Address all correspondence and requests for reprints to: Dr. Ernst Knobil, The University of Texas, Houston, Health Science Center, 6431 Fannin, MSB 7.128, Houston, Texas 77030.
Roy Orval Greep, the 45th President of The Endocrine Society, died on December 5, 1997, in his 92nd year, thus ending a richly rewarding and remarkably accomplished life. His illustrious career was predestined by his early intellectual independence, his insatiable curiosity about the natural phenomena that surrounded him as a boy growing up on a Kansas farm, and by his voracious appetite for the acquisition of new knowledge. These germinal traits were abetted by deeply ingrained habits of hard work, patience, and perseverance that he attributed to his forefathers of pioneering Swedish stock.
Roy Greep began his academic career in a one-room schoolhouse in Longford, KS, population 198, advanced to the 2-yr high school recently established in that community, but dropped out 6 weeks later to, in his words, "pursue interests of more soul-satisfying nature: herding cattle, hunting coyotes, trapping and so forth." Three years later, however, he was persuaded by the perspicacious principal of the high school and by the onerous and relatively unrewarding labors on the farm to return to the classroom. He was admitted to Kansas State Agriculture College in Manhattan, KS, but failed the qualifying examination administered some weeks later. By the time the results became known, however, Roy Greep had already distinguished himself as an outstanding student, was awarded a teaching assistantship, and the qualifying examination not withstanding, was clearly fit for higher education. In his senior year, he was invited to join a research project devoted to the isolation of sex hormones from the urine of cows. Such were not found, but this work forged a link with F. L. Hisaw, one of the founders of American endocrinology, who had similar negative findings. In 1930, this led to an invitation to join Hisaws high-powered laboratory at the University of Wisconsin as a graduate student. The research emphasis in Hisaws group was on the gonadal stimulating activity of pituitary extracts that eventuated in the identification of two factors, FSH and LH, a most controversial matter at the time.
Continued purification of the gonadotropic hormones required the availability of hypophysectomized rats, a preparation perfected by P. E. Smith a few years before. Roy set out to master the technique, working late at night and in secrecy "so as not to arouse expectations." In this endeavor, he was assisted by his wife Eunice, whom he married before leaving Kansas and who remained his companion and helpmate for 66 yr until her death in June of 1997. They attained success in a few weeks of exhausting effort and thus enabled the experiments of Hisaws group that established, unequivocally, the existence of the two gonadotropic hormones. In 1935, the mastery of hypophysectomy and undoubtedly other attributes, prompted Hisaw to invite Roy, who had just received his Ph.D., to accompany him when he was called to a professorship in the Biological Laboratories at Harvard University. In the succeeding three years as a postdoctoral fellow, Roy extended his observations on the actions of gonadotropins in several species and with Ted Astwood, also a fellow in Hisaws lab at the time, demonstrated the luteotropic activity of placental extracts. It is during this time that Greep made the prescient observation that pituitary glands transplanted to the sella turcica of hypophysectomized rats supported normal growth and reproduction, whereas pituitaries transplanted elsewhere in the body, although revascularized equally well, were seemingly inactive. He also made the crucially important observation that normal male and female function could be reestablished in this manner regardless of the donors age or gender. In other words, sexual dimorphism or sexual maturity were not properties intrinsic to the pituitary gland. These seminal observations, published as a brief paper in 1936 (Proc Soc Exp Biol Med 34:754, 1936) presaged the revolution in endocrinology that dethroned the pituitary gland as the "conductor of the endocrine symphony" and placed the hypothalamus in that lofty position thus creating the new discipline of neuroendocrinology that dominates the field to this day.
In 1938, Roy Greep was recruited by Harry B. Van Dyke to join the newly established Squibb Institute for Medical Research. It was there, in collaboration with van Dyke and Chow, that he succeeded in preparing highly purified FSH and LH from swine pituitary glands that were not significantly improved upon in succeeding decades. The recent availability of recombinant human FSH confirmed the controversial early observation of Greep and his colleagues that purified FSH alone given to hypophysectomized subjects, while arguably causing a modicum of follicular development, had no steroidogenic activity. During this time, the group using the finding that LH administered to immature hypophysectomized rats increased the weight of the prostate, developed the specific assay that was the gold standard for this gonadotropin for many years.
In the process of hypophysectomizing rats, a procedure that involves extension of the head of the anesthetized animal by stretching a rubber band around its incisors, Greep, who had reduced the technique to a rapid, highly mechanical exercise, found that on one occasion the rubber band kept slipping off its maxilla. On closer examination, he found that this rat had no front teeth and this marked the beginning of yet another twist in his serendipitous career. Rather than discarding this animal and getting on with the task at hand, which most others would have done, he put it aside and eventually discovered, by judicious breeding, that the toothlessness was a recessive trait inherited in simple Mendelian fashion. These striking findings caught the attention of the dental community and so it came that, in 1944, Greep was invited to present a seminar at the newly created Harvard School of Dental Medicine and shortly thereafter was offered a position there as an assistant professor of Dental Science with a joint appointment as a Teaching Fellow in Anatomy at the Harvard Medical School. He became Dean of the Harvard School of Dental Medicine just 8 years later. The Dental Research Laboratory, as his enterprise was called, generated a number of studies based on the toothlessness trait and the role of PTH in this anomaly as well as on tooth development in general. In addition, he conducted a major investigation with Helen Wendler Deane of the Department of Anatomy on the cytology of the adrenal cortex in the rat and how this was influenced by hypophysectomy, adrenal steroid administration as well as sodium and potassium intake. These studies led to the important observations that while hypophysectomy led to a reduction in the size of the inner two zones, it had no effect on the width of the zona glomerulosa, that electrolyte deprivation caused an enlargement of the zona glomerulosa without perturbing the others, and that the adrenal cortical hypertrophy caused by ACTH administration was largely limited to the zonae fasciculata and reticularis. These findings, coupled with the knowledge that, in the rat, hypophysectomy does not lead to major disturbances in electrolyte metabolism, led Greep and Deane to the prescient conclusion that the zona glomerulosa must be the source of the elusive substance that the chemists had been unable to crystallize from the "amorphous fraction" of adrenal cortical extracts that had a high sodium retaining activity. They further reasoned from these morphological observations that the secretion of this substance was independent of ACTH and that the inner two zones, which were dependent on ACTH, secreted the glucocorticoids, findings that were extended to rhesus monkeys. These conclusions anticipated the discovery of aldosterone (first dubbed electrocortin) by several years and the demonstration that its principal source was indeed the zona glomerulosa.
Roy Greeps active participation in research understandably diminished following his appointment as Dean of the Harvard School of Dental Medicine in 1952, the first dental school dean in the U.S. with only a Ph.D. after his name, a post he held for 15 yr and which he said he much enjoyed after weathering the initial hostility of his peers. During this time, however, his laboratory increased in size and vigor and continued to attract a number of fellows who were able to pursue their own research projects with considerable freedom and independence but always with the unstinting and abiding support of "the Chief." It was during this period that the zoological specificity of GH was firmly established with the demonstration that only GH preparation of primate origin was effective in primates (humans and monkeys), whereas other GH preparations were not. These observations led to the establishment of the first RIA for human GH and, thereby, the elucidation of the physiology of this peptide in humans as well as to the effective treatment of pituitary dwarfism in children.
Roy Greeps interest in reproduction extended far beyond the research laboratory. In the latter part of his professional life he became passionately interested in the unbridled growth of the worlds population and the impact of this phenomenon on the welfare of humankind. His active participation in this global arena was recognized by Harvard University upon his retirement from the Deanship of its dental school in 1967 by his appointment as the John Rock Professor of Population Studies in the School of Public Health and Director of the newly created Laboratory of Human Reproduction and Reproductive Biology on the campus of the Harvard Medical School, an enterprise in the creation of which he played a major role. He was a member of the World Health Organization Expert Advisory Panel on Human Reproduction from 1963 until 1979 and served as consultant and advisor to a number of organizations devoted to the issue of fertility, infertility, and contraception including the pioneering initiative of the American Academy of Arts and Sciences entitled Human Fertility and Population Problems, published under his editorship in 1963.
Following his retirement from Harvard University in 1971, he labored full time for the Ford Foundation as Project Director for a Review of Reproductive Sciences and Contraceptive Development, a massive endeavor that eventuated in the publication of two highly praised and influential volumes entitled Reproduction and Human Welfare, A Challenge to Research, and Frontiers in Reproductive and Fertility Control, respectively.
Roy Greep served The Endocrine Society and the endocrinological community at large with energy and selfless devotion for decades beginning with his appointment to the Editorial Board of Endocrinology in 1950 and becoming its Managing Editor (now Editor-in-Chief) 2 yr later when the journal was in a state of shocking disarray. Greep recounted in his memoirs that the issues of the Journal were months behind, the publishers were threatening to withdraw, and "when the files arrived, they contained eighty-nine manuscripts in envelopes that had never been opened." Roy enlisted his wife Eunice to be editorial assistant and secretary and they labored every evening, often late into the night, doing all the redactory work including the correcting of galley and page proofs and the construction of author and subject indices in addition to all the other chores associated with the editorship of a journal. This was done in the Greep residence in Brookline, without assistance and without compensation. In the 10 yr that the Greeps managed the Journal, not only was it rescued from a certain demise, but it grew in size, scope, and prestige, attaining an honored place in the growing array of scientific journals. In addition, Greep edited and co-edited a number of journals and books, most notably, the eight volume "Section on Endocrinology" of the Handbook of Physiology published by the American Physiological Society. This was a monumental undertaking accomplished over a period of 8 yr, and encompassed in depth and in detail the best of endocrinological research in all its dimensions. The second edition of this important contribution to Endocrinology is just now being readied for publication under the editorship of one of Greeps scientific grandsons, H. M. Goodman.
Greep was one of the founding fathers of the Laurentian Hormone Conference, the annual centerpiece of endocrine research that, for many years, was by invitation only. He was on its board of directors from 1967 to the time of his election as its President in 1972, a post he filled with devotion and distinction until 1985.
He served The Endocrine Society as Chairman of its Publication Committee and as its President in 1965. He was instrumental in the founding of the International Society of Endocrinology and was elected president of that organization, as well as honorary president of the fifth International Congress of Endocrinology held in Hamburg in 1976. He also served as President of the Society for Experimental Biology and Medicine.
The foregoing and Roy Greeps myriad other contributions to endocrinology, far too numerous to mention in this brief recounting, were recognized by the highest honors that the field can bestow. From The Endocrine Society, he was the recipient of the Fred Conrad Koch medal in 1971 and the Distinguished Leadership Award in 1978. The Henry Dale Medal was bestowed upon him by the British Society of Endocrinology and the Carl Hartman Award by the Society for the Study of Reproduction as well as the F. H. A. Marshall Medal from the British Society for the Study of Fertility, this last in 1986. Yet, in the face of his many honors Roy was ever modest and self-effacing but this outward demeanor belied his remarkable erudition and awesome scholarship as reflected in his many published addresses and in his voluminous writings.
Roy Greep had an extraordinary propensity for attracting a large number of young investigators and selflessly guiding their careers. This was the case not only for those in his immediate orbit, but many others around the country and throughout the world who sought his advice and guidance or otherwise came under his influence. A typical comment was one by Seymour Reichlin, a past president of our Society, that was echoed by a number of other endocrinologists belonging to several generations. He wrote: "I was deeply touched by Roys death. Although I never worked with Roy, I had the feeling that he knew me, kept up with my work, and encouraged my publications." He went on to say: "He probably had that effect on everybody." And so he did. As a man of great kindness and generosity, he took great pleasure in seeing the careers of his protégés develop and flourish, in no small measure because of his efforts behind the scenes to push them along. The respect, admiration, and deep affection of the many whose lives he touched is undoubtedly the accolade he would value the most.
Roy Greeps large imprint on endocrinology and the world beyond, by dint of his scientific contributions and those of the scientists that he nurtured and the many people he touched in so many ways, will be a deep and lasting one.
Ernst Knobil
The University of Texas, Houston
Health Science Center Houston, Texas 77030
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