Louis Pasteur

Molecular asymmetry

In Pasteur's early work as a chemist, beginning at the École Normale Supérieure, and continuing at Strasbourg and Lille, he examined the chemical, optical and crystallographic properties of a group of compounds known as tartrates.^[50]

He resolved a problem concerning the nature of tartaric acid in 1848.^{[51][52][53][54]} A solution of this compound derived from living things rotated the plane of polarization of light passing through it.^[50] The problem was that tartaric acid derived by chemical synthesis had no such effect, even though its chemical reactions were identical and its elemental composition was the same.^[55]

Pasteur noticed that crystals of tartrates had small faces. Then he observed that, in racemic mixtures of tartrates, half of the crystals were right-handed and half were left-handed. In solution, the right-handed compound was dextrorotatory, and the left-handed one was levorotatory.^[50] Pasteur determined that optical activity related to the shape of the crystals, and that an asymmetric internal arrangement of the molecules of the compound was responsible for twisting the light.^[43] The (2R,3R)- and (2S,3S)- tartrates were isometric, non-superposable mirror images of each other. This was the first time anyone had demonstrated molecular chirality, and also the first explanation of isomerism.^[50]

Some historians consider Pasteur's work in this area to be his "most profound and most original contributions to science", and his "greatest scientific discovery."^[50]

Fermentation and germ theory of diseases

Pasteur was motivated to investigate fermentation while working at Lille. In 1856 a local wine manufacturer, M. Bigot, whose son was one of Pasteur's students, sought for his advice on the problems of making beetroot alcohol and souring.^[56][3] Pasteur began his research in the topic by repeating and confirming works of Theodor Schwann, who demonstrated a decade earlier that yeast were alive.

According to his son-in-law, René Vallery-Radot, in August 1857 Pasteur sent a paper about lactic acid fermentation to the Société des Sciences de Lille, but the paper was read three months later.^[57] A memoire was subsequently published on 30 November 1857.^[58] In the memoir, he developed his ideas stating that: "I intend to establish that, just as there is an alcoholic ferment, the yeast of beer, which is found everywhere that sugar is decomposed into alcohol and carbonic acid, so also there is a particular ferment, a lactic yeast, always present when sugar becomes lactic acid."^[59]

Pasteur also wrote about alcoholic fermentation.^[60] It was published in full form in 1858.^[61][62] Jöns Jacob Berzelius and Justus von Liebig had proposed the theory that fermentation was caused by decomposition. Pasteur demonstrated that this theory was incorrect, and that yeast was responsible for fermentation to produce alcohol from sugar.^[63] He also demonstrated that, when a different microorganism contaminated the wine, lactic acid was produced, making the wine sour.^[3] In 1861, Pasteur observed that less sugar fermented per part of yeast when the yeast was exposed to air.^[63] The lower rate of fermentation aerobically became known as the Pasteur effect.^[64]

Pasteur's research also showed that the growth of micro-organisms was responsible for spoiling beverages, such as beer, wine and milk. With this established, he invented a process in which liquids such as milk were heated to a temperature between 60 and 100 °C.^[65] This killed most bacteria and moulds already present within them. Pasteur and Claude Bernard completed tests on blood and urine on 20 April 1862.^[66] Pasteur patented the process, to fight the "diseases" of wine, in 1865.^[65] The method became known as pasteurization, and was soon applied to beer and milk.^[67]

Beverage contamination led Pasteur to the idea that micro-organisms infecting animals and humans cause disease. He proposed preventing the entry of micro-organisms into the human body, leading Joseph Lister to develop antiseptic methods in surgery.^[68]

In 1866, Pasteur published Études sur le Vin, about the diseases of wine, and he published Études sur la Bière in 1876, concerning the diseases of beer.^[63]

In the early 19th century, Agostino Bassi had shown that muscardine was caused by a fungus that infected silkworms.^[69] Since 1853, two diseases called pébrine and flacherie had been infecting great numbers of silkworms in southern France, and by 1865 they were causing huge losses to farmers. In 1865, Pasteur went to Alès and worked for five years until 1870.^[70][71]

Silkworms with pébrine were covered in corpuscles. In the first three years, Pasteur thought that the corpuscles were a symptom of the disease. In 1870, he concluded that the corpuscles were the cause of pébrine (it is now known that the cause is a microsporidian).^[69] Pasteur also showed that the disease was hereditary.^[72] Pasteur developed a system to prevent pébrine: after the female moths laid their eggs, the moths were turned into a pulp. The pulp was examined with a microscope, and if corpuscles were observed, the eggs were destroyed.^[73][72] Pasteur concluded that bacteria caused flacherie. The primary cause is currently thought to be viruses.^[69] The spread of flacherie could be accidental or hereditary. Hygiene could be used to prevent accidental flacherie. Moths whose digestive cavities did not contain the microorganisms causing flacherie were used to lay eggs, preventing hereditary flacherie.^[74]

Spontaneous generation

Following his fermentation experiments, Pasteur demonstrated that the skin of grapes was the natural source of yeasts, and that sterilized grapes and grape juice never fermented. He drew grape juice from under the skin with sterilized needles, and also covered grapes with sterilized cloth. Both experiments could not produce wine in sterilized containers.^[3]

His findings and ideas were against the prevailing notion of spontaneous generation. He received a particularly stern criticism from Félix Archimède Pouchet, who was director of the Rouen Museum of Natural History. To settle the debate between the eminent scientists, the French Academy of Sciences offered the Alhumbert Prize carrying 2,500 francs to whoever could experimentally demonstrate for or against the doctrine.^[75][76][77]

Pouchet stated that air everywhere could cause spontaneous generation of living organisms in liquids.^[78] In the late 1850s, he performed experiments and claimed that they were evidence of spontaneous generation.^[79][75] Francesco Redi and Lazzaro Spallanzani had provided some evidence against spontaneous generation in the 17th and 18th centuries, respectively. Spallanzani's experiments in 1765 suggested that air contaminated broths with bacteria. In the 1860s, Pasteur repeated Spallanzani's experiments, but Pouchet reported a different result using a different broth.^[70]

Pasteur performed several experiments to disprove spontaneous generation. He placed boiled liquid in a flask and let hot air enter the flask. Then he closed the flask, and no organisms grew in it.^[79] In another experiment, when he opened flasks containing boiled liquid, dust entered the flasks, causing organisms to grow in some of them. The number of flasks in which organisms grew was lower at higher altitudes, showing that air at high altitudes contained less dust and fewer organisms.^[3][80] Pasteur also used swan neck flasks containing a fermentable liquid. Air was allowed to enter the flask via a long curving tube that made dust particles stick to it. Nothing grew in the broths unless the flasks were tilted, making the liquid touch the contaminated walls of the neck. This showed that the living organisms that grew in such broths came from outside, on dust, rather than spontaneously generating within the liquid or from the action of pure air.^[3][81]

These were some of the most important experiments disproving the theory of spontaneous generation. Pasteur gave a series of five presentations of his findings before the French Academy of Sciences in 1881, which were published in 1882 as Mémoire Sur les corpuscules organisés qui existent dans l'atmosphère: Examen de la doctrine des générations spontanées (Account of Organized Corpuscles Existing in the Atmosphere: Examining the Doctrine of Spontaneous Generation).^[82][83] Pasteur won the Alhumbert Prize in 1862.^[79] He concluded that:

Never will the doctrine of spontaneous generation recover from the mortal blow of this simple experiment. There is no known circumstance in which it can be confirmed that microscopic beings came into the world without germs, without parents similar to themselves.^[3][71]

Silkworm disease

In 1865, Jean-Baptiste Dumas, chemist, senator and former Minister of Agriculture and Commerce, asked Pasteur to study a new disease that was decimating silkworm farms from the south of France and Europe, the pébrine, characterized on a macroscopic scale by black spots and on a microscopic scale by the "Cornalia corpuscles". Pasteur accepted and made five long stays in Alès, between 7 June 1865 and 1869.^[84]

Flacherie resists

In 1878, at the Congrès international séricicole, Pasteur admitted that "if pébrine is overcome, flacherie still exerts its ravages". He attributed the persistence of flacherie to the fact that the farmers had not followed his advice.^[99]

In 1884, Balbiani,^[100] who disregarded the theoretical value of Pasteur's work on silkworm diseases, acknowledged that his practical process had remedied the ravages of pébrine, but added that this result tended to be counterbalanced by the development of flacherie, which was less well known and more difficult to prevent.

Despite Pasteur's success against pébrine, French sericulture had not been saved from damage. (See fr:Sériciculture in the French Wikipedia.)

Immunology and vaccination

Anthrax

Following the results with chicken cholera, Pasteur eventually utilized the immunization method developed for chicken cholera to create a vaccine for anthrax, which affected cattle. In 1877, Pasteur had earlier directed his laboratory to culture the bacteria from the blood of infected animals, following the discovery of the bacterium by Robert Koch.^[106]

When animals were infected with the bacteria, anthrax occurred, proving that the bacteria was the cause of the disease.^[108] Many cattle were dying of anthrax in "cursed fields".^[71] Pasteur was told that sheep that died from anthrax were buried in the field. Pasteur thought that earthworms might have brought the bacteria to the surface. He found anthrax bacteria in earthworms' excrement, showing that he was correct.^[71] He told the farmers not to bury dead animals in the fields.^[109]

Pasteur's interest in creating a vaccine for anthrax was greatly stimulated when on 12 July 1880, Henri Bouley read before the French Academy of Sciences a report from Henry Toussaint, a veterinary surgeon, who was not a member of the academy. Toussaint had developed anthrax vaccine by killing the bacilli by heating at 55 °C for 10  minutes. He tested his vaccine on eight dogs and 11 sheep, half of which died after inoculation. It was not a great success. Upon hearing the news, Pasteur immediately wrote to the academy that he could not believe that dead vaccine would work and that Toussaint's claim "overturns all the ideas I had on viruses, vaccines, etc."^[106] Following Pasteur's criticism, Toussaint switched to carbolic acid (phenol) to kill anthrax bacilli and tested the vaccine on sheep in August 1880. Pasteur thought that this type of killed vaccine should not work because he believed that attenuated bacteria used up nutrients that the bacteria needed to grow. He thought oxidizing bacteria when sitting in culture broth for prolonged periods made them less virulent.^[110]

However, Pasteur's laboratory found that anthrax bacillus was not easily weakened by culturing in air as it formed spores – unlike chicken cholera bacillus. In early 1881, his laboratory discovered that growing anthrax bacilli at about 42 °C made them unable to produce spores,^[111] and he described this method in a speech to the French Academy of Sciences on 28 February.^[112] On 21 March, despite inconsistent results, he announced successful vaccination of sheep. To this news, veterinarian Hippolyte Rossignol proposed that the Société d'agriculture de Melun organize an experiment to test Pasteur's vaccine. Pasteur signed an agreement accepting the challenge on 28 April. Pasteur's assistants, Roux and Chamberland, who were assigned the task of conducting the trial, were concerned about the unreliability of the attenuated vaccine, and therefore Chamberland secretly prepared an alternative vaccine using chemical inactivation.^[12] Without divulging their method of preparing the vaccine to anyone but Pasteur, Roux and Chamberland performed the public experiment on May at Pouilly-le-Fort. ^[12] 58 sheep, 2 goats and 10 cattle were used, half of which were given the vaccine on 5 and 17 May; while the other half was untreated.^[113] On 31 May, Roux and Chamberland next injected the animals with the fresh virulent culture of anthrax bacillus. The official result was observed and analyzed on 2 June in the presence of over 200 spectators, with Pasteur himself in attendance. The results were as Pasteur had bravely predicted: "I hypothesized that the six vaccinated cows would not become very ill, while the four unvaccinated cows would perish or at least become very ill."^[113] However, all vaccinated sheep and goats survived, while unvaccinated ones had died or were dying before the viewers.^[114] His report to the French Academy of Sciences on 13 June concludes:

[By] looking at everything from the scientific point of view, the development of a vaccination against anthrax constitutes significant progress beyond the first vaccine developed by Jenner, since the latter had never been obtained experimentally.^[113]

Pasteur did not directly disclose how he prepared the vaccines used at Pouilly-le-Fort.^[115][111] Although his report indicated it as a "live vaccine",^[113] his laboratory notebooks show that he actually used potassium dichromate-killed vaccine, as developed by Chamberland, quite similar to Toussaint's method.^{[116][55][117]}

The notion of a weak form of a disease causing immunity to the virulent version was not new; this had been known for a long time for smallpox. Inoculation with smallpox (variolation) was known to result in a much less severe disease, and greatly reduced mortality, in comparison with the naturally acquired disease.^[118] Edward Jenner had also studied vaccination using cowpox (vaccinia) to give cross-immunity to smallpox in the late 1790s, and by the early 1800s vaccination had spread to most of Europe.^[119]

The difference between smallpox vaccination and anthrax or chicken cholera vaccination was that the latter two disease organisms had been artificially weakened, so a naturally weak form of the disease organism did not need to be found.^[116] This discovery revolutionized work in infectious diseases, and Pasteur gave these artificially weakened diseases the generic name of "vaccines", in honour of Jenner's discovery.^[120]

Main article: Koch–Pasteur rivalry

In 1876, Robert Koch had shown that Bacillus anthracis caused anthrax.^[121] In his papers published between 1878 and 1880, Pasteur only mentioned Koch's work in a footnote. Koch met Pasteur at the Seventh International Medical Congress in 1881. A few months later, Koch wrote that Pasteur had used impure cultures and made errors. In 1882, Pasteur replied to Koch in a speech, to which Koch responded aggressively.^[11] Koch stated that Pasteur tested his vaccine on unsuitable animals and that Pasteur's research was not properly scientific.^[3] In 1882, Koch wrote "On the Anthrax Inoculation", in which he refuted several of Pasteur's conclusions about anthrax and criticized Pasteur for keeping his methods secret, jumping to conclusions, and being imprecise. In 1883, Pasteur wrote that he used cultures prepared in a similar way to his successful fermentation experiments and that Koch misinterpreted statistics and ignored Pasteur's work on silkworms.^[121]

Rabies

Pasteur's laboratory produced the first vaccine for rabies using a method deveoped by his assistant Roux,^[12] which involved growing the virus in rabbits, and then weakening it by drying the affected nerve tissue.^[71][125] The rabies vaccine was initially created by Emile Roux, a French doctor and a colleague of Pasteur, who had produced a killed vaccine using this method.^[3] The vaccine had been tested in 50 dogs before its first human trial.^[126][127] This vaccine was used on 9-year-old Joseph Meister, on 6 July 1885, after the boy was badly mauled by a rabid dog.^[55][125] This was done at some personal risk for Pasteur, since he was not a licensed physician and could have faced prosecution for treating the boy.^[49] After consulting with physicians, he decided to go ahead with the treatment.^[128] Over 11 days, Meister received 13 inoculations, each inoculation using viruses that had been weakened for a shorter period of time.^[129] Three months later he examined Meister and found that he was in good health.^[128][130] Pasteur was hailed as a hero and the legal matter was not pursued.^[49] Analysis of his laboratory notebooks shows that Pasteur had treated two people before his vaccination of Meister. One survived but may not actually have had rabies, and the other died of rabies.^[129][131] Pasteur began treatment of Jean-Baptiste Jupille on 20 October 1885, and the treatment was successful.^[129] Later in 1885, people, including four children from the United States, went to Pasteur's laboratory to be inoculated.^[128] In 1886, he treated 350 people, of which only one developed rabies.^[129] The treatment's success laid the foundations for the manufacture of many other vaccines. The first of the Pasteur Institutes was also built on the basis of this achievement.^[55]

In The Story of San Michele, Axel Munthe writes of some risks Pasteur undertook in the rabies vaccine research:^[132]

Pasteur himself was absolutely fearless. Anxious to secure a sample of saliva straight from the jaws of a rabid dog, I once saw him with the glass tube held between his lips draw a few drops of the deadly saliva from the mouth of a rabid bull-dog, held on the table by two assistants, their hands protected by leather gloves.

Because of his study in germs, Pasteur encouraged doctors to sanitize their hands and equipment before surgery. Prior to this, few doctors or their assistants practiced these procedures.^[133][134] Ignaz Semmelweis and Joseph Lister had earlier practiced hand sanitizing in medical contexts in the 1860s.^[135][136]

Fermentation

Scientists before Pasteur had studied fermentation. In the 1830s, Charles Cagniard-Latour, Friedrich Traugott Kützing and Theodor Schwann used microscopes to study yeasts and concluded that yeasts were living organisms. In 1839, Justus von Liebig, Friedrich Wöhler and Jöns Jacob Berzelius stated that yeast was not an organism and was produced when air acted on plant juice.^[63]

In 1855, Antoine Béchamp, Professor of Chemistry at the University of Montpellier, conducted experiments with sucrose solutions and concluded that water was the factor for fermentation.^[143] He changed his conclusion in 1858, stating that fermentation was directly related to the growth of moulds, which required air for growth. He regarded himself as the first to show the role of microorganisms in fermentation.^[144][59]

Pasteur started his experiments in 1857 and published his findings in 1858 (April issue of Comptes Rendus Chimie, Béchamp's paper appeared in January issue). Béchamp noted that Pasteur did not bring any novel idea or experiments. On the other hand, Béchamp was probably aware of Pasteur's 1857 preliminary works. With both scientists claiming priority on the discovery, a dispute, extending to several areas, lasted throughout their lives.^[145][146]

However, Béchamp was on the losing side, as the BMJ obituary remarked: His name was "associated with bygone controversies as to priority which it would be unprofitable to recall".^[147] Béchamp proposed the incorrect theory of microzymes. According to K. L. Manchester, anti-vivisectionists and proponents of alternative medicine promoted Béchamp and microzymes, unjustifiably claiming that Pasteur plagiarized Béchamp.^[59]

Pasteur thought that succinic acid inverted sucrose. In 1860, Marcellin Berthelot isolated invertase and showed that succinic acid did not invert sucrose.^[63] Pasteur believed that fermentation was only due to living cells. He and Berthelot engaged in a long argument subject of vitalism, in which Berthelot was vehemently opposed to any idea of vitalism.^[148] Hans Buchner discovered that zymase (not an enzyme, but a mixture of enzymes) catalyzed fermentation, showing that fermentation was catalyzed by enzymes within cells.^[149] Eduard Buchner also discovered that fermentation could take place outside living cells.^[150]

Anthrax vaccine

Pasteur publicly claimed his success in developing the anthrax vaccine in 1881.^[130] However, his admirer-turned-rival Henry Toussaint was the one who developed the first vaccine. Toussaint isolated the bacteria that caused chicken cholera (later named Pasteurella in honour of Pasteur) in 1879 and gave samples to Pasteur who used them for his own works.^[151] On 12 July 1880, Toussaint presented his successful result to the French Academy of Sciences, using an attenuated vaccine against anthrax in dogs and sheep.^[152] Pasteur on grounds of jealousy contested the discovery by publicly displaying his vaccination method at Pouilly-le-Fort on 5 May 1881.^[153] Pasteur then gave a misleading account of the preparation of the anthrax vaccine used in the experiment. He claimed that he made a "live vaccine", but used potassium dichromate^[12] to inactivate anthrax spores, a method similar to Toussaint's. The promotional experiment was a success and helped Pasteur sell his products, getting the benefits and glory.^{[153][154][155][156]}

Experimental ethics

Pasteur's experiments are often cited as against medical ethics, especially on his vaccination of Meister. He did not have any experience in medical practice, and more importantly, lacked a medical license. This is often cited as a serious threat to his professional and personal reputation.^[157][158] His closest partner Émile Roux, who had medical qualifications, refused to participate in the clinical trial, likely because he considered it unjust.^[129] However, Pasteur executed vaccination of the boy under the close watch of practising physicians Jacques-Joseph Grancher, head of the Paris Children's Hospital's paediatric clinic, and Alfred Vulpian, a member of the Commission on Rabies. He was not allowed to hold the syringe, although the inoculations were entirely under his supervision.^[128] It was Grancher who was responsible for the injections, and he defended Pasteur before the French National Academy of Medicine in the issue.^[159]

Pasteur has also been criticized for keeping secrecy of his procedure and not giving proper pre-clinical trials on animals.^[3] Pasteur stated that he kept his procedure secret in order to control its quality. He later disclosed his procedures to a small group of scientists. Pasteur wrote that he had successfully vaccinated 50 rabid dogs before using it on Meister.^{[160][161][162]} According to Geison, Pasteur's laboratory notebooks show that he had vaccinated only 11 dogs.^[3]

Meister never showed any symptoms of rabies,^[129] but the vaccination has not been proved to be the reason. One source estimates the probability of Meister contracting rabies at 10%.^[116]

Legacy

In many localities worldwide, streets are named in his honor. For example, in the US: Palo Alto and Irvine, California, Boston and Polk, Florida, adjacent to the University of Texas Health Science Center at San Antonio; Jonquière, Québec; San Salvador de Jujuy and Buenos Aires (Argentina), Great Yarmouth in Norfolk, in the United Kingdom, Jericho and Wulguru in Queensland, Australia; Phnom Penh in Cambodia; Ho Chi Minh City and Da Nang, Vietnam; Batna in Algeria; Bandung in Indonesia, Tehran in Iran, near the central campus of the Warsaw University in Warsaw, Poland; adjacent to the Odesa State Medical University in Odesa, Ukraine; Milan in Italy and Bucharest, Cluj-Napoca and Timișoara in Romania. The Avenue Pasteur in Saigon, Vietnam, is one of the few streets in that city to retain its French name. Avenue Louis Pasteur in the Longwood Medical and Academic Area in Boston was named in his honor in the French manner with "Avenue" preceding the name of the dedicatee.^[180]

Both the Institut Pasteur and Université Louis Pasteur were named after Pasteur. The schools Lycée Pasteur in Neuilly-sur-Seine, France, and Lycée Louis Pasteur in Calgary, Alberta, Canada, are named after him. In South Africa, the Louis Pasteur Private Hospital in Pretoria, and Life Louis Pasteur Private Hospital, Bloemfontein, are named after him. Louis Pasteur University Hospital in Košice, Slovakia is also named after Pasteur.

A statue of Pasteur is erected at San Rafael High School in San Rafael, California. A bronze bust of him resides on the French Campus of Kaiser Permanente's San Francisco Medical Center in San Francisco. The sculpture was designed by Harriet G. Moore and cast in 1984 by Artworks Foundry.^[181]

The UNESCO/Institut Pasteur Medal was created on the centenary of Pasteur's death, and is given every two years in his name, "in recognition of outstanding research contributing to a beneficial impact on human health".^[182]

The French Academician Henri Mondor stated: "Louis Pasteur was neither a physician nor a surgeon, but no one has done as much for medicine and surgery as he has."^[183]

Pasteur Institute

After developing the rabies vaccine, Pasteur proposed an institute for the vaccine.^[184] In 1887, fundraising for the Pasteur Institute began, with donations from many countries. The official statute was registered in 1887, stating that the institute's purposes were "the treatment of rabies according to the method developed by M. Pasteur" and "the study of virulent and contagious diseases".^[128] The institute was inaugurated on 14 November 1888.^[128] He brought together scientists with various specialties. The first five departments were directed by two graduates of the École Normale Supérieure: Émile Duclaux (general microbiology research) and Charles Chamberland (microbe research applied to hygiene), as well as a biologist, Élie Metchnikoff (morphological microbe research) and two physicians, Jacques-Joseph Grancher (rabies) and Émile Roux (technical microbe research). One year after the inauguration of the institute, Roux set up the first course of microbiology ever taught in the world, then entitled Cours de Microbie Technique (Course of microbe research techniques). Since 1891 the Pasteur Institute had been extended to different countries, and currently there are 32 institutes in 29 countries in various parts of the world.^[185]

Faith and spirituality

His grandson, Louis Pasteur Vallery-Radot, wrote that Pasteur had kept from his Catholic background only a spiritualism without religious practice.^[188] However, Catholic observers often said that Pasteur remained an ardent Christian throughout his whole life, and his son-in-law wrote, in a biography of him:

Absolute faith in God and in Eternity, and a conviction that the power for good given to us in this world will be continued beyond it, were feelings which pervaded his whole life; the virtues of the gospel had ever been present to him. Full of respect for the form of religion which had been that of his forefathers, he came simply to it and naturally for spiritual help in these last weeks of his life.^[189]

The Literary Digest of 18 October 1902 gives this statement from Pasteur that he prayed while he worked:^[190]

Posterity will one day laugh at the foolishness of modern materialistic philosophers. The more I study nature, the more I stand amazed at the work of the Creator. I pray while I am engaged at my work in the laboratory.

Maurice Vallery-Radot, grandson of the brother of the son-in-law of Pasteur and outspoken Catholic, also holds that Pasteur fundamentally remained Catholic.^[191] According to both Pasteur Vallery-Radot and Maurice Vallery-Radot, the following well-known quotation attributed to Pasteur is apocryphal:^[192] "The more I know, the more nearly is my faith that of the Breton peasant. Could I but know all I would have the faith of a Breton peasant's wife".^[14] According to Maurice Vallery-Radot,^[193] the false quotation appeared for the first time shortly after the death of Pasteur.^[194] However, despite his belief in God, it has been said that his views were that of a freethinker rather than a Catholic, a spiritual more than a religious man.^[195][196] He was also against mixing science with religion.^[197][198]

Death

In 1868, Pasteur suffered a severe brain stroke that paralysed the left side of his body, but he recovered.^[199] A stroke or uremia in 1894 severely impaired his health.^{[200][201][202]} Failing to fully recover, he died on 28 September 1895, near Paris.^[55] He was given a state funeral and was buried in the Cathedral of Notre Dame, but his remains were reinterred in the Pasteur Institute in Paris,^[203] in a vault covered in depictions of his accomplishments in Byzantine mosaics.^[204]