After more than two decades of research on prions, Stanley Prusiner of UCSF suggested that mad cow disease must be present in US cows at low levels.
Prusiner, who spoke at a May 30 congressional caucus luncheaon, said the longer animals live, the more likely they are to develop the disease. He said he agreed with a Wisconsin researcher [Prof. R.F. Marsh], who believes mad cow disease was linked to US cows in the mid-1980's.
Prusiner criticized the British government for setting up an expert panel with members chosen by the governmen, rahter than by an independent body such as the National Academy of Sciences. He stopped short of recommending measures to halt the potential spread of the disease in the US, citing the complex chain of economic, political, and scientific variables affecting policy decisions.
Many factors conspired to cause mad cow disease in Britain, including the deregulation of the rendering industry, he said. The fat content increased in meat and bone meal fed to cows. While more than 160,000 cattle have come down with the disease, the numbers peaked in 1992 and are beginning to drop off there. The practises that led to the disease's spread stopped in the late 1980's, he said. Today, there are an estimated 1,000 cows dying of the disease every month.
The California researcher said scientists still don't know whether diseased cows can affect humans. He said it's still unclear what route exposes cows to the disease, whether through cuts in their mouths or [infectious agent] carrried by white blood cells.
He took the opportunity to urge Congress to step up funding of biomedical research.
Lab of Stanley Prusiner, M.D. Neuroscience Graduate Program Office, Room S-865 Medical Sciences Building, Box 0444 513 Parnassus Avenue University of California, San Francisco San Francisco CA 94143-0444 phone: (415) 476-2248 fax: (415) 476-4929 email: Neuroscience@phy.ucsf.eduMy research has focused on an unprecedented class of pathogens called prions which cause neurodegenerative diseases. Nascent prions are created either spontaneously by mutation of a host protein or by exposure of the latter to prions from an exogenous source. Prions are composed largely, if not entirely, of a modified form of the prion protein (PrP) designated PrPSc, yet they can multliply without a nucleic acid genome.
A post-translational, conformational change features in the conversion of cellular PrP (PrPC) into PrPSc in which -helices are transformed into -sheets. Since this structural transition in PrP underlies both the replication of prions and the pathogenesis of CNS degeneration, much of the effort in the laboratory is devoted to elucidating the molecular events responsible for this process. Indeed, prion diseases seem to be disorders of protein conformation. After demonstrating genetic linkage between the PrP gene and the control of scrapie incubation times, we established linkage between a human PrP gene point mutation and development of the fatal, familial disease Gerstmann-Straussler-Scheinker (GSS).
Like humans with GSS, transgenic mice expressing mutant PrP develop neurodegeneration and produce prions de novo as demonstrated by transmission of disease to inoculated recipients. These studies argue that prion diseases can be both inherited and infectious. While PrPSc seems to act as a template for the refolding of PrPC into a second molecule of PrPSc, we recently discovered that formation of PrPSc involves another molecule which restricts prion replication between distant species.
To overcome this restriction, we constructed chimeric human/mouse PrP transgenes; mice expressing this hybrid gene were rendered highly susceptible to human prions. This discovery opens many new investigations of the human prion diseases that previously required apes or monkeys. Identifying the molecule(s), provisionally designated protein X, that participate in the conversion of PrPC into PrPSc is another area of research in the laboratory.
Prions exhibit different patterns of disease which mimic strains of viruses where diversity is encoded within the viral genome. Elucidating the mechanism of prion diversity is a third area of investigation. Whether strains of prions represent distinct conformers of PrPSc or a second, as yet unidentified, molecule features in this process is unknown.
Prusiner, S.B.: The prion diseases. Sci Am 272:70-77, 1995
Telling, G.C., Scott, M., Hsiao, K.K., Foster, D., Yang, S.-L.l, Torchia, M., Sidle, K.C.L., Collinge, J., DeArmond, S.J., Prusiner, S.B.: Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. Proc. Natl. Acad. Sci. USA 91:9936-9940, 1994.
Cohen, F.E., Pan, K.-M., Huang, Z., Baldwin, M., Fletterick, R.J., Prusiner, S.B.: Structural clues to prion replication. Science 264:530-531, 1994.
Westaway, D., DeArmond, S.J., Cayetano-Canlas, J., Groth, D., Foster, D., Yang, S.-L., Torchia, M., Carlson, G.A., Prusiner, S.B.: Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins. Cell 76:117-129, 1994.
Carlson, G.A., Ebeling, C., Yang, S.-L., Telling, G., Torchia, M., Groth, D., Westaway, D., DeArmond, S.J., Prusiner, S.B.: Eveidence for isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice. Proc. Natl. Acad. Sci. USA 91:5690-5694, 1994.