Vaccines: What Everyone Needs To

Know Kristen A. Feemster

Visit to download the full and correct content document:
https://textbookfull.com/product/vaccines-what-everyone-needs-to-know-kristen-a-fee
mster/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Brazil : what everyone needs to know 1st Edition Roett

https://textbookfull.com/product/brazil-what-everyone-needs-to-
know-1st-edition-roett/

Drones : what everyone needs to know 1st Edition Kreps

https://textbookfull.com/product/drones-what-everyone-needs-to-
know-1st-edition-kreps/

The Arctic: What Everyone Needs to Know Klaus Dodds

https://textbookfull.com/product/the-arctic-what-everyone-needs-
to-know-klaus-dodds/

Antarctica: What Everyone Needs to Know® David Day

https://textbookfull.com/product/antarctica-what-everyone-needs-
to-know-david-day/
The Pornography Industry: What Everyone Needs to Know
Shira Tarrant

https://textbookfull.com/product/the-pornography-industry-what-
everyone-needs-to-know-shira-tarrant/

Iran : what everyone needs to know 1st Edition Michael

Axworthy

https://textbookfull.com/product/iran-what-everyone-needs-to-
know-1st-edition-michael-axworthy/

Advertising : what everyone needs to know 1st Edition

Mara Einstein

https://textbookfull.com/product/advertising-what-everyone-needs-
to-know-1st-edition-mara-einstein/

Civil Resistance: What Everyone Needs To Know® Erica

Chenoweth

https://textbookfull.com/product/civil-resistance-what-everyone-
needs-to-know-erica-chenoweth/

Inequality: What Everyone Needs to Know 1st Edition

James K. Galbraith

https://textbookfull.com/product/inequality-what-everyone-needs-
to-know-1st-edition-james-k-galbraith/
 VACCINES
WHAT EVERYONE NEEDS TO KNOW®
 VACCINES
WHAT EVERYONE NEEDS TO KNOW®

KRISTEN A. FEEMSTER

1
 3
Oxford University Press is a department of the University of Oxford. It furthers
the University’s objective of excellence in research, scholarship, and education
by publishing worldwide. Oxford is a registered trade mark of Oxford University
Press in the UK and certain other countries.
“What Everyone Needs to Know” is a registered trademark
of Oxford University Press.
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America.
© Oxford University Press 2018
All rights reserved. No part of this publication may be reproduced, stored in
a retrieval system, or transmitted, in any form or by any means, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by license, or under terms agreed with the appropriate reproduction rights
organization. Inquiries concerning reproduction outside the scope of the above should
be sent to the Rights Department, Oxford University Press, at the address above.
You must not circulate this work in any other form
and you must impose this same condition on any acquirer.
Library of Congress Cataloging-in-Publication
Data Names: Feemster, Kristen A., author.
Title: Vaccines : what everyone needs to know / Kristen A. Feemster.
Description: New York, NY : Oxford University Press, [2017] |
Includes bibliographical references and index.
Identifiers: LCCN 2017033339| ISBN 9780190277901
(hardcover : alk. paper) | ISBN 9780190277918 (paperback : alk. paper)
Subjects: LCSH: Vaccination—Popular works. |
Vaccination—History. | Vaccines.
Classification: LCC RA638 .F44 2017 |
DDC 614.4/7—dc23
LC record available at https://lccn.loc.gov/2017033339
This material is not intended to be, and should not be considered, a substitute for
medical or other professional advice. Treatment for the conditions described in this
material is highly dependent on the individual circumstances. And, while this material
is designed to offer accurate information with respect to the subject matter covered
and to be current as of the time it was written, research and knowledge about medical
and health issues is constantly evolving and dose schedules for medications are being
revised continually, with new side effects recognized and accounted for regularly.
Readers must therefore always check the product information and clinical procedures
with the most up-to-date published product information and data sheets provided by
the manufacturers and the most recent codes of conduct and safety regulation. The
publisher and the authors make no representations or warranties to readers, express
or implied, as to the accuracy or completeness of this material. Without limiting the
foregoing, the publisher and the authors make no representations or warranties as to
the accuracy or efficacy of the drug dosages mentioned in the material. The authors
and the publisher do not accept, and expressly disclaim, any responsibility for any
liability, loss or risk that may be claimed or incurred as a consequence of the use and/
or application of any of the contents of this material.
1 3 5 7 9 8 6 4 2
Paperback printed by LSC Communications, United States of America
Hardback printed by Bridgeport National Bindery, Inc., United States of America
With love to James and our sunshines, TE and FM.
In memoriam to Mom, my greatest superhero.
 CONTENTS

ACKNOWLEDGMENTS xv
ABBREVIATIONS xvii
INTRODUCTION xix

1. What Is a Vaccine and How Do Vaccines Work? 1

What is an antigen? 2
What happens when the immune system is confronted by an antigen? 2
How do cells signal each other in the process of creating antibodies? 3
Which is better, natural immunity or immunity after vaccination? 3
What is the real risk of vaccine-​preventable diseases? 4
What is herd immunity? 5
What happens when immunization rates are not high enough to
achieve herd immunity? 6
How large are most outbreaks? 6
What is the difference between immunization and vaccination? 7
What are the different types of vaccines? 7
Why are there so many types of vaccines? 9
Why do most vaccines require more than one dose? 10
Besides antigens, what else are vaccines made of? 10
Even if these substances are necessary, are they safe? 12
viii Contents

What about thimerosal and autism? 13

Why was thimerosal removed from vaccines in 2001? 13
Do some vaccines contain animal products? 14
Do vaccines use cells from aborted fetuses? 15

2. A Brief History of Vaccines 17

When was the first vaccination delivered in the United States? 17

What is inoculation? 18
Why the controversy? 19
How did we get from inoculation to vaccination? 19
When did smallpox vaccine come to the United States? 20
How well did this early vaccine really work? 21
What was the public response to the new vaccine? 21
How did the public health community make early vaccines safer? 24
What were some of the key developments in vaccine science during
this time? 25
How did vaccine development begin to take off? 25
What were some other important developments for making vaccines? 26
What was the impact of vaccine introduction on disease incidence? 28
What about vaccine introduction in other countries? 28

3. Vaccine Development 31

What factors influence which vaccines get developed? 32

Once a decision to proceed with vaccine development is made, what
are the steps needed to bring a vaccine from an idea to production? 34
What is required for clinical studies? 35
Is there a similar process in other countries? 37
Are there protections for people who participate in clinical trials? 38
How many people are involved in vaccine trials? 39
What happens after clinical development is complete? 40
 Contents ix

What evidence do vaccine developers search for during

development to show that a vaccine works? 41
How long does this whole process take—​from the first exploratory
study to licensure of a new vaccine? 41
Is a vaccine ever approved or used without following these steps? 42
Who is involved in all of these steps from conceptualization
to development? 43
How many vaccine manufacturers are there? 45
What actually happens in vaccine manufacturing? 46
What quality controls govern vaccine manufacturing? 47
Who pays for vaccine development? 48
How much does vaccine development cost? 49
How do manufacturers know how much vaccine to make? 49
Are there vaccine supply shortages? 50
What happens when there are vaccine shortages? 50

4. Vaccine Financing and Distribution 51

How are vaccines distributed once they are licensed? 51

Are there other vaccines used in some places but not others? 52
How much do vaccines actually cost for immunization programs? 53
How large is the vaccine market? 54
Who decides which vaccine should be distributed? 54
What is the National Vaccine Advisory Committee? 56
How does the National Vaccine Advisory Committee impact
vaccine policy? 57
What is the National Vaccine Plan? 57
What are the Decade of Vaccines and the Global Vaccine Action Plan? 58
Once a vaccine is added to an immunization program, how does it
get to the people who need it? 59
What is required to be able to deliver vaccines in a clinic or
community setting? 60
x Contents

How are vaccines purchased by health care facilities? 61

How are vaccines purchased through public insurance? 61
How do people without insurance or who do not qualify for publicly
funded programs access vaccines? 63
Who purchases most of the vaccines in the United States? 63
Who sets priorities for vaccine distribution in non-​US countries? 64
What is the Expanded Program on Immunization? 64
How does the World Health Organization support other countries? 65
How does vaccine financing happen in non-​US countries, including
low-​to middle-​income countries? 66
How are vaccines made more accessible to lower income countries? 66

5. Vaccine Safety 69

What is a vaccine adverse event? 69

How can one determine whether an adverse event is really caused
by a vaccine? 70
How is safety monitored after a vaccine is licensed? 71
Who can report to VAERS? 72
How often are reports submitted to VAERS? 73
What happens when VAERS finds a signal? 73
What are active surveillance networks? 74
What is the difference between the information provided by VAERS
and that provided by these other active surveillance networks? 75
What kind of reactions can occur after vaccination? 75
How often do adverse events really occur? 77
Is Guillain–​Barré syndrome associated with vaccines? 78
What are contraindications to vaccination? 79
What are precautions? 79
Can a person be vaccinated if he or she is on an antibiotic? 80
If a person is immunocompromised because of chemotherapy or an
organ transplant, can he or she receive any vaccines? 80
 Contents xi

If a person was vaccinated before starting chemotherapy, will the

effect of the vaccine last? 81
Should pregnant women receive vaccines? 81
Do live attenuated (weakened virus or bacteria) vaccines ever cause
problems in healthy individuals? 82
What happens when a vaccine-​associated adverse event occurs? 83
What is the National Vaccine Injury Compensation Program? 83
Which vaccines are covered by NVICP? 84
How does NVICP work? 85
How does one qualify for compensation within NVICP? 85
What is the NVICP vaccine injury table and what is in it? 86
Who is responsible for updating the NVICP injury table? 87
Who serves on the ACCV? 88
How many individuals have received compensation from NVICP? 88
Has NVICP compensated any autism claims? 90
How is information about vaccine safety from NVICP communicated? 91
If NVICP depends on published evidence to develop the vaccine
injury table and adjudicate cases, how does one evaluate the
reliability and validity of a study? 92
Who evaluates the reliability of vaccine safety studies? 92
What is the National Academy of Medicine? 93

6. The Vaccine Schedule 95

Who makes the immunization schedule? 95

What is ACIP? 96
When was ACIP first established? 96
How are ACIP members selected? 98
What criteria are used to select members for ACIP? 99
Are members of ACIP paid? 99
How does ACIP make decisions about the immunization schedule? 99
What kind of evidence does ACIP use? 101
xii Contents

How long does it take for ACIP to develop recommendations? 101

What happens after a recommendation is made? 101
How are ACIP recommendations actually implemented? 102
Do states have their own vaccine advisory committees? 102
Why is there only one recommended schedule? 102
What is wrong with following a different schedule, such as
spreading out vaccines, rather than following the recommended
vaccine schedule? 103
Do the number and combinations of vaccines given in the
recommended schedule overwhelm the immune system? 104
How do we know the recommended schedule is safe? 104
How do immunization programs keep track of who needs what? 105

7. Laws and Standard Practices

for Vaccine Administration 107

What is vaccine policy? 107

What are the historical and legal precedents for mandatory vaccination? 108
What are the basic arguments that support immunization requirements? 110
What are the basic arguments against immunization requirements? 110
What kinds of vaccine requirements are employed in the United States? 111
What are the benefits of school-​entry requirements? 112
How does one opt out of school-​entry requirements? 113
What impact do exemption policies have on immunization rates? 115
Have exemption laws changed over time? 116
What has happened with vaccine-​exemption legislation since the
2015 measles outbreak? 116
What are other types of mandatory immunization policies? 117
Do any other settings require immunizations? 118
What other policy strategies are used to increase immunization rates? 119
Are there other countries that have mandatory immunization policies? 119
 Contents xiii

Are there ways to prevent the transmission of vaccine-​preventable

diseases other than vaccination? 120
What do health care providers do if patients or families refuse
a vaccine? 120
Are health care providers liable for vaccine refusal in any way? 121
Can health care providers ask a patient or family to leave the
practice if they refuse vaccines? 121
Why would different providers have different immunization policies,
especially if there is one routine recommended schedule? 122
Are individuals who choose not to vaccinate themselves or their
children ever held responsible for exposing other people to
vaccine-​preventable diseases? 123

8. Vaccine Hesitancy 125

What is vaccine hesitancy? 126

What is meant by the “vaccine confidence gap”? 127
How does vaccine hesitancy manifest? 127
What is the difference between vaccine hesitancy and the anti-​
vaccine movement? 128
Why is it important to define vaccine hesitancy as a spectrum of beliefs? 129
How common is vaccine hesitancy? 129
How is vaccine hesitancy measured? 129
Which individuals may be more or less likely to be vaccine hesitant? 130
Are health care providers ever vaccine hesitant? 131
What are the implications of vaccine hesitancy? 131
What are the practical and economic costs associated with disease
outbreaks that result from vaccine hesitancy? 132
How can vaccine hesitancy be addressed? 133
Where do people get information about vaccines? 134
What are the most reliable sources of information related to vaccines? 135
How can one evaluate the reliability of information? 136
xiv Contents

9. On the Horizon 139

What new vaccines are under development? 139

Vaccines during pregnancy 140
Why are group B streptococcus and respiratory syncytial virus
vaccines being developed for pregnant women? 140
What are the challenges to developing vaccines for pregnant
women? 141
Vaccines for emerging infectious diseases 141
Will we be ready for the next outbreak or pandemic for emerging
infections such as Ebola and Zika viruses? 141
Will there be a new vaccine for Zika virus? 143
Preparing for the next influenza pandemic 144
What is the difference between an epidemic and a pandemic? 144
How does antigenic drift and shift occur? Why does this not
occur with other viruses or bacteria? 145
Are we getting any closer to an influenza vaccine that does not
have to be changed every year? 146
Human Immunodeficiency Virus Vaccines 147
Are we getting closer to a vaccine to prevent human
immunodeficiency virus? 147
Therapeutic vaccines 148
Are vaccines being developed that can treat rather than prevent
illnesses? 148
Disease elimination and eradication 149
What is an endemic disease? 149
How do we achieve elimination or eradication of infectious diseases? 150
What is the Global Polio Eradication Initiative? 151
Can we expect eradication or near eradication of any other
vaccine-​preventable diseases in the next 20 years? 153

APPENDIX 155
SELECTED BIBLIOGRAPHY 167
INDEX 175
 ACKNOWLEDGMENTS

Thank you: To Karen Smith, for your activation energy and

for helping me find the right voice for this book. To my editor,
CZ, for your patience and enthusiasm for this project. To my
colleagues at the Children’s Hospital of Philadelphia Division
of Infectious Diseases and the Philadelphia Department of
Public Health Immunization Program—​I have learned from
your insights, perspectives, and advocacy. To PolicyLab, for
championing this important topic. To Bardia Nabet, Tunmise
Fawole, and Charlotte Moser for help with figures and the
appendix. To Paul Offit, for your critical feedback and guid-
ance throughout. To my sister, Kara, for cheering me onward.
And, most important, to my family for encouraging me to pur-
sue this opportunity and for all of your support every step of
the way.
 ABBREVIATIONS

AAFP American Academy of Family Physcians

AAP American Academy of Pediatrics
ACCV Advisory Commission on Childhood Vaccines
ACIP Advisory Committee on Immunization Practices
ACOG American College of Obstetricians and Gynecologists
ACP American College of Physicians
BCG Bacilli Calmette-​ Guérin
CDC Centers for Disease Control and Prevention
CEP Coalition for Epidemic Preparedness
CISA Clinical Immunization Safety Assessment
DTaP Diphtheria, Tetanus and acellular Pertussis vaccine
DTP Diphtheria, Tetanus and whole cell Pertussis vaccine
EMA European Medicines Agency
EPI Expanded Program on Immunization
EU European Union
FDA Food and Drug Administration
GAVI Global Alliance for Vaccines and Immunizations
GBS Group B Streptococcus
GBS Guillain–​Barré syndrome
GCP Guideline for Good Clinical Practice
HAV Hepatitis A virus
HHS Health and Human Services
HiB Haemophilus influenza Type B
HIV Human immunodeficiency virus
xviii Abbreviations

HPV Human papillomavirus

ICH International Conference on Harmonisation
IIV Inactivated influenza vaccine
IND Investigational New Drug
IOM Institute of Medicine
IPV Inactivated poliovirus vaccine
IVIG Intravenous immunoglobulin
LAIV Live attenuated influenza vaccine
MCV Meningococcal conjugate vaccine
MMR Measles, Mumps and Rubella vaccine
NAM National Academy of Medicine
NIH National Institutes of Health
NVAC National Vaccine Advisory Committee
NVICP National Vaccine Injury Compensation Program
NVPO National Vaccine Program Office
PATH Program for Appropriate Technology in Health
PCV Pneumococcal conjugate vaccine
PRISM Post-​licensure rapid immunization safety monitoring
QALY Quality-​adjusted life year
RSV Respiratory syncytial virus
SAGE Strategic Advisory Group of Experts
SIRVA Shoulder Injury Resulting from Vaccine Administration
Tdap Tetanus, diphtheria and acellular pertussis vaccine
VAERS Vaccine Adverse Events Reporting System
VFC Vaccines for Children
VSD Vaccine Safety Datalink
VZV Varicella Zoster Vaccine
WHO World Health Organization
 INTRODUCTION

Vaccines represent one of the greatest public health advances

of the past 100 years. Their development has brought about
the global eradication of smallpox as well as large reductions
in poliomyelitis, measles, tetanus, Haemophilus influenzae type
b (Hib—​a leading cause of childhood infections), and many
other infectious diseases.
However, the development and implementation of vaccines
has not followed a linear trajectory: Disparities in the adop-
tion of new vaccines continue to persist, and vaccination rates
in both developed and developing countries are not always
sustained. These disparities may be attributable to short sup-
ply, poor infrastructure, or low prioritization of vaccines in
public health spending. However, another important contrib-
utor to the success of vaccination programs is vaccine accept-
ance, a blanket term referring to the public cooperation with
public vaccination schedules. As the perceived risk of vaccine-​
preventable diseases decreases, concerns about vaccine safety
increase. This has contributed to a rise in vaccine hesitancy in
many communities. Health care providers today spend con-
siderable time and effort educating patients and families on
the importance of immunization.
It has become difficult to identify resources that can ade-
quately answer the public’s questions about the risk and ben-
efits of the ever-​expanding list of vaccines available today. This
xx Introduction

is further complicated by the rapid proliferation and dissemi-

nation of misinformation from sources as varied as social media
and scientifically unsound research articles. Recent outbreaks
throughout the world show that vaccine-​preventable diseases
such as pertussis and measles can occur as vaccine hesitancy
increases and immunization rates decrease. This highlights the
importance of communication and trust between health care
providers, patients, and the community to ensure the success-
ful implementation of immunization programs. Many coun-
tries also continue to face challenges in ensuring reliable access
to vaccines, which can further erode trust in the public health
and medical system.
Vaccines are a public health tool: The decision to vaccinate or
not vaccinate impacts both individuals and the people around
them. Accordingly, it is imperative that we are well-​informed
before making a decision about vaccination. This requires an
understanding of (1) how vaccines work, (2) the diseases that
vaccines prevent, and (3) why vaccines are important for indi-
viduals and society. Vaccines and their role in society represent
a complex interplay between sociopolitical systems, culture,
economics, individual beliefs, and health literacy—​and with
that, they provide a multitude of fronts for the introduction
of conflicting messages or incorrect information. This book
aims to provide an objective, informative tool to communicate
facts about vaccines as well as the challenges to implementing
immunization on a population level.
 1
WHAT IS A VACCINE AND HOW
DO VACCINES WORK?

A vaccine is a substance that is given to a person or animal

to protect it from a particular pathogen—​a bacterium, virus,
or other microorganism that can cause disease. The vaccine
prompts an immune response in the body that produces anti-
bodies, which are proteins that fight specific pathogens. The
goal of giving a vaccine is to prompt the body to create anti-
bodies specific to the particular pathogen, which in turn will
prevent infection or disease; it mimics infection on a small
scale that does not induce actual illness. A similar process does
occur when the body confronts actual pathogens, but vaccines
spare individuals from the dangers of disease.
A vaccine can be made from any one of a variety of sources: a
killed or weakened bacteria or virus, a protein or sugar from
the pathogen, or a synthetic substitute. For a vaccine to do its
job, the following need to happen: (1) The vaccine needs to
stimulate antibody production, and (2) the antibodies need to
have avidity (attraction to the specific pathogen). Antibodies
will not work if they do not bind to the invading pathogen.
Vaccine protection also requires that the body recognize the
pathogen and keep making antibodies when they are needed,
which is called immune memory. When this happens, the vacci-
nated body is ready to produce more of these antibodies right
away, whenever the body is exposed to the bacteria or virus.
2 Vaccines

What is an antigen?
Antigens are proteins on the surface of a pathogen that prompt
the production of antibodies by the immune system. Bacteria
and viruses are both covered in antigens, and during the proc-
ess of natural infection, these antigens are what the body rec-
ognizes. Depending on the pathogen, its antigen coating can
be made up of several proteins or several thousand.
Vaccines, on the other hand, are often made using just a
few antigens from a bacteria or virus. This is because some
antigens are better than others at sparking the immune sys-
tem. This is also because it is important to separate the parts
of a pathogen that cause disease and make one sick from those
that induce an antibody response. The ability to cause disease
is called virulence, whereas the ability to induce a protective
immune response is called immunogenicity.
The number of antigens in vaccines is actually quite small
compared to the number of antigens that confront the immune
system during an actual infection (or just from the environ-
ment on a daily basis). For example, the pathogen that causes
whooping cough contains more than 3,000 antigens; the vac-
cine that is used to protect against whooping cough contains
only 3–​5 different antigens. Our immune systems are stimu-
lated all the time, but all stimulation is not the same.

What happens when the immune system is confronted

by an antigen?
When one’s body encounters an antigen (from either a vac-
cine or a natural exposure), it sparks a cascade of events that
constitute an immune response. This response requires com-
munication between several different types of cells and ends
in the creation of memory cells that are equipped to respond
to future invasions by the same antigen. When antigens are
introduced as part of a vaccine, the steps essentially are as
follows:
 What Is a Vaccine and How Do Vaccines Work? 3

1. Antigen is picked up by an antigen-​presenting cell that

shows the antigen to a type of immune cell called a helper
T cell.
2. Helper T cells activate B cells (these make antibodies) or
killer T cells (needed to attack pathogens such as viruses
that live inside of cells).
3. The activated B cells and killer T cells become memory
immune cells that will reactivate during actual infection
and keep the pathogen from invading.

How do cells signal each other in the process of

creating antibodies?
Immune cells emit signals through the secretion of cytokines.
Cytokines are crucial to our immune response in that they
recruit all the cells we need to attack antigens and create mem-
ory cells. Some cytokines are also responsible for the symp-
toms that are generally associated with infection, such as fever.
This is why we may experience a low fever after vaccination: It
means our immune system is in the process of making mem-
ory cells, and cytokines are being employed as part of the com-
munication between cells that contributes to this process.

Which is better, natural immunity or immunity after vaccination?

In general, natural infection results in a more robust, durable
immune response. This is because an actual infection usu-
ally results in a stronger immune response (not to mention an
actual illness), whereas we may need more than one dose of a
vaccine to achieve full protective immunity. After infection, we
make a greater number and greater diversity of antibodies—​
ones that may recognize different parts of a pathogen (i.e., its
antigens). In the case of some pathogens, such as chickenpox
and measles, infection results in lifelong immunity.
However, this is not the case for all pathogens. For exam-
ple, immunity decreases over time after a pertussis (whooping
4 Vaccines

cough) infection. Children younger than age 2 years who are

infected with a certain family of bacteria are not able to mount
an immune response that makes memory cells, so even after
infection, they have no long-​lasting immunity. If a virus or bac-
teria has multiple strains, infection with one strain may not
provide immunity against other strains.
Some vaccines induce a stronger immune response than
natural infection. One example is the human papillomavirus
(HPV) vaccines, which are made from a purified capsid pro-
tein that induces higher antibody levels than are seen in indi-
viduals who have had actual HPV infection. The same is true
of tetanus vaccines: Those who receive the vaccine have more
antibodies than those who survive infection.
However natural immunity may compare to vaccine immu-
nity for a given disease, it is important to remember that natu-
ral immunity comes with the cost of having to endure a disease
or infection, which depending on the illness can result in dis-
ability or death.

What is the real risk of vaccine-​preventable diseases?

Since the advent of vaccines, the incidence of vaccine-​
preventable diseases has decreased dramatically. The risk of
being exposed to many of these diseases is therefore quite
low, and some diseases (including polio and diphtheria) have
been eliminated from the United States. For other vaccine-​
preventable disease, overall incidence has decreased but cases
still occur because available vaccines do not cover all of the
different types of the bacteria or virus. For example, the bac-
terium Pneumococcus, for which a vaccine has existed since the
1980s, continues to cause tens of thousands of cases of pneu-
monia, bloodstream infections, and meningitis every year.
On the other hand, the incidence of some vaccine-​
preventable diseases has persisted and even increased in
recent years. Pertussis (whooping cough) cases have increased
steadily since the 1980s, with nearly 50,000 cases reported
 What Is a Vaccine and How Do Vaccines Work? 5

in the United States in 2012. Pertussis affects all age groups,

although infants have the highest risk of severe disease and
typically require hospitalization. There are also regular out-
breaks of vaccine-​preventable diseases such as mumps, vari-
cella, measles, and Meningococcus (which causes bloodstream
infections and meningitis) in the United States and interna-
tionally. In places where there is reliable access to a developed
medical system, the risk of death due to infection with any of
these pathogens is low, but severe disease can and does still
occur. The global risk of death due to pertussis among infected
infants is approximately 1 in 100; for measles it is 1 in 1,000;
and for Meningococcus across all age groups, the fatality rate
for infected individuals is 1 in 10.
Thus, the actual risk of contracting a vaccine-​preventable
disease is difficult to project. Outbreaks of vaccine-​preventable
diseases generally occur when there are clusters of susceptible
individuals or people who do not have immunity. When this
happens, there is nothing to stop the virus or bacteria from
moving between people. This is a larger issue for pathogens
that are easily spread from person to person, such as pertus-
sis or measles. Vaccination works by reducing the number of
susceptible individuals, thereby stopping transmission; the
bacteria or virus simply runs out of places to go. This is called
herd immunity.

What is herd immunity?

Vaccines work by protecting the individual who is vaccinated.
A vaccinated individual is less likely to become infected, and
if the individual is not infected, he or she cannot spread the
infection to others. When there are many vaccinated people
in a community, there is nowhere for the bacteria or virus to
go—​the group, or herd, becomes immune. So even if there
are a few individuals who are not vaccinated in the group,
they are protected because there is no one around to expose
them to the infection. This works better for some infections
6 Vaccines

compared to others. Viruses or bacteria that are easily trans-

mitted, including measles and pertussis (whooping cough),
require that almost everyone in a given group be vaccinated
in order to achieve herd immunity. Other infections require
close contact for longer periods of time in order for exposure
to result in infection. In these cases, a lower immunization rate
can achieve herd immunity. In this manner, vaccines have had
greater impact on disease rates than they would if every dis-
ease required uniform vaccination rates.

What happens when immunization rates are not

high enough to achieve herd immunity?
When immunization rates are low, more individuals are sus-
ceptible to infection and are at risk of becoming infected. If
anyone does become infected, the lower the immunization
rate, the more opportunities there will be to spread the infec-
tion to other susceptible individuals in their group. When
several cases such as this cluster together, an outbreak occurs.
Outbreaks grow as long as there are more susceptible people
in a given community to become infected and expose others.
Outbreaks slow and eventually end when enough people are
immune—​either because of infection or because of vaccination.

How large are most outbreaks?

The size of an outbreak depends on the number of suscepti-
ble people, the infectivity (or contagiousness) of the pathogen,
and the severity of disease caused by infection. For example,
if a pathogen causes people to become very sick very quickly,
there may be less opportunity for those individuals to go out
and infect others. However, some pathogens, such as pertussis,
can be transmitted before people even know they are infected,
making these infections more difficult to control once they
have started spreading in a community. This is why vaccines
 What Is a Vaccine and How Do Vaccines Work? 7

are used as a response to outbreaks: They prevent people from

becoming infected in the first place.

What is the difference between immunization and vaccination?

Immunization refers to any exposure that provides immunity,
which means that it encompasses both vaccination and natural
infection. Immunization is often referred to as active or passive.
Active immunization occurs when an individual is exposed to
an antigen and then has an immune response that produces
antibodies. Thus, active immunization can take place through
vaccination or natural infection.
Passive immunization occurs when an individual receives
antibodies from other than a first-​hand immune response. The
most common form of passive immunity is pregnant moth-
ers passing antibodies to their fetuses through the placenta;
this provides immune protection to infants for the first sev-
eral months of their lives. Another form of passive immuni-
zation occurs through medical intervention, particularly for
people with immunodeficiencies that keep them from mak-
ing their own antibodies. In these cases, the immunodeficient
individual may receive a blood product that contains antibod-
ies pooled from other people. In cases of exposures to certain
infections, including rabies, a person may be injected with a set
of rabies-​specific antibodies to provide immediate protection.
These antibodies are short-​lived and do not activate immune
memory cells, so the immunization is considered passive.

What are the different types of vaccines?

A vaccine’s composition influences the type and durability of
the immune response it elicits. In this regard, vaccines are clas-
sified into one of six categories: live attenuated, inactivated (or
killed), protein subunit, polysaccharide, polysaccharide conju-
gate, and recombinant.
8 Vaccines

Live attenuated virus vaccines are made from a virus that is

weakened to the point that it cannot cause disease. As viruses,
they act as parasites that depend on other cells to live. With
live attenuated virus vaccines, a weakened virus enters a cell
and reproduces just enough to induce an immune response but
not enough to infect many other cells and cause illness. Three
different methods are available to weaken viruses for vac-
cines. First, a virus could be grown in nonhuman cells. Viruses
that infect humans grow best in human cells, so using nonhu-
man cells, such as chicken cells, as a growth medium ensures
that the virus then will not reproduce very well in humans.
This method is commonly used for chickenpox, measles, and
mumps vaccines. A second method grows virus at tempera-
tures lower than body temperature, thereby robbing the virus
of its ability to reproduce well at body temperature. The third
method combines elements of nonhuman and human viruses,
retaining human virus components that induce the immune
response while the nonhuman parts of the virus ensure the
virus does not reproduce well enough to cause true infec-
tion and illness. This method is used for one of the rotavirus
vaccines.
Inactivated or killed vaccines are made from a whole virus or
bacteria that has been killed or neutralized through the appli-
cation of a second substance—​usually, a tiny amount of formal-
dehyde. Inactivated or killed viruses are not able to reproduce
and cannot cause infection or disease, but because the body is
still exposed to the whole virus, it is able to mount an immune
response. The hepatitis A, polio, and most influenza vaccines
utilize this method.
Protein subunit vaccines work by isolating the antigens or
proteins on bacteria that are known to be important for induc-
ing a protective immune response. Some protein subunit vac-
cines target antigens known to act as toxins. Diphtheria and
tetanus vaccines, for example, are made by inactivating the
toxins that these bacteria produce, creating inactivated toxins
called toxoids. Pertussis vaccines are made from two to up to
Another random document with
no related content on Scribd:
 C’est une des caractéristiques du génie de Henri Poincaré qu’il
réunit un prodigieux esprit d’invention à un esprit critique
extrêmement aiguisé. Sa critique semble même aller parfois
jusqu’au scepticisme; il contemplait sans tristesse les ruines des
théories. Alors que d’autres constatent avec regret que certaines
idées ne s’accommodent plus aux faits, et commencent par penser
que ceux-ci ont été mal vus ou mal interprétés, Poincaré a plutôt une
tendance contraire, bien qu’elle se soit peut-être atténuée dans les
dernières années. Ainsi un jeune physicien ayant cru jadis pouvoir
s’inscrire contre la célèbre expérience de Rowland, d’après laquelle
une charge électrique en mouvement produit un champ magnétique
conformément à la théorie de Maxwell, cette annonce ne parut pas
étonner Poincaré. Nul n’eut moins que lui la notion statique d’une
science se reposant sur quelques conquêtes définitives, et c’est ce
qui explique que plusieurs se soient crus autorisés à tirer de certains
de ses écrits, où il poussait sa tendance critique presque jusqu’au
paradoxe, des conclusions sur la vanité de la Science contre
lesquelles il dut protester.
Quelques Préfaces des Leçons de Poincaré ont vivement attiré
l’attention. Dans l’Introduction du Livre Électricité et Optique, il
discute ce qu’on doit entendre par «interprétation mécanique d’un
phénomène». Cette interprétation est ramenée d’après lui à la
possibilité de la formation d’un système d’équations de Lagrange
avec un certain nombre de paramètres que
l’expérience atteint directement et permet de mesurer. Dans ces
équations figurent l’énergie cinétique et une fonction des forces
. Cette possibilité étant supposée, on pourra toujours déterminer
masses (masses visibles ou cachées) et leurs coordonnées (
) fonctions des (en prenant assez grand), de manière
que la force vive de ce système de masses soit égale à l’énergie
cinétique figurant dans les équations de Lagrange.
L’indétermination est ici très grande, et c’est précisément là qu’en
veut venir Poincaré, dont la conclusion est que, s’il y a une
explication mécanique, il y en a une infinité. Il faut avouer, dirons-
nous, que cette indétermination est même trop grande, car on perd
complètement de vue les corps en présence. Ainsi, suivant les
formes qu’auront l’ensemble des masses partiellement
indéterminées , on n’aura pas nécessairement dans la suite les
mêmes mouvements; il pourra, par exemple, y avoir ou non des
chocs. Que devient aussi la répartition des forces réelles dans les
systèmes en partie fictifs auxquels on est ainsi conduit?
Dans la Préface de sa Thermodynamique, Poincaré, voulant
descendre en quelque sorte jusqu’au fond du principe de la
conservation de l’énergie, conclut que «la loi de Meyer est une forme
assez souple pour qu’on puisse y faire rentrer presque tout ce qu’on
veut». Il semble à la vérité un peu effrayé de sa conclusion, car il
ajoute plus loin qu’il ne faut pas «pousser jusqu’à l’absolu». Nous
retrouverons cet esprit hypercritique, si j’ose le dire, clans certains
écrits philosophiques de Poincaré.
Poincaré, sans cesse curieux de nouvelles théories et de
nouveaux problèmes, ne pouvait manquer d’être attiré par
l’Électromagnétisme qui tient une si grande place dans la Science de
notre époque. On ne saurait trop admirer avec quelle sûreté et
quelle maîtrise il repense les diverses théories, les faisant ainsi
siennes. Il leur donne parfois une forme saisissante, comme quand,
dans l’exposition de la théorie de Lorentz, il distingue entre les
observateurs ayant les sens subtils et les observateurs ayant les
sens grossiers. La considération, bien personnelle à Poincaré, de ce
qu’il appelle «la quantité de mouvement électromagnétique», la
localisation de celle-ci dans l’éther et sa propagation avec une
perturbation électromagnétique sont venues rétablir d’importantes
analogies. Le Mémoire sur la dynamique de l’électron, écrit en 1905,
restera dans l’histoire du principe de la relativité; le groupe des
transformations de Lorentz, qui n’altèrent pas les équations d'un
milieu électromagnétique, y apparaît comme la clef de voûte dans la
discussion des conditions auxquelles doivent satisfaire les forces
dans la nouvelle dynamique. La nécessité de l’introduction dans
l’électron de forces supplémentaires, en dehors des forces de liaison
est établie, ces forces supplémentaires pouvant être assimilées à
une pression qui régnerait à l’extérieur de l’électron. Poincaré
montre encore quelles hypothèses on peut faire sur la gravitation
pour que le champ grafivique soit affecté par une transformation de
Lorentz de la même manière que le champ électromagnétique.
 On sait l’importance qu’a prise aujourd’hui le principe de la
relativité, dont le point de départ est l’impossibilité, proclamée sur la
foi de quelques expériences négatives, de mettre en évidence le
mouvement de translation uniforme d’un système au moyen
d’expériences d’optique ou d’électricité faites à l’intérieur de ce
système. En admettant, d’autre part, que les idées de Lorentz et ses
équations électromagnétiques sont inattaquables, on a été conduit à
regarder comme nécessaire le changement de nos idées sur
l’espace et sur le temps; espace et temps ( ) n’ont plus
leurs transformations séparées et entrent simultanément dans le
groupe de Lorentz. La simultanéité de deux phénomènes devient
une notion toute relative; un phénomène peut être antérieur à un
autre pour un premier observateur, tandis qu’il lui est postérieur pour
un second. Les mathématiciens, intéressés par un groupe de
transformations qui transforment en elle-même la forme quadratique
( = vitesse de la lumière) se sont livrés à
d’élégantes dissertations sur ce sujet et ont sans doute contribué à
la popularité du principe de relativité. A d’autres époques, on eût
peut-être, avant de rejeter les idées traditionnelles de l’humanité sur
l’espace et le temps, passé au crible d’une critique extrêmement
sévère les conceptions sur l’éther et la formation des équations de
l’électromagnétisme; mais le désir du nouveau ne connaît pas de
bornes aujourd’hui. Les objections ne manquent pas cependant, et
d’illustres physiciens, comme Lord Kelvin et Ritz, sans parler des
vivants, ont émis des doutes très motivés. La Science assurément
ne connaît point de dogmes, et il se peut que des expériences
positives précises nous forcent un jour à modifier certaines idées
devenues notions de sens commun; mais le moment en est-il déjà
venu?
Poincaré voyait le danger de ces engouements, et, dans une
conférence sur la dynamique nouvelle, il adjurait les professeurs de
ne pas jeter le discrédit sur la vieille Mécanique qui a fait ses
preuves. Et puis, il a vécu assez pourvoir les principaux
protagonistes des idées nouvelles ruiner partiellement au moins leur
œuvre. Dans tout ce relativisme, il reste un absolu, à savoir la
vitesse de la lumière dans le vide, indépendante de l’état de repos
ou de mouvement de la source lumineuse. Cet absolu va
probablement disparaître, les équations de Lorentz ne représentant
plus qu’une première approximation. Les plus grandes difficultés
viennent de la gravitation, au point que certains théoriciens de la
Physique croient ne pouvoir les lever qu’en attribuant de l’inertie et
un poids à l’énergie, d’où en particulier la pesanteur de la lumière. Si
Poincaré avait vécu, il eût sans doute été conduit à rapprocher des
vues actuelles son essai de 1905 sur la gravitation. Au milieu des
incertitudes qui se présentent aujourd’hui en électro-optique, son
esprit lumineux va nous manquer singulièrement. Il faut avouer que
dans tout cela les bases expérimentales sont fragiles, et peut-être
Poincaré eût-il suggéré des expériences apportant un peu de
lumière dans cette obscurité.
Un des derniers travaux de Poincaré a été une discussion
approfondie de la théorie des quanta, édifiée par Planck, d’après
laquelle l’énergie des radiateurs lumineux varierait d’une manière
discontinue. De ce point de vue «les phénomènes physiques, dit
Poincaré, cesseraient d’obéir à des lois exprimables par des
équations différentielles, et ce serait là sans aucun doute la plus
grande révolution et la plus profonde que la philosophie naturelle ait
subie depuis Newton». Quelque grande, en effet, que doive être
cette révolution, il est permis toutefois de remarquer que des
circonstances plus ou moins analogues se sont déjà présentées.
Ainsi, dans un gaz à la pression ordinaire, ou peut parler de pression
et l’on peut appliquer les équations différentielles de la dynamique
des fluides; il n’en est plus de même dans un gaz raréfié, où il n’est
plus possible de parler de pression. Il faudra peut-être nous résigner
à faire usage, suivant les limites entre lesquelles nous étudions une
catégorie de phénomènes, de représentations analytiques
différentes, si pénible que puisse être cette sorte de pluralisme pour
ceux qui rêvent d’unité. Mais c’est là encore le secret de l’avenir, et il
serait imprudent d’affirmer qu’on ne trouvera pas quelque biais
permettant de rétablir dans nos calculs la continuité.
 V.
Les nombreux écrits de Poincaré, sur ce qu’on appelle la
philosophie des sciences, ont fait connaître son nom à un public très
étendu. Nous entrons ici dans un autre domaine que celui des
recherches proprement scientifiques, et je n’ai pas l’intention
d’étudier à fond cette partie de son œuvre. Il y est tout d’abord
singulièrement difficile de se rendre compte de l’originalité de telle
ou telle étude; ainsi, dans ses écrits sur l’hypothèse dans la Science,
Poincaré s’est rencontré plus d’une fois avec divers auteurs, mais
l’illustration de son nom, consacrée par tant de découvertes
mathématiques, donnait à ses opinions une autorité particulière. La
forme en ces questions est aussi de grande importance. La phrase
concise de Poincaré, allant droit au but, parfois avec une légère
pointe de paradoxe, produit une singulière impression; on est un
moment subjugué, même quand on sent qu’on n’est pas d’accord
avec l’auteur. Mainte page de Poincaré a produit sur plus d’un
lecteur un vif sentiment d’admiration en même temps qu’une sorte
d’effroi et d’agacement devant tant de critique.
On a parlé quelquefois de la philosophie de Poincaré. En fait,
penseur indépendant, étranger à toute école, Poincaré ne chercha
jamais à édifier un système philosophique, comme un Renouvier, un
Bergson ou même un William James. Il a écrit des livres de
«Pensées», où savants et philosophes trouvent ample matière à
réflexions. Il n’est esclave d’aucune opinion, pas même de celle qu’il
a émise antérieurement, et il sera un jour intéressant de suivre
certaines variations de la sa pensée, où l’on voit quelque peu
s’atténuer ce qu’on a appelé son nominalisme. Il fut ainsi conduit à
expliquer certaines affirmations qui, prises trop à la lettre, avaient été
mal comprises et utilisées dans un dessein dont il n’avait aucun
souci.
 Si l’on voulait toutefois caractériser d’un mot les idées de
Poincaré, on pourrait dire que sa philosophie est la philosophie de la
commodité. Dans quelques unes de ses pages, le mot commode
revient constamment et constitue le terme de son explication.
D’aucuns pensent qu’il faudrait donner les raisons de cette
commodité, et, parmi eux, les plus pressants sont les biologistes
toujours guidés par l’idée d’évolution. La commodité résultera pour
eux d’une longue adaptation, et, ainsi approfondie, deviendra un
témoignage de réalité et de vérité. A l’opposé des évolutionnistes,
d’autres ne voient que l’esprit humain tout formé et sa fonction la
pensée. A certaines heures au moins, Poincaré fut de ces derniers,
et cet idéalisme lui a inspiré des pages d’une admirable poésie qui
resteront dans la littérature française; telle cette dernière page de
son Livre sur la valeur de la Science, qui débute par ces mots «Tout
ce qui n’est pas pensée est le pur néant». Entre des doctrines si
différentes toute communication est impossible, et l’on arrive à se
demander si l’on peut discuter de l’origine des plus simples notions
scientifiques, sans avoir à l’avance une foi philosophique à la
formation de laquelle auront d’ailleurs concouru d’autres éléments
que des éléments proprement scientifiques.
Pour ne pas rester uniquement dans les généralités, arrêtons-
nous un moment sur les principes de la Géométrie. Poincaré part
d’un esprit humain, dans lequel l’idée de groupe préexiste et
s’impose comme forme de notre entendement. L’esprit, après un
travail d’abstraction aboutissant aux premiers concepts de la
Géométrie (point, droite, etc.), cherche à exprimer les rapports de
position des corps; il le fait au moyen de l’idée de groupe, prenant le
groupe le plus commode et le plus simple qui est le groupe de la
géométrie dite euclidienne. Les propriétés géométriques ne
correspondent, pour Poincaré, à aucune réalité; elles forment un
ensemble de conventions que l’expérience a pu suggérer à l’esprit,
mais qu’elle ne lui a pas imposées. L’évolutionniste dont je parlais
plus haut voit là de grandes difficultés, non pas seulement pour la
raison banale que la dualité ainsi posée entre l’esprit et le milieu
extérieur est contraire à sa doctrine, mais parce que, cherchant à
retracer la genèse des origines de la Géométrie dans l’espèce
humaine, il lui paraît impossible de séparer l’acquisition des notions
géométriques et celles des notions physiques les plus simples, la
Géométrie ayant dans des temps très anciens fait partie de la
Physique. Sans changer l’ensemble de ces notions, on ne peut,
semble-t-il, remplacer le groupe euclidien par un autre, et les
exemples cités de transport d’un homme dans un autre milieu (où
cet homme commencerait par mourir) sont plus pittoresques que
probants. On retombe ainsi, sous un autre point de vue, sur les
idées de Gauss qui considérait comme un fait expérimental que la
courbure de notre espace est nulle, et regardait, contrairement à
Poincaré, que la géométrie euclidienne est plus vraie que les
géométries non euclidiennes. Il y a sans doute bien des hypothèses,
ne disons pas des conventions, en Géométrie. C’en est une par
exemple, oubliée quelquefois, que notre espace est simplement
connexe. Peu importe quelle est la connexité de l’espace, quand on
se borne à envisager une partie assez petite, celle-ci s’étendît-elle
jusqu’aux lointaines nébuleuses, mais il pourrait en être autrement
quand on considère l’espace dans son ensemble.
Tous les esprits élevés trouveront, dans l’œuvre philosophique et
littéraire de Poincaré, matière à longues réflexions, soit qu’ils se
laissent convaincre par sa dialectique, soit qu’ils cherchent des
arguments contraires. Certaines pages sont d’une austère grandeur,
comme celle où la pensée est qualifiée d’«éclair au milieu d’une
longue nuit». Non moins suggestive est la parenthèse ouverte un
peu avant «étrange contradiction pour ceux qui croient au temps»,
où l’on est presque tenté de voir un demi-aveu. Les inquiétudes
qu’on peut concevoir au sujet de la notion même de loi furent-elles
jamais exprimées avec plus de profondeur que dans l’étude sur
l’évolution des lois? J’ai déjà fait allusion au prétendu scepticisme de
Poincaré. Non, Poincaré ne fut pas un sceptique; à certaines heures,
il fut pris, comme d’autres, d’angoisse métaphysique, et il sut
éloquemment l’exprimer. Mais tournons le feuillet, et le savant,
confiant dans l’effort de l’esprit humain pour atteindre le vrai, nous
apparaît dans des pages admirables sur le rôle et la grandeur de la
Science. Les plus belles peut-être forment cet hymne à l’Astronomie
qu’il faudrait faire lire aux jeunes gens à une époque où tend à
dominer le souci exclusif de l’utile. Aucune des préoccupations de
notre temps ne fut d’ailleurs étrangère au noble esprit de Poincaré;
c’est ce dont témoigne une de ses dernières études sur la morale et
la science, où l’argumentation est irréprochable, si par morale on
entend la morale impérative de Kant.
On ne ferme pas sans tristesse ces volumes d’un contenu si riche
et dont quelques parties auraient été l’objet de nouveaux
développements, si la plume n’était tombée des mains de leur
auteur. Tous ceux qui ont le culte de la Science pure et
désintéressée ont été douloureusement émus par sa mort
prématurée, mais ce sont surtout les sciences mathématiques qui
sont cruellement frappées par cette disparition. Poincaré fut, avant
tout, un profond mathématicien, qui, pour la puissance d’invention,
est l’égal des plus grands. L’heure n’est pas venue de porter un
jugement définitif sur son œuvre que le temps grandira encore, ni de
le comparer aux plus célèbres géomètres du siècle dernier: peut-être
Henri Poincaré fût-il encore supérieur à son œuvre?
[1] On sait qu’un savant Finlandais M. Sundmann vient de donner
une solution complète du problème des trois corps. Il serait injuste
de ne pas reconnaître que les travaux antérieurs de Poincaré ont
eu une grande influence sur les recherches de l’astronome
d’Helsingfors. J’ai fait une étude des Mémoires de M. Sundmann
dans un article récent de la Revue générale des Sciences (15
octobre 1913) et dans le Bulletin des Sciences Mathématiques
(octobre 1913).
[2] C’est en approfondissant cette idée, et en ne craignant pas de
comprendre dans son analyse le cas des chocs que M.
Sundmann est arrivé à une solution du problème de trois corps
(voir la note ci-dessus).

53717 Paris,—Imprimerie Gauthier-Villars, 55, quai des Grands-

Augustins.

AU LECTEUR
L’orthographe d’origine a été conservée et n’a pas été harmonisée, mais les
erreurs clairement introduites par le typographe ou à l’impression ont été
corrigées.
Une table des matières a été ajoutée pour faciliter la tâche du lecteur.
 *** END OF THE PROJECT GUTENBERG EBOOK L'ŒUVRE DE
HENRI POINCARÉ ***

Updated editions will replace the previous one—the old editions will
be renamed.

Creating the works from print editions not protected by U.S.

copyright law means that no one owns a United States copyright in
these works, so the Foundation (and you!) can copy and distribute it
in the United States without permission and without paying copyright
royalties. Special rules, set forth in the General Terms of Use part of
this license, apply to copying and distributing Project Gutenberg™
electronic works to protect the PROJECT GUTENBERG™ concept
and trademark. Project Gutenberg is a registered trademark, and
may not be used if you charge for an eBook, except by following the
terms of the trademark license, including paying royalties for use of
the Project Gutenberg trademark. If you do not charge anything for
copies of this eBook, complying with the trademark license is very
easy. You may use this eBook for nearly any purpose such as
creation of derivative works, reports, performances and research.
Project Gutenberg eBooks may be modified and printed and given
away—you may do practically ANYTHING in the United States with
eBooks not protected by U.S. copyright law. Redistribution is subject
to the trademark license, especially commercial redistribution.

START: FULL LICENSE

THE FULL PROJECT GUTENBERG LICENSE
 PLEASE READ THIS BEFORE YOU DISTRIBUTE OR USE THIS WORK

To protect the Project Gutenberg™ mission of promoting the free

distribution of electronic works, by using or distributing this work (or
any other work associated in any way with the phrase “Project
Gutenberg”), you agree to comply with all the terms of the Full
Project Gutenberg™ License available with this file or online at
www.gutenberg.org/license.

Section 1. General Terms of Use and

Redistributing Project Gutenberg™
electronic works
1.A. By reading or using any part of this Project Gutenberg™
electronic work, you indicate that you have read, understand, agree
to and accept all the terms of this license and intellectual property
(trademark/copyright) agreement. If you do not agree to abide by all
the terms of this agreement, you must cease using and return or
destroy all copies of Project Gutenberg™ electronic works in your
possession. If you paid a fee for obtaining a copy of or access to a
Project Gutenberg™ electronic work and you do not agree to be
bound by the terms of this agreement, you may obtain a refund from
the person or entity to whom you paid the fee as set forth in
paragraph 1.E.8.

1.B. “Project Gutenberg” is a registered trademark. It may only be

used on or associated in any way with an electronic work by people
who agree to be bound by the terms of this agreement. There are a
few things that you can do with most Project Gutenberg™ electronic
works even without complying with the full terms of this agreement.
See paragraph 1.C below. There are a lot of things you can do with
Project Gutenberg™ electronic works if you follow the terms of this
agreement and help preserve free future access to Project
Gutenberg™ electronic works. See paragraph 1.E below.
1.C. The Project Gutenberg Literary Archive Foundation (“the
Foundation” or PGLAF), owns a compilation copyright in the
collection of Project Gutenberg™ electronic works. Nearly all the
individual works in the collection are in the public domain in the
United States. If an individual work is unprotected by copyright law in
the United States and you are located in the United States, we do
not claim a right to prevent you from copying, distributing,
performing, displaying or creating derivative works based on the
work as long as all references to Project Gutenberg are removed. Of
course, we hope that you will support the Project Gutenberg™
mission of promoting free access to electronic works by freely
sharing Project Gutenberg™ works in compliance with the terms of
this agreement for keeping the Project Gutenberg™ name
associated with the work. You can easily comply with the terms of
this agreement by keeping this work in the same format with its
attached full Project Gutenberg™ License when you share it without
charge with others.

1.D. The copyright laws of the place where you are located also
govern what you can do with this work. Copyright laws in most
countries are in a constant state of change. If you are outside the
United States, check the laws of your country in addition to the terms
of this agreement before downloading, copying, displaying,
performing, distributing or creating derivative works based on this
work or any other Project Gutenberg™ work. The Foundation makes
no representations concerning the copyright status of any work in
any country other than the United States.

1.E. Unless you have removed all references to Project Gutenberg:

1.E.1. The following sentence, with active links to, or other

immediate access to, the full Project Gutenberg™ License must
appear prominently whenever any copy of a Project Gutenberg™
work (any work on which the phrase “Project Gutenberg” appears, or
with which the phrase “Project Gutenberg” is associated) is
accessed, displayed, performed, viewed, copied or distributed:
 This eBook is for the use of anyone anywhere in the United
States and most other parts of the world at no cost and with
almost no restrictions whatsoever. You may copy it, give it away
or re-use it under the terms of the Project Gutenberg License
included with this eBook or online at www.gutenberg.org. If you
are not located in the United States, you will have to check the
laws of the country where you are located before using this
eBook.

1.E.2. If an individual Project Gutenberg™ electronic work is derived

from texts not protected by U.S. copyright law (does not contain a
notice indicating that it is posted with permission of the copyright
holder), the work can be copied and distributed to anyone in the
United States without paying any fees or charges. If you are
redistributing or providing access to a work with the phrase “Project
Gutenberg” associated with or appearing on the work, you must
comply either with the requirements of paragraphs 1.E.1 through
1.E.7 or obtain permission for the use of the work and the Project
Gutenberg™ trademark as set forth in paragraphs 1.E.8 or 1.E.9.

1.E.3. If an individual Project Gutenberg™ electronic work is posted

with the permission of the copyright holder, your use and distribution
must comply with both paragraphs 1.E.1 through 1.E.7 and any
additional terms imposed by the copyright holder. Additional terms
will be linked to the Project Gutenberg™ License for all works posted
with the permission of the copyright holder found at the beginning of
this work.

1.E.4. Do not unlink or detach or remove the full Project

Gutenberg™ License terms from this work, or any files containing a
part of this work or any other work associated with Project
Gutenberg™.

1.E.5. Do not copy, display, perform, distribute or redistribute this

electronic work, or any part of this electronic work, without
prominently displaying the sentence set forth in paragraph 1.E.1 with
active links or immediate access to the full terms of the Project
Gutenberg™ License.
1.E.6. You may convert to and distribute this work in any binary,
compressed, marked up, nonproprietary or proprietary form,
including any word processing or hypertext form. However, if you
provide access to or distribute copies of a Project Gutenberg™ work
in a format other than “Plain Vanilla ASCII” or other format used in
the official version posted on the official Project Gutenberg™ website
(www.gutenberg.org), you must, at no additional cost, fee or expense
to the user, provide a copy, a means of exporting a copy, or a means
of obtaining a copy upon request, of the work in its original “Plain
Vanilla ASCII” or other form. Any alternate format must include the
full Project Gutenberg™ License as specified in paragraph 1.E.1.

1.E.7. Do not charge a fee for access to, viewing, displaying,

performing, copying or distributing any Project Gutenberg™ works
unless you comply with paragraph 1.E.8 or 1.E.9.

1.E.8. You may charge a reasonable fee for copies of or providing

access to or distributing Project Gutenberg™ electronic works
provided that:

• You pay a royalty fee of 20% of the gross profits you derive from
the use of Project Gutenberg™ works calculated using the
method you already use to calculate your applicable taxes. The
fee is owed to the owner of the Project Gutenberg™ trademark,
but he has agreed to donate royalties under this paragraph to
the Project Gutenberg Literary Archive Foundation. Royalty
payments must be paid within 60 days following each date on
which you prepare (or are legally required to prepare) your
periodic tax returns. Royalty payments should be clearly marked
as such and sent to the Project Gutenberg Literary Archive
Foundation at the address specified in Section 4, “Information
about donations to the Project Gutenberg Literary Archive
Foundation.”

• You provide a full refund of any money paid by a user who

notifies you in writing (or by e-mail) within 30 days of receipt that
s/he does not agree to the terms of the full Project Gutenberg™
License. You must require such a user to return or destroy all
 copies of the works possessed in a physical medium and
discontinue all use of and all access to other copies of Project
Gutenberg™ works.

• You provide, in accordance with paragraph 1.F.3, a full refund of

any money paid for a work or a replacement copy, if a defect in
the electronic work is discovered and reported to you within 90
days of receipt of the work.

• You comply with all other terms of this agreement for free
distribution of Project Gutenberg™ works.

1.E.9. If you wish to charge a fee or distribute a Project Gutenberg™

electronic work or group of works on different terms than are set
forth in this agreement, you must obtain permission in writing from
the Project Gutenberg Literary Archive Foundation, the manager of
the Project Gutenberg™ trademark. Contact the Foundation as set
forth in Section 3 below.

1.F.

1.F.1. Project Gutenberg volunteers and employees expend

considerable effort to identify, do copyright research on, transcribe
and proofread works not protected by U.S. copyright law in creating
the Project Gutenberg™ collection. Despite these efforts, Project
Gutenberg™ electronic works, and the medium on which they may
be stored, may contain “Defects,” such as, but not limited to,
incomplete, inaccurate or corrupt data, transcription errors, a
copyright or other intellectual property infringement, a defective or
damaged disk or other medium, a computer virus, or computer
codes that damage or cannot be read by your equipment.

1.F.2. LIMITED WARRANTY, DISCLAIMER OF DAMAGES - Except

for the “Right of Replacement or Refund” described in paragraph
1.F.3, the Project Gutenberg Literary Archive Foundation, the owner
of the Project Gutenberg™ trademark, and any other party
distributing a Project Gutenberg™ electronic work under this
agreement, disclaim all liability to you for damages, costs and
expenses, including legal fees. YOU AGREE THAT YOU HAVE NO
REMEDIES FOR NEGLIGENCE, STRICT LIABILITY, BREACH OF
WARRANTY OR BREACH OF CONTRACT EXCEPT THOSE
PROVIDED IN PARAGRAPH 1.F.3. YOU AGREE THAT THE
FOUNDATION, THE TRADEMARK OWNER, AND ANY
DISTRIBUTOR UNDER THIS AGREEMENT WILL NOT BE LIABLE
TO YOU FOR ACTUAL, DIRECT, INDIRECT, CONSEQUENTIAL,
PUNITIVE OR INCIDENTAL DAMAGES EVEN IF YOU GIVE
NOTICE OF THE POSSIBILITY OF SUCH DAMAGE.

1.F.3. LIMITED RIGHT OF REPLACEMENT OR REFUND - If you

discover a defect in this electronic work within 90 days of receiving it,
you can receive a refund of the money (if any) you paid for it by
sending a written explanation to the person you received the work
from. If you received the work on a physical medium, you must
return the medium with your written explanation. The person or entity
that provided you with the defective work may elect to provide a
replacement copy in lieu of a refund. If you received the work
electronically, the person or entity providing it to you may choose to
give you a second opportunity to receive the work electronically in
lieu of a refund. If the second copy is also defective, you may
demand a refund in writing without further opportunities to fix the
problem.

1.F.4. Except for the limited right of replacement or refund set forth in
paragraph 1.F.3, this work is provided to you ‘AS-IS’, WITH NO
OTHER WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED,
INCLUDING BUT NOT LIMITED TO WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR ANY PURPOSE.

1.F.5. Some states do not allow disclaimers of certain implied

warranties or the exclusion or limitation of certain types of damages.
If any disclaimer or limitation set forth in this agreement violates the
law of the state applicable to this agreement, the agreement shall be
interpreted to make the maximum disclaimer or limitation permitted
by the applicable state law. The invalidity or unenforceability of any
provision of this agreement shall not void the remaining provisions.
1.F.6. INDEMNITY - You agree to indemnify and hold the
Foundation, the trademark owner, any agent or employee of the
Foundation, anyone providing copies of Project Gutenberg™
electronic works in accordance with this agreement, and any
volunteers associated with the production, promotion and distribution
of Project Gutenberg™ electronic works, harmless from all liability,
costs and expenses, including legal fees, that arise directly or
indirectly from any of the following which you do or cause to occur:
(a) distribution of this or any Project Gutenberg™ work, (b)
alteration, modification, or additions or deletions to any Project
Gutenberg™ work, and (c) any Defect you cause.

Section 2. Information about the Mission of

Project Gutenberg™
Project Gutenberg™ is synonymous with the free distribution of
electronic works in formats readable by the widest variety of
computers including obsolete, old, middle-aged and new computers.
It exists because of the efforts of hundreds of volunteers and
donations from people in all walks of life.

Volunteers and financial support to provide volunteers with the

assistance they need are critical to reaching Project Gutenberg™’s
goals and ensuring that the Project Gutenberg™ collection will
remain freely available for generations to come. In 2001, the Project
Gutenberg Literary Archive Foundation was created to provide a
secure and permanent future for Project Gutenberg™ and future
generations. To learn more about the Project Gutenberg Literary
Archive Foundation and how your efforts and donations can help,
see Sections 3 and 4 and the Foundation information page at
www.gutenberg.org.

Section 3. Information about the Project

Gutenberg Literary Archive Foundation
The Project Gutenberg Literary Archive Foundation is a non-profit
501(c)(3) educational corporation organized under the laws of the
state of Mississippi and granted tax exempt status by the Internal
Revenue Service. The Foundation’s EIN or federal tax identification
number is 64-6221541. Contributions to the Project Gutenberg
Literary Archive Foundation are tax deductible to the full extent
permitted by U.S. federal laws and your state’s laws.

The Foundation’s business office is located at 809 North 1500 West,

Salt Lake City, UT 84116, (801) 596-1887. Email contact links and up
to date contact information can be found at the Foundation’s website
and official page at www.gutenberg.org/contact

Section 4. Information about Donations to

the Project Gutenberg Literary Archive
Foundation
Project Gutenberg™ depends upon and cannot survive without
widespread public support and donations to carry out its mission of
increasing the number of public domain and licensed works that can
be freely distributed in machine-readable form accessible by the
widest array of equipment including outdated equipment. Many small
donations ($1 to $5,000) are particularly important to maintaining tax
exempt status with the IRS.

The Foundation is committed to complying with the laws regulating

charities and charitable donations in all 50 states of the United
States. Compliance requirements are not uniform and it takes a
considerable effort, much paperwork and many fees to meet and
keep up with these requirements. We do not solicit donations in
locations where we have not received written confirmation of
compliance. To SEND DONATIONS or determine the status of
compliance for any particular state visit www.gutenberg.org/donate.

While we cannot and do not solicit contributions from states where

we have not met the solicitation requirements, we know of no
prohibition against accepting unsolicited donations from donors in
such states who approach us with offers to donate.

International donations are gratefully accepted, but we cannot make

any statements concerning tax treatment of donations received from
outside the United States. U.S. laws alone swamp our small staff.

Please check the Project Gutenberg web pages for current donation
methods and addresses. Donations are accepted in a number of
other ways including checks, online payments and credit card
donations. To donate, please visit: www.gutenberg.org/donate.

Section 5. General Information About Project

Gutenberg™ electronic works
Professor Michael S. Hart was the originator of the Project
Gutenberg™ concept of a library of electronic works that could be
freely shared with anyone. For forty years, he produced and
distributed Project Gutenberg™ eBooks with only a loose network of
volunteer support.

Project Gutenberg™ eBooks are often created from several printed

editions, all of which are confirmed as not protected by copyright in
the U.S. unless a copyright notice is included. Thus, we do not
necessarily keep eBooks in compliance with any particular paper
edition.

Most people start at our website which has the main PG search
facility: www.gutenberg.org.

This website includes information about Project Gutenberg™,

including how to make donations to the Project Gutenberg Literary
Archive Foundation, how to help produce our new eBooks, and how
to subscribe to our email newsletter to hear about new eBooks.