Prion | Research & Encyclopedia Articles

Prion

Scrapie is a disease that attacks the brains of sheep, producing strange behaviors such as the animal's compulsion to scrape off its wool, which gives the disease its name. Scrapie has been known to scientists for more than 250 years, although virtually nothing about its nature or transmission was discovered until very recently. In 1986, a scrapie-like disorder was first noted in a herd of cows in Kent, England. Within five years, the disease had spread to cows throughout the country. Cows inflicted with the disease became very sensitive to sound and touch, walked unsteadily, and trembled and twitched. Scientists were able to determine that scrapie--one in a family of diseases termed spongiform encephalopathies--had been transmitted from sheep to cows. Studies of brains from infected animals showed some common features, especially the presence of rod-shaped particles that clumped together to form larger arrays.

What was the infectious agent in this disease? One possible answer had been suggested in late 1981 by neurologist Stanley Prusiner of the University of California at San Francisco. Prusiner had found that the scrapie agent was a very small particle, not much larger than a nucleic acid molecule. This finding suggested the existence of a virus, a simple pathogen consisting of DNA or RNA encased in a protein coat. However, none of the enzymes that normally disable nucleic acids had any effect on the scrapie agent, while those enzymes that degrade protein did have an effect. Eventually, Prusiner concluded that he was dealing with an entirely new type of infectious particle, a protein with the ability to cause a contagious disease. He called this particle a prion, for "infectious protein."

Prusiner's hypothesis seemed unlikely to his colleagues at first. There was no precedent for the existence of an infectious agent that lacked a mechanism for its own replication (a nucleic acid). Prusiner found one possible answer to that objection in 1988, when he conducted a study of patients afflicted with Gerstmann-Strässler-Scheinker syndrome, a rare spongiform encephalopathy that affects humans. He found in their brain tissue a gene that codes for the production of an abnormal protein similar to the scrapie-like prion. Perhaps, he hypothesized, the defective gene was responsible for the manufacture of the disease-causing protein.

The validity of the prion hypothesis is still being tested and debated, particularly the question of whether or not the abnormal protein is infectious. However, more and more scientists have begun to accept that hypothesis. Today, the prion has been implicated in a half-dozen diseases: scrapie, transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, kuru, Creutzfeldt-Jakob disease, and Gerstmann-Strässler-Scheinker syndrome. All of these diseases develop very slowly, over a period of many months or years. This pattern originally led scientists to suspect that the disease-causing agent was a slow-acting virus. The last three of the prion diseases listed above affect humans, although all are rare.

Kuru was once common among the Fore tribe in New Guinea. The disease was apparently transmitted through the ritual eating of the brain of dead relatives. The discovery of the mechanism by which kuru is transmitted was made by D. Carleton Gajdusek, who earned a share of the 1976 Nobel Prize for physiology or medicine for his work. Some scientists suspect that the prion may also be implicated in Alzheimer's disease and Parkinson's disease.

In the mid-1990s, a new variant of Creutzfeldt-Jakob disease attracted worldwide attention. From 1995 through 1997, this new form of the disease killed at least 19 people in Britain, all relatively young. What sets this type of Creutzfeldt-Jakob disease apart from the older form is that it is thought to be transmissible. Many scientists believe that its victims contracted the disease by eating beef from cows infected with bovine spongiform encephalopathy (BSE), or mad cow disease. In 1985, the first signs of a BSE epidemic began showing up in British cows that had eaten feed containing offals from scrapie-infected sheep. Due to the long incubation period of BSE, the epidemic didn't peak until 1992, and by 1997, about 37,000 animals a year were still being affected.

Although much more research on prions remains to be done, Prusiner saw his work receive the ultimate stamp of scientific approval in 1997, when he was awarded the Nobel Prize in physiology or medicine "for his discovery of prions--a new biological principle of infection." Prusiner, born on May 28, 1942, received his M.D. degree from the University of Pennsylvania in 1968. In that same year, he began an internship at the University of California at San Francisco, where he has spent the bulk of his career.