THOMAS BROENING FOR TIME Stanley Prusiner, M.D.: A neurobiologist awarded the 1997 Nobel Prize in Medicine for his discovery of a new class of disease-causing agents called prions

The Pioneers of Molecular Biology: Stanley Prusiner
	In his search for the cause of brain-wasting diseases, he discovered a deadly new type of protein
	By Jeffrey Kluger

Posted Sunday, February 9, 2002; 10:31 a.m. EST
If there's any scientist you'd think would not be interested in DNA, it's Stanley Prusiner, a man who has devoted his life to investigating infectious agents that don't have so much as a scrap of the stuff. But only by going hunting for DNA in the first place could Prusiner have made the scientific discovery he did—one that earned him a Nobel Prize.

A physician who has spent his entire career at the University of California, San Francisco, Prusiner is arguably the world's leading expert on spongiform encephalopathies—brain-wasting illnesses that include mad cow disease, scrapie and their human variant, Creutzfeldt-Jakob disease. Only 11 years old when Watson and Crick made their discovery in 1953, Prusiner doesn't remember the landmark moment. In 1974, however, when he began studying spongiform encephalopathies, he assumed that there must be some genetic engine driving the diseases. "There was a list of possibilities longer than the number of people working in the field," he recalls.

Some of those possibilities did not seem to make biological sense. Tikvah Alper, a South African researcher, found that the scrapie agent was exceedingly small and resistant to ultraviolet radiation, a form of energy that can be lethal to viruses. It might, she concluded, not be a traditional pathogen at all, but a protein.

Intrigued, Prusiner went hunting for a killer protein. Working with infected brain tissue from mice and hamsters, he began eliminating all of the basic material that should have been present in healthy samples, knowing that whatever was left must be the infectious culprit. When he had distilled out nearly everything in the dish, he found that what remained contained no DNA or RNA and was indeed made up entirely of protein. "I called what I found a prion," he says, "for infectious protein."

Whatever it was called, the thing was nasty. Essentially a normal protein that has become misfolded, it has a tendency to snap into a new position like a mousetrap, triggering healthy proteins around it to do the same. This causes holes to appear in the grey matter, destroying brain function. It took Prusiner until 1982 to get the science nailed down and publish his findings, and it took until 1997 for the Nobel Committee to recognize what he'd done. "There was a lot of skepticism," he says.

Less so now—especially as Prusiner and others are increasingly able to see the prion through the lens of genetics. In about 10% of people with the wasting diseases, the transformation of healthy proteins into unhealthy ones appears to be linked to a mutation on a gene in chromosome 20. Since there are 40 different mutations, there may be 40 different prion diseases.

Prusiner is spending his time these days looking into all those forms and hopes to develop compounds that can prevent the proteins from making the switch. Could similar manipulation take place at the genetic level, allowing doctors simply to erase the coding for the disease? He isn't certain, but he's not inclined to bet against medical science as a whole. "At this point," he says, "we're not even sure what the human lifespan is." With or without DNA in play, there's still an awful lot to learn.

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