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October 7, 1997

Volume 44, Number 7

A Nobel Prize for Alumnus Stanley Prusiner


The history of Penn winners of the Nobel Prize in Medicine starts with Dr. Gerald Edelman (M '54), who shared the prize in 1972 for his work on the chemical structure of antibodies. Next came the 1976 Prize to Dr. Baruch Blumberg (who was on the SAS faculty in anthropology at the time) for his discovery of the antigen involved in Hepatitis B. In 1985 the dual alumnus Dr. Michael Brown (C '62, M '66) shared the Prize for his work in cholesterol and metabolic diseases. That same year, a group of medical faculty including Dr. Patrick Storey shared in the Peace Prize. In Dr. Edelman's year the 1972 Chemistry Prize was also shared by another alumnus whose work contributed to medicine-particularly blood diseases- Dr. Christian Anfinsen, who had taken his master's degree here.

This year's winner of the Nobel Prize in Medicine is Dr. Stanley B. Prusiner (right), a Penn alumnus who was "all by himself against the world" for many years in his pursuit of the prion, a new class of pathogen that is now accepted as the infectious agent in "mad cow disease" and in human neurodegenerative diseases such as Creutzfeldt-Jakob disease.

"Overcoming Skepticism," details the long trail that Dr. Prusiner followed before the scientific community accepted his proofs and began to honor his work. PennMed was among the first to do so, presenting him with the Distinguished Alumnus Award in 1991; he also won a Potamkin Prize from the American Academy of Neurology that year for his work on Alzheimer's disease.

Four others followed in 1992-the NIH's Christopher Columbus Quincentennial Discovery Award, Metropolitan Life Foundation Award, Pittsburgh's Dickson Prize and the Charles A. Dana Award.

He was also elected that year to the National Academy of Sciences. The following year he won the NAS's Richard Lounsbery Prize, and the Fairdner Foundation Award for Oustanding Achievement in Medicanl Science-widely considered to be a predictor of the Nobel. As still others followed in the U.S. (the Bristol-Myers Squibb Award and the Albert Lasker Award in 1994) and abroad (Germany's Paul Ehrlich Prize in 1995; the Israeli-based Wolf Prize and Japan's Keio International Award in 1996), excitement mounted. The clear signal, according to Dr. Britton Chance, the Eldridge Reeves Johnson Professor Emeritus, was his election last year to the Royal Society of London.

The million-dollar Nobel Prize for Dr. Prusiner was announced by the Nobel Committee of Sweden's Karolinska Institute early Monday, setting off a celebration at UC San Francisco-where Dr. Prusiner is professor of neurologyand biochemistry and biophysics-and a chain of congratulations at Penn where he took his B.A. cum laude from the College in 1964, and his M.D. in 1968.

That he is one of the few "solo" winners in medicine in recent decades came as no surprise to his colleagues and mentors at Penn.

As Dr. Britton Chance put it, "Stan is one of the most meritorius of winners, because he had to work against so much doubt and adversity. Nobody believed in the existence of prions for many years, but with his dogged persistence and wonderful integrity he went on until he unlocked the cause of mad cow disease and the rest of the prion diseases." Stanley Prusiner was a member of Dr. Chance's lab at the Johnson Foundation as a medical student-and Stanley Prusiner did not forget: In 1991, when he received the Distinguished Alumnus Award, he told Penn Medicine that "Britton Chance gave me an extraordinary oppportunity to pursue an interest in adipose tissue during four years as a medical student. And I keep wondering today whether, if someone came to me with such a crazy idea, I would let them pursue it in my laboratories." The remark was taken by the magazine as tongue-in-cheek, "because, in fact, he is known for recruiting junior investigators and stimulating them as they start scientific careers."

His faculty advisor at the Foundation and in his pre-med years was Dr. Helen C. Davies, who has since followed the long and meticulous research effort that eventually proved the existence of an infectious agent that does not have RNA or DNA. Another who has taken an intense interest is Dr. Neal Nathanson, who is spending his sabbatical in Dr. Prusiner's lab now. As recently as the August 1997 edition of Nature Medicine, Dr. Nathanson took issue with a book which, he felt, "neither adequately covered or acknowledged" the background of discovery that led to breakthroughs in the prion diseases.

Dr. Prusiner has spent his entire postgraduate career with UC San Francisco, taking his internship there in 1968-69 and his residency in neurology in 1972-74. He joined the UC SF faculty as assistant professor of neurology in residence in 1974. Variously serving in the departments of biochemistry and biophysics and in neurology, he was promoted to associate professor in 1980 to full professor in 1984.

Overcoming Skepticism

Prusiner was cited [for the Lasker Award] for identifying a new class of pathogens, which he named prions. He has reported that these infectious agents are implicated in diseases marked by slow onset with progressive deterioration of the brain and nervous system, including scrapie, a disease affecting sheep; as well as Gerstmann-Strussler-Scheinker disease (GSS), Creutzfeldt-Jakob disease, and kuru in humans.

Prusiner defined the prion in a 1982 paper, "Novel proteinaceous infections particles cause scrapie" (Science, 216:136-44), which has been cited in more than 425 subsequent studies. This work was greeted by skepticism in certain scientific circles. The pathogen, he maintained, was composed only of protein; he did not find DNA or RNA in the prion, contradicting the general belief that all living organisms contain genes.

Further fueling doubts among some of Prusiner's colleagues was his assertion that prion diseases can be inherited as well as infectious. Moreover, he concluded that the normal prion protein has a different shape from the disease form. This, too, was heretical, because it had long been thought that each protein has only one natural conformation.

According to Gutterman, Prusiner's award also recognizes his "many years of very, very painstaking work [amid] a lot of opposition." In the early 1980s, the researcher and his prion theory were the subject of uncomplimentary articles in the scientific and popular press. His detractors maintained that the agent at work in these diseases was a slow-acting virus. While some investigators continue to look for a virus, the scientific community now generally accepts the idea of prions, which are now studied by many former proponents of alternative hypotheses.

Prusiner "was all by himself against the world to prove the point," comments Pierluigi Gambetti, a professor of pathology at Case Western Reserve University School of Medicine who studies prion diseases. The copious data Prusiner produced ultimately won over the skeptics, says Gambetti, noting that he himself originally "had trouble understanding the mechanism." The "breakthrough" that shifted his perspective, recalls Gambetti, was Prusiner's results with transgenic animals.

"The deeper I got into this, the more controversy there was, the more people got angry, the more I wanted to figure out what this [prion] was," says Prusiner. "I couldn't figure out a better problem to work on."

- From The Scientist, Vol:8, #20, pg.1, October 17, 1994 (Copyright, The Scientist, Inc.), published on the occasion of Dr. Prusiner's winning the Albert and Mary Lasker Award