Historical overview of prion diseases: a view from afar

Abstract

The transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of neurodegenerative disorders which include kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia in men, natural scrapie in sheep, goats and mufflons, transmissible mink encephalopathy in ranch-reared mink, chronic wasting disease of mule deer and elk, bovine spongiform encephalopathy or "mad cow disease" and its analogues in several exotic species of antelopes and wild felids in zoological gardens, and feline spongiform encephalopathy in domestic cats. This short review summarizes the history of the research to find the nature of the scrapie agent, especially as I have witnessed it unfolding before my eyes. I review the historical background of TSEs starting from the first description of scrapie in 1732. In 1957, the first prion disease in humans, kuru was described and its transmissibility was demonstrated in 1965 by seminal work of Gajdusek, Gibbs and colleagues, followed by transmission of CJD and then, GSS. In 1982, Stanley B. Prusiner formulated "prion hypothesis" which has dominated the field for the last 30 years. This theory had been recently extended to cover other neurodegenerations which are caused by misfolded proteins; these disease are called prionoids.