ABSTRACT
The Genesis of the Prion Concept from Studies in Mammals The transmissible spongiform encephalopathies (TSEs) of mammals are inexorably fatal
degenerative brain diseases whose etiology has long been debated,1,2 but are widely believed to be caused by an infectious protein. The unusual radiation-resistance of the scrapie agent3 generated a flurry of speculation on its nature, including a surprisingly accurate early ver sion of the protein-only hypothesis.4 It was proposed that an altered form of a cellular protein binds a monomer of the normal form, and in this complex, changes the normal to the abnormal form. This is, in essence, the modern view. The key protein was identified genetically as the Sine gene of mice controlling scrapie incubation period.5 However, it was only 18 years later that Sine was shown to be the gene encoding PrP,6 the major component of the scrapie agent.7
