2 Development of the Prion Concept

Abstract

The prion concept was developed in the aftermath of many unsuccessful attempts to decipher the nature of the scrapie agent. In some respects, the early development of the prion concept mirrors the story of the discovery that DNA is the genetic material of life (Avery et al. 1944; Stanley 1970; McCarty 1985). Prior to the acceptance that genes are composed of DNA (Hershey and Chase 1952; Watson and Crick 1953), some scientists asserted that DNA preparations must be contaminated with protein, which is the true genetic material (Mirsky and Pollister 1946). For more than half a century, many biologists thought that genes were composed of protein and that proteins reproduced as replicas of themselves (Stanley 1935; Haurowitz 1950). The prejudices of these scientists were similar in some ways to those of investigators who vigorously opposed the prion concept. However, the scientists who attacked the hypothesis that genes are composed of DNA had no likely 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 and showed that genes could also be composed of RNA in these small infectious pathogens (Fraenkel-Conrat and Williams 1955; Gierer and Schramm 1956; Diener 1979).

It is on this background...