Kuru

Kuru, a disease once endemic to Papua New Guinea and now virtually extinct, is one of several types of diseases called spongiform encephalopathies, all thought to be caused by abnormal proteins called prions, which riddle the brain with holes. According to proponents of the prion hypothesis, these diseases can arise by direct infection with prions, by inheriting genes that produce faulty proteins, or by accidental genetic mutation. While prion diseases are more frequently seen in animals in the form of scrapie (sheep and goats), transmissible mink encephalopathy, and bovine spongiform encephalitis ("mad cow disease"), human prion diseases are relatively rare.

Kuru occurred among the Fore highlanders of Papua New Guinea, who called it the "laughing death". It was first noted by Vincent Zigas of the Australian Public Health Service and D. Carleton Gajdusek of the U.S. National Institute of Health in 1957. The disease caused its victims to lose coordination and often to develop dementia. This disease affects the brain, and it was probably spread by the Fore practice of honoring the dead by eating their brains. When the Fore highlanders were persuaded to cease consuming human brains, kuru disappeared from Papua New Guinea. About 2,600 cases were identified before the Fore highlanders ended this custom.

The course of the illness runs from three months to one year. Among the major signs of kuru are cerebellar abnormalities such as rigidity of the limbs and clonus (rapid contractions and relaxations of muscles). Often, the victim bursts out in wild laughter for no obvious reason. Toward the end of the disease, the person with kuru is very calm and quiet and unresponsive to stimulation. Finally, the victim succumbs to severe skin ulcers caused by lying in one position for extended periods of time; or to pneumonia caused by stagnation of the blood in the lungs.

Among the other human spongiform encephalopathies caused by prions are Creutzfeldt-Jakob disease (millions of cases worldwide characterized by dementia and loss of coordination); Gerstmann-Straussler-Scheinker disease (found in 50 extended families by 1995); and fatal familial insomnia (trouble sleeping, followed by dementia; found in nine extended families by 1995).

The concept of prions, a term coined by Stanley B. Prusiner as an acronym for "proteinaceous infectious particles," was originally met with great skepticism by most scientists when Prusiner and his co-workers proposed the existence of these proteins 15 years ago. The controversy continues today, although additional evidence has accumulated to support the hypothesis that spongiform encephalopathies are caused by prions rather than viruses.

According to current theory, prion proteins multiply by inducing benign protein molecules to convert themselves into the dangerous form of the molecule simply by changing their shape. In addition, prions underlie both inherited (i.e., familial forms) and communicable forms of diseases. This dual nature of prions-inducing other proteins to become prions, while also being the basis of inherited disease-is otherwise unknown to medical science. Prions can also cause sporadic (i.e., non-communicable, non-inherited) neurodegenerative diseases.

Creutzfeldt-Jakob disease and kuru had been known for many years to be experimentally caused by injecting extracts of diseased brains into the brains of healthy animals. Although these infections were at first thought to be caused by a slow-acting virus, such an agent was never found. Moreover, ultraviolet and ionizing radiation, which destroys genetic material, did not eliminate the ability of brain extracts to cause disease. Prusiner's group eventually determined that scrapie prions contained a single protein that they called PrP ("prion protein"). Further studies showed that PrP is harmless in its so-called benign state, i.e., when the backbone of the protein is twisted into many helices (spirals). PrP converts into its prion form when the backbone stretches out, flattening the overall shape of the protein.

The prion protein multiplies in the brain by a process Prusiner describes as a "domino effect." In one particularly favored hypothesis of prion propagation, a molecule of PrP contacts a normal PrP molecule and induces it to refold into the abnormal, flattened form. The newly transformed proteins then force other proteins to refold into the abnormal form until the prion protein form accumulates to destructive levels.

The discovery that kuru was caused by consumption of infected brains has serious implications in developed countries. For example, cats in England have been infected by eating pet food made from contaminated beef. This has prompted concern that humans might get a prion disease by eating meat from infected cows.