John Richard Pappenheimer

37th APS President (1964-1965)
John Richard Pappenheimer
(b. 1915)

With the diamond anniversary of the Society properly celebrated the preceding year, as John Pappenheimer assumed the presidency in 1964 APS was already planning for the XXIV IUPS Congress to be held in Washington, D.C., in 1968. Pappenheimer later (1967-68) served as chairman of the Program Committee of the congress. His first contribution to the success of these meetings, however, was in persuading Council and then the members of APS to agree to a voluntary assessment that eventually provided some $50,000 for preliminary expenses of the IUPS Congress. At the Ninety-fourth Business Meeting of APS on 11 April 1965, members present "voted to assess themselves $10 each a year for three years to provide unrestricted funds for the International Congress." At that time the "regular" dues were fifteen dollars per year. Pappenheimer wrote of the proposal:

"Your Council strongly supports this measure for the following reasons. . . .

1. The assessment would strengthen both the hand and the spirit of our National Committee in approaching Government and Industry for further support.

2. The assessment would allow each of us to feel that we are fulfilling our role as hosts to physiologists who will be visiting us many for the first time from all parts of the world. For many of us this would be an opportunity to return, in small measure, the hospitality we have enjoyed in other lands.

3. Finally, the assessment would enable us to live up to the precedent and faith of our forebears who contributed personally to their Congress in 1929, at a time when there was no government support whatsoever. A reaffirmation of our faith in the International Congress of Physiology is specially important today as outside sources of support falter under the barrage of requests from those who have come to rely wholly on subsidies."

Born in New York City, John Pappenheimer followed his older sister, Anne (Pappenheimer Forbes), and brother, Alwin Max, Jr., to college in Cambridge, Massachusetts, where all three subsequently became professors Anne in medicine at Massachusetts General Hospital and Alwin in biochemistry/biology at Harvard. John received his B.S. degree from Harvard College in 1936. In the summer following his junior year of college he took the physiology course at the Marine Biological Laboratory at Woods Hole, where his instructors included Laurence Irving, C. Ladd Prosser, and J. K. W. (Ken) Ferguson. Pappenheimer wrote:
"Alan Burton (APS president, 1956-57) was a fellow student, and we competed for the Collecting Net prize. Ferguson had just published his important work with Roughton on carbamino hemoglobin, and together we investigated carbamino reactions in fish blood. Later, I too went to Cambridge, England, to study with Barcroft, Roughton, and Winton. As a graduate student I worked on the thermodynamic efficiency of urine formation in isolated perfused dog kidneys [with Frank Winton and Grace Eggleton (2)]. As part of this work we developed spectrophotometric methods for oxygen saturation in flowing blood (with Glenn Millikan, then fellow of Trinity College). When the war came in 1939 it was natural for me to join forces with Millikan to work on the ear oximeter and on oxygen equipment for military aircraft under the aegis of Detlev Bronk."

Pappenheimer received his Ph.D. degree from Cambridge University in 1940, after having served for a year as demonstrator in pharmacology at University College, London. In his past president's address Pappenheimer wrote of this stage of his training:
"I was fortunate enough to take the Part II Honors course in physiology at Cambridge, England. This was full-time physiology for a year, and the course consisted of one lecture each day followed by reading, reading and more reading. There was relatively little laboratory work and what there was I have mostly forgotten. But we came to know the classical literature of three languages, leading up to the then frontiers in almost all sectors of physiology. I have been everlastingly grateful for this period of intensive study. It provided a framework for subsequent research and teaching and made possible the enjoyment of continued reading in fields outside one's own narrow research interests."

When he returned to this country Pappenheimer was for two years (1940-42) a research fellow and instructor in physiology in the department of Magnus K. Gregersen at the College of Physicians and Surgeons of Columbia University. He then devoted three years (1942-45) to research with Millikan in Bronk's laboratories in the Johnson Foundation at the University of Pennsylvania, as noted above. He moved to Harvard in 1946. In 1953 he was designated a Career Investigator of the American Heart Association (AHA) and thus became a visiting professor at Harvard. In 1969, however, he was appointed to the George Higginson Chair in Physiology while retaining the award of the AHA.

Most of the research for which Pappenheimer is known has been published from the Harvard laboratory. He described it as follows:

"After the war I was eager to resume prewar studies on edema formation in perfused muscle, and this led me to Landis's new department at Harvard. Ideas and techniques I had absorbed from Winton provided the basis for measurements of capillary pressure, pre- and postcapillary resistances, in vivo protein osmotic pressure, and transcapillary fluid movement in perfused muscle (3). The theory of restricted diffusion, molecular sieving, and osmotic transients soon followed and with it the understanding that diffusion permeability differs from flow permeability and their ratio is directly related to the dimensions of aqueous channels through the membrane. By 1951 (4) we were able to characterize the passive permeability properties of muscle capillaries in terms of the molecular dimensions of permeant molecules, on the one hand, and the dimensions of aqueous channels through capillary walls, on the other. The general theory survives to this day (5)."

This is the research by which Pappenheimer is represented in every modern textbook of physiology, although in many cases the name of the author is no longer stated. It has become "what every schoolboy knows."

More recently, having developed a technique for cerebral ventriculocisternal perfusion using unanesthetized goats, Pappenheimer and his associates studied chemical factors involved in control of breathing (6, 8) and induction of sleep (9, 11). They have not been able to isolate and identify the factor present in cerebrospinal fluid that induces slow-wave sleep, but they have discovered that a muramyl peptide present in brain or urine has a potent sleep-promoting action. Whether it is the inducer of natural sleep remains uncertain. This research led to Pappenheimer's current interest in hypoxic insomnia (10) and in the absorption of muramyl peptides from the small intestine. He hopes to report on one of these topics at the One Hundredth Anniversary Meeting of APS.

Pappenheimer became a member of APS in 1946. In 1956 he was selected to present the Society's first Bowditch Lecture in Rochester, New York. Elected to APS Council in 1961, Pappenheimer served there through his year as past president in 1966. Since 1968 he has served as chairman of the Perkins Memorial Fellowship Committee. He was a member of the Editorial Board of Physiological Reviews (1959-63), the Handbook of Physiology Editorial Committee (1961-67; chairman, 1972-78), and the Editorial Board of the American Journal of Physiology (1967-73). He also has been a member of the editorial boards of Review of Scientific Instruments (1949-51), Proceedings of the Society for Experimental Biology and Medicine (1955-61), and Circulation Research (1962-65). He has held office or served in an advisory capacity for the National Research Council (NRC) from 1956 to 1962, the National Heart Institute from 1961 to 1965, the American Institute of Biological Sciences (AIBS) from 1962-1966, Annual Reviews from 1971-1977, and IUPS from 1974 to 1983.

Elected a fellow of the AAAS (Boston) in 1954, Pappenheimer was made a member of NAS in 1965. He was a visiting professor at the Rockefeller University from 1960 to 1963. In 1971 he was given the Carl J. Wiggers Award by the Circulation Group of APS, and in 1979 he received the Ray G. Daggs Award of APS.

The association Pappenheimer began with British physiology when he was a graduate student at Cambridge has continued. He is an honorary member of the British Physiological Society and was an overseas fellow of Churchill College, Cambridge (1971-72), and also Eastman Professor at Oxford (1975-76). Whether his affinity for bicycling developed in the Cambridge of England or of Massachusetts is not known. It served, however, as both an introduction and framework for his past president's address (7). He described his daily "commute" along the Charles River to Boston and related the ride to those forces that seem to be troubling the discipline of physiology, by distributing it among subdisciplines to such a degree that little seems to be left of the parent science. He concluded by noting that his bicycle had gone 15,000 miles and probably would serve for another 15,000. In a more recent communication he reports, "I have already added another 30,000, and I'm projecting an additional 20,000 between now and the turn of the millenium."

One of Pappenheimer's most engaging qualities is the fun he has derived from a career in laboratories and classrooms as well as from riding his bicycle.

Selected Publications

1. Pappenheimer, J. R., M. P. Lepie, and J. Wyman, Jr. The surface tension of aqueous solutions of dipolar ions. J. Am. Chem. Soc. 58: 1851-1855, 1936.

2. Eggleton, M. G., J. R. Pappenheimer, and F. R. Winton. The influence of diuretics on the osmotic work done and on the efficiency of the isolated kidney of the dog. J. Physiol. Lond. 97: 363-382, 1940.

3. Pappenheimer, J. R., and A. Soto-Rivera. Effective osmotic pressure of the plasma proteins and other quantities associated with the capillary circulation in the hindlimbs of cats and dogs. Am. J. Physiol. 152: 471-491, 1948.

4. Pappenheimer, J. R., E. M. Renkin, and L. M. Borrero. Filtration, diffusion and molecular sieving through peripheral capillary membranes. Am. J. Physiol. 167: 13-46, 1951.

5. Landis, E. M., and J. R. Pappenheimer. Exchange of substances through the capillary walls. In: Handbook of Physiology. Circulation., edited by W. F. Hamilton. Washington, DC: Am. Physiol. Soc., 1963, sect. 2, vol. II, chapt. 29, p. 961-1034.

6. Pappenheimer, J. R., V. Fencl, S. R. Heisey, and D. Held. Role of cerebral fluids in control of respiration as studied in unanesthetized goats. Am. J. Physiol. 208: 436-450, 1965.

7. Pappenheimer, J. R. Past-president's address. A bicycle in the age of jets. Physiologist 8: 341-347, 1965.

8. Pappenheimer, J. R. The ionic composition of cerebral extracellular fluid and its relation to control of breathing. Harvey Lect. 61, 1966.

9. Fencl, V., G. Koski, and J. R. Pappenheimer. Factors in cerebrospinal fluid from goats that affect sleep and activity in rats. J. Physiol. Lond. 216: 565-589, 1971.

10. Pappenheimer, J. R. Sleep and respiration of rats during hypoxia. J. Physiol. Lond. 266: 191-207, 1977.

11. Pappenheimer, J. R. Induction of sleep by muramyl peptides. Bayliss-Starling Memorial Lecture. J. Physiol. Lond. 336: 1-11, 1983.