Pasteur–Koch: Distinctive Ways of Thinking about Infectious Diseases Linguistic misunderstandings along with genuine scientific differences over virulence and immunity drove the two geniuses apart Agnes Ullmann ouis Pasteur and Robert Koch are view several of their major achievements before considered the founders of medical they crossed paths. bacteriology. Their paths crossed L only a few times but, as often hap- pens for such geniuses, those encoun- Pasteur Approach to Microbiology Was ters evinced polemics and controversy. Was this Both Theoretical and Practical due to their different backgrounds? Robert Koch was a physician, 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 chemistry. 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 • Louis 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 nature 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 Science Faculty • Robert Koch, a physician, developed a system- in Lille. There he started to study alcoholic atic approach for establishing the causal rela- fermentation in response to a request for tionship between a particular microorganism and a specific disease. him to deal with problems that arose in a distillery in Lille. This proved the first of • An overlapping interest in anthrax 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 vaccines. retical insights. In this case, his realization emeritus research • Despite a friendly encounter at a London meet- that organisms participate in fermentations 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 wine diseases, Institut Pasteur, he showed that specific wine diseases are Paris, France. 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 epidemiology, 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 “pasteurization” very different animal and human diseases. and now applied widely to many different foods 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 Germany. 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 public health-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 Spontaneous Generation experiments with bacteria 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 life 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 19th century, 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 laboratory 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 cholera vibrio the following many generations. year. Based on these observations, Pasteur inoculated chickens with the attenuated chicken 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 immunization in Pouilly- term, Bacillus anthracis. 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 germ theory of disease was thus firmly estab- lished, becoming the fundamental concept on When Koch and Pasteur Meet which medical microbiology was built. in London, their Rivalry Flares Those who were considered members of the Joseph Lister 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.