- Person
- Stanley Prusiner
- Lived
- b. 1942
- Field
- Neurology
- From
- American
The story
By 1982 Stanley Prusiner and his colleagues had concluded that the agent causing scrapie, a fatal brain disease of sheep, was made of protein. Soon afterwards his laboratory found the protein itself, and the following year Leroy Hood determined part of its amino acid sequence. That opened the way to molecular biology, and to an obvious question: where was the gene that carried the instructions for making the protein? If prions were like small viruses, the gene should travel with the infectious particle.
The answer, which came in 1984, was startling. Prusiner's team isolated a gene probe and found that the prion gene is present in all animals tested, including humans. Working with Charles Weissmann, Prusiner cloned the gene, and with George Carlson and David Kingsbury linked it to the control of how long scrapie takes to develop in mice. The researchers showed that the normal prion protein is an ordinary component of white blood cells and many other tissues, and is especially abundant on the surface of nerve cells in the brain. The infectious agent was made from one of the body's own proteins.
This seemed at first to undermine the prion idea. As the Nobel Assembly later put it, critics asked how prions could cause brain disease when the gene was a normal part of every mammal, and concluded that Prusiner must have made a mistake.
The solution came when the team showed that the protein exists in a normal form and a disease-causing form, and that the harmful shape can convert healthy copies. Antibodies developed in Prusiner's laboratory were key to finding the normal form. The Nobel Assembly compared the two forms to Dr Jekyll and Mr Hyde: the same entity in two different manifestations.
Because prions are made from a normal body protein, the immune system does not react to them, which explains why patients show no fever or other signs of infection. The finding also helped explain why prion diseases can be inherited through mutations in the gene, or arise spontaneously when a normal protein misfolds.
Why it matters
Discovering that prions arise from a normal human gene helped explain how prion diseases can be inherited or arise spontaneously, and pointed toward ways of preventing them.
About Stanley Prusiner
Neurologist who discovered prions, infectious proteins with no DNA or RNA, behind mad cow and Creutzfeldt–Jakob disease, winning the 1997 Nobel Prize for a once-derided idea.
More about Stanley Prusiner
- Stanley Prusiner showed prion disease can be inheritedStanley Prusiner's group showed that a mutation in the prion gene causes inherited brain disease, and reproduced the illness in genetically engineered mice.
- Stanley Prusiner founded an institute for brain diseasesIn 1999 Stanley Prusiner founded the Institute for Neurodegenerative Diseases at the University of California, San Francisco, to study illnesses caused by misfolded proteins.
- Stanley Prusiner told the prion story in a memoirIn 2014 Stanley Prusiner published Madness and Memory, his account of discovering prions and of the long scientific battle over an idea once dismissed as heresy.
- Stanley Prusiner discovered prions, a new kind of infectionIn 1982 Stanley Prusiner identified prions, infectious proteins with no DNA or RNA, an idea met with scepticism that won him the 1997 Nobel Prize.
- Stanley Prusiner's prions opened new routes to dementiaThe Nobel Assembly said Stanley Prusiner's discovery of prions could furnish the basis for understanding other dementias such as Alzheimer's disease and for developing new treatments.
- Stanley Prusiner revealed why prions are so hard to destroyStanley Prusiner's work showed that the disease-causing prion protein is extraordinarily stable, resisting enzymes, solvents and temperatures above 100°C, explaining why prions are so hard to kill.
Sources
- The Nobel Prize in Physiology or Medicine 1997, Press release NobelPrize.org
- Stanley B. Prusiner, Biographical NobelPrize.org
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.