2 Development of the Prion Concept

Abstract

The prion concept developed in the aftermath of many unsuccessful attempts to decipher the nature of the scrapie agent (Prusiner 1998). In some respects, the early development of the prion concept mirrors the story of DNA (Avery et al. 1944; Stanley 1970; McCarty 1985). Prior to the acceptance of DNA as the genetic material (Hershey and Chase 1952; Watson and Crick 1953), many scientists asserted that the DNA preparations were contaminated with protein, the true genetic material (Mirsky and Pollister 1946). For more than half a century, many biologists had thought that genes were made of protein and that proteins were reproduced as replicas of themselves (Haurowitz 1950; Stanley 1935). The prejudices of these scientists were similar in some ways to those of investigators who have disputed the prion concept. However, the scientists who attacked the hypothesis that genes are composed of DNA had no well-proven alternative; they had only a set of feelings derived from poorly substantiated data sets that genes are made of protein. In contrast, those who attacked the hypothesis that the prion is composed only of protein had more than 30 years of cumulative evidence showing that genetic information in all organisms on our planet is encoded in DNA. Studies of viruses and eventually viroids extended this concept to these small infectious pathogens (Diener 1979) and showed that genes could also be composed of RNA (Fraenkel-Conrat and Williams 1955; Gierer and Schramm 1956). It is with this background that investigators working on scrapie began to unravel...