Topics In Environmental Physiology And Medicine WALLACE OSGOOD FENN 1893 - 1971 Dr. Fenn's last award, The Honor Medal of the City of Monaco (July, 1971 ) Carbon Dioxide and Metabolic Regulations Edited by Gabriel Nahas and Karl E. Schaefer Satellite Symposium of the XXV INTERNATIONAL CONGRESS OF PHYSIOLOGY July 20 -21 -22 1971 International Conference Center Monte-Carlo, Monaco Springer-Verlag New York . Heidelberg· Berlin 1974 Library of Congress Cataloging in Publication Data Schaefer, Karl Ernst, 1912- compo Carbon dioxide and metabolic regulations. (Topics in environmental physiology and medicine) 1. Carbon dioxide in the body-Addresses, essays, lectures. 2. Carbon dioxide-Physiological effect Addresses, essays, lectures. 3. Metabolic regulation Addresses, essays, lectures. I. Nahas, Gabriel G., 1920- joint compo II. Title. [DNLM: 1. Carbon dioxide-Metabolism. QV314 S294c 1974] QP535.CIS3 574.1'9212 74-6247 ISBN-13:978-1-4612-9833-5 All rights reserved. No part of this book may be translated or reproduced in any form without written permission from Springer-Verlag. © 1974 by Springer-Verlag New York Inc. Softcover reprint of the hardcover 1st edition 1974 ISBN -13:978-1-4612-9833-5 e-ISBN -13 :978-1-4612-9831-1 DOl: 10.10071978-1-4612-9831-1 Preface Wallace O. Fenn (1893-1971) The proceedings of the satellite sym encompass the whole of physiology. His con posium of the XXV International Congress tributions over 50 years covered four main of Physiology on "C0 and Metabolic eras in the development of physiology: 2 Regulations" are dedicated to Wallace muscle, electrolyte, respiratory, and hyper Osgood Fenn. Dr. Fenn had agreed to be baric study. honorary conference chairman of this meet The study of muscle contraction started ing, but was unable to attend because of the in 1922 when Fenn became the first American illness from which he died two months later to work in A. V. Hill's laboratory. Fenn on September 20, 1971. concluded this work by saying, " ... There Wallace O. Fenn was born of an old is a fairly good quantitative relation between New England family in Lanesboro, Massa the heat production of muscles and the work chusetts on August 27, 1893. His father was which they perform; and a muscle which does dean of the Divinity School at Harvard ~ork liberates, ipso facto, an extra supply of University. It was at Harvard that Fenn energy which does not appear in an isometric received his A.B. (1914) and his M.S. (1916). contraction." (Fenn [1923]). A. V. Hill He then started his Ph.D. thesis there under referred to this as the "Fenn effect," and so the plant physiologist W. J. V. Osterhout, it has been known ever since. took a year out to serve as a nutrition officer Fenn's data showed first that if a muscle in the U.S. Army, and finished his degree in shortens it produces more heat than during May 1919. an isometric contraction over the same time From 1919 to 1922 he was instructor in period. He then showed that this extra heat applied physiology under Cecil K. Drinker production was proportional to the external at Harvard, and from 1922 to 1924 was a work done by the muscle. It was clearly not Traveling Fellow of the Rockefeller Institute, determined by the load alone, nor by the with A. V. Hill and Sir Henry Dale, in change in length. This was the first evidence England. In 1924, at the age of 31, he was that shortening is an active process and that appointed professor of physiology at the muscle is not simply a prest retched spring newly formed School of Medicine and shortening passively. Dentistry at the University of Rochester and At the University of Rochester Fenn remained there as chairman for 35 years. In began working on the relationship between 1959 he became Distinguished University the force exerted by muscle and the velocity Professor of Physiology, and in 1962, director with which it shortens. He first described the of the Space Science Center of the University. now familiar force-velocity curve under the Wallace Fenn was truly a universal title "Muscular force at different speeds of physiologist-one of the few who could still shortening." (Fenn (1935]). Fenn and Marsh vii viii Preface fitted the observed curve to an exponential and developed the concept that potassium relationship, which present-day kinetic theory tends to follow the Cori cycle. He was would predict. Andrew Huxley and, later, always quick to seize new opportunities. Richard Podolsky justified the model of When radioactive potassium became avail contraction (based on making and breaking able to him in 1939, Fenn ingested a sample. of cross-bridges between interdigitating slid He was thus the first not only to study the ing filaments) on the grounds that it would kinetics of potassium metabolism, but also to reproduce the force-velocity curve discovered demonstrate potassium incorporation into by Fenn and Marsh. blood cells, which were previously thought to Fenn next studied gas exchange by nerve be impermeable. He showed that nearly all and by muscle. In 1927 he measured for the muscle potassium in the body is exchangeable, first time the quantitative amount of oxygen proving that high intracellular potassium required by a nerve to conduct an impulse. content is not maintained by binding or Similar studies on the metabolism of con sequestration of potassium, but rather by an tracting muscles led him to consider the role active process. of potassium in nerve and muscle activity. Thus, by 1940 Fenn had discovered that At the time, although it was known that contracting muscle produces extra heat muscle fibers were rich in potassium, almost proportional to work; he had described the nothing was known of the mechanisms by force-velocity' relationships; he had dis which cells accumulated and maintained covered the potassium-sodium exchange dur a high potassium content. ing muscle contraction, and in addition, the In the 1930s Fenn pioneered the field mechanism for concentrating potassium in of potassium metabolism. He made the first cells. measurements of potassium, sodium, mag In 1941, at the onset of America's entry nesium, and calcium in nerve. He was the into World War II, he pioneered a completely first to measure intracellular pH in muscle new field, that of respiratory physiology. He and nerve by the CO titration method, focused his attention on the use and applica 2 which still is the most acceptable one today. tion of pressure-breathing devices to extend He showed that intracellular potassium was the aviator's altitude tolerance in non mobile and that muscle potassium shifted in pressurized planes. To simulate these con response to various environmental factors. ditions he installed a low-pressure chamber Fenn showed that during contraction, that was even more primitive than the one potassium was lost from muscle in exchange used 70 years before by Paul Bert in Paris. for sodium and that the process was reversed Exhibiting his usual thriftiness, he purchased in recovery. For the first time he showed that for $500 a tank originally designed to transport sodium could penetrate muscle. All of these beer. This device stood on its end in his observations, performed in the pre-flame laboratory, had a hatch on top, and could photometry era of electrolytes, established barely accommodate two subjects in the the necessary foundation for the Hodgkin sitting position. To enter, one had to climb a Huxley hypotheses concerning initiation and homemade wooden ladder, crawl in through propagation of nerve and muscle impulses the two-foot-wide hatch, and then lower and the magnitude and polarity of electrical himself like an acrobat to a stool six feet potential differences across cell membranes. below. The second man entered on the Fenn showed that potassium escaped shoulder of the first. In this chamber Fenn from muscle during contraction in situ and and his group of young collaborators "flew" that a large part of this potassium appeared nearly impossible missions to altitudes which in the liver. He demonstrated that potassium on occasion reached 50,000 feet (87 mm Hg). uptake was linked with carbohydrate meta Fenn passed out so many times that the dean, bolism, particularly with glycogen deposition, George Whipple, forbade him to enter the Preface ix chamber. The dean of the Medical School of During this period he wrote with the University of Rochester could ill afford Hermann Rahn the "02-C02 diagram," to lose his most brilliant professor, even for which was published by the American the war effort. With his young collaborators Physiology Society and has become the slide (Chadwick, Otis, and Rahn), Fenn developed rule of the respiratory physiologist (Fenn, theory and assembled facts which today form [1946bD· basic cornerstones in pulmonary physiology. In recent years he turned his attention to His previous interest in muscle physiology the basic problems of the effects of hydro contributed to the new attention he directed static pressure per se upon biological pro to the mechanics of breathing. His pressure cesses, an area that he liked to call baro volume diagram of the thorax and lung (Fenn physiology. Bacterial cultures became a [1946aD is now a classical concept. This, favorite organism since they can be pres combined with the measurements of airway surized without a gas phase and also because resistance, allowed him to describe for with them the predicted volume changes the first time the mechanics and work of during metabolic reactions can be modified breathing (Fenn [1951]), and laid the founda by the effects of external pressures. Further tions for the more recent developments in more, bacterial cultures are very inexpensive this area. to raise and maintain. The other problem that intrigued him In addition to his long and productive was the behavior of the alveolar gas exchange. research career he was an outstanding teacher. An article entitled" A theoretical study of the Like all great teachers, he could make difficult composition of the alveolar air at altitude" subjects appear quite simple, always, how set forth the equations that describe the ever, leaving the listener with the feeling that relationships and interactions between O2, many exciting aspects were yet to be explored. CO2, and N2. These equations are today the He also felt it his duty to serve scientific tool of every respiratory physiologist, and societies and scientific advisory bodies when Fenn's graphic display of these on the eyer he was asked. Over the years he chaired 02-C02 diagram were extended many years innumerable committees as adviser for the later in the form of a book. This analysis also National Academy of Science, the National led to the theoretical description of the Research Council, the National Institute of ventilation-perfusion relationships. Health, the United States Army, Navy and In the postwar years Fenn's department, Air Force, and the National Space Agency. with Hermann Rahn and Arthur Otis as He served the American Physiological anchor men, became the training ground for Society in every capacity, as treasurer (1937- respiratory physiologists from the United 40), secretary (1943-46) and president (1946- States and abroad: Arthur Dubois, Marsh 48). Under his presidency the APS was Tenney, Gaby Nahas, Dan Proctor, the late reorganized and an appointed position of Bob Clark, Leon Farhi, Don Gilbert, Pierre executive secretary-treasurer was created. Dejours, Hilding Bjurstedt, Paul Sadoul, Also during Fenn's presidency the APS Tulio Velasquez, Carl Magnus Hesser, Emilio Fall Meetings were instituted. The purpose Agostoni, Sue H. Rodgers, Hugh Van Liew, of this was to draw some papers away from Al B. Craig, Al Soffer, John Knowles, Harold the overcrowded program of the Federation Bitter, Richard Ament, Einar Aksnes, John Meeting and to provide a smaller meeting Chapin, Mike Lategola, Walter Massion, Ben that was more conducive to friendly social Ross, Jim Drorbaugh, Bob Stroud, and many gatherings. The first Fall Meeting was held others. Life-long associations which extended in Minneapolis in September 1948. At this beyond purely scientific endeavors were meeting the custom of having a past-president sealed among many of the pupils in Fenn's address was instituted by Dr. Visscher, then department. President. Fenn's "Physiology on Horse- x Preface back" (Fenn [1949]), the first of these good. But the danger does exist. Another addresses, should be required reading for all danger of easy money is the one-more technician complex, the idea that any prob students in biology. lem can be worked out by adding one more In this piece Fenn humorously empha technician without additional allowance for sizes the importance of basic research with the time to think. Easy money and the empire following anecdote: building complex is partly responsible also for the manpower shortage. In one famous A man called up a veterinarian about case A helped B to obtain a fat grant. Then his sick cat, and described its symptoms. The B in his affluence tried to take two skilled veterinarian understood calf for cat and electrophysiologists away from A's labora prescribed a pint of castor oil which was duly tory to help him on his project. One govern administered (more or less). Some days later ment agency creates so many new jobs by the veterinarian met his client and inquired grants that other government agencies are about the welfare of the patient. The man unable to secure needed personnel. Salary threw up his hands in despair and said that levels rise, which is good, but the overall the cat had had a hard time and had enlisted quality and quantity of good research does the assistance of three other cats. One was not. Thus we have a rising tide of diversion digging holes for him, the second was cover from true scientific work. ing them up and the third was way out in front opening up new territory. We probably Fenn was instrumental in developing need and should have two applied researchers the publications of the American Physio for everyone in basic research, but we cannot logical Society to their present level of do without the latter, the fellows who are out universal excellence. He was a member of in front opening up new fields, developing the Board of Publication Trustees of the new interpretations, new products, new ideas American Physiological Society from its and new methods. How few of the papers in inception in 1933, serving as chairman from our scientific journals are really original and 1950 to 1955. He was chairman of the Board new, in the sense that the theory of relativity, for example, is new ? Yet one such good new when it provided the means to purchase idea is worth a thousand others because it Beaumont House, insisting that Beaumont stimulates a flood of new work. be the home of the Federation. The APS Handbook series was suggested and imple He also cautioned the "foot soldier" mented during his last year as chairman and physiologists not to follow exclusively "men he co-edited the respiration section of the on horseback" who wished to lead scientists Handbooks of Physiology with Dr. Rahn. into large, expensive applied research pro Also during his term on the Board he was grams: instrumental in the founding of the Journal of Applied Physiology in 1948. He and others In these days of easy money for grants felt that much of the applied physiology done in-aid there is a danger of setting up so large during World War II, particularly that on a team of inexpert workers that the accumu human physiology which emphasized man lated data exceed the digestive powers of the and his environment, should be published in responsible investigator. The result is one the scientific literature. APS was the organi type bad research. The investigator over zation to do it; thus the birth of the Journal busies himself to such an extent that he of Applied Physiology, so valuable to all leaves himself no time to think. He is a respiration physiologists. victim of the project complex. He is an Fenn's interests and energies were not empire builder. He should get off his horse confined to APS. He helped Dr. Bronk and go back to his knitting in the Ivory revitalize the Union of American Biological Tower. I do not say that all extensive projects Societies, which became the American Insti are bad. Most are necessarily large and very tute of Biological Sciences, and succeeded in Preface xi getting the APS to be the first charter member In the Fenn household there was a simplicity, of AIBS in 1948. Fenn was always a champion a genuine quality of life that one rarely of AIBS and served as its president from encounters. His son William said it very 1957 to 1958. simply: His interests were also international in scope. He served as a member of the Council It was always surprising to us children, of the International Union of Physiological and I'm sure to his grandchildren too, that Pop was so honored among men, because he Sciences in 1956; was secretary general from never acted at home the way it seemed that 1959 to 1965; presided over the XXIV Con such a man should act. He mowed lawns, gress in Washington in 1968, and at that time, washed dishes, played games with his on the occasion of his 75th birthday, was children, played tricks on them, taught me unanimously elected the president of IUPS. how to throw an outside curve and an inside After the Leiden Congress in 1962 he started curve, cut bushes, felled trees, built docks, the IUPS Newsletter, which today reaches rowed and sailed boats, paddled canoes, physiologists all over the world. He compiled roamed through the woods, picked wild and edited the "History of the International berries, skated remarkably well, and did all Congresses of Physiological Sciences, 1889- the things that fathers do with their families. 1968" and arranged to have a copy for every A little extra measure of energy was present in Pop, or else he was more ready one attending the 1968 Washington congress. than most to use it. When things seemed too He also promoted the inclusion of satellite quiet at home, he was apt to jump up and symposia as an official activity of the inter say, "Let's go cut down a tree," or tackle national congresses. some other difficult task that needed doing, The Dutch composer Jurriaan Andriessen or go off on a picnic. Then there would be a dedicated Fenn his "Respiration Suite" great bustling about, rounding up equip (written for double wind quintet), first per ment, figuring how to attack the project, and formed at the First International Respiration then going at it. Dinner Group meeting at Alphen aan de We had several memorable tree-cutting Rijn, Holland, on September 12, 1962, during operations at our place in Canandaigua, one the time of the Leiden Congress. On the jacket of which was particularly so because almost of the recording is the statement, "An under all of the family, including grandchildren, were in on it. A large old tree had died in the standing of the musical performance of these winter and was leaning slightly over a neigh artists, in a physiological sense, rests to a bor's property and in danger of falling. We large extent on the work of Dr. Wallace O. rigged a strong restraining line to another Fenn and his associates on pressure-volume tree to help control its fall and commenced relationship of the lungs and chest, on the to cut. My brother, David, did most of the composition of alveolar air during breath chain sawing, and notched it properly. holding, and on physiological effects of Finally, it was evident that the tree was about pressure breathing." to come down. All the grandchildren and Finally, Dr. Fenn was more than a great their mothers got a safe distance away and scientist. He was a humanist and a dedicated Dave began the last sawing operation while the rest of us put all the force we could on family man. the rope. Then the tree cracked and tilted In 1919, a few months after obtaining about 30 degrees off vertical. Dave jumped his Ph.D. degree, Wallace O. Fenn married clear and the rest of us took up slack and Clara Bryce Comstock. They had four tugged away. But no matter how we pulled children, two sons and two daughters, and and got it swaying, the tree refused to come thirteen grandchildren. It was a true family, any further. After a couple of minutes of this which many members of the department effort, Pop walked up to have a closer look came to know when visiting the Fenns at at the cut. Then he picked up an axe, gave Highland A venue or at Canandaigua Lake. one mighty blow in the right spot, and down xii Preface she came with a great majestic crash while before and typed himself, such as one the whole gang yelled "Timber" as loud as entitled "The Brownies in the Laboratory." we could. All the grandchildren charged to The passing away of Wallace O. Fenn the tree and climbed into its branches in marks the end of the era, started by Claude triumph, and Pop was the hero of the day. Bernard over a century ago, when a man of genius could encompass and explain all of Dr. and Mrs. Fenn, a most gracious and physiology. kind "grande dame," informally entertained But above all, Dr. Fenn will be remem in their home the various members of his bered by those who knew him well as a truly large department, giving special attention to dedicated man who added a universal foreign visitors isolated from their homeland. dimension to his scientific endeavors. The annual departmental Christmas parties were special occasions never to be G.G.N. forgotten. The highlight was the reading of a K.S. poem Dr. Fenn had composed a few hours N.C.