Ernst Knobil

Ernst Knobil

1926-2000

Ernst Knobil was born in Berlin, Germany, in 1926 to parents of Austrian lineage. The family moved to Paris in 1930 where he attended primary school and the Lycee Claude Bernard. Although this latter school was eponymous for one of the fathers of modern physiology it reportedly had no decisive role for Ernst's subsequent choice of physiology as a career. His family immigrated to the United States in 1940, and in 1942, at the age of 15, he began undergraduate studies at Cornell University. Two years later, he elected to interrupt his studies and enlisted and served in the US Army for two years. He then returned to Cornell to obtain his BS degree in 1948.

At this juncture he decided to definitely pursue a scientific career, and he remained at Cornell in the laboratory of Samuel Leonard, obtaining his PhD in Zoology in 1951. He then took a postdoctoral fellowship with Roy Greep, a previous classmate of Leonard, at the Harvard School of Dental Medicine. In 1953 he joined the faculty in Physiology at Harvard Medical School, being named a Markle Scholar from 1956-1961. The training and experience with Leonard and Greep were to launch a remarkably productive career in physiologic endocrine research lasting over five decades.

During his time at Harvard he made the seminal discovery that only growth hormone from the monkey pituitary gland was able to have an effect in the monkey. This, at the time, innovative finding of a species specificity of pituitary growth hormone led to subsequent major advancement in understanding the physiology and pathophysiology of growth hormone in the human species, including therapeutic approaches. In recognition of this contribution he received the Ciba Award, now the Ernst Oppenheimer Award, from the Endocrine Society, the first of many prestigious awards he was to receive throughout his career.

In 1961 he left Harvard to found the new Department of Physiology at the University of Pittsburgh. As the first Richard Beatty Mellon Professor and Chairman, he built the department over the next 20 years into an internationally recognized teaching and research program. Over his career he personally trained 69 postdoctoral fellows and 6 graduate students, many of whom have since become leaders of university physiology departments and research endeavors throughout the world. In 1994, his previous fellows organized a two day Ernst Knobil Symposium to portray the effect he had had on their professional careers.

While at Pittsburgh he established the Center for Research in Primate Reproduction, and therein directed his research towards understanding the control of the ovulatory menstrual cycle in the primate. He and his associates, through a series of major discoveries, were able to define a functional model of the primate menstrual cycle and to delineate its neuroendocrine control.

Initially, his primate laboratory developed working immunoassays for the measurement of progesterone, estradiol, follicle stimulating hormone and luteinizing hormone {LH} which permitted for the first time an accurate description of the time course of the blood borne hormones throughout the primate ovarian cycle. From this work Dr. Knobil proceeded to demonstrate that the cycle was controlled by the negative and positive feedback of ovarian estradiol on pituitary gonadotropin secretion. During these investigations he also observed that there was episodic secretion of LH and hypothesized that this pulsatile secretion was due to the rhythmic release of gonadotropin releasing hormone {GnRH} from the hypothalamus. He showed that GnRH had to be administered in pulsatile fashion to result in gonadotropin secretion, and reported that reductions in frequency could result in anovulation. He was also able to induce ovulatory menstrual cycles in the premenarcheal monkey with pulsatile GnRH infusions. Finally he was able to localize the neuronal system controlling this episodic release, the so-called GnRH pulse generator to the arcuate nucleus of the hypothalamus. He showed that release of LH was associated with a marked increase in electrophysiologic activity in the hypothalamus. These series of experiments and observations provide the cornerstone of all current approaches to gonadal function and dysfunction and have led to major clinical advancement in dealing with infertility, sexual precocity, along with treatment programs for breast and prostate disease.

In 1981, Ernst left Pittsburgh to become the H. Wayne Hightower Professor and Dean of the University of Texas Medical School at Houston. He also established the Laboratory for Neuroendocrinology at the medical school and continued his work on the pulse generator and electrophysiological analysis of the adenohypophysial neuroendocrine system for the first three years during his deanship and thereafter until shortly before his battle with pancreatic cancer was lost.

Dr. Knobil's contributions to science and education go beyond his basic research and teaching. He provided leadership and wisdom to the innumerable committees that he served on for the NIH. He was also a member of the National Academy of Sciences and the American Academy of Arts and Sciences, was a Past President of the American Physiological Society, the Endocrine Society and the International Society of Endocrinology, and an Honorary Member of many international societies. In 1989 he was named the Ashbel Smith Professor by the regents of the University of Texas in recognition of his lifetime contributions. He was also the recipient of the Koch Award and the Hartman Award, the highest awards of the Endocrine Society and the Society for the Study of Reproduction respectively.

Although strongly devoted to research, science and medicine, and the pursuit of excellence, he also found time to enjoy sailing with his wife, Julie, on the waters of the Gulf of Mexico. In addition, he was a devoted fan of Alfa Romeos, and maintained them, as one might expect, in spotless fashion. I can vividly recall the impish grin on his face when he showed me with obvious pride his certificate from the Bob Bondurant School of High Performance Driving at the International Raceway in Sonoma, California which he had attained in 1978.

Ernst Knobil has made long lasting contributions to our understanding of ovulatory function which has in turn resulted in significant improvement in medical care. He also had a major positive impact on young scientists and physicians in his role as mentor. His quest for excellence, and his integrity, sincerity, and candor are ideals for all of us to attempt to emulate. He certainly enriched the lives of many, and as colleagues and friends we were privileged to have known him and worked with him.

Submitted by Robert K. Creasy, M.D.

Return to In Memoriam