Perspectives in Biology and Medicine

THE ROLE OF CLINICAL INVESTIGATION IN MEDICINE: HISTORICAL PERSPECTIVE FROM THE ROCKEFELLER UNIVERSITY JULES HIRSCH* There is little doubt that the science of clinical investigation, as widely practiced in academic settings in this country 50 years ago, is now disappearing [I]. Some forms of clinical research persist in order to apply the fruits of modern biologic science to the prevention, diagnosis, and alleviation of disease. Tissues and body fluids from hospitalized patients are sampled for research. New drugs and other treatments are evaluated in hospitalized patients in special settings or clinical research centers. Likewise, the outcome of different methods of diagnosis, screening, and treatment is widely observed. But a special investigational clinical encounter, popular in the past, now rarely occurs. I refer to in-patient observation with testing and measuring, often in consultation with colleagues and students, for the purpose of understanding the pathogenesis of a disorder. Often this was done with only a small number of patients, without protocols made so detailed and rigid that modification in the study could be made on the basis of day-to-day observations. Physicians who made major scientific advances utilizing encounters with hospitalized patients in this type of clinical research were recently considered a "vanishing breed" or an "endangered species," and now they have practically vanished. Whether due to financial constraints, legal issues, or fundamental change in the nature of the biologic sciences, the meticulous and deliberate study of hospitalized patients for the purpose of formulating questions about disease and then generating scientific data is now rarely undertaken. It can be argued that it is no longer economically feasible to extend hospitalization for research; the necessary funds might be more effectively applied to studies in laboratory The author wishes to express his particular gratitude to E. H. Ahrens, Jr., for many insights into the problems of clinical investigation and to Rudolph L. Leibel and Michael Rosen baum for critical readings of the manuscript.»Rockefeller University Hospital, 1230 York Avenue, New York, NY 10021.© 1997 by The University of Chicago. All rights reserved. 0031-5982/97/4004-1032101.00 108 Jules Hirsch ¦ Clinical Investigation in Medicine settings to obtain the answers to clinical questions. Yet, there are funded clinical research beds in some academic health care centers, which are often unfilled [2] . As for the legal and ethical issues which arise when human illness becomes a matter for study, these are undoubtedly complex, but can yield to the diligent efforts of institutional review boards. The reasons for the changing pattern of clinical research are more likely to be found elsewhere. The current paradigm of biological science emphasizes the universality of the DNA code, and it is widely believed that all the mysteries of health and disease can be solved by the use of any life form studied in the laboratory; the study of mice, yeasts, bacteria, cells, and subcellular materials is so informative as to render study of the whole organism unnecessary and inefficient. A logical derivative of this belief is that only the final phase of application of laboratory findings, called "translation," requires human subjects. Clinical studies are a last step after new information has been carefully shaped, when a product is poised for clinical application . Furthermore, the methods and practice of molecular genetics and molecular biology may have become too complex and demanding for the involvement of physicians engaged in the care of patients. As compared with the scientist, a physician needs other skills, has other demanding commitments , and thus can no longer be a master of both science and medicine . Therefore, those scientific advances most relevant to the amelioration of human disease may no longer be generated by clinicians, although clinicians will use products generated by the findings of laboratory scientists for the care of their patients. If this analysis is correct, then a long historical connection between attending to the sick and the development of biologic science will come to an end in our time. Before this divorce of science and medicine is finalized, a reminiscence of the marriage might give insight into what will be lost when the two bid each other goodbye. It was early in this century that medicine in this country drew close to science...