Historical Perspectives Centennial: Koch's Discovery of the Tubercle Bacillus

On March 24, 1882, Robert Koch announced to the Berlin Physiological Society that he had discovered the cause of tuberculosis. Three weeks later, on April 10, he published an article entitled "The Etiology of Tuberculosis" (1). In 1884, in a second paper with the same title, he first expounded "Koch's postulates," which have since become basic to studies of all infectious diseases. He had observed the bacillus in association with all cases of the disease, had grown the organism outside the body of the host, and had reproduced the disease in a susceptible host inoculated with a pure culture of the isolated organism.

Koch continued his studies on tuberculosis, hoping to find a cure. In 1890, he announced the discovery of tuberculin, a substance derived from tubercle bacilli, which he thought was capable of arresting bacterial development in_vitro and in animals. This news gave rise to tremendous hope throughout the world, which was soon replaced by disillusionment when the product turned out to be an ineffective therapeutic agent. Tuberculin later proved to be a valuable diagnostic tool.

In 1905, when Koch was awarded the Nobel Prize in medicine, he devoted his acceptance speech to promoting greater understanding of tuberculosis and its causative agent. Koch died in 1910, leaving the scientific community and the world in general with a valuable inheritance of knowledge and understanding resulting from his seminal work on anthrax, cholera, trypanosomiasis, and especially tuberculosis.

In the wake of Koch's discoveries, subsequent progress in conquering tuberculosis has been relatively slow. In the laboratory, recognition of the avian bacillus by Nocard in 1885 and differentiation of bovine and human tubercle bacilli by Theobald Smith in 1898 laid the groundwork for identification of other (nontuberculous) mycobacterial species. Diagnosis of tuberculosis was aided by discovery of the acid-fast nature of the bacillus by Ehrlich in 1882, discovery of X rays by Roentgen in 1895, development of the tuberculin skin test by Von Pirquet and Mantoux in 1907-1908, and preparation of purified protein derivative (PPD) of tuberculin by Seibert in 1931.

In the 1930s, the epidemiologic work of Wade Hampton Frost led to a better understanding of the epidemiology of tuberculosis. In the 1940s, using Seibert's PPD administered by the Mantoux method and chest X-ray examinations, the United States Public Health Service began a series of studies that elucidated further the epidemiology of tuberculosis and made apparent the distinction between tuberculous infection without disease (a positive skin test in the absence of signs and symptoms) and overt clinical tuberculosis.

Treatment has progressed from bed rest, special diets and fresh air, through pneumothorax and other lung-collapse procedures and surgical resection, to specific chemotherapy (streptomycin in 1947, para-aminosalicylic acid in 1949, isoniazid in 1952, and drugs such as rifampin in recent years). With combinations of modern drugs properly administered, tuberculosis is now virtually 100% curable.

Prevention of tuberculosis has been approached in 2 ways. In 1921, Calmette and Guerin developed an attenuated strain of Mycobacterium bovis, which many countries throughout the world have used, with variable results, as a vaccine. The other major approach to prevention has been the treatment of persons with subclinical tuberculous infection (tuberculous infection without disease) with isoniazid.

There have been recent improvements in tuberculosis-control methodology. Effective treatment regimens of 9 months' duration are now available, and research continues in attempts to further shorten treatment. Fluorescence microscopy has made the examination of sputum smears faster, easier, and more accurate. Phage typing is a useful tool for studying the epidemiology of tuberculosis. Newer immunologic techniques offer promise of improved diagnostic tests, and rapid radiometric methods of identifying M. tuberculosis and testing for drug susceptibility are being developed.

In the century since Koch's discovery, advances in prevention, diagnosis, and treatment of tuberculosis--especially treatment--have produced a spectacular decline in tuberculosis mortality and a striking decline in tuberculosis morbidity--primarily in technically advanced countries (Figure 1). Progress has been less dramatic in developing countries. Tuberculosis stubbornly persists as a major worldwide health problem. It is estimated that as many as 10 million cases of tuberculosis may occur throughout the world each year--4-5 million of them highly infectious, and 2-3 million resulting in death. Eradication of tuberculosis, although possibly attainable in technical terms, remains an elusive goal. Reported by Tuberculosis Control Div, Center for Prevention Svcs, Mycobacteriology Br, Bacterial Diseases Div, Center for Infectious Diseases, CDC.

Reference

1. Koch R. Die Atiologic der Tuberkulose. Berliner Klinische Wochenschrift 1882; 15:221-30.

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