The first researcher to isolate the microorganisms that cause tuberculosis and cholera, Robert Koch firmly established the infectious nature of these diseases, making possible the study of their origins.
The period between 1870 and 1900 could arguably be called the golden age of bacteriology. It was during these years that the infectious nature of many forms of disease was firmly established. Further, with the development of techniques for growing microorganisms in pure culture, a process initiated by Robert Koch in his work with anthrax during the 1870’s, it became possible to establish specific organisms as the etiological agents behind specific diseases. It was Koch’s work on the isolation of the tuberculosis bacillus that indicated the necessity of growing microorganisms in pure culture in order to carry out such studies.
During the 1880’s, tuberculosis became the scourge of Europe, as one of every seven deaths was linked to the disease. Many others were undoubtedly infected with the tuberculosis agent but were without symptoms; some of these people served as carriers for the disease. Tuberculosis had been known since antiquity; the Greeks in the time of Hippocrates
Even into the mid-eighteenth century, the precise nature of the disease remained uncertain. The noted German pathologist Rudolf Virchow
Koch began his career as a country physician, gaining experience in clinical studies during the Franco-Prussian War of 1870-1871. Upon his return, he began studies on anthrax, a scourge among farm animals. Koch confirmed the role of the anthrax bacillus as the cause of the illness; more important, he established the methodology for growing the organism in pure culture. Koch’s 1881 paper on methods involved in studying organisms in such cultures, using his plate technique, became known as the bible of bacteriology; Koch himself became internationally known as a result.
Robert Koch.
Koch began his studies into tuberculosis in August, 1881. He was aware of Villemin’s
After he developed a means to visualize the organism, Koch began a systematic study of diseased tissues. He quickly established that all specimens obtained from patients with tuberculosis contained the organism. As the disease progressed, either toward increased severity, or patient recovery, the number of organisms reflected the developments in the disease. If the disease became worse, the numbers increased; if the patient recovered, the number of organisms decreased.
Koch then attempted to grow the organism in pure culture. He used a variety of nutrient media, but it was only when he added coagulated blood serum to the growth cultures that the organism began to grow. Even so, it required several weeks of incubation before colonies of bacteria could be observed to develop on the nutrient material. Koch then inoculated guinea pigs with samples obtained from his pure cultures. These animals developed tuberculosis, with symptoms and pathology identical to those observed in human patients; symptoms were also similar to those in guinea pigs inoculated with material from the human disease. The methodology of this work—isolation and growth of a suspected etiological agent in pure culture, followed by observation of the disease in animals inoculated with this material—became the basis for what is known as Koch’s postulates.
Koch presented his work on isolation of the tubercle bacillus before the Berlin Physiological Society on March 24, 1882. It was fewer than eight months from the time when he had begun work on the problem.
In 1883, Koch turned his attention to the problem of cholera. Endemic in India for centuries, the disease did not reach Europe until 1831. By 1875, it had been associated with four major pandemics; Koch himself had observed the nature of the disease during the European epidemic between 1866 and 1875. The severity and rapid spread of the disease had already established it as one of the most dread diseases of humankind. In 1883, a fresh outbreak occurred in Egypt, threatening to spread again into the continent of Europe. By the request of the Egyptian government, the French established a commission to study the disease under the auspices of Louis Pasteur, but led by Pasteur’s assistants, Pierre-Paul-Émile Roux
Reflecting the ongoing rivalry with the French, the German government likewise established a commission, under the leadership of Koch, which arrived in Egypt in August, 1883. During the course of the epidemic in Egypt, between 60,000 and 100,000 people died. Among the deaths was that of Louis Thuillier. Thuillier had been so respected that Koch put aside his personal dislike for Pasteur and the French and attended Thuillier’s funeral.
Ironically, the German commission arrived after the epidemic had peaked, and it became difficult to obtain sufficient clinical specimens for study. Koch received permission from his government to travel to India, the source of the cholera epidemics, and arrived there in December, 1883. The research program for isolation and identification of the cholera agent was similar to that utilized previously in his studies on tuberculosis. The availability of fresh material allowed Koch to quickly observe the cholera bacillus, and to grow it in pure culture. The agent he described, now called Vibrio cholerae, was identical in appearance to those he had previously observed in Egypt. Unlike the tuberculosis agent, the cholera bacillus could be grown in the laboratory with relative ease. Further, its unusual appearance, that of a curved or comma-shaped organism, made it easy to identify among the multitude of organisms in clinical specimens from the intestines.
In February, 1884, Koch reported the isolation of the cholera organism, but Pasteur and others were skeptical that he had indeed isolated the correct organism; Koch had been unable to reproduce the disease in animals. Nevertheless, the nature of the epidemiology of cholera, and the invariable presence of the organism in such epidemics, established the etiological nature of the comma bacillus.
Robert Koch’s discovery of the microorganisms—the bacteria—that cause both tuberculosis and cholera led to methods for containing tuberculosis and nearly eliminating cholera from the developed world. His laboratory methods, including unique staining techniques and his use of a pure culture to isolate organisms, make Koch the founder of modern bacteriology. In 1905, he was awarded the Nobel
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Brock, Thomas. Robert Koch: A Life in Medicine and Bacteriology. 1988. Reprint. New York: AMS Press, 1999. Written by a noted microbiologist, this biography of Koch also presents a detailed study of his career, based on his correspondence, published work, and contemporary literature on bacteriology. -
Bulloch, William. A History of Bacteriology. London: Oxford University Press, 1938. A classic work on the history of bacteriology. Provides a significant amount of detail on the works of Koch and Pasteur. -
Daniel, Thomas M. Pioneers of Medicine and Their Impact on Tuberculosis. Rochester, N.Y.: University of Rochester Press, 2000. This history of tuberculosis and its treatment includes a chapter on Koch’s pioneering work in bacteriology. -
De Kruif, Paul. Microbe Hunters. New York: Harcourt, Brace & World, 1950. This readable yet detailed account includes the lengthy chapter “Koch: The Death Fighter.” De Kruif makes the world of microbiology accessible to the general reader. -
Dormandy, Thomas. The White Death: A History of Tuberculosis. New York: New York University Press, 2000. This history of tuberculosis examines Koch’s role in isolating the cause of the disease. -
Geison, Gerald. The Private Science of Louis Pasteur. Princeton, N.J.: Princeton University Press, 1995. A detailed biography of France’s most famous chemist, and Koch’s chief rival. -
Golub, Edward. The Limits of Medicine. New York: Random House, 1994. Discusses the role of science and medicine in the treatment and prevention of disease. -
Ryan, Frank. The Forgotten Plague: How the Battle Against Tuberculosis Was Won—and Lost. Boston: Little, Brown, 1992. A popular account of the story of tuberculosis. Emphasis is placed on the spread of the disease in the 1980’s, but the work also includes an extensive history.
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Suppression of Yellow Fever
Emil von Behring; Ferdinand Julius Cohn; Robert Koch; Joseph Lister; Louis Pasteur; Rudolf Virchow.