ABSTRACT
The infectious origin for transmissible spongiform encephalopathy (TSE) was accidentally discovered in 1937 when a population of Scottish sheep was inoculated against a common virus with a formalin extract of brain tissue unknowingly derived from an animal with scrapie. Scrapie was subsequently transmitted experimentally to sheep [Cullie and Chelle, 1939] and later to mice [Chandler, 1961]. In humans, an infectious origin was suspected as a route of propagation of kuru among the cannibalistic tribes of New Guinea, and this was demonstrated in 1966 by transmission of kuru to monkeys in the pioneering studies of Carleton Gajdusek [Gajdusek et al., 1966]. These studies were followed by transmission of Creutzfeldt-Jakob disease (CJD) to animals [Gibbs, Jr., et al., 1968] and, interestingly, a familial form of TSE, Gerstmann-Straussler-Scheinker (GSS) syndrome [Masters et al., 1981]. This chapter describes the various hypotheses proposed for the infectious agent and, in particular, the compelling evidence for the prion hypothesis as well as the criticisms and missing evidence for this novel type of infectious agent.
