In their Perspective “A golden era of Nobel laureates” (23 November 2012, p. [1033][1]), J. L. Goldstein and M. S. Brown call attention to nine physicians who trained at the National Institutes of Health (NIH) in fundamental research from 1964 to 1972 and were subsequently awarded Nobel Prizes. They speculated on factors responsible for this remarkable confluence, contrasting current research and medical education to their experiences. As dean of a research-intensive medical school who also trained at NIH, I offer some alternative perspectives. ![Figure][2] CREDIT: WIKIMEDIA COMMONS The NIH was a magical environment for biomedical research during the 1960s and 1970s. Many young physicians seeking academic careers—and some also wishing to avoid the military draft—spent time in NIH laboratories, some in combination with specialty training. The scientific environment was intoxicating, research resources seemed virtually unlimited, and scientific excellence was the highest value. Many experienced research success and now populate the leadership of biomedical research and academic medicine. Goldstein and Brown also raised important concerns. The first relates to the tension between basic and translational research. The authors point out that whereas many of their later discoveries had clinical impact, they were not conducting “translational research” while at NIH. Few would contest that important biological research need not be translational. Fundamental inquiry into molecular, cellular, and physiologic pathways is foundational to translational and clinical research. Nevertheless, many who launched research careers at NIH did research aimed at understanding disease. The NIH Clinical Center was a hotbed of bedside-to-bench research. Patients with rare and complex disorders stimulated basic investigations of molecular pathways with mentors in labs only a hallway away. We spend too much time today unproductively parsing the definitions and relative value of basic and translational research. All research should be assessed by one criterion: the novelty, importance, and impact of the insights generated. Less important are the motivation of the scientist (e.g., understanding molecules and cells versus understanding disease), whether research links to health, the model system used (e.g., single molecules, mice, or humans), and the department in which it is conducted. A second issue involves the status of research in medical education today. The authors state that while basic science was core to medical education in the 1960s, science is presented in an abbreviated manner today. I do not recognize this as an accurate description of science education in today's medical curricula, at least at research-intensive medical schools. Since the 1960s, the knowledge base within biomedical science has exploded, while important new areas such as health policy, global health, and biomedical ethics have emerged, requiring curricular choices. MD-Ph.D. programs train physician-scientists, and many schools now require scholarly projects of all students. The authors state that in the 1960s, the “best and the brightest” graduates were expected to pursue research careers. We delight when students pursue research, as many do today. We are also delighted when the “best and brightest” pursue clinical care and innovation, education, global health, and policy. Biomedical science is critical to the development of new treatments, but is one of several core missions of medical schools, as reflected in the diverse choices that medical students make. Goldstein and Brown are concerned that NIH has shifted focus from basic science and “curiosity-driven” research to translational research and “big science.” I have considerable sympathy for this view. Research into fundamental mechanisms is critical, and selectively diminished support for such research threatens the scientific enterprise and human health. The development of consortia and “big data” approaches arose from the hypothesis that they enabled discoveries otherwise impossible. Some, such as the human genome project, have fulfilled much if not all of their promise. With others, the jury is still out. The balance between individual curiosity-driven research into basic mechanisms and disease pathogenesis versus big science consortia will evolve, though it's virtually certain that both will be necessary. The nine Nobelists are products of an NIH program in which physician trainees were instilled with passion for fundamental research, and the opportunity for medical students and physicians to be exposed to and inspired by great science is as important now as it was then. But the many opportunities and challenges facing medicine and research today suggest that a more complex solution will be needed. The path forward will determine our success in both biologic discovery and in applying these discoveries to improve the health of the population. [1]: /lookup/doi/10.1126/science.1231699 [2]: pending:yes
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Feb 27, 2024
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