Pasteur–Koch: Distinctive Ways of Thinking about Infectious Linguistic misunderstandings along with genuine scientific differences over virulence and drove the two geniuses apart

Agnes Ullmann

ouis Pasteur and are view several of their major achievements before considered the founders of medical they crossed paths. . Their paths crossed L only a few times but, as often hap- pens for such geniuses, those encoun- Pasteur Approach to Was ters evinced polemics and controversy. Was this Both Theoretical and Practical due to their different backgrounds? Robert Koch was a , 20 years younger than Pasteur, whose interests touched on many scien- Pasteur, a chemist and microbiologist. Neither tific areas, was a keen observer and especially man understood the other’s language. adept at integrating relevant observations into Yet their contributions to microbiology were his conceptual schemes. Born in 1822, Pasteur so complementary that it is difficult to imagine was admitted in 1843 to the scientific section of one without the other. To better understand the the E´ cole Normale Supe´rieure in Paris, where he Pasteur–Koch clash, it seems useful first to re- was trained to become a professor in . At the age of 24, studying the crystal struc- ture of organic molecules, he discovered molecular asymmetry. Ten more years of Summary crystallographic studies convinced Pasteur • , a keen observer who was adept at that one of the fundamental characteristics integrating relevant observations into his con- of living matter was its asymmetric ceptual schemes, studied specific problems from at the molecular level. a practical and sometimes economic point of In 1854, Pasteur was appointed professor view. of chemistry and dean of the Faculty • Robert Koch, a physician, developed a system- in . There he started to study alcoholic atic approach for establishing the causal rela- in response to a request for tionship between a particular and a specific . him to deal with problems that arose in a distillery in Lille. This proved the first of • An overlapping interest in led to an intense rivalry between Pasteur and Koch, with several occasions when he was asked to Koch and his followers embracing a rigid belief study specific problems from a practical as in the specificity and permanence of microbial well as an economic point of view. Often, characteristics, while Pasteur recognized that his insights led to successful practical solu- pathogens attenuate, making them useful in tions, while also providing new, more theo- Agnes Ullmann is . retical insights. In this case, his realization emeritus research • Despite a friendly encounter at a London meet- that organisms participate in director at the ing in 1881, Pasteur and Koch were soon in led him later to formulate the germ theory CNRS and honorary open conflict—in part, because of a mistrans- lated phrase. of infectious disease. professor at the When Pasteur later studied diseases, Institut Pasteur, he showed that specific wine diseases are Paris, .

Volume 2, Number 8, 2007 / Microbe Y 383 associated with particular mi- The silkworm efforts plunged Pasteur more croorganisms. Moreover, heat- broadly into infectious diseases research. For ing wine to 55°C is sufficient to instance, he developed some practices that be- keep its quality intact. This ex- came the foundations of modern , perience led to the process of providing investigative approaches that served partial sterilization, subse- him years later when he was asked to deal with quently called “” very different animal and human diseases. and now applied widely to many different and beverages. Koch’s Career Took Shape with Anthrax Pasteur was never satisfied Studies begun during the 1860s merely to formulate the theoret- ical basis for a given process. In 1860 Pasteur branched out from studying Instead, he took an active inter- fermentation and putrefaction to investigating est in its industrial develop- various specific diseases. At about the same ment and practical applications. time, Robert Koch was earning his medical de- “There are no such things as gree at the University of Go¨ ttingen in . Pasteur pure and applied science,” he Born in 1843, he became a medical doctor in said. “There are only science 1866 and, at the age of 29, became a District and the application of science.” Medical Officer, or Kreisphysikus. Besides these -related official du- ties, Koch had an extensive medical practice. Darwin’s Origin of Species, Pasteur’s Moreover, working on his own, he began doing Debunking of with while also investigat- Darwin published The Origin of Species in ing a disease called anthrax that was worrying 1859, the same year that controversy over spon- farmers all over Europe. In 1873, he began using taneous generation reignited. Responding to microscopes to inspect blood from sheep that that controversy and using very simple devices, died from anthrax. He observed the same rod- Pasteur showed that, provided that germs are shaped structures that the French scientist, completely excluded, “spontaneous generation” Davaine, had named “bacteridia” in an 1863 does not occur. These simple experiments set- report. tled once and for all not only a philosophical By 1874, Koch made a crucial finding while problem, proving that is not spontaneously observing cultured bacteridia. He learned that generated from dead matter, but it also served to they go through a cycle, with motionless rod- establish the new science of microbiology, bas- shaped cells changing into spores. His discovery ing it in part on specialized techniques, including of spores helped to explain findings by Davaine sterilization and aseptic manipulation. and others that sheep become sick with anthrax Toward the middle of the , a not only after being exposed to other infected mysterious disease began to attack French silk- animals but also when exposed to soil, where worm nurseries. The disease then spread else- spores can be harbored for years. where in Europe and then to China and Japan. Working in a primitive that he By 1865 the silkworm industry was decimated constructed at home, Koch obtained cultures of in Western Europe. Although Pasteur knew bacteria from blood of infected animals, then nothing about silkworms, he was asked to take determined that anthrax can be transmitted charge of this problem in France. Intrigued from one mouse to another, reproducibly caus- through his interest in experimental pathology, ing typical lesions. This work laid the method- he accepted the challenge. Soon, in less than a ological foundations for Koch’s postulates, a year, Pasteur became an expert breeder of silk- systematic approach for establishing the causal worms and, through these studies, came into relationship between a particular microorgan- contact with some of the complexities of infec- ism and a specific disease. tious processes. He also established some new Within a few years, Koch developed a num- selection techniques useful for silkworm special- ber of original experimental and diagnostic ists that gained wide recognition and were soon procedures, making him the leader of the Ger- being applied throughout Europe. man school of bacteriology. He achieved im-

384 Y Microbe / Volume 2, Number 8, 2007 mortal fame by isolating the tubercle bacillus “attenuated” character through in 1882 and the vibrio the following many generations. year. Based on these observations, Pasteur inoculated with the attenuated Overlapping Interests in Anthrax cholera cultures and rendered Grow into an Intense Rivalry them resistant to a fully virulent Their overlapping interest in anthrax was the be- strain. From there on, Pasteur ginning of an intense rivalry between Pasteur and directed much of his experimen- Koch. When Koch’s paper on the etiology of an- tal work toward understanding thrax appeared in 1876, Pasteur was 54 and and improving such immuniza- widely known for his work on spontaneous gen- tions, striving to obtain attenu- eration and on the germ theory of fermentation. ated cultures of anthrax with Between 1878 and 1880 Pasteur published a which to vaccinate animals. number of papers on anthrax. In doing so, he In early 1881, Pasteur con- ducted a large-scale test of an- consistently used Davaine’s terminology for Koch the bacterium—bacteridia—rather than Koch’s thrax in Pouilly- term, . However, in a single le-Fort. About 70 sheep were footnote, Pasteur acknowledged Koch’s work vaccinated in two steps: first they were inocu- by referring to “Bacillus anthracis of the Ger- lated with a low-virulence culture; 12 days later, mans.” they were vaccinated again, but with a less- Fortunately, well before this rivalry grew attenuated culture. After another two weeks, the more virulent, Koch and Pasteur continued to vaccinated and unvaccinated sheep were inocu- lated with a virulent anthrax strain. After a few work on anthrax independently, providing fur- days all the unvaccinated sheep were dead, while ther experimental evidence that the anthrax ba- all the vaccinated animals remained healthy. cillus is responsible for causing anthrax. The was thus firmly estab- lished, becoming the fundamental concept on When Koch and Pasteur Meet which was built. in London, their Rivalry Flares Those who were considered members of the invited Koch to attend the Seventh German school of bacteriology discovered many International Medical Congress, which was held bacterial agents of disease, due mainly to the in London during the summer of 1881. Earlier, mastery of Koch and the disciples he trained. In as a surgeon in Glasgow, Lister fell under the general, they developed and used standardized influence of Pasteur and admired his work on techniques for isolating and identifying micro- fermentation and spontaneous generation. bial species by growing them in cultures. The Those interests led Lister to develop the use of germ theory of fermentation and of disease was techniques in . based mainly on a belief of specificity and per- Pasteur also attended the medical congress in manence of the characteristics of microbial spe- London, where he presented a paper on his cies. Under the influence of Koch, this concept results on anthrax attenuation and the success- became a rigid doctrine. It held that the proper- ful sheep that were conducted ear- ties and forms of each microorganism remained lier that spring. Koch presented a laboratory unchanged under all circumstances. demonstration on his plate technique and meth- Meanwhile, members of the French school of ods for staining bacteria. Pasteur attended this bacteriology, who were under the dominating demonstration session and said with admira- influence of Pasteur, focused on another aspect tion, “C’est un grand progre`s, Monsieur.” This of infectious diseases—immunity. For example, praise was a great triumph for Koch, who was Pasteur investigated chicken cholera, caused by 20 years younger than Pasteur. Further, Koch an agent now called Pasteurella, late during the knew that Pasteur could not forget that France 1870s. By chance, he noticed that cultures of had lost the Franco-German war of 1870. chicken cholera sometimes lose their ability to Despite their friendly encounter at the Lon- produce disease and then retain this modified or don meeting, however, Pasteur and Koch were

Volume 2, Number 8, 2007 / Microbe Y 385 soon in open conflict. A few months after the and “all this material served only as a vehicle for London meeting, in the first volume of the “Mit- a violent polemic directed against me.” In his teilungen aus dem Kaiserlichen Gesundheit- answer, in a long and emotional letter, Pasteur samte,” Koch and his students Gaffky and Loef- expressed surprise at the virulence of Koch’s fler published several articles attacking Pasteur’s attack and reviewed his own contributions to work on attenuating anthrax, accusing him of and to science in general. having impure cultures and of making errors On top of the personal and scientific antago- during his studies. “Of these conclu- nisms between Pasteur and Koch, both were sions of Pasteur on the etiology of anthrax, there passionate patriots. Thus, the 1870–1871 war is little which is new, and that which is new is between France and Germany exacerbated their erroneous...Uptonow, Pasteur’s work on an- respective chauvinisms, which colored their thrax has led to nothing,” Koch and his collab- broader behaviors. In 1871, for example, Pas- orators asserted (translated from the original teur returned with words of anger and contempt German). the honorary degree that he received from the Pasteur answered Koch in detail at the fourth University of Bonn. International Congress of and Demog- When Pasteur published his results on raphy, held in Geneva in September 1882. At vaccination in 1885, Koch opposed use of the this memorable meeting, Koch was in the audi- and again minimized the significance of ence when Pasteur presented his speech on at- Pasteur’s work. However, a few years later, tenuation and vaccination. By this time, Koch Koch reversed this tack, using Pasteur’s methods was at the height of his fame after having re- to develop a similar vaccine to protect against ported the discovery of the tubercle bacillus a rabies. When Koch established the Institute for few months earlier. Koch’s response after Pas- Infectious Diseases in , its was designed to teur’s speech was unexpectedly aggressive, lead- be like the Institut Pasteur in Paris. ing to an embarrassing situation. As usual, their personal and national rivalries The Koch-Pasteur Disputes were mixed in whatever they did or said. This Had Broad Implications time, however, a translation problem appar- ently provoked Koch’s unexpectedly aggressive Koch’s refusal to recognize the value of Pasteur’s answer, according to a document held at the attenuation procedure had both practical and Museum of the in Paris. The theoretical implications. Moreover, Koch be- problem was that the two men did not speak or lieved that the biological and chemical charac- understand one another’s language. Pasteur re- teristics of a microbial species were not only ferred to published work of Koch as “recueil specific but also permanent. These views contra- allemand,” meaning collection or compilation dicted Pasteur’s concept that microbial viru- of German works. Professor Lichtheim, who sat lence is not constant but, instead, is a variable next to Koch and was rapidly converting Pas- property of microbial species—a property that teur’s French into German, incorrectly trans- can be lost but also recovered. lated “recueil allemand” as “orgeuil allemand,” Pasteur believed that such variations were of which means “German arrogance.” Not sur- great importance and could help to explain the prisingly, then, Koch angrily protested this un- epidemiology of various infectious diseases. He intended insult, while Pasteur—unaware that suggested that epidemics might arise because of his innocuous phrase had, mistakenly, been a temporary or short-term increase in virulence turned into a stinging insult—remained preter- of a particular microorganism. Further, such naturally calm. changes in virulence might arise when a partic- Koch’s written response to Pasteur was pub- ular microbe acquired virulence that enabled it lished in a paper, “On inoculation against an- to infect a previously unsusceptible animal spe- thrax. A reply to Pasteur’s lecture in Geneva.” In cies. Pasteur wrote: it, Koch attacked Pasteur in a highly insulting Thus, virulence appears in a new light, which manner. Among other insults, Koch wrote, may be disturbing for the future of humanity, “. . . Concerning inoculation against anthrax, unless nature, in its long evolution, has already all what we heard was some completely useless experienced the occasions to produce all possi- data,” “he [Pasteur] is not even a physician,” ble contagious diseases—a very unlikely as-

386 Y Microbe / Volume 2, Number 8, 2007 sumption. What is a microorganism that is The Pasteur-Koch controversy reflected, in innocuous for man or for a given animal spe- part, then-contemporary political antagonism cies? It is a living being which does not possess between France and Germany. On a more per- the capacity to multiply in our body or in the sonal level, the Pasteur and Koch schools of body of the animal. But nothing proves that if microbiology adhered to different methods and the same microorganism should chance to come into contact with some other of the thou- philosophies. Pasteur was deeply interested in sands of animal species in the Creation, it might questions of immunity and in developing spe- invade it, and render it sick. Its virulence might cific means to protect humans or other animal increase by repeated passages through that spe- species against specific infectious diseases. By cies, and might eventually adapt it to man or contrast, Koch favored public health measures domesticated animals. Thus might be brought for controlling infectious diseases. Pasteur’s ap- about a new virulence and new contagions. I proach was to vaccinate individuals, whereas am much inclined to believe that such mecha- Koch’s approach was to rely on sanitary meth- nisms explain how , syphilis, plague, ods to protect populations. Despite both Koch yellow fever, etc. have come about in the course of the ages, and how certain great epidemics and Pasteur being impatient and intolerant and appear from time to time. despite their bitter personal and nationalistic differences, both men defended truth and de- These historical remarks continue to be rele- voted their intellectual powers and their hearts vant, and are especially applicable to HIV/AIDS in service to humanity. and other emergent diseases.

SUGGESTED READING Koch, R. 1881. Zur Aetiologie des Milzbrandes. Mitteilungen aus dem Kaiserlichen Gesundsheitsamte 1:49–79 (see also in the same volume G. Gaffky 80–133, and F. Loeffler 134–187). Koch, R. 1882. U¨ ber die Milzbrandimpfung. Eine Entgegung auf den von Pasteur in Genf gehaltenen Vortrag. In Koch Gesammelte Werke I:207–231. Mayer, R. 1982. Il y a cent ans, a` Gene`ve, au 4e Congre`s international d’Hygie`neetdeDe´mographie,“l’ altercation” Pasteur– Koch. Rev. Med. Suisse Romande 102:805–809. Mollaret, H. H. 1983. Contribution a` la connaissance des relations entre Koch et Pasteur. NTM-Schriftenr. Gesch. Naturwis. Technik, Med., Leipzig 20:57–65. Pasteur, L. 1883. La dissymetrie mole´culaire. (Lecture before the Socie´te´ Chimique de Paris). Pasteur, L. 1876. Etudes sur la bie`re: ses maladies, causes qui les provoquent, proce´de´ pour la rendre inalte´rable, avec une the´orie nouvelle de la fermentation. Gauthier-Villars, Paris. Pasteur, L. 1878. La the´orie des germes et ses applications a` la chirurgie. Bull. Acad. Natl. Me´d., 2e se´r., VII, p. 166–167. Pasteur, L. 1860. Me´moires sur les corpuscules organise´s qui existent dans l’atmosphe`re. Examen de la doctrine des ge´ne´rations spontane´es. Ann. de Sc. Naturelles 44:5–98. Pasteur, L. 1882. De l’atte´nuation des . Quatre`me Congre`s International d’Hygie`neetdeDe´mographie, Gene`ve 1:127–149. Pasteur, L. 1883. La vaccination charbonneuse. Re´ponse au docteur Koch. Rev. Scient. 4:74–84. Pasteur, L. 1881. De l’atte´nuation des virus et de leur retour a` la virulence. Comptes rendus de l’Acade´mie des 92:429–435.

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