Koch's postulates are a set of principles that guide scientific efforts to establish the cause of an infectious disease. Koch's postulates are named after the German physician Robert Koch (1843–1910), who was the first scientist to identify several important pathogens (disease-causing agents). The postulates named after him require a series of observational and experimental conditions to be satisfied before it can be concluded that a particular microorganism causes a certain disease. Because of advances in microbiology over the last century, Koch's postulates have been revised, but they remain relevant to modern research. For example, they have been extended to include nonliving molecular causes of disease such as prions.
Robert Koch was a German medical researcher. He is today famous not only for formulating Koch's but for using them to identify the pathogens that cause some of the deadliest diseases that afflict humankind, including anthrax, cholera, and tuberculosis. Along with the French physician Louis Pasteur (1822–1895), he is considered one of the pioneers of bacteriology (the study of bacteria). Working at home in an improvised laboratory, without assistance from any university, rich patron, or government agency, Koch proved that anthrax is caused by a bacterium—the first occasion on which a disease was shown to be caused by a specific microorganism. Koch received a Nobel Prize in medicine in 1905.
Koch's postulates are four rules for deciding whether the scientific evidence warrants concluding that a certain microorganism is the cause of a disease. They are as follows:
- The organism must be found in all animals that have the disease, not present in healthy animals.
- It must be possible to isolate the organism from a diseased animal and grow it in pure culture (a nonliving nutritional medium in a container).
- It must then be possible to infect a healthy animal with the organisms grown in culture.
- The organism must then be isolated again from the experimentally infected animal.
WORDS TO KNOW
CULTURE: A culture is a single species of microorganism that is isolated and grown under controlled conditions. The German bacteriologist Robert Koch first developed culturing techniques in the late 1870s. Following Koch's initial discovery, medical scientists quickly sought to identify other pathogens. Today bacteria cultures are used as basic tools in microbiology and medicine.
ETIOLOGY: The study of the cause or origin of a disease or disorder.
PATHOGEN: A disease-causing agent, such as a bacteria, virus, fungus, etc.
GERMAN PHYSICIAN ROBERT KOCH, PIONEER OF BACTERIOLOGY
In 1880, German physician Robert Koch (1843–1910) accepted an appointment as a government advisor with the Imperial Department of Health in Berlin. His task was to develop methods of isolating and cultivating disease-producing bacteria and to formulate strategies for preventing their spread. In 1881 he published a report advocating the importance of pure cultures in isolating disease-causing organisms and describing in detail how to obtain them. The methods and theory espoused in this paper are still considered fundamental to the field of modern bacteriology and set the foundation for the first three postulates in what were later described as Koch's postulates. The fourth postulate was added by the plant biologist E.F. Smith in 1905.
Using the principles that were later named in his honor, students of Koch in the late nineteenth century quickly identified the bacteria that cause bubonic plague, diphtheria, gonorrhea, leprosy, syphilis, tetanus, typhoid, and several other diseases.
The power of Koch's postulates as an aid to science, scientists have pointed out, comes not from their rigid application, but from their encouragement of a spirit of scientific rigor. They serve as guidelines—not absolute rules—for collecting the scientific evidence that will prove what the cause of a given disease is. Exceptions to Koch's postulate numerous; for example, many pathogens, including those that cause giardiasis, polio, and AIDS, can be carried asymptomatically, which violates the first postulate. That is, these pathogens can sometimes live and reproduce in an individual without making that individual sick. Koch's original first postulate has, therefore, been clarified, in practice, to “The organism must be found in all animals that have the disease.” Also, not all pathogens can grow in pure culture, as the second postulate requires; viruses and prions, for example, can only reproduce with the help of living cells.
New infectious diseases are emerging at the rate of about one per year, but it is often difficult to discover the cause of a particular infectious disease. Koch's postulates, therefore, remain relevant today. According to the editors of the journal Nature Reviews Microbiology, writing in 2006, “more than 120 years after they were first proposed, Koch's postulates still remain the gold standard for any investigation that sets out to prove the etiology (origin or cause) of an infectious disease.”
One modern example of fulfilling Koch's postulates involves the Australian physician Barry Marshall and his work with the bacterium Helicobacter pylori. Marshall, a gastroenterologist, studied the bacteria in the 1980s, after a colleague noticed that H. pylori was present in the stomachs of patients with gastrointestinal ulcers and not present in patients without ulcers. Marshall set out to determine if H. pylori caused stomach ulcers, and eventually succeeding in growing it in the laboratory. Lacking human test subjects, Marshall first determined that his stomach was without disease, then infected himself by drinking a mixture containing H. pylori. After about a week, Marshall began vomiting, and an endoscopy (examination with a thin, flexible, camera-mounted cable) proved he had developed severe inflammation in the lining of his stomach, from which Helicobacter pylori was recovered. By satisfying Koch's postulates, Marshall had proven that H. pylori could cause disease in humans. This revolutionized the treatment of stomach ulcers, which were until this time, considered caused by stress and excess stomach acid. By the mid 1990s, scientists recognized that stomach ulcers were caused by an infectious agent, and could be successfully treated with antibiotics. Marshall was awarded the Nobel Prize for his discovery in 2005.
Koch's postulates were also been cited in the 1980s in the long and acrimonious debate between the great majority of scientists and American virologist Peter Duesberg (1936–) and a few others over whether AIDS is in fact caused by HIV. Duesberg has long maintained that HIV does not cause AIDS (he claims that recreational and other drugs do). For some years, he argued that HIV had not been shown to be the cause of AIDS according to the standards of Koch's postulates. In the mid–1990s, however, many researchers indicated that all of Koch's postulates had finally been fulfilled and that HIV had indeed been proved to be the cause of AIDS.
CHALLENGES TO KOCH'S POSTULATES
Since the proposal and general acceptance of the postulates, they have proven to have a number of limitations. For example, infections organisms such as some the bacterium Mycobacterium leprae, some viruses, and prions cannot be grown in artificial laboratory media. Additionally, the postulates are fulfilled for a human disease-causing microorganism by using test animals. While a microorganism can be isolated from a human, the subsequent use of the organism to infect a healthy person is unethical. Fulfillment of Koch's postulates requires the use of an animal that mimics the human infection as closely as is possible.
Another limitation of Koch's postulates concerns instances where a microorganism that is normally part of the normal flora of a host becomes capable of causing disease when introduced into a different environment in the host (e.g., Staphylococcus aureus), or when the host's immune system is malfunctioning(e.g., Serratia marcescens).
Despite these limitations, Koch's postulates remain useful in clarifying the relationship between microorganisms and disease.
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Editorial. “Following Koch's Example.” Nature Reviews Microbiology. 3(2005):906.
Vacomo, V., et al. “Natural History of Bartonella Infections (An Exception to Koch's Postulate).” Clinical and Diagnostic Laboratory Immunology. 9(2002):8–18.
National Institute of Allergy and Infectious Disease, National Institutes of Health (U.S. Government). “HIV/AIDS: Koch's Postulates Fulfilled.” September, 1995 <http://www.niaid.nih.gov/Publications/hivaids/12.htm> (accessed February 1, 2007).