melvin j. fregly : a tribute

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MELVIN JAMES FREGLY (1925-1996)

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MELVIN JAMES FREGLY (1925-1996)

Melvin J. Fregly A Tribute

CLARK M. BLATTEIS".' AND MARILYN S. FREGLYb aDepartment of Physiology and Biophysics

The University of Tennessee, Memphis 894 Union Avenue

Memphis, Tennessee 38163 and

bCenter for International Economics and Business Studies College of Journalism and Communications

University of Florida Gainesville. Florida 32611

Dr. Melvin James Fregly, Graduate Research Professor of Physiology at the University of Florida College of Medicine, was a charter member of that depart- ment as well as a member of the National Scientific Committee of this, the 10th International Symposium on the Pharmacology of Thermoregulation. He died suddenly and unexpectedly on January 13, 1996, at 70 years of age. He was a major and much respected contributor to our field, and we are grateful for his many accomplishments, which did so much to advance our discipline. With sincere affection, this volume is dedicated to his memory.

Dr. Fregly was born and reared in Patton, Pennsylvania. He graduated in 1941 from Patton High School, as its valedictorian. But, with the entry of the USA into World War I1 on December 7, 1941, he was soon drafted and sent to the University of Florida in its Army Special Training Program. Subsequently, he was assigned to the 304th Signal Operation Battalion of the 8th US Army and served in the Southeastern Pacific Theater, specifically in New Guinea, the Philip- pines, and Japan. Upon his discharge after the war, Fregly entered Bucknell University in Lewisburg, Pennsylvania, where he earned both his Bachelor's and Master's degrees. He then went on to the University of Rochester and graduated in 1952 with a Ph.D. in physiology under the mentorship of Dr. E. F. Adolph. Their close friendship would continue until Adolph's death in 1986.

Dr. Fregly's academic career began immediately after graduation. His first professional appointment was as instructor in physiology at Harvard Medical School. Four years later, he accepted a call from the about-to-be inaugurated University of Florida College of Medicine, as assistant professor in the Department of Physiology under the chairmanship of Dr. Arthur B. Otis. He moved steadily and rapidly up the ranks, becoming associate professor of physiology in 1960 and full professor in 1965. In 1979, he was appointed the University's first Graduate Research Professor, a position he occupied for the rest of his life. During 1964 and 1965, Dr. Fregly also served as acting chairman of his department, and from 1967 to 1972 he was assistant dean for graduate education at his college.

An overview of Dr. Fregly's bibliography would suggest that he had many, diverse research interests and that he was highly productive in all of them. Indeed,

Corresponding author. 1

2 ANNALS NEW YORK ACADEMY OF SCIENCES

he was prominent at an international level in environmental and thermal physiology as well as in endocrinology (especially thyroidology) and hypertension research. Thus, he contributed more than 500 articles in numerous biological and physiologi- cal journals during his career as well as co-edited five books in these areas, including the very recently published second edition of the American Physiological Society’s Handbook of Physiology, Section 4: “Environmental Physiology.” However, a more detailed analysis of his extensive work reveals that these various interests were, in fact, not unconnected but, to the contrary, intimately linked to one another by the theme that underlay all of Dr. Fregly’s research, uiz., the nature of physiological adaptations as manifestations of physiological regulations. Thus they represented but different approaches to this fundamental issue. He was, in this regard, strongly influenced by his doctoral studies in Dr. Adolph’s laboratory. This was reflected in the subjects of the first three papers he published inde~endently,’-~ which led to over 40 years of ongoing research on the physiologi- cal mechanisms that underlie the homeostatic responses to a variety of both internal and external stressors. He was still actively publishing in this area until his death and, indeed, two of his papers are included in this volume; he was scheduled to present them personally when he was so suddenly taken from us.

Space limitations preclude an exhaustive review of his many discoveries and accomplishments. Four only are mentioned here, as guides to his perspective. One focus of Dr. Fregly’s long-term research was to identify the cause of the thirst manifested by various species upon their return to a thermoneutral environ- ment after exposure to moderate cold (5°C) for as short a duration as 6 h. In collaboration with his students and fellows, he was able eventually to show that this “thermogenic drinking” is stimulated by a relative dehydration that occurs during the cold exposure and involves the P,-adrenergic activation of the renin- angiotensin system, thus implicating both osmoreceptors and angiotensin I1 path- ways in the mechanism of this r e ~ p o n s e . ~

The elucidation of the mechanisms responsible for the hypertension, tachycar- dia and cardiac hypertrophy that develop in rats during chronic exposure to cold was another goal that commanded Dr. Fregly’s attention over the years. In a series of studies’ (including his second paper in this volume), he and his colleagues demonstrated that the features of cold-induced hypertension resemble those of the hypertension caused by dietary salt intake and by corticosterone administration, suggesting that the former may be a naturally occurring analog of the mineralocorti- coid-salt-induced hypertension model; i . e . , that every component of the renin- angiotensin-aldosterone system may contribute to the development of this hyper- tension. By contrast, the cold-induced cardiac hypertrophy was found to be inde- pendent of either pressure overload or tachycardia; it was ultimately attributed to an increased turnover of thyroid hormones in the cold.6

Also dating to his beginning in physiological research was his consuming inter- est in cross-adaptations, i.e., in the possibility that adaptation to a single stressor, e . g . , cold, might evoke responses that could provide either protective or detrimen- tal effects against the responses to a second stressor, e . g . , hypoxia, delivered acutely subsequently (as distinct from exposure to both stressors in combination). He conducted a number of studies over the years on this subject, demonstrating both positive and negative cross-adaptations among various stressors. He collated his and other workers’ data in a review in 1971’ and again in 1996: both times emphasizing the need to investigate this issue further and stressing the practical importance of the knowledge that would be acquired.

To study these phenomena, Dr. Fregly used the classical tools of physiological and pharmacological research ( i . e . , the administration of the putative causative

BLA'ITEIS & FREGLY MELVIN J. FREGLY 3

agent, its precursors, depleting agents, agonists, antagonists, and mimetics, as well as the destruction, chemical or surgical, of the target organ or system), with great success. Dose-response, time-course, and longitudinal studies were his stock- in-trade, all to good avail. As an illustration of his approach, consider, for example, his studies on the possible involvement of angiotensin I1 in thermoregulation. He showed that the systemic administration of angiotensin I1 induced a fall in T, that was mediated centrally via a cholinergic pathway distinct from those mediating the dipsogenic and pressor responses to angiotensin I1 and also different from that controlling the vasodilation of the tail9 (see also his first paper in this volume). Dr. Fregly's favorite animal model was the rat. But he also studied the responses of mice, dogs, frogs, turkeys, and men.

As a teacher, Dr. Fregly understood the importance of bringing young people into the field. In addition to medical and graduate students, he took into his laboratory during summers young students from the Florida statewide apprentice- ship programs for high school students; all were given hands-on experience and equal credit in his publications. All who came in contact with him were inspired by his great enthusiasm, insatiable curiosity, and wonderful precision of mind. Among his most cherished awards was the University of Florida Blue Key, the highest honor bestowed on afaculty member by students in recognition of meritori- ous teaching, research and service.

Dr. Fregly also held important offices both locally and nationally. Nationally, in particular, he served on advisory committees of, to mention only a few, the National Institutes of Health, the Environmental Protection Agency, the Naval Research and Development Command, the National Aeronautics and Space Ad- ministration, and the American Physiological Society, and on the editorial boards of Proceedings of the Society for Experimental Biology, American Journal of Physiology, Journal of Applied Physiology, Physiology and Behavior, and more.

Dr. Fregly leaves a legacy of hundreds of students and fellows that he nurtured, guided, and motivated. He was a gentleman of the highest integrity, with excep- tional dedication to physiology, a very hard worker, a scholar in the finest sense of that word. Maturity, civility, courtesy and consideration were his trademarks. His untimely death leaves us with his memory as a colleague, teacher, and friend, to inspire us and to cherish forever more.

REFERENCES

1. FREGLY, M. J. 1953. Minimal exposures needed to acclimatize rats to cold. Am. J. Physiol. 173: 393-402.

2. FREGLY, M. J. 1954. Cross-acclimatization between cold and altitude in rats. Am. J. Physiol. 176 267-214.

3. FREGLY, M. J. 1954. The effects of extremes of temperature on hypertensive rats. Am. J. Physiol. 176 275-281.

4. FREGLY, M. J. 1982. Thermogenic drinking: mediation by osmoreceptors and angiotensin I1 pathways. Fed. Proc. 41: 2515-2519.

5 . FREGLY, M. J. & N. E. ROWLAND. 1995. Effect of administration of angiotensin I1 and isoproterenol, alone and in combination, on drinking and tail skin temperature of the rat. Pharmacol. Biochem. Behav. 51: 83-88.

FRECLY, M. J., F. ROSSI & J. R. CADE. 1995. A role for thyroid hormones in cold-induced elevation of blood pressure and cardiac hypertrophy. Can. J . Physiol. Pharmacol. 194 1066- 1074.

6.

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7. FREGLY, M. J. 1971. Cross-adaptations and their significance. Rev. Can. Biol. 30:

8. FREGLY, M. J. 1996. Adaptations: some general characteristics. In Handbook of Physiol- ogy, Sec. 4: Environmental Physiology. Vol. 1. M. J. Fregly & C. M. Blatteis, Eds. 3-15. Oxford University Press. New York.

9. WILSON, K. M. & M. J. FREGLY. 1985. Factors affecting angiotensin-11-induced hypo- thermia in rats. Peptides 6 695-701.

223-237.