Stanley B. Prusiner

Neurologist

• Born: May 28, 1942
• Place of Birth: Des Moines, Iowa

SCIENTIST AND PHYSICIAN

Prusiner discovered prions, proteins that can reproduce and cause fatal degenerative neurological diseases. His discovery challenged biological notions that all infectious agents contain either DNA or RNA.

AREAS OF ACHIEVEMENT: Science and technology; medicine

Early Life

Stanley B. Prusiner was born in Des Moines, Iowa, to Jewish parents during World War II. His father was drafted into the US Navy shortly after his birth. Prusiner’s family moved to Cincinnati, Ohio, while his father was in the Navy, and after the war his family returned to Des Moines, where Prusiner attended primary school and his brother Paul was born. In 1952, the family moved back to Cincinnati, so that his father could find a better job as an architect, and there Prusiner attended Walnut Hills High School.

In 1960, Prusiner attended the University of Pennsylvania. He did hypothermia research with Sidney Wolfson and graduated in 1964 with a degree in chemistry. Prusiner remained at the University of Pennsylvania for medical school, and he did research with Britton Chance on brown fat in hamsters. He completed his medical degree in 1968 and then moved to San Francisco for an internship at the University of California, San Francisco (UCSF). In San Francisco, Prusiner met Sandy Turk, and they married. One year later, Prusiner went to the National Institutes of Health to work as a postdoctoral research fellow with Earl Stadtman. There he learned biochemical techniques for protein purification and characterization. In 1972, Prusiner began a residency in neurology at UCSF.

Life’s Work

During his neurology residency, Prusiner examined a female patient who later died from a slow virus infection called Creutzfeldt-Jakob disease (CJD). Slow virus infections so intrigued Prusiner that he decided to make them the subject of his research. From the scientific literature, Prusiner discovered several related slow virus diseases known to afflict humans and animals. These diseases caused similar symptoms and comparable patterns of brain damage, and they included scrapie, which afflicts sheep and goats, and such human diseases as CJD and kuru, a disease unique to the Fore highlanders of Papua New Guinea, who acquire it through ritualistic cannibalism of the brains of deceased tribe members. All of these diseases cause loss of coordination (ataxia) followed by mental deterioration (dementia) and a distinctive type of damage in which large portions of the brain die and are replaced by clear, protein-filled “plaques” (spongiform encephalopathy).

In 1974, Prusiner accepted a position as an assistant professor of neurology at UCSF, and he began researching scrapie. When he isolated plaques from the brains from scrapie-infected sheep, he found that they contained agglomerations of a single protein and no deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). When he injected this purified protein into the brains of mice, those mice contracted scrapie. Prusiner became confident that the cause of scrapie was a single protein, and in 1982 he published a controversial but landmark paper that included his new term “prion,” shorthand for “proteinaceous infectious particle.” Thus these dementias were caused by protein only and not viruses.

In 1984, Prusiner and his collaborators showed that normal cells make a version of the prion protein (PrP). In fact this protein is present on the surface of cells in the brains of all mammals he examined, but it does not make them sick. Instead, there is an abnormal version of the PrP, and this altered version causes the dementias.

In 1988, Karen Hsiao in Prusiner’s laboratory showed that human prion diseases are sometimes inherited. Particular mutations in the gene that encodes the PrP can cause prion diseases. These mutations induce the PrP protein to fold in an aberrant manner, and these aberrantly folded proteins commandeer the normal versions of PrP and force them into the aberrantly folded conformation. These amalgamated clusters of abnormally folded protein kill brain cells and cause the large, clear plaques in the brains of people and animals afflicted with prion diseases.

Over the following decades, Prusiner continued to work in his laboratory at UCSF's Institute for Neurodegenerative Diseases, focusing on using his research involving prions to discover possible preventions and cures for neurodegenerative diseases, especially Alzheimer's disease. In recognition of his discovery and ongoing efforts, President Barack Obama awarded him the National Medal of Science, the nation's highest honor for science and technology, in 2010. At the same time, he played a large role in helping to develop the concept and plan for the new Sandler Neurosciences Center that was built and opened on UCSF's Mission Bay campus in 2012; the facility, which now houses Prusiner's institute, brings together neuroscientists from around the world for the specific purpose of studying the common brain diseases and is one of the largest neuroscience complexes in the world. In 2015, a neurologist working at the facility reported that he and his team had discovered a new kind of prion that is likely responsible for a rare brain disorder similar to Parkinson's disease. Also in 2015, Prusiner's paper "Evidence for alpha-synuclein prions causing multiple system atrophy in humans with parkinsonism," which was published in the Proceedings of the National Academy of Sciences (PNAS) and cited nearly 500 times, was being corrected because of a repeated image. The image of the same control mouse brain slice is used for two panels, the phosphorylated alpha-synuclein and the reactive astrocytes.

Significance

Prusiner won the 1997 Nobel Prize for his discovery of prions. He uncovered a completely new category of disease-causing agents. With this basic understanding of prions in hand, other new prion-based diseases, such as Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia, were discovered. Prusiner’s work also provided an understanding of those mechanisms that underlie other types of dementias, such as Alzheimer’s disease, and established new strategies for drug development and new types of medical-treatment strategies.

Prusiner’s work also provided the groundwork to address the bovine spongiform encephalopathy (BSE) or “mad cow disease” problem in Great Britain. The similarity between the sheep and the cow PrP allows scrapie to move to cows if their feed is tainted with brain material from scrapie-infected sheep. After identifying BSE in 1986, the British government banned the use of animal-derived feed supplements in 1988, and the British BSE epidemic began to decline. The understanding of prion diseases, pioneered by Prusiner, provided the strategy to address this distressing animal health problem.

Bibliography

Corbyn, Zoë. "Stanley Prusiner: 'A Nobel Prize Doesn't Wipe the Skepticism Away.'" Guardian. Guardian News and Media, 24 May 2014. Web. 26 Apr. 2016.

Max, D. T. The Family That Couldn’t Sleep: A Medical Mystery. New York: Random, 2007. Print.

Prusiner, Stanley B. Prion Biology and Diseases. Cold Spring Harbor: Cold Spring Harbor Laboratory, 2003. Print.

Prusiner, Stanley B. “The Prion Diseases.” Scientific American 272.1 (1995): 48–57. Print.

Welle, Elissa. "Nobel Prize Winner's Paper to Be Corrected, According to Co-Author." The Transmitter, 27 Mar. 2024, www.thetransmitter.org/publishing/nobel-prize-winners-paper-to-be-corrected-according-to-co-author/. Accessed 2 Sept. 2024.

Yam, Philip. The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases. New York: Springer, 2003. Print.