A Golden Era of Nobel Laureates

The award of the 2012 Nobel Prize in Chemistry to Robert Lefkowitz brings to nine the number of Nobel laureates who trained in research at the United States National Institutes of Health (NIH) between 1964 and 1972—a remarkable outpouring over such a short period from a single biomedical institution (see the figure). Was there something particular about these recipients, the time, and the place that account for this unprecedented record? We were among the nine, and the parallels in our experiences are striking. All of us graduated from medical school before entering NIH, and all (except Alfred Gilman) took residency training. Gilman and Ferid Murad were the only M.D.-Ph.D.s in the group. For the rest of us, NIH provided our first intense research experience. Some of our mentors were Ph.D.s and some were M.D.s, but they all worked in reductionist systems focused on fundamental mechanisms. The nine of us studied problems ranging from protein synthesis in bacteria to hormone receptors in animal cells. Despite our clinical training and the fact that some of us had patient care duties, our science was far removed from the bedside. The sharp contrast between the uncertainties of the bedside and the relatively “pristine” world of the laboratory provided the stimulus that drove us to pursue careers in fundamental research. The research experience at NIH in the 1960s was intense. Distractions were few. Many of us knew each other, had heated discussions about our research, and wondered whether we had the ability to succeed in a laboratory-based career. After finishing our training, it is surprising that none of us stayed at NIH. We either joined clinical departments or basic science departments in medical schools. Regardless, we all addressed fundamental problems that were relevant to medicine, making primary use of the tools of biochemistry, supplemented with molecular biology as those methods became available. It is noteworthy that four of us received our prizes for discovery of receptors [low-density lipoprotein (LDL) receptors, G protein–coupled receptors, and odorant receptors], and two were honored for discovery of receptor-signaling mechanisms (G proteins and nitric oxide). In the nonreceptor arena, two laureates elucidated a basic mechanism of cancer, and one discovered a new form of infectious neurologic disease. Although none of us performed “translational research,” as currently in vogue, our discoveries influenced drug discovery, medical practice, and human health. ![Figure][1] The Nobel nine. Listed are the Nobel Prize winners who trained at NIH in the years 1964 to 1972. NHLBI, National Heart, Lung, and Blood Institute; NIAID, National Institute of Allergy and Infectious Diseases; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases. CREDIT: Y. HAMMOND/ SCIENCE It is not a coincidence that the 1960s was the decade of the Vietnam War and the doctor draft. Service at NIH substituted for military service in Vietnam, which led some of us to apply to NIH instead of an academic institution. The draft exemption evoked a huge increase in the number of applicants for NIH fellowships. As a result, NIH had its pick of fellows with the strongest academic records. While these factors were important, they would have amounted to nothing if we had not encountered the excitement and rigor then in place at NIH. As research fellows at NIH, we trained with brilliant scientists who had been appointed in previous years. Credit is due to the courageous leaders of the various institutes who chose to appoint basic scientists even when their work did not deal directly with the disease-oriented mission of the institute. Five NIH-career scientists have been honored with Nobel Prizes: Marshall Nirenberg (1968), Julius Axelrod (1970), Christian Anfinsen (1972), D. Carlton Gajdusek (1976), and Martin Rodbell (1994). Four of them were Ph.D. basic scientists, and one (Gajdusek) was a physician-scientist. All five were dominant forces at NIH when we nine were there. Scores of distinguished scientists were trained at NIH in the 1960s, including many who earned election to the U.S. National Academy of Sciences. Others achieved distinction in other ways. Indeed, a substantial portion of the faculties of American medical schools trained at NIH in this remarkable period. Will a single biomedical institution ever again train nine Nobel laureates in a single decade? Under the current conditions, it seems unlikely. The focus of medical schools in the United States has changed. In the 1960s, basic science was at the core of medical education. The brightest graduates were expected to advance their discipline through scientific investigation. Today, medical school curricula tend to condense basic science teaching to a few months instead of the traditional two preclinical years, and the courses focus on a restricted set of disease-relevant “facts” with little to no discussion about where those facts came from or that facts will change as science advances. The joy of finding new facts or overturning old ones is no longer transmitted to students. As well, clinical departments have expanded geometrically as medical schools compete with private hospitals by amassing huge clinical programs. The few scientifically oriented faculty in clinical departments have been diluted to irrelevance by pure clinicians. No wonder that few medical students are choosing to follow paths in basic research. The research emphasis of NIH has gradually shifted. The primary focus is no longer on acquisition of knowledge in basic biological mechanisms. Current emphasis on “translational research” relegates basic science to a back burner. What has been lost is the conviction that progress in medicine rests ultimately on a fundamental understanding of physiology. Individual curiosity-driven science has been replaced by large consortia dedicated to the proposition that gathering vast amounts of correlative data will somehow provide the answer to life's fundamental questions. Is it likely that the best and brightest medical students can be funneled into settings where they can reinforce each other and be inspired by brilliant mentors? If it were to happen, it would require NIH to support teaching and research at a concentrated depth in the basic sciences to open the eyes of medical school graduates to the joy of scientific study. There is a lesson from this golden era of NIH: Ambitious young physicians juxtaposed to cutting-edge basic scientists can themselves make fundamental discoveries. Hopefully, this lesson will help to reconfigure the future. [1]: pending:yes