Stalking the Elusive Prion

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A Nobel laureate chronicles his dogged pursuit of the cause of certain brain diseases.

MADNESS AND MEMORY: The Discovery of Prions—A New Biological Principle of Disease, By Stanley B. Prusiner C’64 M’68 Hon’98, Yale University Press, 2014, $30.

By Jason Karlawish | Near the end of Stanley Prusiner’s memoir of his Nobel Prize-winning research into the cause of such devastating neurological diseases as Creutzfeldt-Jakob Disease (CJD) and Mad Cow Disease, he recounts how, after a talk at the Aspen Institute, his host admonished him for delivering overly sobering remarks on Alzheimer’s disease. “You have to give people some hope,” his host told him. “You need to give them some reason to believe that Alzheimer’s is not hopeless—otherwise, they won’t be interested in supporting your research.”

The comment bothered Prusiner, now director of the Institute for Neurodegenerative Diseases and professor of neurology at the University of California, San Francisco. Throughout his research career, he had been vexed by money—the need for it and the lack of it. But he would not engage in the “dangerous behavior” of distorting his understanding of the facts to fit other people’s desires, he makes clear. Nor will he peddle science’s most potent fundraising tonic: the Elixir of Hope. “For a scientist,” he reflects, “the most important trait is intellectual honesty within himself.”

It is by this ethos that the reader should judge Madness and Memory: The Discovery of Prions—A New Biological Principle of Disease, Prusiner’s memoir of the journey from his humble Midwestern boyhood to the Mount Parnassus of science. Though he provides a detailed account of what he calls “a race to discovery,” his narrative might be better described in terms of an epic quest or even a war. True, no one dies, but a lot of metaphorical blood is shed. Alliances are made and then broken, while great fortresses of reputation are painstakingly constructed and others are ruthlessly torn down. The road to Nobel is paved not only with countless mice and hamsters but with graduate students, post-docs, and fellow scientists. Engage this book not as an autobiography but as the Odyssey of Dr. Stanley Prusiner, scientific explorer and warrior.

He begins at the beginning, convinced that the more we understand the community and places he came from, the better we can understand why, in the face of repeated slings and arrows, he pressed on with his meticulous titration studies, determined to be the first to discover what caused these devastating neurological diseases. We read a detailed account of his lineage from Eastern European Jewish immigrants who came to America one step ahead of the pogroms, and who changed their names to sound more American and moved west in search of work and to escape discrimination. As Jews in the Gentile Midwest, his family feels trapped in its struggle from paycheck to paycheck. His father’s business as an architect never takes off. When Stanley is six, his mother disappears from her son’s life for many months duringa prolonged convalescence from a heart attack, and then at 12, his loving grandmother dies. He remembers none of his grade-school teachers’ names. High school is boring. He’s not allowed to take AP chemistry.

But when he comes to the University of Pennsylvania, something happens. Our seemingly ordinary Midwestern boy begins a transformation. He is drawn into the excitement of intellectual inquiry with such mentors as Sidney Wolfson C’51 GM’59 and the late Britton Chance Ch’35 Gr’40 Hon’85. He studies brain swelling in rats and then how brown fat burns oxygen. He stays on for medical school, followed by more research in Sweden. He rejects the temptations of the sensuous life in a village outside Tangiers. Instead, he ties himself to the mast of a grueling medical internship at UCSF, then returns to the lab. During his three years at the National Institutes of Health, he learns a skill that will serve him well: how to purify proteins.

Now fully grown, our young warrior awaits his quest. In early September 1972, as a busy neurology resident, he is called on to care for a patient with progressive dementia. A slender woman of 60, she is rapidly losing her mind and the control of her motor functions. Two months later, she is “a neurological vegetable.” An autopsy confirms the clinical diagnosis: CJD, one of the diseases then thought to be caused by an as-yet unidentified “slow brain virus.”

Yet the more Prusiner reads about what caused his patient’s rapid decline, the less he understands. How could a person with a viral infection lack the signs of an infection, such as a fever or elevated counts of infection-fighting cells? Then he reads a provocative study by Tikvak Alper (one of several women, along with his mother and grandmother, whose influence is pivotal in his life) suggesting that CJD is caused not by a virus but by some kind of “scrapie agent.” The care he gave his patient is replaced by an obsession to discover what caused her disease.

Prusiner’s career-development award from the NIH involved the study of glutamate metabolism. Had he simply focused on this highly fundable work, he could have led a comfortable professional life in a well-funded domain of science. Instead, he managed to secure a small grant to study the scrapie agent.

The reader presumably knows how this quest will end. Prusiner discovered that brain diseases once thought to be caused by a “slow virus” in fact share a common cause: a proteinaceous infectious particle that he named a prion. Acceptance did not come easily, and he chronicles the fierce scientific disputes that accompanied his discovery in fascinating detail. But as his 1997 Nobel Prize in Physiology/Medicine resoundingly confirmed, prions are now widely accepted as among the causes of neurological diseases.

Prusiner’s task in writing about this is to avoid self-promotion and instead to narrate his quest with candor and insights that tell us what we cannot learn from an annotated bibliography of his papers. He succeeds. He certainly shreds the image of scientists as rational beings living dull, unemotional lives. Scientists are as passionate, arrogant, and ambitious as artists, keen to win honors and marquee billing. Though they often wish that, like novelists, they could name their discoveries, they’ll usually settle for money—the more, the better. Luck—“huge doses of it,” says Prusiner—helps. He mentions his “loving partner” and two daughters, but that’s all we hear of them—and nothing about friends or any other life outside the lab. In the life of the scientist, is there life outside of science?

Each year, universities devote considerable resources to training their young scientists in the responsible conduct of research and, to use Prusiner’s term, the “dangerous behaviors to be avoided” such as doing experiments on humans without their permission, faking data, and stealing results or credit from another scientist. What’s usually missing in this training is how to live the life of a scientist, and the challenges of living honestly with oneself. Madness and Memory should be part of the curriculum.

Jason Karlawish is a professor of medicine, medical ethics, and health policy at Penn and the author of Open Wound: The Tragic Obsession of Dr. William Beaumont [“Arts,” Mar|Apr 2012].
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