Kuru: a half-opened window onto the landscape of neurodegenerative diseases

Kuru, the first human neurodegenerative disease classified as a transmissible spongiform encephalopathy (TSE), prion disease or, in the past, as a slow unconventional virus disease, was first reported to Western medicine in 1957 by Gajdusek and Zigas. A complete bibliography of kuru through 1975 has been published by Alpers et al. The solution of the kuru riddle opened a novel field of biomedical sciences and initiated more than a quarter of century of research that has already resulted in two Nobel prizes (to D. Carleton Gajdusek in 1976 and to Stanley B. Prusiner in 1997) and was linked to a third (to Kurt Wüthrich who determined the structure of the prion protein). Kuru research has impacted the concepts of nucleation-polymerization "protein cancers", and "conformational disorders". This paper is dedicated to Dr. Carleton Gajdusek on the occasion of his 80th birthday. "Kuru" in the Fore (Fig. 1) language means to shiver from fever or cold. The Fore used the noun of the kuru-verb to describe the always fatal disease which decimated their children and adult women but rarely men. It has been and still is restricted to natives of the Fore linguistic group at Papua New Guinea's Eastern Highlands and those neighboring linguistic groups which exchange women with Fore people (Auiana, Awa, Usurufa, Kanite, Keiagana, late, Kamano, Kimi; Fig. 2). Neighboring groups into which kuru-affected people did not settle through marriage or adoption, such as the Anga (Kukukuku), and remote lagaria, Kamano and Auiana people, were not affected. It seems that Kuru first appeared at or shortly after the turn of XX century in Uwami village of Keiagana people and spread to the Awande in the North Fore where the Uwami had social contacts. Within 20 years it had spread further into the Kasokana (in 1922 according to Lindebaum) and Miarasa villages of North Fore, and a decade later had reached the South Fore at the Wanikanto and Kamira villages. Kuru became endemic in all villages that it entered and became hyperendemic in the South Fore region. All native informants stressed the relatively recent origin of kuru. Interestingly enough, when kuru first appeared, it was considered poetically by Fore as similar to "the swaying of casuarinas tree" and kuru was labeled cassowary disease to stress the similarity between cassowary quills and "waving casuarinas fronds". Gajdusek first learned about kuru from Dr. Roy Scragg, director of Public Health in Port Mosby, who had already read a report sent by Dr. Vin Zigas to Dr. John Gunter in 1956. In March 1957, Gajdusek joined Zigas, who at that time was a medical patrol officer in Kainantu, Eastern Highland District of the Territory of Papua New Guinea.