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WHAT CAUSES FATTY UVER AFTER PANCREATECTOMY—AN UNRESOLVED AND FORGOTTEN CONTROVERSY THE 1936-1954 YEARS OF CONTROVERSY LESUE L. BENNETT* They who make up thefinal verdict . . .are not thepartial and noisy readers ofthe hour when it appears; but a court ofangeh, apublic not to be bribed, not to be entreated, and not to be overawed, decides upon every man's title to fame. [R. W. Emerson, "Spiritual Laws"] Introduction Following the isolation of insulin and the demonstration of its usefulness in controlling diabetes mellitus, the belief was widespread that insulin would offer control of the cluster of metabolic abnormalities associated with diabetes. This hope proved elusive and continues to be elusive, as shown by the late-appearing complications following long survival of insulin-treated patients who have diabetes mellitus. Soon after the isolation ofinsulin, the experimental observation was made that depancreatized dogs, the animal prototype for studying diabetes mellitus , developed fatty liver and did not survive a normal life span when maintained on insulin alone. By the early 1930s most investigators recognized that there were two types offatty liver following pancreatectomy of dogs. One was of early onset and was thought to result from insulin deficiency per se, whereas the other was of much slower onset and appeared even though the abnormalities ofcarbohydrate metabolism were controlled by insulin. This latter type could be prevented and survival prolonged by the addition of raw pancreas to the diet, raising the questions of whether there was a pancreatic hormone other than insulin, whether a deficiency of the external secretions of the pancreas was re- * Professor of physiology emeritus and vice-chancellor emeritus, University of California , San Francisco. Present address: 959 Peralta Avenue, Albany, California 94706.© 1983 by The University of Chicago. All rights reserved. 0031-5982/83/2604-0355$01.00 Perspectives in Biology and Medicine, 26, 4 ¦ Summer 1983 | 595 sponsible, or whether some essential dietary component was present in raw pancreas. The issue was further clouded by the demonstration that feeding lecithin would prevent the development of fatty liver and that the active component of lecithin was choline. In the United States for approximately 20 years, from the mid-1930s to the mid-1950s, two laboratories vigorously pursued the question of the prevention and reversal of this latter type of fatty liver following pancreatectomy. Their results led them to opposite views regarding whether the missing element was an external secretion of the pancreas or a new pancreatic hormone. These laboratories were those of the physiologist Dr. I. L. Chaikoff of the University of California and of the surgeon Dr. Lester R. Dragstedt of the University of Chicago. The Years of Controversy In July 1930 Chaikoff joined the faculty of the Department of Physiology of the University of California School of Medicine as an instructor when the department was still geographically located in the Life Sciences Building of the Berkeley campus. He spent the remainder of his professional career there until his death in January 1966. Chaikoff's entire education took place in Toronto, Canada, where he received both his Ph.D. and M.D. degrees from the University of Toronto . He began his graduate work with Prof. J. J. R. Macleod in 1924 and received his Ph.D. in physiology in 1928. His M.D. degree was awarded to him 2 years later, and the summer following its receipt, he came to the University ofCalifornia. His student days in Macleod's laboratory at the University of Toronto coincided with the exciting time shortly after the discovery ofinsulin and during a period when there was great activity directed toward elucidation of its mechanism of action. Although there is no evidence that, while a student in Macleod's laboratory , he participated in studies ofconditions necessary for the long-term survival of depancreatized dogs, he must inevitably have been aware of these investigations which led directly to the first research which he undertook at the University of California. This involved the long-term maintenance of depancreatized dogs and led directly to continued research regarding the cause, prevention, and reversal of the latedeveloping fatty liver in these animals. Soon after his arrival in Berkeley, Chaikoff began this research, as evidenced by the fact that his...


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