Ernst Knobil

52nd APS President (1979-1980)
Ernst Knobil
(b. 1926)

Knobil was born in Berlin, Germany, as a boy attended the Lycee Claude Bernard in Paris, and then continued his education in science in the United States at Cornell University (B.S., 1948; Ph.D., 1951) after two years of service with the U.S. Army (1944-46). From 1951 to 1953 he was a Milton Research Fellow in the laboratory of Roy O. Greep of the Harvard School of Dental Medicine. This led to an appointment in the Department of Physiology of the medical school (1953-61), which he left to become Richard Beatty Mellon professor and chairman of the Department of Physiology at the School of Medicine at the University of Pittsburgh (1961-81). From 1974 to 1981 he was also director of the Center for Research in Primate Reproduction at Pittsburgh. In 1981 he moved again to become dean of the School of Medicine at the University of Texas Health Science Center (1981-84), H. Wayne Hightower Professor of Physiology, and director of the Laboratory for Neuroendocrinology (1981-). He now continues as a full-time investigator in his laboratory.

Knobil's membership in APS dates from 1955. He was a member of the Editorial Board of the Society's journals from 1960 to 1966 and of the Editorial Board for the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology from 1976 to 1978. From 1979 to 1982 he was editor of the American Journal of Physiology: Endocrinology and Metabolism. With Wilbur Sawyer he edited the volumes on the pituitary gland and the hypothalamus of the Handbook of Physiology. His first committee service was on the Committee for the Use and Care of Animals (1962-67). He served on Council from 1969 to 1972 and later served on the Ray G. Daggs Award Committee (1976-79). He became president elect in 1978. As president he was instrumental in increasing APS activities in public affairs with a focus on the issue of animal experimentation.

Early in his career Knobil was honored by designation as a Markle Scholar at Harvard (1956-61). He received the Ciba Award in 1961 and the Fred Conrad Koch Award in 1982, both from the Endocrine Society. In 1983 he was chosen for the Carl G. Hartman Award of the Society for Study of Reproduction, and in 1985 he was given the Axel Munthe Prize in Reproduction. He has the degree Dr. Hon. Causa from the University of Bordeaux (1980) and an honorary Sc.D. from the Medical College of Wisconsin (1983). He is a fellow of AAAS (Boston) and an honorary fellow of the American Association of Obstetricians and Gynecologists, as well as of the American Gynecological Society.

Outside APS, Knobil has served on editorial boards for Endocrinology (1959-75), Annual Review of Physiology (1968-77; editor-in-chief, 1974-77), Psychoneuroendocrinology (1974-77), Neuroendocrinology (1976-80), and Endocrine Reviews (1980-84). A recent addition to the list is Chronobiology International (1984-). For AAMC, Knobil served as a member of the Executive Council for three years (1971-74), of the Administrative Board of its Council of Academic Societies for four years (1970-74), and more recently as a member of the Steering Committee on Information Sciences and Medical Education (1984-). He was a member of the Council of ACDP (1968-71; president, 1969-70); in 1983 he received its Distinguished Service Award. Of the Deutsche Gesellschaft fur Endokrinologie he is an honorary member, as he is of the Japan Endocrine Society; he holds membership also in Great Britain's Society for Endocrinology. Other memberships include the American Society of Zoologists, the International Society for Research in Biology of Reproduction, the Society for Study of Reproduction, the International Society for Neuroendocrinology, the Society for Experimental Biology and Medicine, and the National Society for Medical Research, which he served as a member of the Board of Directors (1977-79). For three years (1968-71) he was a member of the Council of the Endocrine Society (president, 1976-77). He has held a variety of responsibilities for the International Society of Endocrinology, especially in reference to its international congresses; from 1976 to 1984 he was chairman of its Executive Committee and served as president from 1984 to 1988. From 1980 to 1983 he was a member of the U.S. National Committee for IUPS and is currently chairman of its Commission on Endocrinology (1982-).

Many organizations and institutions have asked Knobil to serve as consultant. For NIH he served on the Human Growth and Development Study Section (1964-66), the Reproductive Biology Study Section (chairman, 1966-68), the Advisory Committee on Primate Research Centers (1969-73), the Contraceptive Development Branch (1969-71), the Medical Advisory Board of the National Hormone and Pituitary Program (1980-83), and the Planning Committee for Developmental Endocrinology and Physical Growth of the National Institute of Child Health and Human Development (1984-), an institute he had earlier served as a member of the Population Research Committee of the Center for Population Research (1974-77). For three years (1966-69) he was a member of the National Advisory Council of the Institute of Laboratory Animal Resources of NAS. He served on the Physiology Test Committee of the National Board of Medical Examiners (1970-74) and on the Liaison Committee on Medical Education of the American Medical Association (AMA) and AAMC (1971-74). In addition, he has been asked to serve as consultant to the University of Michigan School of Medicine (1973), Harvard Medical School (1973-74), the Ford Foundation (1974-75), the Uniformed Services University of Health Sciences (1975), the Human Reproduction Unit of the World Health Organization (1976-), the University of Texas Health Science Center at Houston (1979-80), and the Advisory Committee of the Searle Scholars Program (1981-82).

Knobil's research has generated widespread interest both in this country and abroad. He has been invited to deliver the following lectures: Bowditch Lecture of APS in 1965; Gregory Pincus Memorial Lecture of the Laurentian Hormone Conference in 1973; and in 1974 the Upjohn Lecture of the American Fertility Society, the Kathleen M. Osborn Memorial Lecture at the University of Kansas School of Medicine, and the First Annual Hopkins-Maryland Lecture in Reproductive Endocrinology. He gave the Karl Paschkis Lecture of the Philadelphia Endocrine Society in 1975 and in 1978 was Sigma Xi Lecturer at the University of Florida and Second Alza Lecturer in Palo Alto. In 1979 he gave two lectures: the R. D. O'Brien Lecture at Cornell University and the First Transatlantic Lecture of the Society for Endocrinology of Great Britain. The following year (1980) he presented the Lawson Wilkins Lecture of the Pediatric Endocrine Society and the Scientific Lecture for the American Gynecological Society. In 1981 he was at Johns Hopkins for the Second Bard Lecture, in San Francisco for the Sixth Herbert McLean Evans Memorial Lecture, and at the University of Uppsala for the Fourth Carl Gemzell Lecture. Since then he has given the Fourth Annual James H. Leathem Lecture at Rutgers Medical School and the Geoffrey Harris Memorial Lecture of the International Society of Neuroendocrinology, both in 1982; the Ayerst Lecture of the American Fertility Society in 1983; and the Distinguished Guest Lecture for the Society for Gynecological Investigation and the Potter Lecture of Thomas Jefferson University, both in 1984.

Knobil's training in endocrinology involved only two laboratories.

"I began my career as a graduate student in zoology in the laboratory of Samuel L. Leonard, an endocrinologist who was himself a student of F. L. Hisaw and P. E. Smith, two of the founders of American endocrinology. My mentor was a participant in the early development of this discipline in the United States and imparted to me a very personal sense of belonging to this branch of physiology. His Ph.D. thesis recounted the discovery of the ovulatory hormone, now known at LH (Am. J. Physiol. 98: 406-416, 1931). From Leonard, I acquired an abiding love for endocrinology, which has given me immense pleasure and happiness throughout my career. My formal training was completed under the preceptorship of Roy O. Greep, who had been a fellow student of Leonard in Hisaw's laboratory at the University of Wisconsin."

"At Harvard, Greep introduced me to the world of academic medicine, which I entered as an ingenuous postdoctoral research fellow. His unfailing and often undeserved support is directly responsible for the path my professional life has followed. He introduced me to E. M. Landis in the medical school, who offered me an instructorship in his department (1953) the year before he became president of the APS. My years as a member of his faculty had a profound influence, in both style and substance, on the development of the Department of Physiology at the University of Pittsburgh School of Medicine, which I served as founding chairman for twenty years."

"My scientific contributions worthy of any note have all focused on the physiology of the primate adenohypophysis (e.g., refs. 2 and 3). My laboratory established the zoological specificity of growth hormone with the finding that only growth hormone of primate origin is physiologically active in primates (4). This discovery led to the development of a radioimmunoassay for human growth hormone (6) and permitted a host of investigations dealing with control of growth hormone secretion (5, 7)."

"A decade or so ago we began a systematic investigation of control of the menstrual cycle, with the rhesus monkey as an experimental animal (10). This was occasioned by recognition of major species differences in control of reproductive processes and of the fact that findings obtained on one species could not necessarily be extrapolated to another. In the course of this effort, we were the first to describe the time course of progesterone during the ovarian cycle of any species (8, 9) and to elucidate the endocrinologic events of early pregnancy. This provided new insight into the control of the corpus luteum and the role of progesterone in regulation of gonadotropin secretion (11)."

"More recently we have delineated the neuroendocrine control system that governs secretion of gonadotropic hormones throughout the menstrual cycle of the rhesus monkey. In sum, it comprises the arcuate nucleus of the hypothalamus, which mediates an hourly discharge of the hypothalamic hormone, GnRH, with relatively simple negative and positive feedback loops between estrogens and the pituitary gland. We now understand control of the menstrual cycle for the first time. Consequently the ovarian cycle of monkeys is understood better than that of any other species (12, 13)."

For his past president's address (14), Knobil abandoned the societal introspection of his immediate predecessors to consider the classic volume by William Harvey, On the Generation of Animals. Because spermatazoa were unknown, being at that time invisible, Harvey remained puzzled as to just what the male fluid may contribute to development and differentiation of the ovum. Knobil noted that Harvey's treatise is "tedious, repetitive, impossible to summarize, encapsulate, or even to sample adequately." It was begun when he was a student in Padua (ca. 1600), under the teaching of Fabricius, and apparently concluded only shortly before he was persuaded, somewhat against his better judgment, to permit its publication (1651). Knobil remarked that it is five times longer than Harvey's De Motu Cordisand, one judges, five times less conclusive. Nevertheless, Knobil found it to be "vaguely reminiscent" of Claude Bernard's writings.

Commenting on his contributions to neuroendocrinology, one of his friends recently stated that Knobil has qualities that remind one of Claude Bernard, especially in his ability to analyze the integrative and relational aspects of endocrine systems and their controls. Knobil has done this for endocrinology of primates more successfully than anyone of his generation.

Selected Publications

1. Greep, R. O., E. Knobil, F. G. Hofmann, and T. L. Jones. Adrenal cortical insufficiency in the rhesus monkey. Endocrinology 50: 664-676, 1952.

2. Knobil, E., A. Morse, F. G. Hofmann, and R. O. Greep. A histologic and histochemical study of hypophyseal-adrenal cortical relationships in the rhesus monkey. Acta Endocrinol. 17: 229-238, 1954.

3. Knobil, E., R. C. Wolf, R. O. Greep, and A. E. Wilhelmi. Effect of a primate pituitary growth hormone preparation on nitrogen metabolism in the hypophysectomized rhesus monkey. Endocrinology 60: 166-168, 1957.

4. Knobil, E., A. Morse, R. C. Wolf, and R. O. Greep. The action of bovine, porcine and simian growth hormone preparations on the costochondral junction in the hypophysectomized rhesus monkey. Endocrinology 62: 348-354, 1958.

5. Knobil, E., and R. O. Greep. The physiology of growth hormone with particular reference to its action in the rhesus monkey and the species specificity problem. Recent Prog. Horm. Res. 15: 1-69, 1959.

6. Knobil, E., and R. O. Greep. The detection of growth hormone in plasma. In: Hormones in Human Plasma, edited by H. N. Antonaides. Boston, MA: Little, Brown, 1960.

7. Knobil, E. Tenth Bowditch Lecture. The pituitary growth hormone: an adventure in physiology. Physiologist 9: 25-44, 1966.

8. Neill, J. D., E. D. B. Johansson, and E. Knobil. Levels of progesterone in peripheral plasma during the menstrual cycle of the rhesus monkey. Endocrinology 81: 1161-1164, 1967.

9. Neill, J. D., E. D. B. Johansson, and E. Knobil. Patterns of circulating progesterone concentrations during the fertile menstrual cycle and the remainder of gestation in the rhesus monkey. Endocrinology 84: 45-48, 1969.

10. Monroe, S. E., L. E. Atkinson, and E. Knobil. Patterns of circulating luteinizing hormone and their relation to plasma progesterone levels during the menstrual cycle of the rhesus monkey. Endocrinology 87: 453-455, 1970.

11. Knobil, E. On the regulation of the primate corpus luteum. Biol. Reprod. 8: 246-258, 1973.

12. Knobil, E. On the control of gonadotropin secretion in the rhesus monkey. Recent Prog. Horm. Res. 30: 1-46, 1974.

13. Knobil, E. The neuroendocrine control of the menstrual cycle. Recent Prog. Horm. Res. 36: 53-88, 1980.

14. Knobil, E. William Harvey and the physiology of reproduction. Physiologist 24(1): 3-7, 1981.