Stanley B. Prusiner, a maverick American scientist who endured derision from his peers for two decades as he tried to prove that bizarre infectious proteins could cause brain diseases like “mad cow disease” in people and animals, has been awarded the ultimate in scientific vindication: the Nobel Prize in medicine or physiology.
Prusiner, a 55-year-old neurologist at the University of California at San Francisco, was cited Monday by the Swedish Nobel committee “for his pioneering discovery of an entirely new genre of disease-causing agents and the elucidation of the underlying principles of their mode of action.”
The infectious particles that Prusiner discovered, which he named prions (PREE-ons), are made of protein and do not contain any genes or genetic material - a detail that distinguishes them from all other kinds of infectious agents such as viruses, bacteria, fungi and parasites.
Until Prusiner came along, no one knew that simple proteins could reproduce themselves as though they were alive. Indeed, the concept was so revolutionary that he was shunned for years as a man who had overreached the limits of scientific sensibility. Many researchers presumed that the diseases Prusiner attributed to prions - including the sheep illness called scrapie and human ailments such as Creutzfeldt-Jakob and kuru - were actually caused by tiny, slow-growing, undiscovered viruses.
Although some scientists still question the prion hypothesis, a growing body of work from research laboratories around the world has led to a near-consensus that the feisty Prusiner has been correct all along.
“It’s a very, very well-deserved prize,” said Zach Hall, director of the National Institute of Neurological Disorders and Stroke, which funded much of Prusiner’s work during the past 22 years.
“It’s terrific,” said David Baltimore, the Massachusetts Institute of Technology immunologist and 1975 Nobel laureate, who for years counted himself among Prusiner’s doubters. “These are the mythological stories of science - people who have really kept their own faith for so many years and lived through a period of opprobrium and finally are discovered to be right,” Baltimore said. “Stories like these are not that common, but they provide an important lesson for young people in science: They say, “Be true to yourself.’ “
In awarding Prusiner the $1 million prize, the Nobel committee of Sweden’s Karolinska Institute suggested that Prusiner’s discoveries may lead to a better understanding of Alzheimer’s disease and other neurodegenerative syndromes. His work already has proved invaluable in the study of mad cow disease - or bovine spongiform encephalopathy - and the human brain disease called “new variant” Creutzfeldt-Jakob disease, now believed to be caused by eating beef from affected cattle.
In an interview Monday afternoon, Prusiner said that scientists were right to doubt him at the beginning. “I think that science should be very reticent to accept new ideas,” he said. “Ninety-nine percent of new ideas are wrong. We have to be very tough on our colleagues.”
Prusiner learned of the award early Monday morning in Bethesda, Md., where he is serving on an expert committee that is advising the Food and Drug Administration about ways to reduce the spread of prion diseases.
Prions reside naturally in the brain cells of people and animals, and in their normal form they do no harm (though what exactly they do remains unclear). Occasionally, however, a prion mutates into an abnormal shape. In a peculiar process that Prusiner painstakingly documented over many years, these abnormal prions seem to manhandle surrounding normal prions into similarly defective three-dimensional forms.
As newly configured prions convert their neighbors, they multiply throughout the brain like a spreading infection. Entire pockets of brain tissue gradually die from the accumulation of abnormal proteins, leading to a “spongy” appearance characteristic of the prion brain diseases.
Prusiner also showed that prion diseases can sometimes be passed from one species to another. Scientists now have strong evidence, for example, that the 21 recently discovered cases of new variant Creutzfeldt-Jakob disease in Europe (which affects younger people than does standard CJD) were caused by the consumption of beef from cattle with mad cow disease.
Human spongiform brain diseases, which are characterized by poor muscle coordination and memory loss, include Creutzfeldt-Jakob disease, Gertsmann-Straussler-Scheinker disease, fatal familial insomnia, and kuru - an especially fast-killing syndrome spread by ritualistic cannibalism among tribal New Guineans.
Much remains to be learned about why prions occasionally mutate and how those mutant prions cause disease. There is no effective treatment for prion diseases, but Prusiner’s work could help change that someday.
“The discovery of prions gives us a base for finding medicines that will stop the transformation of a normal prion to a pathological prion,” Ralf Petersson, a molecular biology professor at the Karolinska, told the Associated Press.
Prusiner said the only time he was hurt by the decades of skepticism “was when it became personal.” After publication of an especially ridiculing article in Discover magazine 10 years ago, for example - which Prusiner Monday called the “crown jewel” of all the derogatory articles ever written about him - he stopped talking to the press. The self-imposed media exile became increasingly frustrating to science journalists over the past decade as his theories gained scientific credibility.
Asked whether he was willing to clear the slate and reopen channels with reporters now, he replied half-jokingly that it would depend on how the news reports read today.