Robert Koch: A Life in Medicine and Bacteriology

Robert Koch was born on December 11, 1843 in Clausthal, a small mining city in the Harz Mountains of Lower Saxony (Niedersachsen). Although he was much closer to his mother than to his father, of greater influence than his mother was probably his uncle, Eduard Biewend, Koch's mother's brother. Koch desired a university education and his school principal recommended that Robert study for a career in medicine or natural science, or perhaps for a career as a Gymnasium teacher. His principal apparently had some doubt about Robert's ability to apply himself, however, as he emphasized that Koch's success would depend upon his ability to concentrate his energies on a chosen field of study. Vacillating from one possibility to another, Robert strongly favored a career in natural science, since this would have permitted him to partake of research expeditions to foreign lands. Koch's main accomplishment at Gottingen was the winning of a prize of 30 ducats for carrying out a difficult anatomical study of the disposition of the nerves in the ganglia of the uterus. At the completion of this study, Koch presented his work, well illustrated with original drawings, under the title: “On the Presence of Ganglion Cells on the Nerves of the Uterus”. These youthful studies, so remote from his main opus of later years, already reveal the energy, industry, and scientific acumen with which Koch worked. In addition, he served the various clinical services in the hospital, including surgery, obstetrics, psychiatry, and pathology.

Despite his increasing fortunes at Rakwitz, Koch was not content to spend his whole life as a simple country doctor. Now he received an invitation from one of his important patients, the Baron von Unruhe Bomst, to apply for the newly created position as Kreisphysikus in Wollstein. Koch applied in person, was accepted, and in April 1872 he moved to Wollstein to begin one of the most important periods of his life. When Koch arrived at Wollstein he was just a 29-year-old physician; when he left eight years later he was on his way to becoming a renowned world-class scientist. It was at Wollstein Koch carried out his pioneering researches on anthrax and the germ theory of disease. In addition to his medical practice, Koch had all the duties of the Kreisphysikus. He had responsibility for smallpox inoculations, for writing death certificates, for giving advice on general public health matters, and for overseeing the local hospital. He also worked hard at keeping up with advances in medicine, reading many medical journals and books. But not only did he find time for all these medical matters and his research, he also took an interest in archaeological explorations.

Ferdinand Cohn was one of the first botanists in Europe to teach from living plants rather than from dried and pressed specimens. In his early years, Cohn studied algae, but by the 1860s he had turned to a study of bacteria. From careful observation of bacteria, Cohn concluded that different species of bacteria existed and that a morphological classification was possible. Cohn discussed Davaine's work on anthrax and other work that suggested that bacteria might cause contagious diseases. Realizing that Koch's work was of great medical importance, Cohn sent to the Institute of Pathology for someone to come and see Koch's cultures and observations. It was a fateful and dramatic moment, as Cohnheim was the one medical researcher who could not only appreciate the beauty of Koch's work, but could publicize Koch himself. Cohn showed that his spore-forming organism, which he named Bacillus subtilis, was resistant to boiling when spores were present, an exceedingly important discovery for the development of reproducible sterilization techniques. As Cohn's Bacillus subtilis formed spores in the manner of Koch's Bacillus anthracis, it was important to show that the disease anthrax was linked to Koch's specific organism.

Throughout the period after Robert Koch's initial success with anthrax, his self-confidence increased enormously. All his spare time was now occupied with research, and he continued to show new and innovative approaches. Koch also used some o f the spleen o f the dead mouse to inoculate rabbits, which died 24 hours after inoculation. Considering Koch's later detractors, and the tremendous criticisms that he suffered, we can see here, in a nutshell, the essence of Koch's personality. Koch's work on anthrax was strongly based on the idea that a given disease was caused by a single organism. Microscopy o f wound infections was carried out by the German Edwin Klebs independently of Davaine. Building on the animal work of Davaine and the microscopic work of Klebs, Koch carried out extensive investigations at Wollstein and developed the theory that each septic condition was due to a different organism. Koch studied a wide variety of traumatic infective diseases, including tissue gangrene in mice, spreading abscess in rabbits, pyemia in rabbits, septicemia in rabbits, and erysipelas in rabbits. But the connection of Koch's work on sepsis to humans was lacking. Certainly Koch would have worked with humans if he had been in a medical center, but isolated in Wollstein, he lacked the necessary clinical material.

This chapter talks about Robert Koch and his first assistants, Georg Gaffky and Friedrich Loeffler, both of whom were to become major figures in bacteriology. Loeffler had been transferred from the General Headquarters of the Army to the Gesundheitsamt a year earlier, and had worked as an assistant in the hygiene and chemistry laboratories during that time. He is best known for his discovery of the causal agent of diphtheria, Corynebocterium diphtheriae, and for his proof that the causal agent of foot-and-mouth disease was filterable, the first animal virus to be so characterized. In a short time, Koch was surrounded by an enthusiastic group o f dedicated workers. Thus, his position at the Amt brought him not only more space and time for research than he had at Wollstein, but interaction with intelligent colleagues. Koch matured rapidly in this new milieu, moving readily from lone scientist in Wollstein to group leader in Berlin. Koch also had a paper on anthrax which was partly an attack on Pasteur.

One of the main missions of the Imperial Health Office was public health, and Robert Koch and his associates set to work enthusiastically to place various public health practices on a rational basis. Among the most important tasks was the development of methods for sterilization and disinfection. An important consideration in this discussion is the distinction between sterilization, which involves the complete killing of both spores and vegetative cells, and disinfection, in which vegetative cells are killed but spores are not necessarily all killed. Koch’s studies provided the groundwork for subsequent research on chemical disinfection. Koch’s work on chemical sterilization was important not only because it led to the discovery of new and more effective antiseptics and disinfectants, but because it provided a precise and reproducible method for studying the whole disinfection process. The practical application of heat sterilization to bacteriological technique was worked out by Robert Koch and his associates at the Imperial Health Office. The procedures for the experiments with heat could be simpler than those for chemical disinfection, since the agent did not have to be removed after treatment. After cooling, the cultures were transferred to suitable media and their viabilities determined by incubation.

Less than two weeks after Robert Koch returned from his triumphant success in London, he began his research on the etiology of tuberculosis. At the time Koch began his work, one-seventh of all reported deaths of human beings were ascribed to tuberculosis, and if one considered only the productive middle-age groups, one-third of the deaths were due to this dread disease. Tuberculosis had been recognized as a specific disease entity since antiquity. Although tuberculosis of the lungs does not seem to have been common in Egypt, pulmonary tuberculosis (also called phthisis) was well recognized by the Greeks, and extensive descriptions can be found in the writings of Hippocrates and others. Another major form of tuberculosis was subsequently recognized, miliary tuberculosis, in which the lesions are tiny nodules disseminated throughout the body. Koch's aim, from the beginning, was the demonstration of a parasite as the causal agent of tuberculosis. To this end, he employed all of the methods that he had so carefully developed over the previous six years: microscopy, staining of tissues, pure culture isolation, animal inoculation. As is now well known, Mycobacterium tuberculosis, the tubercle bacillus, is very difficult to stain with conventional bacteriological stains because of its extremely waxy nature. The properties of the tubercle bacillus make it extremely difficult to work with, and it is remarkable that Koch achieved such quick success in his experiments.

Throughout most of Koch's career, his relationships with Pasteur were very poor. The reasons for this are complex and difficult to unravel; however, it is clear that the Pasteur-Koch controversy not only influenced the lives of these two outstanding scientists, but also had implications for the development of the microbial sciences. The reasons for this are complex and difficult to unravel; however, it is clear that the Pasteur-Koch controversy not only influenced the lives of these two outstanding scientists, but also had implications for the development of the microbial sciences. Indeed, even the name for the discipline is linked to the controversy: the Pasteur school preferred "microbiology" whereas the Koch school preferred "bacteriology". Evidence for the Pasteur-Koch controversy can be found in the scientific writings of these two savants and in their correspondence. The whole controversy has been masterfully outlined by Mollaret in 1983 and this paper is summarized briefly here. As discussed, Pasteur and Koch first met at London in 1881 at the International Congress of Medicine. Most of Koch's attacks on Pasteur were gratuitous, and can only be explained as the young upstart resenting being ignored by the grand master. Koch's co-workers, Loeffler and Gaffky, were even less polite in their articles published in the same volume of the Mitteilungen. The basis of the controversy between Koch's group and Pasteur was over the validity of Pasteur's method of attentuation.

Up to now, bacteriology had given strong insights into the nature of infectious disease but had led to no remedies. In fact, many physicians criticized the "new bacteriology" because it had not led to any successful cures. But now bacteriology had found not only a cure, but a cure for the greatest scourge of humankind. Tuberculosis in Robert Koch's time was quite different from the disease we have today. In addition to the chronic lung infections we know, many cases of tuberculosis were rampant generalized infections of the body (miliary tuberculosis) or ugly, disfiguring skin infections, mainly around the nose and ears (lupus). Additionally, tuberculosis did not respect social or economic status, affecting rich and poor alike. Activated T cells, derived from the thymus, play a helper role in antibody formation, but also play a direct role in the destruction of cancer cells. Another important role of activated T cells is their involvement in a type of allergic response called delayed-type hypersensitivity. It is in this latter process that Koch's tuberculin played a role. Many of the symptoms of tuberculosis are a result of the delayed hypersensitivity reaction that is brought about by infection with the tubercle bacillus. What Koch found was that an extract of a pure culture of the tubercle bacillus, when injected under the skin of the guinea pig, brings about a remarkable response if the animal is infected.

By 1890 the bacterial etiologies of many important infectious diseases had been determined, following the methods and procedures which Robert Koch had developed. Koch's name is well known in the annals of tropical diseases. He made many important contributions to the study of malaria, sleeping sickness, and numerous viral diseases of veterinary interest. The only organisms ever named for Koch were protozoa: a trypanosome that was thought to be the cause of Rhodesian red water disease of cattle, Theileria kochi (the name was later changed), and an amoeba that was thought to be the cause of simian malaria, Haemamoeba kochi. Koch developed methods for the control of several important cattle diseases in Africa, and his services were widely sought by African governments. Doing bacteriology in a primitive field setting is always a challenge. Although Koch had previous experience with primitive conditions when studying cholera in India, the facilities in Calcutta were actually palatial compared to what could be obtained in South Africa. In 1897, the same year that Koch was in Africa and India, Ronald Ross was carrying out his epochal work on malaria in Calcutta, proving that the parasite is transmitted by the mosquito. This work was to have far reaching consequences for the control of malaria.

Robert Koch was one of the most influential and dedicated medical researchers of the nineteenth century. It can almost be said that Koch created the field of bacteriology. Koch's influence on medical microbiology can be most effectively demonstrated by reference to the table which summarizes the fruits of Koch's concepts and methods. It is still inconceivable that it took Koch only nine months to detect, isolate, and characterize the tubercle bacillus. The slow-growing tubercle bacillus presented numerous experimental difficulties, which Koch overcame in masterful fashion. The two discoveries, the tubercle bacillus and the comma bacillus, coming so quickly one after the other, established Koch's reputation for all time. A Koch myth developed: the great Koch could do no wrong. Advances in food and water bacteriology were built on the foundations which Koch laid. Koch postulated: The suspected pathogen must he constantly present when the disease is present can only be fulfilled by means of microscopic pathology. It was left to others, much later, to explain the Koch phenomenon (as it was called) and assess its significance for infection and immunity. Koch's story can be an inspiration to all who are fascinated by the interplay of science and medicine. In Koch's day, bacteriology was just such an off-beat field. It has been said that science continually opens up new fields to view. Many new fields, whatever they may be, await the coming generations of Robert Kochs!