3 Bioassays of Prions

Abstract

Prior to the experimental transmission of scrapie to goats inoculated with tissue extracts prepared from sheep with scrapie (Cuillé and Chelle 1939), no experimental studies of the disease were possible. Despite the cumbersome bioassays in sheep and goats, some limited information was obtained. For example, the susceptibility of 24 different breeds of sheep was measured after subcutaneous inoculation with brain extract prepared from a sheep with scrapie (Gordon 1946). The resistance of the scrapie agent to inactivation by formalin and heat was also shown using bioassays performed in sheep (Pattison and Millson 1960). The first evidence for strains of prions accumulated with goats that presented with two different clinical syndromes (Pattison and Millson 1961b). One set of prion-infected goats was described as “drowsy” due to the lethargy manifest 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, such as those caused by prions, is their prolonged incubation periods, during which the host is free of recognizable clinical dysfunction. The onset of clinical symptoms marks the end of the incubation period and the beginning of a relatively short, progressive course of illness that ends in death. Although prolonged incubation periods are a fascinating phenomenon, they have been the biggest impediment to prion research. Because animals remain healthy throughout the incubation period, investigators must wait until signs of clinical illness appear before assigning a positive score. In early studies...