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Koch's postulates ( )"Koch"
''
Random House Webster's Unabridged Dictionary ''Random House Webster's Unabridged Dictionary'' is a large American dictionary, first published in 1966 as ''The Random House Dictionary of the English Language: The Unabridged Edition''. Edited by Editor-in-chief Jess Stein, it contained 315, ...
''.
are four criteria designed to establish a
causal relationship Causality (also referred to as causation, or cause and effect) is influence by which one event, process, state, or object (''a'' ''cause'') contributes to the production of another event, process, state, or object (an ''effect'') where the cau ...
between a
microbe A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
and a
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
. The postulates were formulated by
Robert Koch Heinrich Hermann Robert Koch ( , ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. As the discoverer of the specific causative agents of deadly infectious diseases including tuberculosis, cholera (though the bacteri ...
and Friedrich Loeffler in 1884, based on earlier concepts described by Jakob Henle, and refined and published by Koch in 1890. Koch applied the postulates to describe the
etiology Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, ...
of
cholera Cholera is an infection of the small intestine by some strains of the bacterium '' Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting an ...
and
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...
, both of which are now ascribed to
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
. The postulates have been controversially generalized to other diseases. More modern concepts in microbial pathogenesis cannot be examined using Koch's postulates, including
viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...
(which are obligate intracellular parasites) and
asymptomatic carrier An asymptomatic carrier is a person or other organism that has become infected with a pathogen, but shows no signs or symptoms. Although unaffected by the pathogen, carriers can transmit it to others or develop symptoms in later stages of the ...
s. They have largely been supplanted by other criteria such as the
Bradford Hill criteria The Bradford Hill criteria, otherwise known as Hill's criteria for causation, are a group of nine principles that can be useful in establishing epidemiologic evidence of a causal relationship between a presumed cause and an observed effect and have ...
for infectious disease causality in modern public health, and Falkow's criteria for microbial pathogenesis.


The postulates

Koch's postulates are the following: # The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms. # The microorganism must be isolated from a diseased organism and grown in pure
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups ...
. # The cultured microorganism should cause disease when introduced into a healthy organism. # The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent. However, Koch later abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of
cholera Cholera is an infection of the small intestine by some strains of the bacterium '' Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting an ...
and, later, of
typhoid fever Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over severa ...
.
Asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered a ...
or subclinical infection carriers are now known to be a common feature of many infectious diseases, especially viral diseases such as
polio Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe sy ...
, herpes simplex,
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
,
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...
, and
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quick ...
. As a specific example, all doctors and virologists agree that
poliovirus A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species '' Enterovirus C'', in the family of '' Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3. Poliovirus is composed of ...
causes paralysis in just a few infected subjects. The second postulate may also be suspended for certain microorganisms or entities that cannot (at the present time) be grown in pure culture. Viruses also require host cells to grow and reproduce and therefore cannot be grown in pure cultures. The third postulate specifies "should" not "must" because, as Koch himself proved in regard to both
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...
and cholera, not all organisms exposed to an infectious agent will acquire the infection. Noninfection may be due to such factors as general health and proper immune functioning; acquired immunity from previous exposure or vaccination; or genetic immunity, as with the resistance to
malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...
conferred by possessing at least one sickle cell
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chrom ...
. There are a few other exceptions to Koch's postulates. A single pathogen can cause several disease conditions. Additionally, a single disease condition can be caused by several different microorganisms. Some pathogens cannot be cultured in the lab, and some pathogens only cause disease in humans. In summary, an infectious agent can be considered to be a sufficient cause for a disease if it satisfies Koch's postulates. Failing that, the postulates suggest that the infectious agent is a necessary, but insufficient, cause for a disease.


History

Koch's postulates were developed in the 19th century as general guidelines to identify
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s that could be isolated with the techniques of the day. Even in Koch's time, it was recognized that some infectious agents were clearly responsible for disease even though they did not fulfill all of the postulates. Attempts to apply Koch's postulates rigidly to the diagnosis of viral diseases in the late 19th century, at a time when viruses could not be seen or isolated in culture, may have impeded the early development of the field of
virology Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, the ...
. Koch's postulates have been recognized as largely obsolete by
epidemiologists Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...
since the 1950s, so, while retaining historical importance and continuing to inform the approach to microbiologic diagnosis, they are not routinely used to demonstrate causality. Koch's postulates have also influenced scientists who examine microbial pathogenesis from a molecular point of view. In 1988, a molecular version of Koch's postulates was developed to guide the identification of microbial genes encoding
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
factors. That HIV causes AIDS does not follow from Koch's postulates, which may have supported HIV/AIDS denialism. The role of
oncovirus An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the lette ...
es in causing some cancers also does not follow Koch's postulates. New discoveries of methods of infections as a result of Koch and many others' work have shown that some diseases and conditions are not always caused by a single microbe species. According to a 2019 study by Todd and Peters, a newly discovered interaction between the pathogen ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...
'' and "fungal opportunist" ''
Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...
'' is being considered a co-infection that is found in the bodies of sick patients who have different conditions. This kind of synergism was found to be lethal in a separate study conducted by Carlson on mice. When mice were infected with one pathogen independently of the other, sickness resulted but the mice were able to recover. When infected with both pathogens together, the mice had a near-100% mortality rate, showing that some pathogens cannot be as easily isolated or may need extra techniques and steps that better prove causation of the disease.


For the 21st century

Koch's postulates have played an important role in
microbiology Microbiology () is the scientific study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, bacteriology, ...
, yet they have major limitations. For example, Koch was well aware in the case of cholera that the causal agent, ''
Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...
'', could be found in both sick and healthy people, invalidating his first postulate. Furthermore, viral diseases were not yet discovered when Koch formulated his postulates, and there are many viruses that do not cause illness in all infected individuals, a requirement of the first postulate. Additionally, it was known through experimentation that '' Helicobacter pylori'' caused inflammation of the gastric lining when ingested. As evident as the inflammation was, it still did not immediately convince skeptics that ''H. pylori ''was associated with
stomach ulcers Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines ...
. Eventually, skeptics were silenced when a newly developed
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
treatment eliminated the bacteria and ultimately cured the disease. Koch's postulates are also of limited effectiveness when evaluating biofilms, Somni cells, and viruses. Cultivation of biofilms requires cultivation by molecular methods rather than traditional methods, and these alternative methods do not detect the cause of infection, which therefore interferes with the third postulate, that microorganisms should cause disease. For example, Somni cells and viruses cannot be cultured. The Somni cells, also called sleeping cells, become dormant due to strain on the cell. This state of sleep prevents the cell from growing in the culture. This is similar to how viruses cannot grow in
axenic In biology, axenic (, ) describes the state of a culture in which only a single species, variety, or strain of organism is present and entirely free of all other contaminating organisms. The earliest axenic cultures were of bacteria or unicellu ...
culture: viruses must be living to replicate, so the culture is not a suitable host. Byrd and Segre have proposed changes to the postulates to make them more accurate for today's world. Their revisions involve the third postulate: they disagree that a pathogen will always cause disease. Their first revision involves
colonization resistance Colonization resistance is the mechanism whereby the intestinal microbiota protects itself against incursion by new and often harmful microorganisms. Colonization resistance was first identified in 1967, and it was initially referred to as antibio ...
. Colonization resistance allows an organism to feed off of the host and protect it from pathogens that would have caused disease if the organism was not attached to the host. Their second revision is that a community of microbes could help inhibit pathogens even further, preventing the pathogen from spreading disease as it is supposed to. Similar to Byrd and Segre, Rivers suggested revisions to Koch's postulates. He believed that, although the original postulates were made as a guide, they were actually an obstacle. Rivers wanted to show the link between viruses and diseases. Rivers' own postulates are: the virus must be connected to disease consistently; the outcome of experimentation must indicate that the virus is directly responsible for the disease. Contradictions and occurrences such as these have led many to believe that a fifth postulate may be required. If accepted, this postulate would state that sufficient microbial data should allow scientists to treat, cure, or prevent the particular disease. More recently, modern nucleic-acid-based microbial detection methods have made Koch's original postulates even less relevant. These methods enable the identification of microbes that are associated with a disease, but which cannot be cultured. Also, these methods are very sensitive, and can often detect very low levels of viruses in healthy people. These new methods have led to revised versions of Koch's postulates. Fredricks and Relman have suggested a set of postulates for the novel field of microbial pathogenesis. These modifications are still controversial in that they do not account well for established disease associations, such as papillomavirus and
cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...
, nor do they take into account
prion disease Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It i ...
s, which have no nucleic acid sequences of their own.


See also

*
Bradford Hill criteria The Bradford Hill criteria, otherwise known as Hill's criteria for causation, are a group of nine principles that can be useful in establishing epidemiologic evidence of a causal relationship between a presumed cause and an observed effect and have ...
*
Causal inference Causal inference is the process of determining the independent, actual effect of a particular phenomenon that is a component of a larger system. The main difference between causal inference and inference of association is that causal inference ana ...
* Mill's Methods *
Molecular Koch's postulates Molecular Koch's postulates are a set of experimental criteria that must be satisfied to show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen. Genes that satisfy molecular Koch ...
* Willoughby D. Miller


References

{{Reflist, 30em


Further reading


Contagion: Historical Views of Diseases and Epidemics
from Harvard Library


External links


''Die Aetiologie der Tuberculose'' (1882)

''Die Aetiologie der Tuberkulose'' (1884)

''Milestones in Microbiology'' (1962)
Epidemiology Infectious diseases Robert Koch 1884 in biology 1884 in Germany