I was very pleased and honoured when John Collinge and Michael Alpers invited me to share personal recollections about research on kuru and related diseases during the more than 25 years I spent at the National Institutes of Health (NIH). Such reminiscences must be impossibly arbitrary and awkwardly abbreviated when condensed to such a short contribution, so I hope that readers of this paper and others among the many people involved in the work who survive will forgive my inevitable omissions, failures to remember or to credit worthy contributors, and misunderstandings regarding who first conceived of or initiated various aspects of the research. I shall recount my own history at the NIH and summarize a few selected important scientific achievements for which, I believe, NIH research investigators—taken broadly to include some collaborating investigators—were largely responsible, and I shall add a few personal reminiscences.
In July 1966, I arrived at the laboratory of Daniel Carleton Gajdusek in what was then the National Institute of Neurological Diseases and Blindness (NINDB), one of the NIH in Bethesda, Maryland. I came because I was introduced to Carleton's work with kuru by David Lang, infectious disease physician and my mentor during my last year of residency training in paediatrics at the Massachusetts General Hospital in Boston. I came as a Public Health Service (PHS) officer—the Vietnam War having intensified young physicians' interest in PHS-sponsored research—and was later sent, supported by an NIH Special Fellowship sponsored by Carleton, to what was then the Soviet Union. I returned to his laboratory as a civilian research medical officer late in the summer of 1970 and remained with the NIH programme, participating in studies of kuru and related diseases (transmissible spongiform encephalopathies (TSEs) or prion diseases) and other infectious diseases for the next 25 years. At the end of August 1995, I left the NIH to head a small laboratory at the US Food and Drug Administration (FDA) Center for Biologics Evaluation and Research, where I still work today.
By the time I joined Carleton Gajdusek's research group at the NIH, kuru had already been recognized as a novel degenerative brain disease caused by a ‘slow’ scrapie-like infection transmitted to chimpanzees, and kuru's similarities to Creutzfeldt–Jakob disease (CJD) noted. Other animals and cell cultures were already on test as possible assays for infectivity, and collections of tissue samples from cases of CJD had begun. The group's working hypothesis was that the aetiological agent was probably an unconventional virus. Clarence Joseph Gibbs Jr (Joe Gibbs)—working in borrowed space at the US Department of Interior's Patuxent Wildlife Research Center, where the laboratory's primates and other animals were housed—agreed to train me in medical virology and applied primatology; our very close association lasted until Joe's death. I had the bittersweet honour of delivering Joe's final planned public presentation, an invited talk on the pathogenesis of human TSEs before the FDA TSE Advisory Committee, weeks before he died in February 2001. In July 1966, when I arrived at the NIH, Michael Alpers was a Visiting Scientist at NIH and he, Carleton and Joe had just published a monograph on Slow, latent and temperate virus infections (Gajdusek et al. 1965) that was for many years a definitive source of information on kuru and scrapie and that remains an important historical document. In short, I was neither ‘present at the creation’ of Carleton's NIH laboratory nor did I stay until its end.
Carleton's laboratory at the NIH can be considered to have begun 8 years before I arrived. In 1958 he was appointed Visiting Scientist of NINDB, although, as recorded in correspondence regarding kuru with Joseph E. Smadel (figure 1Farquhar & Gajdusek 1981), NIH had already provided logistical support for fieldwork from the summer of the previous year. Carleton had learned of kuru while a Fellow of the National Foundation for Infantile Paralysis in the Melbourne laboratory of Sir Macfarlane Burnet, who appears to have been considerably less enthusiastic about supporting Carleton's involvement in kuru research than was Smadel. In 1956, Smadel had left the Walter Reed Army Institute of Research, Washington, DC, where he had worked with Carleton from 1952, to become Associate Director of NIH. At the NIH, Smadel was the earliest strong proponent of Carleton's ambitious research plans and occupied a position where he could help realize them; Smadel was clearly responsible for recognizing Carleton's promise, inviting him to the NIH, fostering his early career there, and introducing and recommending him to suitable collaborators at the NIH. Many subsequent NIH administrators were also very supportive, at least until 1994.
Gradually, over the years, the main object of TSE research in the NIH laboratory shifted from kuru to other diseases—probably due to a steady decline in kuru cases after the 1960s and the growing number of other TSE cases referred to the group. But kuru remained the first disease among equals when competing for Carleton's attention. There was no time after which kuru research stopped, and I cannot discriminate meaningfully between those NIH colleagues who worked directly with kuru and those who did not—Carleton tried to engage us all in one aspect of kuru or another.
The NIH laboratory remained under Carleton's direction for approximately 38 years; in January 1995, he announced to NIH administrators his intention to end the research programme (prompting me to take another job later that year), and he left NIH the next year. Staff remaining in the laboratory continued to conduct TSE research for 8 more years, as Joe Gibbs attempted to bring Carleton's programme to an orderly conclusion. With the retirement, in July 2004, of Paul Brown, the last investigator actively engaged in TSE research on the NIH Bethesda campus, Carleton's laboratory ceased to exist, although the NIH continues to maintain some laboratory records and a collection of research samples. During his last years at NIH, Paul Brown became the very effective chairman of the FDA's TSE Advisory Committee, and he remains a sought-after consultant.