[The early history of transmissible spongiform encephalopathies exemplified by scrapie]

Transmissible spongiform encephalopathies (TSE) are unique diseases in that they are sporadic, hereditary, and infectious. The transmissible pathogen--the prion--stands out from all other pathogens in being devoid of nucleic acids. Instead its most important and possibly only constituent is a host-encoded protein, the prion protein (PrP), in an alternative conformation induced by post-translational modifications. Thus TSEs belong to and are so far the only transmissible member of the continuously growing group of disorders collectively referred to as protein conformational disorders. During elucidation of these disorders, many different--and contradictory--theories have been put forward. Early researchers, mostly driven by the economic effect of these diseases upon sheep farming, engaged in heavy disputes concerning the heredity vs infectivity of scrapie. After the experimental demonstration of scrapie's infectivity during the twentieth century, research focused on elucidating the nature of the transmissible agent. The current work comprehensively summarizes the early literature available on TSE research.