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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 years---at 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.
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