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|- |(unranked)||Mammalian prion
|- |(unranked)||Kuru prion Kuru (also known as laughing sickness due to the outbursts of laughter that mark its second phase) was first noted in New Guinea in the early 1900s. By the 1950s, anthropologists and Australian government officials reported that kuru ("trembling" in the language of the Fore) was rampant among the South Fore , a single census division of approximately 8,000 individuals within the Okapa subdistrict. This particular group partook in ritual acts of mortuary cannibalism, which behaviour was later determined to be responsible for the epidemic transmission of the disease.
Kuru is now known to be a prion disease, one of several known transmissible spongiform encephalopathies. Understanding the structure and replication of the prion is crucial to interpreting the dynamics of kuru and the several other prion diseases which exist today.
Knowledge of the dynamics of the disease has continued to grow, even though the disease all but disappeared with the termination of cannibalism in New Guinea. The onset of kuru led to a five-decade study of an unfamiliar disease. This particular disease serves as an example of the procedures scientists undergo in order to understand and appreciate all of the aspects of a disease and how potential therapies and solutions can be found.
Kuru among the South Fore
Upon the death of an individual, the maternal kin were responsible for the dismemberment of the corpse. The women would remove the arms and feet, strip the limbs of muscle, remove the brains and cut open the chest in order to remove internal organs. Shirley Lindenbaum , one of the early kuru researchers, states that kuru victims were highly regarded as sources of food, because the layer of fat on victims who died quickly resembled pork. Women also were known to feed morsels such as human brains and various parts of organs to their children and the elderly (Lindenbaum, 1979). It is currently believed that kuru was transmitted among the South Fore through participation in such cannibalism, although opportunistic infection through wounds when removing infectious tissue from the corpse can be assumed to be another cause, as not all cases can be explained by ingestion of infectious tissue.
The kuru epidemic reached its height in the 1960s. Between 1957 and 1968, over 1,100 of the South Fore died from kuru. The vast majority of victims among the South Fore were women. In fact, eight times more women than men contracted the disease. It later affected small children and the elderly at a high rate as well.
Lindenbaum and Vincent Zigas worked among the South Fore in New Guinea trying to identify and catalog the symptoms and possible behavior causing the disease. Daniel Carleton Gajdusek also traveled there in 1957, to study disease patterns in primitive and isolated populations (Gajdusek, 1996). Lindenbaum, Zigas, and Gajdusek were all crucial to explaining the specifics of kuru to the rest of the world.
Symptoms of kuru
In Daniel Gajdusek's studies of kuru, he found the condition of kuru victims to be an upsetting sight. "To see them, however, regularly progress to neurological degeneration in three to six months (usually three) and to death is another matter and cannot be shrugged off." (Gajdusek, 1996:10) Gajdusek reported three main stages in the progression of symptoms:
- The ambulant stage, with unsteadiness of stance, gait, voice, hands, and eyes; deterioration of speech; tremor; shivering; uncoordination in lower extremities that moves slowly upward; and dysarthria (slurring of speech).
- The sedentary stage: patient can no longer walk without support, more severe tremors and ataxia (loss of coordination of the muscles), shock-like muscle jerks, emotional lability , outbursts of laughter, depression, and mental slowing. It is important to note that muscle degeneration has not occurred in this stage, and tendon reflexes are usually still normal.
- The terminal stage, which is marked by inability to sit up without support; more severe ataxia, tremor and dysarthria (slurring of speech); urinary and fæcal incontinence; difficulty swallowing (dysphagia); and deep ulcerations appear. Cerebellar dysfunction is the cause of these conditions.
These symptoms are common among prion diseases, such as Creutzfeldt-Jakob disease (CJD).
Misinterpretations of kuru
Scholars who first studied the disease had two major misconceptions concerning its nature. They first incorrectly postulated that it was a genetic disorder, as it had a tendency to occur among family members. This possibility was eventually ruled out because kuru was too common and too fatal (Lindenbaum, 1979) — such a lethal genetic disorder would drastically reduce the fitness of a population and soon die out of the gene pool.
Gajdusek conducted studies on chimpanzees injected with brain material from a victim. These studies led scientists to hypothesise that the agent was a slow virus, because the chimps developed a very similar condition after a long incubation period. Gadjusek defined a slow virus as a viral disease with an abnormally long incubation period. In humans, kuru had an incubation period with a minimum of two years and maximum of twenty-three (Gajdusek et al., 1966). Later studies showed the slow virus hypothesis to be a misinterpretation as well. Gajdusek’s results however confirmed the infectious, transmissible nature of the prion.
The prion protein
All known prion diseases are fatal. Such diseases are often called spongiform encephalopathies, because they frequently cause the brain to become spongy, that is, riddled with holes (Prusiner, 1995). Well known prion diseases include scrapie, bovine spongiform encephalopathy (BSE or mad cow disease) and Creutzfeldt-Jakob disease (CJD). Less well-known prion diseases include the transmissible mink encephalopathy , chronic wasting disease, feline spongiform encephalopathy , exotic ungulate encephalopathy , Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (Krakauer et al., 1997). Four of these affect humans: Creutzfeldt-Jakob disease, Gerstmann-Strässler-Scheinker syndrome, fatal familial insomnia and kuru. The most common form of prion disease is scrapie, expressed in sheep and goats (Prusiner, 1995). According to Cohen et al. (1994), prions cause a variety of degenerative neurologic diseases that can be infectious, inherited or sporadic in origin. The cause of the sporadic forms is unknown; inherited forms are caused by up to twenty different mutations of the human PrP gene ; and the infectious forms are transmitted through contact with or consumption of previously infected tissues (Prusiner, 1997).
The exact nature of kuru perplexed scholars for decades after the discovery of the ailment, until Stanley B. Prusiner identified and defined prion diseases in 1982 (Prusiner, 1995). Prusiner (1991) classified a prion as an infectious particle composed of a protein that causes neurodegenerative disorders. According to Cashman (1997), prions are infectious agents by biological and medical criteria. However, they are also fairly unique, and properties of prions differ from those of conventional microbes.
Scientists have worked on the prion puzzle since the 1950s, with microbiologists and epidemiologists having been confused by them. Advancements have been made, particularly in the 1990s, as evidenced by Prusiner receiving the Nobel Prize for Physiology or Medicine in 1997. However, it is still difficult to detect prion infection, track its transmission and type the different strains (Cashman, 1997). The Fore's long struggle with kuru serves as a poignant example.
- NR Cashman (1997), "A prion primer". Canadian Medical Journal Association, 157(10):1381–1386.
- FE Cohen, K Pan, Z Huang, M Baldwin, RJ Fletterick and SB Prusiner (1994), "Structural clues to prion replication". Science, 264:530–531.
- DC Gajdusek (1996), "Kuru: From the New Guinea field journals 1957–1962". Grand Street, 15:6–33.
- DC Gajdusek (1973), "Kuru in the New Guinea Highlands". In Spillane JD (ed): Tropical Neurology. New York, Oxford University Press.
- DC Gajdusek, CJ Gibbs and M Alpers (1966), "Experimental transmission of a kuru-like syndrome to chimpanzees". Nature, 209:794.
- DC Gajdusek, PM de Zanotto and M Pagel (1998), "Prion's progress: Patterns and rates of molecular evolution in relation to spongiform disease". Journal of Molecular Evolution, 47:133–145.
- S Lindenbaum (1979), Kuru Sorcery. Mountain View, Ca, Mayfield Publishing Company.
- SB Prusiner (1991), "Molecular biology of prion diseases". Science, 252:1515–1521.
- SB Prusiner (1995), "Prion diseases". Scientific American, 272(1):48–56.
- SB Prusiner (1997), "Prion diseases and the BSE crisis". Science, 278:245–251.
- Stacy McGrath, Kuru: The dynamics of a prion disease.
- This article was adapted with permission from a report "Kuru: The dynamics of a prion disease", authored by Stacy McGrath.
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