In the 1950s and ’60s, several villages in the Oceanic country of Papua New Guinea began to see an odd disease. Villagers of the Fore people in the Eastern Highlands – predominantly women and children – would show an array of frightening symptoms that rapidly worsened over about six months: muscle tremors, uncontrollable laughter, slurring of speech and finally an inability to move and swallow. In the 1960’s, European scientists began to study people with the disease, called kuru for the Fore word for “shiver,” and made two astonishing discoveries. First, that kuru represented a new kind of infectious disease that caused the brain and nervous system to degenerate. Second, that kuru probably resulted from people eating their dead relatives.
Yeah, that’s not a typo. Before the Fore people of Papua New Guinea were known for kuru, they were known for “mortuary feasts,” where villagers would mark the death of a family member by consuming him or her. And not just a nibble here or there – according to a 1979 book by anthropologist Shirley Lindenbaum, “meat, viscera, and brain were all eaten.” That’s a good way to spread a disease caused by prions – the mechanism for kuru eventually discovered by Daniel Carleton Gajdusek in research that won him the 1976 Nobel Prize in Physiology or Medicine. Now, kuru continues to fascinate the scientific community, as a new medical paper presents how the savage disease caused rapid natural selection in Papua New Guinea, selecting for a gene variant that may offer clues to how to treat prion diseases with no known cure.
Prions are also the culprit behind bovine spongiform encephalopathy, better known as Mad Cow Disease, which is thought to have broken out in Britain due to cannibalistic feeding practices in cattle. In short, prion diseases are caused by misshaped proteins that are a bad influence on native prion proteins present in all species, causing them to change shape, clump together, and eventually kill the cell. So when a prion disease enters a person’s nervous system – by, say, eating a person with a prion disease – it tends to wreak havoc in the brain, producing the odd symptoms of kuru or BSE.
At the height of kuru, 1 out of 50 people in some Fore villages succumbed to the untreatable, fatal disease. Women and children tended to die more often from kuru, likely because they usually were given the brains to eat while the men got the good, meaty parts. But what about those who participated in the mortuary feasts, but never contracted the disease? Was there something genetically different about them that made them resistant? Sounds like a case for…evolution!
In a paper published today in the New England Journal of Medicine (presumably the only article in the issue where “cannibalistic mortuary feasts” appears in the abstract) , a group of scientists from London, Papua New Guinea and Australia announce a newly-discovered gene variant that appears to have protected certain people from the ravages of kuru. Most excitingly, that variant shows up at an unusually high rate in the villages were kuru once ran rampant – an fascinating, if tragic, case of natural selection in action.
Researchers sequenced the DNA of more than 2500 people from areas hit hard by kuru and nearby areas that were unaffected, and compared their genes for the native prion protein. Sure enough, one population of older women that survived the kuru outbreak and young people of their families possess a polymorphism that reflects two small changes in their native prion protein gene. These subjects are heterozygous – meaning they have two different copies of the gene – while homozygous subjects with two identical genes for the native prion protein were sensitive to kuru. The most striking statistic is that 75% of young people who came down with kuru were homozygotes, while only about 20-25% of heterozygous older women (who lived during the outbreak) were afflicted with the disease – and even then, it started much later in life.
Those statistics reflect natural selection in action: people resistant to kuru (heterozygotes) stayed alive and reproduced, spreading their variant of the gene to the next generation, while those sensitive to kuru (homozygotes), well, died. Eventually, the heterozygous population wins out – the high number of heterozygotes in this region of Papua New Guinea violates the Hardy-Weinberg equilibrium, which states that gene frequencies should remain constant in a population unless some external force is disrupting the balance.
Furthermore, the identification of a genetic change that makes native prion proteins resistant to the bad influence of prion diseases could help develop treatment for what are currently untreatable diseases. But much more research must be done to figure out how it’s so effective – and why it became such an advantageous target for rapid selection. Raymond Roos, a neurologist at the University of Chicago who studies misfolded proteins and prion disease (and who worked in the past with Gajdusek), said via e-mail that looking at how the kuru-resistant polymorphism changes the shape of the native prion protein – and how it subsequently interacts with “invading” prions – could explain why it is protective. An antibody to that part of the protein that is different in kuru-resistant people could prevent prions from clumping together, creating a new treatment for kuru, BSE, and other prion diseases, Roos speculated.
“Even when diseases are essentially eliminated, they offer lessons,” Roos commented.