In the 1920s, a previously unidentified disease appeared among the Fore people of Papua New Guinea. During the 1950’s, anthropologists determined that the disease was prevalent in the South Fore peoples, a subgroup numbering approximately 8,000, living in the Okapa sub-district of the eastern highlands of New Guinea. The disease was named kuru, meaning ‘shaking death’ in the Fore language, because of the symptoms presented by those infected with it.
Kuru belongs to a class of infectious diseases called transmissible spongiform encephalopathies (TSEs), all of which are characterized by progressive neurodegeneration, and all of which are fatal. The literal translation of spongiform encephalopathy is ‘sponge-like brain disease’; the name describes the characteristic pathology in the brains of infected animals. Other TSEs include scrapie in sheep and goat, bovine spongiform encephalopathy (BSE, or ‘Mad Cow Disease’) in cattle and chronic wasting disease in deer and elk; the human TSEs are kuru, Creutzfeldt-Jakob Disease (CJD), fatal familial insomnia (FFI) and Gerstmann-Straussler-Scheinker (GSS) syndrome. FFI and GSS are extremely rare, inherited TSEs.
During the 1950s and 60s there was an epidemic of kuru among the South Fore, which claimed the lives of more than 1,100. It is now known that the Fore practice of ritualistic mortuary cannibalism caused the kuru epidemic. Female relatives of a deceased individual were responsible for dismembering the corpse; the brain, arms and feet were removed, limbs were stripped of muscle and the chest was opened to remove internal organs. Kuru victims were highly regarded as sources of food because they had layers of fat resembling pork. Of the South Fore, it was the women who primarily took part in these cannibalistic rituals; they occasionally fed morsels of brain and other organs to their children and elderly relatives. As a consequence, the vast majority of South Fore infected with kuru were women, children and the elderly.
The first symptoms of kuru are unsteady gait and stance; later symptoms are tremor, slurred speech, loss of coordination, outbursts of laughter and limb rigidity. The final stages of the disease are marked by an inability to stand, sit up, speak or swallow, and death usually occurs within one year of the onset of the first symptoms. The symptoms of all TSEs are remarkably similar, in both animals and humans.
In 1982, Stanley Prusiner identified the prion protein as the infectious agent responsible for transmitting TSEs (which are also now known as prion diseases), and was subsequently awarded the Nobel Prize for his work. Prusiner first thought that the infectious agent must be a virus. However, extracts from scrapie-infected brain tissue remained infectious after exposure to ultraviolet and ionizing radiation, which destroys nucleic acids. Eventually, the prion protein was singled out as the most likely agent, and the ‘prion hypothesis’ is now generally accepted, although some scientists still dispute it.
‘Prion’ is an abbreviation for proteinaceous infectious particle. The prion protein (PrPC) is a normal cellular protein, consisting of 208 amino acid residues, whose role in neurons is still unknown. According to the prion hypothesis, PrPC is converted to PrPSc, an abnormally folded and pathogenic version, by point mutations in the prion coding sequence. PrPSc has a lower proportion of alpha helices and a higher proportion of beta-pleated sheets compared to PrPC. Whereas PrPC is soluble and can be degraded by proteases, PrPSc is insoluble and partially resistant to proteases. When tissue containing PrPSc is ingested, the protein acts as a ‘seed’, causing normal prion molecules to adopt the abnormal configuration, and then precipitating their accumulation into an insoluble deposit which interferes with the cell’s ability to function properly. Prion diseases are unique in that the infectious agent which causes their transmission is a protein and not, like most other infectious diseases, a microbe.
Although the practice of cannibalism was outlawed in the late 1950s by the Australian government, cases of Kuru continued to appear among the Fore. This prompted Professor John Collinge of University College London to travel to New Guinea to investigate. Between 1996 and 2004, Collinge and his colleagues collected information on the life histories of South Fore tribesmen and women. During the 8 years over which the study was carried out, the researchers identified 11 cases of Kuru. Analysis of DNA from 10 of the 11 cases of Kuru identified suggests that individuals who are homozygous for a particular allele of the prion gene may be more susceptible to TSE infection.
Writing in The Lancet, Collinge concludes that “the minimum estimated incubation periods ranged from 34 to 41 years… [but] incubation periods of infection with human prions can exceed 50 years”. The findings have raised fears of an epidemic of variant CJD in the future. To date, 156 people have died from vCJD in the UK as a result of eating beef from BSE-infected cows. According to Collinge, these individuals “could represent a distinct genetic subpopulation with unusually short incubation periods for BSE.”
There is, however, an alternative: It is possible that some still practice the mortuary ritual, or did so after the ban was imposed; although this would explain the cases of kuru identified by Collinge and his team, it does not necessarily preclude Collinge’s conclusion about the long incubation period for TSEs. Only a thorough investigation of how well the ban on cannibalism was enforced can determine whether or not the South Fore actually stopped practising their rituals in the late 1950s, and only time will tell if there will be an epidemic of vCJD.