In 1881, at the International Medical Congress in London, Robert Koch watched Louis Pasteur demonstrate his anthrax vaccine and then published a review calling the work useless. Pasteur replied in person at the Geneva congress the following year. Koch answered in print with an attack on Pasteur’s competence, his methods and his understanding of the subject, and remarked that since Pasteur was not a physician there was no reason to expect him to understand disease.
The two men who between them established that microorganisms cause illness spent two decades unable to be in the same room. Some of it was national, most of it was temperamental, and a surprising amount of it was productive.
Two Completely Different Scientists
Pasteur was a chemist who had made his name on the handedness of tartaric acid crystals and had come into biology through the practical problems of French industry: why wine spoils, why beer sours, why silkworms die. He worked outward from an effect to its cause, was a superb showman, and thought in terms of what could be prevented.
Koch was a district physician in Wollstein, a small town in what was then Prussian Posen, with a microscope his wife had given him for his birthday and a laboratory partitioned off from his consulting room with a curtain. He worked from the organism outward, distrusted anything he could not photograph, and thought in terms of what could be proved.
The difference in approach is the reason the field ended up with both a method of proof and a method of prevention.
Koch Establishes Causation
Anthrax was the obvious target because the rod shaped organism in the blood of dead sheep was large enough to see easily and had already been observed by Casimir Davaine and others. What nobody had shown was that it caused the disease rather than merely accompanying it.
Between 1873 and 1876 Koch grew the organism in the aqueous humour of an ox’s eye, transferred it through generation after generation, and infected healthy mice with the final culture, which had none of the original blood left in it. He also solved the puzzle of why pastures stayed infectious for years: the bacillus forms spores that survive drying and heat and germinate later.
He wrote to Ferdinand Cohn at Breslau, who was sufficiently impressed by the letter to invite him to demonstrate. Koch arrived with his equipment and spent three days showing the complete life cycle to the assembled faculty. He was thirty two and unknown, and he left as the most talked about bacteriologist in Germany.
The reasoning was formalised in 1884 into what are still taught as Koch’s postulates: the organism must be found in every case of the disease, it must be isolated and grown in pure culture, that culture must produce the disease when introduced into a healthy host, and it must be recoverable from that host. They are not universally applicable, and Koch knew it, since he had already met carriers of cholera who never became ill. As a standard of evidence they replaced argument by plausibility with argument by demonstration.
The Tools Mattered More Than the Postulates
Koch’s laboratory produced the techniques that made bacteriology a routine discipline rather than a heroic one.
- Solid growth media. First potato slices, then gelatine, which melts at body temperature and is digested by many bacteria. The replacement, agar, came from Angelina Hesse, the wife of an assistant, who used it to set fruit jellies in warm weather after learning of it from Dutch East Indies neighbours
- The flat covered dish, introduced by his assistant Julius Petri in 1887, which is why every laboratory bench still carries his name
- Aniline dye staining, which made transparent organisms visible, and photomicrography, so that a claim could be checked by people who had not looked down the microscope themselves
On 24 March 1882 he announced the isolation of the tubercle bacillus. Tuberculosis was killing roughly one in seven people in Europe, and it had been widely held to be hereditary. The lecture is often described as the moment bacteriology became unarguable. Paul Ehrlich, who was in the audience, said it was the greatest scientific experience of his life.
Pasteur Builds the Vaccines
Pasteur was working the other end of the problem. In 1879, through an accident with a culture of chicken cholera left over a summer holiday, he found that a weakened organism failed to kill and left the birds protected against a fresh dose. He named the principle attenuation, and named the whole class of preparations vaccines in honour of Jenner’s cowpox, though nothing about them involved cows.
In May 1881, at Pouilly le Fort, he staged the demonstration that made him famous outside science. Twenty five sheep were vaccinated against anthrax and twenty five were not, and all fifty were then injected with a lethal culture in front of an invited audience of veterinarians, farmers and journalists. Two days later the vaccinated animals were alive and the others were dead or dying.
Koch’s objection to this was not that it had failed. It was that Pasteur had not established what was in his vaccine, that his cultures were probably mixed, and that a spectacle in front of journalists is not the same thing as a controlled result. He had a point: the material actually used at Pouilly le Fort was prepared by Pasteur’s collaborator Chamberland using a chemical method Pasteur had publicly disparaged, and Pasteur’s notebooks, which were kept closed until the 1970s, show that his published account was not entirely straight.
The Insult That May Not Have Happened
The personal rupture is usually dated to the Geneva congress of 1882. Pasteur, speaking in French, referred to a German collection of papers, using the phrase recueil allemand. Koch’s translator rendered it as German arrogance, deutscher Hochmut, and Koch walked out.
The mistranslation story is well attested and may not be the whole explanation, since the two had been trading printed attacks for a year already. But it fixed the quarrel in public and made reconciliation impossible in a decade when France and Germany were still counting the cost of the war of 1870, and when both governments were funding their man as a matter of national credit.
Cholera, and One Decent Moment
In 1883 an epidemic in Egypt drew both a French and a German mission to Alexandria, arriving within weeks of each other and racing for the organism.
The French team lost. Louis Thuillier, Pasteur’s twenty seven year old assistant, caught cholera and died. Koch, the competitor, served as a pallbearer at his funeral and laid wreaths on the coffin, saying that they were modest but of laurel, such as are given to the brave.
Koch went on to India and identified Vibrio cholerae in Calcutta in 1884, and traced it to a specific water tank used by an affected community, a finding that arrives thirty years after John Snow had made the same argument in London without ever seeing the organism.
Each Man’s Worst Moment
Both overreached in the same way, by promising a cure before the evidence was in.
Koch announced tuberculin in 1890 as a remedy for tuberculosis, under pressure from a German government that wanted a triumph. It was a glycerine extract of the bacillus, it did not cure anything, and in some patients it provoked severe reactions. Thousands travelled to Berlin for treatment. Rudolf Virchow’s post mortems on patients who died under it were devastating, and Koch’s refusal to disclose the composition damaged him badly. Tuberculin survives as a diagnostic skin test, which is not what was advertised.
Pasteur’s rabies vaccine of 1885 worked, and was given to the boy Joseph Meister on evidence that would not satisfy any modern regulator. Pasteur was not a physician and was technically practising medicine illegally when he authorised the injections.
What the Rivalry Produced
By the 1890s the argument was effectively over, in the sense that both halves had been absorbed. Koch’s postulates and his culture methods gave the field its standard of proof. Pasteur’s attenuation gave it a way to intervene. Neither is much use without the other: identifying an organism you cannot prevent, or preventing a disease whose cause you cannot name, are both dead ends.
Their students filled the discipline. Koch’s laboratory produced Ehrlich, Behring, Kitasato and Gaffky. The Institut Pasteur produced Roux, Yersin, Calmette and Metchnikoff. The two institutions spent the following century competing, and the rate of progress in infectious disease between 1880 and 1900 is not obviously separable from the fact that neither side could afford to be second.
Pasteur died in 1895, before the Nobel Prizes existed. Koch received the prize in Physiology or Medicine in 1905. The question they had both started from, whether life could arise spontaneously in a broth, had been settled by Pasteur thirty years earlier, and it was the settling of it that made everything they subsequently fought about possible.
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