Perspectives in Biology and Medicine

THE SAGA AND THE SCIENCE OF THE GONADO TROPHINS* ROY O. GBJSEPt It is a signal honor for me to have been selected by the Society for Endocrinology to receive the Henry Dale Award and to present the 1967 Dale Lecture. Along with you and the scientific world of biology and medicine, I have long held the masterful and enduring work ofSir Henry Dale, Nobel laureate, in the highest regard. This occasion is for me a very special and most cherished distinction. The responsibility fills me with a sense ofboth humility and pride. When it came to the difficult matter of planning the nature of this lecture, I turned, as did my predecessors, to the guidance of previous Dale lecturers. Like them, I succumbed to the temptations ofthe autumnal mind to reminisce, to stir the dying embers of the past, and hopefully to add a note of historical perspective in a world of onrushing change and at a time ofunprecedented scientific achievement. I shall speak more about research than about science. Science is faceless, but research is a stimulating personal experience—a richly rewarding way oflife. Parkes and Marrian in their Dale lectures especially emphasized the human side of life in the laboratory, and I shall attempt to extend that tradition. These remarks will be limited mainly to my own involvement with those hormonal factors contributing to the growth and functions of the ovaries and the testes. An attempt will be made to recapture some ofthe excitement and ferment ofthe earlier days when research on the gonadotrophins of pituitary provenance was reaching the peak of its first full bloom. My introduction to the study of the gonadotrophins came in 1930 when I was accepted as a graduate student under Professor Fred- * The Sir Henry Dale Lecture, London, June I, 1967. Permission to reprint has been given by the fournal ofEndocrinology. Publication costs in part were kindly contributed to Perspectives by the Burroughs Wellcome Fund. t Department ofAnatomy, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115. I24 Roy O. Greep · The Gonadotrophins Perspectives in Biology and Medicine · Autumn 1968 erick L. Hisaw at Madison, Wisconsin. Anyone familiar with the history ofresearch on the gonadotrophins will realize immediately that my personal experience and acquaintance with this field do not reach back to its earliest beginnings. Despite however much I may look the part, I am not one ofthe fathers ofendocrine research. The fathers belonged to a generation before me. The names of this small band of pioneering workers spring readily to mind. They were scattered over the face ofthe globe, but among them I may say that the English, Germans, and French had, perhaps, more than their due. By the time Ijoined the cast ofthe gonadotrophin drama, the first act was over and the second had already begun. The setting for the opening act was New York City, where in 1926 and 1927 Smith [1, 2] had already shown, by daily implants offresh pituitary glands and by hypophysectomy of the rat, that the mammalian gonads were unequivocally under the control of substances emanating from the adenohypophysis. But these revelations were not entirely new. Preparations for the opening act had been in the making for some fifteen years. In essence, the results of Smith only demonstrated in firm fashion relationships between the pituitary and the gonads which B. Aschner [3] and Harvey Cushing [4] had uncovered in preliminary manner during the morning hours of this century. A second clue had been provided in 1916 by the work ofB. M. Allen [5] and ofP. E. Smith [6] himselfthrough ablation ofhypophysis in tadpoles. The scientific theater, however, was not then prepared to project the underlying significance of these observations. The pituitary gland, resting in well-recessed obscurity, continued to remain an object of only intermittent curiosity. There were occasional attempts at the preparation ofextracts ofthe gland, and by 1922 such work had advanced to what in retrospect has sometimes been referred to as the "pink soup" stage. In that year H. M. Evans and J. A. Long [7] reported to the National Academy of Science that they had obtained excessive luteinization in young rats by means of a crude pituitary preparation of ox pituitary...