News From Senior Physiologists

As originally published in The Physiologist
Volume 45, Number 4, August 2002, page 230

Letter to Novera Herbert Spector

Virendra B. Mahesh writes: “Thank you for the letter of January 11, 2002 congratulating me on my 70th birthday in April this year. In response to your request, I am giving you, hereby, details of my retirement, how the decision was reached and what I am doing now. 

“The elimination of a designated retirement age in academic life creates both exciting opportunities as well as challenges. The opportunity is the chance to continue to be productive and creative and not be compelled to retire prematurely. The challenge is to identify the appropriate time of retirement. The possibility of staying too long on the job or forced to retire because of decreased productivity or due to becoming non-competitive in the field should be avoided. This is important because the academic environment flourishes only with the constant infusion of new ideas and new approaches. Most importantly, the transition should be made with grace and dignity. 

“The decision for me was a particularly difficult one as I really enjoyed what I was doing with the exception of administrative responsibilities. I was at the Medical College of Georgia for 40 years and for the last 27 years served as the chairman of my department (Department of Endocrinology 1972-1986 and Department of Physiology and Endocrinology 1986-1999). I had been funded continuously as principle investigator for the last 39 years by NIH (my first NIH R01 started nine months after my initial appointment) and held a NIH research-training grant for 35 years. I had served on three regular and several ad hoc NIH study sections including being chair for several since 1975. I had mentored 11 MS students, 25 PhD students and 59 postdoctoral fellows and had over 400 peer-reviewed research publications. I was still active professionally in all aspects of academic life and my institution was anxious for me to continue my appointment. 

“After giving considerable thought to the situation, I came to the conclusion that it was about time when I should spend more time doing things I really enjoy and give up those that are burdensome. I was in an excellent position to initiate change, which is inevitable in the long run, at my pace and under conditions of my choosing. And finally, I was in an excellent position to negotiate resources that would make my future goals feasible. 

“I therefore, decided to retire as Regents Professor and Chairman, Department of Physiology and Endocrinology at the Medical College of Georgia in 1999. I still follow my life long interests to the fullest. As Regents Professor and Chairman Emeritus, I still teach, mentor and collaborate in research. I, thus, continue to participate in the most attractive part of research, that is identifying key questions, generating hypotheses, designing experiments and evaluating results. I leave grant writing, fund raising, and laboratory management to my collaborators. I still participate as ad hoc member of NIH study sections, although not as frequently as I am asked to do. I am serving as editor-in-chief, of the premier journal in the field of reproduction, Biology of Reproduction from July 1, 1999 to June 30, 2004. In addition, I served as councillor and member of the Steering Committee of the Section of Endocrinology and Metabolism of the American Physiological Society from 1999 to 2001. I am currently a member of the Joint Program Committee of the American Physiological Society representing the Section of Endocrinology and Metabolism for a three-year term (2001 to 2004). I go to all major scientific meetings in my area of interest and retain an office at the Medical College of Georgia.”

Letters to Michael Barany

Otakar V. Sirek writes: “I am no longer involved in teaching and research, but have developed my long-standing interest in classical music, particularly in opera. Nevertheless, on my mind are some reflections on the past that I would like to share with my younger colleagues. My thoughts concern two subjects: one is undergraduate teaching, the other is family life of two professionals. It is a highly personal view, based on my 56 years of marriage combined with professional partnership.

“As to undergraduate teaching, there can be no argument that it must be first-rate, if in subsequent studies a student should do well in graduate courses and conduct good research. To that effect there are excellent text books and other teaching aids that should give the undergraduate the necessary ammunition to learn the subject well. However, most undergraduates are young individuals not well-equipped to distinguish essential information from details. An experienced lecturer can help the student to integrate concepts regarding the function of individual organs in relation to the body as whole. In my opinion, it is in this area where formal lectures are important. The additional advantage of formal lectures in a professional faculty is the latitude to allow the teacher to tailor the course to the specific needs of a given discipline in the health sciences.

“As to the family life of two professionals, I feel very strongly that if the union is to succeed, rights and duties need to be responsibly assessed by both partners before marriage. Adherence to commitments is particularly important if the partners intend to have children. Even if everything is planned ahead of time, there will be unforeseen situations where flexibility will be of essence and willingness to substitute for one another sheer necessity. To run careers as scientists and parents is demanding, but nothing is ever achieved without sacrifice. Boys and girls have a right to have their mommy and daddy around; parents have the duty to respect those rights by dividing their quality time and by sharing not only household responsibilities, but also the upbringing of their children. I realize that each family has to make suitable adjustments, depending on the type of employment, age of their offspring and other circumstances, but to me, the basic principle is undeniable: children need both parents if they are to grow up as balanced individuals. In this respect, I can present some credentials, in that both my wife and I were teaching and doing research all our adult lives and succeeded to bring up four children, now adults, who have good family lives and careers to be proud of. At the end of the day, I can say, ‘Yes, challenging it was, but also extremely rewarding.’”

Setsuro Ebashi writes: “Thank you for your congratulatory notes for my 80th birthday.

“After graduation from the University of Tokyo, School of Medicine in 1944, I served the Navy as a surgeon for two years and then started scientific research in the Department of Pharmacology in the University of Tokyo under the guidance of Professor Hiroshi Kumagi, in whose laboratory I had spent much time as an undergraduate and enjoyed its stimulating and comfortable atmosphere. Professor Kumagai, gave me the theme ‘electrophysiology of smooth muscle,’ but I eventually converted to biochemical approach after I read and was deeply impressed by the book ‘Chemistry of Muscular Contraction by Albert Szent-Gyorgyi. I was especially attracted by the demonstration of ATP-induced contraction of glycerol-treated psoas muscle fibers in this book, but soon noticed that fibers shortened never be elongated even after removal of ATP. This is quite different, for example, from acetylcholine-induced contraction of living muscle, where the removal of acetycholine quickly results in relaxation. Inquiring into this puzzling fact, I found in 1952 that the relaxation could be induced by adding muscle extract to the contracted fiber together with ATP. However, soon it was realized that the same experiment had already been done more than a year ago, and, therefore, I had no scientific priority. This was not my disappointment but an encouragement and I pursued the active principle in the extract, relaxing factor, and in 1955 identified it as the microsome fraction of muscle, first isolated by Kielly and Meyerhof as granular-MgATPase in 1948.

“As for mechanism of relaxation, I guessed that it might be the removal of Ca2+ ion from the actoyosin system, but the results of my experiments showed no parallelism between Ca2+-depriving activities of various chelating agents and their relaxing activities. Disappointed by these results, I joined Professor Fritz Lipmann’s laboratory at the Rockefeller Institute in 1958. I was inclined to convert to enzymology under Professor Lipmann, but he advised me to continue my own muscle research. I followed this valuable advice, and one day, having reexamined my previous results obtained in Japan, I found a serious mistake in my previous calculations: after correction there was a precise parallelism between the two activities! At this point I was convinced about the Ca2+-depriving nature of the relaxing factor, and indeed, I could demonstrate that the factor strongly takes up Ca2+ from the medium in the presence of ATP. In the meantime, the factor was shown electronmicroscopically to consist of fragmented sarcoplasmic reticulum. I could also demonstrate that a minute amount of Ca2+ is necessary for the contractile reaction induced by ATP of well-washed Ca2+-free natural actomyosin system. In order to prove this, I had to exert all possible efforts to avoid the contamination of Ca2+ from reagents or exuded from glassware of the day. From these results, a clear picture of the excitation-contraction coupling could be drawn for the first time: the shuttle movement of Ca2+ from the sarcoplasmic reticulum to the contractile system and vice versa cause contraction and relaxation, respectively. 

“Coming back to Japan from New York, I then inquired into the basis of Ca2+ sensitivity of the actomyosin system. A clue was in the fact that actomyosin composed of myosin and a certain preparation of actin was insensitive to Ca2+. At first I thought that denaturation of actin might be responsible to the Ca2+ insensitivity and started to examine various actin preparations. However, I finally reached the conclusion that a protein factor associated with actin, which resembled tropomyosin, was responsible for the Ca2+ sensitivity. The protein factor was then found to consist of two components; one was classical tropomyosin and the other a new protein having a strong Ca2+ binding capacity, named troponin (1965). Thus it was established that the contractile system underlying physiological contraction is composed of four proteins, i.e., two contractile proteins, myosin and actin, and two regulatory proteins, tropomyosin and troponin, and the present view of the molecular mechanism of contraction-relaxation cycle was reached.

“Looking back, I was fortunate to have great teachers, Professor Kumagai, who enthusiastically guided me toward the scientific research and always encouraged me warmly, and professor Lipmann, who gave me invaluable advice and suggestions.” 

Richard V. Andrews: “Please accept my thanks to you and the Committee on Senior Physiologists for remembering my 70th birthday with congratulations. Also, please accept my apology for being so remiss about answering; I was away from my home and office during January until now. 

“I retired from full-time teaching and research in 1997. I could not forecast continuing laboratory research on wild-caught small mammals because of the hanta virus scare, which made animal care committee’s and facilities less than enthusiastic. While I continued field surveys of wild mouse and vole abundance for two years, prospects for gaining financial support are dim, so that I have no further plans for formal research. I continued some part-time teaching of medical and nursing students as emeritus Professor until this past year, but gave those duties to younger faculty as a part of their career development. I now enjoy the freedom that retirement provides for leisure travel.

“I would like to remind younger physiologists that the tradition of our discipline transcends important grounding in technical skills and seeks to explain integrative function of the whole. Participation in the advancement of our science not only requires designing and executing well-controlled experiments, but also encourages transmission of the excitement of discovery to each new generation of students. Both personal involvements in advancement of our science, and in the nurture of students, bring lasting personal satisfaction.

“Once again, thank you for your letter of congratulations.”

W. Ross Adey writes: “I am indeed honored by the invitation of the Members of the Senior Physiologists Committee to mark the occasion of my 80th birthday with a brief description of my current activities and my philosophic approach to research and thinking.

“The actual day of my 80th birthday passed like all previous working days, with its usual tangled web of challenging basic science, clinical evaluations, and the inevitable bureaucracies that have become the uninvited handmaidens of all our science.

“The long term focus of my research interests continues to seek answers to the intrinsic organization of tissues, and how communication between cells may set tissue thresholds for extrinsic and intrinsic stimuli determined by their ensemble behavior, as they “whisper together” in a range of faint and private languages.

“Increasingly, experimental evidence points in this direction from actions of physical agents, including gravitational fields, ionizing radiation, and extrinsic and intrinsic nonionizing electromagnetic fields; and by interactions of imposed nonionizing electromagnetic fields with hormonal regulatory mechanisms. There is the salutary observation, challenging to us all, that the human auditory threshold involves a hair cell vibration of 10-11 meters, or about the diameter of a single hydrogen atom. But by an as yet unknown mechanism, the ear suppresses the vastly larger noise of its thermal atomic and molecular collisions, functioning as an almost ‘perfect’ amplifier close to 0 degree K.
 
“I officially retired six years ago, but this blessed condition seems to have wrought little or no change in the sense of importance, and even urgency, that one feels towards the growing edifice of science. We dare not fail to engender in younger minds a passionate curiosity and an imagination sufficient to kindle their commitment to all that is great and good in the scientific method. Reflecting on major changes wrought in the national medical research scene over the past 40 years, there is a cause for deep and growing concern that research training, and the culture of research accomplishment, have stifled the burning thorn of personal discontent that should be the creative option of all young minds entering on a research career.

“Graduate students are assigned a project that is typically a segment of their advisor’s grand vista. They may not deviate to ask creative ‘what if’ questions. They emerge from the chrysalis of their training, bearing a parchment to the professional market place, affirming proficiency in certain techniques, but in no way proclaiming the arrival of that precious citadel of a creative mind. Carl Djerassi’s novel, Cantor’s Dilemma, might well be required reading for us all. 

“May I conclude with an emergent thought from my own research experience. Formal instruction in physics, theoretical and applied, has become the weakest link for the majority of those entering on a career in medical research. It begins at the high school level. We now discern biological organization based in physical processes at the atomic level, beyond the realm of chemical reactions in the exquisite fabric of biomolecules. Without a versatility in biophysics that matches their typical knowledge in molecular biology and biochemistry, none may cross this threshold to the cutting edge of key areas in future medical research. 

“Thank you for the great privilege of submitting these personal reflections.”

David V. Bates writes: “Many thanks for reminding me so gracefully that my 80th birthday was fast approaching. My recollections of that period of my life when physiological questions dominated it, may be some of historical interest, so here they are. 

“After the trauma of World War II, those of us in clinical work in most disciplines had a natural interest in physiology. Chest physicians were pre-occupied with problems of managing tuberculosis (their traditional bread and butter), and were not interested in trying to design tests of lung function, nor in lung physiology. I can recall the amazement with which we learned about the fundamental work on gas exchanged (the alveolair air equation for example) and lung mechanics that has come out of the wartime research in the US Air Force and Navy. My postgraduate year in 1952 with Julius Comroe in Philadelphia sharpened my perception of the many interesting physiological questions that remained to be investigated; and established my lifelong friendship with Robert Forster and Ward Fowler. Academic medicine in Britain was stagnating, which is why I followed my mentor, Ronald Christie to McGill in 1956. I remember that I took an oscilloscope and camera with me, as we were using this for the first measurements of lung compliance. I also took an Astrup PCO2 apparatus, and we were one of the first groups managing respiratory failure with knowledge of the arterial PCO2. Our work on lung function was greatly stimulated by the development of external counting and the use of Xe133; and those I recruited, particularly Joseph Milic-Emili and Peter Macklem, were destined to add many dimensions to our understanding of lung function. At this time, I established a close intellectual relationship with the Department of Physiology at Dartmouth, under the leadership of the late Marsh Tenney. I had had an exercise treadmill constructed in Bart’s in London (maybe the first in a hospital?), and brought this with me to the Royal Victoria Hospital in Montreal. Our studies of exercise diffusing capacity there brought me into close contact with those, mainly in Scandinavia, interested in exercise physiology.

“The invitation to become Chairman of the Department of Physiology at McGill meant that I gave up my clinical responsibilities, but in exchange I acquired new research space. This I devoted to building a Perspex exposure chamber to define the effects of low concentrations of ozone of the lung if it was breathed during exercise. One highlight of my career as a physiologist was the task of organizing the Respiratory Dinner at the International Physiology Congress in Washington DC in 1968. This was held at the Mayflower Hotel, with a prior reception at the National Geographic Society headquarters. At the dinner, Wallace Fenn (whose birthday it was), Julius Comroe, Andre Cournand, and Ronald Christie were all at the same table. Music was provided by a distinguished group, including the first horn of the Chicago Symphony Orchestra, who had been interested in the respiratory mechanics of blowing wind instruments. 

“In 1972, I was invited to move to the University of British Columbia and to double the size of the medical school. At this point I left the physiological scene, though I continued to keep in touch with the many friends I had made during that period. Five years of that (more than three times the current ‘half-life’ of US Deans of Medicine in that era I think), brought me to 1977, when I returned to clinical bedside teaching and developed a research program in Environmental Epidemiology; this led to one of the first ‘time series’ studies of the association between hospital admissions for acute respiratory disease and daily levels of air pollutants in Southern Ontario. After I retired in 1987, I continued this research interest, in which I am still involved; last year I began co-editing a newsletter on health and air pollution with a colleague (a lawyer) in Washington DC. We have been very much encouraged by the warm reception given to our first issue.

“I have never regretted the 22 years in which I participated in the development of our understanding of lung physiology; the field has, of course, moved on, but I like to think that this occurred because, during that period, we did our work so well. What word of wisdom would I like to pass on? Knowledge is indivisible.”

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