Pasteur-Koch: Distinctive Ways of Thinking about Infectious Diseases
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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
L considered the founders of medical
bacteriology. Their paths crossed
only a few times but, as often hap-
pens for such geniuses, those encoun-
they crossed paths.
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 École Normale Supérieure 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 383associated 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 Göttingen 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, 2007mortal 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-
consistently used Davaine’s terminology for ducted a large-scale test of an-
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. The Those interests led Lister to develop the use of
germ theory of fermentation and of disease was antiseptic techniques in surgery.
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 vaccination 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 progrès, 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 385soon 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 medicine and to science in general.
having impure cultures and of making errors On top of the personal and scientific antago-
during his inoculation 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. . . Up to now, 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 Hygiene and Demog- When Pasteur published his results on rabies
raphy, held in Geneva in September 1882. At vaccination in 1885, Koch opposed use of the
this memorable meeting, Koch was in the audi- vaccine 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 Berlin, 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 Pasteur Institute 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, 2007sumption. 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
the same microorganism should chance to
microbiology adhered to different methods and
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 smallpox, syphilis, plague,
yellow fever, etc. have come about in the course
ods to protect populations. Despite both Koch
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. Über 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, à Genève, au 4e Congrès international d’Hygiène et de Démographie,“l’ altercation” Pasteur–
Koch. Rev. Med. Suisse Romande 102:805– 809.
Mollaret, H. H. 1983. Contribution à la connaissance des relations entre Koch et Pasteur. NTM-Schriftenr. Gesch. Naturwis.
Technik, Med., Leipzig 20:57– 65.
Pasteur, L. 1883. La dissymetrie moléculaire. (Lecture before the Société Chimique de Paris).
Pasteur, L. 1876. Etudes sur la bière: ses maladies, causes qui les provoquent, procédé pour la rendre inaltérable, avec une
théorie nouvelle de la fermentation. Gauthier-Villars, Paris.
Pasteur, L. 1878. La théorie des germes et ses applications à la chirurgie. Bull. Acad. Natl. Méd., 2e sér., VII, p. 166 –167.
Pasteur, L. 1860. Mémoires sur les corpuscules organisés qui existent dans l’atmosphère. Examen de la doctrine des
générations spontanées. Ann. de Sc. Naturelles 44:5–98.
Pasteur, L. 1882. De l’atténuation des virus. Quatrème Congrès International d’Hygiène et de Démographie, Genève
1:127–149.
Pasteur, L. 1883. La vaccination charbonneuse. Réponse au docteur Koch. Rev. Scient. 4:74 – 84.
Pasteur, L. 1881. De l’atténuation des virus et de leur retour à la virulence. Comptes rendus de l’Académie des Sciences
92:429 – 435.
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