n e w s of t h e w e e k
NOBEL PRIZE FOR PRIONS Prusiner wins medicine award for infectious protein concept
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he 1997 Nobel Prize in Physiology or Medicine, including a cash award of about $1 million, was bestowed last week on Stanley B. Prusiner, professor of neurology and biochemistry at the University of California, San Francisco (UCSF). The award honors Prusiner's 1982 proposal that infectious proteins called "prions" cause fatal nervous system disorders and his subsequent research to confirm the proposal. The prion disorders, called transmissible spongiform encephalopathies (TSEs), include scrapie and mad cow disease in animals and Creutzfeldt-Jakob disease in people. These neurodegenerative disorders impair mental ability and muscle control and are ultimately fatal. According to the Nobel Foundation, Stockholm, Prusiner's "discovery provides important insights that may furnish the basis to understand the biological mechanisms" of such dementia-related diseases "and establishes a foundation for drug development and new types of medical treatment strategies." Initially, Prusiner's prion hypothesis was roundly rejected by many researchers because prions lack DNA and RNA, which are present in all other known infectious agents. The prion hypothesis still has its detractors, who believe a hard-to-detect virus may be the cause of TSEs, and Prusiner and others have never been able to completely eliminate this possibility. But the prion concept has gradually gained credibility over the years as evidence for it has accumulated. The infectious agent in TSEs is believed to be a conformational variant of normal prion protein. The variant appears to infect cells by acting as a template for refolding of normal prion protein into the disease-causing form. The precise molecular mechanism of this process is not yet known, but the proposal accounts for the seeming ability of prions to "replicate" in the absence of DNA or RNA. Biochemist Peter T. Lansbury Jr. of Harvard Medical School, whose research focuses on the molecular mechanisms of neurodegenerative diseases, says, "Stan 4 OCTOBER 13, 1997 C&EN
Prusiner: made conceptual leap
Prusiner took an incredible mystery, identified the protein associated with it, and built up a huge case that the protein plays a central role in it. He also lowered the barrier for chemists to enter the field— which is quite an accomplishment in itself. This is essentially a chemical problem, and a lot of structural biologists and biophysical chemists are now working in this area, whereas four or five years ago virtually none were doing so." Professor of medicine and pharmacology Fred E. Cohen of UCSF, one of Prusiner's colleagues, says, "The prize is very exciting, and it's richly deserved. It's certainly enjoyable to watch someone who has spent 20 years working hard on a problem, and who has really defined a whole new area of pathogenesis, be rewarded for that effort. For those of us who come more from the chemistry side, it's also nice to see the conformation of macromolecules looming large in the way people think about major problems in biology." Andrew A. Monjan, chief of the Neurobiology of Aging branch of the National Institute on Aging, Bethesda, Md., an agency that has supported Prusiner's research since 1981, says he had been ex-
pecting Prusiner to win the Nobel Prize. "He's provided a conceptual leap with the prion hypothesis," says Monjan. "Prusiner's body of work has produced new insights into the biology of neurodegenerative disease and new concepts in infection and in how proteins can be altered." Asked if the prion concept is still controversial today, Monjan says no. "There may be some people who are still looking for a hidden virus, but the hypothesis has become mainstream." Charles Weissmann, director of the Institute of Molecular Biology at the University of Zurich, who specializes in prion research, says, "Stan Prusiner has waged a scientific battle for over two decades to convince his colleagues and the world that... an abnormal form of a protein occurring in the brain of all vertebrates" is responsible for TSEs. "He has explored many scientific avenues, including biochemical, genetic, and biophysical approaches, and has accumulated the evidence that has convinced the vast majority of scientists of the correctness of his view. Prusiner is a true pioneer and iconoclast and fully deserves the Nobel Prize he has been awarded," Weissmann concludes. Prusiner, born in 1942 in Des Moines, received an A.B. degree in 1964 from the University of Pennsylvania and an M.D. degree from Perm in 1968. After completing an internship and residency at UCSF, he joined the faculty there in 1974. Stu Borman
Real-world C-H bond activation Details of a mechanism for activating the normally inert carbon-hydrogen bond in room-temperature alkane solution have emerged from experiments using ultrafast infrared spectroscopic techniques. C-H bond activation is potentially useful for converting alkanes into functionalized organic molecules. Thefindingsare the result of a collaborative effort between the research groups of chemistry professors Robert G. Bergman and Charles B. Harris at the University of California, Berkeley, and Lawrence Berkeley National Laboratory in conjunction with senior scientist Heinz Frei at LBNL. Using IR spectroscopic techniques that probed initial events in the femtosecond time scale and subsequent events in the pico- and nanosecond time scales, they determined intermediates and energy
