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3 Bioassays of Prions

Stanley B. Prusiner, Patrick Tremblay, Jiri Safar, Marilyn Torchia, Stephen J. Dearmond


Prior to the experimental transmission of scrapie to inoculated goats with tissue extracts prepared from scrapied sheep (Cuillé and Chelle 1939), no experimental studies of the disease were possible. Despite the cumbersome bioassays in sheep, some limited studies were possible. For example, the susceptibility of 24 different breeds of sheep was measured after subcutaneous inoculation with brain extract prepared from a scrapied sheep (Gordon 1946). The resistance of the scrapie agent to inactivation by formalin and heat was also shown by using bioassays in sheep (Pattison and Millson 1960); moreover, the first evidence for strains of prions was accumulated with goats that presented with two different clinical syndromes (Pattison and Millson 1961b). One set of goats was described as “drowsy” due to the lethargy manifested during the clinical phase of scrapie, and the other was called “hyper” because these animals were highly irritable and easily aroused.

One of the most distinctive and remarkable features of slow infections is their prolonged incubation periods, during which the host is free of recognizable clinical dysfunction. The onset of clinical illness marks the end of the incubation period and the beginning of a relatively short, progressive course, which ends with death. Although prolonged incubation periods are fascinating phenomena, they have been the biggest impediment to scrapie research. Since animals remain healthy throughout the incubation period, investigators must wait until signs of clinical illness appear before assigning a positive score. In early studies of scrapie using sheep, incubation periods of 1–3 years were required.

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