The French Louis Pasteur (1822–1895) and German Robert Koch (1843–1910) are the two greatest figures in medical microbiology and in establishing acceptance of the germ theory of disease (germ theory). In 1882, fueled by national rivalry and a language barrier, the tension between Pasteur and the younger Koch erupted into an acute conflict.

Pasteur had already discovered molecular chirality, investigated fermentation, refuted spontaneous generation, inspired Lister's introduction of antisepsis to surgery, introduced pasteurization to France's wine industry, answered the silkworm diseases blighting France's silkworm industry, attenuated a Pasteurella species of bacteria to develop vaccine to chicken cholera (1879), and introduced anthrax vaccine (1881).

Koch had transformed bacteriology by introducing the technique of pure culture, whereby he established the microbial cause of the disease anthrax (1876), had introduced both staining and solid culture plates to bacteriology (1881), had identified the microbial cause of tuberculosis (1882), had incidentally popularized Koch's postulates for identifying the microbial cause of a disease, and would later identify the microbial cause of cholera (1883).

Although Koch had briefly and, thereafter, his bacteriological followers regarded a bacterial species' properties as unalterable,Felix Löhnis, "Studies upon the life cycles of the bacteria", Part I: "Review of the literature, 1838–1918", Memoirs of the National Academy of Sciences of the United States of America, 1921;61(2):5–335, pp 8, 10–12. Pasteur's modification of virulence to develop vaccine demonstrated this doctrine's falsity. At an 1882 conference, a mistranslated term from French to German during Pasteur's lecture triggered Koch's indignation, whereupon Koch's two bacteriologist colleagues, Friedrich Loeffler and Georg Gaffky, published denigration of the entirety of Pasteur's research on anthrax since 1877.

Tensions between France and Germany

Germany had unified by way of its victory in the Franco-Prussian War (1870–71), seizing Alsace-Lorraine from France. Pasteur was professor in the University of Strasbourg, located in Alsace, where he married the daughter of the rector. Jean Baptiste Pasteur, the only son of Louis and Marie Pasteur, was a soldier in the Franco-Prussian War. The tone set by this war contributed to the rivalry between Koch and Pasteur. The "German Problem", as Germany increasingly gained scientific, technological, and industrial dominance, fed tensions among European nations.Lowe John, The Great Powers, Imperialism and the German Problem 1865–1925 (London: Routledge, 1994), pp. 195–9. Germ theory's applications were embedded in the heightening quest by France, Germany, Britain, and Italy to colonize Africa and Asia with the aid of tropical medicine, a new variant of colonial medicine, while medical scientists in respective nations vied to lead advances.

Koch's bacteriology and anthrax

In 1863, influenced by Pasteur's research on fermentation, fellow Frenchman Casimir Davaine mostly explained the cause of anthrax, but Davaine's explanation was opposed by those who rejected the idea that infection with a microorganism could explain it. In 1840, Jakob Henle had proposed microorganism infections caused diseases, and in 1875 German botanist Ferdinand Cohn weighed in on a controversy in microbiology by declaring that the elementary unit was the cell and that each form of bacteria was constant and naturally divided from the other forms. Influenced by Henle and by Cohn, Koch developed a pure culture of the bacteria described by Davaine, traced its spore stage, inoculated it into animals, and showed it caused anthrax. Pasteur called this a "remarkable achievement". See In pure culture, bacteria tend to keep constant traits, and Koch reported having already observed constancy.

Pasteur undertook investigation, yet gave much credit to Davaine. Meanwhile, Pasteur's researchers always reported variation in their cultures. In 1879, Henri Toussaint identified a bacterial species involved in chicken cholera and named the genus in honor of Pasteur, Pasteurella. In Pasteur's laboratory, a culture of Pasteurella multocida was left out over a weekend exposed to air, and Pasteur and Emile Roux noticed upon return to the laboratory that its virulence to chickens was diminished. Pasteur applied the discovery to develop chicken cholera vaccine, introduced in a public experiment, an empirical challenge to the stance of Koch's bacteriologists that bacterial traits were unalterable.

Pasteur's attenuation and vaccines

From 1878 to 1880, when publishing on anthrax, Pasteur referred to the bacteria by the name given it by Frenchman Davaine, but in one footnote called it "Bacillus anthracis of the Germans". In July 1880 Toussaint reported developing a technique of chemical deactivation to produce anthrax vaccine that successfully protected dogs and cattle, and was praised by the Academy of Science, but Pasteur attacked the feat—chemical deactivation and not virulence attenuation to make a vaccine—as impossible. Pasteur soon introduced his own anthrax vaccine in a highly successful public experiment, and entered commerce with it. Pasteur was criticized by Koch and colleagues.Koch R & Carter KC, Essays of Robert Koch (New York: Greenwood Press, 1987). (Pasteur had not used attenuation, but secretly used Toussaint's technique.)Geison GL, The Private Science of Louis Pasteur (Princeton NJ: Princeton University Press, 1995).

Microbe hunting, cholera, and public health

In 1883, responding to a cholera epidemic in Alexandria, Egypt, both Pasteur and Koch sent missions vying to identify its cause. Koch returned victorious, whereupon Pasteur switched research direction and began development of rabies vaccine. As to public health, Koch's bacteriologists feuded with Max von Pettenkofer—whose miasmatic theory claimed the bacteria was but one causal factor among at least several—but von Pettenkoffer stubbornly opposed water treatment, and the massive cholera epidemic in Hamburg, Germany, in 1892 devastated von Pettenkofer's position, and German public health was grounded on Koch's bacteriology. Meanwhile, Pasteur led introduction of pasteurization in France.

Rabies vaccine and Pasteur Institute

Rabies, uncommon but excruciating and almost invariably fatal, was dreaded. Amid anthrax vaccine's success, Pasteur introduced rabies vaccine (1885), the first human vaccine since Jenner's smallpox vaccine (1796). On 6 July 1885, the vaccine was tested on 9-year old Joseph Meister who had been bitten by a rabid dog but failed to develop rabies, and Pasteur was called a hero.Trueman C, "Louis Pasteur", History Learning Site, 2000–2011, Web. (Even without vaccination, not everyone bitten by a rabid dog develops rabies.) After other apparently successful cases, donations poured in from across the globe, funding the establishment of the Pasteur Institute, the globe's first biomedical institute, which opened in Paris in 1888.

Pasteur Institute trained military physicians in colonial medicine, although French government soon took over this role. The success of Pasteur's modification of bacterial virulence inspired confidence in the universality of Pasteurian science, though Pasteur's researchers preferred the term microbiology over the term bacteriology. Koch discouraged use of rabies vaccine, whose production later became a premise for opening Pasteur Institutes abroad, as in Shanghai, China. The first overseas Pasteur Institute was opened by Albert Calmette in Saigon in French Indochina in 1891, although Pasteur's nephew Adrien Loir was already planning to open one in Australia.

Tuberculin and Robert Koch Institute

In 1882, Koch reported identification of the tubercle bacillus as the cause of tuberculosis,Koch R (1882), "Die atiologie der tuberkulose", in Schwalbe J, ed, Gesammelte Werke von Robert Koch (Leipzig: Georg Thieme, 1912, orig 1910), pp 428–45. cementing germ theory. Koch took his research into a new direction—applied research—to develop a tuberculosis treatment and use the profits to found his own research institute, autonomous from government. In 1890 Koch introduced the intended drug, tuberculin, but it soon proved ineffective, and accounts of deaths followed in news press. Amid Koch's reluctance to disclose tuberculin's formula, Koch's reputation sustained damage, but Koch retained lasting acclaim and received the 1905 Nobel Prize in Physiology or Medicine "for his investigations and discoveries in relation to tuberculosis". Koch accepted government's offer to direct the Institute for Infectious Diseases (1891), in Berlin, a prestigious position but not the kind of institute that Koch had sought. It was later renamed the Robert Koch Institute, which remains a government organization.

American medicine embraces Koch

The monomorphist doctrine of Koch's bacteriologists suggested public health interventions to eliminate bacteria, whereas Pasteur's acceptance of variation suggested attenuating bacterial virulence in the laboratory to develop vaccines. Although inspired by Pasteur's applications suggesting medicine's potential, American physicians traveled to Germany to learn Koch's bacteriology as basic science, though Pasteur emphasized the fuzzy boundary between basic science and applied science.

From 1876 to 1878, the American William Henry Welch trained in Germany pathology, and in 1879 opened America's first scientific laboratory, a pathology laboratory in Bellevue's medical school in New York. While in Germany, Welch had met John Shaw Billings who had been appointed by Daniel Coit Gilman—the first president of the newly forming Johns Hopkins University—to plan Hopkins' hospital and medical school. Named the medical school's first dean in 1883, Welch promptly traveled for training in Koch's bacteriology, and returned to America eager to transform medicine with the "secrets of nature". Hopkins medical school opened in 1894 with Welch emphasizing Koch's bacteriology, which became the foundation of modern medicine.

As "dean of American medicine", William H Welch became the first scientific director of Rockefeller Institute for Medical Research (1901), and appointed his former Hopkins student Simon Flexner the first director of pathology and bacteriology laboratories. Aided by the "Flexner report", published in 1910 while Welch was president of the American Medical Association, Welch's view of science and medicine became the national standard, a transformation of American medical education completed around 1930. As first dean of America's first public health school, founded in 1916 at Hopkins, Welch set the standard for public health, and with Simon Flexner exported the Hopkins model internationally.

Pasteur's image ascends

Although Pasteur died in 1895, eventually over thirty official Pasteur Institutes opened across the globe. Pasteur's team had planned in 1885 to open a rabies-treatment facility in St. Louis, Missouri, and an American Pasteur Institute in New York City, but the plans were abandoned, and America has never hosted an official Pasteur Institute.Pasteur Foundation, "Pasteur Institutes USA: A turn-of-the-century phenomenon" , Remembrance of Things Pasteur, Accessed 5 Sep 2012 on Web.

A number of American copycats appeared, however, starting with "Chicago Pasteur Institute" in 1890, and "New York Pasteur Institute" in 1891. In 1897 a "Pasteur Institute" opened in Baltimore, in 1900 in Pittsburgh and St. Louis, in 1903 in Ann Arbor and Austin, and in 1904 perhaps in Philadelphia. In 1908, Georgia Department of Public Health opened a "Pasteur Department" in Atlanta, California State Hygienic Laboratory opened a "Pasteur Division" in Berkeley, and a "Pasteur Institute" opened in Washington, D.C.