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Luck, Brilliance, and Persistence

Stanley Prusiner
Credit: David Powers, UCSF

PHILADELPHIA, PENNSYLVANIA—To have a momentous scientific career, Nobel laureate Stanley Prusiner told his college classmates in a 17 May speech at the 50th reunion of the University of Pennsylvania’s undergraduate class of 1964, it’s “better to be lucky than brilliant.” In the early 1960s, when the man who would become the sole winner of the 1997 Nobel Prize in physiology or medicine was active in the Alpha Epsilon Pi fraternity, the fraternity had a number of diligent students, said Prusiner’s fraternity brother Robert Gardner in introducing Prusiner’s speech. Prusiner was “one of the pack.”

It must have been a pretty fast pack. Prusiner went on to attend medical school at Penn, then intern at the University of California, San Francisco (UCSF), and conduct research at the National Institutes of Health. He did a residency in neurology at UCSF and then, in 1974, joined the UCSF faculty, where he has remained and now directs the Institute for Neurodegenerative Diseases. His Nobel prize recognizes “his discovery of Prions—a new biological principle of infection,” the prize citation says.

In his speech, Prusiner shared with his classmates three elements of luck that contributed to his success. First, he said, “prions could have turned out to be viruses.” Instead, prions (short for proteinaceous infectious particles), which Prusiner was first to identify as the single cause of the cluster of fatal degenerative brain diseases known as transmissible spongiform encephalopathies (TSEs), turned out to be something that until then was completely unknown—indeed, undreamed of—in biology. Prions are abnormally folded proteins that, though devoid of DNA, are nonetheless susceptible to replication and transmission in mammals, including humans.

TSEs caused by this extraordinary class of pathogens include mad cow disease, also known as bovine spongiform encephalopathy, which affects cattle; scrapie, which affects sheep; and multiple versions of Creutzfeldt-Jakob disease, which affect humans. Prions also appear to be implicated in other progressive neurodegenerative human disorders, including Parkinson’s disease, Lewy Body dementia , and multiple system atrophy, Prusiner said.

The second element of luck that Prusiner identified is that “another scientist could have discovered” the existence of prions, but no one else did. Like many researchers, he could have suffered from what he called the “Obama effect”—when an unknown competitor unexpectedly comes out of nowhere and captures the prize, as Barack Obama did to Hillary Clinton in the run-up to the 2008 presidential election.

Finally, the epidemic of mad cow disease in United Kingdom the 1980s and the fact that the disease could spread to humans attracted worldwide notice, which made Prusiner’s discovery of prions important news. Without this attention, he said, the Nobel prize might have come “20 years later” or not at all.

Luck can indeed play major roles in important scientific careers. Some years ago, we recounted a striking counter-example in the person of Douglas Prasher. Three other men received the 2008 Nobel Prize in chemistry, for research on green fluorescent protein that Prasher had helped originate. Because of a series of misfortunes, when the award was announced, Prasher was working not as a scientist but as a courtesy van driver.

Prusiner’s comments, however, downplayed some other important elements in his success. First, he had the insight to identify and the luxury of spending years working on a single, significant scientific question: the cause of a class of diseases that had stubbornly defied explanation. Even more important than these factors was his dogged determination in the face of withering opposition. Many scientists were “very unhappy” when he published conclusions that violated accepted dogma, Prusiner said. For years he felt “the long arm of the scientific community pressing down on me.” Gardner described those years more plainly: His friend had been “attacked viciously … ridiculed, vilified, denounced,” he said.

So, though necessary, luck was hardly sufficient. For those who want the full story of prions, Prusiner also recounts it—both the complex science and the punishing scientific politics—in a new book, Madness and Memory: The Discovery of Prions—A New Biological Principle of Disease.