MINKOWSKI, OSKAR

(b. Aleksotas, near Kaunas, Russia [now Lithuanian S.S.S.R.], 13 January 1858; d. Fürstenberg, Germany, 18 June 1931)

internal medicine, clinical-experimental pathology.

Minkowski, best known for his discovery and exploration of the role of the pancreas in diabetes, was the son of a wealthy German-Jewish grain trader. His brother Hermann (1864–1909) was a distinguished mathematician who developed the theory of quadratic forms in n-variables, worked on the mathematical physics of space and time, and taught Albert Einstein at Zurich. Another brother was a successful businessman and art collector. Oskar attended school in Kaunas and Königsberg, then studied medicine at Strassburg and Freiburg before qualifying as a doctor of medicine at the University of Königsberg in 1881 under Bernhard Naunyn’s supervision.

Naunyn’s influence determined the direction of Minkowski’s medical career in several ways. First, Naunyn passed on to Minkowski an orientation to medical problems inspired by Johannes Peter Müller, a pioneer of the classical period in nineteenth-century German physiology. Müller had instigated the transition of German medicine from the romantic idealism of its heritage of Naturphilosophie to a more empirical approach. The new empiricism eschewed strictly vitalistic interpretations of physiological phenomena in favor of direct observation and the analysis of mechanical and chemical aspects of physical processes. The approach continued to emphasize physiological processes as a systemic whole, however, rather than particular organs or mechanisms.

Second, Naunyn’s research interests came to form the matrix of Minkowski’s medical preoccupations. A key concept formulated by Justus von Liebig, that of Stoffwechsel, encouraged the investigation of physiological processes by viewing the body as an “economy.” Not quite equivalent to “metabolism,” Stoffwechsel was tinged with vitalism in its principal idea that each living thing needed continually to transform matter in order to maintain its own form. Naunyn’s attention had turned to Stoffwelchsel in the laboratory of Friedrich Theodor von Frerichs, an experimental pathologist. Frerichs interested Naunyn in metabolic pathology and passed on to him the study of the liver and related organs as the great chemical laboratory of the body. Naunyn opened a laboratory for experimental pathology at Königsberg, the first of its kind in connection with a medical clinic in Germany. He explored five broad areas in a path-breaking combination of clinical and experimental research: diabetes mellitus, liver function, the pathology of urinary ammonia and acid, hepatogenous jaundice, spinal injuries and fever.

Third, Naunyn impressed upon Minkowski the priority of the clinical aspect of medicine. At Naunyn’s Königsberg clinic, experimental pathology and pharmacology were united with clinical work in a conscious effort to help the patients. This natural science approach to clinical medicine did much to define both the horizons and the limitations of Minkowski’s work. He belonged to a generation of medical pioneers trained to integrate experimental with clinical pathology in an age still fearful of systematic medical experimentation.

Minkowski’s rare combination of talents made him an ideal disciple of Naunyn. He demonstrated an unusual capacity to analyze problems critically and then synthesize new solutions. Added to a razor-sharp intelligence were the intuition and dexterity of a gifted surgeon. At a time when surgery was only beginning to benefit from antiseptics and other improved techniques, Minkowski proved a virtuoso and an innovator in the operating theater. His skills and versatility led to major contributions to medical knowledge on a wide range of diagnostic and therapeutic problems.

Minkowski’s dissertation was a study of the relationship between electrical stimulation of the brain and blood circulation. His abilities won him an immediate assistantship in Naunyn’s clinic. Ernst Stadelmann, Minkowski’s predecessor, had been analyzing diabetic urine and had isolated an anomalous unknown acid as one of its components. In 1884 Minkowski correctly identified this substance as β-hydroxybutyric acid and related its production to the faulty metabolism of fats. Further study enabled Minkowski to help confirm the role of acidosis in diabetic coma. He attempted to forestall this dreaded final stage of the disease by using a blood gas pump to compensate for depleted alkali reserves and obtained some favorable results. Until the discovery of insulin, alkali therapy remained a last treatment for diabetics showing severe keto acidosis.

Naunyn’s laboratory was also investigating the role of the liver in metabolism. In 1885 Naunyn proposed to observe the effects of total hepatectomy on a dove and chose Minkowski to attempt the intricate and difficult procedure. Unlike some of his colleagues, Minkowski was interested in animal experiments, and he succeeded brilliantly where others had failed. He hepatectomized a series of larger birds such as geese years before others mastered the technique. For anatomical reasons these birds, unlike mammals, survived hepatectomy long enough to measure its effects. Naunyn and Minkowski were mainly interested in determining the origins of bile pigments; in 1886 the hepatectomies allowed Minkowski to demonstrate the liver’s role in hemolytic jaundice.

Minkowski characteristically pursued his researches within the traditional physiological and medical context that accorded the liver a central role in the bodily “economy.” Yet despite the classic experiments of Claude Bernard on the glycogen function of the liver, little about this process was then understood, and pathological investigations into hepatrophy and phosphorism had not been much help. Minkowski sought a key in the waste products of metabolism, and chose to investigate the liver’s function in the production of urine. It was known that neither muscles nor kidneys were responsible for ureapoiesis, the chemical synthesis of ammonia and carbonic acid to form urea. Hepatectomy allowed Naunyn and Minkowski to study several stages of this process, including the formation of ammonia from the decomposition of complex molecules. Minkowski inferred the intermediary stages of carbohydrate metabolism from the presence of lactic and amino acids, and theorized that these recombined in the liver to produce uric acid. While this theory was later disproven, it nevertheless formed the starting point for further investigations of the problem.

Minkowski took special pride in two of his early achievements. In his first contribution to endocrinology he drew upon Rudolf Virchow’s analogy of the pituitary and thyroid glands to suggest in 1887 that pituitary malfunction was the cause of acromegaly. Three years later the theory was verified by Pierre Marie. In 1888 Minkowski contradicted prevalent views on the effects of polyneuritis by demonstrating that severe functional and psychic disturbances to the central nervous system resulted from the disorder.

In 1889 Minkowski followed Naunyn to the medical clinic at Strassburg. Here Naunyn’s experimental pathology was cross-fertilized by the experimental pharmacology of his friend Oswald Schmiedeberg, whose institute was at Strassburg. In this creative atmosphere Minkowski began to make the major contributions of his career.

In April 1889, while visiting the library at Hoppe-Seyler’s institute in Strassburg, Minkowski met Joseph von Mering, who in 1886 had produced experimental diabetes in animals by means of phlorizin, and was now studying the use of certain fats in nutritional therapy. These studies, von Mering told Minkowski, assumed that functional defects of the pancreas rendered the body incapable of splitting fats in digestion. After his own work on the liver, Minkowski’s natural reaction was to challenge von Mering to prove his assumption experimentally by excising the pancreas. Fired by his recent surgical triumphs and, as he later admitted, by the “naive overconfidence of youth,” Minkowski could not resist the counterchallenge of von Mering’s reply that total pancreatectomy was impossible. That same day, according to Minkowski, von Mering assisted him at Naunyn’s clinic in performing a total pancreatectomy on one of Hoppe-Seyler’s laboratory dogs.

A family illness that called him out of town prevented von Mering from moving the depancreatized dog to his own laboratory to study fat resorption. The dog recovered from surgery at Naunyn’s laboratory and was being trained to empty its bladder and bowels into special containers, the usual procedure when metabolic investigations were being conducted. The dog instead urinated repeatedly and frequently on the laboratory floor. Minkowski reprimanded the laboratory attendant. The attendant replied that he had taken the dog out regularly, but that the animal had developed constant polyuria. Minkowski’s experience and training led him to test the urine for sugar, which he measured at more than 10 percent. After pancreatectomizing several more dogs, Minkowski concluded with astonishment that total extirpation of the pancreas invariably induced diabetes mellitus in the dogs. The literature contains no references to a later story that the attraction of flies to the dog’s urine prompted the first test for glycosuria—a story Minkowski later denied.

When von Mering returned a week later, Minkowski informed him of the discovery. But von Mering possessed neither the surgical skills nor a particular interest in following up its implications. Minkowski, on the other hand, characteristically resolved to pursue both the original problem of fat resorption and the new problem of pancreatic diabetes. He shared with von Mering the authorship of the report “Diabetes mellitus nach Pankreas-exstirpation,” which appeared in Zentralblatt für klinische Medizin in 1889 and in Archiv für experimentelle Pathologie und Pharmakologie in 1890. There was no further collaboration. When a colleague suggested that the true discoverer was actually the laboratory attendant who noticed the dog’s polyuria, Minkowski replied that if that was so, then the cleaning woman who left a dust rag on Röntgen’s cathode tubes discovered X rays. Not only was it Minkowski who had grasped the significance of the polyuria, but he alone pursued the far-reaching implications of the initial discovery. Von Mering, who had contributed little more than the lab attendant, was not involved in any further aspect of the work.¹

Minkowski correctly argued that the major achievement in the discovery of pancreatic diabetes was less the surgery or the recognition of its consequence than his grasp of the significance of the discovery for the theory of carbohydrate metabolism. The report of his experiments, published with variations in several journals in 1889 and 1890, was a classic exposition setting the problem of pancreatic diabetes in dogs in the context of medical literature in which pancreatic dysfunction had been seen to accompany, but had never been recognized as a cause of, diabetes in humans. Minkowski detailed his own investigations of pancreatic diabetes and discussed the theoretical and research implications of the possible explanations of the condition.

The most immediate question for Minkowski was whether pancreatic diabetes resulted directly from the removal of some specific pancreatic function or indirectly from some internal trauma induced by the pancreatectomy. The observation that partial pancreatectomy did not lead to diabetes weighed heavily in favor of the former. Next, two possible scenarios suggested themselves to explain the interruption of intermediary metabolic processes caused by pancreatectomy: extirpation of the pancreas might permit the accumulation of some abnormal substance in the metabolic system, or the operation might remove some normal function of the pancreas that enabled the body to metabolize sugar (and the absence of which caused diabetes). Minkowski rejected the first assumption for two reasons. First, his experiments showed that blood transfusions from a diabetic to a normal dog caused no diabetes in the recipient. Second, tying off the pancreatic ducts while the pancreas remained in place did not cause diabetes. Since only total excision had this result, Minkowski concluded that the removal of some pancreatic function necessary for carbohydrate metabolism caused diabetes.

Minkowski realized that further research was needed to uncover this metabolic function of the pancreas. He wondered whether the function was unique to the pancreas, that is, whether total pancreatectomy merely hindered or fully prevented the utilization of sugar. One step would be to undertake more exact quantitative analyses. Meanwhile, however, Minkowski’s study of experimentally induced diabetes led him to consider the role of the pancreas as exclusive. He argued that common theories explaining diabetes as originating in disorders of the nerves, liver, or muscles had no experimental basis. He realized, on the other hand, that the pancreatic function he sought to isolate might well constitute one link in a metabolic chain that could easily be broken at other links. Far from forming a clear hypothesis about an internal secretion of the pancreas, in an 1890 paper, “Diabetes mellitus and Pankreasaffection,” Minkowski used the analogy of proteinuria, a result of kidney disease, to conceptualize the relationship between glycosuria and the pancreas. He had already experimented with oral administration of fresh pancreas and interpreted the extracts’ failure to reduce glycosuria as evidence that it was the metabolic rather than the digestive system that required the mysterious pancreatic function.

The discovery of pancreatic diabetes by von Mering and Minkowski in 1889 encouraged many researchers to seek explanations of the relationship. Minkowski spent much of the next four years following up the clues he had amassed. In 1892 and 1893 he published a second series of reports, including “Weitere Mitteilungen über den Diabetes mellitus nach Pankreasexstirpation” (1892) and “Untersuchungen über den Diabetes mellitus nach Exstirpation des Pankreas” (1893). Minkowski pancreatectomized cats, rabbits, pigs, birds, and frogs to compare the results with those he had achieved on dogs (known to researchers as “Minkowski dogs”). He was able to induce and observe many degrees of diabetes mellitus and came to believe, somewhat erroneously, that in the most advanced stage of diabetes after pancreatectomy, no sugar at all could be metabolized. Against the suggestions of other researchers, he correctly denied any analogous metabolic function between the pancreas and organs such as the intestines or the salivary glands. He reiterated that no other organ shared the role of the pancreas in carbohydrate metabolism.

More important, Minkowski reported the results of transplantation experiments on dogs, confirmed by E. Hédon at Montpellier, in which he removed the greater part of the pancreas and attached the small remaining piece, with its blood supply intact, subcutaneously to the wall of the abdomen. No diabetes resulted until after this remnant was removed. This result strengthened Minkowski’s suspicion that the pancreas “produced something” indispensable for carbohydrate metabolism elsewhere in the body, and the lack of it caused diabetes. Many years later, in a letter of 12 January 1923 to J. J. R. Macleod and in a 1929 paper, he insisted that both this “something” and his earlier references to a “pancreatic function” were meant to denote an internal secretion of the pancreas, and that the only reason for his transplantation experiments had been to demonstrate that the pancreas functioned analogously to other endocrine glands. At the time, he referred only to a “substance,” and in 1906 to an “internally directed secretion.” In the context of the impossibility of isolating such a hypothetical secretion, his terminology remained flexible until the exact function of the substance could be established.

If such a secretion did exist, it had to possess certain properties. Against the view of J.-R. Lépine in France that the pancreas produced an enzyme or other glocolytic substance that entered the bloodstream by way of the lymphatic system, Minkowski contended that sugar was decomposed not in the blood but (more likely) in muscles and tissues. From this and several other factors he argued that the mysterious “something” was not likely to be an enzyme. First, depancreatized dogs showed a rapid decline of glycogen stored in the liver. Second, carbohydrate feedings were followed by carbohydrates in the urine, but pure meat and protein feedings resulted in severe glycosuria. Minkowski theorized that animals manufactured sugar from protein in the ratio D:N, that is, the amount of dextrose eliminated was proportional to the amount of urinary nitrogen. This “Minkowski quotient” became widely used in studies of protein metabolism. Third, Minkowski noted that levorotary sugars were metabolized much more easily than dextrorotary. On the basis of this data he correctly hypothesized that the metabolic role of the pancreas was to create a chemical affinity between sugar molecules circulating in the bloodstream and the organs that normally utilized sugar.

Yet Minkowski reluctantly acknowledged in 1893 that he was no closer to a therapy for diabetes. Pancreas transplantations were impossible because of blood supply problems. He now visualized the pancreatic substance he sought as an analogue to the thyroid preparations that had recently proved a therapeutic marvel against myxedema. As a result, he experimented further with both oral and subcutaneous administration of pancreatic extracts, but to no avail. Subcutaneous injections did lead to reduced glycosuria, but their side effects were so severe that not only were the extracts unusable therapeutically but their positive effectiveness remained in doubt. True to his training as a clinician, Minkowski abhorred premature experimental therapies.

In 1905 and 1906 Minkowski was forced to defend his theories on pancreatic diabetes in the face of criticism from Eduard Pflüger, a respected physiologist at Bonn. Pflüger disputed both the relationship between total pancreatectomy and diabetes and the probable existence of an internal secretion of the pancreas. Minkowski attributed Pflüger’s attacks to a personal vendetta and masterfully demolished his opponents’s main argument. He disproved Pflüger’s theory of nerve stimulation in the duodenum as the cause of glycosuria by totally removing the duodenum in dogs with no resulting glycosuria.

But Pflüger’s claim that extirpation experiments were insufficient to prove the existence of an internal pancreatic secretion that could alleviate diabetic symptoms was not as easily refuted.² In 1906 Minkowski admitted the possibility that his theory of an internal secretion might not fit the puzzle of pancreatic diabetes. Two years later his student Joseph Forschbach performed parabiotic experiments that strongly reinforced the contested theory. Forschbach connected the blood supply of a normal dog to that of a diabetic dog, whose glycosuria diminished dramatically. He also introduced into Minkowski’s laboratory Georg Zuelzer, a Berlin physician who had carried out promising experiments with pancreatic extracts to reduce glycosuria and acidosis. But once again severe toxic effects led Minkowski the clinician to condemn Zuelzer’s extracts as therapeutically impracticable. Minkowski the theorist also disagreed with Zuelzer’s hypothesis that the pancreas worked mainly to modify the effects of adrenalin in the liver. Despite isolated reports to the contrary, the brilliant results expected of organotherapy in pancreatic diabetes remained conspicuosly absent. Until such results could be achieved, the doubts raised by Pflüger and others about the internal secretion hypothesis had to be acknowledged.

Minkowski received the news of the discovery of insulin in Toronto by J. J. R. Macleod, F. G. Banting, J. B. Collip, and C. H. Best in the year 1921–1922 as a vindication of his theories about the role of the pancreas in metabolism. To Zuelzer’s claim for recognition as the father of the new pancreatic hormone, Minkowski replied that he, too, regretted that he had not chemically isolated insulin. The Toronto group sent Minkowski some of the first insulin to be used in Germany, and he served as chairman of the committee established to organize German production of the new hormone. He told his students that while he had hoped to be the father of insulin, he was content with the Canadians’ designation of him as its grandfather.

Minkowski later blamed himself for not the having tried harder, both in his own researches and after Zuelzer’s researches, to eliminate the side effects of pancreatic extracts he had known could lower glycosuria. For several reasons, he felt, the time and place had been wrong for him or Zuelzer to discover insulin. First, microanalytical methods for measuring minute fluctuations in blood sugar levels had only recently been mastered. Second, endoerinology had just developed to the point where internal secretions were sufficiently understood. Third, the talents of the Toronto researchers had been supplemented by limitless amounts of raw materials available to them in North America for both research and the actual production of insulin.

Minkowski’s sensible retrospective analysis of why three decades passed between the discovery of the role of the pancreas in diabetes and the discovery of insulin did not take into account the influence of his own character and training. The very circumspection that his students and colleagues so admired in his approach to experimental and clinical pathology tempted him to pursue medical knowledge more broadly than deeply. The pattern of his researches reinforced his belief that every new fact raised more questions and every new solution contained new puzzles. His theoretical preconceptions led in the same direction—to wide-ranging, almost limitless inquiry. Some remarks in Naunyn’s memoirs suggest, as well, that Minkowski was not passionately ambitious and tended to be content with his routine of medical explorations and teaching.

In practice this meant that Minkowski occupied his time with many problems in addition to pancreatic diabetes. His clinical work took him to Cologne in 1900 to direct the municipal hospital and in 1904 to teach at the Academy for Practical Medicine. From 1905 he headed the medical clinic at Greifswald, and from 1909 he directed the medical clinic and was full professor of internal medicine at the University of Breslau (now Wroclaw, Poland), where he remained until 1926. Students remembered him as a reserved but friendly teacher, at once modest and intellectually formidable.

Minkowski’s clinical work was accompanied by many publications on therapeutic themes and by experimental researches on a wide range of problems. Among his most important contributions in clinical and experimental pathology were continued researches on liver function. He filled out the etiological picture of hemolytic jaundice as originating in disturbances of blood pigments and introduced the idea of the excretion of liver cells into the bloodstream. In a classic article contributed to Naunyn’s Festschrift in 1904, Minkowski theorized correctly that these disturbances resulted from primary changes in the spleen and suggested that splenectomy provided the most effective therapy for the condition.

Minkowski also made important contributions to knowledge of the chemical and pathological role of uric acid. Throughout his career he published often on such topics as purine and nuclein metabolism, fermentation in the stomach, and the role of the esophagus in digestion. His masterpiece in this area involved him as one of the first to identify an excess of uric acid as the cause of gout. The monograph, published in 1930, included a photograph of Minkowski’s own eye to illustrate symptoms of gout.

A third area of deep interest to Minkowski was the pathology of respiration. In 1912 he published several papers on emphysema and a masterful, comprehensive study of the breathing process. These works proved useful during World War I, when Minkowski served as a consulting internist for the German Ninth Army. The War Ministry asked him to study the pathology of gas poisoning. The resulting monograph interwove chemical, physiological, pathological, and therapeutic aspects of this new medical problem. It was not published until 1921, after the issue had largely ceased to interest the German medical community.

Few aspects of internal medicine escaped Minkowski’s critical attention. By the same token, he did not deviate from, but rather brought to fruition, the teachings of Bernhard Naunyn. In both clinical and experimental pathology, Minkowski was primarily a first-rate diagnostician who excelled in discovering the broad patterns of pathological and physiological processes, often using techniques of comparison and analogy. His emphasis on logical reasoning was deeply rooted in traditional approaches harking back to Liebig and Müller. The synthesis of old and new techniques in the laboratories of Naunyn, Minkowski, and their associates contributed substantially to the medical understanding of carbohydrate metabolism and pancreatic diabetes, giving enormous impetus to German experimental pathology. But Minkowski’s approach proved insufficient to unravel the peculiar complexities of the pancreas as an endocrine gland. “No one of us should regret,” he wrote in 1899, “that he might be able to plant only for the next generation. Meanwhile, we can satisfy our own hunger for effective therapies quite nicely on the wild fruits of the old empiricism.”

Despite his outstanding abilities, Minkowski did not accede to the rank of full professor until he was fifty years old. Veiled remarks by Naunyn and other colleagues allude to the tacit anti-Semitism of German government policy as the main reason for his delayed promotion. Nevertheless, he was an influential member of the German Association for Internal Medicine and was internationally recognized as the foremost expert on pancreatic diabetes before the discovery of insulin. In 1923 Minkowski joined a team of physicians called to Moscow to attend Lenin after his final stroke. After retiring to Wiesbaden in 1926, Minkowski longed to return to Berlin, where his married daughter resided. When he finally undertook the move in 1931, his health broke down. He died that year of pneumonia and secondary thrombosis, leaving also a son who inherited the mathematical skills of his uncle Hermann. During World War II, Minkowski’s widow, the former Marie Siegel, moved to Argentina, where she spent her remaining years.

NOTES

1. See Minkowski, “De Lehre vom Pankreas-Diabetes in ihrer geschichtlichen Entwicklung”, in Münehener medizinishe Wochenschrift, 76 , no. 8 (22 February 1929), 310-315. Although this narration of the events surrounding the discovery of pancreatic diabetes follows Minkowski’s and Naunyn’s version, von Mering never contradicate it in any way. British pathologists tended to give more credit to von Mering (and still do!—see V. C. Medvei, A History of Endocrinology [Lancaster, England, 1982]), whose earlier discovery of phlorizin diabetes inspired them to seek an extract that could cure diabetes : German pathologists seem to have leaned the other way, especially after Minkowski’s death, urging that von Mering’s name be removed from the 1890 article. As late as 1913. Mering and Krehi’s Lehrbuch der inneren Medizin included work by Minkowski on the liver and the pancreas, but did not include the pancreas in the chapter on endocrine glands by F. Kraus, Kraus’s section on Stoffwechsel does, however, mention Georg Zuelzer’s attempts to find a workable pancreatic extract.

2. To follow the exchange discussed in this paragraph, see Pflüger, “Über die im tierischen Körper sich vollziehende Bildung von Zucker aus Eiwess und Fett”, in Archiv für die gesamte Physioligie, 103 (1904), 66-70; Minkowski, “Bemerkungen Uber den Pankreasdiabetes. Zur Abwchr gegen Eduard Pflüger”, in Archiv für experimentelle Pathologie und Pharmakologie, 53 (1905), 331-338; Minkowski, “Über die Zuckerbildung im Organismus beim Pankreasdiabetes. Zugleich eine Entgegnung auf die wiederholten Angriffe von Eduard Pflüger,” in Archiv für die gesamte Physiologie, 111 (1906), 13-60; Minkowski, “Die Totalexstirpation des Duodenums”, in Archiv für experimentelle Pathologie und Pharmukologie, 58 (1908), 271-288 : Roy G. Hoskins, The Tide.c of Life (New York, 1933), 311 ; Minkowski, “Die Lehre vom Pankreas Diabetes in ihrer geschichtlichen Entwincklund”, in Münchener medizinishe Wochenschrift, 76 , no.8 (22 February 1929), 310-315; Geog Zuelzer, “Diskussion”, appended to Minkowski. “Über die bisherigen Erfahrungen mit der Insulinbehandlung des Diabetes”, in Deutsches Gesellschaft für Innere Medizin, Verhandlungen, 36th Congress (Kissingen, 1924), 91-108, 136; Minkowski, “Das alte und das neue in der Diabetestherapie.” ibid, 33rd Congress (Wiesbaden, 1921), 225-233; and Karl Loenig. “Organotherapie de Diabetes mellitus”, ibid., 297-302.

BIBLIOGRAPHY

I. Original Works. Virtually none of Minkowski’s personal correspondence survived World War II; a few letters to the discoverers of insulin are in the Insulin Committee records at the University of Toronto Library. The most complete available list of Mickowski’s 14 monographs and over 170 articles was assembled by his student Martin Nothmann and appended to L. Krehl’s obituary as “Oskar Minkowskis Arbeiten”, in Archiv für experimentelle Pathologie und Pharmakologie (hereafter Naunyn-Schmiedebergs Archive), 163 (1931-1932), 626-635. Many of Minkowski’s works were published in that journal Included here are only his key works and others referred to in this article.

“Über das Vorkommen von Oxybuttersäure im Harn bei Diabetes mellitus”, in Naunyn-Schmiedebergs Archive, 18 (1884), 35-55; “Untersuchungen über den Einfluss der Leberexstirpation auf den Stoffwechsel”, ibid., 21 (1886), 41-88; “Diabetes mellitus nach Pankreasexstirpation”, in Zentralblatt für klinische Medizin (1889), no. 23, and in Naunyn-Schmiedebergs Archive, 26 (1890), 371-387, written with Joseph von Mering; “Diabetes mellitus und Pankreasaffection”, in Berliner klinische Wochenschrift, 27 , no. 8 (24 February 1890), 167-169; “Weitere Mitteilungen über den Diabetes mellitus nach Exstirpation des Pankreas”, in Berliner kilinische Wochenschrift (1892), no. 5, 90-94; “Untersuchungen über den Diabetes mellitus nach Exstirpation des Pankreas”, in Naunyn-Schmiedebergs Archiv, 31 (1892-1893), 85-189; “Über experimentelle Therapie”, in Die Therapie der Gegenwart, 40 (1899), 95-96; “Zur Pathogenese des Ikterus”, in Zeitschrift für klinische Medizin, 55 (1904), 34ff,; “Über die Zuckerbildung im Organismus beim Pankreasdiabetes. Zugleich eine Entgegnung auf die wiederholten Angriffe von Eduard pflueger”, in Archiv für die gesamie Physiologie, 111 (1906), 13-60; “Über die bisherigen Erfahrungen mit der Insulinbehandlung des Diabetes”, Deutsche Gesellschaft für Innere Medizin, Verhandlungen, 36th Congress (Kissingen, 1924), 91-40; “Die Lehre vom Pankreas-Diabetes in ihrer geschichtlichen Entwicklung”, in Münchener medizinische Wochenschrift, 76 , no.8 (22 February 1929), 311-315; and “Gicht”, in Georg and Felix Klemperer, eds., Die neue deutsche Klinik (Berlin, 1930).

II. Secondary Literature. For biographical and bibliographical information, see the following obituaries: E. Frank, “Oskar Minkowski zum Gedächtnis!” in Klinische Wochenschrift, 10 , no. 29 (28 July 1931), 1381-1383; G. Klemperer, “Zur Erinnerung an Oskar Minkowski”, in Die Therapie der Gegenwart, 572 (July 1931), 335-336; and L. Krehl, “Oskar Minkowski”, in Naunyn-Schmiedegergs Archiv, 163 (1931-1932), 621-635. See also Frederick M. Allen, Studies Concerning Glycosuria and Diabetes (Boston, 1913); Michael Bliss, The Discovery of Insulin (Toronto and Chicago, 1982); Erich Frank, Pathologie des Kohlehydratstoffwechsels (Basel, 1949); B. A. Houssay, “The Discovery of Pancreatic Diabetes: The Role of Oscar Minkowski”, in Diabetes, 1, no, 2 (March–April 1952), 112-116: Victor Cornelius Medvei. A History of Endocrinology (Lancaster, England, and Boston, 1982); Joseph von Mering and Ludolf von Krehl, eds., Lehrbuch der inneren Medizin, 8th ed. (Jena, 1911); John Theodore Merz, A History of European Thought in the Nineteenth Century, II (Edinburgh and London, 1903); Hans M. Meyer, “Schmiedebergs Werk”, in Naunyn-Schmiedebergs Archiv,92 (1922), 1-17; Bernhard Naunyn, “Oswald Schmiedeberg”, in Naunyn-Schmiedebergs Archiv, 90 (1921), 1-7, and Erinnerungen, Gedanken und Meinungen (Munich, 1925); Karl Opppenheimer, ed., Handbuch der Biochemie des Menschen und der Tiere, III, pt. 1 (Jena, 1910); Karl E. Rothschuh, History of Physiology, Guenter B. Risse, trans, and ed. (Huntington, N.Y., 1973); Hans Peter Schönwetter, Zur Vorgeschichte der Endokrinologie (Zurich, 1968); Swale Vincent, Internal Secretion and the Ductless Glands (London, 1912; 2nd ed., 1922); and F. G. Young, “The Evolution of Ideas about Animal Hormones,” in Joseph Needham, ed., The Chemistry of Life (Cambridge, 1970), 125–155.

Suzanne Zeller
Michael Bliss