The Effect of Pancreas Extract on Depancreatized Dogs: Ernest L. Scott's Thesis of 1911

THE EFFECT OF PANCREAS EXTRACT ON DEPANCREATIZED DOGS: ERNEST L. SCOTT'S THESIS OF 1911 DICKINSON W. RICHARDS, M.D.* The purpose of this article is to publish for the first time the original thesis of E. L. Scott, submitted to the University of Chicago in 1911 (Thesis No. T-10553) in which he reports in full his experiments on the use of pancreatic extracts in depancreatized diabetic dogs. This thesis differs significantly from Scott's paper published in the following year in the AmericanJournal ofPhysiology [1] for reasons which will appear presently . Some ofthe circumstances attending Scott's work at this time will also be described. As background information, the place of Scott's work in the development ofinsulin is reviewed briefly. In the second of the Banting and Best papers on the extraction of the internal secretion of the pancreas, entitled "Pancreatic Extracts" [2] and published in the Journal of Laboratory and Clinical Medicine in 1922, the authors move from the use of extracts made from the pancreas of fetal calf to a series prepared by extracting fresh adult pancreas with alcohol. They state, "It will be seen that the principle upon which the preparation of this latter extract depends is the same as that of E. L. Scott, and the favorable results led us to see whether adult pancreas could be used in place of fetal." This they found to be true, and subsequent extractions were based on this principle. The paper by Scott referred to by Banting and Best had appeared in the American Journal of Physiology in 1912 under the title, "On the Influence ofIntravenous Injections ofan Extract ofthe Pancreas on Experimental Pancreatic Diabetes." Scott believed that the digestive enzymes *Xambert Professor Emeritus of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York. 84 Dickinson W. Richards · Pancreatic Extract Perspectives in Biology and Medicine · Autumn 1966 ofthe pancreas destroyed the internal secretion, on the further hypothesis that this secretion was a protein-like substance, and he devised his method of extraction to destroy or inactivate the digestive enzymes while preserving the internal secretion. He was also concerned about the possibility of oxidation of the latter during extraction, and his method included measures to prevent oxidation. He first tried, as others had done, ligation of the pancreatic ducts (later used successfully by Banting and Best), in order to produce atrophy of the external secretory glands, but was not able in his experiments to produce complete atrophy, and so discarded this approach. He then resorted to extraction of the fresh adult gland, using two methods. In both he ground up the pancreas with sand and warm alcohol. In the first, he then extracted repeatedly with 85 per cent alcohol, took the filtrate, evaporated this to dryness, and, after extracting the residue with ether and discarding the ether, extracted the remaining dry residue in 95 per cent alcohol and used this alcoholic extract. Scott tested his extracts by intravenous injection into depancreatized dogs. He used as testing measurements the fall in urinary sugar output and drop in a previously high D/N (dextrose to nitrogen) ratio. No blood-sugar method was available at that time except one requiring very large amounts of blood, too large for repeated blood tests in the same animal. This first extract, a residue supposedly taken up in 95 per cent alcohol, did not produce the hoped-for fall in sugar output or D/N ratio. Scott then tried a simpler method. He first ground up the fresh pancreas with sand and warm alcohol, as before, then evaporated this to dryness, then extracted the material "for some time" with absolute alcohol. This was poured offand the residue taken up in acidulated water. With this extract, three out of four dogs showed significant drop in sugar output and in D/N ratio, "and, if one dared say it, [the dogs] seemed even brighter for a time after the injection than before it." The fourth dog receiving an older extract showed only a marked "depression" lasting an hour and a half. After this forthright and decidedly encouraging result, the paper ends on a surprisingly hesitant note. The summary states, first, that these...