Pasteur, Koch and American bacteriology

This study traces American awareness of the work of Louis Pasteur and Robert Koch from the 1860s to the 1890s. In the years before the Civil War, American interest in germ theories had appeared at times of epidemics and persisted to a limited extent among physician-microscopists. Discussions of Pasteur's work occurred primarily in the context of spontaneous generation and antisepsis. Few Americans imitated his work on immunology or studied with Pasteur, but his work on immunity influenced their faith in the potential of bacteriology as a solution to problems of infectious disease. Koch's discoveries of the bacterial agents of tuberculosis and cholera stimulated American medical and public health interest in bacteriology in a more practical way. Americans learned Koch's methods by taking his courses and imported them directly into their own laboratories. A context of enthusiasm for science, educational reform, and problems of infectious disease associated with urbanization and changes in agriculture aided the growth of bacteriology in the American context.     

Money and microbes: Robert Koch, tuberculin and the Foundation of the Institute for Infectious Diseases in Berlin in 1891

Starting from an assessment of how far Robert Koch's bacteriology had developed in the late 1880s this paper attempts to analyse different aspects of the process that led to the foundation of the Berlin Institute for Infectious Diseases in 1891. With the development of his supposed cure against tuberculosis, tuberculin, Koch attempted to give his research a new direction, earn a fortune with the profits and become more independent of Prussian government officials who, up to that point, had had a major influence on his career. In the period following the presentation of the cure in autumn 1890, however, it became clear that tuberculin's value in treatment was at most dubious. Thus, the failure of tuberculin meant that Koch had to drop his own plans and accommodate those of the Prussian Ministry of Culture. As a result he assumed directorship of the newly founded Institute for Infectious Diseases in Berlin. Even though this was definitely a prestigious position it reaffirmed Koch's dependency on Prussian government officials and was by no means the kind of institution he had aimed for at the outset.     

100th anniversary of Robert Koch's Nobel Prize for the discovery of the tubercle bacillus

The year 2005 marks the 100th anniversary of Robert Koch's Nobel Prize. Here, we describe the scientific career of Robert Koch, the discoverer of the etiologic agent of tuberculosis but also of those of anthrax, cholera and wound infections. Equally important, Koch developed the methodologies and concepts that made medical microbiology a scientific discipline. Despite great efforts, however, Koch failed to conquer tuberculosis, which still causes enormous health problems worldwide 100 years after his Nobel award.     

Robert Koch

This article traces the origins of bacteriological research, with particular attention to the role of Robert Koch, and his postulates, on infectious agents. By chronologically following Koch's work on anthrax, germ photography and tuberculosis, it shows how the visual representation of germs transformed laboratory research in medical science.     

A harmony of illusions: clinical and experimental testing of Robert Koch’s tuberculin 1890–1900

One of Ludwik Fleck’s ideas about the development of scientific knowledge is that—once a system of interpretation is in place—the process that follows can be characterised as one of inertia: any new evidence comes under a strong pressure to be incorporated into the established frame. This can result in what Fleck called a harmony of illusions (Harmonie der Täuschungen) when contradictory evidence becomes almost invisible or is incorporated into the established frame only by huge efforts.The paper analyses early explanations of the tuberculin reaction as a case study of Fleck’s argument. For Robert Koch, who had presented tuberculin in 1890, the compound was supposed to be a diagnostic tool and a cure for tuberculosis. His conception of its effect was rather peculiar, but strictly in line with ideas on the pathogenesis of infectious diseases he had developed much earlier. After tuberculin was released in late 1890, whether Koch’s conception was convincing depended on the place that a given observer had in the medical world in late-nineteenth-century Germany. Inside Koch’s group, the status of the tuberculin reaction remained stable and tuberculin retained its value as a diagnostic and curative tool. On the other hand, observers from outside that thought collective, and in particular from clinical medicine, soon pointed to flaws in its conception. These critics developed a rather different picture of tuberculin as a mysterious and dangerous drug. No reconciliation followed and what we find instead in German medicine around the year 1900 is the presence of rather contradictory concepts and practices surrounding Koch’s wonder cure.     

Robert Koch and the invention of the carrier state: tropical medicine, veterinary infections and epidemiology around 1900

This paper reassesses Robert Koch's work on tropical infections of humans and cattle as being inspired by an underlying interest in epidemiology. Such an interest was developed from the early 1890s when it became clear that an exclusive focus on pathogens was insufficient as an approach to explain the genesis and dynamics of epidemics. Koch, who had failed to do so before, now highlighted differences between infection and disease and described the role of various sub-clinical states of disease in the propagation and--consequently--in the control of epidemics. Studying pathologies of men and cattle in tropical countries eventually facilitated the application of such measures in Europe through the screening of healthy carriers of typhoid, which was carried out in 1902. The concept of the carrier state can be understood as a spin-off from tropical medicine into the study and control of infectious disease in Europe. With it travelled assumptions that were typical for colonial and veterinary medicine where the health of indigenous individuals or cattle would be a secondary objective compared to the control of diseases in populations.     

Historical perspectives on the etiology of tuberculosis

Robert Koch's 1882 demonstration that the tubercle bacillus was the true cause of tuberculosis established a new understanding of causation in medicine. This scientific breakthrough set in motion an etiological revolution with vast implications for the control of infectious disease, and its ramifications are still being felt today.     

Robert Koch: the grandfather of cloning?

This year marks the centenary of Robert Koch's Nobel Prize for discovering the cause of tuberculosis. Koch was also the first scientist to isolate the anthrax and cholera microbes. Yet perhaps one of his greatest contributions to biology is the least appreciated: his method for propagating individual colonies of bacteria on plates, a technique that came to be called cloning.     

Molecular Koch's postulates applied to bacterial pathogenicity--a personal recollection 15 years later

Koch's postulates were derived from Robert Koch's work on infectious diseases, such as anthrax and tuberculosis, which still engage us to this day. These guidelines were an attempt to establish a standard for identifying the specific causation of an infectious disease and to convince sceptics that microorganisms could cause disease. They were also established to encourage an increasing number of novice microbiologists to use more rigorous criteria before claiming a causal relationship between a microorganism and a disease.     

Linking cause and disease in the laboratory: Robert Koch's method of superimposing visual and 'functional' representations of bacteria

Robert Koch based his claim that specific microorganisms cause particular diseases on laboratory studies. This paper examines how Koch set up a plausible line of argument by using special methods of representing bacteria. One kind of representation consisted in making the bacteria visible; the other mode of representation was based on disease phenomena. Using a range of techniques of isolating and controlling microorganisms, Koch combined these different modes of representation in a way that made his claims convincing. Thus, the microorganism as a specific cause of disease emerged through a chain of repeated processes of selection and representation in the laboratory.     

Value of combining the erythrocyte sedimentation rate test with tuberculin testing in the control of tuberculosis in baboons.

2 batches of baboon infected with tuberculosis were subjected to serial tests with human and bovine tuberculin, while erythrocyte sedimentation rates were estimated concurrently. In the very early stages most but not all reacted to human tuberculin while fewer responded to bovine material. After further development of the disease, tuberculin tests remained positive while sedimentation rates were raised by 10-30 mm per hour. By the time early spread had occurred response to tuberculin was absent but sedimentation rates tended to increase. Advanced cases always tuberculin negative but sedimentation rates were in excess of 50 mm per hour. Such animals were always in good physical condition and represented an insidious danger to other animals and staff in contact with them. Clinical examination failed to reveal cases of tuberculosis except in the terminal stages and no cases were diagnosed by radiography. 2 animals died from apparent anaphylaxis following inoculation of both types of tuberculin. Results showed that use of one or other of these tests alone would not have made possible the elimination of infection.     

Tuberculosis in patients with human immunodeficiency virus infection. Review of current concepts.

Tuberculosis is a frequent complication of human immunodeficiency virus (HIV)-induced immunosuppression. The diagnosis of extrapulmonary tuberculosis in patients with evidence of HIV infection qualifies as a criterion of the acquired immunodeficiency syndrome. Demographic characteristics of patients with tuberculosis and HIV infection vary by region and reflect the degree to which patients with Mycobacterium tuberculosis infection adopt behaviors that put them at risk for HIV infection. The clinical features of tuberculosis in patients with HIV infection are atypical. Extrapulmonary disease, tuberculin anergy, and unusual findings on chest radiographs occur most frequently when tuberculosis afflicts patients with other clinical evidence of HIV infection at the time tuberculosis is diagnosed. Treatment is effective for tuberculosis in HIV-seropositive patients, and isoniazid prophylaxis is recommended for HIV-infected patients with positive tuberculin skin tests.     

Breaking the ties: epistemic significance, bacilli, and underdetermination

One premise of the underdetermination argument is that entailment of evidence is the only epistemic constraint on theory-choice. I argue that methodological rules can be epistemically significant, both with respect to observables and unobservables. Using an example from the history of medicine -- Koch's 1882 discovery of tuberculosis bacteria -- I argue that even anti-realists ought to accept that these rules can break the tie between theories that are allegedly underdetermined. I then distinguish two types of underdetermination and argue that anti-realists, in order to maintain the underdetermination argument, need to do more than show that theories are empirically equivalent: they need to show that a certain kind of underdetermination obtains.     

Christiaan Eijkman

One century ago, Christiaan Eijkman was appointed Professor of Bacteriology at the Utrecht University, The Netherlands. Despite his appointment to teach bacteriology, Christiaan Eijkman made his main contribution to medical science not in bacteriology but in nutrition. He discovered that Beri-Beri was not an infection but a nutritient deficiency (later called vitamin-deficiency) and was awarded the Nobel Prize for Medicine in 1929 for these observations. These landmark studies were made in the former Dutch East Indies. Interestingly, the results of his studies were presented in the Dutch language, in the medical journal of the Dutch East Indies. As a professor of Bacteriology, his work was the beginning of an important school in biochemistry in The Netherlands.     

The colony as laboratory: German sleeping sickness campaigns in German East Africa and in Togo, 1900-1914

This paper is on dangerous human experimentations with drugs against trypanosimiasis carried out in the former German colonies of German East Africa and Togo. Victory over trypanosomiasis could not be achieved in Berlin because animals were thought to be unsuitable for therapeutic laboratory research in the field of trypanosomiasis. The colonies themselves were necessarily chosen as laboratories and the patients with sleeping sickness became the objects of therapeutical and pharmacological research. The paper first outlines Robert Koch's trypanosomiasis research in the large sleeping sickness laboratory of German East Africa and then focuses on the escalating human experiments on trypanosomiasis in the German Musterkolonie Togo, which must be interpreted as a reaction to the starting signal given by Robert Koch in East Africa.     

Lamessende individualpsychologie: sur le rôle de l’expérimentation psychologique dans la psychiatrie d’Emil Kraepelin (seconde partie)

Contemporary historical investigations on Emil Kraepelin’s experimental work have argued variously that the psychological experiment had either no influence on his nosology, or that it was the very precondition of the nosology, or that it skewed the nosology in favor of organic disorders. The first part of this article considered Kraepelin’s experimental research in Wilhelm Wundt’s laboratory in Leipzig during the 1880s. This second part deals with Kraepelin’s work in Heidelberg in the 1890s. It emphasizes the role of the psychological experiment in stabilizing the professional and scientific legitimacy of psychiatry vis-à-vis general medicine and jurisprudence. Above all, it argues that Kraepelin’s experimental research agenda had not just nosological aims, but also clinico-diagnostic aims. Kraepelin believed that his research would help to develop a battery of diagnostic tools that could reveal prodromal symptoms, speed up diagnostic procedures, alleviate institutional overcrowding, and both generate and stabilize psychiatric norms.     

The epidemiologic significance of tuberculosis mycobacteria of the avian type]

Reaction to intradermal injection of tuberculin from Mycobacteria tuberculosis of the avian type proved to be negative in all the 505 students examined who never came in contact with fowl farms. Of 738 local residents it was found to be positive in 23.8% and of 320 workers of fowl farms--in 54.5% of cases. In response to the injection of Koch tuberculin and PPD-L the number of positive reactions in all the mentioned groups constituted 69-80%. A conclusion was drawn on the epidemiological danger of Mycobacteria of the avian type for the workers of fowl farms and, to a certain degree, for the surrounding population.     

Bacterial bioinformatics: pathogenesis and the genome

As the number of completed microbial genome sequences continues to grow, there is a pressing need for the exploitation of this wealth of data through a synergistic interaction between the well-established science of bacteriology and the emergent discipline of bioinformatics. Antibiotic resistance and pathogenicity in virulent bacteria has become an increasing problem, with even the strongest drugs useless against some species, such as multi-drug resistant Enterococcus faecium and Mycobacterium tuberculosis. The global spread of Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) has contributed to the re-emergence of tuberculosis and the threat from new and emergent diseases. To address these problems, bacterial pathogenicity requires redefinition as Koch's postulates become obsolete. This review discusses how the use of bacterial genomic information, and the in silico tools available at present, may aid in determining the definition of a current pathogen. The combination of both fields should provide a rapid and efficient way of assisting in the future development of antimicrobial therapies.     

Epidemiological causality

Epidemiological methods, which combine population thinking and group comparisons, can primarily identify causes of disease in populations. There is therefore a tension between our intuitive notion of a cause, which we want to be deterministic and invariant at the individual level, and the epidemiological notion of causes, which are invariant only at the population level. Epidemiologists have given heretofore a pragmatic solution to this tension. Causal inference in epidemiology consists in checking the logical coherence of a causality statement and determining whether what has been found grossly contradicts what we think we already know: how strong is the association? Is there a dose-response relationship? Does the cause precede the effect? Is the effect biologically plausible? Etc. This approach to causal inference can be traced back to the English philosophers David Hume and John Stuart Mill. On the other hand, the mode of establishing causality, devised by Jakob Henle and Robert Koch, which has been fruitful in bacteriology, requires that in every instance the effect invariably follows the cause (e.g., inoculation of Koch bacillus and tuberculosis). This is incompatible with epidemiological causality which has to deal with probabilistic effects (e.g., smoking and lung cancer), and is therefore invariant only for the population.