Proteins Gone Bad

The following is a guest editorial by Rudy M. Baum, former editor-in-chief of C&EN.

Stanley B. Prusiner has a chip on his shoulder. Despite his 1997 Nobel Prize for the discovery of prions, it is clear that he still bears psychic scars from the disbelief, often bordering on scorn, that greeted his 1982 announcement that he had isolated the agent that causes the neurodegenerative disease scrapie in sheep and that his data indicated that this infectious, self-replicating agent consisted only of protein and did not appear to contain any nucleic acid.

No DNA or RNA to encode its proteins. Clearly heretical. Clearly, in many scientists’ minds, dead wrong.

I bumped into Prusiner at the annual National Academy of Sciences garden party held in late April. I reintroduced myself—we’ve met a couple of times over the years but never established any kind of a relationship—and I recalled to him that I was sitting on the floor of the hallway outside his University of California, San Francisco, lab during the impromptu press conference in February 1982 at which he discussed the discovery of prions after a story on his research had appeared in the San Francisco Chronicle.

“That’s not possible,” he laughed. “You were a baby!”

No, I replied, I was a 29-year-old reporter just finishing up my first year as C&EN’s West Coast correspondent. I wrote the lead News of the Week story on Prusiner’s work (C&EN, March 1, 1982, page 4) based on that press conference. Prusiner published the prion hypothesis and the data that supported it a month later in Science (DOI: 10.1126/science.6801762).

It’s well-known that Prusiner doesn’t like and won’t talk to reporters. He feels he’s often been treated badly by reporters, especially science writer Gary Taubes, who wrote a less-than-flattering profile of Prusiner in a 1986 issue of Discover.

At the garden party, Prusiner told me that he had published a book in 2014, “Madness and Memory: The Discovery of Prions—A New Biological Principle of Disease.” He’d written it, he said, because he didn’t trust any other scientists or reporters to get the story of his research right.

After the garden party, I downloaded “Madness and Memory” to my iPad and read it in two days. It is a remarkable book, both an autobiography and an account of four decades of scientific research that is reminiscent of James Watson’s “The Double Helix.” In the book, Prusiner provides a clear and accessible account of the research in his lab and others that led to the notion that prions—misfolded versions of naturally occurring proteins of unknown function—cause a wide range of neurodegenerative diseases.

Prusiner’s discovery of prions had implications that went far beyond what even he could have imagined in the early days of his research. His obsession with the etiology of an obscure neurodegenerative disease in sheep would, over three decades, lead to an entirely new perspective on neurodegenerative diseases, many of which exact a devastating toll on humans. Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), bovine spongiform encephalopathy (mad cow disease), and chronic traumatic encephalopathy (CTE), to name a few, all may have at their root links to prionlike misfolding of proteins in the brain (see page 11).

But Prusiner’s personality—brash, confident, more than a bit pushy—coupled with the seeming outlandishness of his prion hypothesis, engendered a deep-seated hostility among many scientists, who insisted for years that some kind of virus was the cause of scrapie and related diseases, and some journalists like Taubes, who spent more than a decade raising questions about Prusiner’s science and integrity.

In “Madness and Memory,” Prusiner gets at how science is really done. What comes through is the importance of relationships—both friendships and productive collaborations as well as enmity and bare-knuckle competition. The Prusiner who emerges from “Madness and Memory” is not unlike many other brilliant scientists I’ve gotten to know in my career. He is at times warm and engaging, prickly, charming, thin-skinned, charismatic, insecure, and vindictive.

Today, recognition of Prusiner’s contributions to neuroscience is secure. With “Memory and Madness,” it would seem that Prusiner has had the last word on the subject.

Rudy M. Baum
Editor-at-large