Susan Lindquist is a researcher at the Howard Hughes Medical Institute, located in the department of molecular genetics and cell biology at the University of Chicago. She responds:
"'Prion' is a term first used to describe the mysterious infectious agent responsible for several neurodegenerative diseases found in mammals, including Creutzfeldt-Jakob disease (CJD) in humans. The word itself derives from 'proteinaceous infectious particle'; it refers to the initially heretical hypothesis that the infectious agent causing those diseases consists only of protein, with no nucleic acid genome. (All previously known pathogens, such as bacteria and viruses, contain nucleic acids, which enable them to reproduce.) The prion hypothesis explained why the mysterious infectious agent is resistant to ultraviolet radiation, which breaks down nucleic acids, but is susceptible to substances that disrupt proteins.
"A major breakthrough occurred when researchers discovered that the infectious agent consists primarily of a protein found in the membranes of normal cells, but in this case the protein has an altered shape, or conformation. Some scientists hypothesized that the distorted protein could bind to other proteins of the same type and induce them to change their conformation as well, producing a chain reaction that propagates the disease and generates new infectious material. Since then, the gene for this protein has been successfully cloned, and studies using transgenic mice have bolstered the prion hypothesis. The evidence in support of the hypothesis is now very strong, though not incontrovertible.
"Research on prion diseases has recently accelerated for several reasons. First, the mounting experimental evidence has generated great interest in what appears to be a totally new kind of mechanism of disease. Second, the demonstration that prions are responsible for 'mad cow' disease (bovine spongiform encephalopathy), which has infected large numbers of cattle in Great Britain and panicked the public, has lent new urgency to the quest for a cure--especially since the discovery that infected cows might be responsible for several new cases of CJD in humans. Finally, I and my colleagues have recently determined that a phenomenon much like prion infection exists in yeast.
"In the case of yeast, the phenomenon involves the passing of a particular genetic trait from mother cells to daughter cells, rather than the transmission of an infectious agent from one individual to another. These genetic traits had been known for many years, but their baffling patterns of inheritance (for example, they can be passed along through a cell's cytoplasm, rather than the nucleus where the DNA resides) had eluded explanation. We now know that the genetic trait is transmitted by proteins that are encoded in the nucleus but that can change their conformation in the cytoplasm. Once this change has occurred, the reconfigured proteins induce other newly made proteins of the same type to change their conformation, too. Molecular genetic research on yeast should speed up the resolution of fundamental questions about the workings of protein-folding chain reactions. And more important, it suggests that the prion mechanism is ubiquitous among living things and may be responsible for many phenomena other than neurodegenerative diseases like CJD."
Mark Rogers in the department of zoology and the Biotechnology Centre at University College, Dublin, adds some further information:
"The term 'prion' was coined by Stanley B. Prusiner of the University of California School of Medicine at San Francisco in 1982 to distinguish the infectious agent that causes scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle from other, more typical infectious agents. The prion hypothesis postulates that these diseases are caused not by a conventional virus or bacterium but by a protein that has adopted an abnormal form.