A. Clifford Barger

43rd APS President (1970-1971)
A. Clifford Barger

During his tenure on Council and in presidential offices, Barger led APS into effective programs for improving professional opportunities for minority groups and for women. He has written:

"My most important contributions probably have been in the founding and funding of the Porter Physiology Development Program and the education of minority physiologists through the Porter Physiology Development Committee, as well as the first presidential tour of the predominantly black schools, the organization of a workshop for minorities in research, . . . and support of women in the affairs and offices of the Society."

Born in Greenfield, Massachusetts, as a young man Barger went east and found his professional career almost entirely within ten miles of the Boston Common. He graduated from Harvard University in 1939 and from Harvard's Medical School in 1943. In 1943 and again in 1945 he was a member of the house staff of Peter Bent Brigham Hospital, until he joined the research and then the teaching staff of the Department of Physiology in 1946 under the chairmanship of Eugene M. Landis. Moving steadily upward in rank, he became professor of physiology in 1961 and Robert Henry Pfeiffer Professor two years later. During much of his time in the department, Barger has held also appointments in clinical departments. For example, he was assistant in medicine at Peter Bent Brigham Hospital from 1946 to 1953, until he joined the associate staff of that hospital. In 1959 his title was changed to consultant, and from 1965 he has held a similar title at Children's Hospital Medical Center and at St. Vincent's Hospital. For two years (1974- 76) Barger filled the position of chairman of the Department of Physiology.

Before he became identified with this department, Barger had begun fundamental research in three other settings.

"I was fortunate as an undergraduate to be a student fellow in the Fatigue Laboratory when D. Bruce Dill (23rd president of APS) was director. I worked on the problem of anaerobic glycogenolysis in frog muscle with my Harvard College tutor, Robert E. Johnson (1). (Dr. Johnson later served for more than 20 years as head of the Department of Physiology at the University of Illinois in Urbana.) My next research experience, as an intern at the Peter Bent Brigham Hospital, was the study with George Thorn of the effect of testosterone on exercise endurance in patients with progressive muscular dystrophy. During World War II, I was assigned by the Army to the Climatic Research Laboratory (in Lawrence, MA) to do research on protection of soldiers exposed to cold climates."

"After release from the Army, as a research fellow with Dr. Landis I studied the response of the cutaneous blood vessels during treadmill exercise (2)."

These experiments with Landis led naturally to thirty-five years of ongoing research on pathophysiology of congestive heart failure, renovascular hypertension, and coronary artery disease. Barger and his co-workers first attempted to explain why patients with congestive heart failure retain water and electrolytes and to this end developed a technique for inducing an analogous condition in dogs. They did this by combining operations to produce tricuspid valvular insufficiency with pulmonary arterial stenosis and so created right-sided congestive failure (3). When renal function of the animals was tested, a depressed response to intravenous salt loading was found before there was evidence of any decrease in glomerular filtration rate (4). The results suggested an increased tubular reabsorption of sodium. To test this hypothesis, methods for studying the output of the two kidneys separately were devised, with perfusion of one kidney with hypertonic sodium chloride solution while the other kidney served as a control. Increased tubular sodium reabsorption by the perfused kidney was thereby confirmed (5). Later experiments demonstrated for the first time that unilateral infusion of physiological doses of aldosterone in unanesthetized dogs produces a unilateral kaliuresis with no change in sodium excretion, although in adrenalectomized dogs the same infusion led to both kaliuresis and antinatriuresis (6).

While infusing solutions into renal vessels, Barger and his colleagues discovered that in dogs with congestive failure the cortical nephrons of the kidney had a reduced blood flow, from which they concluded that the outer, shorter nephrons might be "relative salt losers," whereas the inner nephrons with longer loops might be "relative salt retainers." To study differential blood flow more thoroughly, the laboratory developed an inert gas technique for measurement of regional blood flow in kidneys of unanesthetized dogs (7). Similarly unanesthetized animals were later utilized for experiments on the role of the renin-angiotensin-aldosterone system in compensation for congestive heart failure. Here the preliminary operations included permanent placement of catheters and implantation of inflatable cuffs on pulmonary artery and thoracic aorta. When the renin-angiotensin-aldosterone system was inactivated, these animals lost most of their capacity to compensate for the congestive failure (11).

The second of Barger's three primary research interests, renovascular hypertension, is represented in his bibliography by a series of papers, of which five are included here (8-12). The research was made possible by the prior development of methods for inducing chronic changes in blood flow of unanesthetized dogs and so studying sequentially changes in the renin-angiotensin system. The authors found that in salt-depleted dogs maintained on a low-salt diet to prevent water and electrolyte retention, renovascular hypertension is maintained primarily by the renin- angiotensin system (12, 13).

Current work of Barger's laboratory again concerns coronary arterial blood flow and coronary artery disease. New evidence has been provided for a significant role of the vasa vasorum in pathogenesis of coronary artery plaques (14), in confirmation of results published nearly fifty years ago by Winternitz and his colleagues in the Department of Pathology at Yale.

An unusual feature of research in Barger's laboratory has been the production of motion pictures of physiological responses. He and his associate, R. Beeuwkes, were able to photograph renal tubules as they were being injected with silicone rubber through micropipettes. These studies led to others on the vascular-tubular organization of canine and human kidneys and to photographs of neovascularization of atherosclerotic coronary arteries. Shown at the IUPS Meeting in Munich in 1971, at the International Congresses of Nephrology in Mexico in 1972 and in Florence in 1975, at the Annual Meeting of AHA in 1979, and at a FASEB Meeting in 1983, these films have been awarded altogether twelve prizes and medals. Included are three separate Golden Eagle Awards of the Council on International Nontheatrical Events (1973, 1975, 1983) and a gold medal by the International Medical Film Festival held in Parma, Italy, in 1983 for the coronary film.

In his years of service to Harvard and to the Boston medical-scientific community, Barger has been appointed or elected to important offices. In 1957-58, he was president of the Boylston Medical Society and also president of the Massachusetts Society for Medical Research. In 1970 he became president of the Harvard Apparatus Foundation. From 1978 to 1982 he was first master of the Cannon Society of the Harvard Medical School, an academic society that seeks to perpetuate the ideals and legacies of Walter Bradford Cannon. An accomplished historian, Barger is coauthoring a two-volume life and letters of Cannon, the first volume of which is scheduled to appear in time for the centennial of APS.

Nationally, Barger served on committees of NRC (1955-57 and 1957-62) and was a member of the Physiology Study Section of NIH (1960-64) and the Board of Scientific Counselors of the National Cancer Institute (1969-72; chairman, 1972-73). During this period he also was on the Research Committee of AHA (1966-68). In 1971 he joined the Physiology Committee of the National Board of Medical Examiners (chairman, 1973-76). His editorial duties have included Proceedings of the Society of Experimental Biology and Medicine (1960-62), Circulation Research (1963-66), and "Physiology in Medicine" in the New England Journal of Medicine (1971-80).

Honors Barger has received include the Certificate of Merit of the National Society of Medical Research (1958), selection as the Goldblatt Memorial Lecturer (1978) and the Annual Sosman Lecturer of Peter Bent Brigham Hospital (1980), and the Carl J. Wiggers Award of APS (1982). He was elected a fellow of AAAS (Boston) in 1964 and a member of the Institute of Medicine of NAS in 1974. In 1977 the University of Cincinnati conferred on him the degree doctor of science.

Elected to membership in APS in 1949, by 1960-61 he was a member of the Editorial Board of the Society's two primary journals. He was appointed to the newly established Publications Committee (1961-63; chairman, 1962-63) to which he was later reappointed (1966-69). He was elected to Council in 1968, and only a year later he began his presidential terms as president elect. In 1985 he was chosen for the Society's Ray G. Daggs Award. The citation for the presentation read:

"Cliff has also been very deeply involved in the fight by our Society and its members to maintain access to appropriate animal models for our physiological research, working especially closely with the [National] Society for Medical Research and the IUPS."

Barger's designation as cochairman of the Porter Development Committee in 1966 marked the official beginning of his effort to apply resources available to the Society in the interests of minority scientists. Funds distributed by this committee originate from the Harvard Apparatus Foundation, successor to the original Harvard Apparatus Company founded by William Townsend Porter. In a graceful although brief biography of Porter, Barger wrote of how in 1929 Porter offered to give the Harvard Apparatus Company to APS, but Council declined to accept the gift. Porter's response was to set up a nonprofit foundation to run the company, with the net proceeds then turned over to APS to support the Porter Fellowships (16). The total thus made available now exceeds $750,000.

In his past president's address, Barger described the fascinating history of personal interactions among Bowditch, Porter, and Cannon and recounted how funds from the Harvard Apparatus Company were made available for the benefit of young minority-group physiologists (15). Barger conceived this idea and in 1965 persuaded Council to approve it. Cliff Barger will certainly be remembered in the annals of APS, not alone for his contributions to physiology of the heart and kidneys, but perhaps even more for his dedication to the training and careers of scores of young investigators of minority-group backgrounds.

Selected Publications

1. Barger, A. C., and R. E. Johnson.. Anaerobic glycogenolysis in the muscles of Rana pipiens living at low temperature. J. Gen. Physiol. 24: 669-677, 1941.

2. Greenwood, W. F., A. C. Barger, J. R. DiPalma, J. Stokes III, and L. H. Smith. Factors affecting the appearance and persistence of visible cutaneous reactive hyperemia in man. J. Clin. Invest. 27: 187-197, 1948.

3. Barger, A. C., B. B. Roe, and G. S. Richardson. Relation of valvular lesions and of exercise to auricular pressure, work tolerance and to the development of chronic congestive failure in dogs. Am. J. Physiol. 169: 384-399, 1952.

4. Barger, A. C., R. S. Ross, and H. L. Price. Reduced sodium excretion in dogs with mild valvular lesions of the heart, and in dogs with congestive failure. Am. J. Physiol. 180: 249-260, 1955.

5. Rudolph, A. M., S. N. Rokaw, and A. C. Barger. Chronic catherterization of the renal artery. Technic for studying direct effects of substance on kidney function. Proc. Soc. Exp. Biol. Med. 93: 323-326, 1956.

6. Barger, A. C., R. D. Berlin, and J. F. Tulenko. Infusion of aldosterone, 9-alpha- fluorohydrocortisone and antidiuretic hormone into the renal artery of normal and adrenalectomized, unanesthetized dogs: effect on electrolyte and water excretion. Endocrinology 62: 804-815, 1958.

7. Thorburn, G. D., H. H. Kopald, J. A. Herd, M. Hollenberg, C. C. C. O'Morchoe, and A. C. Barger. Intrarenal distribution of nutrient blood flow determined with krypton85 in the unanesthetized dog. Circ. Res. 13: 290, 1963.

8. Gutmann, F. D., H. Tagawa, E. Haber, and A. C. Barger. Renal arterial pressure, renin secretion, and blood pressure control in trained dogs. Am. J. Physiol. 224: 66-72, 1973.

9. Tagawa, H., F. D. Gutmann, E. Haber, E. D. Miller, Jr., A. I. Samuels, and A. C. Barger. Reversible renovascular hypertension and renal arterial pressure. Proc. Soc. Exp. Biol. 146: 975-982, 1974.

10. Miller, E. D., Jr., A. I. Samuels, E. Haber, and A. C. Barger. Inhibition of angiotensin conversion and prevention of renal hypertension. Am. J. Physiol. 228: 448-453, 1975.

11. Watkins, L., Jr., J. A. Burton, E. Haber, J. R. Cant, F. W. Smith, and A. C. Barger. The renin-angiotensin-aldosterone system in congestive failure in dogs. J. Clin. Invest. 57: 1606-1617, 1976.

12. Rocchini, A. P., and A. C. Barger. Renovascular hypertension in sodium-depleted dogs: role of renin and carotid sinus reflex. Am. J. Physiol. 236 (Heart Circ. Physiol. 5): H101-H107, 1979.

13. Kopelman, R. I., V. J. Dzau, S. Shimabukuro, and A. C. Barger. Compensatory response to hemorrhage in conscious dogs on normal and low salt intake. Am. J. Physiol. 244 (Heart Circ. Physiol. 13): H351-H356, 1983.

14. Barger, A. C., R. Beeuwkes III, L. L. Lainey, and K. J. Silverman. Hypothesis: vasa vasorum and neovascularization of human coronary arteries: a possible role in the pathophysiology of atherosclerosis. N. Engl. J. Med. 310: 175-177, 1984.

15. Barger, A. C. Past-president's address. To assist young men and women in the study of physiology: the Porter Development Program. Physiologist 14: 277-285, 1971.

16. Barger, A. C. The meteoric rise and fall of William Townsend Porter, one of Carl J. Wiggers' "Old Guard." Physiologist 25: 407-413, 1982.

In the autumn of 1995 Barger resigned as president of the William Townsend Porter Foundation. He was working on writing the second volume of the life of Cannon before his departure. On March 13, 1996, A. Clifford Barger died at his home in Brookline, MA.