1 An Introduction to Prion Biology and Diseases

Abstract

The history of prions is a fascinating saga in the annals of biomedical science. For nearly five decades with no clue as to the cause, physicians watched patients with a central nervous system (CNS) degenerative disorder called Creutzfeldt-Jakob disease (CJD) die, often within a few months of its onset (Creutzfeldt 1920; Jakob 1921; Kirschbaum 1968). CJD destroys the brain while the body remains unaware of this process. No febrile response, no leukocytosis or pleocytosis, and no humoral immune response is mounted in response to this devastating disease. Despite its recognition as a distinct clinical entity, CJD remained a rare disease; first, it was in the province of neuropsychiatrists and, later, of neurologists and neuropathologists. Although multiple cases of CJD were recognized in families quite early (Kirschbaum 1924;Meggendorfer 1930; Stender 1930; Davison and Rabiner 1940; Jacob et al. 1950; Friede and DeJong 1964; Rosenthal et al. 1976; Masters et al. 1979, 1981a,b), this observation did little to advance understanding of the disorder.

The unraveling of the etiology of CJD is a wonderful story that has many threads, each representing a distinct piece of the puzzle. An important observation was made by Igor Klatzo, Carleton Gajdusek, and Vincient Zigas in 1959, when they recognized that the neuropathology of kuru resembled that of CJD (Klatzo et al. 1959). That same year, William Hadlow suggested that kuru, a disease of New Guinea highlanders, was similar to scrapie, a hypothesis also based on light microscopic similarities (Hadlow 1959). Hadlow’s insight was much more profound that...