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Senior Physiologists' News |
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Letters to Alan Hoffmann Basil I. Hirschowitz writes: “Thank you for asking me to write the reminiscence and also for being patient with my delay in responding. “I currently spend three days a week at the University, largely in clinical research, involving long-term treatment of patients with acid hypersecretion. However, as I enter my ninth decade, I have finally closed my GI clinical practice, bidding farewell to my loyal patients, some of whom I have been treating for more than 40 years. “My currently funded research project, in its 16th year, deals with long-term medical treatment of Zollinger-Ellison syndrome and related hypersecretion disorders. The project has generated, and continuous to generate, enough data and questions to keep us usefully employed in analyzing and reporting results well into retirement. My group and I are actively examining clinical outcomes, as well as risk factors, for clinical manifestations of acid hypersecretion, (both recently published), and the potentially negative effects of potent acid suppression; we are also trying to explain the wide differences in sensitivity to proton pump inhibitors by genotyping P450, and HK TPase. “The current research flows naturally from my longstanding studies, over a period of 55 years, of the physiology and pathophysiology of gastric acid, electrolytes and pepsin secretion in healthy and sick humans, and in many animal models including fistula dogs, rats, chickens, frogs, and guinea pigs as well as isolated peptic cells. This work has always served as the intellectual foundation for my clinical practice. “My first exposure to physiology was at age 17 in my senior year at Witwatersrand University in Johannesburg under the tutelage of the brothers Joe and Teddy Gillman. Their enthusiasm for research and discovery was infectious, and has motivated me ever since. My major research then concerned vagus escape, and I was instructed in preparation of an open chest cat model for these studies by Jack Caunter who had been a technician in Sir Charles Sherrington’s lab in Britain. “After graduating with a B.Sc. in physiology in 1943, I resumed medical school training and served as an instructor in physiology for a year. Following a medical residency in Johannesburg, I spent four years in London, first at the Hammersmith Postgraduate hospital under Sir John McMichael and then with Francis Avery Jones at the Central Middlesex hospital, before moving to the Univ. of Michigan in Ann Arbor in 1953 and then to Temple University in Philadelphia. In 1959 I started the Gastroenterology Division at the Univ. of Alabama at Birmingham (UAB) and have been here happily ever since. “Mine has been a hybrid career, and I always considered myself to be a physiologist working in medicine, shifting between basic and applied science, and equally at home presenting at FASEB as at DDW (Digestive Disease Week), or publishing in AJP as in Gastroenterology and other clinical journals. “Training in medicine influenced my view of physiology as an integrative process. Though I often worked with isolated cells and tissues, I always came back to the whole organism. I never felt that one could tell what time it was by examining the parts of a clock that had been disassembled to find out what made it tick. Moreover, I was not always assured that taking a clock apart allowed one to deduce what had made it tick. As I now struggle to follow the torrents of molecular and other science and as I marvel at the exponential growth of knowledge, I wonder whether my integrative view was, in fact, a useful one-today it would seem old-fashioned, like being a translator of a lost language. “Like Ahab, I have been pursuing a white whale for the last 40 years. I am still trying to solve two related puzzles concerning hypoglycemic stimulation of the gastric vagus in conscious gastric fistula dogs. Insulin hypoglycemia, or cerebral cytoglucopenia by 2-deoxyglucose, evoke a profound central counter-regulation. The first question is, what fuel does the brain then use to do this in the face of lack of glucose? Second, in the same studies, we also found that insulin, (but not 2-DG) in a dose related fashion, independently of glucose, profoundly inhibits even maximally stimulated acid secretion and that inhibition is not affected by giving glucose, but is very rapidly reversed by injecting IV KCl or RbCl . “There is always some hesitation talking about one’s life contributions. Strangely, while I consider myself a physiologist, what I am most widely known for is not physiology, but the invention of the fiberoptic gastroscope in 1956 that made possible fully flexible endoscopy. That invention impacted the practice of gastroenterology in the last 50 years arguably as much as any other single advance. It has since afforded me several awards and honors for which I am grateful. “During the course of my career, I had the good fortune to interact with Horace Davenport in Ann Arbor, Simon Komarov in Philadelphia, Charlie Code and especially Warren Rehm. While working in Ann Arbor, I visited Warren several times in Louisville to seek his help with puzzling gastric secretion data. I remember the tidal wave of enthusiasm lasting long into the night with endless extensions of discussion on yellow lined pads in the converted basement that served as his lab. A few years later at UAB, I was on the Physiology Chairman Search Committee, and invited Warren as an outside advisor to the committee. He came, he saw, and was conquered; he moved to Birmingham to fill the UAB Chair and continued his intense career in gastric secretion until he retired many productive years later. “As for advice to current trainees? We, who are leaving, envy you the opportunities that the rush of science is about to offer you. Defend it and make good use of it. “With best wishes to the physiology fraternity.” John Mixner writes: “Thank you for the letter which was sent to members of APS who were born in 1915. “I retired from Rutgers, the State University of New Jersey, in 1977 as Emeritus Professor of Animal Physiology after serving on the faculty there for 30 years. I immediately moved to Hendersonville, NC where my wife and I developed an outstanding rhododendron and azalea garden over the next 15 years. We were awarded the Bronze Medal of the Southeastern Chapter of the American Rhododendron Society in 1990 in recognition of our contributions to the Society. “Travel photography has been one of my hobbies both before and after retirement. My wife and I have visited over 50 countries around the world, including International Dairy Congresses in London, Paris, Trento, New Delhi, Sydney and Washington, DC, where I have presented papers. “Since 1993 I have lived in Carolina Village, a retirement community in Hendersonville, NC. “My first 15 years at Rutgers were in the research area of: artificial breeding of dairy cattle; metabolism of bull semen; freezing bull semen for use in artificial breeding; measuring the thyroid gland thyroxin secretion rate in dairy cattle; measuring liver and kidney function in dairy cattle. I enjoyed working with graduate students, both MS and PhD candidates. “My second 15 years at Rutgers were as Chairman of the Dairy Science Department (one year) and 14 years as Chairman of the Department of Animal Sciences where my work was mostly administrative.” Letters to Julio Cruz Lawrence Espey writes: “Thank you for the birthday greetings. Other than the usual ‘News’ and ‘Meeting Announcements’ from the APS, I think your note is the first time I have heard from someone within the APS since I became a member in 1967. I am impressed by your willingness to take on this task of communicating with ‘the more mature’ members of the Society. “In response to the information you requested, I continue to work full-time at teaching (giving all the lectures and labs in four courses per year) and research (currently operating on $350,000 from the NSF and $224,000 in intramural funds from Trinity University). I have two full-time research assistants, and one postdoctoral fellow (Haruhiro Kondo). In addition to my teaching and research, I spend considerable time serving as Chair of the University Committee for Commencements and Convocations, and am solely responsible for directing the winter and spring Commencements at this institution. Also, I am currently Acting Chair of our Animal Research Committee, along with serving as a member of several other committees. My hobbies include travel, jogging, and working truly like “a peon” on some property we own in the Texas Hill Country about 60 miles from San Antonio. “I might add that I could have retired five years ago, and made a higher annual salary from our excellent pension plan (TIAA/CREF) than from my regular salary. However, I feel that I am close to bringing my 44 years of research on the physiology of ovulation to a comprehensive ending, and plan to work until I have achieved this goal. “Hopefully, one day, my wife and I might manage to make it to Peru and other parts of South America. A decade ago, we spent a marvelous eight days in Guatemala, and last spring we enjoyed an eight-day cruise along the western coasts of Costa Rica and Nicaragua, but we have not managed to make it further south.” Jorge Fischbarg writes: “Thank you for your kind invitation in behalf of our Society. I am pleased to mark the occasion with some thoughts. “I was born in Argentina, and went to a special high school (Colegio Nacional de Buenos Aires), where I found science. That interest slept while I was in Medical School (and played Tournament chess). However, it resurfaced after graduation. I was admitted to the Department of Biophysics at the University of Buenos Aires in 1961. My group was headed by Jose Zadunaisky, and included Mario Parisi, Virgilio Lew, Oscar Candia, Ricardo Montoreano, Dante Chiarandini, and Marta Piras. Candia, Montoreano and I followed Jose to Louisville, KY, in 1964. I then went to the Committee on Mathematical Biolo-gy, University of Chicago. After two years taking courses, I decided I was an experimentalist first, switched to physiology, finished a PhD under Constantine Spyropoulos, and in 1970 took up a position at Columbia University, where I remain. “Where did all that training go? I think it helped. In 1971, I discovered a tiny electrical potential difference across corneal endothelium that solidified the idea of fluid transport across that layer. That finding also became popular among kidney proximal tubule researchers, who had had a controversy about the electrical activity of their preparation. I next modified the Bourguet technique, after which we could detect fluid movements with 1 nanoliter resolution. With this procedure we discovered the presence of fluid transport in conjunctival epithelium (simultaneously with Vincent Lee), and with my colleague Friedrich Diecke in lens epithelium. “A high point came when in 1976 I went for a sabbatical to the legendary Physiological Laboratory in Cambridge. I interacted there with Guillermo Whittembury, Adrian Hill, and Thomas Zeuthen; I still do. I met Sir Alan Hodgkin; I was curious about the scientific thinking that guided his Nobel-winning research. What struck me was that he frequently resorted to mathematical descriptions of results, which he handled with great ease. Among those I knew, I had only detected such a gift in Hans Ussing and Adrian Hill. “Being fascinated by water passage through membrane proteins, I teamed up with Samuel Silverstein and Ora Rosen. We published a technique to detect volume changes in Xenopus laevis oocytes expressing water-permeable membrane proteins; that procedure was immediately adopted by the laboratories of Alan Verkman and Peter Agre, among others. With Julio Hernandez we came to the conclusion that both channels and transporters have a similar structure involving a complex inner channel, an idea that extends the original unifying conception by Peter Lauger. Our most definitive contribution to this is about to appear. With Juan Carlos Vera we have recently communicated a homology structure of the glucose transporter Glut1. “Fluid transport in epithelia is a major interest of mine, and a major unsolved mystery. A discussion of whether it is transcellular or paracellular has seesawed for years. Lately we are finding evidence that in corneal endothelium the fluid movement is driven by paracellular electro-osmosis, not by transcellular local osmosis across aquaporins. These findings have been met with both great interest and reserve, given that textbooks tend to say otherwise, and that research on aquaporins is immensely popular. Parenthetically, the idea of electro-osmosis is not even mine; it was shown to me by Ussing. But whatever the precise mechanism, there are difficult ways to find out. I hope that tempers will cool down and that we will be able to do just that. In the meantime, the omens are good; my old mathematical bent has resulted in recent contributions that are consistent with paracellular flow from modeling endothelial transport (with F. Diecke) and tight junction electrochemistry (with Andrey Rubashlin, Pavel Iserovich and J. Hernandez). We are presently working in all these areas. “For younger physiologists, I reproduce what I heard from an Infectious Diseases specialist who became Dean of a Medical School: ‘All the advances I have seen in medical practice derive from breakthroughs in basic science laboratories.’ Finally, I mistrust techniques that appear to give answers to all problems. I have found (while using them) that no single technique can do that, including patch clamp, molecular biology, or knockout/mutant animals. To me, the art of matching a problem with the techniques required to solve it is the key to advances in physiology. And if no technique exists, we need to create it. Fashionable research has no role in a demanding quest for solutions.” Donald T. Frazier writes: “Thanks so much for my birthday greetings from you and the APS. As you requested, I will summarize some of the activities in which I am currently engaged. “I retired from the University Of Kentucky College Of Medicine in the year 2000 but accepted a post-retirement appointment which is still in effect. I was the former chair of the Department of Physiology with a joint appointment in Biomedical Engineering. My research program involved control of respiration of which I am still engaged. In fact, we will have an abstract at this year’s Neuroscience meeting in Washington DC. A few years ago we moved our laboratory to the Lovelace Respiratory Research Institute in Albuquerque, New Mexico under the supervision of my associate, Dr. Fadi Xu. He is now completely in charge of the program with me acting as a consultant. I still enjoy helping with all aspects of the program, ie., writing the grants, manuscripts and data analysis. We are planning to submit a continuation of our study on the role of the cerebellum in respiratory regulation this coming spring. Fadi and I have published many papers on the cerebellum and hopefully have established its importance in breathing. “In addition, in 1980 we began our involvement in our Outreach Program for Science and Health Career Opportunities. This interest involved into a free standing Center of which I am still the Director. We have our own building complete with an exhibit area and interactive classroom. I still believe we have the best physiology teaching lab on campus but, come to think of it, we may have the only one. We speak to 5,000 to 7,000 students during the school year either on or off campus. We have a mobile classroom that allows us to take our show on the road to rural areas. In the summer, we hold science camps and motivational programs at various levels and for different lengths of time. Also, we place around 30 undergraduate and high school students in research labs throughout the medical center. Many of our programs have concentrated on under-represented students either culturally or geographically. “We still have one active NIH grant. About six years ago, NIGMS chose us to develop an internet based grant writing course to help faculty from minority institutions be more successful with their proposal submissions. We initiated such a course and have trained over 200 faculties to date. We were recently renewed and are in the process of revising the existing 14 modules and writing two more. Our format is the NIH RO1 with the modules representing the various components of the 398 application. Faculties are brought to our campus for an orientation but go through the course at their home institution. Under development is a peer review process in which the participants can electronically receive feedback as they write the various components of their proposal. “We are constantly up-grading the modules to make sure we are current with all the changes in forms and policies. “I have remained active on campus and the community. I currently serve on four boards (president of two) and one commission. Needless to say I love retirement as it allows one to pick and choose what you do.” W. Curtis Worthington writes: “I became a State of South Carolina retiree officially in 1991 at which time I was Associate Dean for Academic Affairs and the Director of the Waring Historical Library. I am happy to say that I have been allowed to remain the latter ever since. My arrangement with the University is to spend three days a week in the library with a staff consisting of a Curator, an Associate Curator and more recently an Archivist. I work on Tuesdays, Wednesdays and Thursdays. I have devoted the rest of my time for the most part to activities on or in the water. I was brought up on one of the Sea Islands of South Carolina and I have a natural inclination toward the estuaries, creeks, and inlets of the local area. “I have had an interest in history since school days and my interest in the history of medicine was a natural development. I have continued to write on a variety of historical subjects and I recommend it as an excellent way to hang on to at least some of one’s neurons. I’m currently pursuing a biographical work on Thomas Trotter, a British naval surgeon of the late 18th and early 19th centuries. He was a major contributor to reform of the British Navy and wrote poetry, a combination that I found intriguing. “My words of wisdom such as they are: 1) You are not married to the bench. Retirement is not a divorce; 2) Plan in advance for your post retirement life. Know what it is that you are going to be doing after your last day in the lab; 3) Hang on to whatever intellectual activity attracts you and pursue it. The possibilities are endless! “In regards to the disposition of my papers, I’m fortunate in that a formal archive is in the early stages of development here at the Medical University of South Carolina and the Archivist works under my formal purview. I, therefore, have available advice on what to retain and what not to retain conveniently at hand. “Thank you very much for affording me this opportunity to express my rather strong feelings about retirement and what a rewarding period in life it can be.” |
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