| Citation | Stanley B. Prusiner is distinguished for his discovery of prions, a novel class of transmissible pathogens that are devoid of nucleic acid and multiply by inducing changes in protein structure, As late as 1980, all the known causes of infectious disease were nucleic acid-containing agents such as viruses, bacteria and parasite. A group of illnesses characterized by spongiform degeneration of the brain, including Creutzfeldt-Jakob disease and kuru in humans and scrapie in sheep, were known to be transmissible, but their cause remained elusive. In a series of remarkable experiments, Prusiner not only discovered the cause of these diseases, but in doing so he made a conceptual advance that has revolutionized our thinking about the biology of both transmissible and neurodegenerative diseases. He demonstrated that the agents responsible for spongiform degeneration, which are now known as prions, are devoid of nucleic acid, yet induce their own replication. After purifying prions, he discovered that they contain a protein designated PrPSc, the amino acid sequence of which is encoded by a chromosomal gene found in humans and all animals examined. In its normal form, the prion protein (PrP) is called PrPC. Prusiner subsequently showed that PrPSc is derived from PrPC by a process which involves a profound change in the conformation of this protein. Alteration of the tertiary structure of PrP confers upon it the ability to initiate the conversion of PrPC molecules into PrPSc and thus, the capacity to transmit disease. He found that purified prions could exist as amyloid polymers and showed that amyloid plaques in the brains of animals and humans dying of prion diseases are composed of PrPSc. Moreover, prusiner showed that mutation of the PrPgene cause the inherited human prion diseases, including such disorders as Gerstmann-Straussler-Scheinker disease and fatal familial insomnia. These studies explained, for the first time, how a diseaes can be both infectious and genetic. Despite extreme opposition, Prusiner's findings have prevailed and prions, which were intially labelled scientific heresy, are now considered orthodoxy. Prusiner's extraordinary studies have changed the way that physicians and scientists view not only CNS degenerative disorders, including mad cow disease, a recent addition to the growing list of prion disease, but stable metabolic states induce by changes in protein structure, as it thought to be the case for yeast prions. Seldom has the work of one scientist had such profound implictions for future biomedical research. In carrying out his seminal and visionary work, Prusiner showed exceptional creativity, perseverance and courage over a period of 20 years. |