discovery of disease-causing pathogens discovery of disease-causing pathogens the discovery of disease-causing pathogens is an important activity in the field of medical science. many viruses, bacteria, protozoa, fungi, helminthes and prions are identified as a confirmed or potential pathogen. in the united states, a centers for disease control program, begun in 1995, identified over a hundred patients with life-threatening illnesses that were considered to be of an infectious cause, but that could not be linked to a known pathogen. the association of pathogens with disease can be a complex and controversial process, in some cases requiring decades or even centuries to achieve. factors impairing identification of pathogens factors which have been identified as impeding the identification of pathogens include the following: 1. lack of animal models: experimental infection in animals has been used as a criterion to demonstrate a disease-causing ability, but for some pathogens (such as vibrio cholerae, which cause disease only in humans) animal models do not exist. in cases where animal models were not available, scientists have sometimes infected themselves or others to determine an organism's disease causing ability. 2. pre-existing theories of disease: before a pathogen is well-recognized, scientists may attribute the symptoms of infection to other causes, such as toxicological, psychological, or genetic causes. once a pathogen has been associated with an illness, researchers have reported difficulty displacing these pre-existing theories. 3. variable pathogenicity: infection with pathogens can produce varying responses in hosts, complicating the process of showing a relationship between infection and the pathogen. in some infectious diseases, the severity of symptoms has been shown to be dependent on specific genetic traits of the host. 4. organisms that look alike but behave differently: in some cases a harmless organism exists which looks identical to a disease causing organism with a microscope, which complicates the discovery process. 5. lack of research effort: slow progress has been attributed to the small numbers of researchers working on a pathogen. 19th-century discoveries vibrio cholerae (1849-1884) vibrio cholerae bacteria are transmitted through contaminated water. once ingested, the bacteria colonizes the intestinal tract of the host and produces a toxin which causes body fluids to flow across the lining of the intestine. death can result in 2–3 hours from dehydration if no treatment is provided. before the discovery of an infectious cause, the symptoms of cholera were thought to be caused by an excess of bile in the patient; the disease cholera gets its name from the greek word choler meaning bile. this theory was consistent with humorism, and led to such medical practices as bloodletting. the bacterium was first reported in 1849 by gabriel pouchet, who discovered it in stools from patients with cholera, but he did not appreciate the significance of this presence. the first scientist to understand the significance of vibrio cholerae was the italian anatomist filippo pacini, who published detailed drawings of the organism in "microscopical observations and pathological deductions on cholera" in 1854. he published further papers in 1866, 1871, 1876 and 1880, which were ignored by the scientific community. he correctly described how the bacteria caused diarrhea, and developed treatments that were found to be effective. whilst john snow's epidemiological maps were well recognised, and led to the removal of the broad street pump handle, e.g. 1854 broad street cholera outbreak. in 1874, scientific representatives from 21 countries voted unanimously to resolve that cholera was caused by environmental toxins from miasmatas, or clouds of unhealthy substances which float in the air. in 1884, robert koch re-discovered vibrio cholerae as a causal element in cholera. some scientists opposed the new theory, and even drank cholera cultures to disprove it: koch announced his discovery of the cholera vibrio in 1884. his conclusions were based upon the constant finding of the peculiar "comma bacillus" in the stools of cholera patients, and the failure to demonstrate this organism in the feces of other persons. it was not possible to reproduce typical cholera in laboratory animals. at the time the "germ theory" of disease had not yet obtained general acceptance, and koch's announcement was received with considerable skepticism, particularly after it was found that similar "comma bacilli" could be found at times in the feces of persons not suffering from cholera, and often in all sorts of other environments - well and river waters, cheese, etc. we now know that these were saprotrophic species of vibrio, which may be differentiated from the cholera vibrio by cultural and immunological methods. but the correctness of koch's opinion was dramatically demonstrated by von pettenkofer and emmerich who, doubting the etiological relationship of koch's organisms, deliberately drank cultures of it. von pettenkofer developed merely a transient diarrhea, but emmerich suffered from a typical and severe attack of cholera.— by a. t. henrici, the biology of bacteria, dc heath and company, 1939. asin b00085gabk, von pettenkofer considered his experience proof that vibrio cholerae was harmless, as he did not develop cholera from consuming the culture. between 1849 when pouchet discovered vibrio cholerae and 1891, over a million people died in cholera epidemics in europe and russia. in 1995, researchers published a study in science explaining why some persons are able to be infected with cholera without symptoms, possibly explaining why pettenkofer did not get sick. the study showed that a series of genetic mutations in some people provide resistance to cholera toxin; but these mutations come at a price. if too many of them occur in a person, they will develop cystic fibrosis, an incurable and often fatal genetic disorder. 20th-century discoveries giardia lamblia (1681-1975) giardiasis is a disease caused by infection with the protozoan giardia lamblia. infection with giardia can produce diarrhea, gas, and abdominal pain in some people. if untreated, infection can be chronic. in children, chronic giardia infection can cause stunting (stunted growth) and lowered intelligence, infection with giardia is now universally recognized as a disease, and treated by physicians with anti-protozoal drugs. since 2002, giardia cases must be reported to the center for disease control, according to the cdc's reportable disease spreadsheet. the united states national institutes of health gastrointestinal parasites lab studies giardia almost exclusively. http://www3.niaid.nih.gov/labs/aboutlabs/lpd/gastrointestinalparasitessection/nash.htm. : missing or empty |title= (help) however, giardia experienced an extraordinarily long term of emergence, from its discovery in 1681, until the 1970s when it was fully accepted that infection with giardia was a treatable cause of chronic diarrhea: giardia lamblia was first discovered by leeuwenhoeck (1681) who found the parasite in his own stools. it was long considered to be a harmless commensal organism, but in recent years has been recognized as a cause of intestinal disease often acquired by travelers to foreign countries, persons drinking contaminated water in this country, children in day care nurseries and homosexual males. it is the most common pathogenic intestinal parasite in the united states, being found in 4% of stool specimens submitted to state public health laboratories for parasite examination. attesting to its increasing importance in the united states, a symposium on giardiasis, sponsored by the environmental protection agency, was held in the fall of 1978. — by jw smith, giardiasis, 1980 some of the first evidence in modern times of giardia's pathogenicity came during world war ii when soldiers were treated for malaria with the antiprotozoal quinacrine, and their diarrhea disappeared, as did the giardia from their stool samples. in 1954, dr. r.c. rendtorff performed experiments on prisoner volunteers, infecting them with giardia. in the experiment, although some prisoners experienced changes in stool habits, he concluded that these could not be conclusively linked to giardia infection, and also indicated that all prisoners experienced spontaneous clearance of giardia. his experiments were described in the epa symposium on waterborne transmission of giardiasis in 1979: we also included giardia lamblia, which at that time was not generally believed to be an invasive pathogenic parasite of man. giardia was thought in the 1950s to cause occasional problems of diarrhea in children but its appearance was so common and, in adults so lacking in clinical symptomatology, that most considered it a non-pathogen. as a result we felt safe in exposing prisoners to giardia... — by dr. rc rendtorff in an epa symposium on the waterborne transmission of giardiasis - in 1979 in 1954–55, an outbreak of giardia infection occurred in oregon (us), sickening 50,000 people. this was documented in a communication by dr. lyle veazie, which wasn't published until 15 years later in the new england journal of medicine. in the communication, veazie notes that he was unable to find a publisher for his account of the epidemic. the communication was re-published in the epa symposium on waterborne transmission of giardiasis in 1979, and that version included the following quote from the director of the oregon state board of health, suggesting that diarrhea from giardia was still being attributed to other causes by health authorities in 1954: while an unidentified virus seems the most likely etiologic agent, the unusual prevalence of giardia lamblia cysts in stools of patients seems worthy of record. — by oregon state board of health commenting on 1954-55 outbreak of giardiasis, as quoted in veazie, 1979. helicobacter pylori (1892-1982) infection with the bacteria helicobacter pylori is the cause of most stomach ulcers. the discovery is generally credited to australian gastroenterologists dr. barry marshall and dr. j robin warren, who published their findings in 1983. the pair received the nobel prize in 2005 for their work. before this, nobody really knew what caused stomach ulcers, though a popular belief was that the "stress" played a role. some researchers suggested that ulcers were a psychosomatic illness. in h pylori pioneers, dr. marshall noted that other physicians had produced evidence of h. pylori infection as early as 1892. marshall writes that earlier reports were disregarded because they conflicted with existing belief. the first description of h. pylori came in 1892 from giulio bizzozero, who identified acid-tolerant bacteria living in a dog's stomach. later, a theory would be developed that no bacteria could live in the stomach. although the theory has no scientific basis, it would become a stumbling block for scientists, discouraging them for searching for infective causes of stomach ulcers. in 1940, two physicians, dr. a. stone freeberg and dr. louis e. barron published a paper describing a spiral bacteria found in about half of their gastroenterology patients who had stomach ulcers. dr. john lykoudis, a greek physician, was one of the first physicians to treat stomach ulcers as an infectious disease. between 1960 and 1970, he treated over 10,000 ulcer patients in athens with antibiotics. lykoudis tried to publish a paper on his findings, but they conflicted with traditional theory, and his work was never published. lykoudis' experience was followed in 1975 by a further publication in gut magazine that included spiral bacteria living on the borders of duodonal ulcers. the medical significance of steer's findings was disregarded, but he “continued to publish papers on h. pylori, mostly as a hobby." h. pylori can infect the stomach of some people without causing stomach ulcers. in investigating asymptomatic carriers of h. pylori, researchers identified a genetic trait called interleuik-1 beta-31 which causes increased production of stomach acid, resulting in ulcers if patients become infected with h. pylori. patients without the trait do not develop stomach ulcers in response to h. pylori infection, but instead have increased risk from stomach cancer if they become infected. investigation into other gastrointestinal infections has also shown that the symptoms are the result of interaction between the infection and specific genetic mutations in the host.