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Oskar Minkowski: Discovery of the Pancreatic Origin of Diabetes, 1889

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Oskar Minkowski: Discovery of the Pancreatic Origin of Diabetes, 1889 Diabetologia (1989) 32:399-401 Diabetologia 9 Springer-Verlag 1989 Review Oskar Minkowski: Discovery of the pancreatic origin of diabetes, 1889 R. Luft Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden This year, we are celebrating the 100th anniversary of one of the greatest advances in the history of diabetes and of experimental medicine in general: the demon- stration by Oskar Minkowski and Joseph von Mering that diabetes mellitus follows total extirpation of the pancreas. This discovery furnished the starting point for research, which eventually proved that the pancreas produces an internal secretion, and also led to the dis- covery of insulin and its use in the treatment of patients with diabetes. In my presentation I shall concentrate on the main discoverer, Oskar Minkowski; on the discovery as such; and on its place in the debate around "who discovered Fig.l. This photo- insulin?". graph of Oskar Min- kowski (1858-1931) is taken from Fischer I (1933) Biographisches Oskar Minkowski Lexikon. Urban & Schwarzenberg, Berlin Minkowski's history is that of a Jewish family of East-Eu- Vienna ropean origin, whose ambition was to give their children a chance to higher learning - a tradition which was to exert achievements as clinical investigator attracted attention such a marked impact on the natural sciences in Central also outside Strassburg, but it would take a surprisingly Europe and the USAbefore World War II and thereafter. long time until he was promoted. He was turned down He was born in Alexota near Kaunas in Lithuania-Russia from a chair in Halle. From written reports it can be on 13 January 1858. His father was a grain-trader, who noted that this was so because he was of Jewish descent moved his family to Krnigsberg (now Kaliningrad, - although a converted Christian (Kaiser and WOlker, USSR) to escape the policy of anti-semitic persecution 1981). Between 1900-1905 he was chief physician at a adopted by the Czar's government. One of Oskar's community hospital in Krln, and in 1905 was named brothers, Hermann, became a world-famous mathemati- Professor of Medicine in Greifswald. Not until 1909, at cian, professor in Z0rich - where he was a mentor of Ein- the age of 51, did he became "ordinarius" Professor in stein - and later in Greifswald. One of Oskar Minkow- Breslau (now Wroclaw, Poland) where he remained and ski's children, Rudolph Leo, was an astronomer who retired in 1926. During his Breslau years he joined a moved to the USA in 1935, where he became a Professor team of physicians called to Moscow in 1923 to attend at the University of California at Berkeley and also a to Vladimir Lenin after his final stroke - a sign of his member of the National Academy of Sciences. high international standing as a clinician. After his re- Minkowski attended school in Kaunas and Krnigs- tirement he moved to Wiesbaden, and in 1931 finally berg; then studied medicine in Krnigsberg, Freiburg made arrangements to go to Berlin where his married and Strassburg (now Strasbourg, France), graduating as daughter resided. However, at that time his health doctor of medicine at the University of Krnigsberg in broke down, and he died the same year at the Schloss- 1881. His mentor was Professor Bernhard Naunyn who Sanatorium in Fi,irstenberg of bronchopneumonia and was to determine the direction of Minkowski's medical secondary thrombosis. career in the years to come. Minkowski followed Minkowski was married to Marie Siegel. She sur- Naunyn to Strassburg, where he became Associate Pro- vived him but - probably in 1941 - had to leave Ger- fessor of Medicine in 1891. Obviously, Minkowski's many because of the persecution of the Jews. Her es- performances as teacher and physician and his cape was made possible by generous economic support 400 R. Lufl: Oskar Minkowski from Charles Best. She eventually settled in Buenos ing. The pancreas probably played a major role in the Aires, where she received assistance from Bernardo process, and von Meting had tried to resolve this by Houssay. I had the privilege of meeting her at Hous- ligation of the pancreatic ducts, however without suc- say's house during the celebration of his 70th birthday. cess. Minkowski proposed total pancratectomy in dogs Minkowski happened to appear on the medical to prove yon Mering's theory, a procedure which the scene during a period when German medicine was on latter considered impossible to perform. However, Min- its way out of the idealism of its "Naturphilosophical" kowski with experience of removal of the liver in birds - heritage toward a more empirical approach: the inter- perhaps in youthful recklessness - asked von Meting to pretation of physiological phenomena through direct procure a dog for the purpose, von Meting did so the observations and analysis of chemical aspects of physi- same day, and assisted Minkowski in the total removal ological processes. Naunyn was one of the prime of the pancreas. The operation, without any special movers of this transition, and concentrated his interest preparations, was successful, and it was planned short- on metabolic processes (Stoffwechsel) or metabolic pa- ly to use the dog for von Mering's fat studies - yon Mer- thology. He opened in KOnigsberg one of the first la- ing had to leave the place for a few days. It is obvious boratories for experimental pathology. This environ- that neither of them had in mind the possibility of ment, where experimental pathology was combined diabetes appearing after pancreatectomy. While von with clinical work, suited Naunyn's favoutite pupil, Meting was absent, things happened which were to Minkowski, and he readily adopted this new direction. make medical history. As Minkowski reports in a sec- This is well illustrated by so many of his scientific con- ond article in Zbl Klin Med 1889: tributions, which one recalls with astonishment and ad- After extirpation of the pancreas in dogs, diabetes miration: e.g., the identification of beta-hydroxybutyric appears. It starts some days after the operation, and acid in the urine and its relation to fat metabolism; the lasts for weeks until the death of the animal. lowered carbon dioxide tension of the blood in diabetic Glycosuria appears and, in addition, polyuria, coma, and the introduction of alkali treatment for it: marked thirst, severe hunger as well as severe weight total removal of the liver in larger birds and its impact loss and asthenia in spite of ample supply of nutrients. on metabolic processes, e.g., those of bile pigments, and One pancreatectomized dog after fasting for 48 h ex- the role of the liver in haemolytic jaundice. He de- creted 5-6% of sugar in the urine. scribed familial haemolytic anaemia and its origin in A 16 kg dog, on a pure meat diet, excreted daily one disturbance of blood pigments (Chauffard-Minkowski litre of urine containing 6-8% of sugar. After a glucose disease), and made important contributions to the field meal, urinary sugar transitorily reached a value of 13%, of gastric disease. He described Korsakoff's syndrome and most of the glucose given was excreted unchanged. before Korsakoff, and suggested a pituitary origin of The urine of the operated animals also contained acromegaly (1887) three years before the publication of appreciable amounts of acetone. Pien'e Marie. Blood sugar was considerably elevated; in one dog These and other scientific discovmies - in addition it amounted to 0.30%, in a second one 0.46%. to that of the pancreatic origin of diabetes - were ac- The glycogen content of the organs virtually disap- complished before the turn of the century when Min- peared. kowski was 42 years old. It is obvious from reports and The solar plexus was not damaged duringsurgery letters that he was considered to possess the rare combi- and, therefore, the diabetic state must be regarded as a nation of talents, a razor-sharp intelligence, intuition direct consequence of the removal of the pancreas. and the dexterity of a gifted surgeon. Naunyn said Transfusion of blood from a diabetic dog into the about him that "confronting his enormous intelligence, vein of a healthy dog did not induce glycosutia in the I strike sails". The giant in German surgery during the latter. early part of this century, Sauerbruch, called Minkow- Fat resorption was markedly hampered, and so was ski "the greatest experimental pathologist of his time". the utilization of administered protein. This remarkably pertinent, precise report of a bril- liant experiment was published in 1889 by von Mering Diabetes after total pancreatectomy and Minkowski in a paper occupying three-quarters of - an illustration of serendipity a page in Zbl Klin Med, followed by more extensive re- ports in Naunyn-Schmiedebergs Archive (1890) and in Serendipity is the ability to search for one thing and to Arch Exp Pathol Pharmakol (1893). Minkowski should end up by discovering another. The discovery of be credited with the priority of the discovery, yon Mer- diabetes after pancreatectomy illustrates this in an ex- ing, whose prior main contribution to diabetes research cellent way. As Minkowski describes the situation: was the discovery of phloridzin diabetes, assisted at the He and a colleague at the University of Strassburg, first operation, but otherwise did not participate in the Joseph von Meting (1849-1908), were discussing studies on the diabetic state. When going over the rele- whether free fatty acids were essential for fat absorp- vant literature, I did not find any claims by yon Meting tion, a problem which, at the time, occupied yon Mer- to the discovery. It is to Minkowski's credit that he put R. Lufl: Oskar Minkowski 401 yon Mering's and his own name in alphabetical order had a blood sugar lowering effect in animals or patients on the first reports of the work.
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