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News From Senior Physiologists |
Alan F. Hofmann writes: “I am responding to your letter received shortly after my 70th birthday. I apologize for the delay, but I have been too busy to give you a proper response.
“I continue to work on selected problems relating to bile acids. For some four decades, I have devoted my research activities to elucidating the biology and chemistry of these water-soluble, amphipathic end products of cholesterol metabolism. I have tried to define their metabolism and physiological functions in animals and in man and how these functions are perturbed in disease. The research has been translational-from bench to bed and back to the bench. As someone trained in clinical medicine, I have kept my research oriented toward human disease and when possible done experiments in man to validate concepts developed in animals. The work has been fun and involved a variety of disciplines.
“After finishing a residency in internal medicine, I had research training at the National Institutes of Health as a clinical associate where I attempted to educate myself in biochemistry and cell biology. Then I was fortunate to be able to spend three years working under the direction of Bengt Borgstrom at the University of Lund, Sweden where we tried to describe fat digestion using principles of physical chemistry. Returning to the US, I worked on bile acids as related to cholesterol metabolism at the Rockefeller University, and then from 1966 to 1977 served as a co-director of clinical and basic gastrointestinal research at the Gastroenterology Research Unit of the Mayo Clinic and Mayo Foundation. Since 1977, I have been in the Department of Medicine of the University of California, San Diego. At both the Mayo and UCSD, I established a laboratory capable of synthetic organic chemistry, animal and clinical investigation.
“At the Mayo, we discovered that one of the natural bile acids (chenodeoxy-cholic acid) when administered orally would decrease hepatic induce the slow dissolution of cholesterol gallstones. Today, medical dissolution of gallstones has been largely replaced by laparoscopic cholecystectomy, but our work (and that of many others) made this common malady of interest to the scientific community. At UCSD, my colleague, Lee Hagey, initiated a program in cooperation with the Zoological Society of San Diego aimed at defining biliary bile acid composition in vertebrates. Using chromatographic techniques, he has examined the biliary bile acids of hundreds of vertebrates, and discovered several completely new bile acids. With the late Karol Mysels, a renowned physical chemist, we defined the structure activity relationships of bile acids as it relates to micelle formation, as well as the rules of precipitation of insoluble calcium salts of bile acids. During the last ten years, we synthesized a novel conjugated bile acid that was resistant to bacterial attack and have shown that this compound enhances the nutrition of undernourished patients with the short bowel syndrome. At present, with Lee Hagey, I am using the powerful technique of electrospray mass spectrometry to define the prevalence of defective bile acid synthesis in children with constipation.
“Through the years, I have been most fortunate in attracting truly remarkable postdoctoral fellows many of whom have gone on to distinguished careers in clinical medicine. I stopped taking postdoctoral fellows about four years ago because I felt that I was not training them in the powerful techniques of molecular biology whose use appears to be essential for extramural funding. But we have maintained the analytical laboratory that has permitted us to keep thinking about the chemistry of bile acids, and permitted several valuable collaborations.
“From an educational standpoint, I helped to co-found the Undergraduate
Teaching Project of the American Gastroenterological Association. This project
has resulted in the creation of outstanding slides for the teaching of gastrointestinal
physiology and pathophysiology. Four years ago, with the support of the Falk
Foundation, I co-authored a biography of the late Siegfried Thannhauser, once
Professor of Medicine at the University of Freiburg, Germany, a distinguished
clinical investigator and clinician, and author of the first textbook of metabolic
biochemistry in Germany. Thannhauser, who was of Jewish ancestry, was dismissed
from his position by the National Socialists, and emigrated to America to begin
a new career in practice and clinical lipodology at Tufts University Medical
School.
“As I look back on my long career of singe-minded laboratory and clinical
investigation, I am pleased that I have had the thrill of discovery, the satisfaction
of occasionally helping patients, and the friendship of many talented postdoctoral
fellows. My only regret is that I did not have the ability to do this and be
simultaneously a wise and caring physician. I have always been based in a clinical
department, which has kept me humble in the presence of so much ignorance about
human disease, and at the same time, has led to valuable collaborations. My
involvement with the American Gastroenterological Assoc-iation and the American
Association of the Study of Liver Diseases, has precluded me from any extensive
service with the American Physiological Society, surely one of our great national
societies. I have enjoyed the friendship of two of its stalwart statesmen-Horace
Davenport and the late Charles Code.
“If I ad to give any advice to young scientists, it would be to 'know thyself.' It is important to find out early in life whether the thrill of discovery is sufficient to compensate for the sacrifice of time with family and friends that experimental science entails. If it is, then a career in investigation will be rewarding. If it is not, then one should pursue a career that leaves time for the pursuit of the many other pleasures that life offers.
“In the next ten years, health permitting, I will continue to write up unpublished work and pursue collaborations that use our facilities for chemical analysis of bile acids. There will be more time for travel and family (my lovely wife Heli, two daughters, and five grandchildren). I toy with the idea of authoring a monograph that would provide an introduction to the fascinating field of 'cholanology' (the science of bile acids), but I do not know if there is sufficient interest in this small field to justify the immense effort that would be required.
“It has been great fun and it is still continuing.”
Desmond R. H. Gourley writes: “Thank you for remembering my 80th birthday which occurred in the fall of 2002. I will attempt to briefly answer the questions you posed. After earning a doctorate in cell physiology at the University of Toronto, I took postdoctoral training under the direction of Dr. C. L. Gemmill at the University of Virginia. This led to an appointment as Assistant Professor in the Department of Pharmacology in the UVA Medical School in 1951 with subsequent promotions up to Professor of Pharmacology and periods as Acting Chairman and Chairman in 1965-69. An opportunity to help to establish a new medical school took me to Eastern Virginia Medical School in 1973 and I retired from this institution as Professor and Chairman of Pharmacology in 1986.
“I owe much to my mentors, Dr. K. C. Fisher at Toronto and Dr. C. L. Gemmill at Virginia, both of whom encouraged me in my interest in the movement of ions across cell membranes and the effects of drugs on these processes. Like most APS members in academic medicine, I combined laboratory investigations with teaching. I have been particularly interested in new teaching methods and since the late 1940s have participated in the evolution of the animal laboratory part of basic medical science courses into programs of small-group problem-solving exercises. I have always been a strong proponent of pointing medical students in the direction of what they needed to know in order to solve clinical problems and co-edited what I believe was the first comprehensive compilation of learning objectives in medical pharmacology.
“I am not now involved in physiology/pharmacology research. Upon retirement, my wife and I seized the opportunity to indulge our long-postponed interests in other areas. High on our list is expeditionary travel with other scientists to out-of-the-way places in the world that occupies us about two months of the year. This, in turn, has provided us with occasions to study and photograph wild life in natural settings. The adventures and images usually lead to illustrated travelogs presented each year in several venues in Virginia and further afield. This dovetails nicely with our interest in the Wintergreen Nature Foundation that we helped to found and on whose Board I have served in the past.
“In addition to the above activities, my wife and I have devoted much time to family history, another long-standing interest. I write for several genealogical publications and review books for one of them. I also contribute occasional essays to a National Public Radio outlet in central Virginia. There is also hiking in summer and skiing in winter in the Blue Ridge Mountains where we have our home.
“The inevitable aging process is beginning to take its toll on both my wife and me but we are in reasonably good health. Our five sons and their families live in widely scattered locations but e-mail is a wonderful way to keep in touch with them and with old friends.”
Jean M. Marshall writes: “Thank you so much for your congratulatory letter on my 80th birthday, 12/31/02. My reply was delayed by preoccupation with shoveling snow and empting kitty litter, tasks that take considerably longer at my advanced age. You requested some philosophical observations about life and Physiology. Waxing philosophical and sequestering cats are the definitive indications of senility. After this letter I fully qualify on both counts.
“My professional life as a physiologist was one of unqualified pleasure primarily because it was initiated and nurtured by a series of remarkable individuals. To these individuals I owe my undying gratitude. To Abby Turner and Charlotte Haywood, my undergraduate teachers, who introduced me to the wonders and excitement of Physiology. To Wallace Fenn who supervised my graduate work. He was a tolerant, understanding, gentle professor who gave me complete independence and responsibility to make my own mistakes but was always available for support when things went wrong. The perfect mentor. To Harold Burn and Edith Bulbring who tolerated this brash Yank during her postdoctoral years. Their Department was like a family where the latest research findings were frequently shouted from the second floor balcony for everyone to hear. Arguments followed during lunch. Everyone worked hard and played hard! To Philip Bard, Vernon Mountcastle, Jerzy Rose and Otto Krayer who provided encouragement and advice during my early real professional life. Finally to the postdoctoral, medical and undergraduate students who brought youthful enthusiasm, energy, new insights and frequently just plain fun into the lab. As an added bonus to the support and help these individuals also gave me a lifetime of warm friendship. To all of these wonderful people I say 'thanks for the great ride’, and ‘I’m unanimous in that.’
“To my parents who gave me good genes so that now I still can creak around, swim, walk, garden, volunteer and one day/week take the ‘T’ (no sane person drives into Boston) to the Boston Medical Center where I assist (?) a young colleague in the Vascular Research Institute and attend seminars. Although I don’t understand much of what the speaker says the luncheons are great.
“A final philosophical aphorism: the greatest teachers are usually also the greatest researchers. Again my thanks to you and the Society for remembering me at 80. During my next 80 years I intend to become a veterinarian.”
Arthur B. Otis writes: “Thank you for your letter. I no longer do any scientific work, but I do keep in touch with the Physiology Department. My only recent publication (Am J Crit Care Med 161: 345-346, 2000) was by invitation and was based on reminisences. You ask which of my contributions do I think most important. I will leave that for others to judge. Most of them were important to me because they revealed or clarified relationships that I had not previously appreciated. You ask if I have any words of wisdom to pass on to younger colleagues. The following anecdotes may serve.
“While at Iowa as a post doctoral fellow, I had a job offer elsewhere, and I went to my boss, Dr. Bodine for advice. One thing he said I will always remember: ‘Get yourself a sail not an anchor.’
“At the Johns Hopkins my initial responsibility was to ensure that blood sampling and analyses were properly done. After a few weeks Dr. Blalock told me that he wanted me to do some of the catheterizations myself. I pointed out that I didn’t have an M.D. degree. His reply was, ‘Arthur, you should know that degrees don’t amount to a damn.’ So I learned the technique and was soon teaching it to interns and residents.
“Also at the Hopkins part of my appointment was in the Physiology Department where Dr. Philip Bard was chairman. When I had an offer to come to Florida to be the first Physiology Department head in the new medical school, I discussed the matter with Dr. Bard. A word of advice from him was, ‘Just make sure that you don’ t have to go to some damned Dean every time you want a nickel’.
“I have been very fortunate during my 89+ years to have had so many friends, associates, and superiors who have been most helpful in making my life pleasant and productive. I am grateful to them.”
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