Prusiner, Stanley (1942- )

American physician

Stanley Prusiner performed seminal research in the field of neurogenetics, identifying the prion, a unique infectious protein agent containing no DNA or RNA .

Prusiner was born on in Des Moines, Iowa. His father, Lawrence, served in the United States Navy, moving the family briefly to Boston where Lawrence Prusiner enrolled in Naval officer training school before being sent to the South Pacific. During his father's absence, the young Stanley lived with his mother in Cincinnati, Ohio. Shortly after the end of World War II, the family returned to Des Moines where Stanley attended primary school and where his brother, Paul, was born. In 1952, the family returned to Ohio where Lawrence Prusiner worked as a successful architect.

In Ohio, Prusiner attended the Walnut Hills High School, before being accepted by the University of Pennsylvania where he majored in Chemistry. At the University, besides numerous science courses, he also had the opportunity to broaden his studies in subjects such as philosophy, the history of architecture, economics, and Russian history. During the summer of 1963, between his junior and senior years, he began a research project on hypothermia with Sidnez Wolfson in the Department of Surgery. He worked on the project throughout his senior year and then decided to stay on at the University to train for medical school. During his second year of medicine, Prusiner decided to study the surface fluorescence of brown adipose tissue (fatty tissue) in Syrian golden hamsters as they arose from hibernation. This research allowed him to spend much of his fourth study year at the Wenner-Gren Institute in Stockholm working on the metabolism of isolated brown adipocytes. At this he began to seriously consider pursuing a career in biomedical research.

Early in 1968, Prusiner returned to the U.S. to complete his medical studies. The previous spring, he had been given a position at the National Institutes of Health (NIH) on completing an internship in medicine at the University of California San Francisco (UCSF). During that year, he met his wife, Sandy Turk, who was teaching mathematics to high school students. At the NIH, he worked on the glutaminase family of enzymes in Escherichia coli and as the end of his time at the NIH began to near, he examined the possibility of taking up a postdoctoral fellowships in neurobiology. Eventually, however, he decided that a residency in neurology was a better route to developing a rewarding career in research as it offered him direct contact with patients and therefore an opportunity to learn about both the normal and abnormal nervous system. In July 1972, Prusiner began a residency at UCSF in the Department of Neurology. Two months later, he admitted a female patient who was exhibiting progressive loss of memory and difficulty performing some routine tasks. This was his first encounter with a Creutzfeldt-Jakob disease (CJD) patient and was the beginning of the work to which he has dedicated most of his life.

In 1974, Prusiner accepted the offer of an assistant professor position from Robert Fishman, the Chair of Neurology at UCSF, and began to set up a laboratory to study scrapie, a parallel disease of human CJD found in sheep. Early on in this endeavor, he collaborated with William Hadlow and Carl Eklund at the Rocky Mountain Laboratory in Hamilton, Montana, from whom he learnt much about the techniques of handling the scrapie agent. Although the agent was first believed to be a virus, data from the very beginning suggested that this was a novel infectious agent, which contained no nucleic acid. It confirmed the conclusions of Tikvah Alper and J. S. Griffith who had originally proposed the idea of an infectious protein in the 1960s. The idea had been given little credence at that time. At the beginning of his research into prion diseases, Prusiner's work was fraught with technical difficulties and he had to stand up to the skepticism of his colleagues. Eventually he was informed by the Howard Hughes Medical Institute (HHMI) that they would not renew their financial support and by UCSF that he would not be promoted to tenure. The tenure decision was eventually reversed, however, enabling Prusiner to continue his work with financial support from other sources. As the data for the protein nature of the scrapie agent accumulated, Prusiner grew more confident that his findings were not artifacts and decided to summarize his work in a paper, published in 1982. There he introduced the term "prion," derived from "proteinaceous" and 'infectious" particle and challenged the scientific community to attempt to find an associated nucleic acid. Despite the strong convictions of many, none was ever found.

In 1983, the protein of the prion was found in Prusiner's laboratory and the following year, a portion of the amino acid sequence was determined by Leroy Hood. With that knowledge, molecular biological studies of prions ensued and an explosion of new information followed. Prusiner collaborated with Charles Weissmann on the molecular cloning of the gene encoding the prion protein (PrP). Work was also done on linking the PrP gene to the control of scrapie incubation times in mice and on the discovery that mutations within the protein itself caused different incubation times. Antibodies that provided an extremely valuable tool for prion research were first raised in Prusiner's lab and used in the discovery of the normal form of PrP protein. By the early 1990s, the existence of prions as causative agents of diseases like CJD in humans and bovine spongiform encephalopathy (BSE) in cows, came to be accepted in many quarters of the scientific community. As prions gained wider acceptance among scientists, Prusiner received many scientific prizes. In 1997, Prusiner was awarded the Nobel Prize for medicine.

See also BSE and CJD disease; Infection and resistance; Viral genetics