoints
with a fresh and objective analysis of the evidence. In the final chapter we
examine the ultimate extension of the human relationship with the fungi
through our dependence on their wider ecological roles (chapter 10). We
discover the body as an ecosystem flavored with fungi—a pulsing city or
mycopolis—dependent on the fungi that support plants, create soil, filter
rainwater, and spin the carbon cycle.
This is the story of people and fungi, the human-fungus symbiosis that
spans the local to the global, revealing how our lives are influenced through
rich relationships with these extraordinary microorganisms.

OceanofPDF.com
 PART I

Inward
OceanofPDF.com
 2
Touching
FUNGI ON THE SKIN
ALTHOUGH WE MAY be exposed to fungi in the womb, the coating of yeasts
that forms when we are born marks the real beginning of the lifelong human-
fungus symbiosis. Fungi enter the lungs and the digestive system as soon as
we start breathing and breast- or bottle-feeding, but the skin remains the
biggest territory for the fungi throughout life, the place where they dominate
our microbiology. The skin is considered the largest human organ, and the
fungi grow all over it, consuming natural oils and dead cells, supporting and
irritating the folds and furrows of the external tissue or epithelium. They
grow in the greatest numbers on the scalp, where one hundred thousand to
one million yeasts can huddle in the space of a postage stamp.1 If humans
were squeezed together at this density, all eight billion of us would fit into a
city the size of Los Angeles.2 When we look in the mirror and brush our hair,
we have no sense of this congestion, but the fungi are in full swing, stirring
the chemistry of the skin, bossing the tinier bacterial residents around, and
causing the tissues to redden and flake when their routines are disturbed by a
new soap, shampoo, or lotion.
Most of our modesty can be concealed with a bath towel, but the skin
surface available for microbial growth is more extensive, matching the area
of thirty towels if we perform the thought experiment of flattening out the
nooks and crannies of the five million hair follicles.3 The populations of
fungi on this landscape are adjusted from birth to death, with yeasts and
filamentous species coming and going according to rules that we are only
beginning to understand. The numbers and kinds of fungi that grow from
head to toes have also changed throughout history as we have wrapped
ourselves with clothes, slipped on shoes, and doctored the environment with
cosmetics and drug treatments. Going back even farther, the skin
mycobiome has been making and remaking itself since modern humans
emerged from the Rift Valley of Africa.
The skin is not the most inviting place for microorganisms, because food
and water can be scarce. These challenges have led fungi that live on the
scalp to specialize in feeding on the waxy sebum secreted from sebaceous
glands and others to become very good at breaking down the keratin protein
in the outermost layers of the skin. Perspiration provides salty water, and
some of the residents overcome the aridity by producing their own water as
they digest the fats in the sebum. Through these measures, yeasts and molds
luxuriate on the skin. There are even more bacteria on the surface of the
body, but this is where the dimensions of the fungal cells become pivotal.
Although there are ten bacteria for every fungus on the skin, the fungi
outweigh the bacteria by a factor of ten.4 This difference in size explains
why the fungi are so important to the ecology of the skin. Fungi also abound
in the gut, as we will see in chapter 5, but they do not fare quite as well as
the bacteria. One of the reasons for this is that fungi like to be flushed with
oxygen, which is quite limited in the intestines. Many of the gut bacteria are
more flexible in their oxygen requirements, which explains their growth in
the trillions.5
Understanding what fungi do on the skin surface is a work in progress for
experts on the microbiology of the skin, with more questions than answers,
and a lot of conflicting information about the identity of the fungi that
support the clearest complexions, most luxurious hair, and healthiest nails.
The importance of quite subtle changes in the skin mycobiome is illustrated
by a complaint known as sensitive skin syndrome. This skin condition is
very common, affecting more than half of all people, if we include very mild
cases. Symptoms are subjective, making it difficult to diagnose, and include
stinging, burning, and tingling sensations that follow the use of cosmetics
and exposure to everyday irritants. There are no visible signs of sensitive
skin in most patients, but when reddened patches appear we call this
erythema. The mycobiome was implicated in sensitive skin in a study from
South Korea that found a greater diversity of fungi in skin swabs taken from
women with the syndrome relative to control subjects.6 Malassezia yeasts
were the most frequent fungi swabbed from the cheeks of all the women, but
in the patients with sensitive skin, this yeast was diluted by a surge in the
growth of other kinds of fungi, including a mold called Mucor. The
mycobiome differed from case to case, with little uniformity between the
communities of fungi that developed. Fungal involvement in the chronic
skin inflammation in sufferers of psoriasis follows the same pattern as
sensitive skin syndrome, with a greater diversity of fungal species found in
the patches of damaged skin compared with the intervening areas of healthy
skin.7
This research shows that these skin conditions are associated with
disruptions to the normal mycobiome. Dysbiosis is the term used to describe
instances of microbial disturbance, whether they are associated with disease
or not. Turbulent mycobiomes and microbiomes more generally are part of
the normal pandemonium of nature, which makes it doubly difficult to
determine when the appearance of an unusual fungus means that something
is amiss. Although skin inflammation can be a direct response to the growth
of a particular fungal species, we do not refer to complaints like sensitive
skin syndrome as infections. Diagnosis of a fungal infection, or mycosis,
requires a greater level of tissue damage, but we are dealing with a
continuum of symptoms associated with fungi on the skin rather than a clear
distinction between an unsettled mycobiome and more problematic disease.
At both ends of the spectrum of fungal development on the skin, the
behavior of the mycobiome is affected by the response of the immune
system. The immune system has a definite role in shaping the mycobiome,
by permitting some fungi to grow and eradicating others. For its part, the
mycobiome trains the immune system to recognize harmless and harmful
adjustments in numbers and species. When we look at the most serious
mycoses, we often find that they develop after damage to the immune
defenses. Infections of our internal organs are featured in later chapters, but
the mycoses of the skin arise from our continuous interactions with fungi in
the environment and happen to people with perfectly healthy immune
systems.

RINGWORM, ROBERT REMAK, AND RADIATION

Greek and Roman physicians were familiar with ringworm, which they
lumped together with other scalp conditions and called porrigo.8 Public
bathing in ancient Greece and Rome and the practice of pouring olive oil
onto the skin and removing it with a curved blade or strigil was a surefire
remedy against skin parasites.9 But the oiled skin was an invitation for the
growth of fungi, and ringworm was a common complaint in Rome. The first
emperor, Caesar Augustus, was blemished with “a number of hard dry
patches resembling ringworm, caused by vigorous use of the scraper on an
itching skin,” and the affliction may have factored in the suicide of Roman
senator Festus, who was desperately ashamed by “the deformity of a
Ringworme in his face.”10
Ringworm is a general term for fungal infections that can take hold on
any area of the skin. Early references to “rynge-worme” appear in the 1400s,
and toward the end of the seventeenth century John Aubrey, the writer and
pioneering archaeologist, noted the resemblance of the skin lesions to the
fairy rings produced by mushrooms in his Natural History of Wiltshire: “As
to the green circles on the downes, vulgarly called faiery circles (dances), I
presume they are generated from the breathing out of a fertile subterraneous
vapour. (The ring-worme on a man’s flesh is circular. Excogitate a
paralolisme between the cordial heat and ye subterranean heat, to elucidate
this phenomenon.)”11 In other words, if we believe that fairy rings arise from
the release of poisonous fumes from the earth, we might get at the root cause
of ringworm by examining the humors of blood (air), phlegm (water), black
bile (earth), and yellow bile (fire), on which the medicine of Aubrey’s day
depended. This kind of deductive logic is the reason that Aristotle is such a
poor guide to the workings of nature, although a few classical scholars may
disagree with this brusque assessment. In any case, while Aubrey’s
observations did not lead to any treatments for ringworm, he was spot-on
about the similarities between fairy rings and the skin disease. In both cases,
the hyphae of filamentous fungi start growing from single spores, striking
outward in all directions at once to produce circular colonies.
More intentional investigations on disease-causing or pathogenic fungi
began in the nineteenth century. Richard Owen, the famous anatomist,
stirred interest in fungal infections when he discovered “a green vegetable
mould or mucor” in the lungs of a flamingo during the dissection of a bird
that had died in the London Zoo.12 Owen concluded that the fungus was a
parasite that had been growing in the bird before its death. His study was one
of a scattering of early descriptions of the mycosis called aspergillosis,
which also occurs in humans, but the first proof that a fungus was
responsible for human disease came from research on ringworm. In 1842,
twenty-seven-year-old medical researcher Robert Remak conducted a
remarkable and unpleasant experiment by lifting a scab from the scalp of a
patient suffering from ringworm and taping it to his own forearm.13 After
two weeks, he noticed “a strong itching … [and] found a dark red spot the
size of a vest button” at the inoculation site. Removing the crusty spot, he
found the fungus embedded in his skin, proving that it was responsible for
ringworm.
 Remak’s exploration of ringworm belongs to a tradition of professional
commitment by medical researchers that includes deliberate self-infection
with the bacteria and viruses that cause stomach ulcers, yellow fever,
relapsing fever, and venereal diseases, as well as the consumption of
radioactive dyes and self-catheterization of the heart.14 Some experiments in
this vein led to Nobel Prizes, but the ethics of self-experimentation are
problematic, may contravene the Hippocratic oath, and are assuredly at odds
with modern guidelines for good clinical practices. Although his
experimental approach was questionable, Remak clearly established that a
fungus could cause an infection, and, remarkably, he had made this
breakthrough twenty years before Louis Pasteur linked microbes to disease
in his germ theory. Remak cared very little about scientific honors—the
glittering prizes revered by most members of the academy. He was an
unusually humble scientist who refused to take credit for his ringworm
discovery, insisting, instead, that an older colleague had made the crucial
insights. Today, he is recognized as one of the pioneers of medical
mycology, which is the study of fungal infections and their treatment.
Fungi that cause ringworm feed in the outermost layers of the skin, where
older cells are pushed to the surface by the underlying tissues. These cells
are stuffed with fibrous keratin protein and become embedded in a fatty
matrix as they die. This structure has been likened to a brick-and-mortar
wall. It forms a shield against dehydration from the inside and infection from
the outside and is constantly renewed as the oldest cells are shed into the
environment. Hyphae of the ringworm fungi invade this skin layer, releasing
enzymes, digesting the protein and the fat, and expanding into their fairy
rings. Hair and nails are also fashioned from keratin and can become
infected with ringworm fungi. In scalp ringworm, the fungi dive into the hair
follicles and invade the hair shafts, feeding on the keratin until the hairs
become brittle, fracture, and fall out, leaving bare spots on the scalp.
Ringworm fungi belong to the ascomycete group, which includes species
of Penicillium that produce antibiotics, and Aspergillus that cause the lung
infection found by Owen when he dissected the flamingo.15 Ringworm
infections are dubbed with Latin names according to the sites where they
grow and other distinguishing characteristics—tinea capitis for the scalp,
tinea pedis for the foot, tinea unguium for the toenails, and so on. Other skin
infections come under the umbrella of tinea corporis, which includes a
mycosis that spreads between young wrestlers and judo students that has
been given the splendid name tinea corporis gladiatorum.16 Tinea corporis
gladiatorum! If dermatologists pursued more of this kind of creative
nomenclature, their patients might feel a modest elevation upon their
diagnoses: “athlete’s foot” is a bit deflating, so, how about tinea pedis-
athletarum, -gymnasticorum, or -victorum? Just an idea.
Ringworm infections are the commonest type of mycoses, affecting one
billion or more of us at any time.17 Ringworm is an affliction of childhood,
and the number of cases falls abruptly after puberty. This suggests that the
fungi are rebuffed by the hormonal hurricane that alters the chemistry of the
skin secretions, reconditions the immune system, and leaves most of us
feeling quite unsettled for a while. Ringworm infections remain prevalent in
sub-Saharan Africa, where a Kenyan study found that 81 percent of children
from an “informal settlement,” or slum, in Nairobi suffered from tinea
capitis—the scalp infection.18 A separate survey in rural Nigeria showed that
almost half of the children in the ethnic Nok community were infected.19 The
common name for tinea capitis used by the Nok is translated as “spider
web,” which refers to the belief that spiders urinate on the heads of children,
lay their eggs, and create the ringworm patterns of concentric rings when
they spin their webs. At the time of the study, published in 2016, the local
barber was shaving the heads of the children with the worst cases of
ringworm. He sterilized his clippers between shearings by dousing the
blades with denatured alcohol and igniting them with a cigarette lighter.
Poverty and poor hygiene have always been a magnet for ringworm
infections, and they were very widespread in Europe when Robert Remak
showed that they were caused by fungi. Compared with the early treatments
recommended by Western experts, the Nigerian barber’s remedy seems very
gentle. Complete hair removal was a common treatment, which involved
plastering the scalp with molten tar or resin. This paste was left to harden
into a solid cap that was ripped away, carrying infected and uninfected hairs
as well as skin tissue and, I imagine, leaving the poor child blinking in
horror and traumatized for life.20 This seems to have been a popular remedy
in the nineteenth century. Doses of thallium acetate, or rat poison, produced
the same effect, although the drawback of prescribing an oral medication
whose “therapeutic dose is so near the limit of the lethal dose” could not be
ignored when children started dying.21
Ringworm spreads from person to person via infected skin cells, and
outbreaks became common during the industrial revolution among children
living in the “rookeries” or slums of London and other overcrowded cities.
Orphanages and boarding schools—think Nicholas Nickleby—were breeding
grounds for fungi, and then, in the 1890s, there was a medical breakthrough
in the treatment of ringworm: X-ray epilation. Hair loss was observed in
people treated with X-rays for other skin conditions, so the application of the
technology for deliberate hair removal seemed an obvious step. The
effectiveness of the method was undeniable. What could possibly go wrong?
The Lancet published a letter in 1896 suggesting that gentlemen should zap
their chin hairs with X-rays for a few minutes every evening to save the
effort of shaving the next morning.22 This practice failed to catch on, but
women visited “Tricho” salons where cosmetic X-ray machines were used
for removing unwanted hair until 1929.
The danger of the procedure was evident from the fact that the inventor of
these appliances went on to have his left hand amputated to stop the spread
of cancer and experienced the loss of his right hand to ulceration.23 But
enthusiasm for curing ringworm with radiation continued in the 1930s, when
a distinguished London radiologist wrote, “Even if, through some error in
technique, an overdose is given, the worst that can happen is an X-ray
burn.”24 This reckless attitude persisted for decades, and hundreds of
thousands of children were treated before the therapy fizzled out in the
1960s. Radiation exposures varied, and the redirection of the beams toward
different parts of the head during a treatment session reduced the damage to
any single spot. Nevertheless, there is no doubt that children received X-ray
dosages that we reserve for the treatment of brain tumors today, and which,
tragically, may have caused brain tumors in an untold number of these
patients in later life.
The frequent repetition of the word “may” in this book (and other
expressions of possibility rather than certainty) is demanded by the science.
In the ringworm X-ray story, we are not sure that the treatment resulted in
the development of cancer in adulthood. It is very difficult to tie individual
cases of cancer to a particular exposure to radiation, and so we pursue
epidemiological studies in which we gather information on as many
ringworm patients as possible and see what happened to them in later life. If
there is a clear spike in brain tumors in these patients compared with
untreated controls, we edge closer to scientific certainty. If the number of
cancer cases is no greater, or not much greater, than the background, we are
left with an unresolved problem. Some of the studies on ringworm patients
suggest that there is a link between the use of radiation and cancer, while
others do not.25 It is possible that we will never know for sure. Besides the
fear of a cancer diagnosis, some Israeli girls treated with X-rays suffered
from permanent hair loss that left them with lifelong cosmetic and
psychiatric challenges.26 However we look at it, this ringworm treatment was
a low point in medical mycology.
Most ringworm fungi provoke a relatively mild response from the
immune system, and some children with disfiguring skin infections are
spared from intense itching and other symptoms of inflammation. This
blessing is a feature of the limitation of fungal growth to the layers of dead
skin cells and separation from the deeper tissues patrolled by the active cells
of the immune system. The ringworm fungi also use various tricks to
camouflage themselves while they feed on the skin. One of these
mechanisms allows the fungus to conceal molecules on the surface of its
hyphal filaments that otherwise serve as alarm bells for the immune
defenses. This invisibility cloak evolved over tens of millions of years, as
soil fungi adapted themselves for growing on the skin of different kinds of
animals. Relatives of the human ringworm fungi colonize other mammals
without causing any obvious harm, but they can damage our skin if they are
transferred from farm animals or pets. Infections that come from other
animals are called zoonoses, and they are a good reason for avoiding contact
with hedgehogs. Intimacy with hedgehogs does not concern most of us, but
cases of ringworm infections among lovers of these spiny animals are
surprisingly common. Dogs and cats are more common sources of human
ringworm, and the ubiquity of these pets makes these zoonotic infections
inevitable.27 Islamic prohibitions against keeping dogs in the home seem
entirely reasonable from a mycological viewpoint.
Fortunately, the development of antifungal medicines means that
ringworm infections can be cured today without recourse to violent
epilation, rat poison, or X-rays. Griseofulvin was discovered in the 1930s,
and its use for treating ringworm began in the 1950s. It is made naturally by
a species of Penicillium that causes blue mold on harvested apples and is a
close relative of the fungi that produce the penicillin antibiotics.
Griseofulvin is taken as an oral medication and kills the ringworm fungi
from the inside out, making its way to the skin surface where it infiltrates the
hair follicles and destroys the hyphae from the bottom of the hair shafts
toward the tips. It works by disrupting the division of nuclei inside the
hyphae. Other antifungal drugs effective against ringworm include
terbinafine and azole antifungals that disrupt fungal membranes. Apple cider
vinegar, tea tree oil, and raw honey are some of the natural products
promoted as alternative treatments for ringworm. (We look at antifungal
drugs in more detail in chapter 4.)

DANDRUFF
Outbreaks of scalp ringworm in children are uncommon in more prosperous
countries today, and the drug treatments are effective in treating individual
cases when they develop. This does not mean that the scalp has become a
microbiological desert. Far from it. It is a hive of fungal activity throughout
our lives, no matter how many times we wash our hair. Most of the fungi
that grow on the skin do so as yeasts rather than molds, as blobs rather than
webs. This is a good thing, because yeasts stay on surfaces, whereas molds,
or filamentous fungi, are fashioned for penetrating tissues, and nothing good
comes from skin invasion by fungi. Species of Malassezia yeasts are the
dominant fungi on the scalp. They are named for a French anatomist, Louis-
Charles Malassez, who found them growing in skin flakes scraped from
patients suffering from seborrheic dermatitis. Seborrheic dermatitis is an
extreme form of dandruff, sharing many of its characteristics with the
snowiness of hair that afflicts a good chunk of humanity to varying degrees.
Both complaints involve the multiplication of Malassezia in the sebum
exuded from the sebaceous glands. The mouths of these microscopic glands
open into the hair follicles wherever we are hairy, and directly on the skin
surface in places where we are not. Sweat glands are separate things that
release more watery secretions whose evaporation is key to controlling body
temperature.
Sebum is marvelously complicated stuff that contains a mélange of fats
and oils and is produced in varying amounts according to age and sex—more
in men than women—and serves as the dietary staple for the yeasts that live
on the skin. These fungi are so perfectly adapted to life on the skin that they
have lost the ability to produce their own fatty acids like other organisms
and draw everything they need from the sebum. We consume fats, of course,
but our ability to manufacture fatty acids from sugars in the diet is essential
for constructing membranes and performing all kinds of other metabolic
tasks. By surrendering this almost universal biochemical capability, the
evolving yeast saved a great deal of energy and bonded itself to the skin for
the rest of forever.28 Malassezia belongs to the basidiomycete group of fungi
rather than the ascomycetes that include the molds that cause ringworm.
Fungi that form gilled mushrooms are classified as basidiomycetes, but the
closest relative of the dandruff yeast is a fungus that causes a crop disease
called corn or maize smut. (The infected ears become filled with blackened
spores that are used as an ingredient in Mexican cooking called huitlacoche.)
Both of these fungi—dandruff yeast and corn smut—are specialized
organisms that have become completely dependent on their hosts.
Dandruff is an inflammatory condition that develops as the yeast works
its way into the skin, feeding on the sebum and releasing irritating
compounds onto the scalp. This disturbance to the skin chemistry alerts the
immune system, which responds by mobilizing macrophages and killer cells
against the fungus. Itching and skin flaking are symptoms of the unfolding
turmoil on the scalp. Malassezia lives on everyone, so the reason that some
of us are spared dandruff and others itch, scratch, and flake is a bit of a
mystery. What we do know, however, is how to treat it.
Early in my research career, I worked at Yale University with a visiting
scientist from the Soviet Bloc who was very careful with money, saving as
much as he could from his salary to keep him in relative comfort when he
went home. To this end, he collected sachets of ketchup and mayonnaise
from fast-food restaurants rather than purchasing these condiments from the
grocery store. Dandruff was a significant problem for this expert on fungal
physiology, and rather than wasting money on the medicated shampoo that I
recommended, he set off to find some stinging nettles, which, he explained,
are a natural balm for all scalp problems. Finding a patch of nettles behind
our lab building, he boiled the leaves, mixed them with vegetable oil, and
before long his hair shone like Samson’s mane. An alternative remedy
chosen by more than one billion dandruff sufferers comes in plastic squeeze
bottles filled with the best-selling shampoo in the world, namely, Head &
Shoulders, manufactured by the Procter & Gamble Company. This lucrative
product has been on the market since the 1960s.
Dandruff shampoos kill the dandruff fungus with various formulations
containing pyrithione zinc, selenium sulfide, and piroctone olamine. I am
detailing the names of these chemicals so that you can look at the small print
on your shampoo bottles and see which ones you are lathering into your hair.
They kill the fungus by messing up its membranes, which either starves or
poisons the cell.29 The control of dandruff is a triumph of Western science.
Not as spectacular as antibiotics or vaccines, but something to smile about
when you grab the shampoo in the drugstore. I have begun to wonder,
however, if there may be a downside to this pharmacological battle against
the yeasts that have lived peacefully on the human scalp for millennia.
If we use the guesstimate of two hundred thousand years for the origin of
our species, the natural symbiosis between humans and the scalp yeasts
endured for 99.97 percent of our partnership before we began killing them
with shampoo. If a single species of Malassezia was the sole occupant of the
skin microbiome and we struck it down with shampoo in the pursuit of
lustrous unflaked hair, there would be little else to say. But the scalp is a
more complex ecosystem, where multiple kinds of yeasts are found,
filamentous fungi show up with some regularity, and both kinds of fungi
share the neighborhood with bacteria.30 These microorganisms work with
one another, and against each other, rising and falling in numbers as the
bearer of the scalp moves from childhood to adolescence and onward to
adulthood and old age. The daily use of antidandruff shampoos does not
seem to cause any side effects, and we certainly feel blessed by the absence
of itching and flaking if we have experienced the alternative. But another
fungus that grows on the skin has made me think a little deeper about the
consequences of manipulating the mycobiome.

AN EMERGING AND DANGEROUS YEAST

In 2009, a new kind of yeast was discovered in the ear canal of a seventy-
year-old woman in a Tokyo hospital. The DNA signature of this fungus was
sufficiently different from other species that it was given a new name:
Candida auris. Since then, this yeast has become a global plague—plague
may be a term too fearsome, although it is infecting and killing hospital
patients across the world and is resistant to every type of antifungal
medicine. Candida auris grows on the skin of patients who pick up the
fungus in hospitals where it has already made itself at home on other patients
and sticks to the surfaces of medical devices.31 As long as it remains on the
skin it does not do any harm. The problems unfold when the yeast makes its
way into the bloodstream through catheters inserted into veins to deliver
fluids or drugs. Once inside the body, it multiplies by shedding buds from its
cell surface and spreads to the kidneys, heart, brain, and other organs,
causing fever, breathing problems, and fluid retention. The mortality rate for
the worst infections approaches 60 percent. In the same year that this new
species was described in Japan, reports of hospital infections caused by the
yeast came from South Africa and India, and then, in the following year, in
Kenya. Soon, the fungus was spreading across dozens of countries.32
Genetic analysis has shown that there are four distinctive populations of
Candida auris and that this fungus evolved very recently in biological
terms.33 The estimated timeline for this evolutionary process comes from
changes in the DNA sequences of yeasts belonging to the different
populations. The kinds of genetic variations identified in these studies
develop at a relatively constant rate, and so the number of alterations in the
DNA sequences serve as a molecular clock for researchers. This clock
suggests that the oldest population of Candida auris emerged in the middle
of the seventeenth century—around the time of the Great Plague and Great
Fire of London, and that the strains of the fungus that cause the most
aggressive infections developed as recently as the 1980s. Using the
incredible power of whole genome sequencing, we can follow the pulse of
the DNA of this pathogen across four centuries and witness its appearance as
a major threat to human health. This is a remarkable piece of work. A second
discovery shows that the yeast is not completely dependent on human skin,
because it has been found in sediment samples from a salt marsh and a sandy
beach on the Andaman Islands in India.34 How and why it began killing
humans is not known, but there are some clues.
One provocative suggestion is that global warming has led to the
evolution of hyperaggressive yeast strains that can thrive in the warmth of
the human body.35 This seems unlikely, because the increase in average
global temperatures has been too small to push the fungi beyond their
existing comfort zones. The majority of fungi, which we call mesophiles,
grow fastest at 25°C–30°C (77°F–86°F), but many of them can keep
growing until the temperature approaches 40°C (104°F). Our body
temperature is challenging for these fungi rather than crushing. On the other
hand, shifting weather patterns related to global warming may have a
significant effect on the distribution of hotspots for fungal asthma (see
chapter 3) and outbreaks of life-threatening mycoses (see chapter 4).
Setting aside its temperature tolerance, other alterations to the ecological
experience of Candida auris may be more significant in its recent
development as a pathogen. We know that the use of antifungal drugs
introduced in the 1980s has driven the emergence of resistant strains of other
species of Candida, and this process might apply to Candida auris.36 These
medicines, which include ketoconazole and fluconazole, are examples of the
azole antifungals that continue to be used to treat all kinds of fungal
infections. Azoles and other antifungal agents are also used to control fungal
diseases of crop plants, and their presence in the environment is likely to
drive the emergence of resistant strains of fungi that could attack our food
supply and our bodies.37
The use of dandruff shampoo is so pervasive that we do not think of it as
an antifungal agent, but many of us use this as a daily mycobiome disrupter.
Malassezia is the unchallenged monarch of the skin until it is drowned with
toxins when we stand in the shower and lather our hair. The antifungal
agents in these hair products cause monumental changes in the ecology of
the skin, and a fungus that can rise to the challenge by surviving the
shampoo will prosper in the vacuum left by Queen Malassezia. This is
natural selection pure and simple. Precisely the same thing happens when an
antibiotic is used to treat bacterial infections: a strain of the bacteria that
develops resistance takes over from its defenseless relatives, offering the
classic example of evolution by natural selection. This process explains the
emergence of lethal bacterial infections that do not respond to antibiotic
treatment. So, along with the proliferation of antifungal medicines and
agricultural fungicides, the popularity of dandruff shampoo should be
considered as a global invitation for the evolution of worrisome strains of
fungi that can interact with the human body. We do not know why Candida
auris became a problem in the 1980s, but the answer may lie somewhere in
the growing use of antifungal products.

ATHLETE’S FOOT: THE DOWNSIDE OF SHOES

We have remained at the head end of the human-fungus symbiosis for most
of this chapter, and now we move to the feet for the climax. To find the
earliest case of fungal infection caused by an otherwise life-enhancing
invention, we have to look deeply into human history and examine a 5,500-
year-old shoe discovered in an Armenian cave.38 The shoe was made from a
single piece of animal hide, which was wrapped around the foot and laced
together on top. This is the oldest known closed shoe, and the essence of the
design is responsible for athlete’s foot. The Armenian shoemaker was
embarking on an unconscious mycological experiment with a wearable
consumer product, much like the later inventors of contact lenses, which
come with their own fungal complications.39 While a closed leather shoe
provides warmth in temperate climates, protects the wearer from sharp
objects on the ground, and, let’s face it, looks very stylish, it can create a hot
and humid chamber that is as close to perfection for cultivating fungi as a
throbbing stainless-steel incubator in a mycology lab. The result, for
susceptible individuals, is ringworm of the foot, tinea pedis, which may be
the most widespread fungal infection of our species.
 The Romans we met earlier who developed spots of ringworm on the rest
of their oiled bodies avoided the foot complaint by wearing open sandals.
Sandals also protected Latin wearers from a dreadful fungal infection called
mycetoma that is acquired by stepping on thorns bearing the fungus. Forced
into the tissues, this terrible fungus bores interconnected channels or
galleries throughout the foot that open onto the skin surface and discharge a
watery fluid infiltrated with infectious grains.40 Evidence of the disease has
been found in the skeleton of a Roman who died in his late forties or early
fifties in the second or third century AD. The bones of both of his feet have
the moth-eaten look that is characteristic of this mycosis.41 Mycetoma is a
subtropical disease whose distribution suggests that he might have acquired
the infection when he served in one of the North African provinces. Perhaps
he took off his sandals to play the Roman ball game harpastum with the
locals. The infection is also known as Madura foot, after the district of
Madurai in South India, where cases caught the attention of colonial doctors
in the nineteenth century. (Carrying bundles of wood on the head or
shoulders leads to rare cases of Madura head. An image search for this awful
disease should be avoided before bedtime.42) Sporotrichosis caused by the
fungus Sporothrix is another infection that can begin with a thorn prick and
is called rose handler’s disease.43
Returning to the mycological perils of wearing closed shoes, the typical
cause of athlete’s foot is the fungus Trichophyton rubrum, which evolved in
Africa. We know that this fungus arose in Africa because this is where the
species harbors its greatest genetic diversity today.44 This pattern of maximal
genetic variation exists in the homelands of most species of all organisms for
the simple reason that the process of mutation—which is the source of
variation—occurs continuously and has more time to increase the diversity
of a species where it originates than in locations where it arrives as smaller
populations of migrants later in its history. The greatest genetic diversity in
our species is found in Africa, the same continent as Trichophyton, and it
seems certain that we left there together, fungus on foot, and spread across
the planet. Ringworm may have been a minor problem before the exodus,
growing on dead skin cells without moving any deeper. Closed shoes
provided the opportunity for more luxuriant growth of the fungus, and some
strains became more virulent as they encountered stronger resistance from
the immune defenses. The same fungus is one of the species that infects
toenails causing onychomycosis, although poor circulation in older patients
is a major risk factor rather than simply wearing closed shoes.
Powders and creams for treating athlete’s foot have a global market value
approaching $1.7 billion.45 This is not surprising, given the shelf space
occupied by these products in pharmacies. Medicated shampoos are worth
more than $12 billion, and dandruff is the most prevalent health complaint
caused by fungi, although the fact that it is caused by a fungus is a detail that
escapes most sufferers. The overgrowth of vaginal yeast, which we address
in chapter 5, is a comparable problem in terms of the number of cases and
far worse when we consider the symptoms. And, again, many sufferers may
not think of yeasts as fungi. On the other hand, everyone knows that athlete’s
foot is caused by a fungus, which means that the space between our toes, the
web space, is the most familiar interface between the human body and the
mycological world. The discomfort caused by this everlasting pandemic is
one of the most obvious expressions of our deep and evolving relationship
with the fungi. More problematic, although less visible than reddened and
peeling skin between the toes, is the inhalation of fungal spores that
accompanies every breath. This is the subject of chapter 3.

OceanofPDF.com
 3
Breathing
SPORES IN THE LUNGS
I AM OBSESSED with spores and have invested a sizable chunk of my
professional life in understanding how they get into the air.1 This admission
is more likely to attract pity than interest until you consider the beauty of the
dispersal mechanisms used by fungi. Start by lying on the grass next to a
mushroom at night and using your phone flashlight to illuminate the
underside of the fruit body. Move the light around until you see the smoke
that pours and swirls from the cap. That smoke is composed of hundreds of
thousands of spores, which are propelled from the gills by little drops of
water. There is grandeur in this view of life.
Mushrooms are one of the sources of airborne particles that join the
clouds of spores released by the molds that grow on plants and every other
surface in nature. The air is filled with spores, and we inhale them with
every breath. These microscopic specks are destroyed after they stick to the
mucus in our airways, but they carry irritating proteins called allergens that
are as damaging to asthmatic lungs as birds sucked into jet engines. Asthma
and other illnesses that result from the inhalation of spores are the subject of
this chapter.
Air seems to coagulate during an asthma attack, with each inhalation
urgently demanding conscious attention. Suffering from a severe bout of
asthma in England in July 1969, I spent hours bath-robed in front of the
television, watching the coverage of the Apollo 11 mission on the BBC. As
Armstrong and Aldrin explored the lunar surface, the pauses in their
conversations with Mission Control in Houston seemed to synchronize with
the laborious rhythm of my breaths, so that I began to imagine that I was
with them on the Moon. It was an oxygen-deprived hallucination. Looking at
the night sky after Armstrong’s step and the flag planting, it seemed that the
Moon belonged to America. This evidence of the power of science
convinced me that America was the place to be, not this chilly island with its
stifling air supply, but the land that made all things seem possible.
Hamlet was struggling with ennui rather than breathing when he
described the air as “a foul and pestilent congregation of vapors,” but this is
a perfect assessment of the atmosphere for an asthmatic. An English
physician, John Floyer, described the feeling of an asthma attack in his
classic study of the illness, A Treatise of the Asthma, published in 1698:
“The asthma is a laborious respiration, with lifting up of the shoulders, and
wheezing, from the compression, obstruction, and coarctation [narrowing] of
some branches of the bronchia, and some lobes and bladders of the lungs.”2
Anyone who has experienced asthma will recognize the “lifting up of the
shoulders,” which is an automatic reaction to restricted airflow. Sit in a chair,
keep your mouth closed, pinch your nostrils until they start to flare on their
own, and you will feel your shoulders rise after a few restricted breaths.
Asthma reduces the space inside the lungs, and assuming a more upright
position and raising the shoulders are subconscious strategies to force the
airways open, to create more space. Doctor Floyer wrote from personal
experience: “I have suffered,” he wrote, “under the tyranny of the asthma at
least thirty years.”
Fungal spores are responsible for much of the tyranny of asthma. When
we vacuum air though a filter and examine the harvest on its surface with a
microscope, we find particles that look like tiny shards of broken glass,
minute globes and ellipsoidal eggs, broken strands, fallen missiles, and
juggler’s clubs—a toy chest of the insane. These are the spores of fungi,
made visible with the low power of the microscope, along with the larger
pollen grains from plants. Bacterial rods and blobs appear at higher
magnification, while the viruses remain invisible until we view the finest air
filters with an electron microscope. We live in this soup.
Soup is an imperfect metaphor, because air is so thin and spores are so
vanishingly small.3 One hundred thousand spores per cubic meter is
considered a very high concentration by experts on air quality; 10,000 spores
is a moderate number, and 1,000 spores is very low. At rest, we take an
average of twelve breaths per minute and inhale and exhale around six liters
of air. This means that one spore is drawn into the lungs with every other
breath when there are 1,000 spores suspended in each cubic meter of the
surrounding air, five spores per breath at 10,000 spores per cubic meter, and
so on. Some of the spores are immediately expelled when we exhale, others
stick to the mucus in the lungs. Over a lifetime, this equates to lung contact
with more than one billion spores, which is a lot of spores, but amounts to no
more than the weight of a pea.4 How on earth, one may ask, can so slight an
interaction result in decades of suffering for an asthmatic? The answer is
found by grasping what the immune system is programmed to do and why
the hairsprings of this intricate machine respond to unwanted triggers.
The immune system is active every moment of our lives, working flat out
to keep us alive when we are in serious trouble and scanning the body the
rest of the time, alert to microbial intruders and all manner of irritating
materials from the environment. The defenses are also alarmed by our own
cells that become cancerous and purge them from the body before they do
any harm. We distinguish between two arms of the immune system, although
they work together.5 The innate immune system is the first line of defense
that is mobilized when immune cells recognize the chemical signatures of
broad categories of invaders, namely, viruses, bacteria, amoebas, and fungi.
There is very little specificity here. The body senses that it is under attack
and throws the kitchen sink at these intruders. Cells that detect the
unwelcome arrivals release little proteins called cytokines that summon
multiple kinds of immune cells to destroy them. More bespoke defenses
against specific pathogens are furnished by the adaptive immune system,
which uses antibodies to neutralize infectious microorganisms.
Fungal allergies and fungal infections are very different illnesses. Fungal
asthma and other allergies happen when the body is responding to mere
contact with spores rather than trying to stop a fungus from growing in our
tissues. The symptoms of allergy are produced by the adaptive immune
system.6 Many of the spores flowing through the nostrils get trapped on the
nose hairs and in the mucus that lines the upper airways. Those that escape
these obstacles float all the way down into the lungs. Proteins attached to the
surface of the spores dissolve in the lung mucus. These proteins are the
allergens recognized by the bodies of people sensitized to the spores,
meaning that they bind immediately to the surface of cells of the immune
system called mast cells and basophils. This is a chemical reaction, like a
key fitting in a lock—the lock installed on the mast cells and basophils—
which is perfectly shaped to receive the protein key carried by the fungus.
When the key is turned, the immune cells release histamine and other
molecules that cause blood vessels to dilate and the airways in the lung to
constrict and fill with mucus. This is what we mean by inflammation of the
lungs. Asthma is an allergy that can be caused by sensitivity to many irritants
including pollen grains, dust mites, and pet dander, in addition to fungal
spores. Hay fever or allergic rhinitis is another type of allergy that can be
caused by spores.
 FUNGI AS ONE OF THE PRINCIPAL CAUSES OF ASTHMA
Asthma was an inexplicable ailment until the twentieth century. The
confusion in the Victorian era is evident in a booklet titled Spasmodic
Asthma, published in 1879, which suggested that “atmospheric electricity”
was a significant cause of asthma, along with a variety of “vegetable
emanations … also the smell of certain animals … [and] dust of all sorts.”7
This was written by William Steavenson, a London physician and asthma
sufferer, who discussed an assortment of treatments, including tobacco,
hallucinogenic plants, and amyl nitrite (known in recreational settings today
as “poppers”), and concluded, “I hardly want any other remedy so long as I
have my syringe and solution of morphia.” With unlimited access to his
chosen narcotic, he eschewed the therapy recommended by a German
professor, “who relieves his attacks by placing himself on a stool with glass
legs and connecting himself with an electric machine which is worked until
he is able to emit sparks from the ends of his fingers.” Reading Steavenson,
one gets the impression of an asthma enthusiast, someone who reveled in the
study of his condition, although it is worth mentioning that lung
inflammation killed him at the age of forty-one.8
Proof that fungi cause allergies comes from tests in which extracts from
spores are pricked into the skin, and irritated mast cells release histamine
causing inflammation. This immune response produces a pale bump
surrounded by reddened skin and is known as the wheal-and-flare reaction.
What happens on the skin is an imperfect guide to the types of allergens
responsible for inflammation of the lungs, but this test is the next best thing,
when inhaling different dusts to see which ones elicit an asthma attack
carries the risk of death. Although self-experimentation with allergens is a
dangerous venture, this was the approach taken by Charles Blackley, a
Manchester physician, who provoked his own symptoms of hay fever by
deliberately inhaling spores from moldy straw in the 1870s.9 Blackley
showed that spores or something else in the decomposing straw produced an
allergic response. The difference between hay fever and asthma, or hay
asthma, was unclear in his time, and some physicians used the terms
interchangeably. Today, hay fever is the popular term for allergic rhinitis,
which is the nasal allergy caused by pollen released from crop plants and by
fungal spores.
There are three lines of evidence that the inhalation of fungal spores is
one of the principal causes of asthma.10 First, studies have shown high rates
of fungal sensitivity in skin tests among children with severe asthma,
compared, of course, with non-asthmatic controls. Next, asthma attacks and
asthma deaths increase on days when airborne spore counts rise above one
thousand spores per cubic meter; and third, hospital admissions for asthma
increase after a thunderstorm. Thunderstorm asthma is a complicated
business. It has been assumed that spore numbers increase because heavy
rainfall soaks the surface of plants and stimulates the growth of microscopic
yeasts and molds, and the accompanying wind gusts drive the spores of these
active fungi into the air. This is the grow and blow model of dispersal.11 But
when we compare detailed meteorological records with spore counts, it
appears that there is a sharp increase in the number of spores in the hours
just before a storm.12 This is affirmed by many asthmatics who say that they
can forecast thunderstorms from a surge in their breathing difficulties, which
suggests that there is more to this dispersal mechanism than high
windspeeds. Adapting the famous aphorism of H. L. Mencken about answers
to human problems, we can agree, “There is always a well-known solution to
every [mycological] question—neat, plausible, and wrong.”
Despite this evidence, fungi seem to be an afterthought for many
specialists in the study and treatment of asthma. Barring the recruitment of
volunteers to sit in spore-filled wind tunnels and waiting for the asthmatics
to start gasping for breath, there is nothing else that can be done to convince
the skeptics. Asthma is certainly caused by other irritants, but with millions
of tons of fungal spores flying around the planet, the case is pretty tight.
Pollen and hay fever are united in popular thinking, but mold spores and
asthma remain separated. Spores are not even mentioned in Asthma: The
Biography, authored by Mark Jackson in 2009, which is an equivalent
omission to ignoring bullets in a book about gunshot wounds, or cigarettes in
a study of lung cancer.13 Jackson is not alone in the omission of the fungal
connection in asthma. Even some pulmonologists (lung specialists) show
little interest in the evidence that mold spores are a serious problem for
many asthmatics. They have one foot in the twenty-first century and the
other in the nineteenth. Clinical studies on asthma ignore the fungi, and too
many physicians continue to endorse the long-standing claim that it is a
psychosomatic condition, which it is not. This notion is a holdover from the
era when allergies became associated with the educated classes, or “persons
of cultivation,” as one Harley Street physician put it in the 1880s, before he
added that these afflictions were “proof of our [British] superiority to other
races.”14 In the following century, a German doctor pronounced that the
typical allergic patient was a delicate, “lower middle class” child, “ill-
equipped for life and … liable to maladjustment.”15 So, asthma was,
simultaneously, a badge of refinement and of ruination!
Some of the studies that have identified psychiatric contributions to
asthma have ignored the challenge of disentangling cause from effect.16 If
asthmatics display anxiety-related disorders more frequently than non-
asthmatics, this could be explained by the stress caused by their experiences
of the illness and the resulting fearfulness of the invisible “carpet monsters,”
as I put it in an earlier book, that cause their lungs to shut down.17 It is
possible, too, that genes that increase susceptibility to asthma are linked to
other stress responses. If, for example, asthma patients were more likely to
develop depressive disorders, this would not relegate asthma to the lower
status of a psychiatric rather than a physical illness, which is, of course, a
false and damaging distinction in the first place. The tendency to dismiss
idiopathic conditions—those without a known cause—as merely
psychological in origin is quite widespread. Epilepsy, fibromyalgia, irritable
bowel syndrome, and long COVID and other chronic illnesses following
viral infections are examples of health conditions for which we have been
unable to pinpoint a physical cause and have tended therefore to dismiss as
psychosomatic.18
Marcel Proust, the most famous asthmatic, was frustrated by his father,
who regarded his son’s breathlessness as a big pretense that was “due to his
insecure, sensitive, and dependent personality.”19 Proust captured the tragic
nature of this interaction between family and invalid: “the poor suffocating
patient who, through eyes filled with tears, smiles at the people who are
sympathizing without being able to help him.”
 WHY DOES FUNGAL ASTHMA EXIST?
Allergies are caused by an oversensitivity to substances that the body treats
as a threat to survival, when, in fact, the real danger lies in the symptoms of
the allergy rather than the irritant itself. The troublesome proteins on the
fungal spores are part of their structure and include enzymes that the fungus
uses to grow in the soil and on plant surfaces.20 They are harmless unless we
react to them, which begs a question: Why is anyone allergic to fungal
spores?
Compelling answers come from the perspective of evolutionary medicine,
which maintains that many illnesses are rooted in the deep ancestry of Homo
sapiens as well as the more recent history of our species. My favorite idea
comes from the suggestion that the allergic response in the lungs evolved as
a protective mechanism to limit exposure to noxious chemicals and to fungi
that can cause lethal infections.21 By narrowing the airways and reducing
lung capacity, symptoms of asthma certainly reduce the volume of inhaled
air, which would be a good thing if this was not accompanied by suffocation.
But as long as the symptoms of inflammation are short-lived, the cost of
decreased respiration may be worthwhile. Evolution is blind to suffering if
the organism lives long enough to send its genes down the great stream of
time. We have no idea how often our allergic reactions to fungal spores save
us from serious infections. Many of the spores that reach the lungs belong to
fungi that are very unlikely to grow in our tissues, although some show this
capability in patients with impaired immune systems, as we will see later in
this chapter. It is certainly possible that asthma and asymptomatic reactions
to spores are lifesavers.
The risk of inhaling spores that can cause an infection has always been
around because we live on a very fungal planet. The situation worsened
when we abandoned our ancient hunter-gatherer and nomadic lifestyles in
favor of living in agricultural settlements. Cereal agriculture demands grain
storage, and stored grain is easily spoiled by molds, whose spores can
become airborne in huge numbers.22 We see the same phenomenon in cattle
barns, where molds proliferate on animal feed and bedding materials and
create clouds of millions of spores per cubic meter of air when they are
disturbed by the livestock or farm workers. This agricultural explanation of
asthma suggests that a symptomless reaction to spores and pollen that we
possessed earlier in human history ramped up when we began to be exposed
to masses of spores on farms. As long as the children of farmers were not
debilitated by asthma and became parents themselves, the genes that
controlled these relatively mild reactions to spores would have spread. The
perpetuation of these forms of allergy as a protection against infection would
have outweighed the costs.
The jump from relatively innocuous immune responses to spores to
severe asthma may have occurred when families migrated from smaller
agricultural settlements to cities, where interactions with fungi and other
allergens were limited by the relative cleanliness of their homes. This seems
counterintuitive, because urban life separated us from the muck of the farm,
but the cleaner air meant that the immune systems of children in cities was
not conditioned properly. In the first weeks of life, the infant body was not
taught to ignore, or to react very gently, to the moldiness that had been
unavoidable on farms. This led to asthma attacks when children with this
exaggerated sensitivity were exposed to high levels of spores outdoors at
certain times of the year. The problem has become heightened among
children in the modern indoor environment, where severe asthma is an
epidemic in some cities.23 This explanation for asthma and other allergies is
known as the hygiene hypothesis. Children who live with pet dogs and cats
seem to gain some protection against allergies from the early exposure to
their dander, which supports the overall virtue of training the immune
system as soon as possible to deal with the rest of nature. The hygiene
hypothesis remains controversial, and childhood asthma is complicated by
genetic predisposition and may be worsened by bacterial and viral infections
early in life.24
Asthmatic or not, there is no escaping the fungi. All homes are moldy.
Some are very moldy. Molds grow on indoor plants and damp plant pots,
and spoil fruits and vegetables in kitchens. The numbers of spores produced
by fungi can become hazardous in the perpetual dampness of some older
houses and in any building that is soaked by a plumbing leak, damaged roof,
or flooding.25 Encouraged by warm weather and poor airflow, fungi will feed
on the natural plant-based materials in carpeting, in furniture, and on the
paper that covers drywall (or plaster as it is known in the United Kingdom).
The walls of some flooded homes are blackened with spores, and the chairs
and couches become covered with a thick felt of spores. In the worst cases,
the numbers of spores rise well above the threshold of ten thousand spores
per cubic meter of air that can be very problematic for asthmatics. Even the
cleanest homes blossom with mold colonies and brim with their spores.
There is even some evidence that a greater variety of molds grow in homes
that have been scrubbed with cleaning products that kill bacteria, which
mirrors the overgrowth of yeasts on the body when we take antibiotics.26
There is a lot of overlap between the fungi that cause asthma in the urban
environment and the most prevalent species on farms. These are the typical
species that grow on all kinds of plant materials and include Aspergillus,
Alternaria, Penicillium, and Cladosporium—it is very likely that you have
been inhaling some of these spores since you began reading this chapter.
They are, as I have said, everywhere. A few of these fungi are capable of
producing harmful compounds called mycotoxins, but there is no evidence
that they can reach the lungs in sufficient quantities to cause tissue damage
(we examine mycotoxins in chapter 8). The problem with indoor molds is
the same as outdoor molds and lies with allergy.

TREATING ASTHMA
Reducing exposure to allergens may be the best way to prevent asthma
attacks, but this is difficult or impossible if we are unsure about the identity
of the irritants. Vacuuming bedrooms and covering mattresses have been
recommended to reduce the inhalation of proteins present in the feces of dust
mites, but these methods do not turn out to be very helpful.27 The ubiquity of
face masks during the COVID pandemic provided a global test for their
effectiveness in limiting asthma symptoms, but we missed the opportunity to
gather data from patients. There was also some resistance among asthmatics
to wearing face masks because some types produce a small dip in oxygen
levels in the bloodstream, which is problematic for patients whose lung
function is already impaired. Moderate improvements in asthma control have
been reported in Japanese children who wear masks during sleep, whereas
almost half of the American adults with asthma who responded to an online
survey said that masks increased their breathing difficulties.28 There is an
opportunity here for the invention of a mask that traps fungal spores without
reducing oxygen levels, but this may require a motorized pump to increase
the airflow through the filter. With the discomfort and social stigma
associated with wearing the simplest cloth masks, a rubbery helmet that
makes a whirring sound is not going to cut it. Pending technological
advances, asthmatics might consider experimenting with conventional masks
during the moldiest times of the year.
Treatments for asthma symptoms are the same whether fungal spores are
the trigger or pollen grains, pet dander, or dust mites. These range from
drugs that counter the effects of the allergens by dilating the airways in the
lungs to steroids that dampen the activity of the immune system and asthma-
specific drugs that block the explosive response of mast cells when they
latch on to the troublesome allergens.29 The first of the targeted treatments
was discovered by Roger Altounyan, a Syrian-born British physician and
pharmacologist who suffered from severe eczema and asthma.30 In the
1960s, Altounyan studied the effects of drugs based on a chemical isolated
from a plant called bishop’s weed that had been used as a folk medicine to
treat asthma for thousands of years in the Mediterranean. His colleagues at a
drug company had manufactured hundreds of different compounds related to
the medicine from the plant, and Altounyan adopted the role of the
laboratory guinea pig, inducing his own asthma attacks by inhaling dust
particles and seeing which of the chemicals alleviated his breathlessness. He
carried out three thousand tests over eight years. On some occasions, Roger
reduced his lung capacity by 90 percent and had to inject himself with an
emergency medicine to avoid asphyxiation. (It takes an asthmatic to
appreciate his bravery.)
Following a eureka moment in 1963, Roger singled out a compound
called cromolyn as the miracle cure. This was marketed as an inhalable
medicine in 1968, in time to rescue me from a bedridden childhood.
Altounyan also devised the “spinhaler” that was used to deliver the drug.
The spinhaler was fitted with a propeller that began spinning when the user
drew air through the intake by inhaling. Airflow through the spinhaler
distributed cromolyn powder from a disposable capsule. It is still in use
today. Inspiration for the propeller came from Roger’s service as a flight
instructor in the Royal Air Force during the Second World War. Roger was
motivated by his own asthma, balking at the prevailing medical opinion that
his illness was a sign of emotional inadequacy. He died in 1987 at the age of
sixty-five from an asthma attack. He is my hero.
Asthma medicines have diversified and strengthened in recent decades.
This is a very good thing because more than 300 million people suffer from
asthma, and the number is expected to exceed 400 million within the next
few years.31 These statistics are based on physician-diagnosed cases, and the
number of asthmatics doubles to almost 700 million when we consider
online responses from people who say that they have experienced wheezing.
In individual countries, the asthma rates range from a low of one in fifty
people in China to one in three in Australia. There is a general trend toward
higher case numbers in wealthier countries, but there are plenty of
exceptions. Despite their twofold difference in per capita GDP, New Zealand
and Costa Rica have the highest rates of asthma in the world. Variations in
the distribution of particularly irksome fungi could explain the geography of
asthma, although many other factors could also influence the prevalence of
the illness. By whatever mechanism, moving to a different region can prove
a matchless remedy for some asthmatics. This worked for me, with relief
from my breathlessness found by crossing the Atlantic, and its resumption on
return visits to Oxfordshire. Mine is a compelling experiment with a sample
size of me, but the geographical escape mechanism seems to be a common
experience for voluntary and involuntary migrants.32
Allergic rhinitis affects as many people as asthma and has the same
underlying immunological mechanism involving histamine release from
mast cells.33 Inflammation of the nasal passages can spread to the lower
airways, and asthmatics are often plagued by both conditions. Inhalation of
fungal spores can also cause a different illness called hypersensitivity
pneumonitis. Symptoms of pneumonitis include breathing difficulties,
coughing, and fatigue, in the chronic form of the illness, and flu-like
symptoms in an acute response to inhaling huge numbers of spores or other
irritants. The immune response is quite different from the inflammation of
asthma and is similar to the process that underlies rheumatoid arthritis. Farm
workers are frequent victims, which is not surprising, and musicians who
play bagpipes and other wind instruments are also vulnerable to this
condition.34 Spores are a hazard on farms when they overwhelm the lungs of
a worker moving rotting grain or animal feed and bedding, and become a
problem in bagpipes, trombones, saxophones, and tenor horns when
moisture and phlegm from the players combine with the interior coatings of
the instruments to create a matchless breeding ground for fungi. Mushroom
workers are also prone to hypersensitivity pneumonitis for the more obvious
reason that their livelihood depends on cultivating millions of natural spore
fountains in enclosed spaces.
The need for research on fungal allergies and the development of
effective medicines for alleviating the worst symptoms is growing because
climate change is likely to increase the number of spores in the air. Regions
that experience warmer and wetter weather will become especially moldy as
fungi flourishing on plant debris generate more spores. This asthmatic future
is developing already, with a major study from the San Francisco Bay Area
showing that the mold and pollen seasons have been extended every year
since 2002, increasing the number of days when asthmatics are inhaling lots
of spores and pollen.35 Long-term trends in spore counts are very difficult to
predict and will respond to regional differences in weather patterns and
changes in land use, including the clearing of grasslands and forests for
cereal cultivation. Fellow asthmatics: keep your inhalers ready.

FROM ALLERGY TO INFECTION

Fungi that cause asthma and other allergic illnesses are visitors to the human
body, fly-by-nights rather than long-term residents of the mycobiome. Some
of the spores that carry allergens can also germinate in the nasal passages
and the lungs and develop into mycoses, but the healthy body sheds these
along with every other spore and irritating dust particle using mucus as a
trap. With each inhalation, air is vacuumed through the 12-millimeter-wide
windpipe, which divides into the pair of bronchi, and onward into the
narrower airways that branch more than twenty times until they feed into the
alveoli. The alveoli are attached to the tiniest branches in the lungs and look
like bunches of grapes. This glistening labyrinth has a surface area of 100
square meters, which is three or four times larger than the skin and its hair
follicles. Spores and bacteria and other particles stick to the mucus that lines
the breathing apparatus, and this viscous fluid is swept upward by trillions of
cilia attached to the cells lining the tubing that lash around ten times per
second.36 This motion clears the mucus from the microscopic alveoli, all the
way up to the trachea, or windpipe, between the vocal cords, and into the
back of the throat. Mucus reaching the throat is swallowed and dissolves in
the acid bath of the stomach. This mucus conveyor belt runs continuously,
transporting fluid all the way from the alveoli to the throat in about six
hours. Coughing accelerates the waste-removal system by forcing gobbets of
mucus from the lungs into the throat and spraying thousands of droplets into
the air at a speed of 60 miles per hour (100 kilometers per hour). Sneezes are
even more violent, discharging one hundred thousand drops of mucus at
twice the speed of a cough.
We are unconscious of this brilliant machine until it gets clogged, and
fungal infections tend to develop when this happens. Cystic fibrosis is an
illness that messes with the conveyer belt by thickening the mucus. This
means that fungal spores and bacteria are not cleared as swiftly as normal,
and the condition leaves patients open to infection than those with sufficient
fortune to be born with runnier mucus. Spores of Aspergillus species are the
most problematic because they are everywhere and can germinate if they are
not cleared from the lungs. This can lead to allergic bronchopulmonary
aspergillosis (ABPA), which is an illness that worsens mucus buildup and
obstruction of the airways in cystic fibrosis patients.37 ABPA also occurs in
asthmatics whose illness does not respond to the usual medicines. Fungi can
also colonize the lungs and develop into serious infections. Antifungal drugs
can be effective at eliminating these fungi in the short term, but this does not
reduce the risk of a later infection. Any of the health conditions that diminish
lung function increase the likelihood that fungi will settle in the recesses of
our airways and implant themselves in our tissues.
Aspergillus species and other fungi get stuck in the nasal sinuses too and
can expand into a clump of filaments called a fungus ball that presses on the
surrounding tissues. Symptoms range from headaches to pain and tenderness
in the area of the sinuses above and below the eyes and on to changes in
vision and proptosis, when the eyeballs protrude from their sockets. Long
before most patients get to this stage, surgery is performed to remove these
hideous fungal excrescences. Besides aspergillosis, the most prevalent
fungal lung infections are histoplasmosis, blastomycosis, and
coccidioidomycosis, whose names refer to the fungi that cause them.38
Fungal growth in the lungs is countered by the cells of the innate immune
system that hang around in the lungs, primed for action. These are
macrophages and neutrophils that gobble up the germinating spores and
release inflammatory chemicals to recruit more cells to the battle.
Neutrophils are the most abundant type of white blood cell, with twenty
billion or so circulating in the bloodstream, which equates to fifty thousand
in a pinpricked drop. Predatory neutrophils are larger than the spores that
they consume, but the feat of engulfing one is comparable to a human
swallowing a Halloween pumpkin. Neutrophils also deploy chemical
weapons that work as disinfectants and bleaching agents to destroy fungi
without having to eat them.
When the number of neutrophils drops below a critical threshold, the
fungi overcome these defenses and penetrate the walls of the lungs and move
into surrounding tissues. Fungi can also make their way into the bloodstream
and become distributed all over the body in disseminated infections. This
explains why illnesses that reduce neutrophil counts, including leukemia,
anemia, and HIV/AIDS, are associated with aspergillosis and other lung
infections.39 The risk of serious mycoses also increases when the immune
system is upset by steroid medicines used to support patients after organ
transplantation and to treat allergies and autoimmune diseases.40 Cases of
aspergillosis increased during the COVID pandemic when patients who
developed pneumonia were treated with these drugs to control lung
inflammation.41
Aspergillosis is a global infection, whereas the fungi responsible for
histoplasmosis, blastomycosis, and coccidioidomycosis are confined to
particular regions.42 Histoplasmosis, caused by Histoplasma, lives in the
central United States. This mycosis is also known as Ohio Valley disease.
The fungus thrives in bird and bat feces, and so its spores are concentrated in
chicken coops, caves, and abandoned buildings. Everyone in this region is
exposed to the fungus, but its growth in the body is stopped in its tracks by a
functioning immune system. The distribution of Blastomyces, which causes
blastomycosis, overlaps with Histoplasma, and extends northward around
the Great Lakes and southward to the Gulf Coast. It is a soil fungus and is
destroyed by macrophages and neutrophils in the lungs.
Coccidioidomycosis, or San Joaquin Valley fever, is caused by Coccidioides,
which grows in the southwestern United States and northern Mexico and is
also established in parts of South America. It is a soil fungus whose spores
are lifted into the air in dust storms. Like the other mycoses, few people
show any symptoms of infection by this unpronounceable fungus before it is
squelched by the immune system. Dogs are also susceptible to this fungus
and suffer from higher rates of infection and more frequent complications.43
Related species of fungi are responsible for an African version of
histoplasmosis and South American variety of coccidioidomycosis in
humans.
None of these mycoses that begin as lung illnesses are common compared
with the burden of viral infections. Aspergillosis affects 300,000 people
globally every year; the American and African species of Histoplasma cause
100,000 annual infections; 25,000 patients develop coccidioidomycosis; and
blastomycosis is the rarest of the quartet, limited to 3,000 infections in the
eastern United States.44 Regional outbreaks of these diseases occur every
year. Wisconsin is a hotspot for blastomycosis, where humans and dogs are
attacked by the fungus that grows in soils along riverbanks and rotting
vegetation. In the adjoining state of Michigan, more than ninety workers
developed the illness in a paper mill in 2023.45 These disease clusters attract
media attention and encourage the impression that fungal lung infections are
becoming more common, but the evidence is equivocal. Either way, the most
serious symptoms of fungal infection develop when the immune system is in
very bad shape. Antifungal drugs can be effective at halting the growth of
the fungi or eliminating them completely in some patients, but the loss of
those neutrophils means that the infections are liable to reboot from residues
of the fungi in the body or from fresh spores arriving in the lungs. The
mortality rate for these pulmonary mycoses soars in older patients whose
immune systems have collapsed.
 All of these lung infections begin with the inhalation of spores that are
floating in the air. One infectious fungus behaves very differently. This is
Pneumocystis, a yeast that does not produce spores at all. Pneumocystis is
found in the lungs without causing any illness, but develops into a full-
blown, life-threatening form of pneumonia in HIV-positive patients when
they develop AIDS.46 The incidence of Pneumocystis pneumonia, or PCP,
follows the number of AIDS cases, so it is not surprising that this mycosis is
common in Nigeria and other African countries which have the highest rates
of HIV infection. PCP also develops in transplant patients. There are many
unanswered questions about Pneumocystis because it cannot be grown in the
laboratory in culture dishes. We are not even sure how it gets into the lungs,
although outbreaks of the infection in hospitals suggest that the yeast cells of
the fungus are transmitted from person to person in droplets of lung mucus
expelled by coughing or normal breathing. No other fungus seems to be
dispersed in this viral fashion.
Our breathing apparatus is a glorious contraption when it works perfectly.
Hindus believe that we are allotted a predetermined number of breaths for
our lifetime, which approaches five hundred million ins and outs for the
global average life expectancy of seventy-three years. With half a billion
flushes of gas over the 100 square meters of tubing and air sacs in our
bodies, this is the region of greatest contact with the fungi and affords the
greatest prospects for infection. Allergies to spores and the opportunities for
fungi to take root in the lungs fall into the category of unpleasant
interactions with the mycological world. There is a lot of uplifting news to
come in this book, but next we will look at how bad things can get when
fungi spread around the body. Even Proust would agree that these deep-
seated mycoses make an asthma attack seem like une promenade de santé.

OceanofPDF.com
 4
Spreading
OPPORTUNISTS IN THE BRAIN

IN 1997,fifteen-year-old tennis player Sasha Elterman was thrown into the

polluted water of the Yarkon River in Israel when a footbridge constructed
for the Maccabiah Games collapsed. The Maccabiah Games are held every
four years and are often referred to as the Jewish Olympics. Sasha was a
member of the Australian athletics team, which had been crossing the bridge
when the support beams broke. Struggling to keep her head above the
surface, she swallowed and snorted the filthy water before she was dragged
to the muddy bank. One athlete died at the scene, and sixty-seven team
members were taken to local hospitals. None of the injuries seemed to be
life-threatening at first, but within hours many of the victims, including
Sasha, developed breathing difficulties. Three more athletes died over the
next few weeks. Early on, it was thought that they were poisoned by
chemical pollutants in the river, which included oil, solvents, and toxic
heavy metals. These ideas were scrapped a few days later when analysis of
lung tissue from one of the autopsies revealed something else: the threads of
a fungus called Scedosporium.
Sasha was flown to a hospital in Sydney after treatment in Israel and
remained in critical condition for months. She continued to be upbeat during
this ordeal, but the development of a brain infection by the fungus worsened
her prognosis. As the illness progressed, she endured multiple surgeries to
remove infected tissue from her damaged lungs and brain.1 All the while, the
fungus resisted a battery of drug treatments. It kept coming back. Running
out of options, her doctors decided to try a new medicine called
voriconazole, developed by Pfizer in the United Kingdom. As this potent
compound suffused the infected tissues, the microbe began to lose the fight,
disappearing in one location, then another, until, at last, the ghastly fungus
was gone. Three years later, after intensive rehabilitation, Sasha was well
enough to carry the Olympic torch in the relay at the Opening Ceremony of
the 2000 Summer Olympic Games in Sydney.
Sasha’s story tells us something about a very different kind of relationship
between humans and fungi from the lifelong interactions between the body
and the resident mycobiome. Most of the serious mycoses are caused by
fungi that we encounter in the environment every day but that cause
infections only when the immune system is debilitated. Sasha’s fungus was
an oddity that was forced into her body by her accident and battered its way
through her intact immune defenses. To understand this case history, we
need to look at the fungus from the Yarkon River more carefully. Like most
of the fungi in this book, Scedosporium has never been given a common
name. We are stuck with the Latin, which refers to seeds or spores. This fails
to conjure up a distinctive image of the microbe, so imagine looking through
a microscope: within the bright circle, the fungus comes into sharp focus as a
gossamer of cylindrical filaments, plumped with internal droplets of oil and
bristling with stubby side branches bearing oval spores. The fungus is
beautiful in its simplicity when it is grown in a culture dish in an incubator;
sinister when highlighted with purple stain in a thin slice of brain tissue
taken from a refrigerated cadaver in the morgue.
Fungal brain infections in people who come close to drowning are rare
and very difficult to treat when they are diagnosed. A case of Scedosporium
infection in Germany involved a forty-one-year-old woman in an automobile
accident who was thrown from her car into muddy water. She was
resuscitated at the scene but developed several brain abscesses over the next
five days. These appeared as white spots on her MRI scans, some as big as
grapes, and the fungus was identified as the culprit from DNA extracted
from samples of brain tissue. The woman experienced a range of distressing
neurological problems including epileptic convulsions as her doctors
exhausted the catalog of antifungal drugs. Her condition improved,
eventually, and her case history was published after ten years of treatment.2
At that time, she had been in a stable condition for two years, which speaks
to remarkable resilience. A study of more than a hundred cases of infection
by this fungus revealed a median survival time of just four months.
The mechanism that Scedosporium uses to invade the brain has not been
solved, but the central nervous system is an attractive sanctuary from the
point of view of the fungus. Tipping the scales at an average of 1.3
kilograms, the brain contains more calories than a large roast chicken.3
Getting in there is difficult. The hard skull is an obstacle for animal
predators, which explains why lions and other carnivores go for the more
accessible organs slithering from the abdomen when they rip into their prey.
Microbes make their way into the brain via blood vessels that snake through
perforations in the skull called foramina and fissures. This gets them into the
head, but before they can reach the squishy nerve tissue, they have to
overcome the blood-brain barrier, which is a formidable challenge. This is
formed by a layer of cells that lines the interior of the blood vessels feeding
the brain. These cells are wedged together, side to side, preventing large
molecules and any microorganisms circulating in the bloodstream from
passing into the brain. Fungi use a number of different mechanisms for
crossing this hurdle. Some mount a chemical attack, releasing enzymes that
weaken the protective cell layer. Others use a Trojan horse strategy, hiding
inside white blood cells that move across the barrier as part of the natural
operation of the immune system and spilling out on the other side. Once they
find themselves brain-side, the fungal cells multiply, forming the abscesses
that show up as islands of damaged tissue on CT and MRI scans. The
immune defenses are concentrated in the outermost tissues of the brain,
where they resist invaders. Once inside the brain, the fungus is free to do its
worst.
The association between brain infection and traumatic incidents of near
drowning suggest that the blood-brain barrier is weakened by the pressure of
the water forced into the nasal passages. Carried with the water, the fungus
responds by trying to hang on, doing everything it can to survive. In Sasha’s
case, and the German patient, the fungus found food, grew itself in knots,
and spotted the brain with abscesses. This species does not seem to be
especially adapted to growing in brain tissue, but it does a lot of damage
when it finds itself there.
Scedosporium does not confine itself to victims of near drowning. It also
multiplies in patients whose immune systems have been weakened by HIV
infection or cancer, and in those whose defenses are lowered by drug
treatments following organ transplantation.4 The loss of immune function
makes it more likely for a fungus to spread into the bloodstream.
Scedosporium is widely distributed in nature and seems to be particularly
prevalent in water contaminated with sewage from humans or farm animals.
Industrial farms create a perfect habitat for this fungus in the form of the
abundance of animal waste dammed in ponds lined with black plastic and
weighted down with tractor tires around the rim. One spectacularly
unpleasant case history involved a young man in Brazil who died from a
brain infection caused by the fungus three months after he fell into one of
these reservoirs of swine sewage.5 Scedosporium also lives in lake water and
has been found in the soil of potted plants in hospitals. The fact that so few
people become infected with this fungus says everything about the power of
the immune system to protect us, as long as we avoid a rare accident and
nearly drown in water that it calls home.

OPPORTUNISTS
The fungus that sickened Sasha Elterman is one of thirty or more species
that have been identified in brain infections, and these are a subset of the
three hundred kinds of pathogenic fungi that cause disease all over the body.
Given that there are more than seventy thousand species of fungi, and some
experts think there may be more than one million, the nasty ones belong to a
tiny minority—less than 1 percent of the total number of species that have
been described by scientists and given a Latin name.6 The pathogens
represent a splinter group from the great fungal kingdom, whose principal
concern over hundreds of millions of years has been with decomposing dead
plants and partnering with live ones or attacking them. Doing the same
things with animals—rotting, cohabiting, and infecting—is a secondary
profession for the mycological world. Next to these long-standing activities,
making our lives a misery is a very recent specialty. Because humans have
such a short evolutionary history, the fungi that invade human tissues were
occupied with other tasks long before they found themselves inside our
bodies. This explains why, by and large, they are not very good at making
their own way from the outside environment into our tissues. Even though
they are total losers as pathogens compared with viruses, they still cause a
lot of trouble, killing more than 1.5 million people every year. This is an
astonishing toll when we consider that only four hundred thousand people
die from malaria.7
Mortality figures for fungal illnesses, meaning how many infected people
die, match those for tuberculosis, which is caused by a bacterium. Many of
the deaths due to tuberculosis and to fungal disease occur in AIDS patients
whose immune defenses have been overwhelmed by HIV infection.
Physicians who treated AIDS cases in the early 1980s, before the virus was
identified as the cause of the illness, were alarmed by a surge of fungal
infections seen in young men. Patients displayed a form of fungal
pneumonia as their immune systems failed and fungal brain infections
became another sign that someone had developed full-blown AIDS.8 Serious
fungal infections are much less frequent in HIV-positive patients today if
they are receiving the excellent drug therapies that control the virus, but
proper treatments are scarce in parts of sub-Saharan Africa and Southeast
Asia.9
Research on the link between AIDS and fungal infections has helped to
explain how the functioning immune system keeps the body free from these
diseases. The greatest damage from the virus comes from its destruction of a
specific type of white blood cell that is a key player in the seek-and-destroy
mission of the immune system. These are the helper T cells. This also
explains why certain forms of leukemia that deplete these cells are
associated with the same mycoses. A similar reduction in white blood cell
count is seen in patients treated for cancer by chemotherapy or radiation
therapy, as well as in transplant recipients who take drugs to prevent organ
rejection. When the shield of T cells fails, the onboard mycobiome becomes
restless, mottling the skin, plugging the nasal sinuses, whitening the tongue,
and fouling the throat before spreading from the lungs and the gut to the
liver, kidneys, and brain. These harmless symbionts that turn bad are joined
by airborne spores that land on the defenseless body, and we are taken apart
piece by piece. The fungi that drop anchor after immunological damage or
injury are called opportunists or opportunistic pathogens. All of the fungi
that cause serious infections in humans are opportunists. Although only a
few hundred species of fungi have been associated with tissue damage, it is
possible that thousands of fungal species can harm us if they find themselves
in a defenseless body. It has even been suggested that the ability to cause
disease in humans is a defining characteristic of the kingdom.10
This concept of universal pathogenicity seems ridiculous when we think
about mushrooms that grow in the woods, but colonies of these fungi that
form fruit bodies do cause lethal infections.11 Human tissues are not the
preferred food for mushroom mycelia, but these fungi make do when they
find themselves in an unprotected body. Consider the case of a six-year-old
girl with kidney cancer who developed a swelling on her head that split open
and discharged pus. When samples from the wound were transferred to a
culture dish, the pathologists were shocked by the growth of a mycelium of
an ink cap mushroom that lives on animal dung in the wild.12 The girl was
treated successfully by surgery to remove the infected tissue and a course of
antifungal medicines. This was a bizarre infection, although the same
mushroom has been found in lung tissue and can damage heart valves after
cardiac surgery. Authors of a case history from the Mayo clinic involving a
seventy-seven-year-old woman with clots on her replacement mitral valve
titled their report, “Truffle’s Revenge: A Pig-Eating Fungus.”13 The ink cap
mushroom had grown over the “bioprosthetic” valves, which had come from
a pig.
Appearing less menacing than any mushroom—indeed, as harmless as a
loaf of bread—Saccharomyces cerevisiae, the yeast used for raising dough
and brewing beer, causes lethal infections in exceptional instances when it
passes into blood vessels through a catheter. The idea that the fungus
purchased as a freeze-dried powder in the grocery store can kill seems
absurd. But it can, and, like the ink cap, baker’s yeast is a perfect example of
an opportunist.14 It is important to recognize that these are extreme
curiosities in the literature of infectious disease that should not discourage
mushroom hunting or alarm any bakers or brewers. These freakish infections
are astonishingly rare.
The best way to think about opportunistic pathogens is that they sit along
a whole spectrum of behavior, with varying degrees of preparedness and
capabilities for messing up our lives.15 Fungi that cause athlete’s foot and
toenail infections are examples of more purposed pathogens than the ink cap
mushroom because they are so well adapted to growing on skin and nails.
These fungi live parallel lives in soil, where they consume scraps of animal
protein and other organic materials, but they are accomplished at making
themselves comfortable when we pick them up by walking barefoot over
their territory. Contact with these fungi does not necessarily lead to an
infection, however, because some people are affected by athlete’s foot
throughout their lives and others are not.
Returning to the fungi that grow in the brain, they share some
characteristics that are fitted to this loathsome business.16 The ability to grow
at the elevated temperature inside the body is an obvious prerequisite for a
fungus that causes brain infections. This is not asking much of
microorganisms that thrive in the summer temperatures experienced over
much of the planet, but it does discount species adapted to cooler climates.
Fungal pathogens must also be equipped to outwit the remaining strength of
the immune system in weakened hosts. A lot of the brain pathogens appear to
benefit from the presence of melanin within the walls of their cells that gives
them a black or brown color.17 This fungal version of melanin is a different
pigment from the chemical that colors human skin, and it acts as a chemical
mop that neutralizes some of the natural disinfectants produced by the
immune system. Pigmentation may also help the fungus in other ways, by
stabilizing its cells at higher temperatures and furnishing protection against
ultraviolet light. Despite these features that help some fungi grow inside the
body, the prevailing view of experts in medical mycology is that these
opportunists do not want to be there in the first place.
To understand this reasoning, we need to think about evolution. Viruses
and bacteria that cause infectious diseases multiply in our tissues and move
from person to person in droplets released by breathing, sneezing, or
coughing, via skin contact and through sexual behavior. Insects and other
animals act as vectors that transmit viruses and bacteria, and mothers can
pass infections to their developing babies through the placenta and in breast
milk after birth. This list of infection pathways covers most of the ways that
microbes spread between humans. Fungi that grow deep inside the body
have no mechanism for escaping.18 This means that a fungus that forms
colonies in the brain is doomed. It will die with its host. If the corpse
decomposes in soil, the fungus may seep into the dirt as the tissues dissolve
and go on to reproduce in the environment, but there is nothing about
lingering in the host that made the passage worthwhile. Infecting humans is
a dead end for fungi, which explains why they are no good at causing
pandemics like viruses. Molds that cause athlete’s foot are an exception to
this rule, and the yeast Candida auris, which is causing serious infections in
hospital patients, does not threaten the general population (see chapter 2).19
Most fungi are happy in the soil, and we would be happier if they stayed
there. Fungal infections of humans, or mycoses, are part of the noise of
biology that present no advantages to the pathogen or the host. These
mutually harmful relationships have been termed synnecroses.20
 Even though it is content growing outside the human body, another
fungus called Cryptococcus neoformans is remarkably good at causing brain
damage. It has attracted the attention of medical mycologists since it was
identified as the agent of brain infections in AIDS patients. Since then,
cryptococcosis has become a disease of global proportions that is responsible
for more than half a million deaths per year in the developing world. The
fungus spreads through the brain, damaging nerve cells and forming cysts in
different regions. The membranes, or meninges, that surround the brain
become inflamed, and this results in brain swelling. As the infection
develops, symptoms include persistent headaches, neck pain, and
drowsiness, and these can progress to disorientation, difficulty finding
words, nausea and vomiting, leg paralysis, convulsions, strokes, and death.
Although rare infections by this fungus occur in otherwise healthy patients,
most cases of cryptococcosis are associated with weakened immune
defenses, which explains why the disease is more common in countries with
high rates of HIV infection.21
Cryptococcus is a soil fungus whose growth is energized by bird
droppings. Utopia for this fungus is a chicken coop or pigeon roost, and it
does not need to waste any time inside human beings. Getting into us as an
airborne spore is a misstep. Most fungal spores that we inhale are swept
from the narrowest airways to join the conveyer belt of mucus that moves
upward to the throat and drops down into the stomach where the daily dose
of microbes goes to die. Cryptococcus is one of the few organisms that can
dodge this fate when conditions are ripe, cross into the bloodstream from the
lungs, and move through the barrier into the brain.
The ability to outwit the immune system, especially if it is weakened, is
probably a consequence of the natural behavior of the fungus in the soil
where it grows as a form of budding yeast. These cells are preyed on by
amoebas, which consume all kinds of microbes in the soil and digest them in
food vacuoles within their cells. Certain strains of Cryptococcus avoid this
fate and manage to stay alive inside the vacuoles, and the same trick allows
the fungus to survive when it is engulfed by the macrophages of the immune
system that feed like amoebas. (Strains are like breeds rather than separate
species.) They stay inside the food vacuoles of the macrophages, hitchhiking
until they are vomited, unharmed.22 Cell biologists call this mechanism
vomocytosis, so I am not being overly poetic here. The bad stuff unfolds
when a macrophage with stowaway Cryptococcus crosses the blood-brain
barrier and releases its cargo. The life of this fungus will end when the
patient dies, but, in the meantime, it feeds and reproduces by forming buds,
and the brain abscesses multiply with each CT scan.
Treatment options for cryptococcosis are very limited. The handful of
drugs used to combat this infection have serious side effects and have not
been updated since the 1990s.23 Amphotericin B is a natural product isolated
from a soil bacterium. It disrupts the cell membrane of the fungus but also
damages the kidneys. A second medicine, flucytosine, interferes with the
formation of DNA and proteins in the fungus. The problem with this one is
that it causes liver damage. Fluconazole is the third antifungal drug used to
treat cryptococcosis. This belongs to the azole family of antifungal agents
that also target the cell membranes of fungi. It has fewer side effects than the
other medicines, but its drawback is that it limits the growth of the fungus
without killing it. For this reason, it is used for “maintenance therapy,” to
keep patients in a stable condition. It cannot rid them of the infection.
Someone with a strong immune system who contracts the disease can be
cured with a combination of these drugs, whereas the long-term outlook for
a patient with weakened defenses is not as reassuring. The mortality rate for
cryptococcosis for HIV-positive patients approaches 80 percent within one
year of diagnosis in some developing countries. These disheartening
statistics and the inadequate treatment options led the World Health
Organization to rank Cryptococcus in the Critical Priority Group of
pathogens that require urgent interventions, including the development of
new drug therapies.24

THE HORROR OF MUCORMYCOSIS

Few people have ever seen Cryptococcus for themselves, or any of the other
pathogenic fungi that I have described, for that matter. This would take a
microscope and access to samples of infected tissue. You would need to have
taken a microbiology course in medical mycology to have enjoyed this
honor, and these are very few and far between. Surprisingly, however, there
is one type of fungus that can disfigure faces and destroy brain tissue that
almost everyone has seen without a microscope. These are the black bread
molds, which are so common on spoiled tomatoes and other fruit that we do
not give them a second look before relegating the rotting food to the
compost heap. The mycelia of these species of Rhizopus and Mucor feed on
our groceries before forming millimeter-tall translucent stalks tipped with
blackened bulbs. Each of these bulbs contains hundreds or thousands of
microscopic spores that are dispersed by air currents and start new colonies
when they land in our fruit bowls. The stalks are quite beautiful when they
are magnified with a hand lens, appearing as a miniature forest of crystalline
stems bearing their tiny, blackened globes. It is difficult to reconcile this
prettiness with the photographs of swollen, reddened, and sometimes
noseless and eyeless faces of the victims of “mucormycosis” on the internet.
But this is what these fungi can do.
The first thing to make clear is that there is nothing that we can do to
avoid this infection, and that with an estimated two cases of mucormycosis
per million people per year, you are more likely to be attacked by a moose
than a bread mold.25 The reason that the infection is unavoidable is that the
spores of these fungi are floating around indoors and outdoors in huge
numbers and they get trapped in our nostrils every day. The rarity of the
infection is more difficult to explain, but there are some pointers. Many
patients who develop mucormycosis have preexisting illnesses including
cancer and uncontrolled diabetes or have been severely burned. Others are
taking medicines that interfere with their immune systems. Cases also occur
in patients after surgery, and in premature babies.
The bread molds show no subtlety in the biological mechanism of their
attacks. There is none of the Trojan horse behavior seen with Cryptococcus,
which allows the fungus to slip unnoticed into the brain hiding in a
macrophage. In mucormycosis, the spores germinate in the mucus in the
nasal passages, send their filaments into the soft tissues, and wangle their
way into the brain by growing along the walls of the blood vessels. The
disease is a classic example of an opportunistic infection. It has maintained a
stubborn mortality rate above 50 percent for decades because surgery is the
only treatment and involves carving away the infected tissues. This is the
reason that some patients lose an eye to the disease or, worse, are left with a
large opening in the middle of their face. This is as horrible an infection as
one can imagine. It is the stuff of nightmares, and none of the antifungal
drugs seem at all effective in controlling this beast once it takes hold.
Mark Tatum, a forty-four-year-old from Kentucky, suffered a horrific
encounter with one of these fungi in 2000 that destroyed much of his face.
To save his life, surgeons removed his eyes, nose, upper jaw, and masses of
surrounding soft tissue and cheekbone. To counter the pain following this
butchery, he was placed in a drug-induced coma for two months. His wife,
Nancy, said, “His doctors told me it was one of the most extensive surgeries
they’d ever performed on a person’s face.”26 She continued, “When I went
into the critical-care unit … they expected me to faint, but when I looked at
my husband, I just saw Mark.… I looked into the cavity on his face.… I saw
the lining of his brain and the top of his tongue, but I know Mark is more
than his face. He is my husband, the man who gave me everything I had ever
wanted.” Something of his original appearance was restored with a
removable prosthetic mask that was attached to a frame with magnets. His
story was broadcast on television, and his bravery and good humor inspired
people all over the world: “I didn’t do nothing noble,” Mark said, “I just did
what was necessary.” He and Nancy pursued their lives with astonishing
grace until his death in 2005.
Mark Tatum’s infection may have been triggered by his use of steroids to
treat back pain. Corticosteroid drugs work by dampening the inflammatory
response that is one of the foundations of our immune defenses, meaning
that they can make us more likely to become infected by fungi. This is the
reason for the epidemic of mucormycosis in India during the COVID-19
pandemic. More than four thousand “black fungus” deaths were reported by
the summer of 2021 in patients treated with corticosteroids to mitigate the
hyperimmune reaction to the virus known as the cytokine storm.27 (This
storm of inflammatory compounds damages the lungs and other organs and
was a leading cause of death from COVID-19.) On the plus side, steroid
treatment was a lifesaver for many patients who were critically ill with
COVID-19, and the number of fungal infections remains vanishingly small
among the hundreds of millions of people treated with steroids for other
illnesses.
Another forceful illustration of the link between steroid use and fungal
infections comes from an outbreak of a different mycosis in patients given
spinal injections with a corticosteroid for pain control in 2012. Across the
United States, there were more than seven hundred cases of meningitis and
spinal infections, and sixty-three patients died. An investigation by the
Centers for Disease Control determined that the infections were caused by a
fungus called Exserohilum, which normally grows on grasses.28 Batches of
the drug preparation were contaminated with the fungus. It would be
difficult to think of a more powerful demonstration of the connection
between the immune system and development of fungal disease. The
injection of the fungus into the spine along with a drug designed to muzzle
the immune system guaranteed disaster. This tragic accident illustrates how
modern medical practices can make us vulnerable to the oddest kinds of
fungal disease.

THE BRAIN MYCOBIOME

Even though the chain of events leading to most serious fungal infections is
rarely as clear as the meningitis cases caused by the contaminated spinal
injections, we can find answers by examining the medical records of patients
before their infections, identifying the fungi growing in their tissues, and
tracking the progression of their illnesses. Sometimes we can develop a
pretty good picture of what happened, but other case histories remain
baffling. Why one person in a million with an apparently healthy immune
system develops an incurable infection by a fungus that seems to be present
in just about every soil or water sample on the planet is beyond our
comprehension. Whether a physician knows how their patient became
infected, or has no idea, the options for treating the illness are the same and
remain too limited for comfort.
This sense of uncertainty in the field of medical mycology has grown
with the highly controversial claim that fungi may be involved in
Alzheimer’s disease and other neurological conditions. This idea has been
spurred by the identification of fungal DNA in brain tissue from Alzheimer’s
patients sampled at autopsy.29 The DNA comes from a range of species, and
the work is backed up with microscopic images of yeast cells and filaments
in samples from different regions of the brain. Alzheimer’s disease is
associated with the presence of specks of misfolded proteins in the brain
known as amyloid plaques. Plaques are important because they are part of
the inflammatory response that is characteristic of Alzheimer’s disease and
are linked to the death of nerve cells. They may develop when the body’s
immune system begins to attack the tissues that it is supposed to protect.
This is the autoimmune model for the disease. A second idea is that the
inflammation and formation of plaques is a response to an infection.30 This is
supported by experiments on mice infected with Candida yeast, whose
brains become damaged with plaque proteins.
The work on fungi in the brain is so new that no definitive conclusions
can be drawn yet, and the problem for scientists is the stubborn challenge of
separating cause from effect. It is possible that Alzheimer’s has an
underlying cause that has nothing to do with infection and that the fungi and
other microbes arrive once the brain is already damaged. If the fungal
connection is supported by other experiments, the next thing we need to
figure out is whether the fungi migrate to the brain from elsewhere in the
body or whether they come from the environment. Are brain fungi long-term
residents or recent immigrants?
Some investigators have reached beyond the available data to suggest that
fungi are part of a cryptic microbiome that lives inside the brain before the
development of any neurological disease. In a very limited study, they have
found bacteria clustered around star-shaped cells called astrocytes in samples
of healthy brain tissue taken from fresh cadavers.31 In addition to bacteria,
traces of fungal DNA have been detected in these brains. Fusarium is the
most frequent type of fungus that has been identified. Many investigators
remain skeptical about these findings, and it is possible that the brain
samples in these studies were contaminated after the death of their owners.
Inflammation of brain tissue features in other neurological diseases,
raising interest in the possibility of a widespread fungal connection in many
neurological conditions whose mechanisms have always seemed puzzling.
Amyotrophic lateral sclerosis (ALS) is the dreadful disease that afflicted the
physicist Steven Hawking. It is also known as Lou Gehrig’s disease, after the
famous baseball player who died in 1941. In a speech at Yankee Stadium on
July 4, 1939, Gehrig described his illness as a “bad break” and went on to
describe himself as “the luckiest man on the face of the earth,” which makes
me think of the bravery of Mark Tatum. Nerve cells that control voluntary
muscles are destroyed in ALS, meaning that patients lose control of their
conscious movements. Candida and other fungi have been found in the
brains of ALS patients, but the question of cause or effect remains.32
Genetics seem to be a factor in 5–10 percent of ALS cases, but the majority
are described as sporadic, in the sense that they develop without any clear
predisposing factor (spontaneous or idiopathic are better terms). This pattern
of illness is consistent with the influence of some unidentified environmental
factor, such as an infectious agent.
The brains of people who die from Parkinson’s disease are also colonized
by fungi.33 DNA and cells of Candida and Fusarium show up again, along
with the scalp yeast Malassezia, and Botrytis—a fungus that is a common
pest of fruits and flowers. After the Canadian American actor Michael J. Fox
was diagnosed with Parkinson’s disease in the 1990s, there was a lot of
interest in the phenomenon of disease clustering in ostensibly noninfectious
illnesses. Fox’s case had the unusual attribute of being one of four diagnoses
of Parkinson’s disease among the cast and crew of a television series that
had been filmed in British Columbia in the late 1970s.34 There are many
possible explanations for a disease pattern of this kind, but exposure to a
particular microorganism could play some undiscovered role in these life-
changing and life-ending illnesses. We seem to be a long way from a
definitive answer. The reports of fungi in brain tissue have survived the
rigors of peer review to appear in excellent journals, but most of the work
has come from a single group of scientists and deserves a lot more attention.
The body is such an intricate machine that its endurance, day in and day
out, can seem miraculous. After all, there are so many things that can go
wrong with a creature that depends on an infinitude of fine-spun biological
mechanisms. On the other hand, we are the recent products of a successful
evolutionary history that has compelled our twenty thousand genes and
trillions of cells to work together for at least as long as it takes for us to
reproduce. This much is self-evident. We would not be here at all if we were
really as fragile as many of us fear. The body develops as a comfortable
home for herds of microbes, and rather than surviving as individuals, we
have already seen in this book how we teem with invisible life—fungal and
otherwise. Far from immaculate, the body prevails as a mobile ecosystem
harmonized by the brilliance of the immune system. While any fungi that
live in a healthy brain seem to be rare, we find a very different situation in
the digestive system, to whose more prosperous mycobiome we turn now.

OceanofPDF.com
 5
Digestion
YEASTS IN THE GUT
HOW WOULD YOU rate your digestive system? Does it operate like a well-
oiled machine or a malodorous trash compactor? Most of us would
probably say, “Somewhere in between,” and add that its performance varies
from day to day. An uneventful and ignorable intestine is the gold standard
gut, but even the best of bowels are rattled by an ill-chosen meal. The
trillions of bacteria in the microbiome of the digestive system have received
a lot of attention, whereas the fungi that wax and wane in their midst have
played second fiddle or been ignored—until now. New species of fungi are
introduced to the body on fresh fruits and vegetables, and others are long-
term residents in the gut. Some of the newcomers die in the stomach acid,
and others survive downstream to make war and peace with the existing
microbes in the intestine or ride within the waste until they escape from the
body. The fungi are there for the whole journey from mouth to esophagus to
stomach and onward to the small intestine, large intestine, rectum, and
beyond. This is the richest and most mysterious part of the human-fungus
symbiosis.
Until recently, the study of the fungi that affected human health was
limited to the fungi that cause ringworm on the skin and life-threatening
infections of our internal organs. This constituted the study of medical
mycology in the twentieth century. In hospitals, mycologists who were
brought in to look at cases of serious disease examined the fungi seen in
microscope preparations of tissue samples and grew the fungi isolated from
patients in culture dishes. These techniques enabled them to identify the
fungi and advise physicians on treatment methods. Although mycologists
were aware that some fungi grew in the gut, these yeasts were barely
mentioned. They did not seem to be doing anything significant. The
application of methods to amplify the DNA of microorganisms from
samples of feces did not make much difference, at least initially, because
the techniques were perfected for identifying bacteria (mentioned in chapter
1). This led to the treatment of the gut microbiome as a giant onboard
bacteriome. Untangling the fungi from this assortment remains difficult.
Fungal genomes are ten times bigger than bacterial genomes, and we
need to read longer stretches of fungal DNA to stand any chance of
identifying species. This is happening now with the aid of advances in DNA
sequencing that allow faster and more accurate reads of longer strings of
As, Ts, Gs, and Cs, along with the development of more sophisticated
computer programs for analyzing the information gathered from fecal
samples. Mycobiome research has also benefited from the efforts of
investigators who have begun to discriminate between traces of fungi that
are introduced with our food and the dominant species that actually run the
active mycobiome (see the discussion of ghost gut fungi in the appendix).
Another obstacle to a more inclusive view of the gut microbiome is the
relative scarcity of the fungi. With trillions of bacteria in the gut and only
billions of fungi, fungi have been treated by bacteriologists as a minority
group overseen by the ruling prokaryotes. This mathematical imbalance
appears to discount the significance of the fungi in the chemistry of the gut
until we factor in the relative bulk of the fungal cell. Revisiting the facts
from chapter 1, the yeast cells that live in the gut are one hundred times
bigger than the bacteria and present a huge collective surface area for
interactions with the body. This more myco-centric view of the gut is
changing the ecological description of the body and has significant
implications for our health and well-being. As reliable information begins to
emerge from mycobiome research, we are discovering that the fungi are
game changers in gastroenterology.

GEOGRAPHY AND THE MYCOBIOME

A revealing study from China compared the gut mycobiomes of Hong Kong
residents with people of different ethnicities from Yunnan.1 Yunnan
Province is in Southwest China and is home to twenty-five ethnic groups
that speak multiple languages and consume a glorious range of traditional
foods including bitter fruits and vegetables, flowers, pickles, yak jerky, and
insects. Fungi are attached to all of these foods, and people in Yunnan add
more fungi to their diet by cooking the wild mushrooms that grow in
abundance in this region. Wild food consumption increases the diversity of
the fungal DNA sequences detected in the fecal samples from Yunnan, but,
crucially, this does not mean that more kinds of fungi actually live in the
gut. The molecular techniques are so sensitive that we can amplify traces of
rare organisms passing through the gut that have no influence on health at
all. For this reason, it is essential to apply a data filter that excludes the
weakest signals so that we can concentrate on the fungi that matter. When
we do this, we find some interesting patterns among rural and urban
populations in China.
An overwhelming difference between the gut fungi in Yunnan and Hong
Kong is seen in the abundance of two species of yeasts: Saccharomyces
cerevisiae, the food yeast, and a species of Candida.2 The study shows
plenty of Saccharomyces in the Hong Kong population and very little
Candida; the reverse is true for the rural residents of Yunnan. The
difference arises from life in the city, because we find that people from the
various ethnic groups that migrate to Hong Kong lose their Candida and
gain Saccharomyces. The plot deepens when we examine the health of the
rural population. Analysis of blood samples reveals that the urban residents
have better indications of liver function than the rural Chinese. This benefit
seems to be related to the prevalence of the food yeast in the gut rather than
abstinence from alcohol. The growth of Candida in the rural population
seems to have some positive effects too, because more of this yeast was
associated with higher levels of good cholesterol and lower levels of
obesity. So, each fungus comes with its own benefits. The food yeast,
Saccharomyces, in the Hong Kongers comes from baked goods and
processed foods and may not be active as it passes through the gut, but this
makes no difference in the mycobiome. Even if they are dead, the cells of
fungi carried with food can change the chemistry of the gut if there are
plenty of them, stimulate the growth of bacteria, and activate the immune
system.3
Moving westward, Sardinia is designated as a Blue Zone country, where
people enjoy unusually long and active lives. There are ten times more
centenarians per capita on this Italian island than in the United States. Diet,
genetics, daily exercise, and social cohesion are some of the presumed
explanations for the longevity of these people, and indeed, the liveliness of
the older Sardinians compares rather favorably with their contemporaries
shuffling around the American Midwest. But what about their mycobiomes?
Saccharomyces shows up in the Sardinians of all ages, along with
Penicillium.4 Penicillium is a distinctive member of the gut mycobiome that
usually grows as branching filaments rather than budding yeast cells. It
seems likely that this is another food import, because it is critical in cheese
fermentation and Sardinians eat a lot of cheese made from sheep and goat
milk. Many other fungi rise and fall alongside the species carried in the
food, but it is not clear whether any of them are associated with longevity.
When we look at the fungi in fecal samples of Americans, we find the
same fungi or close relatives of the Chinese and Sardinian species, with the
addition of Malassezia yeast that we encountered as a skin resident in
chapter 3.5 Geographical differences in the gut fungi found in South
Africans appear to be related to diet, but these are ancillary to the universal
gut yeasts.6 Taken together, these studies leave us with a picture of a core
mycobiome within the gut that is assembled from a small number of fungal
species that show up all over the world, whatever food we eat. Regional
diets add or subtract from this microbial foundation, affecting the relative
number of cells of different species, but Candida and a few of its
compatriots are always there. The gut fungi seem to be very resilient and
adapt to the continuous changes in the quantity and qualities of the food
processed in the gut after each meal. These onboard yeasts act as buffers
against the wholesale dissolution of the mycobiome even in cases of severe
gastrointestinal illnesses. This reboot of the core mycobiome is
accomplished by the rapid multiplication of the survivors after a population
crash.
The discovery of a core mycobiome is very useful because this
community of the commonest fungi found in the healthy gut can be
compared with the mixtures of fungi that develop in various diseases.
Recent research on the mycobiome has improved on the earlier surveys of
the kinds of fungi found in the gut and is beginning to show which ones are
present in the largest numbers and how they are interacting with the bacteria
and the immune system. Through these studies, it has become clear that
something is amiss with the mycology of the gut in many of the illnesses
associated with diet and the function of the GI tract. A growing body of
evidence suggests that fungi are involved in obesity, inflammatory bowel
diseases, and even in the development of cancer. This has convinced some
specialists that the fungi are a missing link in medicine.
 OBESITY
This inquiry into the role of the gut fungi in disease begins with obesity,
which affects more than one in ten adults, reduces mobility, and increases
the risk of developing manifold illnesses. A lot of research on obesity
involves fattening mice with a carbohydrate-rich diet. As the mice get
heavier, they show metabolic changes, including fat buildup in the liver and
accompanying alterations in the populations of fungi in their guts.7 Even
though some fungi increase and others decrease as the mice become fatter,
the mycobiome does not wobble in a predictable fashion. The only thing we
can say for certain is that the mycobiome is sensitive to rich diets and the
resulting increase in weight. Even without any fattening, mice fed an
“exotic” fungus that grows in yogurt produces an immediate disturbance to
the resident fungi and bacteria in the gut.8 These experiments highlight the
sensitivity of the gut mycobiome to diet, with changes to the core
communities of microbes resulting from a short-term or continuing change
in diet or even from a single unusual meal.
Studies on human obesity have revealed some interesting changes in our
onboard fungi, although there is nothing in these findings that offers any
immediate help in the search for new approaches to weight loss. Although
the fungal DNA from fecal samples indicates that there are different
mixtures of yeasts in obese and non-obese people, these are quite modest.
What we hope to find in a comparison of this kind is something that
distinguishes the two groups of participants—a red flag of a microbe that
shouts Weight-Loss Fungus! This germ does not appear to exist, although a
study from Spain found that species of Mucor, the bread mold, were present
in non-obese participants and rare in the obese cohort.9 They went on to
show that the absent molds began to appear in the obese participants when
they followed a weight-loss diet and that the signals from a variety of
Mucor species became more frequent as the patients lost weight. The
activities of these fungi in the gut are unknown, but their responsiveness to
the metabolism of the host parallels the reactions of other kinds of fungi in
the mouse mycobiome studies.
The ebb and flow of Mucor and other fungi in the mycobiome as we gain
or lose weight could be passive fluctuations in which the fungi play no
active role. Mucor, for example, may be a commensal fungus, meaning that
it lives in the guts of lean individuals without helping or harming them. It is
also possible that some of the fungi reinforce the status quo by releasing
chemical compounds that assist in the digestion of food in a way that serves
as a buffer against weight gain. Other fungi may work to bolster the obese
state, making it more difficult to lose weight even when the number of
calories is reduced in a new diet. We need to know a lot more about the
chemical communications between the fungi and the body before we can
take this idea of a supervisory relationship for the gut mycobiome any
further, but this is a distinct possibility.

GASTROINTESTINAL DISEASE MYCOLOGY

The handful of species of Candida that serve as the core of the gut
mycobiome are part of the standard equipment of the human body—true
symbionts, rather than transients, and we would probably be in trouble
without them.10 I say probably, because we do not know what would happen
if these fungi were completely eliminated from the digestive system.
Candida yeasts are a constant throughout life. Other fungi come and go as
we get older and change our diets, but Candida is with us for the long haul.
Problems develop when the number of these yeasts snowballs, which is
what happens in inflammatory bowel disease (IBD).11 IBD is an umbrella
term for chronic inflammation of the bowel that can be manifested as
Crohn’s disease in the small intestine and ulcerative colitis in the colon and
rectum.
The symptoms of IBD and the growth of Candida flare up in tandem,
suggesting a causal relationship in which the illness simulates the fungus,
and the fungus worsens the disease symptoms. This model of IBD is
exciting from a therapeutic point of view. In a more straightforward fungal
infection, we try to eliminate the fungus to resolve the tissue damage. In a
chronic condition like IBD, the fungus is part of the healthy body, and the
symptoms of the illness might be alleviated by repressing the fungus rather
than ridding it entirely. This gentler approach to treatment could be
achieved, at least in principle, by modifying the diet—if we could agree on
the foods that pacify Candida, or by finding an effective supplement. We
will look at dietary intervention at the end of this chapter, but there is
another more direct strategy for revamping the fungi in the gut: fecal
transplantation.
Fecal transplantation is a controversial treatment for digestive disorders
in which small samples of feces (equal to three tablespoons) from healthy
donors are implanted in the intestine of sedated recipients using a
colonoscope. In an Australian study of patients with colitis, the transplants
by colonoscopy were followed by repeated transfers by enemas
administered by the patients themselves for eight weeks.12 This intensive
therapy produced remarkable results, with a decrease in ulceration in one-
third of the patients and complete remission from their IBD symptoms. The
strongest signal from the mycobiome was a decrease in the levels of
Candida after fecal transplantation, and this was accompanied by an
increase in the diversity of the bacteria. The mycobiome and the bacteriome
—the fungi and the bacteria in the microbiome—were exchanging their
footings in the gut. The greatest success was enjoyed by patients who
showed the highest levels of Candida relative to other fungi before
treatment. One interpretation of this finding is that there was so much of the
yeast in the IBD patients that it was crowding out the healthy bacteria.
Fecal transplantation seems to work by resetting the populations of
microbes, which results in a decrease in inflammation that allows the
intestine to heal. We certainly need more research on this surprising therapy.
Inflammation is the first line of defense against harmful germs, and we
would be ruined without it. But when inflammation comes on too strong,
the body is overwhelmed by the mobilization of immune cells and release
of irritating chemicals, swelling of blood vessels, sensation of heat, and
other symptoms. Too much stimulation can be lethal. Too little is deadly
too. This is the Goldilocks principle of immunology. In a healthy digestive
system, the immune system is responsive to any signs that fungi and
bacteria are infiltrating the tissue of the gut wall, and our cells are probably
patching and repairing tiny nicks and leaks all the time. This tempo is just
right. Colitis and other illnesses develop when the inflammation spreads
over larger areas of the gut wall and the tissue damage overwhelms the
repair mechanisms. Continuous or chronic inflammation is a disastrous
instance of unconscious self-injury. We should think about this when we see
advertisements about health foods or herbal medicines that promote optimal
health by stimulating the immune system.13
The immune system is alerted to the presence of fungi by the distinctive
nature of the molecules on their cell surface. These trademark compounds
include enzymes and other proteins decorated with sugars that we call
mannoproteins. The immune system is programmed to react to these flags
from the time we are born and the mycobiome begins to develop on the skin
and inside the digestive system. One of the puzzles about the mycobiome is
why the fungi that start growing on the body in infancy begin to damage the
gut wall in some adults. The answer lies in a combination of factors,
including other health conditions that may weaken the tissue barriers and
allow the fungi to overcome the normal obstacles to infection. This
vulnerability may have a genetic foundation and increase with aging or it
may follow a viral infection. A very provocative study from China revealed
a surge in the number of Candida cells in the guts of patients hospitalized
with COVID-19 or with influenza.14 These changes to the mycobiome have
the potential to upset the immune system, trigger inflammation, and even
increase the likelihood of fungal infection. It sems that viruses can impact
the ecology of the whole body by agitating the fungi and bacteria in the gut.
Fungal infections can spread from the digestive system to other parts of
the body when the immune system is damaged, and Candida reveals itself
as a lethal enemy in these cases of disseminated disease. Candida does this
by switching from growth as a budding yeast to extending as filamentous
hyphae that pierce the gut wall and reach the interior of blood vessels. The
fungus switches from yeasts to filaments to move beyond the bowel, back
into yeasts to tumble in the bloodstream, and then again into invasive
filaments when it is delivered to solid tissues by the capillaries. This
flipping between growth forms occurs whenever Candida escapes from its
settled life as a benign resident in the body, where it is kept in check by
other fungi, its bacterial neighbors, and the immune system, and engages in
a population explosion. We are the unfortunate hosts for this ecological
exercise. The temperamental behavior of the fungi is as clear in the gut as
we have seen elsewhere in the body.15
 The disruption of the mycobiome in irritable bowel syndrome (IBS) is
very similar to the dysbiosis measured in IBD, with an overall drop in the
diversity of the fungi and an increase in Candida. A study on fungi and IBS
from the Netherlands also found an increase in Saccharomyces.16 IBS is
usually treated as a less serious complaint than IBD because it is not
accompanied with continuous intestinal inflammation. Even so, the
symptoms of these illnesses overlap, and IBS can be debilitating. Some
doctors believe that IBD and IBS are manifestations of the same illness
with different degrees of inflammation. Anxiety and depression are
described as comorbidities for both conditions, meaning that patients
diagnosed with IBD and IBS are more likely to suffer from these mood
disorders. This is reminiscent of the claims about asthma and anxiety
discussed in chapter 3 and the impossibility of separating cause from
consequence.

FUNGI AND CANCER

Inflammation is a big player in the development of tumors, which raises the
possibility that the mycobiome may be involved in some cancers.17 Early
diagnosis of IBD, before age thirty, is a risk factor for colorectal cancer,
suggesting a progression from severe inflammation of the gut wall to the
formation of noncancerous polyps called adenomas, and the later
transformation of these growths into malignant tumors. The mycobiome
changes as the health of the gut declines, with shifting ratios of different
groups of fungi, but we do not see a universal pattern. One study showed a
rise in the level of Malassezia yeasts, rather than Candida, and analysis of
polyps revealed other fungi related to Malassezia that tend to be better
represented on the skin. But the absence of a common denominator among
the revolving populations of fungi indicates that the gut fungi are
responding to inflammation in IBD rather than causing the illness. This
does not mean that the fungi are irrelevant—far from it, because the chaotic
mycobiome may exacerbate the tissue damage resulting from the tumors
developing in the wall of the intestine.
The active participation of the mycobiome in the progression of cancer is
supported by recent studies in which fungi have been detected along with
bacteria inside tumors in the intestine, pancreas, lungs, and other body
sites.18 DNA from Candida and Saccharomyces yeasts is found in the
tumors in all of these tissues, with Candida predominating in most places.
We know that this DNA has not strayed from outside the tumors because
microscopic images show fungal cells inside cancer cells and macrophages.
Live cells of the fungi have even been isolated from tumors of the colon
and grown in culture dishes. These findings show that there is nothing
passive about the fungi within tumors. They are growing within the
cancerous tissues, insinuating themselves between the cancer cells, and
some are being consumed by the macrophages of the immune system.
Fungal DNA is also found in the bloodstream of patients with late-stage
metastatic cancer. This suggests that the fungi are leaking through the
weakened capillary walls that also allow the cancer cells to migrate to other
parts of the body.
The investigators involved in this research believe that the
destabilization of the mycobiome and the entry of fungal cells into tissues
can be used as new markers for the development of cancer. This means that
the identification of fungal DNA in a blood test or a biopsy sample could be
useful in determining the developmental stage of a tumor and helping
patients and doctors decide how to proceed with treatment. Whether the
fungi are misbehaving in tissues damaged by the growth of a tumor
(consequence) or stimulating its development in some way (cause) remains
to be seen.

MYCOLOGICAL MIGRATIONS: ORAL AND GENITAL FUNGI

Although different mixtures of fungi are found in the gut mycobiome and
the skin mycobiome, yeasts spread from one to the other at the beginning
and end of the digestive system. Skin fungi settle into the mouth and gut
fungi seep into the vagina. We begin with the mouth. A peck on the cheek
transfers fungi from person to person, and more intimate contact via lips
and tongue adds to the oral broth. Spores are vacuumed from the air as we
breathe, and the mouth is smeared with fungi clinging to food and floating
in drinks. Few of these nomads survive, but the strongest yeasts join the
populations swarming along the gumline and coating the tongue and palate.
A founding dollop of a few hundred yeast cells swells into the millions in a
few hours if the conditions are perfect, but the mouth is a demanding place.
Beyond the attentions of the immune defenses, fungi must cope with the
climatic swings of the mouth as we clear our throats and speak, flood the
oral cavity with hot and cold liquids, and attack the biofilms with a
toothbrush, until, at last, we leave the mycobiome alone and embrace the
sandman. As we snooze, the fungi are at work, feeding and reproducing,
poisoning some bacteria, cooperating with others, and preparing for sunrise
and the first cup of coffee.
Preparation on the part of a fungus sounds fantastical, but the sensitivity
of fungi to their surroundings is well established, and experiments show
that they possess the rudiments of memory that enable them to ready
themselves for a stressful change in conditions.19 This behavioral
complexity is demonstrated by the fungal response to salt exposure. When
the salt concentration in a culture is increased, yeasts respond with a flurry
of biochemical changes to resist dehydration, and the mistreated cells
respond more swiftly when they are aggravated a second time. We say that
they are primed, and this protects the cells against other harmful treatments
including heat shocks and flushing with hydrogen peroxide (which acts as a
damaging oxidizing agent). It follows that this simple response could allow
the fungi of the oral mycobiome to buffer themselves against the morning
espresso bath. Coffee is a problem for fungi because it damages their DNA,
and some yeasts have a transport system that expels caffeine if it gets into
the cell. By anticipating the morning brew, these fungi have an opportunity
to fortify their membranes before the sun rises to keep the bitterness at bay.
Fungal sensitivity and consciousness are revisited in chapter 10.
Most of the fungi that live in the mouth are the familiar residents of the
mycobiome found in other locations. Yeasts are prominent, and Candida
and Malassezia dominate a pair of microbial communities that we call
mycotypes.20 When Malassezia is the most abundant fungus, it is associated
with a rich mixture of bacteria and other fungi. This mycotype is found in
healthy mouths. In smokers with active tooth decay and other indications of
poor oral hygiene, the Candida ecotype emerges, in which the diversity of
other fungi and bacteria falls. The healthy Malassezia mycotype is replaced
by the unhealthy Candida mycotype.21 The rise of the second population of
yeasts is a reliable sign of dental problems and is found in children with
tooth decay and in older people who have lost their teeth and wear dentures.
Rather than causing tooth loss, Candida may reinforce a wider decline in
oral health by reducing the growth of protective fungi and bacteria and
resisting natural repair mechanisms.
The problems multiply with the formation of resistant coatings or
biofilms of bacteria and fungi on the tooth surface. These layers of
microorganisms thicken and become acidic when sugars stimulate the
growth of Candida that nestles alongside the bacteria. Biofilms are involved
in tooth decay, and the stimulatory effect of sugars may explain why
children who overload with candy are prone to cavities. Studies on elderly
patients also support the link between diet and changes in the oral
mycobiome that may accelerate tooth decay: much higher levels of Candida
were found in saliva from patients in Japan and the Netherlands who wore
dentures compared with their peers with natural teeth.22 Interestingly, levels
of Candida also tend to be higher in older people who live in nursing homes
compared with those who live in their own homes. Diet may be a less
significant factor here, with the presence of other health problems in people
who move into nursing homes having a knock-on effect on the oral
mycobiome.
Moving to the vagina, Candida is the biggest player in this ecosystem.
The commonest species is Candida albicans, which is detected in at least
20 percent of women and is responsible for vulvovaginal candidiasis, with
symptoms of itching, burning, and discharge. Some antibiotics stimulate the
overgrowth of this yeast by eliminating the bacteria that help manage the
fungi in the normal community of microbes on the body. Recurrent
candidiasis, which is defined as four or more episodes per year, affects
hundreds of millions of women.23 This can be a debilitating condition.
There is no cure, and treatment relies on suppressing the growth of the
fungus with antifungal medicines. Annual medical spending on this
complaint soars into billions of dollars in the United States alone. In the
limited studies of the vaginal mycobiome, all of the fungi identified on this
part of the body surface are species of Candida. Healthy populations of
Candida have a protective effect against the development of intrauterine
adhesions by modulating the growth of bacteria and less common fungi in
the cervical canal and middle vagina that can damage these sensitive
tissues.24 Men are also affected by this yeast, albeit rarely, when candidiasis
develops on the surface of the penis following contact with a partner with
the vaginal form.
When we consider the importance of Candida in the oral mycobiome, its
dominance of the vagina, prevalence in the gut, and presence on the skin,
this yeast materializes as the most important fungus in human health. We
have seen the power of many other fungi in supporting and collapsing our
health, but in terms of the overall operation of the human ecosystem, this
yeast is unchallenged as the fungus at the heart of the human being. We are
human yeasts, Homo mycosapiens or Homo fermentalis.

RIPPLE EFFECTS OF THE GUT FUNGI

With mycobiome research in the early stages of sorting fact from fiction, or
facts with an impact on health from those without, the case for a link
between gut fungi and illnesses whose symptoms are expressed in other
parts of the body is building. Some of these claims seem unlikely at first,
but the revelations about the fungi that live in our bodies are so surprising
that we should keep an open mind. If my mycology professor had told me
when I first looked at fungal spores through a microscope in the 1980s that
some of these tiny grains belonged to fungi that could be found in the colon,
I would have thought him batty.
Vaginal delivery and breastfeeding have a protective effect against the
development of asthma in children and are associated with different gut
microbes than the ones found in C-sectioned and bottle-fed babies (see
chapter 1). Problems in the development of the immune system in asthmatic
children offer a hypothetical link to the gut microbiome and shifts in the
numbers and kinds of yeasts that are seen in asthmatic children.25 Early
treatment with antibiotics is another risk factor for asthma, which
strengthens the fungal connection according to the following chain of logic:
fungi can be highly allergenic → fungi grow in the infant gut → gut fungi
are disturbed by antibiotics → infants that receive antibiotics are at greater
risk of developing asthma ⇒ [ergo] disturbing the mycobiome can lead to
asthma.
An obvious obstacle to embracing the idea that fungal unrest or
dysbiosis in the gut can provoke asthma is the physical separation of the
digestive and respiratory systems. Eating does not affect breathing in any
noticeable way, and breathing dust does not cause intestinal distress. This
segregation of organs is an essential element of the way that medical
students learn about human anatomy, lungs this week, kidneys next,
although the connections should be emphasized as often as possible. For
example, the immunological systems that protect the gut and the lung are
coupled through the blood and lymph vessels, and we recognize this
intimacy with the term gut-lung axis.26
Similar ripple effects between the gut mycobiome and illnesses
presented in other parts of the body have been proposed for other conditions
that seem unrelated to gut function. The number of budding Candida cells
soars in type 1 and type 2 diabetes, and multiple species of Candida appear
in the guts of children with type 1 insulin-dependent diabetes. The overall
diversity of fungi in the gut mycobiome also seems to increase in some liver
diseases and decrease in others. Candida flares are seen in hepatitis,
cirrhosis of the liver, and a disease called primary sclerosing cholangitis
(PSC) that damages the bile duct.27 PSC is also known as Walter Payton’s
disease, after the famous American football player who died in 1999 from
bile duct cancer caused by this condition. Multiple sclerosis is the most
controversial of these putative correlations, with different patterns of fungal
abundance seen in patients with this chronic autoimmune disease.28 In the
absence of a consensus in the mycobiome experiments, it seems most likely
that the fungi are responding to the gut inflammation that develops in
multiple sclerosis patients rather than playing any causal role.

OPTIMIZING THE GUT MYCOBIOME

There is a tendency to view the body as a temple ruined by modernity. This
viewpoint is entirely reasonable when we consider the frightful nature of
processed foods saturated with sugar and salt, lacking all traces of fiber, and
delivering the calories required for weight maintenance by a sasquatch
rather than a slothful human. Those with sufficient tenacity and affluence to
eat a more balanced diet that emphasizes plants and get some exercise can
feel happier in the twenty-first century and reflect on the likelihood that
they are likely to live longer than most representatives of our species
throughout history.
So, what can we do to promote a balanced mycobiome in the gut that
may support our overall health? The fungible concept of the healthy
mycobiome makes me wary of any dietary recommendations, and my
fungible waistline is unlikely to inspire confidence in my readers. Other
commentators on the mycobiome are bullish enough to recommend food
and behavioral choices to improve the mycobiome, attain digestive
wellness, and lose weight. Mahmoud Ghannoum, a distinguished medical
mycologist at the University Hospitals Cleveland Medical Center, is the
most prominent advocate of mycobiome manipulation, which he explains in
his book Total Gut Balance: Fix Your Mycobiome Fast for Complete
Digestive Wellness (2019).29 Eve Adamson, an award-winning author on
dieting, is credited as a cowriter, and the book includes sixty “Mycobiome
Diet” recipes. There is a lot of useful information on fungi in Total Gut
Balance, and Ghannoum explains that Candida is a harmless resident until
dysbiosis sets in and the fungus reveals its darker side. The science is
leavened with advice about smoking cessation, yoga, and meditation, which
is very reasonable but strays from the mycobiome. The recipes look very
appetizing in the photographs, but the only study on the impact of the
Mycobiome Diet on the mycobiome was published by Ghannoum himself
in the Journal of Probiotics and Health.30
Pending advances in mycobiome research, there is little dietary advice
supported by scientific evidence that will guarantee a healthy mycobiome.
Healthy people tend to have healthy mycobiomes, and a great range of
illnesses are accompanied by unhealthy mixtures of fungi and bacteria.
There is a frustrating circularity to this relationship and few ways to
intervene and use the onboard microorganisms to treat disease. Candida is
the obviously problematic fungus in many debilitating conditions that
involve the mycobiome, and dampening this yeast when it grows to the
exclusion of everything else could be helpful. The effective treatments for
vaginal yeast contain low doses of antifungal drugs and are applied as
topical agents. Use of the same medicines to treat Candida in the gut has
the unwelcome effect of damaging the other fungi whose growth we want to
support. We do not want to eliminate any organism that might be an
essential partner in the healthy human ecosystem. Coconut oil, undecylenic
acid (from castor oil), and oregano leaf extract are dietary supplements that
are advertised as treatments for yeast overgrowth. Coconut oil, which is
recommended in the Mycobiome Diet, has a proven effect on the
mycobiome of mice, reducing Candida overgrowth and restoring the
healthy mixture of fungal species.31 This is not much to go on, but with few
side effects, coconut oil is worth trying as a dietary remedy. Reducing
Candida through dietary changes seems unlikely to resolve any serious
condition like IBD, but any relief from the crippling symptoms would be
marvelous.
The key to a healthy mycobiome may lie in preventing an unhealthy one
from developing in the first place, and the most direct way to satisfy the
needs of our fungi is to feed them properly. While the Mycobiome Diet
totters on a weak scientific foundation, the recipes and other advice offered
by Mahmoud Ghannoum push readers in the right direction, away from
processed foods and toward a sensible diet that tastes good and emphasizes
plants. If your digestive system operates like a well-oiled machine, pay
attention to what you are eating and keep doing so. If it misbehaves,
interrogate someone with a happier gut and find out what they have been
eating. Clearer advice about optimizing the mycobiome will come as this
scientific inquiry moves on from naming the fungi in the gut to figuring out
what they are doing in there. This will be expensive and time-consuming
and require collaborations among specialists in gastroenterology who know
the intestine, bioinformatics experts who read DNA for a living,
immunologists who understand immunology, and mycologists infatuated
with fungi.
From this inward examination, in part I, of the fungi that live on the
body for better or worse, supporting and damaging our health, we move
outward, in part II, looking at the ways that we interact with fungi outside
the body. We begin with chapter 6, on mushrooms, molds, and yeasts in the
diet.

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 PART II

Outward
OceanofPDF.com
 6
Nourishing
MOLDS AND MUSHROOMS IN OUR
DIETS
MILK CURDS are stiffened and blue-veined in the coolness of caves; sausages
are bloomed with white powder as they hang drying on strings; beans and
cereals dissolve into soy sauce and jellify into tempeh; bread dough rises;
and grains and grapes are transformed into beer and wine. Humans crafted
these foods for millennia without any idea that microscopic fungi were
threading through cheese and bubbling in vats. All they knew was that their
diets were invigorated by experimenting with raw foods, and they marveled
at the handiwork of their gods. Biotechnology began as this monkish pursuit.
In our time we are applying the same genetic techniques that have identified
the fungi that grow on the body to understand the ecology of food. Who
would have guessed that a cheese wedge is one of the wonders of the
microbial world? In this chapter we explore the foodie extension of the
human-fungus symbiosis that takes us from the body to the farm and to
fermentation towers brimming with mycelia that make chicken nuggets
without chickens.
Penicillium is the cheesemaker. The name of this mold, which means
brush, refers to its bristly stalks topped with chains of spores that resemble
tiny dreadlocks.1 In nature, these spores are blown into the air or catch on the
hairs of passing insects, and each particle of fungus carries the genes for
making a mycelium in a new location. Most spores land in places without
food and water, where they shrivel and die, but a small proportion survive
and go on to craft the next generation of spores. And so it goes, and has gone
on, from spore to spore for millions of years, conveying the instructions for
making this fungus.2 Cheesemakers circumvent the wild dispersal
mechanism and add the spores of the fungus directly to their milk curds.
Penicillium is the first Latin name or genus of hundreds of fungal species
that grow everywhere and feed on everything, spoil food, make toxins and
antibiotics, and flavor cheeses and preserved meats. Another genus,
Aspergillus, is equally influential on agriculture, medicine, and food.
Penicillium and Aspergillus are filamentous fungi that do not produce
mushrooms or any macroscopic fruit bodies at all. They are the iconic
molds, or “moulds,” in British spelling. Along with the brewing and baking
yeast Saccharomyces cerevisiae, these microbes occupy the top spots in the
human-fungus symbiosis: not in terms of the mycobiome and human health
—Candida takes that award—but as prizewinners for supporting
civilization.

BREWING AND CHEESEMAKING: THE FIRST

FERMENTATIONS
To understand the best-partner nomination for Penicillium, we begin with a
visit to a salt mine in Austria and look at the feces left by an Iron Age miner
more than 2,600 years ago. This archaeological treasure was left in a
mineshaft in the mountains that tower above the beautiful alpine village of
Hallstatt. People were digging here for thousands of years before the miner
took his historic bathroom break, and this amazing mine remains active
today. The sample of paleofeces is the size of a grape, and it was preserved
by the saltiness of the mine. It is very fibrous in structure, which is
consistent with a high-fiber diet that included barley and other cultivated
cereals whose remnants are visible under the microscope. The miner had
also eaten apples paired with Roquefort cheese and quenched his thirst with
beer. He was a proto-gourmand whose repast would not be amiss in a
fashionable bistro today. There are no physical traces of the cheese and beer,
of course, but analysis of DNA in the paleofeces by a team of researchers led
by Frank Maixner at the Institute for Mummy Studies in Italy identified the
cheesemaking fungus, Penicillium roqueforti, and brewer’s yeast,
Saccharomyces cerevisiae.3 Both fungi had become part of the salt miner’s
gut mycobiome, in the same way that every fungus that we eat flows through
the digestive system, interacting with the intestinal bacteria, triggering
immune reactions, and affecting our health. Maixner’s study provides a
snapshot of the unfolding relationship between humans and fungi in Europe
before the Roman conquest—the way that the diets of laborers were
enriched by fungal fermentation.
Our collaboration with fungi began with the transformation of sugars into
alcohol by yeast, symbolized as C6H12O2 → CH3CH2OH, which is the most
consequential chemical reaction in human history.4 My hunch is that palm
wine was the archetypal brew in tropical Africa, where people found that the
sweet sap drained from palm trees fermented spontaneously in the sun. This
idea is supported by the discovery of fractured starch grains from wine
palms and sorghum on the surface of 105,000-year-old stone grinding tools
in a cave in Mozambique. It is tempting to think that the early humans were
processing palm stems and grass seeds to make the kinds of artisanal brews
that remain popular in Africa today.
The oldest clear evidence of brewing comes from the analysis of pottery
remains showing that rice wine was fermented in Chinese villages nine
thousand years ago.5 Wherever it began, brewing was the first deliberate
application of the chemical wizardry of the fungi. This was deliberate in the
sense that the brewers learned to prepare their ingredients in a way that
stimulated fermentation, although they obviously had no concept of the
invisible yeasts and molds that performed this alchemy. Indeed, early
brewers interpreted the formation of alcohol through their religions and
showed their appreciation by worshipping festive deities that included the
Daoist god Yidi in China, the Sumerian beer goddess Ninkasi, and the
Yoruba spirit Ogoun in Africa.
The extension of human-fungus symbiosis from brewing with yeasts to
cheesemaking with molds was the next technological breakthrough that
bears the stamp of serendipity. Cattle and other mammals were originally
domesticated to furnish settlements with a reliable supply of meat. Milking
was a later inspiration. Milk is rich in fat and protein, but genetic research
shows that the early herders belonged to lactose intolerant populations and
would have found fresh milk unpalatable.6 Butter was one of the early
solutions to the lactose problem, which concentrates the milk fat and allows
a good deal of the lactose sugar to drain away in the buttermilk.
Cheesemaking works in a different way, by separating the fats in the curds
and expressing a lot of the sugar in the whey. By churning butter and
fermenting cheeses, herders produced palatable and nutritious foods that
took up less space than gallons of milk and lasted a lot longer before
spoiling.
Yogurt was another early dairy product that is fermented by microbes.
Residues in Neolithic pottery show that yogurt drinks were fermented from
mare’s milk in Central Asia and that cheeses were made from cow’s milk in
northern Europe at least seven thousand years ago. In his Histories, written
around 430 BC, Herodotus described the Scythian use of mare’s milk to
make kumis, which is a mildly alcoholic drink that remains popular in Russia
and other countries. Lactic acid bacteria dominate yogurts, and yeasts are
unwelcome because they spoil the taste. Yeasts are more amiable in kumis,
where they produce alcohol and create the frothiness of this drink, which has
been called the champagne of the steppes.
 BLUE CHEESES
By the time the armies of Julius Caesar conquered Gaul in 50 BC, cheese
had become a widespread part of the Western European diet. In the first
century AD, Pliny described a range of cheeses imported to Rome from its
empire in his Naturalis Historia, and Petronius detailed a soft wine-soaked
cheese served at the end of a banquet in his Satyricon.7 Pliny praised the
cheeses from southern France without specifying Roquefort (as some
promoters have claimed), but blue cheeses were produced long before then,
as the salt miner testified through his ancient deposition.
According to legend, Roquefort cheese was discovered by a French
shepherd who put his bread and cheese in a cave for safekeeping when he
ran off in pursuit of a young maiden. Months later, he returned to the cave
and found his cheese metamorphosed into a blue-marbled delicacy. There
have been, no doubt, many distracted shepherds, but science has shown that
the Roquefort legend is a crock. Contrary to long-standing ideas about this
Penicillium evolving as a cave dweller, it is a domesticated variety of a
fungus that rots vegetation and thrives on farm silage stored as winter feed
for livestock.8 The only reason that it grows in caves is because its spores are
taken into them by cheesemakers in the commune of Roquefort-sur-Soulzon
in southern France and added to curds clotted from ewes’ milk. Here, the
curds are shaped into wheels and allowed to drain before salting and spiking
with needles to aerate the cheese. This stimulates the growth of the mold,
along with complementary bacteria. Afterward, the cheeses mature in caves
for at least three months as the fungus performs its sorcery in the cool humid
air. As the wheels age, their veins are colored by the blue-green spores of the
fungus.
By transferring cultures of the fungi that produced the most successful
batches of Roquefort onto chunks of moldy bread, early cheesemakers
selected a strain of Penicillium with the strongest combination of
characteristics. They wanted one that grew slowly to ensure a steady
maturation process and produced plenty of spores that would serve as a
vigorous starter for fresh batches of cheese. These artisans were engaged in
the practice of artificial selection that we usually associate with the
domestication of plants and animals. And as the fungus got better at making
the blue-veined cheese in the caves, our amorous shepherd was contributing
to the Roquefort story by choosing lambs from ewes of the Lacaune sheep
with the richest milk and puppies from sheepdogs that were the best at
herding them. Across the centuries, selective breeding worked its magic on
the molds, sheep, and dogs to craft the perfect cheese.
Penicillium and other fungi work in combination with bacteria to create
masterpieces like Roquefort. Bacteria break down the lactose in milk, and
the accompanying acidification promotes coagulation. Fungi added to the
resulting curds feed on the milk fat, which controls the consistency of the
cheese, and they are also responsible for producing the distinctive aroma and
taste during the maturation process. The strain of the fungus that makes
Roquefort in the eponymous French township is maintained in laboratories
today to ensure its unwavering behavior when it is added to the curds. Other
strains of Penicillium roqueforti create the sweet, nutty crumbliness of
Stilton from England and subtler creaminess of Danish Blue from cow’s
milk. Cashel Blue from Ireland is another win for this species of fungus, but
milder blue cheeses, including Gorgonzola and Blue d’Auvergne are made
by a relation called Penicillium glaucum.
Another mold, Penicillium camemberti, makes the soft white crusts of
Camembert and Brie.9 These creamy cheeses originated in northern France.
Brie was produced in the Middle Ages, and its crust had a blue-gray color
until the twentieth century, before cheesemakers selected for strains that
form a pure white surface. The growth of the mold is controlled by
refrigeration, and the crusts are flattened by their wrappers, which stifle the
slow expansion of the fungus. When the wrapper is removed, its folds are
left as impressions in the white fungus that has grown along the seams,
seeking opportunities to escape. If the unwrapped cheese is left at room
temperature, it can turn fluffy. This is nurtured in some cheese varieties, like
the firmer and hazel-nutty Saint-Nectaire, which becomes covered with poil
de chat, or cat’s hair. The fungi that grow the hairs and darken the cheese
surface are species of Mucor, extending the activities of these versatile
species of fungi from the gut mycobiome, where they are common
occupants, to the microbial communities of the cheese and back again when
we eat them.
 Saint-Nectaire, which comes from Auvergne in the middle of France, is
fermented and ripened by an exceptionally complicated succession of fungi
and accompanying bacteria.10 Multiple species of yeasts start by growing in
the milk curds, breaking down the milk fat and reducing the acidity, which
allows bacteria to multiply; molds join the fray as latecomers to firm and
fluff the crust. Ten billion microbes can grow in a gram of cheese.11 The
populations of different fungi and bacteria rise and fall as the cheese ages,
reflecting changes in the availability of nutrients and the give and take
between microbes that ranges from cooperation to chemical warfare. The
intricacy of some of these interactions is astonishing. One mind-bending
study on Saint-Nectaire shows that bacteria use the fungal hyphae as
physical guides, like miniature railroad lines, for high-speed travel through
the rind.12 This collaboration is limited to certain types of bacteria, which has
the effect of controlling the mixture of microbes in the maturing cheese.
Other microbial performances, most of them unknown, animate—or, to be
more precise, fungate—the taste, smell, color, and texture of every cheese,
whose brilliance arises from their dalliance with death, edging so close to
decomposition yet brimming with life. A cheese is, as American author
Clifton Fadiman wrote, “milk’s leap toward immortality.”13
The removal of lactose and production of a compact and spoilage-
resistant food explains why cheesemaking began in the Neolithic. The
availability of this high-calorie dairy product must have been a godsend
during the winter months in northern latitudes when fresh meat and
vegetables were scarce. Cheese has another great advantage over raw milk in
its safety. The Listeria bacterium that grows in raw milk is inhibited by the
activity of the preferred bacteria and yeasts in cheeses. Artisan cheeses made
from unpasteurized milk are not immune from this dangerous form of
spoilage, but cheesemaking has become such an exacting business that cases
of listeriosis from cheese are extremely rare. If we accept the minuscule risk
of listeriosis from these raw milk products, we access new dimensions in the
cheese universe, hundreds of sensational varieties that may have the
additional benefit of contributing to a healthy digestive system when
samples of cheese microbes merge with the gut microbiome.14
 None of these prehistoric advantages of cheese explain why we are
attracted to the strong flavors of blue cheese. To understand the pleasures of
Roquefort and its rivals, we need to think about the evolution of our sense of
smell. The fungi in blue cheeses produce volatile compounds that belong to
the groups of chemicals that perfumiers mix in their fragrances. We find
these alluring for the same reasons that we are attracted to zesty citrusy
odors, whose underlying appeal evolved as a stimulus for finding wild fruits.
Fungi are not interested in attracting us with these smells and seem to make
these volatile chemicals to repel other microorganisms.15 The explanation for
turophilia (cheese-loving) becomes more complicated when we consider the
popularity of washed-rind cheeses, whose aromas are produced by bacteria.
Consider the shockingly sudoriferous Limburger from Belgium, whose smell
is produced by a bacterium that is a culprit in foot odor. The taste for
Limburger and other maximally pungent cheeses, like Stinking Bishop and
Époisses, probably lies somewhere in our sexual attraction to certain body
odors and pheromones. The bewitching power of this mephitic matter on
other animals is illustrated by the effectiveness of Limburger as bait for
trapping malarial mosquitoes that are programmed to respond to the same
signals in human sweat.16

FERMENTED MEAT, FISH, CEREALS, AND BEANS

Moving from la fromagerie to la charcuterie, we find more evidence of the
culinary skills of Penicillium in the whitish bloom on the skins of the dry-
cured meats hanging from strings. Some meat producers inoculate their
sausages by dipping them in a starter culture of spores before they are placed
in drying rooms to mature. Others allow their sausages to become colonized
by fungi without any human interference. Either way, the fungi change the
taste of the sausages as they feed on the fats and proteins in the meat and
contribute to the characteristic aromas of these regional delicacies. The fungi
also absorb water from the raw meat, which accelerates the drying process.
They also fend off other molds that cause spoilage, including species that
produce toxins. Penicillium nalgiovense is the commonest fungus used to
cure meats and is used by the major manufacturers.17 This fungus is joined
by Penicillium salamii on Italian salami, soppressata, and capocollo, whose
spores float around in the rooms where the raw meat is packed into casings.18
The same fungus is obviously an expert in meat curing because it also grows
on air-dried ham in Slovenia.
Because fungi and their spores are everywhere on the lookout for food,
and because they are so skilled in decomposing the rest of nature, they
colonize every kind of raw food that we harvest and compete with us for all
of the available calories. The resulting spoilage is terrifically harmful from
the perspective of the farmer and consumer, but this is balanced by the
protection afforded by the elite group of food fungi whose growth we have
encouraged for thousands of years. All of the uses of fungi to protect and
modify raw foods must have been discovered by accident and perfected by
experimentation. This is exactly what happened with brewing and
cheesemaking, where nothing is left to chance today.
Regional loyalties to some fermentations are more difficult to
comprehend than others. Fungi and bacteria that ferment Greenland shark
meat make it safe to eat without making it appealing to eat. The resulting
chewy snack, which is an Icelandic treat called hákarl, has a memorable
bouquet of stale urine. It is one of the wonders of the culinary world,
rejected by the palates of most tourists who try a cube of the stuff during a
visit to the volcanic island. The preparation of hákarl has not changed in any
fundamental way since the Viking Age because it is crafted automatically by
microbes that are ready to pounce on the flesh as soon as it is exposed to the
air. Icelanders ferment the shark flesh in tubs with perforated bottoms that
allow the fluid to drain away for up to six weeks. After this preparatory
relaxation, hákarl is left dangling in drying sheds for a few months before it
is eaten. The raw shark meat is poisonous and is detoxified during this
lengthy polishing, which is an undeniably good thing. When a sample of the
final product is spiked with a toothpick, it might be mistaken for a piece of
cheese until one is distracted by the sense that somewhere close by, a cat
with a bladder infection has relieved itself with great enthusiasm. This
impression of feline incontinence is replaced by much ghastlier scenarios if
you proceed to put it in your mouth. Hoping that this book will sell well in
Iceland, I should add that these comments are based on online reviews rather
than personal experience. Every country has its culinary quirks, and I am
sure that plenty of Icelanders who enjoy hákarl are revolted by Marmite, the
salty black paste that is revered in my birthplace. Marmite also has its place
in this chapter, as a fungal product that is formulated from yeast cells
exhausted from the labor of crafting beer.
Hákarl is fermented by a chaotic mixture of bacteria, yeasts, and molds,
and this ensemble of microorganisms—the hákarl microbiome—differs in
every sample of the snack sold in stores.19 This is a change from the
microbiomes of blue cheeses, in which one fungus steps up to overrule the
others in every batch. An anaerobic bacterium (meaning that it is suffocated
by oxygen) is found in all of the hákarl that has been tested, and a yeast is
there too, but the rest of the fungi are all over the place, with a salmagundi of
yeasts and molds chewing away in the chunks of flesh. And yet, this is a
form of fermentation that is controlled, to some extent, by the draining and
drying, which makes me wonder how much worse shark flesh could taste if
it decomposed without any management?
Traveling east of Iceland, continuing this foray through the world of
rotten fish, we could taste herring, or surströmming, in Sweden, which
smells like an open sewer; various species of fish dried, salted, and
resurrected as momone in Ghana; fesikh from Egypt; and onward to an
extensive menu of fish and fish sauces in Asia.20 Bacteria and fungi
collaborate in the preparation of all of these foods. Some, like hákarl,
ferment spontaneously; others are inoculated with starters of grains
colonized by fungi maintained for this purpose. The resulting foods add
flavor to diets, notwithstanding the revulsion experienced by nonnatives, and
preserve them from the automatic decomposition that poisons and liquefies
fish in the open air. Each of these ethnic foods is a tribute to the resilience
and ingenuity of local human populations that strengthened their symbioses
with the fungi.
A sauce fermented from fish intestines called garum was a staple in the
Roman Empire. It was as popular as tomato ketchup and was manufactured
outside cities to spare urban residents from its awful smell. Worcestershire
sauce includes anchovies and tamarind fruit in its secret recipe and may hint
at the glories of garum that disappeared with the empire.21 The history of
Worcestershire sauce is as murky as the genesis of the other foods in this
chapter, with a tale about a colonist returning from India with a fever for a
chutney deflating when a former employee of Lea & Perrins—the British
manufacturer—discovered that the gentlemen named by the company had
never set foot in the country. With or without any culinary espionage, the
recipe for this Indian-inspired sauce was developed in the city of Worcester
by two chemists, John Wheeley Lea and William Perrins, and has been sold
since the succession of Queen Victoria (1837). Yeasts and bacteria complete
the exacting eighteen-month cultivation process, which is a trade secret.
Soy sauce has a clearer pedigree, with scholarly sources converging on its
beginnings in China and later introduction to Japan in the thirteenth century
by a Zen monk returning from a pilgrimage. The oldest techniques for
fermenting soy sauce were probably adapted from recipes for fish sauce to
align with Buddhist sutras advocating vegetarianism. Soy sauce is made
from a mixture of soybeans and wheat by kōji, which is the term for the
Aspergillus mold that breaks down the proteins in these ingredients and
produces glutamate, which gives the sauce its umami or savory taste. Brine
is added to the brew for a second-stage fermentation, in which bacteria
produce lactic acid and yeasts flavor the sauce as they digest sugars.22 The
Japanese company Kikkoman is the largest producer of soy sauce, which
traces its origins to the seventeenth century. Soy sauce has also been
produced in Korea for centuries, where other fungi and bacteria engage in a
lengthy preparation of seasoned cabbage to create the glorious staple kimchi.
Fungal foods are powerful emblems of national and regional identity, and
their manufacture in other countries has invited claims of cultural
appropriation. Producers have engaged in fierce battles over trademarks, and
protections have been instituted in many places including the French
appellation d’origine contrôlée for cheeses and other agricultural products.
As Europeans embraced Penicillium as their chief cheese fungus, people
in Asia worked with Mucor and related bread molds to craft solid foods from
beans and cereals, including sufu in China, idli in India, and oncom and
tempeh in Indonesia.23 The consistency of these products ranges from the
spreadable sufu, which has been compared with cream cheese, to the firm
slabs of tempeh. Each of these products is the creation of a complex
community of fungi and bacteria that performs a controlled breakdown of
proteins and complex carbohydrates to create a more digestible food and
adds flavors that range from bland to the demonic. Tempeh has the widest
global distribution and is the most overtly fungal of these fermentations in
taste and appearance, with whole soybeans glued together by wefts of white
mycelium, producing something like an inverted Camembert cheese. It is a
popular meat substitute that is especially good when it is cooked after
marinating in barbecue sauce and is also served as crispy fritters in East Java
called tempeh kemul. The reference to ferments with a demonic flavor
applies to regional versions of Chinese sufu that have been ranked at the far
end of a disturbing continuum of tastes that runs from floral to cadaverous
and fecal.
The continental differences between the mold species used in the fungal
technologies of Europe and Asia are striking and seem to have arisen from
the type of food that was fermented rather than the geographical patterns of
fungal distribution. All of the fungi were busy with other jobs before
domestication: Penicillium spores wafting from rotting vegetation were
tempted by milk curds in the cool air of France, and other molds growing on
animal dung leapt at the opportunity to ferment fresh soybeans in the tropics
of Java.24 The Aspergillus recruited to make soy sauce in China was also
doing its own thing in nature, feeding on wild grasses for millions of years
before its employment by humans. In each case, a combination of local
agricultural produce, climate, and human ingenuity produced new kinds of
food. There is a fine line between the spoilage and improvement of foods by
fungi. Any mold that produced toxins when it started growing on milk curds
or sausage skins was sure to be discarded: nobody was going to use it as a
starter for the next batch of cheese or cured meat. But when harmless molds
showed up with unusual smells they were in with a chance. Some artisans
threw them out, but others must have found them sufficiently interesting to
give them a try, which is why we have blue cheese in France and salami in
Italy. Hákarl and surströmming must have been born from desperate hunger.
Region by region, over the millennia, the human-fungus symbiosis
flourished as people discovered that certain manifestations of moldiness
preserved and improved food rather than reducing it to a putrid sludge.
Greater control over the outcome of these fermentations was achieved by
cultivating fungi on starters that could be mixed into the raw foodstuffs. This
stopped other molds from taking hold and spoiling the fermentation. Starters
included funky bread for cheesemaking in caves and moldy rice added to
cooked soybeans to forge the blocks of tempeh. As the centuries passed, the
human-fungus symbiosis deepened, and the technologies were refined long
before anyone understood the nature of the strange partners that cobwebbed
our food and clouded our drinks.

THE QUORNIAN AGE

Solutions to the mysteries of fermentation began in the nineteenth century,
when Louis Pasteur and his contemporaries proved that the bacteria and
fungi seen with microscopes were the living agents of food spoilage and
brewing. This spurred the deliberate application of microbes in the
production of foods and medicines that we call biotechnology. With
considerable hubris, a blue road sign declares South San Francisco “The
Birthplace of Biotechnology.” This claim rests on the accomplishments of
the biotech giant, Genentech, which was born there in 1976, but it is worth
considering that the Pasteur Institute in Paris was established in 1887, twenty
years before South San Francisco was a city. There are, after all, plenty of
hotspots in the history of biotechnology. With considerable bias, and no road
sign, I argue that Cincinnati is the real birthplace of American biotechnology
because this was the site of the first yeast factory after the Civil War.25 And
what about the village of Marlow Bottom in Buckinghamshire? In 1967, a
team of food researchers began scouring the planet in search of a mold that
would convert starch into protein. Some of the fungi did not grow very well,
others grew fine but produced toxins, and then, on April 1, 1968, a species of
Fusarium was isolated from a compost heap in the village that became the
source of the superlative meat substitute trademarked as Quorn.26 The
superlative fungus had been growing under the noses of the investigators, a
half-hour walk from their laboratory headquarters.
Today, the Quorn fungus is cultivated in 50-meter-tall fermentation
towers, where it is circulated by a column of rising air bubbles and fed with
corn syrup, ammonia, and minerals. Energized by the glucose in the syrup,
the filaments of this mold reach out and branch into mini-mycelia and
concentrate as crumbles of the cholesterol-free foodstuff called mycoprotein.
Beginning with one gram of the fungus, each fermentation cycle produces
1,500 tons of Quorn. This is processed into meatless nuggets, sausages, and
burgers that are sold in frozen food sections of grocery stores around the
world.
Quorn is a very successful product that is enjoyed by those of us who
have reduced or eliminated meat-eating and miss the texture of cooked flesh.
Tempeh has a similar meat-like structure, but Quorn is a less ambitious food
that does not raise any suspicions. Tempeh always makes me think about
what I am eating, whereas there is nothing moldy about Quorn at all. It is so
good as a breaded nugget that it should, logically, end the torture of broiler
chickens. It is ironic that the development of mycoprotein as a tasty
substitute for chicken has happened at the same time that chicken breeders
and processors have been working toward increasingly tasteless lumps of
meat so that the fungus and the animal are practically indistinguishable.
If, however, the urge to eat Quorn derives from the idea that it is
environmentally sustainable, we need to think again, because it isn’t, or isn’t
very. And this is the problem with all manufactured fungal protein products
and all nonedible fungal products like packaging materials made from
mushrooms: they are very energy intensive. Plants are sustainable because
they make their own food. Fungi, like animals, must feed on other organisms
or their remains. If the Quorn fungus was content eating agricultural waste,
that would be a more environmentally benign proposition. It would be
decomposing something we cannot digest and turning it into artificial
chicken nuggets. But Quorn is raised on corn syrup, which is trucked to the
manufacturing plants in heated tanks, and the fungus is propelled around its
fermenter stacks using powerful electric motors, fertilized with ammonia,
and on, and on. Carbon dioxide billows into the air at every stage of the
fermentation process, as it does whenever we make things. We can judge
that Quorn is better for the environment than meat or fish, but carbon
neutrality is as elusive as the battery-powered car whose only emission is
water.27
Like the other food molds described in this chapter, the Quorn Fusarium
is related to fungi that destroy crops, spoil harvested grains, and infect
humans. Fusarium is a huge genus that encompasses as many as a thousand
species, including fungi that live in soil, plant pathogens that attack wheat
and barley, and another species that is driving the commercial banana toward
extinction. This presents a marketing challenge, which is why we refer to
mycoprotein rather than fungus protein, mold nuggets, or mildew meals.
Some Fusarium species produce toxins (see chapter 8), but the Quorn
Fusarium has never caused any problems as it swirls in its colossal
fermenters.28 Other molds are also being raised on an industrial scale to
produce enzymes that flavor and color fruit juices, tenderize meat, process
cereals for animal feed, and prepare ingredients for baking and brewing.
Fungal enzymes remove lactose from milk, modify milk formulas for
infants, and are used to coagulate milk without using rennet that comes from
calf stomachs. Enzymes from filamentous fungi are also used to turn
cornstarch into the corn syrup that sweetens sodas, breakfast cereals,
candies, cookies, and most of the rest of the inventory of prepackaged junk
foods. Incidentally, the syrup used to raise Quorn is produced from
cornstarch using Aspergillus enzymes, and yeast is grown on the same stuff
to manufacture bioethanol.
Fungal biotechnology, which began with palm wine and fermented milk,
has evolved into a global industrial partnership between humans and fungi.
Fungi have crept into the modern diet, one box, bottle, and aluminum can at
a time, until we cannot live a day without them. The economic value of this
symbiosis to the economy of the United States exceeds $1 trillion, which is
comparable to the annual revenue from the automotive industry.29

BACK TO THE WOODS

Fermentation comes from the Latin fermentare, which means to leaven or
make bread dough rise, and its meaning had been extended to describe
bubbling, effervescing, and alcoholic fermentation by the 1600s. Yeast is
breaking down sugars in all these processes. It is doing what comes naturally
to every fungus and defines the kingdom—namely, decomposition. So,
fermentation describes forms of disassembly, decomposition, or decay that
we have learned to control to ensure the formation of useful rather than
useless breakdown products. Once we recognize that some form of
decomposition drives all of the industrial applications of fungi, the repulsive
smell of some fermented foods makes complete sense. Although we do not
tend to think about wood rotting as an example of fermentation, the fungi
that do this in nature are performing the same kind of chemical
transformations as the fungi in blue cheese, soy sauce, and tempeh. For this
reason, we might expect mushrooms to be as nutritious as Roquefort cheese
or mycoprotein burgers, but we would be wrong. Although the structure of a
Quorn nugget is similar to the internal anatomy of a mushroom, Quorn is
packed with protein, whereas a mushroom is composed of indigestible fiber
and pumped-up with water. Mushrooms are very light on calories because
their colonies or mycelia feed on plant debris. Mycelia may come across
some scraps of animal protein from time to time and grab some snacks from
tree roots if they belong to a mycorrhizal fungus, but the developing
mushroom is never going to be flooded with sugars like a mold in an
industrial fermenter.
The fruit body arises from the mycelium as a platform for releasing
spores. Over the span of 150 million years, the fungi that produce these
umbrella-shaped sex organs found ways to make sensibly sturdy structures
that support the gills using the bare minimum of energy. This economy was
achieved by absorbing water like a sponge to stay upright rather than
developing stiffening tissues like the fibers in a plant. With their watery
interior, mushrooms are a poor food source for animals. Gram for gram,
mycelia have the same energetic value as cheese, whereas gilled mushrooms
that grow from them have no more calories than a lettuce. Truffles are a
luxurious exception to this rule because they evolved to attract animals for
dispersal and are as fattening as Roquefort.30
Nobody ever got fat eating mushrooms. Oysters, portobellos, porcini, and
other above-ground mushrooms contain a healthy mix of minerals, but
nothing that we do not consume in larger quantities in a serving of fruit or a
bowl of breakfast cereal. Mushrooms are eaten for pleasure, not for survival.
They add texture to recipes and some of them pack spectacular flavors. They
are also served in weight-loss diets, including the M-Plan, promoted by
several celebrities, which recommends replacing one daily meal with a plate
of mushrooms cooked in as little oil as possible. This is a straightforward
approach to reducing calories and is no more or less effective than
substituting a salad without any dressing for a richer meal. It is also difficult
to stick with, and the body tends to oppose the loss of calories in the
mushroom dish by stimulating greater food intake in the meal that follows.
Part of the appeal of the M-Plan and other diets that emphasize mushrooms
comes from the widespread belief that fungi have almost magical powers—
always unspecified—that can help reshape the body more than vegetables.
This illusion is also part of the allure of medicinal mushrooms, which is the
topic of chapter 7.

OceanofPDF.com
 7
Treating
MEDICINES FROM FUNGI

A GERMAN COUPLE hiking in the mountainous border between Italy and

Austria in 1991 came across a corpse, half frozen in a glacier and slumped,
face down, in a slurry of melting ice. They had discovered the mummified
body of a forty-four-year-old man who had died more than five thousand
years ago. We call him the Iceman, or Ötzi, which is a reference to the Ötzal
Alps where he was found. An arrowhead was lodged in his shoulder blade,
and the Iceman’s body bore other scars of combat including a head wound.
He may have bled to death or died from hypothermia before snow and ice
preserved his slender body and belongings. A pair of smooth white cuttings
from the flesh of a shelf fungus were threaded on ribbons of leather, and a
little pouch contained fragments of another fungus that served as a
firelighter.1 Ötzi was a Neolithic mycologist.
The white trinkets came from a fungus called the birch conk or polypore.
Ötzi would have had no trouble finding this mushroom. It is a common
parasite of older birch trees, which rots the trunk of the tree before bursting
through the papery bark to form a squidgy clod that expands into the shape
of a horse hoof. As the fruit body matures, a layer of tiny vertical tubes
develops on the bottom of the hoof that opens into thousands of tiny holes—
poly-pores. Pursuing a circadian rhythm, with maximum activity during the
nighttime, the fungus drops millions of spores per hour from these pores. It
grows best on trees weakened by drought or stressed by overcrowding, and
the birches are left so frail that they topple with a little shove.
In 1998, an Italian anthropologist studying the mummy proposed that
Ötzi had used “measured doses” of the fungus to induce “strong though
short-lived bouts of diarrhea.”2 This was a remedy, he said, for internal
parasites, whose eggs were identified in Ötzi’s mummified rectum.
Treatments for intestinal worms would certainly have been valuable in Ötzi’s
time, when the human gut was a more festive arena than today’s plumbing
system, with (to the tune of “My Favorite Things”) Roundworms in most
guts and hookworms in plenty / Segmented tapeworms that make you feel
empty / Many amoebas and pinworms like strings / These were a few of our
nightmarish things. Ötzi had one of the commonest parasites, the human
whipworm, which is a roundworm or nematode that causes painful bowel
movements and loss of appetite in heavy infections.3 Few readers will have
encountered this parasite, but everyone in Ötzi’s tribe would have known
them.
But the case for Ötzi’s use of the birch polypore as a worm treatment is
very flimsy. Diarrhea is a symptom of worm infestation rather than a
treatment, although temporary relief might come from emptying the bowel.
There is no evidence, in any case, that the birch polypore works as a
laxative, nor that the Iceman measured his doses of the fungus. However,
these baseless ideas were published in a top-tier medical journal, The Lancet,
and attracted a lot of media attention. With the imprimatur of this periodical,
few readers questioned the credibility of the medicinal claim, and Ötzi
became idolized as an aboriginal apothecary who trudged through the snow
to bear witness, in mummified form, to the ancient wisdom that we have
lost.
Misrepresentation afflicts the whole field of research on medicinal
mushrooms, making it difficult to tease out fact from fiction, but this is the
brief of this chapter. Although the birch fungus does not seem to have been
used by anyone as a worm remedy, it was adopted as a medicine to treat
other conditions. It appears in the literature on traditional medical practices
in Russia and Central Europe as an antiseptic and styptic (to stop bleeding).
The birch fungus is also mentioned as an anti-inflammatory and anticancer
agent and, more specifically, as a veterinary cure for vaginal tumors in dogs.4
Mushroom poultices have certainly been useful for treating minor wounds,
but I bet that Ötzi kept the conk for a different purpose. A polypore species
that grows on willows was carried by Blackfoot people, or Niitsitapi, and
members of other nations of the Northern Plains in the same way as the
Iceman, who carved white beads from the fruit bodies and hung them on
rawhide thongs.5 Museum collections in Alberta, Canada, include Blackfoot
charms made from human scalps decorated with these white beads. They
were also sewn onto sacred robes and worn on necklaces. One archival
photograph from the early twentieth century shows a chain of the fruit
bodies around the neck of a horse, looking like the modern rhythm beads
familiar to equestrians. Native Americans seem to have imbued their fungus
with spiritual significance, and Ötzi may have revered the birch polypore for
similar reasons. This is a more logical interpretation than creating a story
about the deworming properties of a fungus from thin air.

MUSHROOM THERAPIES
Illustrations of mushrooms in Neolithic petroglyphs are expressions of the
earliest conscious relationships between humans and fungi. We do not know
the significance of fungi to these people, but the psychoactive properties of
some species suggest that they would have featured in animist religions (this
is discussed further in chapter 9). Wherever mushrooms were plentiful,
people would also have learned to avoid the poisonous kinds, cook the
tastiest ones, and gather a few special fruit bodies as medicines. Although
the practical uses of the fungi diversified, they never escaped their
association with the supernatural. This blurring of the distinction between
medicine and magic continues today and is the foundation of the
multibillion-dollar market for mushroom extracts.6
The medicinal mushroom business depends on fewer than a dozen fungi
that are advertised as therapeutic stars. Reishi or lingzhi is a bracket fungus
with a polished red surface; shiitake is an unassuming brownish umbrella
with gills; maitake, or hen-of-the-woods, grows at the base of old trees as an
outpouring of crowded gray flaps; and turkey tail erupts from decomposing
logs as thin fans patterned with vivid stripes. Three more will cover the
“medicinal seven”: cordyceps fruits from dead caterpillars as a firm pencil-
sized stalk; chaga erupts from wounded birch trees (same as Ötzi’s conk)
before splitting and drying into a charcoaled lump; and lastly, lion’s mane
matures as a rounded wodge of pure white spines that looks like a frozen
waterfall.7
All of these fungi are described as medicinal mushrooms, and none of
them have proven medicinal effects. Devotees of medicinal mushrooms will
disagree with this statement, so it is worth restating: many people believe
that mushrooms are useful for treating illnesses, and some of these claims
may be true, but they are not backed up by dependable scientific evidence.
Mushrooms and mushroom extracts are not like other drugs, because they
are treated as foods rather than medicines in the United States and are sold as
dietary supplements and herbal remedies. This means that they escape the
stringent testing and regulation applied to over-the-counter medicines,
including painkillers and cough treatments and the drugs prescribed by
doctors. The absence of regulation may seem refreshing for people tired of
government interference in their lives, but this leaves us at the mercy of the
businesses that market medicinal mushrooms. For all their faults, the major
pharmaceutical companies are forced to follow some rules and are self-
disciplined by the continuous threat of lawsuits by consumers.
 Medicinal mushrooms are sold as slices of dried fruit bodies and powders
and, with no requirement for the manufacturers to identify the active
ingredients, we cannot assess the potency of one product line relative to
another. Imagine buying a bottle of aspirin and learning that the pills
contained nothing but chalk. We would be reasonably upset, yet a shameless
company could fill capsules with cornstarch mixed with a pinch of anything
mushroomy and sell them as cordyceps supplement with no legal
repercussions. This is not an exaggeration: there are no industry-wide
standards for assessing the ingredients in medicinal mushroom products.
Web postings proclaim medicinal mushrooms as wellsprings of “health-
boosting vitamins, minerals, and antioxidants” and “nutrients that support
the body’s natural immune functions and balance.”8 The term “well-being”
tends to crop up a lot and is as difficult to define as “nutraceutical,” with
which it is often associated. The language of the industry is demeaning to
anyone with a modicum of intelligence, but most of us are predisposed to
wishful thinking when it comes to health issues. It is easy to feel aloof when
we are feeling tiptop, not so much when we are, indeed, drifting into the
arena of the unwell. As long as the consumer does not favor mushrooms to
the exclusion of life-saving prescription drugs, these potions are harmless,
and the remarkable power of the placebo effect can be worth the purchase
price.

LION’S MANE AND BETA-GLUCANS

The lion’s mane mushroom, or hedgehog fungus, offers a useful case study
for a particular species. The mycelium of this fungus feeds on dead trees and
can keep fruiting for decades from the same log until the wood dissolves into
the forest floor. The mushroom is a naked spore factory that operates as an
inside-out polypore by discharging spores from the surface of its spines. Its
medicinal status rests on the experimental effect of extracts from the fruit
bodies on the growth of isolated nerve cells in culture dishes. Rats fed the
powdered mushroom have also shown increased levels of nerve growth
factor (NGF), which is a chemical messenger that contributes to the
maintenance of the nervous system.9 The chemicals in lion’s mane that are
responsible for these effects are called hericenones and erinacines, referring
to the Latin name of the fungus, Hericium erinaceus, meaning hedgehog-
hedgehog. In addition to the research on cultured nerve cells and rats, a
human study from Japan examined the effect of daily doses of powdered
lion’s mane on patients diagnosed with mild cognitive impairment.10 After
sixteen weeks of treatment, patients given mushroom capsules improved
their scores on a standard screening test for dementia relative to controls.
These investigations are an interesting starting point for more research,
not for marketing a mushroom as a medicine with proven curative powers.
Tero Isokauppila, author of Healing Mushrooms, is less cautious. He says
that lion’s mane “can potentially reverse the cognitive deterioration that
creeps up on all of us as we age,” which is supported by the Japanese study,
and goes on to describe the successful use of the mushroom in healing brain
damage.11 Paul Stamets, founder of FungiPerfecti, “Makers of Host
Defense® Mushrooms,” is similarly excited about this species. His website
says that a daily dose of the fungus, in the form of capsules, “optimizes
nervous and immune system health.”12 In business since 1980, FungiPerfecti
adds the following caveat to its endorsements of nutritional supplements:
“This product is not intended to diagnose, treat, cure or prevent any disease.”
Less restrained promoters of medicinal mushrooms declare that lion’s
mane “prevents neurodegenerative diseases like Alzheimer’s and
Parkinson’s”; is a treatment for depression and anxiety, digestive ulcers, and
cancer; reduces the risk of heart disease; and helps manage diabetes.
According to some websites, lion’s mane cures erectile dysfunction, while
contrary sources of online wisdom declare that the mushroom reduces
libido.13 The truths and fabrications about lion’s mane illustrate the way that
a scattering of scientific experiments supporting the pharmacological effects
of a fungus become stretched into fantastical declarations about mushrooms
as the universal panacea—the discovery of the philosophers’ stone that
eluded the alchemists of the Middle Ages.
The nerve agents isolated from lion’s mane have not been found in other
mushrooms, whereas another group of medicinal compounds are common as
muck, loaded into the cell walls of every fungus. These are the beta-glucans,
which are components of the hyphae that form mycelia and the squishy flesh
of mushrooms. Beta-glucans also come from oats and barley. Glucans are
polymers of sugars or polysaccharides. Cellulose, which is made by plants,
is another polysaccharide. Molecules of cellulose are assembled as thin
strands, which are packed lengthwise to form fatter threads, like the wires
inside electrical cables. Cellulose passes through the gut intact, where it
serves as the bulk of the indigestible fiber in our diet. The sugars that form
beta-glucan molecules are connected in a different fashion, which allows the
smaller ones to dissolve in water, making them part of the soluble fiber in
the diet. These smaller molecules bind to the surface of macrophages and
other cells involved in the innate immune defenses that are stationed in the
wall of the intestine.14
Beta-glucans are recognized by the immune systems of all animals from
butterflies to bison on dry land and crabs to cetaceans at sea. Even the
sponge ancestors of the whole animal kingdom are irritated by beta-
glucans.15 This universal response to beta-glucans speaks to the supportive
relationships that have been forged between fungi and animals from the
evolutionary get-go, as well as the mortal threat posed by fungal infections.
The human immune system recognizes beta-glucans as a measure of the
status of the fungi on the body along this spectrum of interactions. It is
attentive to beta-glucans released from yeasts and other fungi passing
harmlessly along the gut without provoking an inflammatory reaction. A
more aggressive response is mounted when larger pulses of beta-glucans are
detected from a fungus that is damaging our tissues.
From the foundation of beta-glucan science, followers of alternative
medicine have turned these sugary strings into the mycological equivalent of
ass gelatin—a traditional Chinese balm, also known as donkey-hide glue,
which is a miracle treatment for cancer. Ass gelatin does not, of course, cure
any forms of cancer, but that has not interfered with its traditional uses. The
positive thing about beta-glucans is that they do have proven effects on the
immune system, which is one of the few reliable facts that can be established
about medicinal mushrooms. This immune activity has led investigators to
pay serious attention to beta-glucans, and there have been several controlled
trials to see if they might prove useful as cancer therapies.
The traditional applications of mushrooms for treating cancer are
provocative, but the immunological logic is very weak. Why should a
chemical compound that stimulates the immune system to combat fungi turn
our defenses against our own cells that have become cancerous? The most
hopeful answer is that an immune system aroused by any stimulus might be
better at recognizing and clearing cancer cells than a weakened immune
system. Slender support for this idea comes from the effect of beta-glucans
as adjuvants—compounds that increase the action of another medicine.
Lentinan, which is a preparation of beta-glucans from shiitake mushrooms,
has been used in the treatment of stomach cancer in Japan for many years.16
Coupling conventional chemotherapy with lentinan injections appears to
increase the survival time of patients for an average of four months, and
similarly supportive effects have been reported for the treatment of lung
cancer in China.17 There is some hope here.
Like the work on lion’s mane, the preliminary studies on lentinan from
shiitake encourage further research. But they do not justify the astounding
successes of medicinal mushrooms imagined by their disciples, according to
whom, beta-glucans are “considered the best immune modulators globally,”
and are well on their way to being acclaimed as “a 21st Century Miracle.”18
If beta-glucans turn out to be beneficial, this would reinforce the regular
consumption of mushrooms as part of any healthy diet. Mushrooms certainly
add flavor and texture to our meals without many calories (see chapter 6),
but grocers have refrained, so far, from advertising jars of sliced buttons or
fresh portobellos as the secrets to longevity. Dr. Djibril Ba, from the College
of Medicine at Penn State, is more bullish, suggesting that eating the fruit
bodies of any fungus lowers the odds of dying from any cause.19 His
evidence comes from a cohort study in which participants answered
questionnaires between 1988 and 1994, and their fate—dead or alive—was
assessed twenty years later. The survivors were more likely than their
unfortunate peers to have reported eating some kind of mushroom in any
quantity and in any form in the twenty-four hours before they were
questioned. In principle, this means that someone who ate a bowl of
mushroom soup on the day before they filled out a questionnaire, or said that
they did so, tended to live longer than someone who did not, or did not
remember doing so. The proposed effect was modest, meaning that
mushroom eaters were 14 percent less likely to die from all causes, which
would include mortal illnesses and, one imagines, falling off ladders,
gunshot wounds, suicide, and shark attacks. The figures from this study
suggest that one in five fifty-year-old men who ate mushrooms at the
beginning of the study died before age seventy, compared with one in four
who did not eat mushrooms. Dr. Ba has also scoured through
epidemiological data and found that mushroom consumption is associated
with a lower risk of developing cancer and suffering from depression.20
If eating fruit bodies is as beneficial as Dr. Ba claims, he will receive a
Nobel Prize, and mushrooms and every food containing fungi will be
marketed as the elixirs of life, which, come to think of it, is exactly what
purveyors of medicinals have been doing for years. However, what the
cohort studies actually show is that there seems to be a weak relationship
between eating mushrooms and staying alive, but this does not mean that
eating them has any direct effect on longevity or happiness. Something about
the lifestyles of the mushroom eaters influenced their survival, or something
about the people who did not eat mushrooms influenced their demise.
Regarding the proposed antidepressive effect of eating mushrooms, a Polish
investigator, Piotr Rzymski, suggested that the enjoyment of foraging for
wild mushrooms might explain the promotion of mental health in Ba’s
study.21 This seems unlikely, given the rarity of mushrooming among
Americans, but it points to the confounding variables in a study of this kind
and the need for caution in interpreting cohort studies. If mycophobes rode
motorcycles more than mycophiles, this would explain the protective effect
of the fungi. Pick other less risky variables in human behavior and we might
find faint statistical signals of well-being among people who do crossword
puzzles or keep goldfish.
Students of medicine and journalism would benefit from reviewing and
discussing cohort studies like this as lessons in critical thinking and
scientific objectivity. Something interesting could come from Dr. Ba’s
investigations on mushroom eating, but to accept the notion that mushrooms
cure cancer would be an act of naivete comparable to belief in the Easter
Bunny. For an example of good practices in mushroom medicine, students
should consult an authoritative review published in the American Journal of
Medicine in 2021.22 The authors of this study analyzed almost 1,500
published studies on the effects of mushrooms on cardiovascular health and
concluded that only seven of them, or 0.5 percent, were sufficiently reliable
to recommend further investigation.

OBJECTIVITY AND OPTIMISM

A few years ago, I published an article titled “Are Mushrooms Medicinal?”
in the journal Fungal Biology, which was downloaded more than any
previous paper in the history of the periodical.23 Supportive emails arrived
from fellow scientists, but a much larger number of messages questioned my
intelligence and motives. One critic asked, “Did you even do a lit review on
the topic before you wrote this paper?” and continued, “It just seems like
you’re being willfully ignorant, intentionally misleading, or have an
interesting criteria [sic] for what constitutes validity.” My criteria [sic] is,
show me the evidence, which is codified in Hitchens’s razor, or
epistemological rule, authored by the late journalist Christopher Hitchens:
“What can be asserted without evidence can also be dismissed without
evidence.”24 Another correspondent was perplexed by my judgment and
suggested that I read their patent applications.
Here is the first sentence from my contrarian essay: “Despite the
longstanding use of dried mushrooms and mushroom extracts in traditional
Chinese medicine, there is no scientific evidence to support the effectiveness
of these preparations in the treatment of human disease.” And here is the
last: “It is time to treat anti-aging tonics made from mushrooms as a sad
phase in the history of mycology and proceed with the exploration of novel
compounds with the potential to change the course of our modern plagues.”
The importance of mushrooms in Chinese medicine is a good argument in
favor of their usefulness in some applications. If there is no evidence for
their value in treating illnesses, why would they have been endorsed by
practitioners for so long? Part of the difficulty in answering this question lies
in the philosophical gulf between Chinese and Western medicine. We know
that shiitake mushrooms have been cultivated on logs in China for centuries
and have been prescribed for replenishing qi, which is translated as the vital
energy that flows through the body. This concept overlaps with the humors
of the Greek physicians, which held sway in European medicine for two
thousand years and were mentioned in chapter 2. Now we demand evidence
of changes in blood sugar if a drug is used to treat diabetes, or a drop in
blood pressure after swallowing an antihypertensive medicine.
The continuing claims made for the uses of mushrooms should stretch
anyone’s credulity. To illustrate, I will search for “shiitake” combined
separately with each of the following illnesses and health conditions starting
with the letter a: acne, AIDS, Alzheimer’s disease, anthrax, arthritis, asthma,
and autism. Shiitake is endorsed as a treatment for all of them.25 Pick a
different letter and see for yourself. Inspired by Mr. Hitchens, I offer my
own razor:
A cure alleged for everything is an effective treatment for nothing.
By deifying shiitake and other species of fungi, the medicinal mushroom
magicians—the champions of champignons—betray themselves as con
artists to anyone willing to ask a few questions. Some of these latter-day
shamans are deliberate scammers, others know no better, and I am aware
that I am howling at the moon. Belief in the baseless powers of medicinal
mushrooms may also be strengthened by the widespread skepticism toward
medical authority.
All of this is unfortunate for the study of mycology because mushrooms
are probably brimming with undiscovered medicines that might be
developed using modern pharmacological methods. Why then, one might
ask, has there been such a rich history of drug discovery in plants, while
most of the woodland fungi have been ignored? Aspirin, ephedrine, opiates,
and quinine were used by herbalists in the form of unrefined preparations
from plants for thousands of years before any attempts at purification. The
historical success of these plant extracts in medicine argues for a similar
impact of mushrooms, but confusion about their nature (“these bastard
plants, or excrescences”) and toxicity (“some are very venomous and full of
poison”) meant that they were neglected by the great herbalists of Europe.
The quotes come from the English herbalist John Gerard (1545–1612), who
endorsed the attitude of the Roman poet Horace toward fungi: “Pratensibus
optima fungis natura est [mushrooms from the meadows are best]; aliis male
creditur [others are not to be trusted].”26 This advice comes from his Satires,
which served as a Roman self-help guide to a life of contentment and
reflected the danger of misidentifying mushrooms. Chinese healers were
more adventurous and became experts in identifying the wild mushrooms
that they used to treat illnesses. But without the Western transition from
herbalism to pharmacology, practitioners of traditional Chinese medicine
made no attempt to purify individual compounds from fungi. They saw no
need to do so, and the disjunction between traditional and Western medicine
endures today.
These are some of the factors that explain the absence of pharmacological
interest in the fungi until the twentieth century. This means that we are
playing catch-up and is why we need to apply the most up-to-date methods
to explore this natural pharmacopeia.27 The theoretical argument for drug
prospecting from fungal fruit bodies—namely, that they are likely to be there
—is bolstered by the plethora of powerful medicines that have already come
from fungi. The first antibiotic, penicillin, from an English strain of
Penicillium, was discovered in the 1920s; a second antibiotic called
cephalosporin was isolated from a Sardinian mold in the 1940s; and
cyclosporin, which prevents organ rejection after transplants, came from a
Norwegian fungus in the 1970s. Lovastatin, a cholesterol-lowering drug
isolated from an Aspergillus species, entered clinical trials in the 1980s, and
a variety of antifungal agents isolated from one fungus to treat infections
caused by another fungus are also synthesized by molds. The oldest fungal
medicine is ergotamine, which is produced by the ergot fungus that infects
cereals and has been prescribed as a treatment for migraines for more than a
century. (Ergot poisoning is featured in chapter 8.)
All of these medicines come from the feeding colonies of molds rather
than mushrooms, although some of them are manufactured in the lab today
without any participation by a living fungus. Lovastatin from Aspergillus has
also been found in oyster mushrooms, but at levels that are too low to have
any effect on cholesterol levels in the bloodstream. The search for
mushroom medicines is complicated by differences in chemical activity
between the fruit bodies and their supporting mycelia.28 These develop
because the fungi balance their metabolic processes between the feeding
mycelium and the reproductive mushroom to sustain both phases of the life
cycle without wasting energy. The way forward in the search for medicines
from mushroom-forming fungi—from their fruit bodies or supporting
mycelia—lies in the study of genomics. By sequencing and manipulating
whole genomes of fungi, we can search for the genes that control the
formation of useful chemical compounds. If we want to find new sources of
antibiotics that belong to classes of chemicals that are already known to
destroy bacteria, we can unearth them by analyzing little pieces of a
mushroom. Even if the mushroom does not make any of the antibiotics, the
fruit body will contain the genes for doing so if its mycelium is chugging
them out in the soil.
Finding the instructions is difficult because they are buried within the tens
of billions of As, Ts, Gs, and Cs in the fungal DNA. The workaround
involves breaking up the genome into hundreds of scraps called artificial
chromosomes and seeing what each segment of DNA can do on its own.29
This technology is known as genome mining. It allows investigators to pore
over the DNA of a fungus, strand by strand, like pirates pulling necklaces
from a treasure chest. Rather than selecting mushrooms randomly,
researchers can be guided by information on the traditional uses of
mushrooms.30 If Eastern Europeans have been using a particular bracket
fungus to treat rheumatism for centuries, this is a good candidate for drug
prospecting. Even if chemists have failed to find active chemicals in earlier
studies, the fungus may be worth a second look because its DNA may harbor
the instructions for making something useful. Genome mining has the power
to transform the medicinal uses of mushrooms into a science.
While mushroom medicine has gone nowhere, the yeast used for brewing
and baking has transformed the pharmaceutical industry as an infinitely
pliable platform for drug production. Ordered to make human insulin using
the human gene, yeast complies and produces half of the global supply of
injectable insulin to combat diabetes. Modified with a DNA sequence from
the human papilloma virus (HPV), yeast translates this into copies of the
protein that forms the shell of the viral particle. Separated from the yeast,
this protein is injected as a vaccine against HPV, which has the potential to
eliminate the form of cervical cancer linked to this infection.31 Another
medicine from genetically modified yeast is used to treat an age-related eye
condition, and there is a lot of research on using yeast cells to synthesize
painkillers. When we consider antibiotics from molds and all these drugs
manufactured by yeast, it is evident that fungi are an indispensable source of
modern medicines. To add new compounds from fungi to the pharmacy, we
need to bring the chemistry of mushrooms into the mainstream.

FROM THE NEOLITHIC TO THE ANTHROPOCENE

Ötzi’s world was filled with mythology and mycology. The Iceman’s woods
and meadows were a mycological wonderland, and his childhood would
have been filled with stories about toadstools, and witches, and wood spirits.
We will never know why Ötzi carried the birch conks, whether they were
charms, or if he valued them as medicinals. As a plentiful and diverse
resource, people would have put fungi to use in one way or another, even if
they learned to steer clear of most of them for fear of poisoning. All we can
say with any confidence is that some mushrooms were handy first aids for
treating wounds and that others were sought for their hallucinogenic
properties (which are described in chapter 9). The challenge in the twenty-
first century is to reengage with the therapeutic possibilities of mushrooms
without resorting to superstition in treating disease. Science needs to work
alongside a sense of mycological curiosity to find the pharmaceutical riches
in the woods.
My confidence in the abundance of undiscovered mycological medicines
is increased by the chemical makeup of some of the least conspicuous
mushrooms. Smaller than thumbnails, beautiful as any flower, bird’s nest
fungi sit on broken twigs waiting for raindrops. Drops falling into the cups
flick the spore-chocked eggs into the air. Each discharged egg drags a sticky
harness—think tiny chameleon tongue—that wraps around a grass stalk,
bringing the fungus to a halt after a one-second flight.32 The discovery of
antibiotics in these acrobatic species began with a chance observation made
by Alex Olchowecki, a graduate student at the University of Alberta in the
1960s.33 Alex noticed that bacteria contaminating a culture of one of these
fungi were wiped out from the region closest to the growing hyphae. A
similar bacterium-free halo was observed around hyphae of Penicillium
notatum by another Alex, Alexander Fleming, in 1928. Fleming’s discovery
of penicillin led to a Nobel Prize in 1945, shared with Howard Florey and
Ernst Chain, who did the hard work in antibiotic development. Olchowecki
did not receive any prizes for discovering the antibiotic from the bird’s nest
fungus, called cyathin, but went on to enjoy a distinguished career at the
University of Manitoba.
Work on the chemistry of the bird’s nest fungi has continued, and a whole
class of antibiotics belonging to the “cyathane diterpenes” has been found in
these pretty little mushrooms. None are as powerful as penicillin at killing
bacteria, but some of these molecules stimulate the growth of nerve cells,
like the drugs isolated from lion’s mane.34 Cyathanes purified from bird’s
nests also work against cultures of cancer cells. The detection of antibiotics
in the bird’s nest fungi increases the odds that some useful molecules are
hiding in fairy bonnets and eyelash cups, pinwheels, violet corals, orange
jellies, bleeding mycenas, and the rest of the woodland fungi. Now is the
time for investigators and investors to get serious: carpe boletum, as Horace
would have said, if he had developed a more favorable opinion of
mushrooms. On the other hand, the search for medicines in fruit bodies is
likely to reveal as many toxins as treatments, and we consider the ruinous
nature of some of the prettiest mushrooms in chapter 8.

OceanofPDF.com
 8
Poisoning
TOXINS IN MUSHROOMS AND MOLDS
LIKE OTHER FACETS of the relationship between humans and fungi, the
presence of fungi in the diet and the uses of medicinal mushrooms are
mixtures of conscious and unconscious interactions. We have seen how
fungi are front and center in the fermentation of cheeses and staple foods in
Asian cuisine, and that molds have become the “meat” of mycoprotein
nuggets. Beer brewing, winemaking, and bread leavening by yeast are other
obvious examples of the hidden role of fungi in our diet. But eating
mushrooms, whether for food or medicine, is the most conspicuous part of
human mycophagy and has assumed such significance in human culture
that it is the first thing that most people consider in our associations with
fungi. In this chapter we look at mushroom poisoning and our equally
unintentional exposure to the toxins produced by molds.
On Easter weekend in 2020, Dr. Anna Whitehead, a physician in New
Zealand, picked some mushrooms beneath an oak tree and cooked them
with fresh fish for lunch. She said that she had planned to check what they
were but became distracted by work and sautéed slices of the fruit bodies
without thinking. She awoke early the next morning and began vomiting
green liquid. Suspecting what might have happened, she staggered upstairs
and searched for images of poisonous mushrooms on her computer.
“Immediately, a picture of death cap mushroom[s] flashed up. I recognized
it instantly as the type of mushroom I had picked and eaten.”1 She rang for
an ambulance. After a day in hospital hooked to an IV in her arm to keep
her hydrated, the symptoms subsided, and she went home. Disaster averted?
Not quite.
A few hours later the nausea returned, worse now. The classic
honeymoon period associated with death cap poisoning was over, and she
returned to the hospital. Toxins from the fungus had been circulating in her
bloodstream, killing cells in her liver. The pain in her abdomen was
agonizing. She seemed to be dying. But her doctors and nurses pulled a Hail
Mary by resuming IV support, and after two days in a critical care unit her
liver began to recover. Dr. Whitehead had dodged the reaper. In interviews
she said, “I have never ever felt so terrible,” far worse than the side effects
of the chemotherapy she had received to treat cancer long before the
poisoning. She also remembered the strong flavor of the pale green caps,
which she had thought was the way wild mushrooms are supposed to taste.
Other survivors of poisoning have said that the death cap is the most
delicious mushroom they have ever eaten. If a physician like Dr. Whitehead
can make an almost fatal error, what hope is there for the rest of us?

A GUIDE TO EDIBILITY
Poisonous mushrooms, sometimes distinguished from the harmless species
with the name toadstool, seem a very remote threat in the twenty-first
century. They are more likely to be associated with fairy tales about witches
in the woods than part of a liberal education. But with a renaissance in
interest in foraging for wild food, anyone who plans to eat wild mushrooms
needs to pay attention.2 The death cap, Amanita phalloides, deserves special
notice because it is an invasive species that has spread from Europe across
the world and is poisoning people who mistake it for native species that are
edible.3 We must think carefully before eating any fruit body that we find in
the wild. My recommendation for safe mushrooming is to limit foraging to
a selection of the tastiest species—to become intimate with their appearance
and leave the rest of them to get on with the job of being mushrooms.
When the weather has been warm and wet at the end of the summer, the
“savory seven” in the midwestern United States, overlapping with the
“medicinal seven” in chapter 7, begins with oyster mushrooms, jutting from
logs like shellfish from rocks, but with the taste of a delicately perfumed
version of a white button mushroom rather than the briny minerality of a
fresh bivalve.4 This subtle oyster-mushroomy flavor is easily lost by
overcooking, but nobody would eat them raw. Lion’s mane, the medicinal
mushroom, tastes much the same. Young puffballs with pure white innards
are gill-less buttons with nothing to offer the epicure besides the surprise of
serving them as cooked discs on a pizza, or in any other dish where
cultivated mushrooms are expected to appear. Chicken of the woods and
maitake are a nudge more interesting in the kitchen: firmer than oysters,
they carry a fruity or woodsy fragrance that works well in soups and stews.
And, more flavorful than their peers, fruity chanterelles and earthy-nutty
porcini rise above the butter and garlic absorbed by their flesh if they are
not overcooked. There is an obvious seasonality to this list, with morel
species replacing these edibles in the spring, but it is difficult, though not
impossible, to confuse any of these mushrooms with poisonous species.
This pedestrian advice will dismay more adventurous mushroomers who
lionize false morels, Gyromitra species, which contain a toxin that is
converted into rocket propellant unless it is boiled away before eating;
edible webcaps that are difficult to distinguish from deadly poisonous ones;
and even a few kinds of benign amanitas—grisettes and blushers—whose
doppelgängers include death caps and the aptly named fool’s mushrooms
and destroying angels.5 Serious mushroomers are so deeply invested in
identifying fungi that they are unlikely to make mistakes, but the rest of us
should be very careful. By flagging the minority of truly deadly mushrooms
with skull and crossbones symbols, guidebooks and websites can leave the
naive mushroomer with the impression that most of the other mushrooms
are edible. Although this is tru-ish, edibility does not equate with
palatability. The delicious ones are as scarce as the poisonous, and the taste
of most mushrooms varies from chewy-cardboardy to soggy-cardboardy.
Safety lies in highlighting the appetizing and unmistakably harmless
mushrooms, rather than encouraging people to abandon themselves to the
carnival of fruit bodies of varying shapes, sizes, colors, smells, and
edibility. Fish are like mushrooms: a few are delicious, some are poisonous,
and most make dismal meals and should be allowed to get on with being
fish.
The savory seven is adjustable for other regions, although errors occur
when a favored mushroom happens to resemble a lethal species like the
death cap. None of my midwestern treats look like anything toxic, but the
situation is different in Asia, where an assortment of mushrooms collected
from the surrounding forests are sold in local markets. These delicacies in
southeast Asia include species of Amanita with pale yellow caps and cream
caps. Other than these subtle differences in color, these fungi have all the
hallmarks of the mushrooms called destroying angels—white gills, ring
flopping down the top of the stem, and the bottom of the stem stuck in a
cup. This explains why unwary foragers familiar with the edible amanitas in
Asia are tricked by poisonous ones in North America.6 California
mushroomers have made similar errors in confusing death caps for Pacific
amanitas, known as coccora or coccoli, which have a fishy smell and can be
substituted for seafood in ceviche.7

ALPHA-AMANITIN
The deliberate substitution of lethal for edible amanitas is chronicled in the
story of the assassination of Emperor Claudius by his wife, Agrippina, in
AD 54. The most satisfying version of the plot begins with Caesar’s
mushroom, which is an edible amanita. This orange-capped mushroom is
eaten in its egg form, known as ovolo buono in Italy, before the fruit body
emerges and expands like an umbrella. Claudius adored this mushroom,
which made death caps the perfect murder weapon. There are other readings
of his death, but this one provides the most satisfying end to this disgraceful
tyrant.8 Caesar’s mushroom is a rare example of a mushroom that tastes best
raw, served in thick slices dressed with a little olive oil and lemon juice, and
is so sought after that it has been given protected status to prevent over-
collecting.9
While most poisonings result from failures in mushroom identification,
the medical literature includes a few cases in which people have knowingly
eaten death caps in suicide attempts. A sad case in Italy involved a young
woman who had learned a lot about mushrooms from her father, who was a
keen amateur mycologist, collected three large death caps and made sure
that she ate a lethal quantity.10 She would have died but was rushed by her
parents to the hospital, where she was saved with a liver transplant. A
stranger story of mushroom poisoning involves a bizarre case of
experimentation by a Turkish man who ate two death caps to determine
whether they were safe: “He told the household that if nothing happened to
him, they could eat the remaining mushrooms together the next day.”11
Hours after his meal he developed severe symptoms of gastrointestinal
distress and, after some resistance, was taken to the emergency room by his
family. Once in the hospital he responded to rehydration and recovered after
a few days. This was a remarkable comeback because he had consumed
three times the fatal dose of death caps.
After the flesh of a death cap dissolves in the stomach, its toxins are
absorbed from the gut and circulate around the body.12 The worst of the
poisons is alpha-amanitin. Amanitin interferes with an indispensable
enzyme that ratchets itself along DNA strands, reading and transcribing the
genetic code in the first step of protein synthesis. Cells exposed to amanitin
shut down without a continuous supply of proteins, and the liver is wrecked
as it concentrates the toxin from the bloodstream. Amanitin can be mopped
up by drinking a jet-black slurry of activated charcoal immediately after
eating the mushrooms. This remedy is useless after the toxin reaches the
small intestine and the poisoning symptoms proceed. Once this happens, the
best treatment is intravenous therapy to maintain hydration and give the
body a fighting chance to flush the toxin away in the urine. Poison that is
not filtered by the kidneys is returned to the bloodstream, where it
recirculates and pummels the liver afresh. Amanitin is one thousand times
deadlier than aspirin.13 Experimental treatments include dialysis to assist the
natural action of the kidneys. Some physicians also suggest draining the
bile duct, which conveys the toxin from the liver and gall bladder into the
small intestine, to help eliminate the poison. Evidence for the effectiveness
of these treatments is limited. The same uncertainty applies to the use of
high doses of penicillin to increase the excretion of amanitin in the urine,
and to silymarin, a drug extracted from milk thistle plants that offers some
protection to liver cells.
Decades of alcoholism do not come close to matching the acute liver
damage resulting from eating a single death cap mushroom, and an organ
transplant is the only option when the liver does not rebound.
Transplantation is followed by lifetime support to prevent rejection and this,
ironically, can be provided by two drugs that come from molds: cyclosporin
produced by a soil fungus (see chapter 7), and myophenolic acid (MPA)
from a Penicillium. The Penicillium that produces MPA grows on mudflats,
sand, stored fruit, wood, and the surface of decomposing mushrooms. This
offers a circular mycological meditation, from a disastrous woodland foray
to a liver transplant and on to a life-sustaining treatment with a medicine
produced by a mold that grows on mushrooms: from fungal illness to fungal
cure.
While the death cap is an expert in liver damage, Smith’s amanita attacks
the kidneys. This renal specialist grows in the Pacific Northwest, which
presents a problem because it is mistaken for the delicious matsutakes,
which have a cult following in the region.14 Most victims recover kidney
function a few weeks after their encounter with this species, but this
poisoning syndrome is another reason to be wary about eating any
mushroom wearing a ring and sitting in a cup. This does not mean,
unfortunately, that the cupless and ringless mushrooms are safe. Far from it.
Amanitin is also produced by the autumn skullcap, which is a little brown
mushroom.15 This is a species of Galerina that decomposes wood and
produces clusters of fruit bodies and has been eaten by unwary shroomers
who think they have found psychotropic psilocybes. Skullcaps are cupless
mushrooms that can come with or without a thin ring on the upper part of
the stem, making a mockery of any simple rules for recognizing toxic fungi.

ALL MUSHROOMS ARE POISONISH

Although alpha-amanitin causes most of the serious poisonings, the list of
problematic mushrooms goes way beyond fruit bodies containing this
compound.16 Thirty or more species of webcaps contain orellanine, which is
a toxin that targets the kidneys. The symptoms of webcap poisoning can be
obscured by a honeymoon period, like the delay after eating death caps, but
continuing for weeks before the injuries become evident. In other
mushroom poisonings, the toxins have not been identified. Yellow knight
poisoning is the best example of this kind of cryptic toxicity, in which
something in the fruit bodies causes muscle damage. The yellow knight is a
flat-capped mushroom that grows in coniferous forests and has been eaten
in many European countries for centuries. It has been fried, boiled, and
pickled, listed as a favorite in mushroom guides and cookbooks, and was
celebrated as a wild food without any concern for its safety until clusters of
poisonings were reported from France, Poland, Lithuania, and Germany.
The first dozen cases were admitted to French hospitals between 1992 and
2000.17 Creatine kinase levels in the bloodstream of the patients soared,
which was a marker for muscle breakdown, and their urine darkened with
proteins and blood cells. Patients felt nauseous, sweated profusely, and
experienced leg weakness that left some of them unable to walk. Most
recovered within a couple of weeks, but three of the patients died.
 What happened here? Yellow knight has a lot of look-alikes, so it is
possible that the poisoning was caused by a different species of mushroom.
But there is an alternative idea that says more about our dietary relationship
with the fungi. Cases of yellow knight poisoning reported from Lithuania in
a 2016 study included a fifty-six-year-old man who had eaten generous
helpings of the mushroom three times a day for a week.18 Other comparably
fanatical patients had consumed the fungus daily for a week or more, which
raises the crucial issue of dosage and the adage attributed to Paracelsus, the
Renaissance physician: dosis sola venenum facit, the dose makes the
poison. The same rule applies to everything we eat. Potatoes, for example,
contain the toxic alkaloid solanine, although one would have to eat a sack
of tubers at a sitting to be poisoned by them.19 What if yellow knight and
every other mushroom contains toxins, and dosage is the deciding factor in
the development of poisoning symptoms?
Rodents fed huge quantities of a variety of powdered mushrooms show
the same spikes in creatine levels found in humans poisoned with yellow
knights.20 The mushrooms in these unpleasant studies included shiitake and
chanterelles, and other indications of tissue damage were observed in mice
fed masses of white button mushrooms. The doses imposed on the mice
were staggering, equivalent to force-feeding a human fifty portobello
mushrooms per day. The value of these experiments, which did not identify
any toxins in the mushrooms, lies in their implication that any mushroom
that is safe in moderation might be harmful in excess. Almost every species
seems capable of upsetting the digestive system, so we need to avoid eating
any mushroom by the bucket.21 On the other hand, people who enjoy
collecting and cooking a few fresh yellow knights from time to time should
continue doing so. This does not mean, of course, that anyone should flavor
their omelets with a little diced death cap.

THE PRETTIEST POISONOUS MUSHROOM

One of the prettiest mushrooms in all creation sits at the ruinous end of the
toxicity scale. This fungus is the poison fire coral, whose scarlet fingers
emerge from leaves littering the woodlands of Asia and Oceana and shed
spores from their silky surface. Fire coral bears a passing resemblance to
the medicinal mushroom reishi, which is why it is sometimes picked in
error and steeped in hot water to make tea. This snafu replaces the
mushroom of immortality, which is the nickname for reishi, with the
mushroom of skin and hair loss, blood disorders, and brain damage.22 The
fire coral contains potent poisons called satratoxins, and a pea-sized piece
of the fungus has proven lethal. Bizarre symptoms of acral skin peeling on
the palms of the hands and soles of the feet, and alopecia, distinguish
poisoning by fire coral from every other mushroom. Damage to the brain
and bone marrow are also unique to the fire coral.
Corals or club fungi fruit as colorful spikes that range from fine wires
that stand tall and straight, like dried spaghetti, to fatter stubs, and branched
forms that resemble antlers, menorahs, and tiny painted cauliflowers.23 A
few species are popular edibles, including multiple species of chunky corals
known as escobetas, or scrubbing brushes, in Mexico.24 More than one
thousand species of coral fungi have been described, and a good number
cause nausea and intestinal turbulence. The following entry in a guidebook
illustrates the difficulties in foraging for edible ones: “Ramaria flava is
reported to be edible but of only moderate quality; however, it could easily
be confused with Ramaria formosa, which is seriously poisonous, causing
stomach pains and diarrhea if eaten. There is another reason why this coral
fungus should not be collected in Britain: it is a very rare find.”25 Anyone
who seeks coral fungi must be a very serious mycophile. These daredevils
look at all mushrooms as potential edibles, evaporating the toxins from
some of the dangerous species by cooking and reveling in nature with
something akin to the attitude of big wave surfers or free climbers.
My reversal of their behavior—treating all mushrooms outside a grocery
store with suspicion—will seem farcical to these experimental
mycophagists, who may counter with “no one gets out of here alive,” as Jim
Morrison, of the Doors, and many others, have opined. They are modern
McIlvainians, whose forebear, Captain Charles McIlvaine (1840–1909),
tasted every mushroom he found to enrich the descriptions in his
doorstopper of a book, One Thousand American Fungi, published in 1900.26
Commenting on a group of mushrooms known for their laxative properties,
this indomitable veteran of the Civil War wrote, “Wherever and however
they grow, Hypholomas are safe. I have eaten them indiscriminately since
1881.”
To go beyond the obviously noxious mushrooms tarred by millennia of
poisonings, the McIlvaine method is the only way to widen the list of
harmful and harmless fungi. With the nickname Old Ironguts, McIlvaine
did not offer the most trustworthy advice on safety, but as the sample size of
consumers has increased, printed and virtual mushroom guides offer a
wealth of information for foragers committed to a little research.

WHY SOME MUSHROOMS ARE VERY POISONOUS

Larger animals expend more energy chewing and digesting fruit bodies than
they get back in calories, which suggests that the chemical pathways that
manufacture toxins in mushrooms probably evolved to repel insects and
other tiny animals like nematode worms.27 These smaller invertebrates have
the opportunity to avoid the watery filaments that make up most of the fruit
body and eat spores and other specialized cells in the mushroom that pack
storage fats. This nutritional reward is enough to power the growth of insect
grubs because we find some of the poisonous fruit bodies riddled with
larvae. These insects are obviously impervious to the toxins.
When mushrooms decided to become poisonous, in an unconscious
evolutionary sense, they opted to make chemicals that attacked the
fundamental workings of their insect enemies as well as their unintended
human targets. Making chemicals with this kind of generalized hostility
toward life carries the occupational hazard of self-poisoning, but
mushrooms have reengineered their proteins to be less sensitive to them.28
They also benefit from operating as immobile platforms. Unlike a
poisonous snake, which slides around with onboard venom sacs, the mature
fruit body does not need to maintain an active metabolism and can poison
the tissues of its stem and cap without any consequences. All the mushroom
must do is stay upright and avoid damaging the cells on the gill surfaces
until they finish producing the spores. The extreme toxicity of mushrooms
like the death cap probably developed as a defense against their enemies as
they gained resistance via a form of evolutionary arms race.
 WITCHCRAFT AND WISDOM
In countries like Germany and Poland, where collecting wild mushrooms is
an important part of the national culture, skills in fungal identification have
been passed from generation to generation.29 This basic mycological
wisdom triumphed over long-standing superstitions about mushrooms
among these mycophilic people and allowed them to avoid death caps while
harvesting chanterelles. Poisonings still happened, of course, but there was
no point blaming the local witch when it was obvious that someone had
picked the wrong species. Outbreaks of fungal poisoning in medieval
Europe that slew whole communities were a different matter. These
epidemics were mystifying, because the toxin came from a tiny fungus that
sprouted on rye and other cereals and was ground into the flour to make
bread. Nobody demonstrated a solid link between this fungus and the
plague that became known as ergotism in the seventeenth century, and
supernatural explanations prospered in the knowledge vacuum of the Dark
Ages.
Ergotism erupted after rainy summers, striking villagers with nausea,
headaches, and vomiting; they lost the feeling in their fingers and toes,
suffered convulsions and tetanus-like cramps, became unable to speak, and
bit through their own tongues.30 This was exactly what one would wish
upon one’s worst enemies. Maddened by their afflictions, some sufferers
felt that insects were crawling beneath their skin, which is a symptom called
formication, and others were consumed by feelings of intense heat. The
burning sensation was described as ignis sacer, or holy fire, and seen as a
punishment from God. Gangrene set into limbs starved of blood, fingers
and toes turned black and broke off at the joints, and arms and legs were
lost in the most extreme cases. These were the wages of sin.
Gangrenous symptoms predominated in some outbreaks, convulsions in
others. The fungus, Claviceps, produces ergot alkaloids that interfere with
the flow of nerve impulses and muscle contraction, wreaking havoc
throughout the body. The ergot poisons are examples of mycotoxins, which
is a term reserved for the toxins produced by molds rather than
mushrooms.31 In addition to narrowing blood vessels and making muscles
seize, some mixtures of the ergot alkaloids produce behavioral changes and
hallucinations. This diversity of disorders reflects the chemical virtuosity of
the ergot fungus. It is a one-stop bioweapons center, whose real aim in life
is to eat cereals without any competition from other microorganisms or
from animals. After infecting the rye plant, the fungus takes possession of
one or more of the flowers, growing in the place of healthy grains and
protruding from the ears as firm black pellets, curved like bananas. These
are the ergots, whose name comes from a word in Old French for a cock’s
spur, which is a perfect simile. The toxic alkaloids are mixed into the flour
when the ergots are milled along with the healthy rye grains.
Ergotism was recognized in the ancient world, with a plausible mention
on an Assyrian tablet, but the earliest undisputed descriptions come from
the Christian era, when rye bread became a staple in Western Europe.
Ergotism became known as St. Anthony’s fire, after the relics of the
eponymous desert father became associated with miraculous cures for the
scourge. Spontaneous abortion was another of the shocking effects of
ergotism, which led to the deliberate use of raw ergots to assist with labor
and to induce abortions in unwanted pregnancies. Purified ergometrine,
which is one of the alkaloids, was introduced as a drug to prevent
hemorrhage after childbirth in the 1930s and played a significant role in the
reduction of the maternal death rate.32 Ergometrine is also used to induce
the delivery of the placenta. Another alkaloid, ergotamine, is used to treat
migraine headaches, and a variety of synthetic drugs based on the structures
of the ergot chemicals have other uses in medicine. This is an example of
healing with poisons in Western medicine, which was a central principle of
Chinese medicine more than a thousand years ago.33
Lysergic acid is a precursor for the ergot alkaloids, forming a chemical
skeleton that the fungus decorates and prunes to craft a whole family of
toxins.34 This was isolated from ergot and used to produce LSD by Albert
Hoffman, the famous Swiss chemist who discovered its psychedelic
properties through self-experimentation in the 1940s. Hoffman went on to
isolate another fungal alkaloid from mushrooms rather than ergots. This
was psilocybin, which stars in chapter 9.
Lysergic acid and closely related compounds in the fungus are presumed
responsible for the frightening hallucinations experienced by victims of
ergotism in the Middle Ages and must have added to the sense among the
villagers that they were dealing with the occult. Divine punishment was a
popular interpretation of these dreadful visitations, along with witchcraft
and demonic possession. The psychedelic horror of ergotism is thought to
have inspired the nightmarish figures in the triptych The Temptation of
Saint Anthony, painted on hinged wooden panels by Hieronymus Bosch in
1501, or thereabouts.35 Flying fish circle the sky, and a winged demon
carries Saint Anthony to a ghastly forum occupied by a man with the face of
a pig and other monstrosities. Anthony gestures toward Christ, who stands
in a grotto separated from the anarchy, and symbols of ergotism include a
severed foot and a village burning in the background.
Ergotism may have caused the outbreak of delirium and seizures among
girls in colonial Massachusetts in the 1690s, but the court in the infamous
Salem witch trials favored a supernatural source. Nineteen villagers were
hung for witchcraft, and a twentieth martyr, a man, was crushed to death
under a plank weighted with rocks in an attempt to obtain a confession.36
Although ergotism may have been at the root of this debacle, other causes
have been suggested, and the arousal of mass psychogenic illness or
hysteria within a community of religious extremists seems likelier than the
fungus.

MYCOTOXINS FROM MOLDS

The fearful poisonings caused by fungi have led to mycological
explanations for other events in world history, including the Plague of
Athens, the Black Death, the rise of Calvinism, and the Great Fear at the
start of the French Revolution.37 The evidence for these connections varies
from weak to nonexistent, but the idea that we can apply modern science to
decipher ancient mysteries is often more appealing than the truth that some
historical riddles are unsolvable. Facts can be fitted to theories, and even
when the original musings are dismissed by objective scholarship they
persist in the popular imagination. The Athenian Plague, described by
Thucydides in the History of the Peloponnesian Wars, is an interesting case
study. Many of the symptoms of the plague described by Thucydides,
including burning sensations, violent spasms, and the loss of fingers and
toes, dovetail with ergotism, and this connection was first proposed by a
German toxicologist in the nineteenth century. Later experts on ergotism
pointed out that the fungus could not have caused the deaths of thousands of
Athenians in 430 BC because they did not eat rye, but the tie-in to fungi
was resurrected with the suggestion that the ancient Greeks could have been
wasted by toxins produced by a different mold growing on stored wheat,
which was a staple.38 This keeps fungi on the list of possible causes of the
Athenian Plague, although an infectious bacterium or virus is a safer bet.
Outbreaks of food poisonings are obviously limited to the direct
consumption of the toxin, but they can resemble the impact of an infectious
disease when a large enough population is compelled to eat a lot of the
same thing under conditions of famine. The Athenians might have been
forced to eat moldy grain during the interminable siege of their city by the
Spartans. A more convincing case of mold poisoning played out in the
region of Orenburg on the Russian steppes in the 1940s.39 Severe food
shortages during and after the Second World War led people to eat fallen
grain. Lying under the winter snow, a species of Fusarium began to rot the
unharvested crop, permeating the cereal with poisonous trichothecenes. The
syndrome produced by consuming these chemicals is described as
alimentary toxic aleukia, or ATA. ATA begins with nausea, vomiting, and
diarrhea, like some mushroom poisonings, and is followed by widespread
hemorrhaging of blood vessels that can progress to organ failure. The loss
of blood flow to the skin results in infections by bacteria that accumulate in
disfiguring facial wounds. Estimates suggest that one in ten people in the
region were sickened with ATA; the number of deaths is unknown. This
disaster was as diabolical as one of the historical outbreaks of ergotism,
with the difference that there was no question about the cause: no witch
trials, no need for self-flagellation, just suffering caused by a mold.
Ergotism and ATA are a distant threat now, but we absorb traces of
mycotoxins from our food every day.40 They are an unavoidable part of the
diet, because molds contaminate the entire food chain from cereals to fruits,
vegetables, dairy products, and meat. Even farmed fish carry traces of
mycotoxins from the feeds used in aquaculture. Mycotoxins flow in our
blood whatever we choose to eat, which is another illustration of the way
that the threads of the human relationship with the fungi permeate every
facet of our lives.41
Aflatoxins are the most widespread and troubling mycotoxins in the
modern diet. They are made by species of Aspergillus and tuck themselves
into our DNA, where they cause mutations that can increase the lifetime
risk of liver cancer.42 Aflatoxins also damage the gut and cramp the immune
system, making us more susceptible to viral infections. At high doses they
can cause birth defects, and later in life they are implicated in
neurodegenerative diseases. This is a pretty damning rap sheet. Aflatoxins
pose the greatest risks in developing countries, where hot and humid
climates stimulate the growth of the molds on corn, peanuts, and other
staple foods. Kenya is considered a hotspot for aflatoxin poisoning.43
In the United States, the USDA monitors the level of aflatoxins in
peanuts, almonds, and pistachio nuts. Even with this surveillance, it is
impossible to shield these commodities from mold growth, and the USDA
permits low levels of aflatoxins in peanut butter and other foods. Public
interest in this issue has forced the manufacturers of peanut butter to
address the presence of traces of these natural toxins in the iconic American
sandwich spread at a time when they are also dealing with more widespread
concerns about peanut allergies in children. Interest in aflatoxins has
supported a premium price for Valencia peanuts from New Mexico, where
the dry climate reduces mold growth on the crop before and after
harvesting. Cats and dogs are also affected by aflatoxins and are highly
susceptible to poisoning because their diet is so uniform. This has led to
regulations on mycotoxin levels in pet foods.
Most of our interactions with mycotoxins occur when we absorb these
foodborne contaminants from the gut, but the lungs are a second sponge for
toxins. Agricultural workers are most at risk if they inhale dust from
contaminated grains. Cultures of lung cells treated with aflatoxins lose
some of their ciliary strength, meaning that the hairs that normally move
mucus in the lung beat more slowly when the cells absorb the toxins.44 This
adds to the problems of allergic illness in workers who inhale spores from
moldy grain in silo operations without state-of-the-art air purifiers and dust
masks (see chapter 3). Occupants of homes and buildings that become
blackened with mold spores after flooding may also be exposed to
mycotoxins, but the available evidence suggests that the dosages would be
too low to cause any harm.45
“Blackened” is the operative word here because a mold named
Stachybotrys, vilified as the “toxic black mold,” became a public health
pariah when it was linked to lung bleeding and infant deaths in Cleveland,
Ohio, in the 1990s.46 This fungus grows on the thick paper that covers the
surface of drywall or gypsum board when it becomes soaked with water and
produces a whole gamut of mycotoxins. It is a nasty piece of work, but its
role in the Cleveland tragedy is unproven. The spores of the black mold are
sticky and are not blown into the air very easily. This limits the number of
spores that anyone is likely to inhale and means that the dose of the toxin
carried on these particles is vanishingly small. Under conditions of massive
mold growth, however, the jury is still out. The developing lungs of infants
are likely to be very sensitive to mycotoxins, and this mold may be
dangerous when it grows in dense patches on nursery walls. It has also been
suggested that volatile chemicals that evaporate from the mold colonies
may become toxic in confined spaces.47 The funky smells of damp houses,
wet clothing, and spoiled food are produced by some of these compounds.
While we cannot detect most of these gases, dogs have been trained to sniff
out areas of mold contamination in buildings by following these scents.
Putting aside the potential risks of mycotoxins and volatile compounds in
homes, fungal asthma is an incontrovertible menace to children, which
means that excessive mold exposure is always a serious problem for public
health.
Mycotoxins are the natural chemical weapons used by fungi in their
internecine wars of mold against mold, driven by the ceaseless competition
for food.48 Millions of tons of spores circulate in the atmosphere, drizzling
every surface, softly, invisibly, always. As each spore germinates, its hyphal
threads nudge against other tiny mycelia and the battles commence with the
exchange of poisons between combatants. Some mold strains collapse,
others neutralize the incoming mycotoxins and counter with their own
antifungal cocktails. This biological warfare has been fought by the fungi
across hundreds of millions of years.49
 In addition to fighting other fungi, ergot has extended its repertoire of
specialized alkaloids to strike bacteria, nematode worms, and insects. This
wholesale violence is needed because the ergots would be consumed by
these soil organisms when they fall to the ground at the end of the growing
season. The fungus must ward off these pests to get through the winter
before its spores can infect the next cereal crop in the spring. Our
vulnerability to poisoning by this fungus is a gruesome by-product of the
conflict between the fungus and its insect enemies with whom we share the
same types of nerve and muscle cells. The human body is equipped with
some impressive detoxification systems, but the ergot alkaloids and many
other mycotoxins have retained their virulence against us.
We have enjoyed much greater success in handling the widespread
mycotoxin that is made by yeast to disable other microbes when they begin
to grow in the sweetness of grape must and beer wort. The physiological
adaptation of the body to yeast alcohol has been refined over hundreds of
thousands of years, and our cultural relationship with this mycotoxin is part
of the story of the rise of modern civilization.50 Through its effects on the
nervous system, alcohol ranks as a potent psychoactive drug, although it is
rarely described in this manner. This special designation belongs to a subset
of fungal metabolites that assume control of the brain and whose action is
considered in chapter 9.

OceanofPDF.com
 9
Dreaming
USING MUSHROOMS TO TREAT
DEPRESSION
MAGIC MUSHROOMS light up the brain like fireflies in a meadow. Waves of
nerve activity rise, crest, and dissolve from spot to spot across the brain,
with islands of impulses crackling here, dampening there, as consciousness
is disconnected from the usual flow of information. The brainwaves on
mushrooms are similar to those in intense dreaming, with the twist that the
temporary uncoupling from everyday thinking via the mushroom can have a
lasting effect on our mindset when we reconnect. Anxiety and depression
can lose some of their bite; life can seem less brutish. A mushroom dream is
like a vacation to a tropical island or a canoeing trip along a pristine river,
with the surprising benefit that the peace found during the break stays with
you when it is over.
Exceptional dreams and dreamlike states that have been described as
visions share many of the characteristics of a mushroom trip. In the Hebrew
Bible, the prophet Ezekiel recalled a series of divine apparitions that he
witnessed in Babylonia: “And I saw the creatures, and look, one wheel was
on the ground by the creature on its four sides. The look of their wheels was
like chrysolite [green gemstones], and a single likeness the faces of them
had, and their look and their fashioning as when a wheel is within a
wheel.”1 I have been haunted by a similar vision since a luminous dream in
which the night sky, powdered with stars, began to swirl, with pools of light
revolving in the blackness. And as I looked, each wheel opened into more
wheels, galaxies spinning inside galaxies and particles within atoms in a
spectacle of infinite regress. For one glorious moment it seemed that nature
was unveiling itself, the revelation increasing in magnification toward the
germ of it all. Then I awoke, filled with wonder, and trying to hold on to the
picture. The night sky has not danced in my unconscious since then. Like
Caliban,
The clouds methought would open and show riches
Ready to drop upon me, that when I waked
I cried to dream again
(SHAKESPEARE, THE TEMPEST, ACT 3, SCENE 2)

The details of the ancient prophecy and my dream were products of their
time. Ezekiel was stirred by Mesopotamian imagery of fiery chariots and
four-faced gods; my vision was drawn from reading popular books on
cosmology, yet the sense of an epiphany seems similar. I cannot speak with
authority for Ezekiel, but my fireflies came drug-free.
Magic mushrooms containing the psychedelic compound psilocybin
provoke the same sense of transcendence over the commonplace perception
of life. The brain on mushrooms produces some of the hallmarks of the
rapid eye movement or REM stage of sleep but is heightened by the
preservation of consciousness. The user is introduced to a form of lucid
dreaming—dreaming while awake.2 A straightforward mechanistic
explanation of this process is elusive, which is not surprising in light of our
bewilderment about how any of our emotions unfold in the nervous system.
We know that love is made in the brain but have no notion of how it is
encoded, accessed, augmented, or lost.

HOW PSILOCYBIN RATTLES THE BRAIN

After decades of scientific neglect, psilocybin has become a subject of
intensive research, and some broad consensus is emerging on some of the
neurological processes that govern the mushroom dream. Electrical
impulses are conveyed along neurons through the movement of charged
atoms or ions across their membranes. When these signals reach the end of
the cells, they cause the release of chemical neurotransmitters that stimulate
or block the generation of fresh impulses in the next neurons in the circuit.
Serotonin is one of the neurotransmitters that perform this slower relay of
sparks from cell to cell. When we consume psilocybin, a chemical group
projecting from the ring structure of this little molecule is trimmed away in
the liver, producing psilocin. The structure of the psilocin molecule is so
similar to serotonin that it undoes the normal transmission of nerve
impulses between cells.3 Serotonin performs multiple roles in human
physiology, ranging from the control of the unconscious process of
digestion to the conscious emotion of happiness. If too much is released in
the nervous system, the body responds with agitation and muscle cramping;
too little and we lose motivation and can descend into depression.
To get a sense of the consequences of psilocybin consumption
(psilocybin that is converted into psilocin), it is helpful to consider the
complexity of the brain, which operates as an immense network of switches
that turn on and off, relaying and blocking signals. Both ends of each nerve
cell branch like fibrous tree roots to create as many as ten thousand
connections between each of the hundred billion neurons in the brain,
amplifying the signals through a circuit of one quadrillion (1015) living
transistors.4 Comparisons with computers are fraught with difficulties, but
the processing power of the brain matches a petascale supercomputer
capable of one quadrillion computations per second.5 With this complexity
comes vulnerability, which explains the potency of the magic mushroom.
Serotonin receptors are found throughout the nervous system but are
particularly concentrated in the frontal cortex, which is the center of
consciousness—our experience of life. As serotonin’s twisted sister,
psilocin activates some cortical circuits and stifles others, satirizing the
world that we take for granted.

PHYSICAL AND EMOTIONAL SYMPTOMS OF PSILOCYBIN

USE
Physical symptoms produced by the use of psilocybin result from the
stimulation and repression of neural networks that normally respond to
serotonin and include increases in heart rate and blood pressure, sweating,
muscle twitching, facial numbness, nausea, lack of coordination, and
headaches. These begin about twenty minutes after eating the mushrooms,
differ greatly from person to person, and are usually mild. If we did not
favor the uplifting psychological effects of psilocybin, these reactions
would be seen as expressions of mushroom poisoning. Not on a par with the
death cap, of course, but poisoning nevertheless, which is why many
mushroom guides place a skull and crossbones symbol next to entries for
Psilocybe species that contain the drug.
The psychological effects of psilocybin are similarly diverse. Some brain
circuits are aroused and become overloaded with information while other
parts of the brain are pushed into a dreamlike state. These changes in brain
activity are visualized in patients who lie with their head inside the giant
donut of a magnetic resonance imaging or MRI machine after they have
consumed purified psilocybin. MRI experiments show cross-talk between
parts of the brain that normally work in isolation, a reduction in blood flow
to areas involved in logical thinking, and an increase in nervous activity in
the deeper parts of the brain that control our emotions.6 Sound and vision
become tangled in some of these excursions, so that music is viewed as a
kaleidoscope of colors. This desegregation of the brain is called synesthesia.
More frequently, our sense of individuality or ego dissolves, which leads to
impressions of harmony and kinship with the rest of nature.7 This is henosis
and is the root of the encounters with God described by some psilocybin
users.
Ego is lost when psilocin interferes with a brain circuit called the default
mode network, or DMN. The DMN is concentrated in the prefrontal cortex
and connects with hubs of neurons nestled farther back and deeper in the
brain. Our sense of self is maintained in the DMN, and this is where the
mushroom subverts our narcissistic programming. Imagine you are a
passenger on a cruise ship that strikes an iceberg. In the seconds following
the collision, normal activity in your DMN is suspended while other parts
of the brain gather the information needed to figure out what has happened
and plan a response. You are too frantic at that moment to be aware that you
have raced onto the deck wrapped in a towel and wearing a shower cap.
Ego has departed, albeit temporarily. Later, when it has become clear that
the ship is sinking and that the lifeboats have left without you, the DMN has
the last word as you resume contact with your sense of self, remove the
shower cap, and are flooded with anxiety. Any feeling of positivity would
be welcome in this hopeless situation, and this is where mushrooms can
become our saviors. If you had swallowed a baggie of them when the ship’s
hull was ripped open, the psilocin would have disengaged the DMN from
the alarming messages flowing from elsewhere in the brain, pushing you
into a dreamlike state and leaving you more philosophical about the
prospect of the frigid water.8
The soothing effect of magic mushrooms on passengers on a sinking
ship is a matter of conjecture, but there is plenty of evidence that psilocybin
can reduce our fearfulness in less dramatic situations. Multiple studies have
shown that psilocybin is a useful treatment for clinical depression and can
even foster a sense of well-being in patients with terminal illnesses.9 In a
trial conducted at Johns Hopkins University in 2016, patients with life-
threatening cancer diagnoses reported feelings of greater life satisfaction
after receiving high dosages of the drug. These improvements in attitude
were sustained in 80 percent of the participants six months after their
treatment. Follow-up interviews with surviving patients in 2020 revealed
that the majority remained enthusiastic about their treatment, rating it
personally meaningful and spiritually significant. Reflecting on the
psilocybin treatment, one of the patients in the longer study wrote, “It’s
hard to explain.… Something in me softened, and I realized that everyone is
just trying (mostly) to do the best they can. Even me. And that matters,
since we are all connected.” Another said, simply, “I have a greater
appreciation and sense of gratitude for being alive.”10 These profoundly
positive changes in outlook are astounding. Given the choice, how many of
us would choose intimacy with psilocybin rather than raw cognition on the
last lap?
Psilocybin has also proven useful in the treatment of PTSD and
alcoholism, and researchers are studying whether the drug can be used to
treat anorexia nervosa.11 In addition to affecting the function of the existing
circuitry in the brain, studies on mice show that psilocybin use can boost
the number of connections between neurons.12 The possibility, however
slim, that a single dose can stimulate long-term rewiring of the brain has
far-reaching implications for treating a host of health conditions. With
depression and other mental illnesses afflicting hundreds of millions of
people worldwide, psilocybin has already attained the status of a miracle
drug in the opinion of some health-care professionals. With international
attention to this unfolding research, pharmaceutical companies big and
small are looking at magic mushrooms as a once-in-a-lifetime investment
opportunity.13 One of the challenges to this new industry is the long-
standing illegality of growing mushrooms to produce psilocybin, but the
mycological laws are evolving swiftly.

NORMALIZING PSILOCYBIN USE

In the U.S. elections in November 2020, Oregon voters passed Ballot
Measure 109, legalizing the use of psilocybin for therapeutic purposes, by a
comfortable margin. Measure 109 charged the Oregon Health Authority
with developing the regulations for licensing growers to produce magic
mushrooms and for licensed “facilitators” to provide “psilocybin services”
in specialized clinics.14 The authors of the measure pointed to the
prevalence of mental illnesses in the region and crafted the legislation to
“improve the physical, mental, and social well-being of all people in this
state.” Many health-care professionals objected; they wanted to see further
studies and were concerned about the unspecified credentials of the
facilitators who would counsel patients and shepherd them during their
sessions. Unmoved by these arguments, the majority of voters looked
forward to a happier future and scheduled the first clinics to open in 2023.
The most compelling case in favor of Measure 109 was made by people
who said that their lives had been transformed by psilocybin. Mara
McGraw was one of the brave proponents of the measure who shared her
story with the media. Mara had undergone surgery, radiation, and
chemotherapy for a rare form of neuroendocrine cancer for three years
before she faced the necessity of making her end-of-life decisions. “After
chemo failed, I went to a pretty dark place,” she said.15 Prescription
antidepressants proved useless. Hearing about psilocybin treatment in
Canada, she decided to give it a try. The psychoactive drug changed
everything: “I felt an immediate release from the fear,” she said in a video
news conference. “I just felt fine and I felt like I rejoined everything in the
universe.” Her despair melted as the drug from the magic mushroom lit up
her brain.
The evident benefits of psilocybin therapy outweigh the mild physical
side effects of the drug, but there are concerns about the harmful
psychological responses in a minority of patients. In a survey of almost two
thousand patients, 84 percent said that they believed that they had benefited
from psilocybin, which aligns with the results of many other studies.16
Other respondents experienced a negative impact, with 3 percent saying that
they had behaved aggressively or violently after consuming mushrooms and
8 percent seeking psychiatric treatment that they associated with the use of
the drug. There have also been cases of self-harm and suicide attempts
among psilocybin users, which speaks to the importance of taking the drug
under some kind of supervision.
Some of the challenges to accepting psilocybin as a useful medicine are
related to its popularity as a recreational drug, which began in the 1960s.
The negative image of psilocybin includes an enduring myth about an
epidemic of magic mushroom and LSD users throwing themselves from
buildings. Antipathy toward magic mushrooms is reinforced by the
ludicrous claims of contemporary popularizers of mycology about the
cosmic mysteries unveiled by psilocybin. Plenty of attention has been given
to the historical players in the psilocybin story in other books, so a précis
will suffice here: ethnomycologist Gordon Wasson and his wife, Valentina,
excited millions of American magazine readers with their stories about the
use of hallucinogenic mushrooms in Mexico in the 1950s.17 Wasson
collected hallucinogenic mushrooms in Mexico with Roger Heim, a French
botanist, and Albert Hofmann, a Swiss chemist, who isolated psilocybin
from cultures grown from these fruit bodies in 1958. Research on the
effects of psilocybin was conducted by Timothy Leary at Harvard
University in the 1960s, and Terence McKenna took “heroic doses” of
psilocybin and published a guide to growing magic mushrooms in the
1970s.18
McKenna became a counterculture hero, and his increasingly deranged
pronouncements discouraged more rational thinking about psychedelic
mushrooms. One of his baseless claims centered on the chemical structure
of psilocybin. McKenna declared that this was so unusual that it must have
originated elsewhere in the galaxy. He went on to postulate that psilocybin
mushrooms were a higher form of intelligence that had arrived from outer
space and shaped the evolution of the human brain. Although he faces some
stiff competition, McKenna’s alien mushroom theory is one of the least
enlightening things ever written about fungi. Returning to terrestrial
mycology, recent genetic research has revealed a lot about the actual origins
of magic mushrooms.
 HOW MUSHROOMS MAKE PSYCHEDELICS
Psilocybin is produced by three hundred species of Psilocybe mushrooms
and by other fungi belonging to three distantly related groups of fungi.
Psilocybe cubensis, which grows on cow dung in nature, is cultivated
indoors to furnish plentiful, year-round, and largely illegal sources of the
drug. With interest in the therapeutic value of psilocybin overtaking its
recreational use, researchers are investigating the industrial production of
the drug in bacteria and yeast transformed with fungal genes.19 The
advantage of these microbes over the mushrooms is that they could produce
huge quantities of pure psilocybin without any of the difficulties of raising
and harvesting fruit bodies for drug extraction. This is a complicated
project, with some similarities to the creation of the genetically modified
(GM) microbes that produce insulin. If this is successful, psychedelic
Frankenyeast will manufacture the drug in industrial fermenters in
psilocybin breweries.
Psilocybin synthesis involves four enzymes that restructure the starting
material, which is an amino acid called tryptophan, into psilocybin in the
tissues of the mushroom.20 The genes that encode these enzymes are
clustered on a single chromosome in some of the fungi; in other species
they are strung out and separated by genes that perform other functions.21
Genetic comparisons between the species of magic mushrooms suggest that
psilocybin synthesis evolved in one group of fungi and spread to other
families by the process of horizontal gene transfer.22 Most genes are
transferred vertically, by inheritance from parent to offspring, but horizontal
gene transfer between organisms in the same generation is common in some
groups of microbes. It appears that psilocybin genes spread in this sideways
manner from the mycelium of a magic species to the mycelium of an
unmagical fungus and cast a spell on any animal that ate it. However this
gene migration happened, psilocybin synthesis has prospered as a
transferable skill in the fungi, which suggests that it must be doing
something useful for them.
 WHY MUSHROOMS MAKE PSYCHEDELICS
Insect attraction seems the best reason for a mushroom to make
psychedelics, though the evidence for this is slim. Experiments suggest that
flies, like humans, experience mood elevation on psilocybin. This is
demonstrated by dropping flies in water and timing how long they continue
to struggle to climb out.23 Flies that have been fed psilocybin remain more
active and keep trying to escape even when the situation seems hopeless.
This seems a little like the patients in the human psilocybin study diagnosed
with a terminal illness. Rather than providing a free antidepressant for the
insects, the mushroom must profit from this interaction. Spore dispersal is
the most important service provided for fungi by insects.24 Flies called
fungus gnats are hatched from eggs laid in psilocybes and could carry
spores from their nurseries when they take to the wing as adults.25
This is all very speculative. However, the ability of a mushroom to
attract flies by agitating their nervous systems aligns perfectly with the
management of insect behavior by other kinds of microscopic fungi.
Zombie ants, infected by tropical species of the fungus Ophiocordyceps,
climb into the canopy of trees and bite down on leaf veins before the stalks
of the fungus explode through their heads and spray spores into the air. This
climbing behavior positions the fungus in the optimal location for the
dispersal of its spores in wind. Other fungi as well as viruses and parasitic
worms compel insects to behave in the same way. The uniformity of this
response to infection suggests that the different parasites are exploiting the
normal climbing behavior in insects for the purpose of dispersal.26
Psilocybin has not been detected in these fungi, but it is produced by
another fungus that infects cicadas and turns their abdominal tissues into
masses of powdery spores.27 Not content with sterilizing the insect, this
parasite causes infected male cicadas to waggle their wings like females,
attracting other males who receive a dose of spores when they mount their
moldy mates. Compared with these astonishing feats of mind control, the
mood-enhancing effect of psilocybin on insects and humans seems quite
modest.
The colors of some mushrooms may be related to insect attraction, but
this is an inconsistent trait among the hallucinogenic species. Psilocybes are
inconspicuous brown mushrooms that seem unlikely to act as visual
beacons for insects, although they do turn blue when they are bruised or
broken.28 The spotted caps of the fly agaric mushrooms offer a stronger
visual cue that may lure insects. Pieces of these fruit bodies steeped in milk
have been used as fly traps in Europe for centuries.29 The polka dot pattern
is destroyed when the mushroom is broken into the milk, so the fungus
must also create a smell that attracts flies. Despite the use of the fungus as a
fly trap, its name seems to refer to the devil, the lord of the flies, not to the
insects.30
Fly agarics produce muscimol, which impersonates the neurotransmitter
gamma-aminobutyric acid, or GABA, rather than serotonin. Neurons
sensitive to muscimol have an inhibitory effect on the nervous system,
reducing the transmission of impulses and acting as a sedative. There are
more than a dozen different types of GABA receptor in the human brain,
and muscimol binds more tightly to some than to others. This is the reason
for the range of symptoms of fly agaric ingestion, including euphoria, lucid
dreaming, changes in size perception, and feelings of weightlessness. These
are described as the Alice in Wonderland syndrome, which is also
recognized in patients suffering from viral infections, migraines, epilepsy,
and brain damage.31 The synesthesia provoked by psilocybin also comes
with muscimol, but with its properties as a psychedelic “downer,” this
compound is an unlikely candidate for treating depression. (Other sedatives
may be useful as antidepressants, including the synthetic drug ketamine,
which binds to a different receptor than muscimol.32) Like psilocybes, fly
agarics can cause serious poisonings in people who consume large doses of
the mushroom or are unusually sensitive to the chemistry of this fungus.33
Human interactions are not part of the evolutionary programming of any
of the magic mushrooms. We arrived too recently in their 150-million-year
history to dictate the modification of the chemistry of these mushrooms by
natural selection and, in any case, the huge numbers of prehistoric insects
are bound to have been better at dispersing spores than humans and our
ancestors. We get high on psilocybin and muscimol for the simple reason
that we have the same brain chemistry as flies. Nevertheless, magic
mushrooms may have exerted a supreme influence on civilization through
religion, which is the most surprising extension of the human-fungus
symbiosis.

MUSHROOMS AND THE CROSS

Familiarity with the contemporary human attraction to magic mushrooms,
coupled with archaeological evidence and ethnographic studies, suggests
that we have consumed fruit bodies containing psilocybin and other
hallucinogenic compounds for millennia.34 Rock carvings in North Africa
featuring bizarre figures holding and sprouting mushrooms bolster ideas
about the ritual use of fungi in the Neolithic, although we know nothing
about the beliefs of the artists. The oldest clear evidence of mushroom
worship comes from Mesoamerica and includes pre-Columbian stone
carvings and pottery with fruit-body shapes, paintings of Mixtec gods
offering mushrooms, and descriptions of the ceremonial consumption of
mushrooms by Aztecs. Uninformed by neuroscience, our ancestors were
bound to have interpreted the astounding effects of psychotropic fungi in
supernatural terms. Minutes after receiving these mycological sacraments,
their gods would have materialized in the form of dazzling creatures and
mushroom men bearing prophesies from the sky. Ezekiel seems to have
seen something like this following his vision of the psychedelic chariot,
with “the look of fire with radiance all round. Like the look of a rainbow …
the likeness of the glory of the Lord.”35 It is not surprising that there has
been a good deal of speculation about Ezekiel’s experimentation with
mushrooms.
Author Robert Graves recognized Ezekiel’s description in his own
experience of an orchard paradise after eating psilocybes.36 Graves had been
in Mexico at the time with his friend Gordon Wasson. Beginning with the
shamanistic use of fly agarics in Russia, which had been reported by
European explorers in the nineteenth century, Wasson pursued evidence of
the ritualistic use of mushrooms in other parts of the world. In his book,
Soma: Divine Mushroom of Immortality (1968), Wasson identified the fly
agaric as the vital ingredient in the ritual drink described in the Vedic
Sanskrit text, the Rigveda.37 A decade later he argued that LSD-like
alkaloids from the ergot fungus stimulated the visions in ancient Greek
ceremonies known as the Eleusinian Mysteries. But despite his enthusiasm
for mycological explanations for religious practices, he was unmoved by
the possible roots of Christianity in the worship of the fly agaric. This idea
was developed by John Allegro, an English archeologist, who wrote The
Sacred Mushroom and the Cross (1970).38 Allegro was convinced that he
had discovered a Sumerian code hidden in the Greek text of the gospels,
which revealed the beliefs of a fertility cult whose rituals included the
consumption of hallucinogenic mushrooms.
Allegro’s bizarre translation of the Bible was rejected by myriad
scholars, and the book was mocked in reviews. An eminent theologian
writing in The Times of London spoke for many when he dismissed his
psychedelic fertility cult as “a sensationalist lunatic theory.”39 Allegro’s
book included a photograph of a wall painting of Adam and Eve in
Plaincourault Chapel in France, which features the serpent coiled around
the Tree of Knowledge holding the forbidden fruit in its mouth toward Eve.
Following the descriptions of earlier authors, Allegro believed that the
thirteenth-century artist had pictured a giant mushroom tree bearing the
spotty caps of fly agarics. Wasson favored the more conventional
interpretation of the tree as a stylized Italian pine and rejected Allegro’s
translation of the Bible. This is interesting, given Wasson’s credulity when
it came to other ambiguous instances of mycological symbolism. It has
been argued that financial ties with the Vatican through his banking career
with J. P. Morgan & Co. may have swayed his opinion when it came to
Christianity.
Whether or not the Plaincourault painting shows a mushroom or a pine
tree, very credible mushrooms appear in other medieval artworks, including
wall paintings in other churches in France and in Turkey, stained glass
windows in Chartres Cathedral, a German tapestry, and the famous Great
Canterbury Psalter.40 Some of these compositions are mushroom-shaped
objects rather than fungi, but an objective review of the surprising variety of
images suggests that mushrooms were accepted as important religious
symbols in the early church. Why else would they have been displayed in
these commissions? Although his translations of scripture are fanciful, it
seems that Allegro had recognized a genuine trace of mycology in
Christianity.
Superstition and religion seem hard-baked into human nature. The
scientific impulse is innate too: at our best we live by logic and conduct
simple experiments when we have the opportunity to test our ideas. But in
our age of scientific fruits and failures, the sky gods persist as invisible
helpmates and moral judges across the planet. Faith in most gods would
have developed without psilocybin and muscimol, but it is easy to imagine
that their psychedelic power led to the ritual use of magic mushrooms and
the invention of priesthoods. Without claiming that the Bible is a coded
message from a fertility cult, perhaps mushrooms did play a role in the
origins of Judeo-Christian practices. Wall paintings in churches do not lead
this inquiry very far, but they do show that mushrooms are intertwined with
the ancestry of monotheism. If we had never swallowed the fruit bodies,
human cultures might have evolved along very different agnostic
trajectories.
We can take this mycological exploration of faith a step further to
question the reality of any god. Mystical feelings of various kinds are a
common response to psilocybin use in controlled experiments.41 Two-thirds
of the respondents in one study who said that they were atheists before
using psilocybin changed their minds after consuming magic mushrooms
and believed that they had encountered some form of “ultimate reality.”42
The faithful changed their minds too. Those who identified themselves as
monotheists before taking psilocybin tended to lose this belief in favor of a
broader idea of a benevolent intelligence in the universe. So rather than
placing us closer to some holy spirit or demon who was waiting in the
wings, it seems more logical to conclude from these studies that the alkaloid
in these fungi conjured the gods via an avalanche of nerve impulses. There
is a god-producer in the brain rather than a god-receptor.43

PSILOCYBIN AND THE ENTROPIC BRAIN

What do the effects of psilocybin say about the quotidian experience of life,
that users feel so elevated and rank the effects among their most profound
adventures? Aldous Huxley (1894–1963) was the most eloquent champion
of the idea that psychedelic drugs overcome the “reducing valve” of the
brain, which filters a surfeit of sensations gathered by our senses and feeds
the conscious brain with slivers of information needed to stay alive.44 In The
Doors of Perception (1954), Huxley recounted his experiments with
mescaline extracted from the peyote cactus. Mescaline is a serotonin
agonist, like psilocybin and LSD, and produces similar psychedelic effects.
High on the drug, Huxley looked at a flower arrangement and glimpsed
“what Adam had seen on the morning of his creation—the miracle, moment
by moment, of naked existence.” Without psychedelic drugs, Huxley wrote
that our awareness is limited to “the ruts of ordinary perception.” In his
earlier novel, Brave New World (1932), he had imagined a global palliative
called soma, after the Vedic libation, which soothed and pacified the
citizens of the World State.45
The opening of the reducing valve has been described as an increase in
neural entropy.46 This is entropy in a metaphorical sense rather than an
authentic measurement of physical disorder. In the normal conscious state,
we access information via a small subset of the available pathways. When
mushrooms are added to the nervous system, the entropy of the brain
increases as the connections between nerve cells spread across multiple
regions, producing synesthesia, the loss of ego, and other expressions of
enhanced networking. Obsessive-compulsive behavior is a good example of
the kind of rigid thinking or low-entropy brain activity that can be relieved
with psilocybin. Clinical depression is another. Caffeine has a comparably
uplifting entropic effect. Coffee has no proven use in treating any mental
illness, but the modest increase in connectivity and entropy probably
explains the boost in creativity that is a blessing of the first cup in the
morning—the fleeting sense of genius that is replaced by the lesser wit of
the day. REM sleep has some similarities to this high-entropy state too. At
the extremities of brain entropy, way beyond the normal effect of
psilocybin, the psychotic brain illustrates the disastrous outcome of a surfeit
of connectivity or disorder. McKenna may have found his way to these
extremities of brain entropy with his heroic doses of the drug. To each their
own.
 In the search for relief from depression and anxiety, it is useful to
consider why deep unhappiness is so prevalent. As imperfect products of
evolution, there must be a natural imperative at work. Psychologists have
wrestled with this question for decades, and although there is no completely
satisfying answer, depression seems to emerge from a combination of bad
wiring and the cryptic advantages of wariness, self-doubt, and sadness.47
The bad wiring is strung between the more primitive lizard brain and the
outermost cortex, where our consciousness and sense of self interact with
the primal urges to feed, escape, attack, and copulate. Wariness is inevitable
and protective, but the power of negative thinking is more problematic.
Mild depression might be useful if it provides us with the opportunity to
ruminate on a problem and reach a solution. It could also serve as an
incentive device that is so unpleasant that it urges us to move on from a
shattering experience. Deep relentless depression has no purpose. In his
study of depression titled The Anatomy of Melancholy, Robert Burton
(1577–1640) wrote, “What cannot be cured must be endured.”48
Mushrooms offer an alternative.

TO SHROOM OR NOT TO SHROOM

As calls to legalize psilocybin use grow, and corporations and governments
seek to control the production of the drug, we need to be mindful of the
implications of urging such abundant happiness in a frequently mordant
mammal. Mortal illness and the approach of death can open Huxley’s
reducing valve without shrooms. Author Chris Paling described eating toast,
his first solid food after six weeks on intravenous support in hospital: “I
spread the butter. The aroma of it melting into the slightly charred bread is
intoxicating.… I chew slowly. Another bite. Heaven.”49 Close to his death
in 1994, British playwright Dennis Potter described the blossom on his
plum tree: “I see it is the whitest, frothiest, blossomest blossom that there
ever could be, and I can see it. Things are both more trivial than they ever
were, and more important than they ever were, and the difference between
the trivial and the important doesn’t seem to matter. But the nowness of
everything is absolutely wondrous.”50
 It is sad that mortal illness and the approach of death are needed to taste
the toast and see the blossomest blossom, but the euphoria felt in extremis
or on psilocybin is unsustainable, and Huxley’s “ruts of ordinary
perception” keep us alive. But by opening the valve a little, we light up the
brain wiring for deeper thinking and creativity. The downside with using
mushrooms to do so is that they can create an ungovernable flow of
information.51 The resulting feelings of oneness with the universe and
empathy with the gods are entertaining, but they will not solve any
mysteries or lead to meaningful insights about the cosmos. Remarkably,
however, these festivities appear to soothe brains damaged by childhood
abuse or battlefield trauma and promise to ease the universal disquiet at the
end of life. We have not found anything else with these amazing properties.
And from the mushroom magic that opens and closes the doors of
perception and has given us religion, we examine the global symbiosis with
fungi that preserves life on the surface of the earth in the final chapter.
Without these wider ecological interactions, there would be none of the
more intimate expressions of the human-fungus symbiosis.

OceanofPDF.com
 10
Recycling
THE GLOBAL MYCOBIOME

KEPLER 1649c is an Earth-sized planet in the constellation of Cygnus, three

hundred light-years from our solar system. With its close orbit to a small
star, climate models suggest it is quite Earth-like in temperature.1 If Kepler
1649c is watery, it seems likely to harbor life, and if it accommodates
anything more complicated than our bacteria, it is certain to be populated
with fungi. Confidence in this untestable hypothesis is born from
understanding the essence of fungi on Earth. Our fungi are the agents of
entropy, transforming the energy captured in the web of life into the raw
materials for the continuous regeneration of the biosphere. Without a group
of organisms with these properties, the ecosystems of rocky worlds like
Kepler 1649c would stall as planetary compost heaps of untappable energy.
They must be there.
Mycology will evolve in its own way on this alien world, but some of its
features are a given. Kepler’s fungi will grow as filaments that permeate the
solid refuse and multiply as yeasts on surfaces and suspended in fluids. The
shapes of these cells will differ in detail from our species, but not in kind,
because filamentous molds and budding yeasts are streamlined solutions to
the challenges of growing in solids and liquids. Natural selection will craft
them within the constraints of the environment on Kepler as it has on Earth.
There will be mushrooms too, which will cast spores into the autumnal
breeze of Kepler’s sunny hemisphere. Not fly agarics, of course, but stalked
platforms of one kind and another that score the same goal of sending genes
into the future. Beyond these bare necessities, Kepler’s mycology will be
determined by the characteristics of the rest of the planet’s biology. If there
are brains, the fungi will have found ways to lure some of their owners to
help with spore dispersal and to dispel others from eating them. Supportive
symbioses with the molds are as inevitable as damaging mycoses, and every
Keplerian will carry a mycobiome. Mycology will be part of astrobiology
across the cosmos—if not on Kepler 1649c, then elsewhere in the galaxy on
other potentially habitable planets. There is no reason to think that there is
anything like a human anywhere else, but there is going to be something like
a fungus.
Back on Earth, the indelible nature of the human-fungus symbiosis
ensures that our collaboration will continue to evolve, unconsciously and
consciously, for better and worse, in health and in sickness. This chapter
begins with the greatest extension of this interrelationship, which may be the
most difficult to appreciate because it is so distanced from the body. This is
the life support system that exists in the soil and in the plants that energize
every food chain on land and oxygenate the atmosphere. We depend on
botany, and plants depend on fungi.2 Fungi support plants through their
mycorrhizal associations, as endophytes that live inside their tissues, and by
forming a protective shield of hyphae on leaf surfaces. On the flip side of
their botanical roles, fungi decimate crops, exterminate forest trees, and
compost the lot.3 Fungi are the resurrection and the life.

SYMBIOSES WITH PLANTS

Attempts to categorize many species of fungi that interact with plants as
faithful mutualists (advantage fungus/advantage host), commensals
(advantage fungus/host unaffected), or parasites (advantage fungus/host
destroyed) are futile because they slide between these categories. The
distinction between servant and slayer is blurred by fungi that are mutualists
or commensals with some plants and parasites of others, and by mutualists
that attack the tissues of their hosts when they are weakened by drought or
old age.4 In previous chapters we have seen how some of the fungi that we
encounter all the time show a similar shift in behavior from harmless or even
supportive interactions with the body to lethal pathogens when the immune
system is compromised. Returning to the mutualisms that support plants,
ectomycorrhizas between mushrooms and tree roots have become part of the
general knowledge of ecology. They are introduced to children in elementary
school, illustrated in posters and dioramas in nature centers, and enter
informal conversations about the environment. Ectomycorrhizal fungi
support trees by clothing their root tips with mycelia, radiating hyphae into
the soil, and delivering water and dissolved minerals to their partners. There
is nothing charitable about this: clamped to the roots, the fungus drains as
much sugar from the plant as it allows. Research on these fungi has shown
that their mycelia can create networks of filaments between the roots of
adjacent trees and act as pathways for sharing resources within forests.5 The
importance of these interconnections for the trees remains controversial,
however, and it is possible that the fungi are the chief beneficiaries of these
underground webs.
Mushrooms growing beneath trees can seem remote from our concerns,
but mycorrhizas are critical for forest health, and we benefit from the
resulting carbon capture, oxygen production, and water purification.
Supplies of lumber and other forest products are also reliant on these
underground symbioses. Equally inconspicuous synergies with fungi exist
through agriculture, where a different kind of mycorrhizal connection
nourishes crop plants. These symbioses are called arbuscular mycorrhizas,
and they are established with species in most plant families. Arbuscule,
meaning a shrublike structure, is the term for the delicately branched
connections that these fungi plug into root cells. This internal linkage or
endomycorrhiza contrasts with the ectomycorrhizas that grow on the surface
of roots and squeeze between their outermost cells.
Rice, corn, and wheat provide half of the calories consumed by humans,
and the roots of all three of these staple plants are endowed with arbuscules.
The fungi in these symbioses act as natural fertilizers by mopping up
nitrogen, phosphorus, and potassium in the soil and sharing them with their
plants.6 When the same trio of elements are provided to the crops as NPK
fertilizer, the natural mycorrhizas disappear.7 They are lost because the fungi
are unnecessary when the cereal roots are bathed with a supernatural
abundance of these elements in the soil. Something similar happens to the
healthy mycobiome in the digestive system when we poison the gut
microbes with fast food.8 Refined sugars and artificial sweeteners are
quickly absorbed into the bloodstream, bypassing the community of bacteria
and fungi needed to process complex carbohydrates (chapter 5). Fungicides
are another problem for mycorrhizas. Sprayed on crops to control the rusts,
smuts, blights, and blasts that plague monocultures, these chemicals trickle
into the soil and kill the beneficial fungi before they can form mycorrhizas
with the plants.9 This is like the trickle-down effect of medicated shampoos
that control dandruff and have the potential to squash some of the supportive
fungi on the rest of the skin (chapter 2).
Using the same molecular genetic methods that have been developed for
work on the human mycobiome, plant scientists have documented the rise
and fall of populations of mycorrhizal fungi in croplands. The disturbance or
dysbiosis resulting from intensive farming has not been recognized as a great
loss to agribusiness because crop productivity keeps increasing through the
mechanization of agriculture, chemical control of weeds and pests, and
introduction of ever more vigorous cereal cultivars.10 Nevertheless,
agricultural practices that promote mycorrhizas are becoming popular. No-
till farming avoids tearing the mycelia of mycorrhizal fungi apart before the
seeds are planted, and soil enrichment with manure stimulates fungal
growth.11 The addition of spores as seed dressings is another strategy that
provides seedlings with a preparatory mycobiome that can jumpstart the
formation of mycorrhizas.12 Dusting seeds with supportive fungi is
reminiscent of the baptismal coating of newborn babies with yeasts from the
mother (chapter 1). Through these neonatal get-togethers, the roots of
germinating plants are transformed into mycorrhizas, and we begin our
lifetimes as myco-humans.

THE NECROMYCOBIOME
Fungi collaborate with plants and animals throughout their lives and rot
them after death. Decomposition by fungi returns nutrients to the soil and
carbon dioxide to the atmosphere. Fresh roots and their fungi soak up the
minerals released by decay, leaves absorb sunlight and CO2, and the great
wheel of the carbon cycle keeps turning. Fungi mingle with bacteria, insects,
and worms in a fallen tree, each contributing to the process of decomposition
in a distinctive fashion. Mycelia of mushrooms use the pressure in their
filamentous hyphae to force their way into the wood and release enzymes
that turn the trunk into powder and pulp. Bacteria crowd along the surface of
the hyphae, fermenting the chemicals leaking from the fungi; beetles gouge
galleries through the wood where yeasts blossom in the damp darkness,
roundworms puncture the hyphae to feed on their juices, and fungi retaliate
with toxins and sticky traps. All of this happens relentlessly, year after year,
until the tree vanishes. Hardened brackets and hoofs of perennial fruit bodies
on the surface of the rotting wood are joined by annual flushes of fleshy
mushrooms as the external evidence of the internal decomposition. Spores
from these fruitings are dispersed in pursuit of new sources of food, driving
cycle upon cycle of life, death, and decay.
Fungi rot animals quite differently. Plants are made from sugars linked in
chains to form cellulose and other polysaccharides that make up the dry
weight of the plant. The fungi are the champions of releasing sugars from
these materials. Animals are made from proteins and fats that are more
susceptible to breakdown by bacteria, but yeasts grow in the slurry of the
dead intestines and filamentous fungi set to work on the tougher tissues.
Together with maggots that writhe in the froth and beetles that nibble at the
sinews, the bacteria and fungi form the necrobiome that gathers at the
postmortem banquet to dissolve the dead into the soil.13
The fungi of the necromycobiome change as the human corpse bloats,
enters the phase of active decay, and becomes skeletonized. In the bloat
stage the gut microbes destroy the digestive tissues, releasing gases that
distend the cadaver and force “purge fluid” from the nose and mouth. This is
when the greatest diversity of fungi is found in the body, including Candida
yeasts and the familiar Aspergillus, Mucor, and Penicillium molds.14 In the
active stage of decomposition the diversity falls, and a mixture of specialized
molds and yeasts works alongside the bacteria and maggots that liquefy the
skin, muscles, and internal organs. Skeletonization leaves little food for the
fungi apart from the hair and nails, which are digested by the species that
cause ringworm in life.
The inevitability of our eventual decay is a fact of life that most of us
would like to ignore. But we gain wisdom by understanding and embracing
the part that we play in this grand terrestrial circus. The German philosopher
Heidegger, among others, suggested that the affirmation of our own limited
timeline allows us to transcend everyday experience and seek greater agency
in life.15 Some people find solace in this meditation, and burial suits
impregnated with fungi have been marketed as biodegradable attire for
enriching forest ecosystems after our demise.16 This posthumous
contribution to fertilizing the woods is a laudable ambition, and “green
burials” of all kinds are a less poisonous exit plan than the use of embalming
chemicals to keep the body looking cadaverous. Unfortunately, however, the
advertised colonization of the burial suits with mycelia of oyster and shiitake
mushrooms is not going to aid human decomposition because these are
white-rot fungi that digest cellulose. In the unlikely event that oysters and
shiitakes came across the body of a pirate in the wild (who missed his
traditional burial at sea), they would remove all trace of his wooden leg, but
little else.17
 SPOILING ART AND RESTORING SOIL
Wooden legs and everything else that we saw, chisel, and pulp from trees are
prone to decomposition by fungi. Air and moisture condemn cut wood to
decay without the defenses against fungi provided in the living tree or
chemical preservatives in cut lumber. The seeds of destruction are resting in
the soil and drifting in the air, always ready to strike. The oldest surviving
woodwork is the 12,500-year-old Shigir Idol discovered in a Russian peat
bog in 1890. The lack of oxygen preserved the chiseled face and zigzag
etchings of the five-meter-tall larch wood figurine, which is more than twice
the age of Ötzi the iceman (see chapter 7).18 Civilizations came and went as
the Shigir Idol rested in the bog, and the fungi erased all trace of their
carpentry beyond rings of postholes found at Woodhenge, near Stonehenge,
and other Neolithic settlements in Europe.
Paintings are damaged by fungi too. Millennia before the early Mesolithic
Siberians carved the Shigir Idol, artists decorated the walls of the Lascaux
caves with pigments ground from local minerals. Within a few years of their
discovery in 1940, the paintings showed signs of corrosion as the breath and
sweat of thousands of visitors increased the humidity of the caves and
acidified the damp rock. Electric lighting installed in the vaults caused a
green alga to spread over the walls, along with patches of mold.19 The
Lascaux caves were closed to the public in 1963, but the microbiological
damage has persisted. The problems are intensified by insects that disperse
fungi in the caves, including a mold that blackens the walls and ceiling.20
Michelangelo had to remove mold spots from the damp lime that served
as the canvas for his fresco in the Sistine Chapel, and medieval wall
paintings in churches throughout Europe are threatened by fungal spoilage.21
Fungal hostility toward our art and artifacts is relentless. Whatever we
produce, they do their best to dissolve. Manuscripts and books in library
collections become moldy if the climate is not controlled, film and
videotapes can be ruined by fungi, and faces in photographs become blurred
by tiny mycelia growing on the gelatin. Only digital images archived in
clouds are safe. Fungi spot shoes, handbags, and everything else made from
leather. Spots of mildew on a favorite jacket develop for the same reason that
a fungus grows on our skin. Try as we might, we cannot insulate ourselves
from the fungi.
In his 1665 masterpiece Micrographia, Robert Hooke published the
earliest images of microscopic fungi, including a bread mold growing on a
sheepskin book cover. Centuries later we are still playing catch-up with the
universe of organisms and objects revealed with Hooke’s microscope.
Whether we see them or not, there is a fungus on everything, decomposing
its substance or sitting there as spores. Fungi have been cleaning up the mess
made by the rest of biology for hundreds of millions of years, turning dead
plants into compost and compost into soil, threading their way through
animal dung and, as we have seen, dissolving the fibrous parts of animal
corpses.
These skills in recycling are vital for soil regeneration after forest fires,
and mycorrhizas can help plants regain a roothold in land deforested by
timber harvesting and mining operations. We can also use mycelia to break
down many of the nastiest pollutants that we release into the environment
and to reconfigure other chemicals to reduce their toxicity.22 White rot fungi
use some of the enzymes that are effective in wood decomposition to
detoxify cancerous hydrocarbons produced when fossil fuels are burned.
They are good at this because the ringed structure of these molecules is
similar to the lignin in wood that they are accustomed to rotting. Other fungi
are effective at breaking down agricultural pesticides and herbicides,
pharmaceutical wastes, dyes, and detergents. Mycelia also clean soils by
concentrating toxic elements from the water that trickles over their hyphae.
Through this natural form of filtration, fungi may even help remediate
radioactive soil.23 Although we are a long way from extending this flair for
detoxification from the lab to the farm field and industrial site, pilot studies
on these remarkable processes offer a welcome distraction from the
continuous newsfeed of planetary gloom.

FASHIONABLE FUNGI
Highlights of this science have trickled into popular culture, where
mushrooms have been embraced as the instruments of recycling that refresh
the planet and support new life. This newfound love of mycology echoes the
associations between mushrooms and fertility made by indigenous people
across the world.24 According to their traditional beliefs, the Blackfoot
Indians imagined that giant puffballs, or kakató’si, were created by fallen
stars. They painted the fruit bodies as white circles arising from a dark band
along the bottom edge of tipi covers to symbolize the birth of life.25 Now that
the global scale of environmental damage is beyond any sensible question,
the fungi have become widespread symbols of hope. After three hundred
years of esoteric research and public disdain, fungi have become sexy.26
Mushrooms have been embraced as emblems of beauty and countercultural
cool in film and fashion, music, best-selling books, and inspirational
lectures. Art installations with mycological themes have included giant
mushrooms made from woven willow branches, living sculptures of heads
grown from mycelia on wood chips and bristling with fruit bodies, and
elaborate carvings and metalworks. Mushroom jewelry is very trendy too.
Ofer Grunwald, an Israeli artist, and his colleagues have created dot
paintings with Aspergillus spores in tiny drops of agar jelly. Applied to
sheets of glass, the drops form visible patterns when the spores germinate
into tiny mycelia that color each dot.27 Some of the designs are influenced by
contemporary Australian Aboriginal art, and the participation of the fungi
adds an extra dimension of individuality to every dot in the paintings. When
the spherical spore of the mold germinates, its first thread can come from
any point on its surface. The placement of the first branch to emerge from
this hypha is similarly mutable, and the position of the second branch, and
the branches from branches, so that within an hour of growth the tiny
mycelia assume unique shapes in their drops. Although there is a high degree
of predictability in the overall form of the growing fungus, its detailed
geometry is a one-time creation. The colony is like a snowflake, whose
precise details arise at one place and time in the universe and will never
occur again. (This not as impressive as it sounds, perhaps, because nothing
in biology is ever repeated. Even when cells and embryos have identical
genes, they are unique in their physical minutiae.) Time-lapse photography
captures the emergence of shape and color in the dot paintings over two or
three days. There is a sense in which the arrow of time is reversed in this act
of creation: rather than destroying works of art, the molds make art in
Grunwald’s hands by extracting energy from their jelly.
The creative impulse of the fungi is also expressed in vegan leather made
from sheets of mycelia cultured in shallow trays and other fabrics produced
by compressing blocks of mycelium grown on grains and wood chips. These
materials have been crafted into handbags and clothing by famous designers
and advertised as eco-alternatives to leather goods.28 Vegan leather has also
been adopted by shoemakers, which reverses the mildewing of shoes by
fungi to the manufacturing of shoes by fungi.

QUEER MYCOLOGY
As mycology follows this new phase of its evolution, superstitions about the
fungi continue to influence opinions about their unimportance on one side
and their overwhelming significance on the other. This continuum of
responses runs from mycophobes who dislike everything fungal to fanatics
who believe that fungi can save the planet. In this vein, Patricia Kaishian and
Hasmik Djoulakian have proposed that mycology is harmed by pervasive
mycophobia that can be understood from the perspective of queerphobia:
“Mycology is a science that, by its very nature, challenges paradigms and
deconstructs norms. Mycology disrupts our mostly binary conception of
plants versus animals.… Fungi are seen as poisonous, agents of disease,
degenerate, deadly, freaky, gross, and weird—language historically leveled
against both queer and disabled people—and as having no positive
interrelationships with their environment(s).”29 It is certainly true that fungi
have suffered centuries of stereotyping that has burdened mycologists and
inhibited progress in understanding their biology. Mycology has always been
a nonconformist field. Kaishian and Djoulakian suggest that, although this
has led many people to conclude that the fungi are “perverse and unworthy
of formal investigation,” others have found their strangeness inspiring. This
tension has created tight-knit groups of researchers who work outside the
better-known scientific disciplines, but has also encouraged frustrating ideas
about the supernatural powers of fungi as medicinal cure-alls and
environmental saviors. It can be difficult for the real science of mycology to
overcome these half-truths and falsehoods.
 Changing perceptions of the fungi are palpable among professional
biologists. For most of the previous century, articles on biodiversity in
scientific journals guesstimated the number of animal and plant species and
skipped the fungi. Plant ecologists went about their business as if fungi did
not exist, or virtue-signaled in seminars by mentioning mycorrhizas, and
there seemed no place for mycology in zoology. But today, the fungi are on
full display in pyramids of species, often as fly agaric icons; mycorrhizas are
part of general biological knowledge; and the gut mycobiome of every
animal is being scrutinized. This level of awareness seemed out of reach
when I began my research career. Like the parents of actors concerned about
their children’s career choice, my dad was troubled when I told him that I
intended to specialize in mycology for my doctoral degree—enough to
consult a mycologist who happened, conveniently, to have retired in our
Oxfordshire village. This was C. T. Ingold (1905–2010), a legendary figure
in twentieth-century mycology who spent seventy years studying fungal
spores.30
Ingold told dad that the study of fungi was an outstanding choice for a
young scientist and that there would be dedicated departments of mycology
in the universities before long. This was an overreach. The number of
academic mycologists has actually declined since Ingold’s forecast, and
mycology departments are as scarce as hen’s teeth.31 On the other hand,
researchers specializing in the study of medical mycology and plant diseases
have attracted significant funding, and fungi are included in many areas of
ecological research. And although they do not call themselves mycologists,
yeast geneticists and biotechnologists who work with fungi are also
employed in most research universities. As the classical taxonomists who
named and organized the fungi have retired, mycology has emerged from the
dust of their herbaria. Mycology has evolved from the study of isolated
species to the interactions between fungi and other organisms.

THE CONSCIOUS MYCOBIOME

The study of these interactions with the human body is brimming with
possibilities because the science has so far to go and the life of the
mycobiome is new to our consciousness. Most of the time we have no
awareness of the activities of the mycobiome at all. Our trillions of cells go
about their business, and the fungi go about theirs. We may wonder why our
scalp is itchy and what makes us sneeze when we brush past a mildewed
houseplant, but the fungi do not distract us from the to-do list for the day.
There is an equity between the involuntary reactions of the body to the
presence of fungi and the behavior of the yeasts and molds as they feed on
the waxes of the scalp, snuffle around in the gut lining, and fight the immune
system.32 We are complete coequals at the cellular level: fungal cells are
every bit as perceptive and responsive as human cells.
The sensitivity of fungal cells is axiomatic. Hyphal filaments detect
ridges on surfaces, grow around obstacles, and deploy a patch and repair
system when they are injured. They react to confinement too, altering their
growth rate, becoming narrower and branching less frequently. This allows
them to adapt to the texture of the soil and the anatomy of plant and animal
tissues as they push ahead and forage for food. Fungi also show evidence of
learning and memory in experiments, responding to stress more effectively
after training with a heat shock and growing in the direction where they
found food in the past (see chapter 4). They are not thinking, in the sense
that a brained animal thinks, but the fundamental mechanisms that allow a
hypha to process information are the same as those at work in our bodies.
Every thought in our lifetimes of thinking is processed by the billions of
nerve cells in the brain and draws on cascades of reactions between proteins
and other molecules. Every response of a fungal mycelium to its
environment involves related cascades of signaling molecules. The
difference between thinking and reacting is a matter of scale rather than
essence. How could it be any other way, when all life is made from cells?
Estimates of the density of hyphae in grassland suggest that there can be
between 10 billion and 1 trillion hyphae in one cubic meter of soil, and as
many as 130 trillion hyphal tips cultivated in the same volume of straw or
sawdust. These numbers are comparable to the density of neurons in the
human brain, although nervous systems amplify their processing power by
forming synapses that allow each nerve cell to connect with thousands of
neighbors. Despite the incredible numbers of hyphae, the potential for
communication is probably limited to the slow passage of chemical signals,
and the fungus is unlikely to be relaying anything other than “I’m hungry,”
“I just found food,” and “Will you mate with me?” This covers most of
human discourse too, of course, but you get the point. Fungi do not dream or
dread.
Claiming any consciousness for the fungi is dangerous territory. There is
an eager audience for fantastical tales about fungi, especially if they are
stretched from a few scientific observations. The inner language of
mushrooms is a particularly awkward proposal, derived from the analysis of
electrical spikes measured by sticking electrodes into blocks of mycelia.33
The authors of this work concluded that the “complexity of fungal language
is higher than that of human languages,” based on a published scale in which
French was identified as the least sophisticated European tongue. There is an
event horizon in mycological thinking that is crossed when enthusiasm and
ego exceed experimental evidence. One wonders whether potatoes employ a
different syntax when their weak voltages are tapped to power LED clocks.

THE LUNAR EXTENSION OF THE MYCOBIOME

The interpretation of images of blobs on the surface of Mars from the
Opportunity rover as puffballs and other mushrooms is a comparable flight
of fancy.34 This discovery came too late for Terence McKenna, who would
have seen confirmation of his declarations about fungal spores arriving on
Earth from space (see chapter 9). By the time McKenna developed his
theory of cosmic migration, NASA had begun working in the other direction
by transporting some of Earth’s mycology into space. The Apollo missions
extended the mycobiome to the Moon, when a dozen astronauts walked their
fungi around on the lunar surface and left samples of the species from their
guts along with urine and food wrappers in jettison bags. A photograph taken
by Neil Armstrong during the Apollo 11 mission shows one of these white
bags dropped from the lander. With lunar temperatures ranging from boiling
to deep freezing, the bagged microbes are long dead, but their DNA will be
readable if future visitors retrieve the Apollo refuse.35
Decades before the invention of the terms “microbiome” and
“mycobiome,” NASA scientists studied changes in the “fungal autoflora” of
the astronauts on the Apollo 14 and Apollo 15 missions. Their interest in the
microbiology of the body was way ahead of its time. The first methods for
identifying bacteria and fungi from their DNA were not developed until the
late 1970s, which limited the analysis of the astronaut mycobiome to
identifying the fungi that could be grown from skin swabs and samples of
astronaut feces. Filamentous fungi and yeasts were isolated from the swabs,
and Candida yeasts were cultured from the fecal samples collected before,
during, and after the missions.36 The most interesting observation was the
loss of fungi during the spaceflights and on the lunar surface. The number of
species declined in space because the astronauts ate sterilized food, and there
were no fungi in space that could reinforce their surviving mycobiomes.
NASA has always expressed concerns about contaminating the rest of the
solar system with our microorganisms, but they cannot be dislodged from
spacecraft. The problems begin with the assembly of space vehicles in
cleanrooms.37 Bacteria and fungi dodge the best efforts to sterilize the air
supply and materials carried into these facilities. The microbiomes of the
engineers are another source of fresh contaminants. The spores of
Aspergillus and other molds found in the cleanrooms must have bypassed the
air filters, and Malassezia and Candida yeasts discovered on surfaces
probably originated on the workers. A rarified mixture of fungi persists on
the International Space Station (ISS) in orbit, and some of them are expected
to multiply in the absence of their earthbound competitors in this closed
environment.38 Experiments have demonstrated the tenacity of some fungi
subjected to high doses of ultraviolet radiation, but nothing can survive on
the outside of spacecraft exposed to the desiccating vacuum of space and the
cosmic rays that obliterate DNA. There are no mushrooms on Mars.
The fungi growing on the skin and in the guts of astronauts on the ISS
change during the mission, with a significant increase in the abundance of
Malassezia yeasts on the skin. This seems to be related to changes in the
amount of sebum produced by astronauts in space.39 As the duration of space
missions extends over years, the natural mixtures of microbes on the bodies
of the astronauts are bound to disappear. Pathogens could prosper with the
loss of species that normally keep them in check, and these anomalies are
likely to be amplified by changes in the immune systems of the astronauts.
Along with cosmic radiation, bone loss without gravity, muscle atrophy, and
psychological stress, the disruption of our fungi is a factor that may make
human space exploration impossible.40 The good news is that we do not need
rocket science to survive on Earth. We have everything we need biologically
—other than the will to overcome the appalling selfishness of human nature.
Appreciating the fungi is part of this terrestrial mission. This can begin with
something as simple as looking at a mushroom—this beautiful oddity of
nature—or inhaling the wondrous scent of a handful of rotting pine needles.
There is so much beauty in this orgy of decomposition.
______
During our foray into the mycobiome we have encountered yeasts that live
on the skin and a community of fungi roosting in the digestive system. These
permanent residents of the human-fungus symbiosis are joined by spores that
cause allergies and invasive pathogens that produce lethal infections. As we
have seen, we can also think of the extensions of the mycobiome through our
interactions with mushrooms that have fed and poisoned humans for
millennia, and hallucinogenic species that have aroused deep superstitions
and inspired religions. Other cultural relationships with fungi include
brewing and baking with yeast and the use of filamentous fungi to ferment
milk and make cheese. Rusts and smuts that ruin crops, and molds that spoil
our harvests and homes, are part of the story too. These are examples of our
partnership and competition with fungi throughout history and overlap with
the modern engineering of yeasts and molds to produce life-saving drugs.
This is the story of the fungi near and far, which support the biosphere by
forming mycorrhizas with plants, rotting the wastes of biology, enriching the
soil, and purifying water. Life without fungi is impossible. There are as
many of them living on the human body as there are stars in the Milky Way
and, more importantly, they have a far greater influence on our lives than all
but one of these galactic incinerators. They are everywhere and will outlive
us by an eternity: in myco speramus.

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 Appendix
GHOST GUT FUNGI

MYCOBIOME RESEARCH is challenging, and a lot of misinformation has made

its way into published studies. The problems begin with the indirect nature
of the experiments. We cannot watch the fungi as they make their way
along the gut, and many of them will not grow in culture dishes when they
are collected from samples of feces. The only option for studying our
onboard fungi is to identify them from their DNA signatures. From the
resulting species lists we can infer things about the activities of the fungi in
the gut because we know, for example, that one fungus digests fats and
another consumes sugars, that this yeast can cope with low levels of
oxygen, and its relative interferes with bacterial growth. At a time when
identifying viruses using the polymerase chain reaction, or PCR, has
become routine, analyzing fungi from their DNA might seem
straightforward. But fungal genomes can be thousands of times bigger than
viral genomes, which presents some technical difficulties, and there is
another problem in separating the real gut fungi and signals from ghost gut
fungi. Real gut fungi live in the gut or are ferried along in food; ghosts are
cases of mistaken identification.
To make sense of the strings of As, Ts, Gs, and Cs amplified from fecal
samples, investigators compare the sequences of fungi with reference DNA
sequences associated with species catalog in online databases. This is called
sequence alignment. Ghost fungi arise from fake strings of As, Ts, Gs, and
Cs produced by faults in the sequencing process and from weak matches
that come from using DNA sequences that are too short for an accurate
reading. Additional problems can be traced to faulty databases in which 10
percent or more of the archived DNA sequences are linked to the wrong
species names.1 For these reasons, the more reliable studies disregard the
rarer matches to species whose sequences do not appear frequently in the
samples and compare longer DNA sequences before concluding that a
positive identification has been made.2
These technical errors are compounded by the lack of mycological
training among the scientists scrutinizing the mycobiome. This has led to
the publication of comical lists of species allegedly found in human feces
that include toadstools that fruit from termite mounds, fungi that live inside
eucalyptus trees, and tiny mushrooms that grow below the water in
Argentinian lakes.3 The names of these ghost fungi come from real fungi
found in nature whose DNA sequences overlap a little—just enough to be
confusing—with the DNA sequences of fungi amplified from the fecal
samples. I came across a particularly daft example of this at a scientific
conference when I spotted the name of a stinkhorn on a poster display about
the infant mycobiome. The student presenting this work expressed no
qualms when I suggested that this was an unlikely match. This stinkhorn, I
explained, was a relative of a mushroom that looks like an erect penis and
attracts carrion flies to its slime-covered tip. The presence of this fungus in
the body was as improbable as finding a rhinoceros. He countered that he
was simply reporting the data obtained from his computer search.4
Some of my colleagues may accuse me of duplicity here because I have
criticized the work of taxonomists by writing about long-standing problems
with the naming of fungal species.5 They have a point. If we abandon the
practice of giving names to fungi, who is going to recognize that something
is wrong with identifying a termite fungus or a stinkhorn in a mycobiome
study? Having conceded this, it is essential to remain skeptical that fungi
dubbed with the same Latin name belong to the same species and behave in
the same way. This is vital for clinical studies, because some versions or
strains of the same “species” can have very different effects on the human
body than others. The diversity of the fungi is at once enthralling and
frustrating.
 A list of the fungal species identified correctly in a sample of feces
comprises long-term symbionts that spend their lives inside us and
transients relayed with recent meals. Most mycobiome studies report the
relative abundance of the different microbes. Pie charts are a good way to
illustrate these results. When Candida albicans occupies a 70 percent
wedge of the pie, this shows that seven of every ten strands of fungal DNA
extracted from the sample came from this common yeast. Continuing with
this hypothetical analysis, a 20 percent wedge might be occupied by
Malassezia restricta (which also lives on the scalp), with the remaining 10
percent of the pie divided among a dozen rarer species. This pie chart shows
that most of the mycobiome is populated by two fungi, which is interesting,
but it does not tell us anything about the number of cells. In a depleted
mycobiome with a total of a hundred million fungal cells, the relative
abundance estimate in the example suggests that 70 million Candida cells
are present in the gut; in a richer mycobiome overflowing with 40 billion
cells, there could be around 30 billion cells of this omnipresent yeast. The
pie chart showing relative abundance would look the same either way, and
the missing information on actual numbers could have significant health
implications. Until recently, many studies have ignored this inadequacy and
simply reported relative abundance, but a growing number of investigators
are taking the next step and measuring numbers using real-time PCR or
qPCR, where the q stands for quantitative.
Traditional or old-school PCR measures the amount of DNA that has
been amplified at the end of the PCR reactions. The Candida reading in the
example shows that 70 percent of the DNA at the end came from this
fungus. In qPCR, the increase in DNA is measured as the cycles of the PCR
reactions proceed.6 This means that the signal from Candida will increase
swiftly in the early cycles because there are a lot of Candida cells
containing Candida DNA at the beginning. The signals from the rare fungi
build more slowly because there is so little starting material. In the qPCR
method, the amplification of the DNA is monitored using fluorescent dyes
that bind to the DNA of the target species. To relate the intensity of the
fluorescence to the number of cells, the same qPCR reactions are run on
samples containing known numbers of fungal cells that have been grown in
culture.

OceanofPDF.com
Notes
 CHAPTER ONE
1. Nicholas P. Money, Fungi: A Very Short Introduction (Oxford: Oxford University Press, 2016).
The fungal kingdom and the animal kingdom have been married in one of ten supergroups of
organisms, called the opisthokonts in modern biology. This uninspiring name refers to the
arrangement of shared cell structures called cilia and should be replaced with a more evocative name:
mycozoans would be better.
2. Candida is the Latin name of a genus of fungi that contains two hundred species of yeasts. It
derives from candidus, meaning white, which is the color of the colonies of these yeasts dotted on a
culture dish. Candida species have been found in Biscayne Bay, Florida; in deep-sea sediments
beneath the turquoise waters of the Bahamas; in lakes and rivers in Brazil; and in grassland and
agricultural soils. Candida grows on plants and inside the guts of insects, birds, and other animals. It
is simpler to list the places where Candida is absent than to list its residences. The human
mycobiome supports a half dozen species of Candida. Candida albicans is the dominant vaginal
yeast and is the most frequent Candida species found in the gut and elsewhere in the body.
3. The interplay between fungi and bacteria in all ecosystems is a growing area of research: Aaron
Robinson, Michal Babinski, Yan Xu, Julia Kelliher, Reid Longley, and Patrick Chain, “A Centralized
Resource for Bacterial-Fungal Interactions Research,” Fungal Biology 127, no. 5 (2023): 1005–1009.
4. Patrick M. Gillevet, Masoumeh Sikaroodi, and Albert P. Torzilli, “Analyzing Salt-Marsh Fungal
Diversity: Comparing ARISA Fingerprinting with Clone Sequencing and Pyrosequencing,” Fungal
Ecology 2, no. 4 (2009): 160–167.
5. Maonon Vignassa, Jean-Christophe Melle, Frédéric Chiroleu, Christian Soria, Charléne
Leneveu-Jenvrin, Sabine Schorr-Galindo, and Marc Chillet, “Pineapple Mycobiome Related to
Fruitlet Core Rot Occurrence and the Influence of Fungal Species Dispersion Patterns,” Journal of
Fungi 7, no. 3 (2021): 175; Golam Rabbani, Danwei Huang, and Benjamin J. Wainwright, “The
Mycobiome of Pocillopora acuta in Singapore,” Coral Reefs (2021), https://doi.org/10.1007/s00338-
021-02152-4; Luigimaria Borruso, Alice Checcucci, Valeria Torti, Federico Correa, Camillo Sandri,
Daine Luise, Luciano Cavani, et al., “I Like the Way You Eat It: Lemur (Indri indri) Gut Mycobiome
and Geophagy,” Microbial Ecology 82 (2021): 215–223.
6. Ibrahim Hamad, Mamadou B. Keita, Martine Peeters, Eric Delaporte, Didier Raoult, and Fadi
Bittar, “Pathogenic Eukaryotes in Gut Microbiota of Western Lowland Gorillas as Revealed by
Molecular Survey,” Scientific Reports 4 (2014): 6417; Alison E. Mann, Florent Mazel, Matthew A.
Lemay, Evan Morien, Vincent Billy, Martin Kowalewski, Anthiny Di Fiore, et al., “Biodiversity of
Protists and Nematodes in the Wild Nonhuman Primate Gut,” ISME Journal 14, no. 2 (2020): 609–
622; Ashok K. Sharma, Sam Davison, Barbora Pafčo, Jonathan B. Clayton, Jessica M. Rothman,
Matthew R. McLennan, Marie Cibot, et al., “The Primate Gut Mycobiome-Bacteriome Interface Is
Impacted by Environmental and Subsistence Factors,” NPJ Biofilms and Microbiomes 8 (2022): 12.
7. James Cole, “Assessing the Calorific Significance of Episodes of Human Cannibalism in the
Palaeolithic,” Scientific Reports 7 (2017): 44707. The body of an adult male weighing 66 kilograms
(146 pounds) contains an estimated 144,000 calories.
8. Ghee C. Lai, Tze G. Tan, and Norman Pavelka, “The Mammalian Mycobiome: A Complex
System in a Dynamic Relationship with the Host,” WIREs Systems Biology and Medicine 11, no. 1
(2019): e1438.
9. Lawrence A. David, Corinne F. Maurice, Rachel N. Carmody, David B. Gootenberg, Julie E.
Button, Benjamin E. Wolfe, Alisha V. Ling, et al., “Diet Rapidly and Reproducibly Alters the Human
Gut Microbiome,” Nature 505, no. 7484 (2014): 559–563.
10. The number of bacteria in the gut microbiome comes from Ron Sender, Shai Fuchs, and Ron
Milo, “Revised Estimates for the Number of Human and Bacteria Cells in the Body,” PLoS Biology
14, no. 8 (2016): e1002533. Metagenomic analysis of fecal samples suggests that more than 99
percent of the DNA sequences come from bacteria, with the remaining sequences associated with
archaea, viruses, and eukaryotes. Fungi are the most abundant of the eukaryotes in the gut, and we
can come up with rough estimates of cell numbers from the relative abundance of sequences, which
varies from 0.03 to 0.1 percent of the total, corresponding to 11 to 38 billion cells. This estimate is
rounded to a maximum of 40 billion cells in the text. The mass, cumulative length, and surface area
calculations for the cells are based on spherical bacteria and fungi with diameters of 1 μm and 4 μm,
respectively. There is a good deal of wiggle room in these figures, but they serve as a useful order-of-
magnitude guide to the scope of the mycobiome. The thousand-to-one ratio of bacteria to fungi in the
microbiome (0.1 percent) appears in several studies, including the following review article: Tonya L.
Ward, Dan Knights, and Cheryl A. Gale, “Infant Fungal Communities: Current Knowledge and
Research Opportunities,” BMC Medicine 15 (2017): 30. The lower published estimate of 0.03 percent
for the fungal abundance in the gut microbiome comes from Stephen J. Ott, Tanja Kühbacher, Meike
Musfeldt, Philip Rosenstiel, Stephan Hellmig, Ateequr Rehman, Oliver Drews, et al., “Fungi and
Inflammatory Bowel Diseases: Alterations of Composition and Diversity,” Scandinavian Journal of
Gastroenterology 43, no. 7 (2008): 831–841. The gut surface area measurement was published in the
same journal: Herbert F. Helander and Lars Fändriks, “Surface Area of the Digestive Tract—
Revisited,” Scandinavian Journal of Gastroenterology 49, no. 6 (2014): 681–689.
11. Indications that fungi play a relatively minor role in the gut microbiome come from research
showing that the gut mycobiome is monopolized by species delivered in our food, including yeasts in
bread, and should not be classified as true colonizers: Thomas A. Auchtung, Tatiana Y. Fofanova,
Christopher J. Stewart, Andrea K. Nash, Matthew C. Wong, Jonathan R. Gesell, Jennifer M.
Auchtung, et al., “Investigating Colonization of the Healthy Adult Gastrointestinal Tract by Fungi,”
mSphere 3, no. 2 (2018): e00092-18. Thomas Auchtung and colleagues also found that frequent teeth
cleaning reduced the levels of Candida albicans in the gut. Presumably, teeth cleaning removes this
yeast from the mouth before it is swallowed, whereas people who are strangers to the toothbrush are
more likely to harbor higher levels of Candida in their digestive systems. An earlier study advised
caution in interpreting metagenomic data on gut fungi because the techniques are so powerful that
they identify species that are present in such low numbers that their biological effects must be
negligible: Mallory J. Suhr and Heather E. Hallen-Adams, “The Human Gut Mycobiome: Pitfalls and
Potentials—A Mycologist’s Perspective,” Mycologia 107, no. 6 (2015): 1057–1073.
12. Katarzyna B. Hooks and Maureen A. O’Malley, “Contrasting Strategies: Human Eukaryotic
versus Bacterial Microbiome Research,” Journal of Eukaryotic Microbiology 67, no. 2 (2020): 279–
295.
13. World Health Organization, WHO Fungal Priority Pathogens List to Guide Research,
Development and Public Health Action (Geneva: World Health Organization, 2022),
https://www.who.int/publications/i/item/9789240060241.
14. Daniel B. DiGiulio, “Diversity of Microbes in Amniotic Fluid,” Seminars in Fetal and
Neonatal Medicine 17, no. 1 (2012): 2–11.
15. Kent A. Willis, John H. Purvis, Erin D. Myers, Michael M. Aziz, Ibrahim Karabayir, Charles
K. Gomes, Brian M. Peters, et al., “Fungi Form Interkingdom Microbial Communities in the
Primordial Human Gut That Develop with Gestational Age,” FASEB Journal 33 (2019): 12825–
12837; Linda Wampach, Anna Heintz-Buschart, Angela Hogan, Emilie E. L. Muller, Shaman
Narayanasamy, Cedric C. Laczny, Luisa W. Hugerth, et al., “Colonization and Succession within the
Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life,”
Frontiers in Microbiology 8 (2017): 738.
16. Matthew S. Payne and Sara Bayatibojakhi, “Exploring Preterm Birth as a Polymicrobial
Disease: An Overview of the Uterine Microbiome,” Frontiers in Immunology 5 (2014): 595. Some
studies have raised concerns about the formation of biofilms of Candida on IUDs: Francieli Chassot,
Melyssa F. N. Negri, Arthur E. Svidzinski, Lucélia Donatti, Rosane M. Peralta, Terezinha I. E.
Svidszinski, and Marcia E. Consalro, “Can Intrauterine Contraceptive Devices Be a Candida
albicans Reservoir?,” Contraception 77, no. 5 (2008): 355–359. There is some evidence that the
presence of an IUD throughout a pregnancy can boost the number of fungi in the amniotic fluid. In
rare cases, amniocentesis can also introduce fungi and other microbes into the birth sac: Yohei Maki,
Midori Fujisaki, Yuichiro Sato, and Hiroshi Sameshima, “Candida Chorioamnionitis Leads to
Preterm Birth and Adverse Fetal-Neonatal Outcome,” Infectious Diseases in Obstetrics and
Gynecology 2017 (2017): 9060138.
17. Between the ages of one and six months, the average daily intake of breast milk is 750
milliliters. One milliliter of breast milk contains 350,000 fungal cells: Alba Boix-Amorós, Cecilia
Martínez-Costa, Amparo Querol, Maria C. Collado, and Alex Mira, “Multiple Approaches Detect the
Presence of Fungi in Human Breastmilk Samples from Healthy Mothers,” Scientific Reports 7
(2017): 13016. This means that we gulp down more than two hundred million fungal cells per day in
the first months of life. Similar numbers of bacteria were detected in an earlier analysis of breast milk
samples: Alba Boix-Amorós, Maria C. Collado, and Alex Mira, “Relationship between Milk
Microbiota, Bacterial Load, Macronutrients, and Human Cells during Lactation,” Frontiers in
Microbiology 7 (2016): 492.
18. Lisa J. Funkhouser and Seth R. Bordenstein, “Mom Knows Best: The Universality of Maternal
Microbial Transmission,” PLoS Biology 11, no. 8 (2013): e1001631.
19. Michael Obladen, “Thrush—Nightmare of the Foundling Hospitals,” Neonatology 101, no. 3
(2012): 159–165; Thomas J. Walsh, Aspasia Katragkou, Tempe Chen, Christine M. Salvatore, and
Emmanuel Roilides, “Invasive Candidiasis in Infants and Children: Recent Advances in
Epidemiology, Diagnosis, and Treatment,” Journal of Fungi 5, no. 1 (2019): 11.
20. “Caesarean Section Rates Continue to Rise, amid Growing Inequalities in Access,” World
Health Organization, June 16, 2021, https://www.who.int/news/item/16-06-2021-caesarean-section-
rates-continue-to-rise-amid-growing-inequalities-in-access-who. Live births by C-section vary, from
less than 20 percent in Israel and Scandinavian countries to 45 percent in South Korea and more than
half of all births in Turkey.
21. “Infant and Young Child Feeding,” UNICEF, last updated December 2022,
https://data.unicef.org/topic/nutrition/infant-and-young-child-feeding/#; “Breastfeeding,” Centers for
Disease Control and Prevention, accessed July 25, 2023,
https://www.cdc.gov/breastfeeding/index.htm. There is a lot of variation in the rate of breastfeeding
across the United States, with more than two-thirds of babies in some states being breastfed for at
least the first six months, declining to less than 40 percent of infants in Mississippi and Alabama.
22. Thomas A. Auchtung, Christopher J. Stewart, Daniel P. Smith, Eric W. Triplett, Daniel Agardh,
William A. Hagopian, Anette G. Ziegler, et al., “Temporal Changes in Gastrointestinal Fungi and the
Risk of Autoimmunity during Early Childhood: The TEDDY Study,” Nature Communications 13
(2022): 3151.
23. Lene Lange, Yuhong Huang, and Peter K. Busk, “Microbial Decomposition of Keratin in
Nature—A New Hypothesis of Industrial Relevance,” Applied Microbiology and Biotechnology 100,
no. 5 (2016): 2083–2096; Hermann Piepenbrink, “Two Examples of Biogenous Dead Bone
Decomposition and Their Consequences for Taphonomic Interpretation,” Journal of Archaeological
Science 13, no. 5 (1986): 417–430.
 CHAPTER TWO
1. Katarzyna Polak-Witka, Lidia Rudnicka, Ulrike Blume-Peytavi, and Annika Vogt, “The Role of
the Microbiome in Scalp Hair Follicle Biology and Disease,” Experimental Dermatology 29, no. 3
(2020): 286–294; Dong H. Park, Joo W. Kim, Hi-Joon Park, and Dae-Hyan Hahm, “Comparative
Analysis of the Microbiome across the Gut-Skin Axis in Atopic Dermatitis,” International Journal of
Molecular Sciences 22 (2021): 4228.
2. This thought experiment begins with a size comparison of yeasts and humans. A yeast cell with
a diameter of 4 × 10−6 m (4 μm) has a cross-sectional area of 1.3 × 10−11 square meters (m2). The
floorspace occupied by a standing human with a modest allowance for arm movement is 0.1 m2,
which is thirteen billion times larger than the outline of a yeast. One million yeasts growing in a one
square centimeter patch of skin fill 13 percent of the available space. Crowded like yeasts, the current
human population would occupy 1/0.13 × 8 × 109 × 0.1 m2 = 6.2 × 109 m2 = 6,200 square kilometers,
which equals the contiguous urbanized area of Los Angeles. This density represents a five-hundred-
fold increase in the current population of Los Angeles.
3. Robert L. Gallo, “Human Skin Is the Largest Epithelial Surface for Interaction with Microbes,”
Journal of Investigative Dermatology 137, no. 6 (2017): 1213–1214. Gallo cites the widely accepted
surface area estimates of 2 square meters (m2) for the skin, 30 m2 for the gut, and 50 m2 for the lungs.
If we include the invaginations of the hair follicles, sweat glands, and sebaceous glands, the epithelial
surface of the skin increases to at least 30 m2. A 140-by-70-centimeter bath towel has an area of 1 m2.
4. The best estimates suggest that fewer than one hundred billion bacterial and fungal cells live on
the skin, which compares with the estimated forty trillion occupants of the gut microbiome.
5. The highest levels of oxygen are found close to the wall of the gut, which is supplied by a rich
system of blood vessels. Most of this oxygen is consumed by the microbiome and independent
chemical reactions that keep the gut lumen anoxic: Elliot S. Friedman, Kyle Bittinger, Tatiana V.
Esipova, Likai Hou, Lillian Chau, Jack Jiang, Clementina Mesaros, et al., “Microbes vs. Chemistry
in the Origin of the Anaerobic Gut Lumen,” Proceedings of the National Academy of Sciences USA
115, no. 16 (2018): 4170–4175. Some bacteria can live with or without oxygen. They are called
facultative anaerobes. Very few fungi have this flexibility, which means that fungal growth must be
limited to locations next to the interior of the gut wall.
6. Hye K. Keum, Hanbyul Kim, Hye-Jin Kim, Taehun Park, Seoyung Kim, Susun An, and Woo J.
Sul, “Structures of the Skin Microbiome and Mycobiome Depending on Skin Sensitivity,”
Microorganisms 8, no. 7 (2020): 1032.
7. Zuzana Stehlikova, Martin Kostovcik, Klara Kostovcikova, Miloslav Kverka, Katernia Juzlova,
Filip Rob, Jana Hercogova, et al., “Dysbiosis of Skin Microbiota in Psoriatic Patients: Co-occurrence
of Fungal and Bacterial Communities,” Frontiers in Microbiology 10 (2019): 438. Settled and well-
defined communities of fungi are destabilized in cases of sensitive skin syndrome and psoriasis and
replaced with different collections of fungi on each patient. This is a mycological instance of the
Anna Karenina principle, or AKP—namely, all happy mycobiomes are alike, but each unhappy
mycobiome is unhappy after its own fashion. The AKP has been applied to science, politics, and
economics, wherever it seems that there are more ways for the subject that is being examined to be
unstable and dysfunctional than to be stable and functional. Microbiologists have found that about
half of all diseases associated with changes to the communities of microbes on the body follow the
AKP: Jesse R. Zaneveld, Ryan McMinds, and Rebecca Vega Thurber, “Stress and Stability: Applying
the Anna Karenina Principle to Animal Microbiomes,” Nature Microbiology 2 (2017): 17121;
Zhanshan S. Ma, “Testing the Anna Karenina Principle in Human Microbiome-Associated Diseases,”
iScience 23, no. 4 (2020): 101007. The reason that variety rules the mycobiome in some illnesses and
a single fungus emerges in others may come down to the role played by the fungi. According to this
idea, the Anna Karenina principle applies when fungi respond to an illness rather than causing it to
develop, and multiple species flare up as the tissue damage unfolds. See discussion of colon cancer in
chapter 5.
8. Geoffrey C. Ainsworth, Introduction to the History of Medical and Veterinary Mycology
(Cambridge: Cambridge University Press, 1976).
9. Keith Liddell, “Skin Disease in Antiquity,” Clinical Medicine 6, no. 1 (2006): 81–86.
10. The translation of Suetonius, The Twelve Caesars, by Anthony S. Kline, explains that
Augustus used the scraper very vigorously to relieve his itching. The standard translations convey the
false impression that the use of the scraper caused the skin blemishes,
https://www.poetryintranslation.com/PITBR/Latin/Suethome.php. The quote about Festus comes
from the poet John Donne, who wrote a defense of suicide in 1608: Biathanatos, ed. M. Rudnick and
M. Pabst Battin (New York: Garland, 1982), 66. The classical source for this story was the Roman
poet Martial, who did not specify that Festus was suffering from ringworm: “o’er his very face crept
black contagion.” This quote comes from Martial, Epigrams, vol. 1, ed. and trans. David R.
Shackleton Bailey, Loeb Classical Library (Cambridge, MA: Harvard University Press, 1993),
epigram 78, pp. 78–79. Donne’s sources are evaluated by Don C. Allen, “Donne’s Suicides,” MLN
56, no. 2 (1941): 129–133.
11. John Aubrey, The Natural History of Wiltshire: Written between 1656 and 1691, ed. J. Britton
(London: J. B. Nichols, 1847), 37.
12. Ainsworth, Introduction, 4–5; Richard Owen, “On the Anatomy of the Flamingo
(Phaenicopteris ruber, L.),” Proceedings of the Zoological Society of London 2 (1832): 141–145.
The bird dissected by Owen had suffered from aspergillosis caused by a species of Aspergillus. The
earliest report of human aspergillosis involved a sinus infection in a French soldier in the eighteenth
century: M. Plaignaud, “Observation sur un Fongus du Sinus Maxillaire,” Journal de Chirurgie
(Paris) (1791): 111–116. After several surgeries, the patient was cured with the use of a “branding
iron introduced through the nose by means of a cannula.… The fungal growths, burnt to their root,
never reappeared.” The fungus that caused pulmonary aspergillosis was described by John Hughes
Bennett, a British physician working in Edinburgh, who examined sputum samples from infected
patients: John H. Bennett, “XVII. On the Parasitic Vegetable Structures Found Growing in Living
Animals,” Transactions of the Royal Society of Edinburgh 15, no. 2 (1844): 277–294. Under the
microscope, Bennett saw “the most beautiful and regular vegetable structure” of transparent tubes
with “joints composed of distinct partitions … constricted like certain kinds of bamboo.” He also
described “bead-like rows” of spores in the clinical samples. Infectious hyphae had been described in
the previous century by William Arderon, who illustrated a freshwater roach whose tail was bristling
with filaments: Ainsworth, Introduction, 3–4. This fish infection is caused by a microorganism
classified as a water mold, rather than a fungus, and is known as saprolegniasis.
13. Editorial, “Robert Remak (1815–1865),” Journal of the American Medical Association 200,
no. 6 (1967): 550–551; Andrzej Grzybowski and Krzysztif Pietrzak, “Robert Remak (1815–1865):
Discoverer of the Fungal Character of Dermatophytoses,” Clinical Dermatology 31, no. 6 (2013):
802–805. Other pioneers in the study of fungal infections of the skin included Johannes Lukas
Schönlein (1793–1864) and David Gruby (1810–1898). Schönlein was inspired by the work of
Agostino Bassi (1773–1856), who demonstrated that a fungus caused a disease of silkworms in the
1830s. Bassi was the first scientist to show that a microorganism could cause a disease in an animal.
 14. Brian P. Hanley, William Bains, and George Church, “Review of Scientific Self-
Experimentation: Ethics History, Regulation, Scenarios, and Views among Ethics Committees and
Prominent Scientists,” Rejuvenation Research 22, no. 1 (2019): 31–42. Experiments on gonorrhea
and syphilis were performed in the eighteenth century by a British surgeon, John Hunter. Hunter may
have inoculated one or more of his patients with infected pus rather than himself, which would have
been criminal as well as unethical: George Qvist, “John Hunter’s Alleged Syphilis,” Annals of the
Royal College of Surgeons of England 59, no. 3 (1977): 206–209.
15. Most ringworm infections in humans are caused by species of Trichophyton. These are
classified in a family of ascomycete fungi called the Arthrodermataceae. Trichophyton rubrum is the
commonest cause of tinea corporis. Trichophyton violaceum is a very close relative that causes hair
and scalp infections. Other species include Trichophyton mentagrophytes, which infects humans
when it is transferred from dogs, cats, and other pets. Skin infections are also caused by species of
Epidermophyton, Microsporum, and Nanizzia, which belong to the same family as Trichophyton.
Readers interested in exploring the taxonomy of these fungi should consult the following sources: G.
Sybren de Hoog, Karoline Dukik, Michel Monod, Ann Packeu, Dirk Stubbe, Marijke Hendrickx,
Christiane Kupsch, et al., “Toward a Novel Multilocus Phylogenetic Taxonomy for the
Dermatophytes,” Mycopathologia 182, nos. 1–2 (2017): 5–31; P. Zhan, K. Dukik, D. Li, J. Sun, J. B.
Stielow, B. Gerrits van den Ende, B. Brankovics, et al., “Phylogeny of Dermatophytes with Genomic
Character Evaluation of Clinically Distinct Trichophyton rubrum and T. violaceum,” Studies in
Mycology 89 (2018): 153–175.
16. Brian B. Adams, “Tinea Corporis Gladiatorum,” Journal of the American Academy of
Dermatology 47, no. 2 (2002): 286–290; D. M. Poisson, D. Rousseau, D. Defo, and E. Estève,
“Outbreak of Tinea Corporis Gladiatorum, a Fungal Skin Infection Due to Trichophyton tonsurans, in
a French High Level Judo Team,” Eurosurveillance 10, no. 9 (2005): 562.
17. Felix Bongomin, Sara Gago, Rita O. Oladele, and David W. Denning, “Global and Multi-
National Prevalence of Fungal Diseases—Estimate Precision,” Journal of Fungi 3 (2017): 57.
18. J. N. Moto, J. M. Maingi, and A. K. Nyamache, “Prevalence of Tinea Capitis in School Going
Children from Mathare, Informal Settlement in Nairobi, Kenya,” BMC Research Notes 8 (2015): 274.
19. Josephine Dogo, Seniyat L. Afegbua, and Edward C. Dung, “Prevalence of Tinea Capitis
Among School Children in Nok Community of Kaduna State, Nigeria,” Journal of Pathogens
(2016): 9601717.
20. A. K. Gupta and R. C. Summerbell, “Tinea Capitis,” Medical Mycology 38, no. 4 (2000): 255–
287.
21. Morris Gleich, “Thallium Acetate Poisoning in the Treatment of Ringworm of the Scalp:
Report of Two Cases,” JAMA 97, no. 12 (1931): 851. In his paper, Gleich referred to the deaths of
fourteen children in an orphanage in Grenada, Spain, who received an accidental overdose of
thallium acetate for ringworm in 1930. A year after the publication of Gleich’s paper, a British
dermatologist endorsed the continued use of rat poison for treating ringworm: John T. Ingram,
“Thallium Acetate in the Treatment of Ringworm of the Scalp,” British Medical Journal 1, no. 3704
(1932): 8–10. Ingram wrote, “There is no serious evidence against the use of thallium acetate …
[t]hough toxic symptoms may occasionally be encountered, they are seldom severe, and the patient
invariably recovers,” which was not very reassuring.
22. Anonymous, “ ‘X’ Rays as a Depilatory,” The Lancet 147, no. 3793 (1896): 1296.
23. S. Cochrane Shanks, “Thallium Treatment of Ringworm,” British Medical Journal 1 (1932):
121.
 24. Rebecca Herzig, “The Matter of Race in Histories of American Technology,” in Technology
and the African-American Experience: Needs and Opportunities for Study, ed. Bruce Sinclair
(Cambridge, MA: MIT Press, 2004), 179–180.
25. Roy E. Shore, Miriam Moseson, Naomi Harley, and Bernard S. Pasternack, “Tumors and
Other Diseases Following Childhood X-Ray Treatment for Ringworm of the Scalp (Tinea capitis),”
Health Physics 85, no. 4 (2003): 404–408.
26. Liat Hoffer, Shifra Shvarts, and Dorit Segal-Engelchin, “Hair Loss Due to Scalp Ringworm
Irradiation in Childhood: Health and Psychosocial Risks for Women,” Israel Journal of Health
Policy Research 9 (2020): 34.
27. Esther Segal and Daniel Elad, “Human and Zoonotic Dermatophytoses: Epidemiological
Aspects,” Frontiers in Microbiology 12 (2021): 713532. Geophilic mycoses are caused by fungi that
come from an external source in the environment like soil or decomposing plant material.
28. Andriana M. Celis Ramírez, Adolfo Amézquita, Juliana E. C. Cardona Jaramillo, Luisa F.
Matiz-Cerón, Juan S. Andrade-Martínez, Sergio Triana, Maria J. Mantilla, et al., “Analysis of
Malassezia Lipidome Disclosed Differences among the Species and Reveals Presence of Unusual
Yeast Lipids,” Frontiers in Cellular and Infection Microbiology 10 (2020): 338. Parasitic wasps that
lay their eggs on caterpillars have followed the same evolutionary path as Malassezia and extract
their fatty acids from their hosts.
29. Minji Park, Yong-Joon Cho, Yang W. Lee, and Won H. Jung, “Understanding the Mechanism
of Action of the Anti-Dandruff Agent Zinc Pyrithione against Malassezia restricta,” Scientific
Reports 8 (2018): 12086.
30. Hee K. Park, Myung-Ho Ha, Sang-Gue Park, Myeung N. Kim, Beom J. Kim, and W. Kim,
“Characterization of the Fungal Microbiota (Mycobiome) in Healthy and Dandruff-Afflicted Human
Scalps,” PLoS ONE 7, no. 2 (2012): e32847.
31. Diana M. Proctor, Thelma Dangana, D. Joseph Sexton, Christine Fukuda, Rachel D. Yelin,
Mary Stanley, Pamela B. Bell, et al., “Integrated Genomic, Epidemiologic Investigation of Candida
auris Skin Colonization in a Skilled Nursing Facility,” Nature Medicine 27 (2021): 1401–1409.
32. Suhail Ahmad and Wadha Alfouzan, “Candida auris: Epidemiology, Diagnosis, Pathogenesis,
Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in
Healthcare Facilities,” Microorganisms 9 (2021): 807.
33. Nancy A. Chow, José F. Muñoz, Lalitha Gade, Elizabeth L. Berkow, Xiao Li, Rory M. Welsh,
Kaitlin Forsberg, et al., “Tracing the Evolutionary History and Global Expansion of Candida auris
Using Population Genomic Analyses,” mBio 11, no. 2 (2020): e03364-19.
34. Path Arora, Prerna Singh, Yue Wang, Anamika Yadav, Kalpana Pawar, Ashtosh Singh, Gadi
Padmavati, et al., “Environmental Isolation of Candida auris from the Coastal Wetlands of Andaman
Islands, India,” mBio 12, no. 2 (2021): e03181-20.
35. Arturo Casadevall, Dimitrios P. Kontoyiannis, and Vincent Robert, “On the Emergence of
Candida auris: Climate Change, Azoles, Swamps, and Birds,” mBio 10, no. 4 (2019): e01397-19;
Brendan R. Jackson, Nancy Chow, Kaitlin Forsberg, Anastasia P. Litvintseva, Shawn R. Lockhart,
Rory Welsh, Snigdha Vallabhaneni, et al., “On the Origins of a Species: What Might Explain the Rise
of Candida auris?,” Journal of Fungi 5, no. 3 (2019): 58. The putative link between an increasing
number of fungal infections and the warming climate has entered popular consciousness with the
help of an HBO drama screened in 2023 called The Last of Us. The television series was referenced
in an opinion article in the New York Times: Neil Vora, “ ‘The Last of Us’ Is Right: Our Warming
Planet Is a Petri Dish,” New York Times, April 6, 2023. For information on mesophiles, see Sarah C.
Watkinson, Lynne Boddy, and Nicholas P. Money, The Fungi, 3rd ed. (Amsterdam: Academic Press,
2016), 173–174. Changes in rainfall and other weather patterns rather than temperature may be more
important in the spread of mycoses in some regions: Anil A. Panackal, “Global Climate Change and
Infectious Diseases: Invasive Mycoses,” Journal of Earth Science and Climate Change 1 (2011):
108.
36. Ewa Ksiezopolska and Toni Gabaldón, “Evolutionary Emergence of Drug Resistance in
Candida Opportunistic Pathogens,” Genes 9, no. 9 (2018): 461.
37. Lise N. Jørgensen and Thies M. Heick, “Azole Use in Agriculture, Horticulture, and Wood
Preservation—Is It Indispensable?,” Frontiers in Cellular and Infection Microbiology 11 (2021):
730297; Paul E. Verweij, Maiken C. Arendrup, Ana Alastruey-Izquierdo, Jeremy A. W. Gold, Shawn
R. Lockhart, Tom Chiller, and P. Lewis White, “Dual Use of Antifungals in Medicine and
Agriculture: How Do We Help Prevent Resistance Developing in Human Pathogens?,” Drug
Resistance Updates 65 (2022): 100885.
38. Ron Pinhasi, Boris Gasparian, Gregory Areshian, Diana Zardaryan, Alexia Smith, Guy Bar-
Oz, and Thomas Higham, “First Direct Evidence of Chalcolithic Footwear from the Near Eastern
Highlands,” PLoS ONE 5, no. 6 (2010): e10984.
39. Contact lens solutions keep the eye clean with hydrogen peroxide, which works as a general
disinfectant, and other compounds with more specific antimicrobial properties. The combination of
natural cleansing and contact lens solutions works fine unless the cleaning fluids become
contaminated with fungi. This is what happened in the United States in 2005 and 2006, when an
outbreak of fungal keratitis affected 130 patients. One-third of the patients suffered eye damage that
was serious enough to require corneal transplants. The CDC traced these cases to batches of contact
lens solution manufactured by Bausch and Lomb, Inc., and legal settlements to victims have cost the
company an estimated $1 billion. The fungus that caused this eye damage was a species of Fusarium,
which normally grows on plants. Its spores must have landed in the lens solution during manufacture.
Fungal keratitis continues to be a problem for wearers who are not careful to wash their lenses with
fresh cleaning solutions. Y. Wang, H. Chen, T. Xia, and Y. Huang, “Characterization of Fungal
Microbiota on Normal Ocular Surface of Humans,” Clinical Microbiology and Infection 26, no. 1
(2020): 123.e9–123.e13; Sisinthy Shivaji, Rajagopalaboopathi Jayasudha, Gumpili S. Prashanthi,
Kotakonda Arunasri, and Taraprasad Das, “Fungi of the Human Eye: Culture to Mycobiome,”
Experimental Eye Research 217 (2022): 108968; Arthur B. Epstein, “In the Aftermath of the
Fusarium Keratitis Outbreak: What Have We Learned?,” Clinical Ophthalmology 1, no. 4 (2007):
355–366.
40. A description of mycetoma of the foot in the three-thousand-year-old Indian Atharvaveda is
the oldest record of a human mycosis; Ainsworth, Introduction, 1–2. Readers interested in this
disease should consult Henry Vandyke Carter’s book based on his observations in Bombay, where he
served with the Indian Medical Service: On Mycetoma; Or, the Fungus Disease of India (London: J.
& A. Churchill, 1874). Carter was the illustrator of Gray’s Anatomy, and his hand-colored drawings
of ferocious foot infections in On Mycetoma make this a collector’s item.
41. Kristina Killgrove, Thomas Böni, and Francesco M. Galassi, “A Possible Case of Mycetoma
in Ancient Rome (Italy, 2nd–3rd Centuries AD),” https://doi.org/10.31235/osf.io/2vjxk.
42. Bikash R. Behera, Sanjib Mishra, Manmath K. Dhir, Rabi N. Panda, and Sagarika Samantaray,
“ ‘Madura Head’—A Rare Case of Craniocerebral Maduromycosis,” Indian Journal of Neurosurgery
7 (2018): 159–163. Madura hand is another rare presentation of this mycosis: K. Rahman, M. Naim,
and M. Farooqui, “Mycetoma of Hand—An Unusual Presentation,” Internet Journal of Dermatology
8, no. 1 (2009), https://ispub.com/IJD/8/1/4863.
 43. Rosane Orofino-Costa, Priscila M. de Macedo, Anderson M. Rodrigues, and Andréa R.
Bernardes-Engemann, “Sporotrichosis: An Update on Epidemiology, Etiopathogenesis, Laboratory
and Clinical Therapeutics,” Anais Brasileiros de Dermatologia 92, no. 5 (2017): 606–620. Roses
have prickles rather than thorns, so the infection mechanism for sporotrichosis involves a prickle
prick rather than thorn prick, if we insist on the correct botanical definitions. Sporotrichosis is
another example of a zoonotic mycosis that can be spread to humans from their pet cats.
44. Yvonne Gräser, Janine Fröhlich, Wolfgang Presber, and Sybren de Hoog, “Microsatellite
Markers Reveal Geographic Population Differentiation in Trichophyton rubrum,” Journal of Medical
Microbiology 56, no. 8 (2007): 1058–1065; P. Zhan, K. Dukik, D. Li, J. Sun, J. B. Stielow, B. Gerrits
van den Ende, B. Brankovics, et al., “Phylogeny of Dermatophytes with Genomic Character
Evaluation of Clinically Distinct Trichophyton rubrum and T. violaceum,” Studies in Mycology 89
(2018): 153–175.
45. “Athlete’s Foot (Tinea Pedis) Treatment Market to Reach US$1.7 Bn by End of 2027,”
PharmiWeb.com, April 1, 2021, https://www.pharmiweb.com/press-release/2021-04-01/athlete-s-
foot-tinea-pedis-treatment-market-to-reach-us-17-bn-by-end-of-2027.
 CHAPTER THREE
1. My modest contributions to experimental mycology represent an extension of the pioneering
studies on fungal spores by A. H. R. Buller (1874–1944) and Philip Gregory (1907–1986). Buller
was the Einstein of mycology, and Gregory is known as the father of modern aerobiology, which is
the study of spores and other airborne biological particles. Like me, Buller and Gregory suffered
from asthma. By developing methods for measuring the concentrations of airborne spores, Gregory
and his colleagues were responsible for drawing attention to fungi as a cause of allergy: Philip H.
Gregory and John M. Hirst, “Possible Role of Basidiospores as Air-borne Allergens,” Nature 170
(1952): 414. Asthma is not a qualification for spending decades studying spores. After all, one of the
most influential mycologists of the twentieth century, C. T. Ingold (1905–2010), had no breathing
issues, published papers on spores over a span of seventy years, and lived to the age of 104.
2. Alex Sakula, “Sir John Floyer’s A Treatise of the Asthma (1698),” Thorax 39, no. 4 (1984):
248–254.
3. A spherical spore with a diameter 4 µm has a volume of 3.4 × 10−17 m3; 100,000 of these spores
occupy a space of 3.4 × 10−12 m3. If these spores are dispersed evenly in one cubic meter of air, each
spore will sail in a volume of air that is three hundred billion times larger than itself.
4. The inhalation of four hundred liters of air per hour (or 0.4 m3), with an average spore
concentration of five thousand spores per cubic meter, over a lifespan of seventy-nine years, exposes
the individual to 1.4 billion spores: 5,000 m−3 × 0.4 m3 × 24 × 365 × 79 = 1.4 × 109 spores. The total
volume of these spores, based on the volume of the individual spore (calculated from note 3 above),
equals 1.4 × 109 × 3.4 × 10−17 m3 = 4.8 × 10−8 m3 = 4.8 × 10−5 L = 0.05 mL. The density of a spore is
close to water, so the estimated mass of spores inhaled over a lifetime is 0.05 g or 50 milligrams,
which is a bit lighter than a garden pea.
5. Paul Klenerman, an immunologist from the University of Oxford, provides a nice introduction
to immunology: The Immune System: A Very Short Introduction (Oxford: Oxford University Press,
2018). The authoritative source on allergy is a weighty, two-volume book: A. Wesley Burks, Stephen
T. Holgate, Robyn E. O’Hehir, David H. Broide, Leonard B. Bacharier, Gurjit K. Khurana Hershey,
and R. Stokes Peebles, Middleton’s Allergy: Principles and Practice, 9th ed. (Amsterdam: Elsevier,
2020).
6. Immunoglobulin E (IgE) is the antibody that plays a vital role in type I hypersensitivity
reactions found in asthma and other allergic diseases. IgE is also a component of the immune
reaction against parasitic worms. There is growing evidence that the innate immune system is also
involved in asthma: Stephen T. Holgate, “Innate and Adaptive Immune Responses in Asthma,”
Nature Medicine 18 (2012): 673–683.
7. William E. Steavenson, Spasmodic Asthma: A Thesis for the M.B. Degree of the University of
Cambridge (Cambridge: Deighton, Bell & Co., 1879).
8. Anon., “Obituary: William Edward Steavenson, M.D. Cantab., M.R.C.P.,” British Medical
Journal (June 6, 1891): 1261–1262. He died from influenza and bronchitis. Bronchitis is the most
common complication of influenza. It is an inflammatory illness like asthma and shares the same
type of antibody response involving immunoglobulin E (IgE): Christopher E. Brightling, “Chronic
Cough Due to Nonasthmatic Eosinophilic Bronchitis: ACCP Evidence-Based Clinical Practice
Guidelines,” Chest 129, no. 1 suppl. (2006): 116S–121S.
9. Kathryn J. Waite, “Blackley and the Development of Hay Fever as a Disease of Civilization in
the Nineteenth Century,” Medical History 39, no. 2 (1995): 186–196.
 10. David W. Denning, B. Ronan O’Driscoll, Cory M. Hogaboam, Paul Bowyer, and Robert M.
Niven, “The Link between Fungi and Severe Asthma: A Summary of the Evidence,” European
Respiratory Journal 27, no. 2 (2006): 615–626; Gavin Dabrera, Virginia Murray, Jean Emberlin,
Jonathan G. Ayres, Christopher Collier, Yoland Clewlow, and Patrick Sachon, “Thunderstorm
Asthma: An Overview of the Evidence Base and Implications for Public Health Advice,” Quarterly
Journal of Medicine 106, no. 3 (2013): 207–217. The phenomenon of fungal-induced thunderstorm
asthma was not recognized until 1983, when an asthma “epidemic” in Birmingham was linked to
high levels of spores associated with a storm: G. E. Packe, P. S. Archer, and Jon G. Ayres, “Asthma
and the Weather,” The Lancet 322, no. 8344 (1983): 281; H. Morrow Brown and Felicity Jackson,
“Asthma and the Weather,” The Lancet 322, no. 8350 (1983): 630.
11. The grow and blow model was originally proposed for the dispersal of the fungus
Coccidioides, but seems likely to apply to other species: James D. Tamerius and Andrew C. Comrie,
“Coccidioidomycosis Incidence in Arizona Predicted by Seasonal Precipitation,” PLoS ONE 6, no. 6
(2011): e21009.
12. Agnieszka Grinn-Gofroń and Agnieszka Strzelczak, “Changes in Concentration of Alternaria
and Cladosporium Spores during Summer Storms,” International Journal of Biometeorology 57, no.
5 (2013): 759–768; Ajay Kevat, “Thunderstorm Asthma: Looking Back and Looking Forward,”
Journal of Asthma and Allergy 13 (2020): 293–299; Nur S. Idrose, Shyamali C. Dharmage, Adrian J.
Lowe, Katrina A. Lambert, Caroline J. Lodge, Michael J. Abramson, Jo A. Douglass, et al., “A
Systematic Review of the Role of Grass Pollen and Fungi in Thunderstorm Asthma,” Environmental
Research 181 (2020): 108911.
13. Mark Jackson, Asthma: The Biography (Oxford: Oxford University Press, 2009). Jackson is
concerned with the social history of asthma rather than the science, but mention of fungal spores
would not have been amiss.
14. Morell Mackensie, Hay Fever and Paroxysmal Sneezing, 4th ed. (London: J. & A. Churchill,
1887), 10.
15. Erich Wittkower and M. D. Berlin, “Studies in Hay-Fever Patients (the Allergic Personality),”
Journal of Mental Science 84 (1938): 352–369. This paper was specific in its study of hay fever, as a
seasonal allergy, but the wider concept of “the allergic personality” embraces the psychological
characteristics of asthma patients.
16. Renee D. Goodwin, “Toward Improving Our Understanding of the Link between Mental
Health, Lung Function, and Asthma Diagnosis. The Challenge of Asthma Measurement,” American
Journal of Respiratory and Critical Care Medicine 194, no. 11 (2016): 1313–1315.
17. Nicholas P. Money, Carpet Monsters and Killer Spores: A Natural History of Toxic Mold
(New York: Oxford University Press, 2004).
18. Cornelia Witthauer, Andrew T. Gloster, Andrea H. Meyer, and Roselind Lieb, “Physical
Diseases among Persons with Obsessive Compulsive Symptoms and Disorder: A General Population
Study,” Social Psychiatry and Psychiatric Epidemiology 49, no. 12 (2014): 2013–2022.
19. O. P. Sharma, “Marcel Proust (1871–1922): Reassessment of His Asthma and Other
Maladies,” European Respiratory Journal 15, no. 5 (2000): 958–960. Proust wrote much of his In
Search of Lost Time in a cork-lined bedroom in Paris in an attempt to escape his invisible airborne
enemies.
20. Paul Bowyer, Marcin Fraczek, and David W. Denning, “Comparative Genomics of Fungal
Allergens and Epitopes Shows Widespread Distribution of Closely Related Allergen and Epitope
Orthologues,” BMC Genomics 7 (2006): 251; Viswanath P. Kurup and Banani Banerjee, “Fungal
Allergens and Peptide Epitopes,” Peptides 21, no. 4 (2000): 589–599.
 21. Noah W. Palm, Rachel K. Rosenstein, and Ruslan Medzhitov, “Allergic Host Defences,”
Nature 484 (2012): 465–472; Michael Gross, “Why Did Evolution Give Us Allergies?,” Current
Biology 25, no. 2 (2015): R53–55; Alvaro Daschner and Juan González Fernández, “Allergy in an
Evolutionary Framework,” Journal of Molecular Evolution 88, no. 1 (2020): 66–76.
22. Grain silos packed with moldy barley create dense clouds of spores when they are unloaded,
with one study showing a peak concentration of one billion spores per cubic meter of air: John Lacey,
“The Microbiology of Moist Barley Storage in Unsealed Silos,” Annals of Applied Biology 69, no. 3
(1971): 187–212. Sampling of the airborne dust during cereal harvesting in Lincolnshire in the 1970s
showed a peak concentration of two hundred million spores per cubic meter of air: C. S. Darke, J.
Knowelden, J. Lacey, and A. Milford Ward, “Respiratory Disease of Workers Harvesting Grain,”
Thorax 31, no. 2 (1976): 294–302. Twenty three percent of the farm workers in this study reported
symptoms of wheezing and other respiratory complaints, but the remaining 77 percent of employees
said that they were symptom-free. A similar spore count was recorded from a Swedish storehouse
filled with wood chips used for fuel: Göran Blomquist, Gunnar Ström, and Lars-Helge Strömquist,
“Sampling of High Concentrations of Airborne Fungi,” Scandinavian Journal of Work, Environment,
and Health 10, no. 2 (1984): 109–113. Other records of high spore concentrations include
measurements of 128 million spores per cubic meter of air in a Portuguese cork factory, forty million
spores per cubic meter in Finnish cow barns, and twenty million spores per cubic meter in Norwegian
sawmills: John Lacey, “The Air Spora of a Portuguese Cork Factory,” Annals of Occupational
Hygiene 16, no. 3 (1973): 223–230; Rauno Hanhela, Kyösti Louhelainen, and Anna-Liisa Pasanen,
“Prevalence of Microfungi in Finnish Cow Barns and Some Aspects of the Occurrence of Wallemia
sebi and Fusaria,” Scandinavian Journal of Work, Environment, and Health 21, no. 3 (1994): 223–
228; Wijnand Eduard, Per Sandven, and Finn Levy, “Exposure and IgG Antibodies to Mold Spores in
Wood Trimmers: Exposure–Response Relationships with Respiratory Symptoms,” Applied
Occupational and Environmental Hygiene 9, no. 1 (1995): 44–48. A ten-year follow-up study of the
workers exposed to the phenomenal levels of spores in the Norwegian sawmills found no evidence of
long-term health effects: Karl Færden, May B. Lund, Trond M. Aaløkken, Wijnand Eduard, Per
Søstrand, Sverre Langård, and Johny Kongerud, “Hypersensitivity Pneumonitis in a Cluster of
Sawmill Workers: A 10-Year Follow-Up of Exposure, Symptoms, and Lung Function,” International
Journal of Occupational and Environmental Health 20, no. 2 (2014): 167–173. The use of dust
masks has become routine since the original study of sawmills. The Guinness World Records refers to
a global all-time record concentration of 194 million spores per cubic meter of air that was measured
in Wales, but I have been unable to track down the source of this measurement:
https://www.guinnessworldrecords.com/world-records/450409-largest-fungal-spore-count.
23. Lisa A. Reynolds and B. Brett Finlay, “Early Life Factors That Affect Allergy Development,”
Nature Reviews Immunology 17, no. 8 (2017): 518–528; B. Campbell, C. Raherison, C. J. Lodge, A.
J. Lowe, T. Gislason, J. Heinrich, J. Sunyer, et al., “The Effects of Growing Up on a Farm on Adult
Lung Function and Allergic Phenotypes: An International Population-Based Study,” Thorax 72, no. 3
(2017): 236–244.
24. Andrew H. Liu, “Revisiting the Hygiene Hypothesis for Allergy and Asthma,” Journal of
Allergy and Clinical Immunology 136, no. 4 (2015): 860–865.
25. Money, Carpet Monsters.
26. Indoor molds seem to blossom in the vacuum created by the removal of the bacteria: Laura-
Isobel McCall, Chris Callewaert, Qiyun Zhu, Se J. Song, Amina Bouslimani, Jeremiah J. Minich,
Madeline Ernst, et al., “Home Chemical and Microbial Transitions across Urbanization,” Nature
Microbiology 5, no. 1 (2020): 108–115.
 27. My parents tried this remedy for me without success. The dust mite allergen is described by
Andy Chevigné and Alain Jacquet, “Emerging Roles of the Protease Allergen Der p 1 in House Dust
Mite–Induced Airway Inflammation,” Journal of Allergy and Clinical Immunology 142, no. 2 (2018):
398–400. Allergen avoidance as an asthma treatment is addressed by E. M. Rick, K. Woolnough, C.
H. Pashley, and A. J. Wardlaw, “Allergic Fungal Airway Disease,” Journal of Investigational
Allergology and Clinical Immunology 26, no. 6 (2016): 344–354.
28. Keigo Kainuma, Akihiko Terada, Reiko Tokuda, Mizhuo Nagao, Nobuo Kubo, and Takao
Fujisawa, “Wearing a Mask during Sleep Improved Asthma Control in Children,” Journal of Allergy
and Clinical Immunology 131 (2013): AB4; Barbara J. Polivka, Kamal Eldeirawi, Luz Huntington-
Moskos, and Sharmilee M. Nyenhuis, “Mask Use Experiences, COVID-19, and Adults with Asthma:
A Mixed-Methods Approach,” Journal of Allergy and Clinical Immunology: In Practice 10, no. 1
(2022): 116–123. Face masks appear to be effective in reducing the symptoms of allergic rhinitis:
Erdem Mengi, Cüneyt Orhan Kara, Uğur Alptürk, and Bülent Topuz, “The Effect of Face Mask
Usage on the Allergic Rhinitis Symptoms in Patients with Pollen Allergy during the Covid-19
Pandemic,” American Journal of Otolaryngology 43, no. 1 (2022): 103206.
29. Eric K. Chu and Jeffrey M. Drazen, “Asthma: One Hundred Years of Treatment and Onward,”
American Journal of Respiratory and Critical Care Medicine 171, no. 11 (2005): 1202–1208.
30. Sheldon G. Cohen, “Asthma among the Famous: Roger E. C. Altounyan (1922–1987) British
Physician and Pharmacologist,” Allergy and Asthma Proceedings 19, no. 5 (1998): 328–332; Jack
Howell, “Roger Altounyan and the Discovery of Cromolyn (Sodium Cromoglycate),” Journal of
Allergy and Clinical Immunology 115, no. 4 (2005): 882–885.
31. Teresa To, Sanja Stanojevic, Ginette Moores, Andrea S. Gershon, Eric D. Bateman, Alvaro A.
Cruz, and Louis-Phillipe Boulet, “Global Asthma Prevalence in Adults: Findings from the Cross-
Sectional World Health Survey,” BMC Public Health 12 (2012): 204; I. Asher and N. Pearce, “Global
Burden of Asthma among Children,” International Journal of Tuberculosis and Lung Disease 18, no.
11 (2014): 1269–1278.
32. Elizabeth H. Tham, Evelyn X. L. Loo, Yanan Zhu, and Lynette P.-C. Shek, “Effects of
Migration on Allergic Diseases,” International Archives of Allergy and Immunology 178 (2019):
128–140. Born in Birmingham, A. H. R. Buller (see note 1 above) escaped his asthma on the
Canadian Prairies when he moved to Winnipeg in 1904 to found the Department of Botany at the
University of Manitoba. He wrote that, “so far as the number of microorganisms is concerned, the
climate of Central Canada during the winter must be one of the best in any civilised country in the
world”: Arthur H. R. Buller, and Charles W. Lowe, “Upon the Number of Micro-organisms in the Air
of Winnipeg,” Transactions of the Royal Society of Canada, ser. 3, 4 (1910): 41–58.
33. Daniel L. Hamilos, “Allergic Fungal Rhinitis and Rhinosinusitis,” Proceedings of the
American Thoracic Society 7, no. 3 (2010): 245–252; Peter Small, Paul K. Keith, and Harold Kim,
“Allergic Rhinitis,” Allergy, Asthma, and Clinical Immunology 14, suppl. 2 (2018): 51.
34. Ulrich Costabel, Yasunari Miyazaki, Annie Pardo, Dirk Koschel, Francesco Bonella, Paolo
Spagnolo, Josune Guzman, et al., “Hypersensitivity Pneumonitis,” Nature Reviews Disease Primers
6, no. 1 (2020): 65; J. Davidson, J. McErlane, K. Aljboor, S. L. Barratt, A. Jeyabalan, A. R. L.
Medford, A. M. Borman, and H. Adamali, “Musical Instruments, Fungal Spores and Hypersensitivity
Pneumonitis,” QJM 112, no. 4 (2019): 287–289.
35. Bibek Paudel, Theodore Chu, Meng Chen, Vanitha Sampath, Mary Prunicki, and Kari C.
Nadeau, “Increased Duration of Pollen and Mold Exposure Are Linked to Climate Change,”
Scientific Reports 11 (2021): 12816.
 36. Michael R. Knowles and Richard C. Boucher, “Mucus Clearance as a Primary Innate Defense
Mechanism for Mammalian Airways,” Journal of Clinical Investigation 109, no. 5 (2002): 571–577;
Ximena Bustamante-Marin and Lawrence E. Ostrowski, “Cilia and Mucociliary Clearance,” Cold
Spring Harbor Perspectives in Biology 9, no. 4 (2017): a028241.
37. Avani R. Patel, Amar R. Patel, Shivank Singh, Shantanu Singh, and Imran Khawaja, “Treating
Allergic Bronchopulmonary Aspergillosis: A Review,” Cureus 11, no. 4 (2019): e4538; Avani R.
Patel, Amar R. Patel, Shivank Singh, Shantanu Singh, and Imran Khawaja, “Diagnosing Allergic
Bronchopulmonary Aspergillosis: A Review,” Cureus 11, no. 4 (2019): e4550.
38. Aaron S. Miller and Robert W. Wilmott, “The Pulmonary Mycoses,” in Kendig’s Disorders of
the Respiratory Tract in Children, 9th ed., ed. Robert W. Wilmott, Andrew Bush, Robin R. Deterding,
Felix Ratjen, Peter Sly, Heather J. Zar, and Albert P. Li (Philadelphia: Elsevier, 2019), 507–527e3.
39. Pamela P. Lee and Yu-Lung Lau, “Cellular and Molecular Defects Underlying Invasive Fungal
Infections—Revelations from Endemic Mycoses,” Frontiers in Immunology 8 (2017): 735.
40. Russell E. Lewis and Dimitrios P. Kontoyiannis, “Invasive Aspergillosis in Glucocorticoid-
Treated Patients,” Medical Mycology 47, suppl. 1 (2009): S271–S281.
41. Tobias Lahmer, Silja Kriescher, Alexander Herner, Kathrin Rothe, Christoph D. Spinner,
Jochen Schneider, Ulrich Mayer, et al., “Invasive Pulmonary Aspergillosis in Critically Ill Patients
with Severe COVID-19 Pneumonia: Results from the Prospective AspCOVID-19 Study,” PLoS ONE
16, no. 3 (2021): e0238825.
42. Shawn R. Lockhart, Mitsuru Toda, Kaitlin Benedict, Diego H. Caceres, and Anastasia P.
Litvintseva, “Endemic and Other Dimorphic Mycoses in the Americas,” Journal of Fungi 7 (2021):
151.
43. L. F. Shubitz, C. D. Butkiewicz, S. M. Dial, and C. P. Lindan, “Incidence of Coccidioides
Infection among Dogs Residing in a Region in Which the Organism Is Endemic,” Journal of the
American Veterinary Medical Association 226, no. 11 (2005): 1846–1850.
44. The numbers are taken from Felix Bongomin, Sara Gago, Rita O. Oladele, and David W.
Denning, “Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision,” Journal
of Fungi 3 (2017): 57, which also serves as a useful source of data for other chapters.
45. “Fungal Diseases: Blastomycosis,” CDC, accessed July 15, 2023,
https://www.cdc.gov/fungal/diseases/blastomycosis/index.html; Katrina Thompson, Alana K. Sterkel,
and Erin G. Brooks, “Blastomycosis in Wisconsin: Beyond the Outbreaks,” Academic Forensic
Pathology 7, no. 1 (2017): 119–129; Keith Matheny, “Fungal Infection Outbreak Affects 90+
Workers at Escanaba Paper Mill,” Detroit Free Press, April 8, 2023.
46. P. Lewis White, Jessica S. Price, and Matthijs Backx, “Pneumocystis jirovecii Pneumonia:
Epidemiology, Clinical Manifestation and Diagnosis,” Current Fungal Infection Reports 13 (2019):
260–273; Gilles Nevez, Philippe M. Hauser, and Solène Le Gal, “Pneumocystis jirovecii,” Trends in
Microbiology 28, no. 12 (2020): 1034–1035; R. Benson Weyant, Dima Kabbani, Karen Doucette,
Cecilia Lau, and Carlos Cervera, “Pneumocystis jirovecii: A Review with a Focus on Prevention and
Treatment,” Expert Opinion on Pharmacotherapy 22, no. 12 (2021): 1579–1592.
 CHAPTER FOUR
1. Alon Tal, Pollution in a Promised Land: An Environmental History of Israel (Berkeley:
University of California Press, 2002), 1–4.
2. Sandra C. Signore, Christoph P. Dohm, Gunter Schütze, Mathias Bähr, and Pawel Kermer,
“Scedosporium apiospermum Brain Abscesses in a Patient after Near-Drowning—A Case Report
with 10-Year Follow-Up and a Review of the Literature,” Medical Mycology Case Reports 17
(2017): 17–19.
3. P. Hartmann, A. Ramseier, F. Gudat, M. J. Mihatsch, W. Polasek, and C. Geisenhoff, “Das
Normgewicht des Gehirns beim Erwachsenen in Abhängigkeit von Alter, Geschlecht, Körpergröße
und Gewicht,” Pathologe 15 (1994): 165–170.
4. Karoll J. Cortez, Emmanuel Roilides, Flavio Quiroz-Telles, Joseph Meletiadis, Charalampos
Antachopoulos, Tena Knudsen, Wendy Buchanan, et al., “Infections Caused by Scedosporium spp.,”
Clinical Microbiology Reviews 21, no. 1 (2008): 157–197.
5. P. A. Kowacs, C. E. Soares Silvado, S. Monteiro de Almeida, M. Ramos, K. Abrão, L. E.
Madaloso, R. L. Pinheiro, et al., “Infection of the CNS by Scedosporium apiospermum after Near
Drowning: Report of a Fatal Case and Analysis of Its Confounding Factors,” Journal of Clinical
Pathology 57 (2004): 205–207.
6. “Stop Neglecting Fungi,” Nature Microbiology 2 (2017): 17120.
7. Felix Bongomin, Sara Gago, Rita O. Oladele, and David W. Denning, “Global and Multi-
National Prevalence of Fungal Diseases—Estimate Precision,” Journal of Fungi 3, no. 4 (2017): 57.
8. The fungus Pneumocystis jirovecii causes pneumocystis pneumonia in AIDS patients (see
chapter 3).
9. “Fungal Disease: C. neoformans Infection Statistics,” CDC, accessed July 15, 2023,
https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/statistics.html.
10. Priority for the claim that all fungi are opportunists seems to lie with Raymond
Vanbreuseghem (1909–1993), who was a mycologist at the Institute for Tropical Medicine in
Antwerp: R. Vanbreuseghem and C. de Vroey, “Systemic Opportunistic Fungal Infections,”
Postgraduate Medical Journal 55 (1979): 593–594.
11. Anuradha Chowdhary, Shallu Kathuria, Kshitij Agarwal, and Jacques F. Meis, “Recognizing
Filamentous Basidiomycetes as Agents of Human Disease: A Review,” Medical Mycology 52, no. 8
(2014): 782–797.
12. C. Correa-Martinez, A. Brentrup, K. Hess, K. Becker, A. H. Groll, and F. Schaumburg, “First
Description of a Local Coprinopsis cinerea Skin and Soft Tissue Infection,” New Microbes and New
Infections 21 (2018): 102–104.
13. Erin L. Greer, Todd J. Kowalski, Monica L. Cole, Dylan V. Miller, and Larry M. Baddour,
“Truffle’s Revenge: A Pig-Eating Fungus,” Cardiovascular Pathology 17, no. 5 (2008): 342–343.
14. Adela Enache-Angoulvant and Christophe Hennequin, “Invasive Saccharomyces Infection: A
Comprehensive Review,” Clinical Infectious Diseases 41, no. 11 (2005): 1559–1568. A strain of
Saccharomyces cerevisiae that is used as a probiotic is implicated in many cases. Some yeast
specialists regard this as a different species called Saccharomyces boulardii, although the distinction
between species and strains is a matter of opinion rather than science in this instance. Rare cases of
invasive disease caused by ordinary yeast strains used in baking have also been reported.
15. Arturo Casadevall and Liise-anne Pirofski, “The Damage-Response Framework of Microbial
Pathogenesis,” Nature Reviews Microbiology 1, no. 1 (2003): 17–24; Mary A. Jabra-Rizk, Eric F.
Kong, Christina Tsui, M. Hong Nguyen, Cornelius J. Clancy, Paul L. Fidel, and Mairi Noverr,
“Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework,”
Infection and Immunity 84, no. 10 (2016): 2724–2739; Antonis Rokas, “Evolution of the Human
Pathogenic Lifestyle in Fungi,” Nature Microbiology 7, no. 5 (2022): 607–619.
16. Arturo Casadevall, “Determinants of Virulence in the Pathogenic Fungi,” Fungal Biology
Reviews 21, no. 4 (2007): 130–132; Cene Gostinčar, Janja Zajc, Metka Lenassi, Ana Plemenitaš,
Sybren de Hoog, Abdullah M. S. Al-Hatmi, and Nina Gunde-Cimerman, “Fungi between
Extremotolerance and Opportunistic Pathogenicity on Humans,” Fungal Diversity 93 (2018): 195–
213.
17. One of the fungi blackened with melanin that causes impromptu brain infections has another
complicated Latin name: this is Cladophialophora bantiana. To begin pronouncing Latin names of
species you should speak the syllables out loud, clay-doe-fi-al- and so on, slowly at first, then repeat
the chain faster and you will soon sound as seductive as a Roman bard. Cladophialophora is a soil
fungus with a global distribution that forms lovely velvety colonies when it is grown in a culture
dish. This fungus is especially worrying because it infects people with intact immune systems and
kills about 70 percent of its victims. Early symptoms of infection include headaches, seizure, arm
pain, and ataxia—or loss of muscle coordination. The fungus produces chains of spores that become
airborne, and so we assume that it gets into us through the lungs or nasal passages. We have no idea
why this ubiquitous fungus infects a tiny fraction of the people who must come in contact with its
spores all the time. Studies on the immune systems of patients suggest that they may have an
underlying vulnerability that would not be noticed if they had not been diagnosed with this fungus,
but that is all we know. Treatments are limited to the surgical removal of infected tissue and use of
powerful antifungal drugs, but the high mortality figures speak for themselves. This is a very
unpleasant fungus: Todd P. Levin, Darric E. Baty, Thomas Fekete, Allan L. Truant, and Byungse Suh,
“Cladophialophora bantiana Brain Abscess in a Solid-Organ Transplant Recipient: Case Report and
Review of the Literature,” Journal of Clinical Microbiology 42, no. 9 (2004): 4374–4378; Jon
Velasco and Sanjay Revankar, “CNS Infections Caused by Brown-Black Fungi,” Journal of Fungi 5,
no. 3 (2019): 60.
18. Patient-to-patient transmission of pneumocystis pneumonia seems to be an exception among
the mycoses (see chapter 3).
19. Emily Monosson, Blight: Fungi and the Coming Pandemic (New York: W. W. Norton, 2023).
20. Synnecrosis means dying together: José P. Veiga, “Commensalism, Amensalism, and
Synnecrosis,” in The Encyclopedia of Evolutionary Biology, vol. 1, ed. Richard M. Kliman (Oxford:
Academic Press, 2016), 322–328. All biology is a battle, bellum omnium contra omnes, as Hobbes
said. There is no generosity in nature, only nightmares in the making, as I say on rare occasions when
the charms of the fungi fail to sweeten my view of life.
21. Peter G. Pappas, “Cryptococcal Infections in Non-HIV-Infected Patients,” Transactions of the
American Clinical and Climatological Association 124 (2013): 61–79.
22. Judith N. Steenbergen, Howard Shuman, and Arturo Casadevall, “Cryptococcus neoformans
Interactions with Amoebae Suggest an Explanation for Its Virulence and Intracellular Pathogenic
Strategy in Macrophages,” Proceedings of the National Academy of Sciences USA 98, no. 26 (2001):
15245–15250; Rhys A. Watkins, Alexandre Andrews, Charlotte Wynn, Caroline Barisch, Jason S.
King, and Simon A. Johnston, “Cryptococcus neoformans Escape from Dictyostelium Amoeba by
Both WASH-Mediated Constitutive Exocytosis and Vomocytosis,” Frontiers in Cellular and
Infection Microbiology 8 (2018): 108.
 23. Liliana Scorzoni, Ana C. A. de Paula e Silva, Caroline M. Marcos, Patricia A. Assato, Wanessa
C. M. A. de Melo, Haroldo C. de Oliveira, Caroline B. Costa-Orlandi, et al., “Antifungal Therapy:
New Advances in the Understanding and Treatment of Mycosis,” Frontiers in Microbiology 8 (2017):
36.
24. “Fungal Disease: C. neoformans Infection,” CDC, accessed July 15, 2023,
https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/index.html; World Health
Organization, WHO Fungal Priority Pathogens List to Guide Research, Development and Public
Health Action (Geneva: World Health Organization, 2022); Abbygail C. Spencer, Katelyn R.
Brubaker, and Sylvie Garneau-Tsodikova, “Systemic Fungal Infections: A Pharmacist/Researcher
Perspective,” Fungal Biology Reviews 44 (2023): 100293. A relative of Cryptococcus neoformans
called Cryptococcus gattii also causes serious brain infections and is proficient at doing so in people
with perfectly healthy immune systems: Lamin Saidykhan, Chinaemerem U. Onyishi, and Robert C.
May, “The Cryptococcus gattii Species Complex: Unique Pathogenic Yeasts with Understudied
Virulence Mechanisms,” PLoS Neglected Tropical Diseases 16, no. 12 (2022): e0010916.
25. Dimitrios P. Kontoyiannis, Hongbo Yang, Jinlin Song, Sneha S. Kelkar, Xi Yang, Nkechi Azie,
Rachel Harrington, et al., “Prevalence, Clinical and Economic Burden of Mucormycosis-Related
Hospitalizations in the United States: A Retrospective Study,” BMC Infectious Diseases 16 (2016):
730.
26. Sylvia Slaughter, “Love Endures in the Face of Sorrow,” The Tennessean, January 12, 2003,
pp. 6–13.
27. Mahnoor Sukaina, “Re-Emergence of Mucormycosis in COVID-19 Recovered Patients
Transiting from Silent Threat to an Epidemic in India,” JoGHR 5 (2021): e2021067; Neil Stone,
Nitin Gypta, and Ilan Schwartz, “Mucormycosis: Time to Address This Deadly Fungal Infection,”
Lancet Microbe 2, no. 8 (2021): e343–e344.
28. Jana M. Ritter, Atis Muehlenbachs, Dianna M. Blau, Christopher D. Paddock, Wun-Ju Shieh,
Clifton P. Drew, Brigid C. Batten, et al., “Exserohilum Infections Associated with Contaminated
Steroid Injections: A Clinicopathologic Review of 40 Cases,” American Journal of Pathology 183,
no. 3 (2013): 881–892.
29. Diana Pisa, Ruth Alonso, Alberto Rábano, Izaskun Rodal, and Luis Carrasco, “Different Brain
Regions Are Infected with Fungi in Alzheimer’s Disease,” Scientific Reports 5 (2015): 15015; Ruth
Alonso, Diana Pisa, Ana M. Fernández-Fernández, and Luis Carrasco, “Infection of Fungi and
Bacteria in Brain Tissue from Elderly Persons and Patients with Alzheimer’s Disease,” Frontiers in
Aging Neuroscience 10 (2018): 159.
30. Bodo Parady, “Innate Immune and Fungal Model of Alzheimer’s Disease,” Journal of
Alzheimer’s Disease Reports 2, no. 1 (2018): 139–152; Yifan Wu, S. Du, J. L. Johnson, H.-Y. Tung,
C. T. Landers, Y. Liu, B. G. Seman, et al., “Microglia and Amyloid Precursor Protein Coordinate
Control of Transient Candida Cerebritis with Memory Deficits,” Nature Communications 10 (2019):
58.
31. Kelly Servick, doi:10.1126/science.aaw0147; R. C. Roberts, C. B. Farmer, and C. K. Walker,
“The Human Brain Microbiome: There Are Bacteria in Our Brains!,” paper presented at the
Neuroscience 2018 Conference, November 6,
https://www.abstractsonline.com/pp8/#!/4649/presentation/32057.
32. Ruth Alonso, Diana Pisa, Ana Fernández-Fernández, Alberto Rábano, and Luis Carrasco,
“Fungal Infection in Neural Tissue of Patients with Amyotrophic Lateral Sclerosis,” Neurobiology of
Disease 108 (2018): 249–260.
 33. Diana Pisa, Ruth Alonso, and Luis Carrasco, “Parkinson’s Disease: A Comprehensive Analysis
of Fungi and Bacteria in Brain Tissue,” International Journal of Biology Sciences 16, no. 7 (2020):
1135–1152.
34. Mary Duenwald, “Parkinson’s ‘Clusters’ Getting a Closer Look,” New York Times, May 14,
2002.
 CHAPTER FIVE
1. Yang Sun, Tao Zuo, Chun P. Cheung, Wenxi Gu, Yating Wan, Fen Zhang, Nan Chen, et al.,
“Population-Level Configurations of Gut Mycobiome across 6 Ethnicities in Urban and Rural
China,” Gastroenterology 160, no. 1 (2021): 272–286.
2. The Candida species in the Chinese study was Candida dubliniensis. This gut fungus,
discovered in Ireland in the 1990s, has a global distribution.
3. Emily A. Speakman, Ivy M. Dambuza, Fabián Salazar, and Gordon D. Brown, “T Cell
Antifungal Immunity and the Role of C-Type Lectin Receptors,” Trends in Immunology 41, no. 1
(2020): 61–76.
4. Lu Wu, Tiansheng Zeng, Massimo Deligios, Luciano Milanesi, Morgan G. I. Langille, Angelo
Zinellu, Salvatore Rubino, et al., “Age-Related Variation of Bacterial and Fungal Communities in
Different Body Habitats across the Young, Elderly, and Centenarians in Sardinia,” mSphere 5, no. 1
(2020): e00558-19.
5. Andrea K. Nash, Thomas A. Auchtung, Matthew C. Wong, Daniel P. Smith, Jonathan R. Gesell,
Matthew C. Ross, Christopher J. Stewart, et al., “The Gut Mycobiome of the Human Microbiome
Project Healthy Cohort,” Microbiome 5, no. 1 (2017): 153.
6. Mubanga H. Kabwe, Surendra Vikram, Khodani Mulaudzi, Janet K. Jansson, and Thulani P.
Makhalanyane, “The Gut Mycobiota of Rural and Urban Individuals Is Shaped by Geography,” BMC
Microbiology 20, no. 1 (2020): 257.
7. Eric van Tilburg Bernardes, Veronika K. Pettersen, Mackensie W. Gutierrez, Isabelle Laforest-
Lapointe, Nicholas G. Jendzjowsky, Jean-Baptiste Cavin, Fernando A. Vicentini, et al., “Intestinal
Fungi Are Causally Implicated in Microbiome Assembly and Immune Development in Mice,” Nature
Communications 11, no. 1 (2020): 2577; Tahliyah S. Mims, Qusai A. Abdallah, Justin D. Stewart,
Sydney P. Watts, Catrina T. White, Thomas V. Rousselle, Ankush Gosain, et al., “The Gut
Mycobiome of Healthy Mice Is Shaped by the Environment and Correlates with Metabolic Outcomes
in Response to Diet,” Communications Biology 4, no. 1 (2021): 281.
8. Katherine D. Mueller, Hao Zhang, Christian R. Serrano, R. Blake Billmyre, Eun Y. Huh,
Philipp Wiemann, Nancy P. Keller, et al., “Gastrointestinal Microbiota Alteration Induced by Mucor
circinelloides in a Murine Model,” Journal of Microbiology 57, no. 6 (2019): 509–520.
9. M. Mar Rodríguez, Daniel Pérez, Felipe J. Chaves, Eduardo Esteve, Pablo Marin-Garcia,
Gemma Xifra, Joan Vendrell, et al., “Obesity Changes the Human Gut Mycobiome,” Scientific
Reports 5 (2015): 14600.
10. William D. Fiers, Iris H. Gao, and Iliyan D. Iliev, “Gut Mycobiota Under Scrutiny: Fungal
Symbionts or Environmental Transients?,” Current Opinion in Microbiology 50 (2019): 79–86.
11. Mario Matijašić, Tomislav Meštrović, Hana Čipčić Paljetak, Mihaela Perić, Anja Barešić, and
Donatella Verbanac, “Gut Microbiota beyond Bacteria—Mycobiome, Virome, Archaeome, and
Eukaryotic Parasites in IBD,” International Journal of Molecular Sciences 21 (2020): 2668; Umang
Jain, Aaron M. Ver Heul, Shanshan Xiong, Martin H. Gregory, Elora G. Demers, Justin T. Kern,
Chin-Wen Lai, et al., “Debaryomyces Is Enriched in Crohn’s Disease Intestinal Tissue and Impairs
Healing in Mice,” Science 371 (2021): 1154–1159. There has been a lot of interest in a putative link
between antibodies called ASCAs produced in response to proteins in the cell wall of baker’s yeast,
Saccharomyces cerevisiae, and the development of Crohn’s disease: Heba N. Iskandar and Matthew
A. Ciorba, “Biomarkers in Inflammatory Bowel Disease: Current Practices and Recent Advances,”
Translational Research 159, no. 4 (2012): 313–325. Some research shows that although these
antibodies play a role in gut inflammation they are not correlated with the consumption of the dietary
yeast in baked foods and beer: Anne S. Kvehaugen, Martin Aasbrenn, and Per G. Farup, “Anti-
Saccharomyces cerevisiae Antibodies (ASCA) Are Associated with Body Fat Mass and Systemic
Inflammation, But Not with Dietary Yeast Consumption: A Cross-Sectional Study,” BMC Obesity 4
(2017): 28.
12. Irina Leonardi, Sudarshan Paramsothy, Itai Doron, Alexa Semon, Nadeem O. Kaakoush, Jose
C. Clemente, Jeremiah J. Faith, et al., “Fungal Trans-Kingdom Dynamics Linked to Responsiveness
to Fecal Microbiota Transplantation (FMT) Therapy in Ulcerative Colitis,” Cell Host and Microbe
27, no. 5 (2020): 823–829.
13. Arthur C. Macedo, André O. V. de Faria, and Pietro Ghezzi, “Boosting the Immune System,
from Science to Myth: Analysis [of] the Infosphere with Google,” Frontiers in Medicine 6 (2019):
165.
14. Yao Zuo, Hui Zhan, Fen Zhang, Qin Liu, Eugene Y. K. Tso, Grace C. Y. Lui, Nan Chen, et al.,
“Alterations in Fecal Fungal Microbiome of Patients with COVID-19 during Time of Hospitalization
until Discharge,” Gastroenterology 159, no. 4 (2020): 1302–1310.
15. Bing Zhai, Mihaela Ola, Thierry Rolling, Nicholas L. Tosini, Sar Joshowitz, Eric R. Littmann,
Luigi A. Amoretti, et al., “High-Resolution Mycobiota Analysis Reveals Dynamic Intestinal
Translocation Preceding Invasive Candidiasis,” Nature Medicine 26 (2020): 59–64; Bastian
Seelbinder, Jiarui Chen, Sasha Brunke, Ruben Vazquez-Uribe, Rakesh Santhaman, Anne-Christin
Meyer, Felipe Senne de Oliveira Lino, et al., “Antibiotics Create a Shift from Mutualism to
Competition in Human Gut Communities with a Longer-Lasting Impact on Fungi Than Bacteria,”
Microbiome 8 (2020): 133.
16. Sara Botschuijver, Guus Roeselers, Evgeni Levin, Daisy M. Jonkers, Olaf Welting, Sigrid E.
M. Heinsbroek, Heleen H. de Weerd, et al., “Intestinal Fungal Dysbiosis Is Associated with Visceral
Hypersensitivity in Patients with Irritable Bowel Syndrome and Rats,” Gastroenterology 153, no. 4
(2017): 1026–1039.
17. Natalia Vallianou, Dimitris Kounatidis, Gerasimos Socrates Christodoulatos [such a great
name that I had to waive the citation style of middle name initial only], Fotis Panagopoulos, Irene
Karampela, and Maria Dalamaga, “Mycobiome and Cancer: What Is the Evidence?,” Cancers 13
(2021): 3149.
18. Berk Aykut, Smruit Pushalkar, Ruonan Chen, Qianhao Li, Raquel Abengozar, Jacqueline I.
Kim, Sorin A. Shadaloey, et al., “The Fungal Mycobiome Promotes Pancreatic Oncogenesis via
Activation of MBL,” Nature 574 (2019): 264–267; Jessica R. Galloway-Peña and Dimitrios P.
Kontoyiannis, “The Gut Mycobiome: The Overlooked Constituent of Clinical Outcomes and
Treatment Complications in Patients with Cancer and Other Immunosuppressive Conditions,” PLoS
Pathogens 16, no. 4 (2020): e1008353; Lian Narunsky-Haziza, Gregory D. Sepich-Poore, Ilana
Livyatan, Omer Asraf, Cameron Martino, Deborah Nejman, Nancy Gavert, et al., “Pan-Cancer
Analyses Reveal Cancer-Type-Specific Fungal Ecologies and Bacteriome Interactions,” Cell 185, no.
20 (2022): 3789–3806; Anders B. Dohlman, Jared Klug, Marissa Mesko, Iris H. Gao, Steven M.
Lipkin, Xiling Shen, and Iliyan D. Iliev, “A Pan-Cancer Mycobiome Analysis Reveals Fungal
Involvement in Gastrointestinal and Lung Tumors,” Cell 185, no. 20 (2022): 3807–3822.
19. Nicholas P. Money, “Hyphal and Mycelial Consciousness: The Concept of the Fungal Mind,”
Fungal Biology 125 (2021): 257–259.
20. Ecologists use the term ecotype to describe a population of a species of plant or animal that is
adapted to a local environment. An ecotype is a variant within a species. Mycotype is used in a
different way to describe a community of fungi that is identified by the presence of single species of
fungus. Enterotype is another term used to distinguish between different versions of the gut
microbiome based on their bacterial composition.
21. B. P. Krom, S. Kidwai, and J. M. Ten Cate, “Candida and Other Fungal Species: Forgotten
Players of Healthy Oral Microbiota,” Journal of Dental Research 93, no. 5 (2014): 445–451; B. Y.
Hong, A. Hoare, A. Cardenas, A. K. Dupuy, L. Choquette, A. L. Salner, P. K. Schauer, et al., “The
Salivary Mycobiome Contains 2 Ecologically Distinct Mycotypes,” Journal of Dental Research 99,
no. 6 (2020): 730–738.
22. M. N. Zakaria, M. Furuta, T. Takeshita, Y. Shibata, R. Sundari, N. Eshima, T. Ninomiya, et al.,
“Oral Mycobiome in Community-Dwelling Elderly and Its Relation to Oral and General Health
Conditions,” Oral Diseases 23, no. 7 (2017): 973–982; Eefje A. Kraneveld, Mark J. Buijs, Marc J.
Bonder, Marjolein Visser, Bart J. F. Keijser, Wim Crielaard, and Egija Zaura, “The Relation between
Oral Candida Load and Bacterial Microbiome Profiles in Dutch Older Adults,” PLoS ONE 7, no. 8
(2012): e42770. Changes in the oral mycobiome associated with dentures were superimposed on a
huge disparity between the baseline levels of Candida in the two populations: the saliva of the
Japanese patients contained an average of ten thousand Candida cells per milliliter, compared with
up to one hundred million yeast cells in the same volume of spit from the Dutch patients. It is
possible that this discrepancy was due to the use of different DNA primers in these studies.
23. David W. Denning, Matthew Kneale, Jack D. Sobel, and Riina Rautemaa-Richardson, “Global
Burden of Recurrent Vulvovaginal Candidiasis: A Systematic Review,” Lancet Infectious Diseases
18, no. 11 (2018): e339–e347; Brett A. Tortelli, Warren G. Lewis, Jennifer E. Allsworth, Nadum
Member-Meneh, Lynne R. Foster, Hilary E. Reno, Jeffrey F. Peipert, et al., “Associations between
the Vaginal Microbiome and Candida Colonization in Women of Reproductive Age,” American
Journal of Obstetrics and Gynecology 222, no. 5 (2020): 471.e1–e9.
24. Ning-Ning Liu, Xingping Zhao, Jing-Cong Tan, Sheng Liu, Bo-Wen Li, Wang-Xing Xu, Lin
Peng, et al., “Mycobiome Dysbiosis in Women with Intrauterine Adhesions,” Microbiology Spectrum
10, no. 4 (2022): e0132422.
25. Erik van Tilburg Bernardes, Mackenzie W. Gutierrez, and Marie-Claire Arrieta, “The Fungal
Microbiome and Asthma,” Frontiers in Cellular and Infection Microbiology 10 (2020): 583418.
26. Raphaël Enaud, Renaud Prevel, Eleonora Ciarlo, Fabien Beaufils, Gregoire Wieërs, Benoit
Guery, and Laurence Delhaes, “The Gut-Lung Axis in Health and Respiratory Diseases: A Place for
Inter-Organ and Inter-Kingdom Crosstalks,” Frontiers in Cellular and Infection Microbiology 10
(2020): 9.
27. Tomasz Gosiewski, Dominika Salamon, Magdalena Szopa, Agnieska Sroka, Maciej T.
Malecki, and Malgorzata Bulanda, “Quantitative Evaluation of Fungi of the Genus Candida in the
Feces of Adult Patients with Type 1 and 2 Diabetes—A Pilot Study,” Gut Pathogens 6 (2014): 43; A.
M. Yang, T. Inamine, K. Hochrath, P. Chen, L. Wang, C. Llorente, S. Bluemel, et al., “Intestinal
Fungi Contribute to Development of Alcoholic Liver Disease,” Journal of Clinical Investigations
127, no. 7 (2017): 2829–2841; Lu Jiang, Peter Stärkel, Jian-Gao Fan, Derrick E. Fouts, Petra Bacher,
and Bernd Schnabl, “The Gut Mycobiome: A Novel Player in Chronic Liver Diseases,” Journal of
Gastroenterology 56, no. 1 (2021): 1–11.
28. Jessica D. Forbes, Charles N. Bernstein, Helen Tremlett, Gary Van Domselaar, and Natlaie C.
Knox, “A Fungal World: Could the Gut Mycobiome Be Involved in Neurological Disease?,”
Frontiers in Microbiology 9 (2019): 3249; Saumya Shah, Albertu Locca, Yair Dorsett, Claudia
Cantoni, Laura Ghezzi, Qingqi Lin, Suresh Bokoliya, et al., “Alterations of the Gut Mycobiome in
Patients with MS,” EBioMedicine 71, no. 1 (2021): 103557.
 29. Mahmoud Ghannoum with Eve Adamson, Total Gut Balance: Fix Your Mycobiome Fast for
Complete Digestive Wellness (Woodstock, VT: Countryman Press, 2019).
30. M. Ghannoum, C. Smith, E. Adamson, N. Isham, I. Salem, and M. Retuerto, “Effect of
Mycobiome Diet on Gut Fungal and Bacterial Communities of Healthy Adults,” Journal of
Probiotics and Health 8, no. 1 (2020): 215.
31. Kearney T. W. Gunsalus, Stephanie N. Tornberg-Belanger, Nirupa R. Matthan, Alice H.
Lichtenstein, and Carol A. Kumamoto, “Manipulation of Host Diet to Reduce Gastrointestinal
Colonization by the Opportunistic Pathogen Candida albicans,” mSphere 1, no. 1 (2015): e00020-15.
 CHAPTER SIX
1. The genus Penicillium was named by Heinrich Friedrich Link in 1809, who described the spore
stalks or conidiophores produced from the mycelium as fertilibus erectis apice penicillatis, meaning
raised fertile [branches] with brush-like tips: Heinrich F. Link, “Observationes in Ordines Plantarum
Naturales: Dissertatio Ima,” Gesellschaft Naturforschender Freunde zu Berlin Magazin 3, no. 1
(1809): 3–42.
2. Pencillium evolved in the Cretaceous. This is the timing that we infer from the DNA clocks in
multiple species of Penicillium that appear to have been ticking for more than seventy million years:
Jacob L. Steenwyk, Xing-Xing Shen, Abigail L. Lind, Gustavo H. Goldman, and Antonis Rokas, “A
Robust Phylogenomic Time Tree for Biotechnologically and Medically Important Fungi in the
Genera Aspergillus and Penicillium,” mBio 10 (2019): e00925-19.
3. Frank Maixner, Mohamed S. Sarhan, Kun D. Huang, Adrian Tett, Alexander Schoenafinger,
Stefania Zingale, Aitor Blanco-Míguez, et al., “Hallstatt Miners Consumed Blue Cheese and Beer
During the Iron Age and Retained a Non-Westernized Gut Microbiome until the Baroque Period,”
Current Biology 31, no. 23 (2021): 5149–5162.
4. Nathaniel J. Dominy, “Ferment in the Family Tree,” Proceedings of the National Academy of
Sciences USA 112, no. 2 (2015): 308–309; Nicholas P. Money, The Rise of Yeast: How the Sugar
Fungus Shaped Civilization (Oxford: Oxford University Press, 2018).
5. Jiajing Wang, Leping Jiang, and Hanlong Sun, “Early Evidence for Beer Drinking in a 9000-
Year-Old Platform Mound in Southern China,” PLoS ONE 16, no. 8 (2021): e0255833. Jiajing Wang
and colleagues identified microfossils of filamentous fungi and yeast in the pottery remains.
Filamentous fungi are used as starters in rice wine fermentation to break down starch into sugars, and
yeast feeds on the sugars, producing alcohol. Incidentally, rice wine is really rice beer because it is
made from grains that contain starch that is converted into sugars in the first step of the fermentation,
called saccharification. Wines are made from grape must and other fruit juices, which are full of
sugars so that yeast can get to work without this saccharification step.
6. Laure Segurel, Perle Guarino-Vignon, Nina Marchi, Sophie Lafosse, Romain Laurent, Céline
Bon, Alexandre Fabre, et al., “Why and When Was Lactase Persistence Selected For? Insights from
Central Asian Herders and Ancient DNA,” PLoS Biology 18, no. 6 (2020): e3000742; William T. T.
Taylor, Julia Clark, Jamranjav Bayarsaikhan, Tumurbaatar Tuvshinjargal, Jessica T. Jobe, William
Fitzhugh, Richard Kortum, et al., “Early Pastoral Economies and Herding Transitions in Eastern
Eurasia,” Scientific Reports 10 (2020): 1001; Mélanie Salque, Peter I. Bogucki, Joanna Pyzel, Iwona
Sobkowiak-Tabaka, Ryszard Grygiel, Marzena Szmyt, and Richard P. Evershed, “Earliest Evidence
for Cheese Making in the Sixth Millennium BC in Northern Europe,” Nature 493 (2013): 522–525.
7. Pliny, Natural History, trans. Harris Rackham, Loeb Classical Library 353 (Cambridge, MA:
Harvard University Press, 1942), Book XI, XCVII, 582–585, lines 240–242; Petronius, Satyricon,
trans. Michael Heseltine, rev. Eric H. Warmington, Loeb Classical Library 15 (Cambridge, MA:
Harvard University Press, 1987), 148–149, line 66. The cheese description in the Satyricon comes
from Habinnas, a guest at the feast of Trimalchio, who is asked about an earlier dinner.
8. Emilie Dumas, Alice Feurtey, Ricardo C. Rodríguez de la Vega, Stéphanie Le Prieur, Alodie
Snirc, Monika Coton, Anne Thierry, et al., “Independent Domestication Events in the Blue-Cheese
Fungus Penicillium roqueforti,” Molecular Ecology 29 (2020): 2639–2660.
9. Jeanne Ropars, Estelle Didiot, Ricardo C. Rodríguez de la Vega, Bastien Bennetot, Monika
Coton, Elisabeth Poirier, Emmanuel Coton, et al., “Domestication of the Emblematic White Cheese-
Making Fungus Penicillium camemberti and Its Diversification into Two Varieties,” Current Biology
30, no. 22 (2020): 4441–4453, e1–e4.
10. Marie-Christine Montel, Solange Buchin, Adrien Mallet, Céline Delbes-Paus, Dominique A.
Vuitton, Nathalie Desmasures, and François Berthier, “Traditional Cheeses: Rich and Diverse
Microbiota with Associated Benefits,” International Journal of Food Microbiology 177 (2014): 136–
154.
11. Eric Dugat-Bony, Lucille Garnier, Jeremie Denonfoux, Stéphanie Ferreira, Anne-Sophie
Sarthou, Pascal Bonnarme, and Françoise Irlinger, “Highlighting the Microbial Diversity of 12
French Cheese Varieties,” International Journal of Food Microbiology 238 (2016): 265–273.
12. Yuanchen Zhang, Erik K. Kastman, Jeffrey S. Guasto, and Benjamin E. Wolfe, “Fungal
Networks Shape Dynamics of Bacterial Dispersal and Community Assembly in Cheese Rind
Microbiomes,” Nature Communications 9 (2018): 336.
13. Clifton Fadiman, Any Number Can Play (Cleveland, OH: World Publishing, 1957), 105. In the
same book (106), Fadiman described Roquefort as “Ewe-born, cave-educated, [and] perfected by
moldy bread.”
14. Montel et al., “Traditional Cheeses.” Raw milk is enriched in vitamins that are lost in
pasteurization, contains a healthier mixture of fats than processed milk (according to some
nutritionists), and may even confer some protection against the development of asthma and other
allergies in children.
15. Thibault Caron, Mélanie Le Piver, Anne-Claire Péron, Pascale Lieben, René Lavigne, Sammy
Brunel, Daniel Roueyre, et al., “Strong Effect of Penicillium roqueforti Populations on Volatile and
Metabolic Compounds Responsible for Aromas, Flavor and Texture in Blue Cheeses,” International
Journal of Food Microbiology 354 (2021): 109174.
16. B. G. J. Knols and R. De Jong, “Limburger Cheese as an Attractant for the Malaria Mosquito
Anopheles gambiae s.s.,” Parasitology Today 12, no. 54 (1996): 159–161.
17. Monika Coton, Franck Deniel, Jérôme Mounier, Rozenn Joubrel, Emeline Robieu, Audrey
Pawtowski, Sabine Jeuge, et al., “Microbial Ecology of French Dry Fermented Sausages and
Mycotoxin Risk Evaluation during Storage,” Frontiers in Microbiology 12 (2021): 737140. Concerns
have been raised about the possibility of mycotoxin contamination of cheeses, but there have been no
proven cases of poisoning associated with cheese consumption: Alan D. W. Dobson, “Mycotoxins in
Cheese,” in Cheese: Chemistry, Physics and Microbiology, 4th ed., ed. Paul L. H. McSweeney,
Patrick F. Fox, Paul D. Cotter, and David W. Everett (London: Academic Press, 2017), 595–601.
18. Giancarlo Perrone, Robert A. Samson, Jens C. Frisvad, Antonia Susca, Nina Gunde-
Cimerman, Filomena Epifani, and Jos Houbraken, “Penicillium salamii, A New Species Occurring
during Seasoning of Dry-Cured Meat,” International Journal of Food Microbiology 193 (2015): 91–
98.
19. Andrea Osimani, Ilario Ferrocino, Monica Agnolucci, Luca Cocolin, Manuela Giovannetti,
Caterina Cristani, Michela Palla, et al., “Unveiling Hákarl: A Study of the Microbiota of the
Traditional Icelandic Fermented Fish,” Food Microbiology 82 (2019): 560–572. Most of the sharks
are killed as bycatch, and their great age adds to this tragedy: Greenland sharks are the longest-lived
vertebrates, with a maximum estimated life span approaching four hundred years.
20. There are frequent comparisons between the smell of surströmming and open sewers on the
internet. This delicacy is one of the exhibits that can be tasted at the Disgusting Food Museum in
Malmö (https://disgustingfoodmuseum.com/). Fermented fish dishes from Asia are described in the
following review article: Yutika Narzary, Sandeep Nas, Arvind K. Goyal, Su S. Lam, Hermen Sarma,
and Dolikajyoti Sharma, “Fermented Fish Products in South and Southeast Asian Cuisine:
Indigenous Technology Processes, Nutrient Composition, and Cultural Significance,” Journal of
Ethnic Foods 8 (2021): 33.
21. David Downie, “A Roman Anchovy’s Tale,” Gastronomica 3 (2003): 25–28; Brian Keogh,
The Secret Sauce: A History of Lea & Perrins (Worcester, UK: Leaper Books, 1997).
22. Kotaro Ito and Asahi Matsuyama, “Koji Molds for Japanese Soy Sauce Brewing:
Characteristics and Key Enzymes,” Journal of Fungi 7 (2021): 658.
23. M. J. Robert Nout and Kofi E. Aidoo, “Asian Fungal Fermented Food,” in The Mycota, vol.
10, Industrial Applications, ed. Martin Hofrichter (Berlin: Springer, 2010), 29–58.
24. Climate may help to explain why the Mucor infections of humans described in chapter 4 are
more common in India and other parts of Asia than Europe.
25. Money, The Rise of Yeast, 52.
26. Jack A. Whittaker, Robert I. Johnson, Tim J. A. Finnigan, Simon V. Avery, and Paul S. Dyer,
“The Biotechnology of Quorn Mycoprotein: Past, Present and Future Challenges,” in Grand
Challenges in Fungal Biotechnology, ed. Helena Nevalainen (Cham, Switzerland: Springer
International Publishing, 2020), 59–79.
27. Pedro F. Souza Filho, Dan Andersson, Jorge A. Ferreira, and Mohammad J. Taherzadeh,
“Mycoprotein: Environmental Impact and Health Aspects,” World Journal of Microbiology and
Biotechnology 35, no. 10 (2019): 147; Maurizio Cellura, Maria A. Cusenza, Sonia Longo, Le Q. Luu,
and Thomas Skurk, “Life Cycle Environmental Impacts and Health Effects of Protein-Rich Food as
Meat Alternatives: A Review,” Sustainability 14 (2022): 979; Florian Humpenöder, Benjamin L.
Bodirsky, Isabelle Weindl, Hermann Lotze-Campen, Tomas Linder, and Alexander Popp, “Projected
Environmental Benefits of Replacing Beef with Microbial Protein,” Nature 605, no. 7908 (2022):
90–96.
28. Robert King, Neil A. Brown, Martin Urban, and Kim E. Hammond-Kosack, “Inter-Genome
Comparison of the Quorn Fungus Fusarium venenatum and the Closely Related Plant Infecting
Pathogen Fusarium graminearum,” BMC Genomics 19 (2018): 269.
29. The market for fungal products is dominated by yeast. See Nicholas P. Money, “The Fungus
That’s Worth $900 Billion a Year,” OUPblog, February 25, 2018,
https://blog.oup.com/2018/02/fungus-worth-900-billion/.
30. The energy value of gilled mushrooms varies from 22 to 31 calories per 100 grams for raw
white button mushrooms to 44 calories per 100 grams of shiitake; 100 grams of romaine lettuce
contains 20 calories. Measurements of the calorific value of truffles vary between studies and for
different truffle species, but the high energy value of these fungi relative to gilled mushrooms is
consistent. A study from China, for example, measured 378 calories per 100 grams of three species of
Tuber from Yunnan, which matches the calorific value of Roquefort cheese. See U.S. Department of
Agriculture, “Mushrooms, White, Raw,” April 1, 2019, https://fdc.nal.usda.gov/fdc-app.html#/food-
details/169251/nutrients; Xiangyuan Yan, Yanwei Wang, Xiaoyu Sang, and Li Fan, “Nutritional
Value, Chemical Composition and Antioxidant Activity of Three Tuber Species from China,” AMB
Express 7, no. 1 (2017): 136.
 CHAPTER SEVEN
1. U. Peintner, R. Pöder, and T. Pümpel, “The Iceman’s Fungi,” Mycological Research 102, no. 10
(1998): 1153–1162.
2. Luigi Capasso, “5300 Years Ago, the Ice Man Used Natural Laxatives and Antibiotics,” The
Lancet 352, no. 9143 (1998): 1864. Capasso’s work was refuted by Håkan Tunón and Ingvar
Svanberg, “Laxatives and the Ice Man,” The Lancet 353, no. 9156 (1999): 925–926, who wrote,
“Ethnobotanical data from preindustrial Northern Europe show that the fungus has had several non-
medical uses, such as to protect metal blades from rust, to sharpen razors, as toys, floats or
pincushions. So it is odd that Capasso concludes that the fungi kept by the Ice Man were used to treat
a worm infection and not for any other purpose.… We find it astonishing that Capasso draws so
many conclusions from such a limited amount of data.”
3. Powerful drugs, including ivermectin, which was made famous during the COVID-19
pandemic, paralyze and kill the worms, and modern sanitation allows us to avoid the worms in the
first place. Insouciant attitudes toward intestinal parasites are among the unearned privileges of
today’s affluence that must be judged naive against the global burden of billions of active infections
by hookworms, roundworms, and Ötzi’s whipworm: Rachel L. Pullan, Jennifer L. Smith, Rashmi
Jasrasaria, and Simon J. Brooker, “Global Numbers of Infection and Disease Burden of Soil
Transmitted Helminth Infections in 2010,” Parasites Vectors 7 (2014): 37.
4. Ulrike Grienke, Margit Zöll, Ursula Peintner, and Judith M. Rollinger, “European Medicinal
Polypores—A Modern View on Traditional Uses,” Journal of Ethnopharmacology 154, no. 3 (2014):
564–583.
5. Robert A. Blanchette, “Haploporus odorus: A Sacred Fungus in Traditional Native American
Culture of the Northern Plains,” Mycologia 89, no. 2 (1997): 233–240.
6. Investors view the medicinal mushroom industry as fragmented, meaning that hundreds of
companies share the market in different countries. Decentralization can be good for consumers and
provides plenty of opportunities for small-scale entrepreneurs to develop new product lines. This
contrasts with the market for prescription and over-the-counter drugs, which is controlled by a few
very powerful pharmaceutical companies. See “Global Mushroom Market (2020 to 2025)—Global
Industry Trends, Share, Size, Growth, Opportunity and Forecast—ResearchAndMarkets.com,”
Business Wire, July 1, 2020, https://www.businesswire.com/news/home/20200701005442/en/Global-
Mushroom-Market-2020-to-2025--Global-Industry-Trends-Share-Size-Growth-Opportunity-and-
Forecast--ResearchAndMarkets.com; Allana Akhtar, “5 ‘Functional’ Mushrooms the Wellness
Industry Is Obsessed with, from Lion’s Mane to Turkey Tail,” YahooMoney, April 7, 2022,
https://money.yahoo.com/5-functional-mushrooms-wellness-industry-135455865.html.
7. Cordyceps is an ascomycete, more closely related to yeast than gilled mushrooms, and chaga is
a mass of fungal tissues that does not produce any spores.
8. “Health Benefits of Mushrooms,” WebMD, September 12, 2022,
https://www.webmd.com/diet/health-benefits-mushrooms; “What Is the Nutritional Value of
Mushroom Powder?,” Om (blog), May 11, 2021, https://ommushrooms.com/blogs/blog/nutritional-
value-of-mushroom-powder-m2.
9. Koichiro Mori, Yutaro Obara, Mitsuru Hirota, Yoshihito Azumi, Satomi Kinugasa, Satoshi
Inatomi, and Norimichi Nakahata, “Nerve Growth Factor-Inducing Activity of Hericium erinaceus in
1321N1 Human Astrocytoma Cells,” Biological and Pharmaceutical Bulletin 31, no. 9 (2008): 1727–
1732; Mari Shimbo, Hirokazu Kawagishi, and Hidehiko Yokogoshi, “Erinacine A Increases
Catecholamine and Nerve Growth Factor Content in the Central Nervous System of Rats,” Nutrition
Research 25, no. 6 (2005): 617–623. Although these are brief reports, they are the best publications
on the effects of lion’s mane on cultured nerve cells and rat brains. Most of the published studies on
Hericium would never pass peer review in reliable scientific journals. One detailed analysis of the
fungus looked promising: Hsing-Chun Kuo, Chien-Chien Lu, Chien-Heng Shen, Shui-Yi Tung,
Meng Chiao Hsieh, Ko-Chao Lee, Li-Ya Li, et al., “Hericium erinaceus Mycelium and Its Isolated
Erinacine A Protection from MPTP-Induced Neurotoxicity through the ER Stress, Triggering an
Apoptosis Cascade,” Journal of Translational Medicine 19 (2021): 67. I used the past tense, looked,
because the study was retracted when the editors of the journal learned that the research was
associated with a Taiwanese company called Grape King Bio, Ltd., which produces extracts from the
mushroom.
10. Koichiro Mori, Satoshi Inatomi, Kenzi Ouchi, Yoshihito Azumi, and Takasi Tuchida,
“Improving Effects of the Mushroom Yamabushitake (Hericium erinaceus) on Mild Cognitive
Impairment: A Double-Blind Placebo-Controlled Clinical Trial,” Phytotherapy Research 23, no. 3
(2009): 367–372.
11. Tero Isokauppila, Healing Mushrooms: A Practical and Culinary Guide to Using Mushrooms
for Whole Body Health (New York: Avery, 2017).
12. “Lion’s Mane Capsules,” FungiPerfecti, accessed July 15, 2023,
https://fungi.com/products/lions-mane-capsules.
13. “Top 5 Lions Mane Health Benefits for Managing Erectile Dysfunction Effectively,” Cure My
Erectile Dysfunction, accessed July 15, 2023, https://curemyerectiledysfunction.com/top-5-lions-
mane-health-benefits-for-managing-erectile-dysfunction-effectively; “Lion’s Mane Can Reduce Your
Libido/Sex-Drive,” Boost Your Biology (blog), August 17, 2020,
https://www.ergogenic.health/blog/lions-mane-can-decrease-your-libido-sex-drive.
14. Hidde P. van Steenwijk, Aalt Bast, and Alie de Boer, “Immunomodulating Effects of Fungal
Beta-Glucans: From Traditional Use to Medicine,” Nutrients 13 (2021): 1333.
15. Kurt Buchmann, “Evolution of Innate Immunity: Clues from Invertebrates via Fish to
Mammals,” Frontiers in Immunology 5 (2014): 459.
16. Kenji Ina, Takae Kataoka, and Takafumi Ando, “The Use of Lentinan for Treating Gastric
Cancer,” Anti-cancer Agents in Medicinal Chemistry 13, no. 5 (2013): 681–688.
17. Yiran Zhang, Meng Zhang, Yifei Jiang, Xiulian Li, Yanli He, Pengjiao Zeng, Zhihua Guo, et
al., “Lentinan as an Immunotherapeutic for Treating Lung Cancer: A Review of 12 Years Clinical
Studies in China,” Journal of Cancer Research and Clinical Oncology 144 (2018): 2177–2186.
18. “Medical Health Benefits of Beta-Glucans in Medicinal Mushrooms,” WENY News, July 20,
2021, https://www.weny.com/story/44338597/medical-health-benefits-of-beta-glucans-in-medicinal-
mushrooms; Christopher Hertzog, Beta Glucan: A 21st Century Miracle? (Bangkok: Booksmango,
2014).
19. Djibril M. Ba, Xiang Gao, Joshua Muscat, Laila Al-Shaar, Vernon Chinchilli, Xinyuan Zhang,
Paddy Ssentongo, et al., “Association of Mushroom Consumption with All-Cause and Cause-Specific
Mortality among American Adults: Prospective Cohort Study Findings from NHANES III,” Nutrition
Journal 20, no. 1 (2021): 38.
20. Djibril M. Ba, Xiang Gao, Laila Al-Shaar, Joshua E. Muscat, Vernon M. Chinchilli, Robert B.
Beelman, and John P. Richie, “Mushroom Intake and Depression: A Population-Based Study Using
Data from the US National Health and Nutrition Examination Survey (NHANES), 2005–2016,”
Journal of Affective Disorders 294 (2021): 686–692; Djibril M. Ba, Paddy Ssentongo, Robert B.
Beelman, Joshua Muscat, Xiang Gao, and John P. Richie, “Higher Mushroom Consumption Is
Associated with Lower Risk of Cancer: A Systematic Review and Meta-Analysis of Observational
Studies,” Advances in Nutrition 12, no. 5 (2021): 1691–1704.
21. Piotr Rzymski, “Comment on ‘Mushroom Intake and Depression: A Population-Based Study
Using Data from the US National Health and Nutrition Examination Survey (NHANES), 2005–
2016,’ ” Journal of Affective Disorders 295 (2021): 937–938.
22. Chayakrit Krittanawong, Ameesh Isath, Joshua Hahn, Zhen Wang, Sonya E. Fogg,
Dhrubajyoti Bandyopadhyay, Hani Jneid, et al., “Mushroom Consumption and Cardiovascular
Health: A Systematic Review,” American Journal of Medicine 134, no. 5 (2021): 637–642.e2.
23. Nicholas P. Money, “Are Mushrooms Medicinal?,” Fungal Biology 120, no. 4 (2016): 449–
453.
24. Christopher Hitchens, God Is Not Great: How Religion Poisons Everything (New York:
Twelve, 2009), 150.
25. In addition to the web pages referring to the curative powers of the mushroom, many of the
“shiitake acne” and “shiitake asthma” sites describe severe skin allergies in some people who
consume the raw mushroom and in workers in the mushroom industry who handle the fruit bodies
during packaging.
26. John Gerard, The Herball, or, Generall Historie of Plantes, 2nd ed., enlarged and amended by
Thomas Johnson (London: Adam Islip, Joice Norton, and R. Whitakers, 1633), 1578, 1583; Horace,
Satires, Epistles, and Ars Poetica, trans. H. Rushton Fairclough, Loeb Classical Library 194
(Cambridge, MA: Harvard University Press, 1929), Satires Book II, IV, 188–189, lines 20–21.
27. The study of medicinal mushrooms is lost in a madhouse of misrepresentation and
pseudoscience that includes crackpot cures for terminal illnesses. For light relief, I nominate Robert
Rogers, registered herbalist and author of Mushroom Essences: Vibrational Healing from the
Kingdom Fungi (Berkeley, CA: North Atlantic Books, 2016), for The Batshit Crazy Award in
Mycology. Rogers claims that mushrooms “express energy fields,” which can be channeled by skilled
practitioners to “help peel away the steel bars of long-held emotional and mental imprisonment.”
There are many contenders for the award, but a sentence from the blurb of the book by Roger should
satisfy the judges: “Similar to flower essences, but made under a lunar cycle, mushroom essences
work subtly to bring deep healing to the mind and body; they are particularly well suited for working
with the ‘shadow’ or unintegrated parts of the psyche.” Ötzi would have slapped Robert with his
birch conks.
28. Won C. Bak, Ji H. Park, Yong A. Park, and Kang H. Ka, “Determination of Glucan Contents in
the Fruiting Bodies and Mycelia of Lentinula edodes Cultivars,” Mycobiology 42, no. 3 (2014): 301–
304; Juan Chen, Xu Zeng, Yan L. Yang, Yong M. Xing, Qi Zhang, Jia Li, Ke Ma, et al., “Genomic
and Transcriptomic Analyses Reveal Differential Regulation of Diverse Terpenoid and Polyketides
Secondary Metabolites in Hericium erinaceus,” Scientific Reports 7, no. 1 (2017): 10151; Marcus
Künzler. “How Fungi Defend Themselves against Microbial Competitors and Animal Predators,”
PLoS Pathogens 14, no. 9 (2018): e1007184. Some medicinal mushroom companies choose to
highlight these distinctions and emphasize that they are selling extracts from fruit bodies rather than
mycelia. Others suggest that mycelia are superior sources of medicinals to mushrooms, and still more
ignore the potential difference in chemistry between the two sources. In the end, neither claim affects
consumers because the active compounds are never specified. Uncertainties about the marketing of
extracts from fruit bodies versus mycelia is one aspect of wider concerns about the labeling of fungal
products as foods and alternative medicines. A DNA barcoding study of different food products
containing “wild mushrooms” revealed that many contained common cultivated mushrooms, and that
some of the ingredient labels misrepresented the species of fungi in dried powders, soups, and pasta
sauces: W. Dalley Cutler II, Alexander J. Bradshaw, and Bryn T. M. Dentinger, “What’s for Dinner
This Time? DNA Authentication of ‘Wild Mushrooms’ in Food Products Sold in the USA,” PeerJ 2,
no. 9 (2021): e11747.
29. Kenneth D. Clevenger, Jin W. Bok, Rosa Ye, Galen P. Miley, Maria H. Verdan, Thomas Velk,
Cynthia Chen, et al., “A Scalable Platform to Identify Fungal Secondary Metabolites and Their Gene
Clusters,” Nature Chemical Biology 13, no. 8 (2017): 895–901; Claudio Greco, Nancy P. Keller, and
Antonis Rokas, “Unearthing Fungal Chemodiversity and Prospects for Drug Discovery,” Current
Opinion in Microbiology 51 (2019): 22–29; Matthew T. Robey, Lindsay K. Caesar, Milton T. Drott,
Nancy P. Keller, and Neil L. Kelleher, “An Interpreted Atlas of Biosynthetic Gene Clusters from
1,000 Fungal Genomes,” Proceedings of the National Academy of Sciences USA 118, no. 19 (2021):
e2020230118; Kirstin Scherlach and Christian Hertweck, “Mining and Unearthing Hidden
Biosynthetic Potential,” Nature Communications 12 (2021): 3864.
30. Carsten Gründemann, Jakob K. Reinhardt, and Ulricke Lindequist, “European Medicinal
Mushrooms: Do They Have Potential for Modern Medicine?—An Update,” Phytomedicine 66
(2020): 153131.
31. Ravinder Kumar and Piyush Kumar, “Yeast-Based Vaccines: New Perspective in Vaccine
Development and Application,” FEMS Yeast Research 19, no. 2 (2019): foz007.
32. I read a book about bird’s nest fungi (the only one on this subject) as a student and was struck
with the intricate design of these things. Later, when I found them for the first time in Colorado, I felt
something of “the tide of emotion” experienced by Stendhal in the Basilica di Santa Croce in
Florence, where he visited the tombs of Machiavelli and Galileo, and saw the chiaroscuro frescos of
Volterrano: “As I emerged from the porch of Santa Croce … I walked in constant fear of falling to
the ground.” The French author’s response has been memorialized in a psychosomatic condition
called Stendhal’s syndrome that describes tourists swooning before great works of art. This diagnosis
should be extended to people with an exceptional sensitivity toward the fungi: “Sanctus stercore,” I
thought in English when I gazed upon the tiny nests of the species whose Latin name is Cyathus
stercoreus. Pursuing my mycological expression of Stendhal’s syndrome, I anticipate feeling quite
emotional if I am fortunate enough to visit the Basilica Santa Croce, where, beneath the fresco, lies
the tomb of Pier Antonio Micheli (1679–1737). Micheli is celebrated as the father of experimental
mycology for his experiments with mushroom spores, described in his magnum opus, Nova
Plantarum Genera, published in 1729. There is a striking statue of Micheli in the colonnade outside
the Uffizi, and he is also memorialized in street names in Florence and Rome. Sources: Harold J.
Brodie, The Bird’s Nest Fungi (Toronto: University of Toronto Press, 1975); Stendhal, Rome, Naples
and Florence, trans. Richard N. Coe (Richmond, UK: John Calder, 1959), 301–302; Iain Bamforth,
“Stendhal’s Syndrome,” British Journal of General Practice 60, no. 581 (2010): 945–946.
33. Olchowecki’s original observations on the antibiotic stimulated the doctoral research of
another student, Bhavdish Narain Johri, whose dissertation was the foundation for all the subsequent
work on the cyathins: B. N. Johri, H. J. Brodie, A. D. Allbutt, W. A. Ayer, and H. Taube, “A
Previously Unknown Antibiotic Complex from the Fungus Cyathus helenae,” Experientia 27 (1971):
853; A. D. Allbutt, W. A. Ayer, H. J. Brodie, B. N. Johri, and H. Taube, “Cyathin, a New Antibiotic
Complex Produced by Cyathus helenae,” Canadian Journal of Microbiology 17, no. 11 (1971):
1401–1407. Harold Brodie wrote the book on the bird’s nest fungi that I read as a student titled The
Bird’s Nest Fungi (Toronto: University of Toronto Press, 1975), and introduced a crumb of mirth,
intentionally or otherwise, into an otherwise dry scientific article on mycelial mergers with the
subheading, “Attempts at Mating with Cyathus olla.” Less than a crumb.
 34. Emma Dixon, Tatiana Schweibenz, Alison Hight, Brian Kang, Allyson Dailey, Sarah Kim,
Meng-Yang Chen, et al., “Bacteria-Induced Static Batch Fungal Fermentation of the Diterpenoid
Cyathin A3, a Small-Molecule Inducer of Nerve Growth Factor,” Journal of Industrial Microbiology
and Biotechnology 38, no. 5 (2011): 607–615; Christian Bailly and Jin-Ming Gao, “Erinacine A and
Related Cyathane Diterpenoids: Molecular Diversity and Mechanisms Underlying Their
Neuroprotection and Anticancer Activities,” Pharmaceutical Research 159 (2020): 104953.
 CHAPTER EIGHT
1. “Celebratory Meal a Near Death Experience,” Raglan Chronicle, May 9, 2020,
https://www.raglanchronicle.co.nz/the-chronicle/2020/05/celebratory-meal-a-near-death-experience/;
John Weekes, “Waikato Doctor Nearly Dies after Death Cap Mushroom Poisoning,” Stuff, May 11,
2020, https://www.stuff.co.nz/national/health/121464993/waikato-doctor-nearly-dies-after-death-cap-
mushroom-poisoning.
2. William E. Brandenburg and Karlee J. Ward, “Mushroom Poisoning Epidemiology in the
United States,” Mycologia 110, no. 4 (2018): 637–641; Jeremy A. W. Gold, Emily Kiernan, Michael
Yeh, Brendan R. Jackson, and Kaitlin Benedict, “Health Care Utilization and Outcomes Associated
with Accidental Poisonous Mushroom Ingestions—United States, 2016–2018,” MMWR Morbidity
and Mortality Weekly Report 70 (2021): 337–341. Between 1999 and 2016, more than seven
thousand Americans were poisoned by mushrooms every year, with 60 percent of cases reported for
children younger than six, and few resulting in more than brief gastrointestinal distress. During this
period, there were seven or fewer fatalities per year from mushroom poisoning, which was
comparable to the number of lethal snake bites.
3. Anne Pringle and Else C. Vellinga, “Last Chance to Know? Using Literature to Explore the
Biogeography and Invasion Biology of the Death Cap Mushroom Amanita phalloides (Vaill. ex
Fr.:Fr.) Link,” Biological Invasions 8 (2006): 1131–1144; Anne Pringle, Rachel I. Adams, Hugh B.
Cross, and Thomas D. Bruns, “The Ectomycorrhizal Fungus Amanita phalloides Was Introduced and
Is Expanding Its Range on the West Coast of North America,” Molecular Ecology 18 (2009): 817–
833.
4. Here are the corresponding Latin names: oyster mushrooms, Pleurotus ostreatus; lion’s mane,
Hericium erinaceus; common puffballs, Lycoperdon perlatum; giant puffballs, Calvatia gigantea;
golden chanterelles, Cantharellus cibarius; and porcini, ceps, or king boletes, Boletus edulis.
5. Dennis R. Benjamin, Mushrooms: Poisons and Panaceas—A Handbook for Naturalists,
Mycologists, and Physicians (New York: W. H. Freeman & Co., 1995). Amanita vaginata is the
grisette; Amanita rubescens is the blusher; the fool’s mushroom is Amanita verna; and the destroying
angels are Amanita bisporigera, Amanita ocreata, and Amanita virosa.
6. Britt A. Barnyard, “The Real Story behind Increased Amanita Poisonings in North America,”
FUNGI Magazine 8, no. 3 (2015): 6–9.
7. Chad Hyatt, The Mushroom Hunter’s Kitchen: Reimaging Comfort Food with a Chef Forager
(San Jose, CA: Chestnut Fed Books, 2018), 107–109.
8. Nicholas P. Money, Mushrooms: A Natural and Cultural History (London: Reaktion Books,
2017), 137–138.
9. I refer readers interested in mushroom conservation to a prescient essay whose publication
attracted a great deal of baseless dissent by mushroomers: Nicholas P. Money, “Why Picking Wild
Mushrooms May Be Bad Behaviour,” Mycological Research 109, no. 2 (2005): 131–135.
10. Paolo Scocco, Giampietro Rupolo, and Diego De Leo, “Failed Suicide by Amanita phalloides
(Mycetismus) and Subsequent Liver Transplant: Case Report,” Archives of Suicide Research 4
(1998): 201–206.
11. Ismail Yilmaz, Fatih Ermis, Ilgaz Akata, and Ertugrul Kaya, “A Case Study: What Doses of
Amanita phalloides and Amatoxins Are Lethal to Humans?,” Wilderness and Environmental
Medicine 26, no. 4 (2015): 491.
 12. Yongzhuang Ye and Zhenning Liu, “Management of Amanita phalloides Poisoning: A
Literature Review and Update,” Journal of Critical Care 46 (2018): 17–22; Juliana Garcia, Vera M.
Costa, Alexandra Carvalho, Paula Baptista, Paula G. de Pinho, Maria de Lourdes Bastos, and Félix
Carvalho, “Amanita phalloides Poisoning: Mechanisms of Toxicity and Treatment,” Food and
Chemical Toxicology 86 (2015): 41–55. Death caps contain three groups of toxins: amatoxins,
phallotoxins, and vomitoxins.
13. The lethal dose of alpha-amanitin is estimated to be 0.1–0.3 milligrams per kilogram body
weight (from Yilmaz et al., “A Case Study,” 491–496), which compares with 300–500 milligrams per
kilogram for aspirin. Incidentally, alpha-amanitin is ten thousand times less deadly than botulinum
toxin, or Botox, with an LD50 of 30 nanograms per kilogram. LD50 is the amount of a substance that
kills half of the laboratory animals in an experiment. These estimates refer to oral administration.
14. Patrick L. West, Janet Lindgren, and B. Zane Horowitz, “Amanita smithiana Mushroom
Ingestion: A Case of Delayed Renal Failure and Literature Review,” Journal of Medical Toxicology
5, no. 1 (2009): 32–38.
15. Brandon Landry, Jeannette Whitton, Anna L. Bazzicalupo, Oldriska Ceska, and Mary L.
Berbee, “Phylogenetic Analysis of the Distribution of Deadly Amatoxins among the Little Brown
Mushrooms of the Genus Galerina,” PLoS ONE 16, no. 2 (2021): e0246575.
16. Julian White, Scott A. Weinstein, Luc De Haro, Regis Bédry, Andreas Schaper, Bary H.
Rumack, and Thomas Zilker, “Mushroom Poisoning: A Proposed New Clinical Classification,”
Toxicon 157 (2019): 53–65.
17. Regis Bedry, Isabelle Baudrimont, Gerard Deffieux, Edmond E. Creppy, Jean P. Pomies, Jean
M. Ragnaud, Michel Dupon, et al., “Wild-Mushroom Intoxication as a Cause of Rhabdomyolysis,”
New England Journal of Medicine 345 (2001): 798–802.
18. Piotr Rzymski and Piotr Klimaszyk, “The Yellow Knight Fights Back: Toxicological,
Epidemiological, and Survey Studies Defend Edibility of Tricholoma equestre,” Toxins 10, no. 11
(2018): 468.
19. A one-kilogram potato contains between 20 and 130 milligrams of solanine hydrochloride, and
mice studies provide an LD50 estimate of 42 milligrams of solanine per kilogram body weight.
Using these numbers, a human would need to eat more than 20 kilograms of potatoes to absorb a
comparable dose. Poisonings have occurred among people who have eaten more modest quantities of
potatoes containing exceptionally high levels of solanine, which can develop when the tubers become
spoiled in storage. Potatoes belong to a toxic family of plants that includes deadly nightshade, which
carries a lethal dose of atropine in a few of its onyx-black berries. See National Center for
Biotechnology Information, “PubChem Compound Summary for CID 118796405, Solanine HCl,”
accessed July 17, 2023, https://pubchem.ncbi.nlm.nih.gov/compound/Solanine-HCl.
20. Petteri Nieminen and Anne-Mari Mustonen, “Toxic Potential of Traditionally Consumed
Mushroom Species—A Controversial Continuum with Many Unanswered Questions,” Toxins 12, no.
10 (2020): 639.
21. Even morels upset some people: Benjamin, Mushrooms, 278.
22. Hikoto Ohta, Daisuke Watanabe, Chie Nomura, Daichi Saito, Koichi Inoue, Hajime
Miyaguchi, Shuichi Harada, et al., “Toxicological Analysis of Satratoxins, the Main Toxins in the
Mushroom Trichoderma cornu-damae, in Human Serum and Mushroom Samples by Liquid
Chromatography–Tandem Mass Spectrometry,” Forensic Toxicology 39 (2021): 101–113.
23. Fungi with coral shapes belong to the basidiomycetes and the ascomycetes. The fire coral is an
ascomycete, whereas the hundreds of species of Clavaria or fairy clubs, Ramaria, and other
“clavarioid” fungi, are basidiomycetes.
 24. Luis E. Alonso-Aguilar, Adriana Montoya, Alejandro Kong, Arturo Estrada-Torres, and
Roberto Garibay-Orijel, “The Cultural Significance of Wild Mushrooms in San Mateo Huexoyucan,
Tlaxcala, Mexico,” Journal of Ethnobiology and Ethnomedicine 10 (2014): 27.
25. “Ramaria flava (Schaeff.) Quél.,” First Nature, accessed July 15, 2023, https://www.first-
nature.com/fungi/ramaria-flava.php; Pamela M. North, Poisonous Plants and Fungi in Colour
(London: Blandford Press, 1967), 109–110.
26. Charles McIlvaine, One Thousand American Fungi: How to Select and Cook the Edible; How
to Distinguish and Avoid the Poisonous (Indianapolis, IN: Bowen-Merrill Co., 1900). I have
celebrated the extraordinary life and career of Captain McIlvaine in an earlier book: Mushrooms: A
Natural and Cultural History (London: Reaktion Books, 2017), 84–86.
27. Normal Mier, Sandrine Canete, Alain Klaebe, Luis Chavant, and Didier Fournier, “Insecticidal
Properties of Mushroom and Toadstool Carpophores,” Phytochemistry 41, no. 5 (1996): 1293–1299.
28. Paul A. Horgen, Allan C. Vaisius, and Joseph F. Ammirati, “The Insensitivity of Mushroom
Nuclear RNA Polymerase Activity to Inhibition by Amatoxins,” Archives of Microbiology 118
(1978): 317–319.
29. Frank M. Dugan, Fungi in the Ancient World: How Mushrooms, Mildews, Molds, and Yeast
Shaped the Early Civilizations of Europe, the Mediterranean, and the Near East (St. Paul, MN: APS
Press, 2008).
30. The literature on ergotism is voluminous. The following pair of papers on the Norwegian
history of the phenomenon are relevant to outbreaks of ergotism in other regions: Torbjørn Alm and
Brita Elvevåg, “Ergotism in Norway, Part 1: The Symptoms and Their Interpretation from the Late
Iron Age to the Seventeenth Century,” History of Psychiatry 24, no. 1 (2013): 15–33, and “Ergotism
in Norway, Part 2: The Symptoms and Their Interpretation from the Eighteenth Century Onwards,”
History of Psychiatry 24, no. 2 (2013): 131–147.
31. The value of this distinction dissolves with the formation of satratoxins by the poison fire coral
because satratoxins are also produced by molds. The presence of the same toxins in mushrooms and
molds is explained by the fact that some fungi that produce mushrooms have a second identity as
molds. A brief explanation of this complex feature of fungal life cycles is provided by Sarah C.
Watkinson, Lynne Boddy, and Nicholas P. Money, The Fungi, 3rd ed. (Amsterdam: Academic Press,
2016), 20–21. The fire coral is an ascomycete mushroom, which is a closer relation to morels than
gilled mushrooms and boletes, and its asexual stages are classified as species of Trichoderma: Gary J.
Samuels and D. J. Lodge, “Three Species of Hypocrea with Stipitate Stromata and Trichoderma
Anamorphs,” Mycologia 88, no. 2 (1996): 302–315.
32. Caroline De Costa, “St Anthony’s Fire and Living Ligatures: A Short History of Ergometrine,”
Lancet 359, no. 9319 (2002): 1768–1770.
33. Yan Liu, Healing with Poisons: Potent Medicines in Medieval China (Seattle: University of
Washington Press, 2021).
34. Carolyn A. Young, Christopher L. Schardl, Daniel G. Panaccione, Simona Florea, Johanna E.
Takach, Nikki D. Charlton, Neil Moore, et al., “Genetics, Genomics and Evolution of Ergot Alkaloid
Diversity,” Toxins (Basel) 7, no. 4 (2015): 1273–1302.
35. Laurinda S. Dixon, “Bosch’s ‘St. Anthony Triptych’—An Apothecary’s Apotheosis,” Art
Journal 44 (2014): 119–131.
36. Linnda R. Caporael, “Ergotism: The Satan Loosed in Salem?,” Science 192, no. 4234 (1976):
21–26.
37. P. Salway and W. Dell, “Plague at Athens,” Greece and Rome 2, no. 2 (1955): 62–69; Mary K.
Matossian, Poisons of the Past: Molds, Epidemics and History (New Haven, CT: Yale University
Press, 1989).
38. A. J. Holladay and J. C. F. Poole, “Thucydides and the Plague of Athens,” The Classical
Quarterly 29 (1979): 282–300; Jane Bellemore, Ian M. Plant, and Lynne M. Cunningham, “Plague of
Athens—Fungal Poison?,” Journal of the History of Medicine and Allied Sciences 49, no. 4 (1994):
521–545. The German pharmacologist and toxicologist Rudolf Kobert (1854–1918) believed that the
symptoms of the plague might have been caused by a combination of a smallpox outbreak in a
population already weakened by ergotism.
39. Abraham Z. Joffe, “Alimentary Toxic Aleukia,” in Algal and Fungal Toxins, ed. Solomon
Kadis, Alex Ciegler, and Samuel J. Ajl (New York: Academic Press, 1971), 139–189; and “Fusarium
poae and F. sporotrichioides as Principal Causal Agents of Alimentary Toxic Aleukia,” in Mycotoxic
Fungi, Mycotoxins, Mycotoxicoses: An Encyclopedic Handbook, vol. 3, Mycotoxicoses of Man and
Plants: Mycotoxin Control and Regulatory Practices, ed. Thomas D. Wyllie and Lawrence G.
Morehouse (New York: Marcel Dekker, 1978), 21–86.
40. Outbreaks of ergotism in the twentieth century included a spate of cases among Jewish
immigrants from Central Europe living in Manchester in 1927, and 250 poisonings in the town of
Pont St. Esprit in southern France in the 1950s. Although ergotism fits many of the facts of the mass
psychosis that afflicted the residents of Pont St. Esprit, mercury contamination of bread flour is one
of several alternative explanations. Other eruptions occurred in India, and ergotism continues to flare
up in Ethiopia: Sarah Belser-Ehrlich, Ashley Harper, John Hussey, and Robert Hallock, “Human and
Cattle Ergotism since 1900: Symptoms, Outbreaks, and Regulations,” Toxicology and Industrial
Health 29, no. 4 (2013): 307–316.
41. Noreddine Benkerroum, “Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action,”
International Journal of Environmental Research and Public Health 17, no. 2 (2020): 423; Stephanie
Kraft, Lisa Buchenauer, and Tobias Polte, “Mold, Mycotoxins and a Dysregulated Immune System:
A Combination of Concern?,” International Journal of Molecular Sciences 22, no. 22 (2021): 12269.
42. J. W. Bennett and M. Klich, “Mycotoxins,” Clinical Microbiology Reviews 16, no. 3 (2003):
497–516.
43. Yun Yun Gong, Sinead Watson, and Michael N. Routledge, “Aflatoxin Exposure and
Associated Human Health Effects, a Review of Epidemiological Studies,” Food Safety (Japan) 4, no.
1 (2016): 14–27.
44. Robert J. Lee, Alan D. Workman, Ryan M. Carey, Bei Chen, Philip L. Rosen, Laurel
Doghramji, Nithin D. Adappa, et al., “Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary
Function,” Scientific Reports 6 (2016): 33221.
45. Dr. Harriet Burge, a distinguished professor in the Harvard School of Public Health,
demonstrated the improbability of significant inhalational exposure to mycotoxins in mold-damaged
homes by calculating the number of spores inhaled per hour: Harriet A. Burge, “Fungi: Toxic Killers
or Unavoidable Nuisances?,” Annals of Allergy, Asthma, and Immunology 87 (2001): 52–56.
46. Nicholas P. Money, Carpet Monsters and Killer Spores: A Natural History of Toxic Mold
(New York: Oxford University Press, 2004).
47. Joan W. Bennett, “The Fungi That Ate My House,” Science 349 (2015): 1018; Arati A.
Inamdar, Shannon Morath, and Joan W. Bennett, “Fungal Volatile Organic Compounds: More Than
Just a Funky Smell?,” Annual Review of Microbiology 74, no. 1 (2020): 101–116.
48. Nandhitha Venkatesh and Nancy P. Keller, “Mycotoxins in Conversation with Bacteria and
Fungi,” Frontiers in Microbiology 10 (2019): 403; Daniel G. Panaccione, “Origins and Significance
of Ergot Alkaloid Diversity in Fungi,” FEMS Microbiology Letters 251, no. 1 (2005): 9–17.
 49. The potency of mycotoxins has not been lost on military strategists, and molds are
undoubtedly part of secret bioweapons research. Mary K. Klassen-Fischer, “Fungi as Bioweapons,”
Clinics in Laboratory Medicine 26, no. 2 (2006): 387–395; Edyta Janik-Karpińska, Michał
Ceremunga, Joanna Saluk-Bijak, and Michał Bijak, “Biological Toxins as the Potential Tools for
Bioterrorism,” International Journal of Molecular Sciences 20 (2019): 1181.
50. Nicholas P. Money, The Rise of Yeast: How the Sugar Fungus Shaped Civilization (Oxford:
Oxford University Press, 2018).
 CHAPTER NINE
1. Robert Alter, The Hebrew Bible, vol. 2, Prophets (New York: Norton, 2019), Ezekiel 1:15–17,
pp. 1054–1055; Jacques M. Chevalier, A Postmodern Revelation: Signs of Astrology and the
Apocalypse (Toronto: University of Toronto Press, 1997), 223–263; Shawn Z. Aster, “Ezekiel’s
Adaptation of Mesopotamian Melammu,” Die Welt des Orients 45, no. 1 (2015): 10–21.
2. Flavie Waters, Jan D. Blom, Thien T. Dang-Vu, Allan J. Cheyne, Ben Alderson-Day, Peter
Woodruff, and Daniel Collerton, “What Is the Link between Hallucinations, Dreams, and
Hypnagogic-Hypnopompic Experiences?,” Schizophrenia Bulletin 42, no. 5 (2016): 1098–1109;
Rainer Kraehenmann, “Dreams and Psychedelics: Neurophenomenological Comparison and
Therapeutic Implications,” Current Neuropharmacology 15, no. 7 (2017): 1032–1042; Camila Sanz,
Federico Zamberlan, Earth Erowid, Fire Erowid, and Enzo Tagliazucchi, “The Experience Elicited by
Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive
Substance Reports,” Frontiers in Neuroscience 12 (2018): 7; Benjamin Baird, Sergio A. Mota-Rolim,
and Martin Dresler, “The Cognitive Neuroscience of Lucid Dreaming,” Neuroscience and
Biobehavioral Reviews 100 (2019): 305–323. Lucid dreaming refers to dreams in which we become
aware that we are dreaming as the action takes place, but there does not seem to be a clear distinction
between this experience and very vivid dreams like my fantasy of the swirling cosmos.
3. Psilocin slips through cell membranes more easily than serotonin and binds with receptor
proteins inside nerve cells. Serotonin stays on the outside. This difference may explain some of the
longer-term effects of the mushroom alkaloid on the nervous system: Maxemiliano V. Vargas, Lee E.
Dunlap, Chunyang Dong, Samuel J. Carter, Robert J. Tombari, Shekib A. Jami, Lindsay P. Cameron,
et al., “Psychedelics Promote Neuroplasticity through the Activation of Intracellular 5-HT2A
Receptors,” Science 379 (2023): 700–706.
4. Jiawei Zhang, “Basic Neural Units of the Brain: Neurons, Synapses and Action Potential,” May
30, 2019, arXiv:1906.01703.
5. The description of the brain as a computer is apt, as long as we recognize the limitations of this
metaphor. Unlike a digital computer, the brain is an analog device that processes information by
gathering data from multiple sources to produce approximate answers or personal representations
rather than the precise and unvarying output of computers. The digital description is more useful at
the cellular level because each of the nerve cells in the brain is limited to transmitting or blocking an
incoming electrical signal: Romaine Brette, “Brains as Computers: Metaphor, Analogy, Theory or
Fact?,” Frontiers in Ecology and Evolution 10 (2022): 878729; Blake A. Richards and Timothy P.
Lillicrap, “The Brain-Computer Metaphor Debate Is Useless: A Matter of Semantics,” Frontiers of
Computer Science 4 (2022): 810358. It is also noteworthy that the three-pound ball of jelly in the
skull draws no more energy than a lightbulb, whereas the supercomputer lives in an air-conditioned
vault and consumes more electricity than a small city.
6. Drummond E.-W. McCulloch, Gitte M. Knudsen, Frederick S. Barrett, Manoj K. Doss, Robin
L. Carhart-Harris, Fernando E. Rosas, Gustavo Deco, et al., “Psychedelic Resting-State
Neuroimaging: A Review and Perspective on Balancing Replication and Novel Analyses,”
Neuroscience and Biobehavioral Reviews 138 (2022): 104689.
7. N. L. Mason, K. P. C. Kuypers, F. Müller, J. Reckweg, D. H. T. Tse, S. W. Toennes, N. R. P. W.
Hutten, et al., “Me, Myself, Bye: Regional Alterations in Glutamate and the Experience of Ego
Dissolution with Psilocybin,” Neuropsychopharmacology 45 (2020): 2003–2011.
 8. Lea J. Mertens, Matthew B. Wall, Leor Roseman, Lysia Demetriou, David J. Nutt, and Robin L.
Carhart-Harris, “Therapeutic Mechanisms of Psilocybin: Changes in Amygdala and Prefrontal
Functional Connectivity during Emotional Processing after Psilocybin for Treatment-Resistant
Depression,” Journal of Psychopharmacology 34, no. 2 (2020): 167–180. The amygdala, or
amygdala nuclei, are paired clusters of neurons buried in the brain that are involved in processing
memories, making decisions, and controlling fear, aggression, and anxiety.
9. Nina Schimmel, Joost J. Breeksema, Sanne Y. Smith-Apeldoorn, Jolien Veraart, Wim van den
Brink, and Robert A. Schoevers, “Psychedelics for the Treatment of Depression, Anxiety, and
Existential Distress in Patients with a Terminal Illness: A Systematic Review,” Psychopharmacology
(Berlin) 239, no. 1 (2022): 15–33.
10. Gabrielle I. Agin-Liebes, Tara Malone, Matthew M. Yalch, Sarah E. Mennenga, K. Linnae
Ponté, Jeffrey Guss, Anthony P. Bossis, et al., “Long-Term Follow-Up of Psilocybin-Assisted
Psychotherapy for Psychiatric and Existential Distress in Patients with Life-Threatening Cancer,”
Journal of Psychopharmacology 34, no. 2 (2020): 155–166.
11. Erwin Krediet, Tijmen Bostoen, Joost Breeksema, Annette van Schagen, Torsten Passie, and
Eric Vermetten, “Reviewing the Potential of Psychedelics for the Treatment of PTSD,” International
Journal of Neuropsychopharmacology 23, no. 6 (2020): 385–400; Michael P. Bogenschutz, Stephen
Ross, Snehal Bhatt, Tara Baron, Alyssa A. Forcehimes, Eugene Laska, Sarah E. Mennenga, et al.,
“Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the
Treatment of Adult Patients with Alcohol Use Disorder: A Randomized Clinical Trial,” JAMA
Psychiatry (2022), doi:10.1001/jamapsychiatry.2022.2096; Meg J. Spriggs, Hannah M. Douglass,
Rebecca J. Park, Tim Read, Jennifer L. Danby, Frederico J. C. de Magalhães, Kirsty L. Alderton, et
al., “Study Protocol for ‘Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study,’ ” Frontiers
in Psychiatry 12 (2021): 735523.
12. Richard E. Daws, Christopher Timmermann, Bruna Giribaldi, James D. Sexton, Matthew B.
Wall, David Erritzoe, Loer Roseman, et al., “Increased Global Integration in the Brain after
Psilocybin Therapy for Depression,” Nature Medicine 28, no. 4 (2022): 844–851; Ling-Xiao Shao,
Clara Liao, Ian Gregg, Pasha A. Davoudian, Neil K. Savalia, Kristin Delagarza, and Alex C. Kwan,
“Psilocybin Induces Rapid and Persistent Growth of Dendritic Spines in Frontal Cortex In Vivo,”
Neuron 109, no. 16 (2021): 2535–2544.
13. Sean McClintock, “Why Investors Are Turning toward Psychedelic Healthcare Companies,”
Fortune, September 4, 2021; Yeji J. Lee, “What to Know about the Booming Psychedelics Industry
Where Companies Are Racing to Turn Magic Mushrooms and MDMA into Approved Medicines,”
Insider, June 30, 2022; Michelle Lhooq, “With Magic Mushrooms, Small Businesses Lead, Hoping
Laws Will Follow,” Bloomberg Businessweek, July 21, 2022.
14. “Oregon Psilocybin Services Section Summary of Measure 109: Listening Session December
13–15, 2021,” Oregon Health Authority, December 2021,
https://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/Documents/M109-Summary-2021-
Dec.pdf.
15. Andrew Selsky, “Oregon Voters Face 2 Drug Measures on November Ballot,” AP News,
November 4, 2020.
16. Theresa M. Carbonaro, Matthew P. Bradstreet, Frederick S. Barrett, Katherine A. MacLean,
Robert Jesse, Matthew W. Johnson, and Roland R. Griffiths, “Survey Study of Challenging
Experiences after Ingesting Psilocybin Mushrooms: Acute and Enduring Positive and Negative
Consequences,” Journal of Psychopharmacology 30, no. 12 (2016): 1268–1278.
 17. Andy Letcher, Shroom: A Cultural History of the Magic Mushroom (London: Faber and Faber,
2006).
18. O. T. Oss and O. N. Oeric, Psilocybin: Magic Mushroom Grower’s Guide (Berkeley, CA:
And/Or Press, 1976). Otos is derived from the Greek word meaning insatiate (never satisfied) and
oneiric is an adjective that refers to dreams. The coauthors were pseudonyms for McKenna, who
wrote the foreword for his book under his real name.
19. N. Milne, P. Thomsen, N. Mølgaard Knudsen, P. Rubaszka, M. Kristensen, and I. Borodina,
“Metabolic Engineering of Saccharomyces cerevisiae for the de Novo Production of Psilocybin and
Related Tryptamine Derivatives,” Metabolic Engineering 60 (2020): 25–36; William J. Gibbons,
Madeline G. McKinney, Philip J. O’Dell, Brooke A. Bollinger, and J. Andrew Jones, “Homebrewed
Psilocybin: Can New Routes for Pharmaceutical Psilocybin Production Enable Recreational Use?,”
Bioengineered 12, no. 1 (2021): 8863–8871.
20. Janis Fricke, Felix Blei, and Dirk Hoffmeister, “Enzymatic Synthesis of Psilocybin,”
Angewandte Chemie International Edition 56, no. 40 (2017): 12352–12355; R. C. Van Court, M. S.
Wiseman, K. W. Meyer, D. J. Ballhorn, K. R. Amses, J. C. Slot, B. T. M. Dentinger, et al., “Diversity,
Biology, and History of Psilocybin-Containing Fungi: Suggestions for Research and Technological
Development,” Fungal Biology 126, no. 4 (2022): 308–319.
21. Hannah T. Reynolds, Vinod Vijayakumar, Emile Gluck-Thaler, Hailee Brynn Korotkin, Patrick
Brandon Matheny, and Jason C. Slot, “Horizontal Gene Cluster Transfer Increased Hallucinogenic
Mushroom Diversity,” Evolution Letters 2, no. 2 (2018): 88–101.
22. Kevin McKernan, Liam Kane, Yvonne Helbert, Lei Zhang, Nathan Houde, and Stephen
McLaughlin, “A Whole Genome Atlas of 81 Psilocybe Genomes as a Resource for Psilocybin
Production,” F1000Research 10 (2021): 961.
23. M. Hibicke and C. D. Nichols, “Validation of the Forced Swim Test in Drosophila, and Its Use
to Demonstrate Psilocybin Has Long-Lasting Antidepressant-Like Effects in Flies,” Scientific
Reports 12 (2022): 10019. Psilocybin appears to boost the optimism of fruit flies immersed in water
without any means of escape. This experiment is a scaled-down version of an unpleasant laboratory
test in which rodents are dropped into glass cylinders filled with water to induce feelings of
hopelessness. The animals struggle to climb out of the water before giving up and resorting to
paddling to stay afloat. Animals attempt to escape this hopeless situation longer and harder if they are
treated with antidepressants, which seems to parallel the development and relief of depression in
humans. Like mice and rats, fruit flies fed with psilocybin struggle longer than controls, who give up
the ghost after a few seconds. The details of the experiment show that the fruit flies respond to
immersion in water with periods of immobility interspersed with activity and a shortening of the
immobile periods under the influence of psilocybin. Fungus gnats have not been tortured in the same
way, but their brains are similar to fruit flies, and our brains are constructed from the same cellular
hardware as those of insects.
24. Although most spores are dispersed from gilled mushrooms by wind, insects that visit fruit
bodies consume spores and carry them in their digestive systems when they fly away. These spores
are deposited in the feces of the insects, which provides nutritional support for the growth of the
young mycelia when they germinate. The insect attraction model for psilocybin is supported by the
presence of the highest levels of the compound in the caps of these mushrooms: Klára Gotvaldová,
Kateřina Hájková, Jan Borovička, Radek Jurok, Petra Cihlářová, and Martin Kuchař, “Stability of
Psilocybin and Its Four Analogs in the Biomass of the Psychotropic Mushroom Psilocybe cubensis,”
Drug Testing and Analysis 13 (2021): 439–446.
 25. Ali R. Awan, Jaclyn M. Winter, Daniel Turner, William M. Shaw, Laura M. Suz, Alexander J.
Bradshaw, Tom Ellis, et al., “Convergent Evolution of Psilocybin Biosynthesis by Psychedelic
Mushrooms,” bioRxiv (2018), https://doi.org/10.1101/374199.
26. Brian Lovett, Raymond J. St. Leger, and Henrik H. de Fine, “Going Gentle into That
Pathogen-Induced Goodnight,” Journal of Invertebrate Pathology 174 (2020): 107398. “Pathogen-
Induced Good Night” would be Thomasian and make more grammatical sense.
27. Greg R. Boyce, Emile Gluck-Thaler, Jason C. Slot, Jason E. Stajich, William J. Davis, Tim Y.
James, John R. Cooley, et al., “Psychoactive Plant- and Mushroom-Associated Alkaloids from Two
Behavior Modifying Cicada Pathogens,” Fungal Ecology 41 (2019): 147–164.
28. Claudius Lenz, Jonas Wick, Daniel Braga, María García-Altares, Gerald Lackner, Christian
Hertweck, Markus Gressler, et al., “Injury-Triggered Blueing Reactions of Psilocybe “Magic”
Mushrooms,” Angewandte Chemie International Edition 59, no. 4 (2020): 1450–1454.
29. Quentin Carboué and Michel Lopez, “Amanita muscaria: Ecology, Chemistry, Myths,”
Encyclopedia 1 (2021): 905–914.
30. In English, fly was a familiar term for a demon in the sixteenth century. Reginald Scot, The
Discoverie of Witchcraft (London: William Brome, 1584), refers to “a flie, otherwise called a divell
or familiar” (III, xv, p. 65), and “Beelzebub, which signifieth the lord of the flies, bicause he taketh
everie simple thing in his web” (xix, p. 518). Pieces of the mushroom soaked or boiled in milk attract
flies that are poisoned by ibotenic acid, which is the precursor or prodrug of muscimol: Mateja
Lumpert and Samo Kreft, “Catching Flies with Amanita muscaria: Traditional Recipes from Slovenia
and Their Efficacy in the Extraction of Ibotenic Acid,” Journal of Ethnopharmacology 187 (2016):
1–8.
31. Jan D. Blom, “Alice in Wonderland Syndrome: A Systematic Review,” Neurology Clinical
Practice 6, no. 3 (2016): 259–270.
32. L. Alison McInnes, Jimmy J. Qian, Rishab S. Gargeya, Charles DeBattista, and Boris D.
Heifets, “A Retrospective Analysis of Ketamine Intravenous Therapy for Depression in Real-World
Care Settings,” Journal of Affective Disorders 301 (2022): 486–495.
33. Francesca I. Rampolli, Premiila Kamler, Claudio C. Carlino, and Francesca Bedussi, “The
Deceptive Mushroom: Accidental Amanita muscaria Poisoning,” European Journal of Case Reports
in Internal Medicine 8, no. 3 (2021): 002212. The same toxins are responsible for poisonings by the
panther cap, Amanita pantherina: Leszek Satora, Dorota Pach, Krysztof Ciszowski, and Lidia
Winnik, “Panther Cap Amanita pantherina Poisoning Case Report and Review,” Toxicon 47, no. 5
(2006): 605–607.
34. The literature on ethnomycology is vast. If readers are unfamiliar with this subject and are
interested in exploring it further, a simple web search will lead to a wealth of online essays, books,
and podcasts on the topic. The following paper also provides a helpful overview of the field: Giorgio
Samorini, “The Oldest Archeological Data Evidencing the Relationship of Homo sapiens with
Psychoactive Plants: A Worldwide Overview,” Journal of Psychedelic Studies 3, no. 2 (2019): 63–80.
35. Alter, Hebrew Bible, vol. 2, Ezekiel 28:13–14, p. 1136.
36. Robert Graves, “Mushrooms, Food of the Gods,” The Atlantic, August 1957,
https://www.math.uci.edu/~vbaranov/nicetexts/eng/mushrooms.html.
37. R. Gordon Wasson, Soma: Divine Mushroom of Immortality (New York: Harcourt, Brace &
World, 1969); Kevin Feeney, “Revisiting Wasson’s Soma: Exploring the Effects of Preparation on the
Chemistry of Amanita Muscaria,” Journal of Psychoactive Drugs 42, no. 4 (2010): 499–506.
38. John M. Allegro, The Sacred Mushroom and the Cross: A Study of the Nature and Origins of
Christianity within the Fertility Cults of the Ancient Near East (London: Hodder & Stoughton, 1970).
 39. C. F. Evans, “The Scholars and the World of God,” The Times (London), November 11, 1971.
Wasson was appalled by Allegro’s shoddy scholarship, writing, “I think that he jumped to
unwarranted conclusions on scanty evidence. And when you make such blunders as attributing the
Hebrew language, the Greek language, to Sumerian—that is unacceptable to any linguist. The
Sumerian language is parent to no language and no one knows where it came from.” This critique is
quoted from the following compilation: Jan Irvin, “The Defamation of Allegro,” in Jan Irvin and
Andrew Rutajit, Astrotheology and Shamanism (San Diego: The Book Tree, 2005), 51–58,
http://www.johnallegro.org/the-defamation-of-allegro-by-jan-irvin-excerpted-from-astrotheology-
shamanism/.
40. Jerry B. Brown and Julie M. Brown, The Psychedelic Gospels: The Secret History of
Hallucinogens in Christianity (Rochester, VT: Park Street Press, 2016); and “Entheogens in Christian
Art: Wasson, Allegro, and the Psychedelic Gospels,” Journal of Psychedelic Studies 3, no. 2 (2019):
142–163.
41. R. R. Griffiths, W. A. Richards, U. McCann, and R. Jesse, “Psilocybin Can Occasion Mystical-
Type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance,”
Psychopharmacology 187 (2006): 268–283; R. R. Griffiths, W. A. Richards, M. W. Johnson, U.
McCann, and R. Jesse, “Mystical-Type Experiences Occasioned by Psilocybin Mediate the
Attribution of Personal Meaning and Spiritual Significance 14 Months Later,” Journal of
Psychopharmacology 22, no. 6 (2008): 621–632.
42. Roland R. Griffiths, Ethan S. Hurwitz, Alan K. Davis, Matthew W. Johnson, and Robert Jesse,
“Survey of Subjective ‘God Encounter Experiences’: Comparisons among Naturally Occurring
Experiences and Those Occasioned by the Classic Psychedelics Psilocybin, LSD, Ayahuasca, or
DMT,” PLoS ONE 14, no. 4 (2016): e0214377.
43. For a provocative and objective article about the interpretation of mystical experiences
produced by drug use, see Huston Smith, “Do Drugs Have Religious Import?,” Journal of
Philosophy 61, no. 18 (1964): 517–530.
44. Aldous Huxley, The Doors of Perception & Heaven and Hell (New York: Harper, 2009).
Huxley’s description of the flower arrangement appears on pp. 16–17. Huxley took his title from
William Blake, The Marriage of Heaven and Hell (undated poem written in the 1790s), and Jim
Morrison, the name of his band. Without the assistance of mushrooms, Blake wrote, “If the doors of
perception were cleansed every thing would appear to man as it is, Infinite.”
45. Aldous Huxley, Brave New World (London: Chatto and Windus, 1932), and Brave New World
Revisited (New York: Harper, 1958).
46. Robin L. Carhart-Harris, Robert Leech, Peter J. Hellyer, Murray Shanahan, Amanda Feilding,
Enzo Tagliazucchi, Dante R. Chialvo, et al., “The Entropic Brain: A Theory of Conscious States
Informed by Neuroimaging Research with Psychedelic Drugs,” Frontiers in Human Neuroscience 8
(2014): 20; Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas, Robin Carhart-Harris, Yonatan
S. Prl, Enzo Tagliazucchi, and Rodrigo Cofre, “A Mechanistic Model of the Neural Entropy Increase
Elicited by Psychedelic Drugs,” Scientific Reports 10 (2020): 17725.
47. Steven D. Hollon, Paul W. Andrews, Daisy R. Singla, Marta M. Maslej, and Benoit H.
Mulsant, “Evolutionary Theory and the Treatment of Depression: It Is All About the Squids and the
Sea Bass,” Behavior Research and Therapy 143 (2021): 103849.
48. Robert Burton, The Anatomy of Melancholy (Oxford: John Litchfield and James Short, for
Henry Cripps, 1621), Part II, Sect. 3. The quote derives from Horace’s Odes, I.24.
49. Chris Paling, A Very Nice Rejection Letter: Diary of a Novelist (London: Constable, 2021),
151.
 50. W. Steven Gilbert, The Life and Work of Dennis Potter (Woodstock, NY: Overlook Press,
1998), 294.
51. Microdosing has become a popular approach to achieving the supposed creative benefits of the
drug without losing practical contact with the immediate tasks of the day: Federico Cavanna,
Stephanie Muller, Laura A. de la Fuente, Federico Zamberlan, Matías Palmucci, Lucie Janeckova,
Martin Kuchar, et al., “Microdosing with Psilocybin Mushrooms: A Double-Blind Placebo-
Controlled Study,” Translational Psychiatry 12 (2022): 307. Unfortunately, this study found no
evidence that microdosing increased feelings of well-being, creativity, or cognitive function beyond a
placebo effect.
 CHAPTER TEN
1. Stephen R. Kane, Zhexing Li, Eric T. Wolf, Colby Ostberg, and Michelle L. Hill, “Eccentricity
Driven Climate Effects in the Kepler-1649 System,” Astronomical Journal 161, no. 1 (2020): 31.
Kepler 1649c is three quadrillion kilometers from Earth, and it would take six million years for
peopled or unpeopled probes to get there.
2. Yinon M. Bar-On, Rob Phillips, and Ron Milo, “The Biomass Distribution on Earth,”
Proceedings of the National Academy of Sciences USA 115, no. 25 (2018): 6506–6511. Plants make
up 80 percent of the weight of the biosphere; 2 percent of the biomass lives in fungi, and animals
contribute less than 1 percent to the sum of biology. Land plants make up most of the billions of tons
of botany, and one-third of the weight of plants is in their roots, where they form mycorrhizas with
fungi.
3. Billions of elms and American chestnuts were wiped out in the twentieth century, and
eucalyptus trees and pines are plagued by rusts today. Roderick J. Fensham and Julian Radford-
Smith, “Unprecedented Extinction of Tree Species by Fungal Disease,” Biological Conservation 261
(2021): 109276; Erin Shanahan, Kathryn M. Irvine, David Thoma, Siri Wilmoth, Andrew Ray,
Kristin Legg, and Henry Shovic, “Whitebark Pine Mortality Related to White Pine Blister Rust,
Mountain Pine Beetle Outbreak, and Water Availability,” Ecosphere 7, no. 12 (2016): e01610. These
pandemic diseases are spread by global commerce and exacerbated by climate change.
4. N. C. Johnson, J. H. Graham, and F. A. Smith, “Functioning of Mycorrhizal Associations along
the Mutualism-Parasitism Continuum,” New Phytologist 135, no. 4 (1997): 575–586; Nancy-Collins
Johnson and James H. Graham, “The Continuum Concept Remains a Useful Framework for Studying
Mycorrhizal Functioning,” Plant and Soil 363 (2013): 411–419; Marc-André Selosse, Laure
Schneider-Maunoury, and Florent Martos, “Time to Re-Think Fungal Ecology? Fungal Ecological
Niches Are Often Prejudged,” New Phytologist 217 (2018): 968–972. Even the supposedly saintly
mycorrhizal fungi can stray from their benevolence toward plants by becoming antagonistic toward
their hosts and behaving as parasites. Truffles are ectomycorrhizal with oaks and hazels and create
clear patches around their hosts called brûlés by parasitizing weeds and grasses that compete for soil
nutrients: I. Plattner and I. R. Hall, “Parasitism of Non-Host Plants by the Mycorrhizal Fungus Tuber
melanosporum,” Mycological Research 99, no. 11 (1995): 1367–1370. Matsutake species seem
particularly catholic, feeding as mutualists, as parasites, and as saprotrophs on dead roots: Wang Yun,
Ian R. Hall, and Lynley A. Evans, “Ectomycorrhizal Fungi with Edible Fruiting Bodies 1. Tricholoma
matsutake and Related Fungi,” Economic Botany 51, no. 3 (1997): 311–327; Lin-Min Vaario, Taina
Pennanen, Tytti Sarjala, Eira-Maija Savonen, and Jussi Heinonsalo, “Ectomycorrhization of
Tricholoma matsutake and Two Major Conifers in Finland—An Assessment of In Vitro Mycorrhiza
Formation,” Mycorrhiza 20, no. 7 (2010): 511–518; Wang Yun, “Matsutake: A Natural
Biofertilizer?,” in Handbook of Microbial Fertilizers, ed. M. K. Rai (Binghamton, NY: Food
Products Press, 2006), 497–541.
5. Suzanne W. Simard, David A. Perry, Melanie D. Jones, David D. Myrold, Daniel M. Durall, and
Randy Molina, “Net Transfer of Carbon between Ectomycorrhizal Tree Species in the Field,” Nature
388 (1997): 579–582. The importance of the fungi in nutrient transfer between trees was questioned
when this classic study was published and remains controversial: David Robinson and Alastair Fitter,
“The Magnitude and Control of Carbon Transfer between Plants Linked by a Common Mycorrhizal
Network,” Journal of Experimental Botany 50, no. 330 (1999): 9–13; Monika A. Gorzelak, Benjamin
H. Ellert, and Leho Tedersoo, “Mycorrhizas Transfer Carbon in a Mature Mixed Forest,” Molecular
Ecology 29 (2020): 2315–2317; Justine Karst, Melanie D. Jones, and Jason D. Hoeksema, “Positive
Citation Bias and Overinterpreted Results Lead to Misinformation on Common Mycorrhizal
Networks in Forests,” Nature Ecology and Evolution (2023), https://doi.org/10.1038/s41559-023-
01986-1.
6. Thomas I. Wilkes, “Arbuscular Mycorrhizal Fungi in Agriculture,” Encyclopedia 1 (2021):
1132–1154; Manjula Novindarajulu, Philip E. Pfeffer, Hairu Jin, Jehad Abubaker, David D. Douds,
James W. Allen, Heike Bücking, et al., “Nitrogen Transfer in the Arbuscular Mycorrhizal Symbiosis,”
Nature 435 (2005): 819–823; Joanne Leigh, Angela Hodge, and Alastair H. Fitter, “Arbuscular
Mycorrhizal Fungi Can Transfer Substantial Amounts of Nitrogen to Their Host Plant from Organic
Material,” New Phytologist 181, no. 1 (2009): 199–207; Sally E. Smith, Iver Jakobsen, Mette
Grønlund, and F. Andrew Smith, “Roles of Arbuscular Mycorrhizas in Plant Phosphorus Nutrition:
Interactions between Pathways of Phosphorus Uptake in Arbuscular Mycorrhizal Roots Have
Important Implications for Understanding and Manipulating Plant Phosphorus Acquisition,” Plant
Physiology 156, no. 3 (2011): 1050–1057; Kevin Garcia and Sabine D. Zimmermann, “The Role of
Mycorrhizal Associations in Plant Potassium Nutrition,” Frontiers in Plant Science 5 (2014): 337.
7. Ruairidh J. H. Sawers, M. Rosario Ramírez-Flores, Víctor Olalde-Portugal, and Uta
Paszkowski, “The Impact of Domestication and Crop Improvement on Arbuscular Mycorrhizal
Symbiosis in Cereals: Insights from Genetics and Genomics,” New Phytologist 220, no. 4 (2018):
1135–1140; Jeremiah A. Henning, Evan Weiher, Yali D. Lee, Deborah Freund, Artur Stefanski, and
Stephen P. Bentivenga, “Mycorrhizal Fungal Spore Community Structure in a Manipulated Prairie,”
Restoration Ecology 26 (2018): 124–133.
8. Laura A. Bolte, Arnau V. Vila, Floris Imhann, Valerie Collij, Ranko Gacesa, Vera Peters, Cisca
Wijmenga, et al., “Long-Term Dietary Patterns Are Associated with Pro-Inflammatory and Anti-
Inflammatory Features of the Gut Microbiome,” Gut 70, no. 7 (2021): 1287–1298; Bernard Srour,
Melissa C. Kordahi, Erica Bonazzi, Mélanie Deschasaux-Tanguy, Mathilde Touvier, and Benoit
Chassaing, “Ultra-Processed Foods and Human Health: From Epidemiological Evidence to
Mechanistic Insights,” Lancet Gastroenterology and Hepatology 7 (2022): 1128–1140. The explicit
effect of a fast-food diet on the gut fungi is inferred from studies on mice (see chapter 5): Tahliyah S.
Mims, Qusai Abdallah, Justin D. Stewart, Sydney P. Watts, Catrina T. White, Thomas V. Rousselle,
Ankush Gosain, et al., “The Gut Mycobiome of Healthy Mice Is Shaped by the Environment and
Correlates with Metabolic Outcomes in Response to Diet,” Communications Biology 4, no. 1 (2021):
281; Jata Shankar, “Food Habit Associated Mycobiota Composition and Their Impact on Human
Health,” Frontiers in Nutrition 8 (2021): 773577.
9. Karin Hage-Ahmed, Kathrin Rosner, and Siegred Steinkellner, “Arbuscular Mycorrhizal Fungi
and Their Response to Pesticides,” Pest Management 75, no. 3 (2019): 583–590; Anna Edlinger,
Gina Garland, Kyle Hartman, Samiran Banerjee, Florine Degrune, Pablo García-Palacios, Sara
Hallin, et al., “Agricultural Management and Pesticide Use Reduce the Functioning of Beneficial
Plant Symbionts,” Nature Ecology and Evolution 6 (2022): 1145–1154; Gavin Duley and Emanuele
Boselli, “Mutual Plant-Fungi Symbiosis Compromised by Fungicide Use,” Communications Biology
5 (2022): 1069.
10. Megan H. Ryan and James Graham, “Little Evidence That Farmers Should Consider
Abundance or Diversity of Arbuscular Mycorrhizal Fungi When Managing Crops,” New Phytologist
220, no. 4 (2018): 1092–1107; Matthias C. Rillig, Carlos A. Aguilar-Trigueros, Tessa Camenzind,
Timothy R. Cavagnaro, Florine Degrune, Pierre Hohmann, Daniel R. Lammel, et al., “Why Farmers
Should Manage the Arbuscular Mycorrhizal Symbiosis,” New Phytologist 222, no. 3 (2019): 1171–
1175.
 11. Zahangir Kabir, “Tillage or No-Tillage: Impact on Mycorrhizae,” Canadian Journal of Plant
Science 85, no. 1 (2015): 23–29; Xingli Lu, Xingneng Lu, and Yuncheng Liao, “Effect of Tillage
Treatment on the Diversity of Soil Arbuscular Mycorrhizal Fungal and Soil Aggregate-Associated
Carbon Content,” Frontiers in Microbiology 9 (2018): 2986; Chen Zhu, Ning Ling, Junjie Guo, Min
Wang, Shiwei Guo, and Qirong Shen, “Impacts of Fertilization Regimes on Arbuscular Mycorrhizal
Fungal (AMF) Community Composition Were Correlated with Organic Matter Composition in Maize
Rhizosphere Soil,” Frontiers in Microbiology 7 (2016): 1840.
12. Inês Rocha, Isabel Duarte, Ying Ma, Pablo Souza-Alonso, Aleš Látr, Miroslav Vosátka, Helena
Freitas, et al., “Seed Coating with Arbuscular Mycorrhizal Fungi for Improved Field Production of
Chickpea,” Agronomy 9 (2019): 471.
13. M. Eric Benbow, Philip S. Barton, Michael D. Ulyshen, James C. Beasley, Travis L. DeVault,
Michael S. Strickland, Jeffery K. Tomberlin, et al., “Necrobiome Framework for Bridging
Decomposition Ecology of Autotrophically and Heterotrophically Derived Organic Matter,”
Ecological Monographs 89, no. 1 (2019): e01331; Peter G. Kennedy and François Maillard,
“Knowns and Unknowns of the Soil Fungal Necrobiome,” Trends in Microbiology 31, no. 2 (2023):
173–180.
14. J. J. C. Sidrim, R. E. Moreira Filho, R. A. Cordeiro, M. F. G. Rocha, E. P. Caetano, A. J.
Monteiro, and R. S. N. Brilhante, “Fungal Microbiota Dynamics as a Postmortem Investigation Tool:
Focus on Aspergillus, Penicillium and Candida Species,” Journal of Applied Microbiology 108
(2010): 1751–1756; Xiaoliang Fu, Juanjuan Guo, Dmitrijs Finkelbergs, Jing He, Lagabaiyila Zha,
Yadong Guo, and Jifeng Cai, “Fungal Succession during Mammalian Cadaver Decomposition and
Potential Forensic Implications,” Scientific Reports 9 (2019): 12907.
15. Zohreh Shariatinia, “Heidegger’s Ideas about Death,” Pacific Science Review B: Humanities
and Social Sciences 1, no. 2 (2015): 92–97. This short paper by an Iranian scholar covers the
essentials of Heidegger’s thinking on death without a hint of philosophical jargon.
16. Katie Rogers, “Mushroom Suits, Biodegradable Urns and Death’s Green Frontier,” New York
Times, April 22, 2016.
17. Piratical metaphors are very helpful for explaining biological facts: Nicholas P. Money and
Mark W. F. Fischer, “What Is the Weight of a Single Amoeba and Why Does It Matter?,” American
Biology Teacher 83, no. 9 (2021): 571–574.
18. Thomas Terberger, Mikhail Zhilin, and Svetlana Savchenko, “The Shigir Idol in the Context of
Early Art in Eurasia,” Quaternary International 573 (2021): 1–3.
19. Joëlle Dupont, Claire Jacquet, Bruno Dennetière, Sandrine Lacoste, Faisl Bousta, Geneviève
Orial, Corinne Cruaud, et al., “Invasion of the French Paleolithic Painted Cave of Lascaux by
Members of the Fusarium solani Species Complex,” Mycologia 99, no. 4 (2007): 526–533.
20. Pedro Martin-Sanchez, Alena Novakova, Fabiola Bastian, Claude Alabouvette, and Cesareo
Saiz-Jimenez, “Two New Species of the Genus Ochroconis, O. lascauxensis and O. anomala Isolated
from Black Stains in Lascaux Cave, France,” Fungal Biology 116 (2012): 574–589.
21. Laura Zucconi, Fabiana Canini, Daniela Isola, and Giulia Caneva, “Fungi Affecting Wall
Paintings of Historical Value: A Worldwide Meta-Analysis of Their Detected Diversity,” Applied
Sciences 12 (2022): 2988.
22. Nahid Akhtar and M. Amin-Ul Mannan, “Mycoremediation: Expunging Environmental
Pollutants,” Biotechnology Reports (Amsterdam) 26 (2020): e00452; A. Arun and M. Eyini,
“Comparative Studies on Lignin and Polycyclic Aromatic Hydrocarbons Degradation by
Basidiomycetes Fungi,” Bioresource Technology 102, no. 17 (2011): 8063–8070.
 23. Roc Tkavc, Vera Y. Matrosova, Olga E. Grichenko, Cene Gostinčar, Robert P. Volpe, Polina
Klimenkova, Elena K. Gaidamakova, et al., “Prospects for Fungal Bioremediation of Acidic
Radioactive Waste Sites: Characterization and Genome Sequence of Rhodotorula taiwanensis
MD1149,” Frontiers in Microbiology 8 (2018): 2528. The fungus in this study is a yeast rather than a
filamentous fungus, which is unusually tolerant to gamma radiation.
24. Anna Lowenhaupt Tsing, The Mushroom at the End of the World: On the Possibility of Life in
Capitalist Ruins (Princeton, NJ: Princeton University Press, 2015); Alison Pouliot, The Allure of the
Fungi (Clayton South, Australia: CSIRO Publishing, 2018).
25. A. Johnson, “Blackfoot Indian Utilization of the Flora of the Northwestern Great Plains,”
Economic Botany 24 (1970): 301–324; William R. Burk, “Puffball Usages among North American
Indians,” Journal of Ethnobiology 3 (1983): 55–62.
26. The study of the fungi began in 1729 with the publication of Micheli’s Nova Plantarum
Genera (see chapter 7, note 32). Corrado Nai and Vera Meyer, “The Beauty and the Morbid: Fungi as
Source of Inspiration in Contemporary Art,” Fungal Biology and Biotechnology 3 (2016): 10; Regine
Rapp, “On Mycohuman Performances: Fungi in Current Artistic Research,” Fungal Biology and
Biotechnology 6 (2019): 22.
27. Ofer Grunwald, Ety Harish, and Nir Osherov, “Development of Novel Forms of Fungal Art
Using Aspergillus nidulans,” Journal of Fungi 7, no. 12 (2021): 1018.
28. Emily Farra, “You Aren’t Tripping: Fungi Are Taking Over Fashion,” Vogue, April 2, 2021.
29. Patricia Kaishian and Hasmik Djoulakian, “The Science Underground: Mycology as a Queer
Discipline,” Catalyst: Feminism, Theory, Technoscience 6, no. 2 (2020): 1–26.
30. Nicholas P. Money, “Obituary: Cecil Terence Ingold (1905–2010),” Nature 465 (2010): 1025.
31. Martin Grube, Ester Gaya, Håvard Kauserud, Adrian M. Smith, Simon Avery, Sara J. Fernstad,
Lucia Muggia, et al., “The Next Generation Fungal Diversity Researcher,” Fungal Biology Reviews
31, no. 3 (2017): 124–130.
32. Nicholas P. Money, “Hyphal and Mycelial Consciousness: The Concept of the Fungal Mind,”
Fungal Biology 125, no. 4 (2021): 257–259; Kristin Aleklett and Lynne Boddy, “Fungal Behaviour:
A New Frontier in Behavioural Ecology,” Trends in Ecology and Evolution 36, no. 9 (2021): 787–
796. Each cubic centimeter or milliliter of brain tissue contains sixty-eight million neurons, which is
similar to the maximum number of hyphae that can be packed into the same volume of soil.
33. Mohammad Mahdi Dehshibi and Andrew Adamatzky, “Electrical Activity of Fungi: Spikes
Detection and Complexity Analysis,” Biosystems 203 (2021): 104373; Andrew Adamatzky,
“Language of Fungi Derived from Their Electrical Spiking Activity,” Royal Society Open Science 9,
no. 4 (2022): 211926.
34. Rhawn G. Joseph, Richard Armstrong, Xinli Wei, Carl Gibson, Olivier Planchon, David
Duvall, Ashraf M. T. Elewa, et al., “Fungi on Mars? Evidence of Growth and Behavior from
Sequential Images,” Journal of Cosmology 29, no. 4 (2021): 480–550.
35. DNA profiles from human blood samples can be recovered after they are burned and reach a
temperature of 1,000 degrees Celsius: A. Klein, O. Krebs, A. Gehl, J. Morgner, L. Reeger, C.
Augustin, and C. Edler, “Detection of Blood and DNA Traces after Thermal Exposure,” International
Journal of Legal Medicine 132, no. 4 (2018): 1025–1033.
36. Gerald R. Taylor, Mary R. Henney, and Walter L. Ellis, “Changes in the Fungal Autoflora of
Apollo Astronauts,” Applied Microbiology 26, no. 5 (1973): 804–813.
37. Adriana Blachowicz, Snehit Mhatre, Nitin K. Singh, Jason M. Wood, Ceth W. Parker, Cynthia
Ly, Daniel Butler, et al., “The Isolation and Characterization of Rare Mycobiome Associated with
Spacecraft Assembly Cleanrooms,” Frontiers in Microbiology 13 (2022): 777133.
 38. Aleksandra Checinska, Alexander J. Probst, Parag Vaishampayan, James R. White, Deepika
Kumar, Victor G. Stepanov, George E. Fox, et al., “Microbiomes of the Dust Particles Collected from
the International Space Station and Spacecraft Assembly Facilities,” Microbiome 3 (2015): 50.
39. Takashi Sugita, Takashi Yamazaki, Otomi Cho, Satoshi Furukawa, and Chiaki Mukai, “The
Skin Mycobiome of an Astronaut during a 1-Year Stay on the International Space Station,” Medical
Mycology 59, no. 1 (2021): 106–109.
40. Donatella Tesei, Anna Jewczynko, Anne M. Lynch, and Camilla Urbaniak, “Understanding the
Complexities and Changes in the Astronaut Microbiome for Successful Long-Duration Space
Missions,” Life 12 (2022): 495.

APPENDIX
1. Jie Tang, Iliyan D. Iliev, Jordan Brown, David M. Underhill, and Vincent A. Funari,
“Mycobiome: Approaches to Analysis of Intestinal Fungi,” Journal of Immunological Methods 421
(2015): 112–121; Robert Edgar, “Taxonomy Annotation and Guide Tree Errors in 16S rRNA
Databases,” PeerJ 6 (2018): e5030.
2. Amanda K. Dupuy, Marika S. David, Lu Li, Thomas N. Heider, Jason D. Peterson, Elizabeth A.
Montano, Anna Dongari-Bagtzoglou, et al., “Redefining the Human Oral Mycobiome with Improved
Practices in Amplicon-Based Taxonomy: Discovery of Malassezia as a Prominent Commensal,”
PLoS ONE 9, no. 3 (2014): e90899; Mallory J. Suhr and Heather E. Hallen-Adams, “The Human Gut
Mycobiome: Pitfalls and Potentials—A Mycologist’s Perspective,” Mycologia 107, no. 6 (2015):
1057–1073.
3. Analysis of the fungi found in the sputum of asthma patients in Wandsworth, in south London,
identified some rather unlikely species: Hugo C. van Woerden, Clive Gregory, Richard Brown, Julian
R. Marchesi, Bastiaan Hoogendoorn, and Ian P. Matthews, “Differences in Fungi Present in Induced
Sputum Samples from Asthma Patients and Non-Atopic Controls: A Community Based Case Control
Study,” BMC Infectious Diseases 13 (2013): 69. Hugo Cornelis and his team from the Cardiff
University School of Medicine reported that one of the species that was prevalent in the lungs of
asthma patients and absent in non-asthmatic controls was Termitomyces clypeatus. This fungus
produces a large mushroom that was discovered in the 1920s in a bamboo thicket in the Democratic
Republic of the Congo, then the colony of the Belgian Congo, where it was fruiting from an
abandoned termite mound. The mycelium of this mushroom is farmed by termites, who consume
scraps of wood and plant leaves and defecate onto a spongy “comb” that is colonized by the fungus.
Most of the plant matter eaten by the insects is indigestible, like the fiber in our diet, which is where
the mushroom comes in. By decomposing the fiber, the fungal mycelium becomes enriched with
protein and fat that serves as the perfect food for the termites. The description of this species was not
published until 1951: Roger Heim, “Les Termitomyces du Congo Belge Recueillis par Madame M.
Goossens-Fontana,” Bulletin du Jardin Botanique de l’État Bruxelles 21, no. 3, 4 (1951): 205–222.
Termitomyces clypeatus has a wide geographical distribution and is sold in local markets in
Cameroon and Nigeria as a flavorful mushroom with purported medicinal properties: Oumar
Mahamat, Njouonkou André-Ledoux, Tume Chrisopher, Abamukong Adeline Mbifu, and Kamanyi
Albert, “Assessment of Antimicrobial and Immunomodulatory Activities of Termite Associated
Fungi, Termitomyces clypeatus R. Heim (Lyophyllaceae, Basidiomycota),” Clinical Phytoscience 4
(2018): 28. Wandsworth is a land of many splendors, but termite mounds are scarce. The presence of
this mushroom in the sputum samples alleged by Van Worden was cited uncritically by Laura Tipton,
Elodie Ghedin, and Alison Morris, “The Lung Mycobiome in the Next-Generation Sequencing Era,”
Virulence 8, no. 3 (2017): 334–341, which illustrates how errors can persist in the literature when
investigators have minimal knowledge of the organisms that show up in the DNA analyses. Besides
this African toadstool, the extensive list of species identified from the lungs of asthmatic Londoners
in the Van Worden study included a wood-rotter from forests in the Southern Hemisphere, a fungus
that grows inside eucalyptus trees in South Africa, and, strangest of all, a little mushroom that fruits
beneath the water in cold Argentinian lakes. The wood-decay fungus supposedly found in this study
is Grifola sordulenta; Lasiodiplodia gonubiensis is the South African endophyte; and Gloiocephala
aquatica is the aquatic mushroom. There are many other species listed in this report that are also
unlikely to be floating in the fragrant air of London.
4. Through this encounter I had, inadvertently, changed places with Professor Heinz Wolff (1928–
2017), a well-known British academic, who stopped by my demonstration of sperm release in ferns at
a science fair in Oxford, England, in the late 1970s, and peered into my microscope. I was very
pleased with myself for figuring out how to coerce explosions of swimming spermatozoids from tiny
fern plantlets. Wolff asked me in his German accent why I had bothered to do this, saying, “But vot
experiment hev you performed here?” (Think Peter Sellers as Dr. Strangelove.) It was a good
question. My project was observational and only minimally experimental, and I admitted as much.
He was not impressed and left my table shaking his head at what he appeared to perceive as a brief
conversation with a sixteen-year-old imbecile. My science teacher was more supportive and cursed
Wolff, after he was beyond earshot, with a shocking train of expletives. The prize winners that day
were boys from a private school (ours was the local “comprehensive”) who had developed a nuclear
reactor or something similarly impressive.
5. Nicholas P. Money, “Against the Naming of Fungi,” Fungal Biology 117 (2013): 463–465. In
this publication, I wrote, “For 250 years mycologists have tried to reconcile fungal diversity with the
Linnean fantasy of a divine order throughout nature that included unambiguous species. This effort
has failed and today’s taxonomy rests on an unstable philosophical foundation.” We lack a robust
definition of a fungal species, which has led to treating some populations of fungi that are only
distantly related as members of the same species, and, in other cases, assigning more than one name
to fungi that others regard as single species.
6. Petr Kralik and Matteo PandRicchi, “A Basic Guide to Real Time PCR in Microbial
Diagnostics: Definitions, Parameters, and Everything,” Frontiers in Microbiology 8 (2017): 108; M.
N. Zakaria, M. Furuta, T. Takeshita, Y. Shibata, R. Sundari, N. Eshima, T. Ninomiya, et al., “Oral
Mycobiome in Community-Dwelling Elderly and Its Relation to Oral and General Health
Conditions,” Oral Diseases 23, no. 7 (2017): 973–982.

OceanofPDF.com
 Illustrations

Chapter Small fungal colony or mycelium of branching hyphae. Fungi

1 growing in this form extract nutrients from solid materials
including human tissues. Source: F. Felder, Lumott, LLC.
Chapter Fungi multiplying as budding yeasts. Yeasts grow on the skin
2 surface including the scalp. Source: Kallayanee Naloka /
Shutterstock.
Chapter Spores of the mold Alternaria are among the most common
3 causes of asthma and other allergies. Source: The Mycological
Society of Japan, image from Junji Nishikawa and Chiharu
Nakashima, “Morphological and Molecular Characterization
of the Strawberry Black Leaf Spot Pathogen Referred to as the
Strawberry Pathotype of Alternaria alternata,” Mycoscience
60, no. 1 (2019): 1–9.
Chapter Stalks of the fungus Rhizopus tipped with sporangia
4 containing airborne spores. Rhizopus grows on rotting fruit
and can also cause lethal brain infections. Source: Christos
Georghiou / Shutterstock.
Chapter The digestive system is colonized with fungi from mouth to
5 anus. Source: Shutterstock.
Chapter Spores of the fungus Fusarium that is used to produce
6 mycoprotein. Source: Kallayanee Naloka / Shutterstock.
Chapter Beautiful fruit bodies of bird’s nest fungi that are the source of
7 antibiotics called cyathanes. ©2013 Insil Choi.
Chapter Small fungal colony or mycelium of branching hyphae. Fungi
1 growing in this form extract nutrients from solid materials
including human tissues. Source: F. Felder, Lumott, LLC.
Chapter St. Anthony of Egypt, whose relics became associated with the
8 miraculous cure of ergotism in the Middle Ages. The victim of
ergotism in this sixteenth-century woodcut is suffering from
the ignis sacer or holy fire, which was a burning sensation in
the extremities caused by vasoconstriction, and has lost one of
his legs below the knee to gangrene. Source: World History
Archive / Alamy Stock Photo.
Chapter Fruit bodies of a species of Psilocybe with hallucinogenic
9 properties. ©2022 Insil Choi.
Chapter Mycorrhizal symbiosis between the roots of a tree and the
10 mycelia of mushrooms that are fruiting at the surface of the
soil. ©2022 Insil Choi.

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 Index

Allegro, John, 153–154, 216–217n39

allergic rhinitis, 43–45, 51
allergy, 42–43, 47–53
alpha amanitin, 129–131
ALS (amyotrophic lateral sclerosis), 71
Altounyan, Roger, 50–51
Alzheimer’s disease, 69–70, 115
Amanita muscaria (fly agaric), 4, 151–154
Amanita phalloides (death cap), 126–132, 134–135
Anna Karenina principle, 25, 183n7
antibiotics, 121, 123–124
antifungal agents, 34–37, 58
Apollo missions, 41, 171–173
art, 152–154, 167–168; spoilage of, 165–166
aspergillosis, 27, 53–55
Aspergillus, 28, 94, 103–104, 107, 121–122, 139, 167, 184n12
asthma, 2, 40–52
athlete’s foot, 37–39
Aubrey, John, 26–27

bacterial interactions, 73–89, 163–164

beta glucans, 115–117
birch conk or polypore, 110–111, 123
bird’s nest fungi, 123–124, 207n32
Blackley, Charles, 44
blastomycosis, 55
blood-brain barrier, 59–60, 66
brain mycobiome, 69–72
brewing, 95–96
Buller, A. H. R., 188n1, 192n32

calories in mushrooms, 108–109, 203n30

cancer, 82–83
Candida, 179n2; Candida albicans, 5, 85–86, 177, 180–181n11; Candida auris, 35–37, 64
cephalosporin, 121
cheese, 93–100
Cladophialophora, 195n17
Claviceps (ergot fungus), 135–136
coccidioidomycosis, 55
consciousness of fungi, 170–171
contact lens keratitis, 187n39
coughing, 53
COVID-19, 54, 68–69, 81
Cryptococcus, 65–66
cyclosporin, 12, 121, 130

dandruff, 32–35; treatments, 34

death cap. See Amanita phalloides
deaths from fungal infections (statistics), 10, 61
diabetes, 87
diet, 75–79, 93–109; optimization of, 87–89
DNA analysis, 74–75, 175–178
dry-cured meats, 100–101
dysbiosis, 25–26, 86–87, 162–163

economic value of fungi, 107

edible mushrooms, 108–109, 127–128
ergotism, 135–137
evolutionary medicine, 47–48
Exserohilum, 69
extraterrestrial mycology, 159–160, 171–173
Ezekiel, 143, 153

fashionable fungi, 167–168

Floyer, John, 41–42
fly agaric. See Amanita muscaria
fungal cells, numbers of, 8–9, 23–24, 75, 180n10, 183n3
fungal infections, deaths from, 10, 61
fungi, economic value of, 107
Fusarium, 70–71, 105–107, 187n39

Galerina, 131
genome mining, 122
geography and the mycobiome, 75–77
Gyromitra (false morel), 128

hákarl, 101–102, 104

hay fever. See allergic rhinitis
herbalism, 120–121
histoplasmosis, 55
HIV/AIDS, 54, 56, 60–62, 65, 66
HPV (human papilloma virus) vaccine, 123
Huxley, Aldous, 155–156
hygiene hypothesis, 48
hypersensitivity pneumonitis, 51–52
hyphae (definition), 4; growth mechanisms, 17, 27, 28, 32, 81, 161, 163, 167; sensitivity, 170–171

IBD (inflammatory bowel disease), 79–82

IBS (irritable bowel syndrome), 81–82
indoor molds, 48–49, 140
Ingold, C. T., 169
insulin, 122–123

lentinan, 117
lion’s mane, 114–115, 127, 204n9, 208n4
lovastatin, 121–122

Madura foot. See mycetoma

magic mushrooms, 142–158; and Christianity, 153–155; legalization of, 147–148
Malassezia, 25, 32–35, 77
McKenna, Terence, 149
McIlvaine, Charles, 133–134
meconium, 13
medicinal mushrooms, 112–124
Mucor, 25, 67, 78, 98, 103
mucormycosis, 66–69
multiple sclerosis, 87
mushroom poisoning, 125–135
mushrooms, calories in, 108–109, 203n30
mycetoma, 38
mycobiome (definition), 3, 5–6
mycophobia, 168
mycorrhizas, 161–163
mycotoxins, 137–141
mycozoans, 179n1

necromycobiome, 163–165
numbers of fungal cells, 9, 23–24, 75, 180n10, 183n3

obesity, 77–79
onychomycosis, 39
Ophiocordyceps, 151
opportunists, 61–69
oral fungi, 83–85
Ötzi, 110–112
Owen, Richard, 27

parasites, 111–112
Parkinson’s disease, 71, 115
Penicillium, 76, 94–98, 100–101, 103–104, 121, 124, 130, 200n1
Pneumocystis, 56
Proust, Marcel, 46
PSC (primary sclerosing cholangitis), 87
psilocybin (and psilocin), 143–151
psoriasis, 25

queer mycology, 168–169

Quorn, 105–107, 108

Ramaria (coral fungus), 132–133

Remak, Robert, 27–28
Rhizopus, 67
ringworm, 26–32; treatments, 29–32

Saccharomyces cerevisiae, 4, 63, 75–76, 81–82, 94–95, 194n14, 197–198n11

Scedosporium, 58–60
seborrheic dermatitis, 32–33
sensitive skin syndrome, 25
sneezing, 53
soy sauce, 103
spoilage of art, 165–166
spore concentrations (airborne), 42, 52, 190–191n22
Sporothrix, 38
sporotrichosis, 38
Steavenson, William, 44, 189n8
surströmming, 102, 104, 202n20

tempeh, 103–104
thunderstorm asthma, 45
tinea capitis, 28–32
traditional Chinese medicine, 119–121
Trichophyton, 38–39, 185n15

vaginal fungi, 85–86

Wasson, Gordon, 149, 153–154

white blood cells, 7–8
World Health Organization (WHO), 10, 16, 66

yeasts. See Candida; Saccharomyces cerevisiae

yellow knight mushrooms, 131–132
yogurt, 96

zoonoses, 31–32

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