William F. Ganong

50th APS President (1977-1978)
William F. Ganong
(b. 1924)

Known to his friends usually as "Fran," or occasionally as "Bill," Ganong is a mammalian physiologist, an endocrinologist, and a neurobiologist. In fact, he belongs to a discipline that intersects all three of these parent fields, the specialty of neuroendocrinology. His career developed pari passu with the emergence and maturing of research in this area (13). Whereas only a few years ago he was regarded as a "pioneer," he is now recognized as one of the founding fathers of the science.

"My first exposure to intensive research was with Peter Forsham in Thorn's laboratory at the Peter Bent Brigham Hospital when I was a senior medical student. This stimulated my interest in the neural control of pituitary secretion, and at that time, the only neuroendocrine research in the United States was being conducted by David Hume in the Surgical Research Laboratory at Harvard. Subsequently, I became his postdoctoral fellow and spent three years in his laboratory. My research interest remains the broad field of neuroendocrinology, including the production of hormones by neurons and endocrine-brain interactions."

"I set as my initial research goal elucidation of the mechanisms regulating aldosterone secretion. With the demonstration that renin via angiotensin II was a major regulator of aldosterone, I became interested in the control of renin secretion, and then in the neural components of this process. In the last few years, I have begun to work on the extravascular renin-angiotensin systems in the brain and the pituitary gland."

"My first paper (1) is a favorite, partly because it was my first but also because it introduced a treatment of the Guillain-Barre syndrome that proved to be useful. I had always had a secret ambition to be "immortalized" by having my name attached to a syndrome, and I am pleased that the Lown-Ganong-Levine syndrome grew out of my second paper (2). I also published several papers on Korean hemorrhagic fever before settling down to fundamental physiological research."

"The years with Hume were active and stimulating. I was able to show that hypothalamic lesions block compensatory and stress-induced adrenocortical hypertrophy (3). Don Fredrickson and I showed that in the dog, as in the rat, the hypothalamus regulates TSH [thyroid-stimulating hormone] secretion (4)."

"In California, I focused on regulation of aldosterone secretion. Mulrow and I found that aldosterone takes 30-60 minutes to exert its effect on the kidney (5). This, and similar findings by Berger and associates, led Edelman to experiments that showed that aldosterone acts by way of DNA [deoxyribonucleic acid], RNA [ribonucleic acid], and synthesis of new protein. Mulrow and I also found that there is a humoral factor other than ACTH [adrenocorticotropin] involved in regulation of aldosterone secretion and that it comes from the kidney (6). It is renin acting via angiotensin II (8). This work was carried out independently of, and yet simultaneously with, experiments of J. O. Davis and his associates."

"We have also studied factors that regulate sensitivity of the zona glomerulosa. In animals on a low-sodium diet the sensitivity of the zona glomerulosa to ACTH is markedly increased (10). Sensitivity to angiotensin II is also increased, and exogenous renin can duplicate the effect of sodium depletion in sodium-replete dogs. Thus, angiotensin II is the "ACTH of the zona glomerulosa." Later (11, 12) we began to study the regulation of renin secretion with particular emphasis on neural components (as did Winer and his associates in Kansas City)."

"We have recently become interested in other aspects of the interactions between the brain and the renin-angiotensin system, as well as the distribution of renin and of angiotensin II and of converting enzyme (14). We have found also that the brain-renin-angiotensin system plays an important role in regulation of anterior pituitary secretion and that inhibiting the action of angiotensin II in the hypothalamus prevents the LH [luteinizing hormone] surge and ovulation (16). Finally, we have studied the anterior pituitary-renin-angiotensin system and found that gonadotropes contain angiotensin II-like immunoreactivity (15). Recently we have shown that norepinephrine acts via postsynaptic alpha-2 receptors in the hypothalamus to inhibit ACTH and stimulate growth hormone secretion (17). I can add that I am one of the few investigators who has successfully hypophysectomized a deer (9) and, with Clegg and others, demonstrated that light penetrates into the brain of mammals (7). I do not view this last as one of my more weighty achievements, but it has certainly attracted attention and generated peculiar comments."

Ganong was born in Northampton, Massachusetts, and entered Harvard College (1941) just in time to be caught up in wartime disjointing of college and professional education. Drafted into the U.S. Army and assigned to the infantry, he finally was enrolled in the ASTP in Georgetown College in Washington, D.C., for a year of premedical study and then assigned for two years to the University of Virginia Medical School in Charlottesville (1945-47). Harvard meanwhile decided that they could award him an A.B. degree in 1946, and at long last (1947) he was able to transfer to the Harvard Medical School, from which he graduated in 1949. For the next two years he was a member of the house staff in medicine at Peter Bent Brigham Hospital and then was recalled to the Army as a medical officer assigned to duty in Japan and Korea. From 1952 to 1955 he was able to return to Harvard as a research fellow in medicine and surgery for training in the laboratories of George W. Thorn and David M. Hume, respectively. His clinical research preparation came to an end in 1955, however, when he accepted a position in the department of Leslie L. Bennett at the University of California at Berkeley. Three years later the department was moved to San Francisco, where by 1964 Ganong held the rank of professor. In 1982 he became the Jack D. and DeLoris Lange Professor of Physiology. He served some years as vice-chairman of the Department of Physiology, and from 1970 he has been its chairman.

A member of APS from 1957, Ganong has served the Society in many different capacities. In 1969-70 he was chairman of the Neuroendocrine Discussion Group, one of the informal groups associated with APS. He was elected to APS Council in 1975 and as president elect the following year. He belongs to the category of former presidents who had originally intended to practice medicine, as well as to the group who are graduates of Harvard Medical School. As president, he initiated the Financial Development Committee (chairman, 1980-83), which seeks alternative sources of support for the Society to alleviate partially the dues burden on the membership. His more recent services to APS are as a member of the council of the Section on Endocrinology and Metabolism (1983-) and as a member of the Publications Committee (1984-).

During the year Ganong was president of APS, three movements that had been in progress earlier finally came to realization. One was broadening the bases of membership, so that the Society might become more representative of physiology as a whole, and inclusive rather than exclusive. Another was a more active participation of members in both state and federal governmental policies relating to biomedical research. The third was final settlement of the question of equity of the several societies in the assets of FASEB.

Ganong has held major office also in most of the other professional and scientific societies of which he is a member. He has been a member of Council (1970-73) and chairman of the Nominating Committee (1980-81) of the Endocrine Society, a member of Council (1972-76) and vice-president of the International Society for Neuroendocrinology (1976-80), and a member of Council (1974-75) and president (1976-77) of ACDP. For six years (1975-81) he was a member of the U.S. National Committee for IUPS (chairman, 1976-79). A member of the Council of Academic Societies of AAMC, he was on their Administrative Board from 1981 to 1987. The California Heart Association (1965-70), the Ciba Award Committee of AHA (1980-83), the Lawrence Berkeley Laboratory (1975-82), and the Smokeless Tobacco Research Council (1983-) are among the institutions he has served in consultation. For NIH he has been a member of numerous study sections and panels, including the Neurology A Study Section (1971-75) and the Task Force on Hypertension (1975-78). Besides these he has served on various committees of the Society for Experimental Biology and Medicine, the International Society of Endocrinology, FASEB, and the Society for Neuroscience. Two of his memberships are uncommon in APS: the society of Brigham Surgical Alumni and the 38th Parallel (Korea) Medical Society. During his military service in Korea he received a combat zone promotion from first lieutenant to captain.

Editorial responsibilities Ganong has fulfilled include the journals of the Society (1960-66), Endocrinology (1961-73), Proceedings of the Society for Experimental Biology and Medicine (1962-69), Medcom (1968-78), Neuroendocrinology (1968-73), the Journal of Pharmacology and Experimental Therapeutics (1969-75), and those he currently holds for Neuroscience, the Italian Journal of Physiological Sciences, and Excerpta Medica; he is currently editor-in-chief of Neuroendocrinology.

Ganong earned distinction in each of the colleges where his peripatetic career as a student took him. With his first formal venture into neuroendocrinology he was awarded the Boylston Medical Society Prize in 1949 for his paper on "Control of ACTH secretion." Later honors include a corresponding membership in the Chilean Endocrine Society (1966) and receipt of the Golden Hippocrates Award presented by the Instituto Farmacoterapico Italiano (1970). He presented the Sherrington Society Lecture in London (1976) and the Starling Memorial Lecture in Jamaica (1978), received the teaching award of ACDP (1978), and delivered the Centennial Distinguished Lecture at the University of Arkansas (1979), the Nelson Lecture at Rutgers University (1980), the Macallum Lecture at the University of Toronto (1980), and the Jane Russell Wilhelmi Lecture at Emory University (1982). He became a fellow of AAAS in 1980 and an honorary member of the Argentine Society of Physiological Sciences in 1982.

Physiologists unfamiliar with the scope of Ganong's research will nevertheless know of his textbooks and other volumes he has written or edited: Review of Medical Physiology (Lange Medical Publications, Los Altos, CA), now in its twelfth edition; the two-volume work on Neuroendocrinology edited by Martini and Ganong (1966, Academic Press, New York); and nine volumes of the series Frontiers in Neuroendocrinology (first with Oxford University Press, New York, and then with Raven Press, New York). In adding these titles to his list of favorite publications, Ganong wrote, "It is obvious that I have invested a fair amount of libido in "Review of Medical Physiology." Prospective textbook writers will be pleased to learn this recipe for success.

Selected Publications

1. Stillman, J. S., and W. F. Ganong. The Guillain-Barre syndrome: report of a case treated with ACTH and cortisone. N. Engl. J. Med. 246: 293-296, 1952.

2. Lown, B., W. F. Ganong, and S. A. Levine. The syndrome of short P-R interval, normal QRS complex and paroxysmal rapid heart action. Circulation 5: 693-706, 1952.

3. Ganong, W. F., and D. M. Hume. Absence of stress-induced and "compensatory" adrenal hypertrophy in dogs with hypothalamic lesions. Endocrinology 55: 474-483, 1954.

4. Ganong, W. F., D. S. Fredrickson, and D. M. Hume. The effect of hypothalamic lesions on thyroid function in the dog. Endocrinology 57: 355-362, 1955.

5. Ganong, W. F., and P. J. Mulrow. Rate of change in sodium and potassium excretion after injection of aldosterone into the aorta and renal artery of the dog. Am. J. Physiol. 195: 337-342, 1958.

6. Ganong, W. F., and P. J. Mulrow. Evidence of secretion of an aldosterone-stimulating substance by the kidney. Nature Lond. 190: 1115-1116, 1961.

7. Ganong, W. F., M. D. Shepherd, J. R. Wall, E. E. Van Brunt, and M.T. Clegg. Penetration of light into the brain of mammals. Endocrinology 72: 962-963, 1963.

8. Lee, T. C., E. G. Biglieri, E. E. Van Brunt, and W. F. Ganong. Inhibition of aldosterone secretion by passive transfer of antirenin antibodies to dogs on a low sodium diet. Proc. Soc. Exp. Biol. Med. 119: 315-318, 1965.

9. Hall, T. C., W. F. Ganong, and E. B. Taft. Hypophysectomy in the Virginia deer: technique and physiologic consequences. Growth 30: 382-392, 1966.

10. Ganong, W. F., and A. T. Boryczka. The effect of a low sodium diet on the aldosterone-stimulating activity of angiotensin II in dogs. Proc. Soc. Exp. Biol.. Med. 124: 1230-1231, 1967.

11. Loeffler, J. R., J. R. Stockigt, and W. F. Ganong. The effect of alpha- and beta-adrenergic blocking drugs on the increase in renin secretion produced by stimulation of the renal nerves. Neuroendocrinology 10: 129-138, 1972.

12. Nolly, H. L., I. A. Reid, and W. F. Ganong. The effect of theophylline and adrenergic blocking drugs on the renin response to norepinephrine in vitro. Circ. Res. 35: 575-579, 1974.

13. Ganong, W. F. The brain and the endocrine system: a memoir. In: Pioneers in Neuroendocrinology II edited by J. Meites, B. T. Donovan, and S. M. McCann. New York: Plenum, 1978, p. 189-200.

14. Brownfield, M. S., I. A. Reid, D. Ganten, and W. F. Ganong. Differential distribution of immunoreactive angiotensin and converting enzyme in the brain. Neuroscience 7: 1759-1769, 1982.

15. Steele, M. K., M. S. Brownfield, and W. F. Ganong. Immunocytochemical localization of angiotensin immunoreactivity in gonadotrops and lactotrops of the rat anterior pituitary gland. Neuroendocrinology 35: 155-158, 1982.

16. Steele, M. K., R. V. Gallo, and W. F. Ganong. A possible role for the brain renin-angiotensin system in the regulation of LH secretion. Am. J. Physiol. 245 (Regulatory Integrative Comp. Physiol. 14): R805-R810, 1983.

17. Ganong, W. F., J. Challett, H. Jones, Jr., S. L. Kaplan, M. Karteszi, R. D. Stith, and L. D. Van de Kar. Further characterization of the putative alpha-adrenergic receptors in the brain that affect blood pressure and the secretion of ACTH, growth hormone and renin in dogs. Endocrinol. Exp. 16: 191-204, 1982.