Editing Louis Pasteur (section)

== Research ==

=== Molecular asymmetry ===
[[File:Pcrystals.svg|thumb|Pasteur separated the left and right [[crystal]] shapes from each other to form two piles of crystals: in solution one form rotated light to the left, the other to the right, while an [[Racemic mixture|equal mixture]] of the two forms canceled each other's effect, and does not rotate the [[polarized light]].]]

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]].<ref name="Flack" />

He resolved a problem concerning the nature of [[tartaric acid]] in 1848.<ref>L. Pasteur (1848) [http://gallica.bnf.fr/ark:/12148/bpt6k2983p/f539.item.r=.zoom "Mémoire sur la relation qui peut exister entre la forme cristalline et la composition chimique, et sur la cause de la polarisation rotatoire"] {{Webarchive|url=https://web.archive.org/web/20161021035454/http://gallica.bnf.fr/ark:/12148/bpt6k2983p/f539.item.r=.zoom |date=21 October 2016 }} (Memoir on the relationship that can exist between crystalline form and chemical composition, and on the cause of rotary polarization)," ''Comptes rendus de l'Académie des sciences'' (Paris), '''26''': 535–538.</ref><ref>L. Pasteur (1848) [https://books.google.com/books?id=gJ45AAAAcAAJ&pg=PA442 "Sur les relations qui peuvent exister entre la forme cristalline, la composition chimique et le sens de la polarisation rotatoire"] (On the relations that can exist between crystalline form, and chemical composition, and the sense of rotary polarization), ''Annales de Chimie et de Physique'', 3rd series, vol. 24, no. 6, pp.&nbsp;442–459.</ref><ref>George B. Kauffman and Robin D. Myers (1998)[https://web.archive.org/web/20060117144722/http://192.129.24.144/licensed_materials/00897/papers/0003006/36kau897.pdf "Pasteur's resolution of racemic acid: A sesquicentennial retrospect and a new translation,"] ''The Chemical Educator'', vol. 3, no. 6, pp. 1–4, {{doi|10.1007/s00897980257a}}</ref><ref name=Gal>Joseph Gal: ''Louis Pasteur, Language, and Molecular Chirality. I. Background and Dissymmetry'', Chirality ''23'' ('''2011''') 1–16.</ref> A solution of this compound derived from living things [[Optical rotation|rotated]] the [[plane of polarization]] of light passing through it.<ref name="Flack">H.D. Flack (2009) [http://crystal.flack.ch/dox/sh5092.pdf "Louis Pasteur's discovery of molecular chirality and spontaneous resolution in 1848, together with a complete review of his crystallographic and chemical work,"] {{Webarchive|url=https://web.archive.org/web/20190908211420/http://crystal.flack.ch/dox/sh5092.pdf |date=8 September 2019 }} ''Acta Crystallographica'', Section A, vol. 65, pp.&nbsp;371–389.</ref> 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.<ref name="cohn" />

Pasteur noticed that crystals of tartrates had small faces. Then he observed that, in [[racemic mixture]]s 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.<ref name="Flack" /> 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.<ref name=Chirality>{{cite web|title=Louis Pasteur|url=https://www.sciencehistory.org/historical-profile/louis-pasteur|website=[[Science History Institute]]|access-date=20 March 2018|date=June 2016|archive-date=21 March 2018|archive-url=https://web.archive.org/web/20180321132243/https://www.sciencehistory.org/historical-profile/louis-pasteur|url-status=live}}</ref> The (2''R'',3''R'')- and (2''S'',3''S'')- tartrates were isometric, non-superposable mirror images of each other. This was the first time anyone had demonstrated [[Chirality (chemistry)|molecular chirality]], and also the first explanation of [[isomer]]ism.<ref name="Flack" />

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."<ref name="Flack" />

=== 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.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|page=79|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n101/mode/2up}}</ref><ref name=Ligon /> 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.<ref>{{cite book|last1=Vallery-Radot|first1=René|title=La vie de Pasteur|date=1907|publisher=Librairie Hachette|location=Paris|page=98|url=https://archive.org/stream/laviedepasteur01vallgoog#page/n110/mode/2up|language=fr}}</ref> A memoire was subsequently published on 30 November 1857.<ref>{{cite journal|last1=Pasteur|first1=Louis|title=Mémoire sur la fermentation appelée lactique|journal=Comptes Rendus Chimie|year=1857|volume=45|pages=913–916|url=http://gallica.bnf.fr/ark:/12148/bpt6k30026.image.r=+COMPTES+RENDUS+++DES+S%C3%89ANCES+DE+L.f915.langFR|language=fr|access-date=11 March 2017|archive-date=12 March 2017|archive-url=https://web.archive.org/web/20170312141626/http://gallica.bnf.fr/ark:/12148/bpt6k30026.image.r=+COMPTES+RENDUS+++DES+S%C3%89ANCES+DE+L.f915.langFR|url-status=live}}</ref> 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 acid bacteria|lactic yeast]], always present when [[Lactic acid fermentation|sugar becomes lactic acid]]."<ref name=manchester2007>{{cite journal|last1=Manchester|first1=K.L.|title=Louis Pasteur, fermentation, and a rival|journal=South African Journal of Science|year=2007|volume=103|issue=9–10|pages=377–380|url=http://www.scielo.org.za/scielo.php?pid=S0038-23532007000500008&script=sci_arttext|access-date=26 October 2014|archive-date=26 October 2014|archive-url=https://web.archive.org/web/20141026053500/http://www.scielo.org.za/scielo.php?pid=S0038-23532007000500008&script=sci_arttext|url-status=live}}</ref>

This memoir on alcoholic fermentation was published in full form in 1858.<ref>{{cite journal|last1=Pasteur|first1=Louis|title=Nouveaux faits concernant l'histoire de la fermentation alcoolique|journal=Comptes Rendus Chimie|year=1858|volume=47|pages=1011–1013|language=fr}}</ref><ref>{{cite journal|last1=Pasteur|first1=Louis|title=Nouveaux faits concernant l'histoire de la fermentation alcoolique|journal=Annales de Chimie et de Physique |series=3rd Series|year=1858|volume=52|pages=404–418|language=fr}}</ref> [[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.<ref name=Barnett>{{cite book|last1=Barnett|first1=James A.|last2=Barnett|first2=Linda|title=Yeast Research: A Historical Overview|year=2011|publisher=ASM Press|location=Washington, DC|isbn=978-1-55581-516-5|url=https://books.google.com/books?id=ZwisBAAAQBAJ}}</ref> He also demonstrated that, when a different microorganism contaminated the wine, lactic acid was produced, making the wine sour.<ref name=Ligon /> In 1861, Pasteur observed that less sugar fermented per part of yeast when the yeast was exposed to air.<ref name=Barnett /> The lower rate of fermentation aerobically became known as the [[Pasteur effect]].<ref>{{cite book|editor1-last=Zimmermann|editor1-first=F.K.|editor2-last=Entian|editor2-first=K.-D.|title=Yeast Sugar Metabolism|date=1997|publisher=CRC Press|isbn=978-1-56676-466-7|pages=20–21|url=https://books.google.com/books?id=VSQZ1AVg74oC&pg=PA20}}</ref>
[[File:Louis Pasteur experiment.jpg|thumb|left|Pasteur experimenting in his laboratory]]
[[File:LouisPasteurMonumentLille.jpg|thumb|[[Institut Pasteur de Lille]]]]

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&nbsp;°C.<ref name=Bowden /> This killed most bacteria and moulds already present within them. Pasteur and [[Claude Bernard]] completed tests on blood and urine on 20 April 1862.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R.L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|page=104|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n125/mode/2up}}</ref> Pasteur patented the process, to fight the "diseases" of wine, in 1865.<ref name=Bowden>{{cite book|last1=Bowden|first1=Mary Ellen|last2=Crow|first2=Amy Beth|last3=Sullivan|first3=Tracy|title=Pharmaceutical achievers: the human face of pharmaceutical research|year=2003|publisher=Chemical Heritage Press|location=Philadelphia|isbn=978-0-941901-30-7|url=https://books.google.com/books?id=4yPPE0xHEmkC&pg=PA6}}</ref> The method became known as [[pasteurization]], and was soon applied to beer and milk.<ref name=Nelson2009>{{cite journal|last1=Nelson|first1=Bryn|title=The Lingering Heat over Pasteurized Milk|journal=Chemical Heritage Magazine|year=2009|volume=27|issue=1|url=https://www.sciencehistory.org/distillations/article/lingering-heat-over-pasteurized-milk|access-date=20 March 2018|archive-date=21 March 2018|archive-url=https://web.archive.org/web/20180321192530/https://www.sciencehistory.org/distillations/article/lingering-heat-over-pasteurized-milk|url-status=live}}</ref>

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.<ref name=Listerine>{{cite journal|last1=Hicks|first1=Jesse|title=A Fresh Breath|url=http://www.chemheritage.org/discover/online-resources/thanks-to-chemistry/listerine.aspx|journal=Chemical Heritage Magazine |access-date=27 January 2015 |url-status=dead |archive-url=https://web.archive.org/web/20160611130657/http://www.chemheritage.org/discover/online-resources/thanks-to-chemistry/listerine.aspx|archive-date=11 June 2016}}</ref>

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.<ref name=Barnett />

In the early 19th century, [[Agostino Bassi]] had shown that [[muscardine]] was caused by a fungus that infected silkworms.<ref name=Hatcher /> Since 1853, two diseases called ''[[pébrine]]'' and ''[[flacherie]]'' had been infecting great numbers of [[silkworm]]s 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.<ref name=Berche>{{cite journal|last1=Berche|first1=P.|title=Louis Pasteur, from crystals of life to vaccination|journal=Clinical Microbiology and Infection|year=2012|volume=18|issue=s5|pages=1–6|doi=10.1111/j.1469-0691.2012.03945.x|pmid=22882766|doi-access=free}}</ref><ref name="Schwartz">{{cite journal|last1=Schwartz|first1=M.|year=2001|title=The life and works of Louis Pasteur|journal=Journal of Applied Microbiology|volume=91|issue=4|pages=597–601|doi=10.1046/j.1365-2672.2001.01495.x|pmid=11576293|doi-access=|s2cid=39020116}}</ref>

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]]).<ref name=Hatcher>{{cite book|last1=Hatcher|first1=Paul|last2=Battey|first2=Nick|title=Biological Diversity: Exploiters and Exploited|date=2011|publisher=John Wiley & Sons|isbn=978-0-470-97986-0|pages=88–89, 91|url=https://books.google.com/books?id=FpQpedSpeWMC&pg=PA89}}</ref> Pasteur also showed that the disease was hereditary.<ref name="Keim pp. 87-88">{{cite book|last1=Keim|first1=Albert|last2=Lumet|first2=Louis|title=Louis Pasteur|date=1914|publisher=Frederick A. Stokes Company|pages=87–88|url=https://archive.org/stream/louispasteur00keim#page/86/mode/2up}}</ref> 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.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|page=141|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n161/mode/2up}}</ref><ref name="Keim pp. 87-88" /> Pasteur concluded that bacteria caused flacherie. The primary cause is currently thought to be viruses.<ref name=Hatcher /> 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.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|page=156|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n175/mode/2up}}</ref>

=== Spontaneous generation ===
[[File:Coldecygne.svg|thumb|Bottle en ''col de cygne'' ([[swan neck flask|swan-neck bottle]]) used by Pasteur]]
[[File:Louis Pasteur Experiment.svg|thumb|Louis Pasteur's pasteurization experiment illustrates the fact that the spoilage of liquid was caused by particles in the air rather than the air itself. These experiments were important pieces of evidence supporting the germ theory of disease.]]
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.<ref name=Ligon />

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 [[Muséum d'Histoire Naturelle de Rouen|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.<ref name=Magner>{{cite book|last1=Magner|first1=Lois N.|title=History of the Life Sciences|year=2002|publisher=Marcel Dekker|location=New York|isbn=978-0-203-91100-6|pages=251–252|edition=3|url=https://books.google.com/books?id=YKJ6gVYbrGwC&q=Pasteur+spontaneous+generation}}</ref><ref>{{cite journal|last1=Roll-Hansen|first1=Nils|title=Experimental Method and Spontaneous Generation: The Controversy between Pasteur and Pouchet, 1859–64|journal=Journal of the History of Medicine and Allied Sciences|year=1979|volume=XXXIV|issue=3|pages=273–292|doi=10.1093/jhmas/XXXIV.3.273|pmid=383780|s2cid=39800747|url=http://pdfs.semanticscholar.org/ac3d/ed2ccb23bb9274305eb49bb422979276273f.pdf|archive-url=https://web.archive.org/web/20190303003149/http://pdfs.semanticscholar.org/ac3d/ed2ccb23bb9274305eb49bb422979276273f.pdf|url-status=dead|archive-date=3 March 2019}}</ref><ref>{{cite journal|last1=Farley|first1=J|last2=Geison|first2=GL|title=Science, politics and spontaneous generation in nineteenth-century France: the Pasteur-Pouchet debate|journal=Bulletin of the History of Medicine|year=1974|volume=48|issue=2|pages=161–198|pmid=4617616}}</ref>

Pouchet stated that air everywhere could cause spontaneous generation of living organisms in liquids.<ref>{{cite book|last1=Keim|first1=Albert|last2=Lumet|first2=Louis|title=Louis Pasteur|date=1914|publisher=Frederick A. Stokes Company|pages=64|url=https://archive.org/stream/louispasteur00keim#page/64/mode/2up}}</ref> In the late 1850s, he performed experiments and claimed that they were evidence of spontaneous generation.<ref name="porter" /><ref name=Magner /> [[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.<ref name=Berche />

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.<ref name="porter" /> 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.<ref name=Ligon /><ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|pages=96–98|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n117/mode/2up}}</ref> Pasteur also used [[swan neck flask]]s 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.<ref name=Ligon /><ref>{{cite book|last1=Keim|first1=Albert|last2=Lumet|first2=Louis|title=Louis Pasteur|date=1914|publisher=Frederick A. Stokes Company|pages=63–67|url=https://archive.org/stream/louispasteur00keim#page/62/mode/2up}}</ref>

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'').<ref>{{Cite web|last=Pasteur|first=Louis|year=1882|title=Mémoire sur les corpuscules organisés qui existent dans l'atmosphère: examen de la doctrine des générations spontanées|url=https://wellcomecollection.org/works/njdg2696|url-status=live|access-date=1 May 2021|website=Wellcome Collection|language=en|archive-date=1 May 2021|archive-url=https://web.archive.org/web/20210501062347/https://wellcomecollection.org/works/njdg2696}}</ref><ref>{{Cite journal|last=Carter|first=K. C.|year=1991|title=The development of Pasteur's concept of disease causation and the emergence of specific causes in nineteenth-century medicine|url=https://pubmed.ncbi.nlm.nih.gov/1802317|journal=Bulletin of the History of Medicine|volume=65|issue=4|pages=528–548|jstor=44442642|pmid=1802317|access-date=1 May 2021|archive-date=25 January 2022|archive-url=https://web.archive.org/web/20220125231811/https://pubmed.ncbi.nlm.nih.gov/1802317/|url-status=live}}</ref> Pasteur won the Alhumbert Prize in 1862.<ref name="porter">{{cite journal|last1=Porter|first1=JR|title=Louis Pasteur: achievements and disappointments, 1861.|journal=Bacteriological Reviews|year=1961|volume=25|issue=4|pages=389–403|pmid=14037390|pmc=441122|doi=10.1128/MMBR.25.4.389-403.1961}}</ref> He concluded that:{{blockquote|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.<ref name="Ligon" /><ref name="Schwartz" />}}

=== 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 [[Bombyx mori|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 "[[Emilio Cornalia|Cornalia]] corpuscles". Pasteur accepted and made five long stays in [[Alès]], between 7 June 1865 and 1869.<ref>Jimmy Drulhon, ''Louis Pasteur. Five years in the Cévennes'', Ed. Hermann, 2009. Pasteur stayed and carried out his scientific work at the [[magnanerie]] of Pont Gisquet, on the road to Saint-Jean-du-Pin.[https://www.google.fr/maps/@44.121694,4.059807,3a,75y,179.7h,70.21t/data=!3m4!1e1!3m2!1sufDCWdKLIc2BJ7ebZ8HMrg!2e0 See Google Street.] {{Webarchive|url=https://web.archive.org/web/20220407210606/https://www.google.fr/maps/@44.121694,4.059807,3a,75y,179.7h,70.21t/data=!3m4!1e1!3m2!1sufDCWdKLIc2BJ7ebZ8HMrg!2e0|date=7 April 2022}}</ref>

==== Initial errors ====
Arriving in Alès, Pasteur familiarized himself with pébrine and also<ref>"He had known it [= flacherie] for a long time, since his first stay in the South in 1865, where one of the two farms that had served as a starting point departure to his deductions was affected by this disease, at the same time as that of the corpuscles." Émile Duclaux, ''Pasteur, Histoire d'un esprit'', pp. 218–219, available on [https://gallica.bnf.fr/ark:/12148/bpt6k764468/f223.table Gallica] {{Webarchive|url=https://web.archive.org/web/20220126152716/https://gallica.bnf.fr/ark:/12148/bpt6k764468/f223.table |date=26 January 2022 }}.</ref> with another disease of the silkworm, known earlier<ref>"This denomination of ''white-dead'', used by the Abbé de Sauvages and several other writers, is inaccurate; this is why I thought it necessary to add that of ''dead-flats'', vulgarly used in several departments, and which designates very well the state of softness and flaccidity in which the worms dead of this disease are found. " Pierre Hubert Nysten, ''Research on the diseases of silkworms'', Paris, 1808, p. 5, available on [https://books.google.com/books?id=1tRIAAAAIAAJ&pg=PA12 Google Books].</ref> than pebrine: [[flacherie]] or dead-flat disease. Contrary, for example, to [[Jean Louis Armand de Quatrefages de Bréau|Quatrefages]], who coined the new word ''pébrine'',<ref>See account of Quatrefages reproduced in L. Pasteur, ''Études sur la maladie des vers à soie'', Paris, 1870, Complete Works of Pasteur, t. 4, p. 27, [https://gallica.bnf.fr/ark:/12148/bpt6k73599/f40.table online] {{Webarchive|url=https://web.archive.org/web/20220126152711/https://gallica.bnf.fr/ark:/12148/bpt6k73599/f40.table |date=26 January 2022 }}.</ref> Pasteur made the mistake of believing that the two diseases were the same and even that most of the diseases of silkworms known up to that time were identical with each other and with pébrine.<ref>"But the cases of association were so frequent, precisely because the disease of the corpuscles was so widespread, that Pasteur had thought that the two conditions were linked to each other and should disappear together. " (Émile Duclaux, ''Pasteur, Histoire d'un esprit'', pp. 218–219, [https://gallica.bnf.fr/ark:/12148/bpt6k764468/f223.table online] {{Webarchive|url=https://web.archive.org/web/20220126152716/https://gallica.bnf.fr/ark:/12148/bpt6k764468/f223.table |date=26 January 2022 }}.) Pasteur expressed this opinion, in particular in " Nouvelles études sur la maladie des vers à soie ", Comptes rendus de l'Académie des sciences, t. 63 (1866), pp. 126–142: "I am very much inclined to believe that there is no actual actual disease of silkworms. The disease complained of seems to me to have always existed, but to a lesser degree. (...) Furthermore, I have serious grounds for believing that most of the diseases of the silkworm which have been known for a long time are linked to the one which occupies us, muscardine and, perhaps, grasserie excepted. (p. 136). Available at [https://gallica.bnf.fr/ark:/12148/bpt6k30204/f136.table Gallica] {{Webarchive|url=https://web.archive.org/web/20220126152722/https://gallica.bnf.fr/ark:/12148/bpt6k30204/f136.table |date=26 January 2022 }}. Same thing in a letter of June 27, 1866, to Dumas: "all the other so-called ancient diseases of the silkworm, minus the ''muscardine'' and perhaps the ''grasserie'', such as the disease of '' motrs -flats'', ''petits'', ''passis'', ''arpians'', are only forms of the actual disease. " (Pasteur, ''Correspondance'', t. 2, p. 265. Quoted by Ph. Decourt, ''Les vérités indésirables'', Paris, 1989, p. 173, and by P. Pinet, ''Pasteur et la phiolosophie'', Paris, 2004, p. 158.</ref> It was in letters of 30 April and 21 May 1867 to Dumas that he first made the distinction between pébrine and flacherie.<ref>"Sur la maladie des vers à soie. Lettre de M. L. Pasteur à M. Dumas", Comptes rendus de l'Académie des sciences, meeting of 3 June 1867, t. 64, p. 1113. Available at [https://gallica.bnf.fr/ark:/12148/bpt6k3021f/f1122.table Gallica] {{Webarchive|url=https://web.archive.org/web/20220407215406/https://gallica.bnf.fr/ark:/12148/bpt6k3021f/f1122.table |date=7 April 2022 }}.</ref>

He made another mistake: he began by denying the "parasitic" (microbial) nature of pébrine, which several scholars (notably [[Antoine Béchamp]])<ref>Philippe Decourt, ''Les vérités indésirables'', Paris, 1989, pp. 165–193, accuses Pasteur of a denial of justice towards Antoine Béchamp, who studied pebrine at the same time as Pasteur and immediately affirmed the parasitic nature of the disease.</ref> considered well established. Even a note published on 27 August 1866 by [[Édouard-Gérard Balbiani|Balbiani]],<ref>Balbiani, Balbiani, " Recherches sur les corpuscules de la pébrine et sur leur mode de propagation ", Comptes rendus de l'Académie des Sciences, session of 27 August 1866, vol. 63 (1866), pp. 388–391, available at [https://gallica.bnf.fr/ark:/12148/bpt6k30204/f388.table Gallica] {{Webarchive|url=https://web.archive.org/web/20220126152715/https://gallica.bnf.fr/ark:/12148/bpt6k30204/f388.table |date=26 January 2022 }}. Balbiani begins in this manner: "Among all the contradictory opinions which have been expressed on the nature of the corpuscles of the pébrine, the most debatable, in my opinion, is that which consists in assimilating them to anatomical elements either normal, or more or less altered., or to morbid products such as pus globules, etc. This opinion was refuted more than eight years ago by Professor Lebert (...); but I believe I can also bring, against the way of seeing cited above, more decisive proofs, based on the observation of the phenomena which these corpuscles present in their evolution, phenomena which put beyond doubt their close relationship with the parasitic organisms. known under the name of ''Psorospermia''".</ref> which Pasteur at first seemed to welcome favourably<ref>"As for the opinions expressed by Mr. Balbiani on the nature of the corpuscles, although I do not share them, I will take great care to examine them, for two reasons: because they are from a skilful observer, and because I still only have preconceived views on the objects they concern, to which I do not agree more than reason. There is more: I earnestly hope that the ideas of MM. Balbiani and Leydig are true (...)". Pasteur, "Observations au sujet d'une Note de M. Balbiani relative à la maladie des vers à soie", ''Comptes rendus de l'Académie des Sciences'', meeting of 10 September 1866, vol. 63 (1866), pp. 441–443.</ref> had no effect, at least immediately.<ref>On 29 May 1867, Pasteur wrote to Dumas again: "Despite all that I would have to say about the notes of Béchamp, Estor, Balbiani and on the articles that the first two insert in the ''Messager du Midi'', I take your advice, I do not answer. If you knew how erroneous it is to say that this disease is not constitutional and only parasitic. Its essential character is precisely its constitutional character. " (Quoted by Ph. Decourt, ''Les vérités indésirables'', Paris, 1989, p. 190.)</ref> "Pasteur is mistaken. He would only change his mind in the course of 1867".<ref>P. Debré, ''Louis Pasteur'', Flammarion, 1994, p. 219. In his ''Études sur la maladie des vers à soie'' (''Studies on silkworm disease''), published in 1870 (Pasteur's Complete Works, vol. 4, available at [https://gallica.bnf.fr/ark:/12148/bpt6k73599 Gallica] {{Webarchive|url=https://web.archive.org/web/20220126152720/https://gallica.bnf.fr/ark:/12148/bpt6k73599 |date=26 January 2022 }}), Pasteur reports that he consulted Leydig on the question of the living nature of corpuscles. (One of his letters to Leydig is from December 1866.) He admits that "in substance" he adopted the opinions of Leydig and Balbiani, but he contradicts them on the question of the mode of formation of the corpuscles (pp. 135, 137 and 138). In 1884, Balbiani will examine Pasteur's theory on the development of corpuscles and will conclude as follows: "I believe that it is useless to dwell any longer on the observations of M. Pasteur, which I think I can characterize with a single word by saying that their author proves in it how little he is familiar with the researches of biology. But with this reservation, I do justice to his work, which has rendered sericulture farmers a real service by enabling them to recognize a healthy seed from a diseased seed. " (G. Balbiani, ''Leçons sus les sporozoaires'', Paris, 1884, pp. 160–163, [https://archive.org/details/leonssurlesspo00balb online.]) On Pasteur's errors in the study of silkworms and his own judgment on these errors, see Richard Moreau, "Le dernier pli cacheté de Louis Pasteur à l'Académie des sciences", La vie des sciences, ''Comptes rendus'', série générale, t. 6, 1989, n° 5, pp. 403–434, [https://www.academie-sciences.fr/archivage_site/fondations/lp_pdf/Plis_07_1869.pdf online] {{Webarchive|url=https://web.archive.org/web/20220130215818/https://www.academie-sciences.fr/archivage_site/fondations/lp_pdf/Plis_07_1869.pdf |date=30 January 2022 }}.</ref>

==== Victory over pébrine ====

At a time where Pasteur had not yet understood the cause of the pébrine, he propagated an effective process to stop infections: a sample of chrysalises was chosen, they were crushed and the corpuscles were searched for in the crushed material; if the proportion of corpuscular pupae in the sample was very low, the chamber was considered good for reproduction.<ref>Louis Pasteur, ''Études sur la maladie des vers à soie''; Œuvres complètes, t. 4, pp. 166–167, available at [https://gallica.bnf.fr/ark:/12148/bpt6k73599/f195.table Gallica] {{Webarchive|url=https://web.archive.org/web/20220126152711/https://gallica.bnf.fr/ark:/12148/bpt6k73599/f195.table |date=26 January 2022 }}.</ref> This method of sorting "seeds" (eggs) is close to a method that Osimo had proposed a few years earlier, but whose trials had not been conclusive.<ref>Pasteur mentions Osimo's ideas in Louis Pasteur, ''Études sur la maladie des vers à soie'', Œuvres complètes, t. 4, pp. 38–39, available at [https://gallica.bnf.fr/ark:/12148/bpt6k73599/f57.table Gallica] {{Webarchive|url=https://web.archive.org/web/20220126152724/https://gallica.bnf.fr/ark:/12148/bpt6k73599/f57.table |date=26 January 2022 }}. Summarizing a development by Émile Duclaux (Émile Duclaux, ''Pasteur, histoire d'un esprit'', Sceaux, 1896, p. 198, available at [https://gallica.bnf.fr/ark:/12148 /bpt6k764468/f203.notice Gallica] {{Webarchive|url=https://web.archive.org/web/20070706205222/http://gallica.bnf.fr/ark:/12148 |date=6 July 2007 }}), P. Debré wrote that Pasteur was "led to propose a seed sorting method almost identical to that recommended a few years earlier by Orcino [read: Osimo]. If the latter had failed, asserts Pasteur, it was through a lack of confidence; which, of course, is not his case. " P. Debré, ''Louis Pasteur'', Flammarion, 1994, p. 210.</ref> By this process, Pasteur curbed pébrine and saved much of the silk industry in the Cévennes.<ref>Patrice Debré, Louis Pasteur, Flammarion, 1995, p. 246.</ref><ref>Elie Reynier, ''La soie en Vivarais'', 1921, [http://www.nemausensis.com/ardeche/soie/LaMaladie.htm online] {{Webarchive|url=https://web.archive.org/web/20220104215910/http://www.nemausensis.com/ardeche/soie/LaMaladie.htm |date=4 January 2022 }}.</ref>

==== Flacherie resists ====
[[File:Pasteur by Lafon 1883.jpg|thumb|Portrait of Louis Pasteur by François Lafon (1883)]]
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.<ref>(''Comptes rendus sténographiques du Congrès international séricicole, tenu à Paris du 5 au 10 septembre 1878''; Paris, 1879, pp. 27–38. ''Œuvres complètes'' of Pasteur, t. 4, pp. 698–713, spec. 699 and 713; available on [http://gallica2.bnf.fr/ark:/12148/bpt6k73599.image.f746.langEN.tableDesMatieres Gallica] {{Webarchive|url=https://archive.today/20130801101453/http://gallica2.bnf.fr/ark:/12148/bpt6k73599.image.f746.langEN.tableDesMatieres |date=1 August 2013 }}.</ref>

In 1884, [[Édouard-Gérard Balbiani|Balbiani]],<ref>G. Balbiani, ''Leçons sus les sporozoaires'', Paris, 1884, pp. 160–163, 167–168,  [https://archive.org/details/leonssurlesspo00balb online].</ref> 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.){{circular reference|date=March 2025}}

=== Immunology and vaccination ===
==== Chicken cholera ====
Pasteur's first work on vaccine development was on [[chicken cholera]]. He received the bacteria samples (later called ''Pasteurella multocida'' after him) from [[Jean Joseph Henri Toussaint|Henry Toussaint]].<ref name="Plotkin pp. 35-36">{{cite book|editor1-last=Plotkin|editor1-first=Stanley A.|title=History of Vaccine Development|date=2011|publisher=Springer|isbn=978-1-4419-1339-5|pages=35–36|url=https://books.google.com/books?id=Wf2jS_4lCOAC&pg=PA39}}</ref> Being unable to conduct the experiments himself due to a stroke in 1868,<ref>{{cite book |last1=Descour |first1=L. |title=Pasteur and his work |date=1922 |publisher=Frederick A. Stokes Company |location=New York}}</ref> Pasteur relied heavily on his assistants Emile Roux and Charles Chamberland. The work with chicken cholera was initiated in 1877, and by the next year, Roux was able to maintain a stable culture using broths.<ref name=":0">{{Cite journal|last=Barranco|first=Caroline|date=28 September 2020|title=The first live attenuated vaccines|url=https://www.nature.com/articles/d42859-020-00008-5|journal=Nature Milestones|language=en|access-date=30 April 2021|archive-date=2 August 2021|archive-url=https://web.archive.org/web/20210802072726/https://www.nature.com/articles/d42859-020-00008-5|url-status=live}}</ref> As documented later by Pasteur in his notebook in March of 1880,<ref>{{cite journal |last1=Murnane |first1=John P |last2=Probert |first2=Rebecca |title=The relationship between Rose Anna Shedlock (c1850-1878) and Emile Roux (1853-1933) |journal=Journal of Medical Biography |date=August 25, 2024 |volume=online first |pages=1–8 |doi=10.1177/09677720241273568 |pmid=39183561 |doi-access=free |pmc=12056263 }}</ref><ref>{{cite book |last1=Bazin |first1=Herve |title=Vaccination: a History |date=2011 |publisher=John Libby |location=Esher, United Kingdom}}</ref> in October of 1879, being delayed in returning to the laboratory due to his daughter’s wedding and ill health, he instructed Roux to start a new chicken cholera culture using bacteria from a culture that had sat since July. The two chickens inoculated with this new culture showed some symptoms of infection, but instead of the infections being fatal, as they usually were, the chickens recovered completely. After further incubation of the culture for an additional 8 days, Roux again inoculated the same two chickens. As was also noted by Pasteur in his notebook in March of 1880, and contrary to some accounts, this time the chickens died. Thus, although the attenuated bacteria did not provide immunity, these experiments provided important clues as to how bacteria could be artificially attenuated in the laboratory. As a result, upon Pasteur’s return to the laboratory, the focus of the research was directed at creating a vaccine through attenuation. 

In February of 1880, Pasteur presented his results to the French Academy of Sciences as "''Sur les maladies virulentes et en particulier sur la maladie appelée vulgairement choléra des poules'' (On virulent diseases, and in particular on the disease commonly called chicken cholera)" and published it in the academy's journal (''[[Comptes rendus de l'Académie des Sciences|Comptes-Rendus hebdomadaires des séances de l'Académie des Sciences]]''). He attributed that the bacteria were weakened by contact with oxygen.<ref name="Plotkin pp. 35-36" /> He explained that bacteria kept in sealed containers never lost their virulence, and only those exposed to air in culture media could be used as vaccine. Pasteur introduced the term "attenuation" for this weakening of virulence as he presented before the academy, saying:{{blockquote|We can diminish the microbe's virulence by changing the mode of culturing. This is the crucial point of my subject. I ask the Academy not to criticize, for the time being, the confidence of my proceedings that permit me to determine the microbe's attenuation, in order to save the independence of my studies and to better assure their progress... [In conclusion] I would like to point out to the Academy two main consequences to the facts presented: the hope to culture all microbes and to find a vaccine for all infectious diseases that have repeatedly afflicted humanity, and are a major burden on agriculture and breeding of domestic animals.<ref name=":1">{{Cite journal|last=Smith|first=Kendall A.|year=2012|title=Louis pasteur, the father of immunology?|journal=Frontiers in Immunology|volume=3|pages=68|doi=10.3389/fimmu.2012.00068|pmc=3342039|pmid=22566949|doi-access=free}}</ref> }}

In fact, Pasteur's vaccine against chicken cholera did not consistently produce immunity, and has subsequently been proven to be ineffective.<ref>"This way, which the genius of Pasteur had opened and which became so fruitful, soon proved to be closed with regard to the anti-pasteurellic vaccination of the hen. Difficulties arose in the regularity of attenuation and maintenance of virulence to a definite and fixed degree." (G. Lesbouyries, ''La pathologie des oiseaux'', Paris, 1941, p. 340; quoted by Hervé Bazin, ''L'Histoire des vaccinations'', John Libbey Eurotext, 2008, p. 155.)</ref>

==== 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.<ref name=":1" />
[[File:Albert Edelfelt - Louis Pasteur - 1885.jpg|thumb|''Louis Pasteur in his laboratory'', painting by [[Albert Edelfelt|A. Edelfeldt]] in 1885]] When animals were infected with the bacteria, anthrax occurred, proving that the bacteria was the cause of the disease.<ref>{{cite book|last1=Keim|first1=Albert|last2=Lumet|first2=Louis|title=Louis Pasteur|date=1914|publisher=Frederick A. Stokes Company|pages=123–125|url=https://archive.org/stream/louispasteur00keim#page/122/mode/2up}}</ref> Many cattle were dying of anthrax in "cursed fields".<ref name=Schwartz /> 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.<ref name=Schwartz /> He told the farmers not to bury dead animals in the fields.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|pages=303–305|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n323/mode/2up}}</ref> 

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 [[Jean Joseph Henri Toussaint|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&nbsp;°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."<ref name=":1" /> 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.<ref>{{cite book|last1=Tizard|first1=Ian|editor1-last=Schultz|editor1-first=Ronald D.|title=Veterinary Vaccines and Diagnostics|date=1998|publisher=Academic Press|pages=12–14|chapter-url=https://books.google.com/books?id=i4s1YpGVFB8C&pg=PA12|chapter=Grease, Anthraxgate, and Kennel Cough: A Revisionist History of Early Veterinary Vaccines|isbn=978-0-08-052683-6}}</ref>

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&nbsp;°C made them unable to produce spores,<ref name="Bazin p. 196">{{cite book|last1=Bazin|first1=Hervé|title=Vaccinations: a History: From Lady Montagu to Jenner and genetic engineering|date=2011|publisher=John Libbey Eurotext|isbn=978-2-7420-1344-9|pages=196–197|url=https://books.google.com/books?id=IC8QBAAAQBAJ&pg=PA196}}</ref> and he described this method in a speech to the French Academy of Sciences on 28 February.<ref>{{cite journal|last1=Pasteur|first1=L.|last2=Chamberland|first2=C.|last3=Roux|first3=E.|title=Le vaccin de charbon|journal=Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences|year=1881|volume=92|pages=666–668|url=http://gallica.bnf.fr/ark:/12148/bpt6k7351t/f665.item.r=+COMPTES+RENDUS+++DES+S%C3%89ANCES+DE+L.langFR.zoom|language=fr|access-date=4 March 2017|archive-date=4 March 2017|archive-url=https://web.archive.org/web/20170304201227/http://gallica.bnf.fr/ark:/12148/bpt6k7351t/f665.item.r=+COMPTES+RENDUS+++DES+S%C3%89ANCES+DE+L.langFR.zoom|url-status=live}}</ref> 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.<ref name="Geison1995" /> 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.<ref name="Geison1995" /> 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.<ref name=":2">{{Cite journal|last1=Pasteur|first1=Louis|last2=Chamberland|last3=Roux|year=2002|title=Summary report of the experiments conducted at Pouilly-le-Fort, near Melun, on the anthrax vaccination, 1881.|journal=The Yale Journal of Biology and Medicine|volume=75|issue=1|pages=59–62|pmc=2588695|pmid=12074483}}</ref> 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."<ref name=":2" /> However, all vaccinated sheep and goats survived, while unvaccinated ones had died or were dying before the viewers.<ref>{{Cite journal|last=Smith|first=Kendall A.|year=2005|title=Wanted, an Anthrax vaccine: Dead or Alive?|journal=Medical Immunology|volume=4|issue=1|pages=5|doi=10.1186/1476-9433-4-5|pmc=1087873|pmid=15836780 |doi-access=free }}</ref> His report to the French Academy of Sciences on 13 June concludes:{{blockquote|[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.<ref name=":2" />}}Pasteur did not directly disclose how he prepared the vaccines used at Pouilly-le-Fort.<ref>{{cite book|editor1-last=Plotkin|editor1-first=Stanley A.|title=History of Vaccine Development|date=2011|publisher=Springer|isbn=978-1-4419-1339-5|pages=37–38|url=https://books.google.com/books?id=Wf2jS_4lCOAC&pg=PA37}}</ref><ref name="Bazin p. 196" /> Although his report indicated it as a "live vaccine",<ref name=":2" /> his laboratory notebooks show that he actually used [[potassium dichromate]]-killed vaccine, as developed by Chamberland, quite similar to Toussaint's method.<ref name="Giese">{{cite book|editor1-last=Giese|editor1-first=Matthias|title=Molecular Vaccines: From Prophylaxis to Therapy|volume=1|date=2013|publisher=Springer|isbn=978-3-7091-1419-3|page=4|url=https://books.google.com/books?id=CLm8BAAAQBAJ&pg=PA4}}</ref><ref name="cohn">{{cite web| url=http://eri.louisville.edu/~eri/fos/interest1.html| title=Pasteur| author=Cohn, David V| publisher=University of Louisville| date=18 December 2006| access-date=2 December 2007| quote=Fortunately, Pasteur's colleagues Chamberland and Roux followed up the results of a research physician Jean-Joseph-Henri Toussaint, who had reported a year earlier that carbolic-acid/heated anthrax serum would immunize against anthrax. These results were difficult to reproduce and discarded although, as it turned out, Toussaint had been on the right track. This led Pasteur and his assistants to substitute an anthrax vaccine prepared by a method similar to that of Toussaint and different from what Pasteur had announced.| archive-date=23 March 2017| archive-url=https://web.archive.org/web/20170323234134/http://eri.louisville.edu/~eri/fos/interest1.html| url-status=live}}</ref><ref>{{cite book| author= Loir, A| title=Le mouvement sanitaire| year=1938| pages=18, 160| chapter=A l'ombre de Pasteur|chapter-url=https://books.google.com/books?id=WElmkgEACAAJ}}</ref>

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.<ref>{{cite book|editor1-last=Artenstein|editor1-first=Andrew W.|title=Vaccines: A Biography|date=2009|publisher=Springer|isbn=978-1-4419-1108-7|page=10|url=https://books.google.com/books?id=ewdL8ilILZAC&pg=PA10}}</ref> [[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.<ref>{{cite book|last1=Bazin|first1=Hervé|title=Vaccinations: a History: From Lady Montagu to Jenner and genetic engineering|date=2011|publisher=John Libbey Eurotext|isbn=978-2-7420-1344-9|pages=66–67, 82|url=https://books.google.com/books?id=IC8QBAAAQBAJ&pg=PA66}}</ref>

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.<ref name=Giese /> Pasteur's development of artificially weakened pathogens revolutionized work in infectious diseases, and he gave these artificially weakened diseases the generic name of "[[vaccine]]s", in honour of Jenner's discovery.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|page=332|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n351/mode/2up}}</ref>

{{Main|Koch–Pasteur rivalry}}
In 1876, [[Robert Koch]] had shown that ''[[Bacillus anthracis]]'' caused anthrax.<ref name="De Paolo">{{cite book|last1=De Paolo|first1=Charles|title=Epidemic Disease and Human Understanding: A Historical Analysis of Scientific and Other Writings|date=2006|publisher=McFarland|isbn=978-0-7864-2506-8|pages=103, 111–114|url=https://books.google.com/books?id=Xcz7Y9qVGQMC&pg=PA103}}</ref> 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.<ref name="ullmann" /> Koch stated that Pasteur tested his vaccine on unsuitable animals and that Pasteur's research was not properly scientific.<ref name=Ligon /> 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.<ref name="De Paolo" />

==== Swine erysipelas ====
In 1882, Pasteur sent his assistant [[Louis Thuillier]] to southern France because of an [[epizootic]] of [[swine erysipelas]].<ref>{{cite book|editor1-last=Plotkin|editor1-first=Stanley A.|title=History of Vaccine Development|date=2011|publisher=Springer|isbn=978-1-4419-1339-5|page=39|url=https://books.google.com/books?id=Wf2jS_4lCOAC&pg=PA39}}</ref> Thuillier identified the bacillus that caused the disease in March 1883.<ref name=Berche /> Pasteur and Thuillier increased the bacillus's virulence after passing it through pigeons. Then they passed the bacillus through rabbits, weakening it and obtaining a vaccine. Pasteur and Thuillier incorrectly described the bacterium as a figure-eight shape. Roux described the bacterium as stick-shaped in 1884.<ref>{{cite book|last1=Bazin|first1=Hervé|title=Vaccination: A History|date=2011|publisher=John Libbey Eurotext|isbn=978-2-7420-0775-2|page=211|url=https://books.google.com/books?id=orjaA_7sYZQC&pg=PA211}}</ref>

==== Rabies ====
[[File:Louis Pasteur Vanity Fair 8 January 1887.jpg|thumb|upright|Captioned "[[Rabies|Hydrophobia]]", caricature of Pasteur in the London magazine ''[[Vanity Fair (British magazine)|Vanity Fair]]'', January 1887<ref>{{Cite web |title=959.025 {{!}} Collections Online |url=https://collections.thackraymuseum.co.uk/object-959-025 |access-date=2024-05-29 |website=collections.thackraymuseum.co.uk}}</ref>]]
Pasteur's laboratory produced the first vaccine for [[rabies]] using a method developed by his assistant Roux,<ref name="Geison1995" /> which involved growing the virus in rabbits, and then weakening it by drying the affected nerve tissue.<ref name=Schwartz /><ref name="wood">{{cite journal|last1=Wood|first1=Margaret E.|title=Biting Back|url=https://www.sciencehistory.org/distillations/magazine/biting-back|journal=Chemical Heritage Magazine|volume=28|number=2|page=7|access-date=20 March 2018|date=3 June 2016|archive-date=21 March 2018|archive-url=https://web.archive.org/web/20180321130516/https://www.sciencehistory.org/distillations/magazine/biting-back|url-status=live}}</ref> 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.<ref name=Ligon /> The vaccine had been tested in 50 dogs before its first human trial.<ref>{{cite book|first1= Sue Vander|last1=Hook |title= Louis Pasteur: Groundbreaking Chemist & Biologist |publisher= ABDO|url= https://archive.org/details/louispasteurgrou0000vand|url-access= registration|year=2011 |page=[https://archive.org/details/louispasteurgrou0000vand/page/8 8]|isbn=978-1-61714-783-8 }}</ref><ref>{{cite web|last1=Corole D|first1=Bos|title=Louis Pasteur and the Rabies Virus – Louis Pasteur Meets Joseph Meister|url=https://www.awesomestories.com/asset/view/LOUIS-PASTEUR-MEETS-JOSEPH-MEISTER-Louis-Pasteur-and-the-Rabies-Virus|publisher=Awesome Stories|access-date=22 November 2014|year=2014|archive-date=29 November 2014|archive-url=https://web.archive.org/web/20141129064133/https://www.awesomestories.com/asset/view/LOUIS-PASTEUR-MEETS-JOSEPH-MEISTER-Louis-Pasteur-and-the-Rabies-Virus|url-status=live}}</ref> This vaccine was used on 9-year-old [[Joseph Meister]], on 6 July 1885, after the boy was badly mauled by a rabid dog.<ref name="cohn" /><ref name="wood" /> 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.<ref name=van /> After consulting with physicians, he decided to go ahead with the treatment.<ref name=Wasik /> Over 11 days, Meister received 13 inoculations, each inoculation using viruses that had been weakened for a shorter period of time.<ref name=Jackson /> Three months later he examined Meister and found that he was in good health.<ref name=Wasik /><ref name=trueman>{{cite web|author= Trueman C|title= Louis Pasteur|url= http://www.historylearningsite.co.uk/louis_pasteur.htm|work= HistoryLearningSite.co.uk|access-date= 3 July 2013|archive-date= 20 May 2015|archive-url= https://web.archive.org/web/20150520170850/http://www.historylearningsite.co.uk/louis_pasteur.htm|url-status= live}}</ref> Pasteur was hailed as a hero and the legal matter was not pursued.<ref name=van /> 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.<ref name=Jackson /><ref>{{cite book|editor1-last=Artenstein|editor1-first=Andrew W.|title=Vaccines: A Biography|date=2009|publisher=Springer|isbn=978-1-4419-1108-7|page=79|url=https://books.google.com/books?id=ewdL8ilILZAC&pg=PA79}}</ref> Pasteur began treatment of Jean-Baptiste Jupille on 20 October 1885, and the treatment was successful.<ref name=Jackson /> Later in 1885, people, including four children from the United States, went to Pasteur's laboratory to be inoculated.<ref name=Wasik /> In 1886, he treated 350 people, of which only one developed rabies.<ref name=Jackson /> 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.<ref name="cohn" />

In ''[[The Story of San Michele]]'', [[Axel Munthe]] writes of some risks Pasteur undertook in the rabies vaccine research:<ref>{{cite book|last1=Munthe|first1=Axel|title=The Story of San Michele|date=2010|orig-year=First published 1929|publisher=Hachette UK|isbn=978-1-84854-526-7|chapter-url=https://books.google.com/books?id=XOfWJdqYoHYC|chapter=V: Patients}}</ref>
{{blockquote|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.<ref>{{Cite journal|last=Melin|first=Maxwell David|year=2016|title=The Industrial Revolution and the Advent of Modern Surgery|url=https://ojs.stanford.edu/ojs/index.php/intersect/article/view/819|journal=Intersect: The Stanford Journal of Science, Technology, and Society|language=en|volume=9|issue=2|pages=online (1–13)|access-date=25 August 2021|archive-date=25 August 2021|archive-url=https://web.archive.org/web/20210825051413/https://ojs.stanford.edu/ojs/index.php/intersect/article/view/819|url-status=live}}</ref><ref>{{Cite journal|last=Magerl|first=Mary Ann|year=2008|title=Operating Room Sanitation: Routine Cleaning Versus Terminal Cleaning|url=https://linkinghub.elsevier.com/retrieve/pii/S1556793108000211|journal=Perioperative Nursing Clinics|language=en|volume=3|issue=2|pages=143–148|doi=10.1016/j.cpen.2008.01.007|access-date=25 August 2021|archive-date=26 May 2021|archive-url=https://web.archive.org/web/20210526013701/https://linkinghub.elsevier.com/retrieve/pii/S1556793108000211|url-status=live}}</ref> [[Ignaz Semmelweis]] and [[Joseph Lister]] had earlier practiced hand sanitizing in medical contexts in the 1860s.<ref>{{Cite journal|last1=Vermeil|first1=T.|last2=Peters|first2=A.|last3=Kilpatrick|first3=C.|last4=Pires|first4=D.|last5=Allegranzi|first5=B.|last6=Pittet|first6=D.|year=2019|title=Hand hygiene in hospitals: anatomy of a revolution|url=https://linkinghub.elsevier.com/retrieve/pii/S0195670118304821|journal=Journal of Hospital Infection|language=en|volume=101|issue=4|pages=383–392|doi=10.1016/j.jhin.2018.09.003|pmid=30237118|s2cid=52306024|access-date=25 August 2021|archive-date=19 February 2022|archive-url=https://web.archive.org/web/20220219175842/https://linkinghub.elsevier.com/retrieve/pii/S0195670118304821|url-status=live}}</ref><ref>{{Cite journal|last=Larson|first=E|year=1989|title=Innovations in health care: antisepsis as a case study.|journal=American Journal of Public Health|language=en|volume=79|issue=1|pages=92–99|doi=10.2105/AJPH.79.1.92|pmc=1349481|pmid=2642372}}</ref>