Franklyn G. Knox

59th APS President (1986-1987)
Franklyn G. Knox
(b. 1937)

As the most recent twenty-five year history of APS began in 1963 with Hermann Rahn presiding at the anniversary meeting in Coral Gables, Florida, it will come to a climax in 1987 at the Centennial Celebration at the FASEB Meeting in Washington, D.C., with Franklyn G. Knox in the chair. In 1963 Knox was an M.D./Ph.D. student with Donald Rennie in Hermann Rahn's department at the State University of New York at Buffalo and journeyed to the Coral Gables meeting with his wife and two small children. A scientific "generation," therefore, is exactly twenty-five yearsat least in this instance. In anticipation of the coming anniversary, Knox has written:

As president of the American Physiological Society, I will have the distinct honor of presiding over the Centennial Celebration recognizing the One Hundredth Anniversary of the Society. The 1987 Spring Meeting of FASEB will be held in Washington, D.C., and will have the theme "A Century of Progress in Physiology." An impressive opening ceremony with the Marine Band is planned for the Washington Convention Center. The program for the meeting will be built around progress in physiology with both retrospective and prospective analysis of the field. These program activities will be complemented by publication activities of important historical books. In the meantime, the Society looks forward to the next century of progress through strengthening the roles of the sections of the American Physiological Society so that the Society can be in the strongest position to respond to the changing future.

Knox was born in Rochester, New York, and completed all his professional education at the now State University of New York at Buffalo. He received the B.S. degree in 1959 and the M.D. and Ph.D. degrees in 1965. The last of these represented training in the Department of Physiology and led to a position as staff associate at the National Heart Institute (1965-68). From there he moved to the University of Missouri, where he was promoted to an associate professorship in the Department of Physiology in 1970. The following year he joined the faculty of the newly organized Mayo Medical School. He became professor of physiology and of medicine and also chairman of the Department of Physiology and Biophysics in 1974. For five years (1978-1983) he was also the Associate Director of Graduate Education: Research Training and Degree Programs of the Mayo Graduate School of Medicine. In 1983 he moved a step higher to become dean of the Mayo Medical School and Director for Education for the Mayo Foundation. Knox has written of his education, training, and faculty positions:
"My decision to become a physiologists was preceded by my decision to have a research career. As an undergraduate student working in Gerhard Levy's laboratory in Buffalo, I was impressed by the power of the scientific method to make contributions to society. Subsequently I applied to medical school with the objective of further training toward a research career. It wasn't until I did summer research as a medical student in Donald Rennie's laboratory in the Department of Physiology that I began to consider a career as a physiologist. Consideration of this career track led to the development of an M.D./Ph.D. program. The Department of Physiology at Buffalo was under the leadership of Hermann Rahn and was noted for its particular strengths in respiratory physiology. With Rennie's interest in the kidney, it was natural that my thesis should be in the area of the respiration of the kidney. Rennie served as a role model for the kind of career that I envisioned in research and teaching in physiology."

"My postdoctoral research training in the Laboratory of Kidney and Electrolyte Metabolism at the National Institutes of Health with Robert W. Berliner was a particularly exciting training experience. In addition to learning the micropuncture technique, there was interaction with a large number of enthusiastic young investigators who have subsequently developed leadership positions in renal physiology and nephrology. Berliner allowed for the individual creativity of these individuals, but in the context of intimate critique of the data as they unfolded day by day. Thus we would anticipate a noon flight of the 'Eagle' in which he would ask, "Do you have any numbers?" It was a vibrant and exciting place to train."

"James O. Davis invited me to join the faculty at the University of Missouri, where I had the opportunity to press the long-term objective of independent research and teaching into action. Given my background from Buffalo, I taught the respiratory physiology section of the medical school course and developed the teaching around a case of emphysema. I remember one student's essay, "Don't kiss me, I'm trying to breath" in which the mechanics of respiration and emphysema were discussed and the necessity for pursed lips to maintain resistance in the airway to prevent airway collapse was explained."

"John Shepherd and Jim [James C.] Hunt recruited me to Mayo at the time of the development of Mayo Medical School. This was a particularly exciting time because of the opportunities for developing a medical curriculum in an institution noted for its excellence in medicine and with the opportunity to develop innovative approaches with a small class of students. Shepherd served as a role model for outstanding effectiveness in administrative activities, and I subsequently succeeded him as department chairman. After approximately a decade as department chairman, I again succeeded Shepherd as Director for Education for the Mayo Foundation and dean of the Mayo Medical School. The Medical School, Graduate School, and School of Health-Related Sciences have grown and flourished, and the most significant accomplishment is the establishment of Mayo as an independent degree-granting institution."

Knox has been elected a fellow of AAAS (1985) and of the Council on Circulation of AHA. He has served AHA on the Board of Directors (1982-) and Executive Committee (1983) and in varied capacities on the Council on Kidney in Cardiovascular Disease (1977-) and the Council for High Blood Pressure Research (1974-). He is a member of AMA, the American Society for Clinical Investigation, and the Association of American Physicians. He has been a member of the Nominating Committee of the American Society of Nephrology (1979) and the Council of Deans of AAMC; he is currently on the Selection Committee for the AAMC Award for Distinguished Research in the Biomedical Sciences (1985-). He was president of ACDP (1981-1982) and a member of the Physiology Test Committee of the National Board of Medical Examiners (1980-81); he currently is a member of the U.S. National Committee for IUPS (1985-1988). He has performed review and advisory functions for the National Kidney Foundation (1980-83), the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases (1979-83), and for the NIH Division of Research Grants (1983-87); chairman of General Medicine B Study Section, 1986-87).

Knox was elected to membership in APS in 1969. He was a member of the Program Committee for eight years (1973-76 and 1977-82; chairman, 1981-82), chairman of the Renal Section (1975-77), APS representative to the AAMC Council on Academic Societies (1979-83), and chairman of the Committee on Committees (1983-85). He is a member of the Long-Range Planning Committee (1984-) and of the Subcommittee on International Physiology (1985-). Elected to Council in 1982, he became president elect in 1985.

Having served the Society as a member of the Editorial Board of the American Journal of Physiology: Renal, Fluid and Electrolyte Physiology (1976-80), Knox was appointed to the Publications Committee in 1984. He has provided editorial service also as a member of editorial boards or as a consultant for Circulation Research, Journal of Clinical Investigation, Kidney International, Mineral and Electrolyte Nephrology, American Journal of Kidney Diseases, and the Journal of Laboratory and Clinical Medicine (editor, 1979-80). Many of these responsibilities developed from his own research interests.

Knox began research while, as an undergraduate student at Buffalo, he worked in Gerhard Levy's laboratory in the School of Pharmacy. His first paper (1) involved the bioassay of thyroid preparations, utilizing the capacity of the thyroid preparation to prevent propylthiouracil-induced goiters. Later in his career he returned to studies of thyroid and parathyroid hormones on renal function (6, 7). For his Ph.D. dissertation he studied the effects of osmotic diuresis on sodium reabsorption and oxygen consumption by the kidney in the laboratory of Donald W. Rennie in the School of Medicine (2). This began his ongoing interest in control of renal sodium excretion. He found that osmotic diuresis markedly decreases the number of sodium ions transported per mole of oxygen utilized and concluded that the osmotic diuresis enhances the backflux of sodium in proximal tubules. Many of his later publications have followed this theme.

While he was in Berliner's laboratory at the National Heart Institute, Knox learned micropuncture techniques and analyzed the effect of changes in blood volume on proximal sodium reabsorption (3). His first publication as an independent investigator was a study of furosemide natriuresis, carried out after he had moved to the University of Missouri (4). The earliest of the "favorite publications" he selected from the Mayo laboratories established the relative contributions of various nephron segments in control of sodium excretion (5). Of a paper published a year later (6), Knox wrote:

"This paper is particularly important because the control experiments were surprising and led to an entirely new phase of research on regulation of phosphate transport by proximal tubules. We were using hyperoncotic albumin solution preferentially to expand plasma volume at the expense of interstitial fluid volume and to determine the effects on renal sodium handling. Ultimately, because of control experiments with dextran solutions, we discovered that the effects of hyperoncotic albumin were not due to plasma volume expansion, but rather to binding of plasma calcium by the albumin and subsequent release of parathyroid hormone. This hormone, in turn, had an unexpectedly large effect on sodium ions in the proximal tubule, as well as on phosphate reabsorption. This led to a significant body of work dealing with intrarenal phosphate metabolism. Further work pointed the way to involvement of segments other than the proximal tubules in control of phosphate excretion (7). Our contributions to the understanding of renal phosphate handling were summarized in the Twenty-second Bowditch Lecture of the APS (8)."

A new era of renal physiology opened with the discovery that nephrons deep in the kidney have functions surprisingly different from those located near the surface (9). Previously it was generally assumed that superficial nephrons are representative of nephrons throughout the kidney. On the contrary, proper interpretation of micropuncture results must include the possibility of nephron heterogeneity. This work was extended to include sodium, as well as phosphate, handling and served to help resolve the long-standing issue of the mechanism for escape from salt-retaining effects of mineralocorticoids (10). Finally, Knox selected a recent paper with Erik Ritman "because of its importance for the future" (11). It utilized high-speed dynamic spatial reconstruction techniques with advanced computers to bring renal physiology "into the modern era of noninvasive measurement of organ function."

The halo shining with a "soft blue light" that Hermann Rahn first identified in 1963 continues to illuminate the brow of presidents of APS. It seems especially appropriate that at the 1987 Centennial Meeting it will be worn by one of Rahn's most illustrious disciples, Franklyn Knox.

Selected Publications

1. Levy, G., and F. G. Knox. The biological activity of orally administered thyroid. Am. J. Pharm. 133: 255-266, 1961.

2. Knox, F. G., J. S. Fleming, and D. W. Rennie. Effects of osmotic diuresis on sodium reabsorption and oxygen consumption of the kidney. Am. J. Physiol. 210: 751-759, 1966.

3. Knox, F. G., S. S. Howards, F. S. Wright, B. B. Davis, and R. W. Berliner. Effect of dilution and expansion of blood volume on proximal sodium reabsorption. Am. J. Physiol. 215: 1041-1048, 1968.

4. Knox, F. G. Effect of increased proximal delivery on furosemide natriuresis. Am. J. Physiol. 218: 819-823, 1970.

5. Knox, F. G., E. G. Schneider, L. R. Willis, J. W. Strandhoy, and C. E. Ott. Effect of volume expansion on Na excretion in the presence and absence of increased delivery from the proximal tubule. J. Clin. Invest. 52: 1642-1646, 1973. 6. Knox, F. G., E. G. Schneider, L. R. Willis, J. W. Strandhoy, C. E. Ott, J. L. Cuche, R. S. Goldsmith, and C. D. Arnaud. Proximal tubule reabsorption following hyperoncotic albumin infusion: role of parathyroid hormone and dissociation from plasma volume. J. Clin. Invest. 53: 501-507, 1974.

7. Knox, F. G., and C. Lechene. Distal site of action of parathyroid hormone on phosphate reabsorption. Am. J. Physiol. 229: 1556-1560, 1975.

8. Knox, F. G. The intrarenal metabolism of phosphate. Physiologist 20(6): 25-31, 1977.

9. Knox, F. G., J. A. Haas, T. Berndt, G. R. Marchand, and S. P. Youngberg. Phosphate transport in superficial and deep nephrons in phosphate loaded rats. Am. J. Physiol. 233 (Renal Fluid Electrolyte Physiol. 2): F150-F153, 1977.

10. Kohan, D. E., and F. G. Knox. Localization of the nephron sites responsible for mineralocorticoid escape in rats. Am. J. Physiol. 239 (Renal Fluid Electrolyte Physiol. 8): F149-F153, 1980.

11. Knox, F. G., and E. L. Ritman. The intrarenal distribution of blood flow: a new approach. Kidney Int. 25: 473-479, 1984.