Scrapie is a neurological disease of sheep first described in England, France and Germany in the early 18th century. Affected sheep rub their coat against a tree or building as if it itches. Hence the name 'scrapie'. In French, it is 'La tremblante', for the shaking of the animal due to ataxia, another symptom. The human form of the disease was described in the 1920's in Germany and Austria. It's various forms are called Creutzfeldt-Jakob Disease (CJD), or Gerstmann-Strausler-Scheinker Disease (GSS), or Fatal Familial Insomnia (FFI). An epidemic form of the disease was discovered by Zigas & Gajdusek in 1957 among a canabalistic tribe in New Guinea. They called the disease Kuru. Hadlow noted the similarity of Kuru brain pathology (spongiform change) to that of scrapie, and suggested that animals innoculated with Kuru material be kept a long time. With this hint, Gibbs and Gajdusek showed that Kuru brain material, as well as that of CJD and GSS, were infectious for monkeys.
In 1966, Alper showed that scrapie was very UV-resistant, compared to known viruses, and suggested that perhaps scrapie was infectious without a required nucleic acid. In 1967, Griffith proposed three mechanisms by which this might happen. They were 1) a protein that turns on its own transcription, 2) an altered form of a protein that catalyzes the conversion of the normal form into the same altered form through formation of an oligomer--like a crystal seed, and 3) an antibody that stimulates its own production. Griffith proposal 2) is essentially the modern 'protein only' prion model.
PrP, the prion protein, was first identified in 1968 by Dickinson as a gene called Sinc affecting scrapie incubation period in mice, but there was no suspicion at that time as to its role. In 1982, Prusiner identified PrP as a protease-resistant protein in brains of scrapie-infected animals, not found in normal animals. With the cloning of the PrP gene, Prnp, by Weissmann and Chesebro, it became clear that PrP was host encoded, and Carlson showed that Prnp was identical to Sinc. The finding by Prusiner and Collinge that human inherited CJD was associated with mutations in Prnp, and transgenic experiments by Prusiner further solidified the importance of PrP in the disease. Weissmann's demonstration that PrP was necessary for scrapie left only demontration that it is sufficient to be done. This has not yet been achieved.
