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Oskar Minkowski’s Team Missed the Nobel Prize

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Zülzer decided to have his extract examined at the Department of Internal Medicine in Breslau where Oskar Minkowski had just been appointed to the chair of Internal Medicine after leaving Greifswald. Minkowski’s collaborator, Joseph Forschbach was asked to carry out the investigations and he began doing so in December 1909. Minkowski later regretted not having looked more closely at this work. Zülzer’s preparations were sent from Berlin to Breslau. Forschbach injected the extract intravenously in 3 experiments on two pancreatectomized dogs. In all three experiments glucosuria decreased immediately after the injection (from 8.2 to 1.3%, from 7.8 to 2.98%, and from 5.63 to 0.68% glucose in the urine) and increased later on. Blood glucose was never measured. Encouraged by these results, Forschbach also administered the extract to people with diabetes. In the first one, glucosuria remained the same after the injection – but the preparation was already 16 days old. The second patient was a 33-year-old man weighing 58 kg. Glucosuria decreased slightly. However, he observed an increase in body temperature, tachycardia, and nausea [8]. Although the experiments on dogs showed an astonishing effect, Forschbach judged the preparation unsuitable for treatment: “The patients showed an almost frightening prostration, the pulse was hunting, in both cases vomiting occurred” [6]. This devastating judgement of a famous working group was of course a terrible setback for Zülzer. In 1914, Forschbach wrote in his textbook: “The attempts to find an organotherapy by administering pancreatic extracts or stimulating the internal secretion of the gland, according to the assumption of a pancreatogenic nature of diabetes, failed. The practitioner must therefore refrain from using the pancreatic hormone prepared by Zülzer” [9]. This Forschbach study, not carried out carefully and badly summarized, was frequently quoted in later years. Mac­Leod mentioned Zülzer in his Noble Prize lecture: “In 1907 Zülzer published results which must be considered, in the light of what we now know, as really demonstrating the presence of the antidiabetic hormone in alcoholic extracts of pancreas. But unfortunately, even although several diabetic patients were benefited by administration of the extracts, the investigations were not sufficiently completed to convince others, and, apparently, Zülzer himself was discouraged in continuing them because of toxic reactions in the treated patients.” Banting also mentioned Zülzer in his Nobel Prize lecture: “In 1908, Zülzer tried alcoholic extracts on six cases of diabetes mellitus and obtained favorable results, one case of severe diabetes becoming sugar free. His extracts were then tried by Forschbach in Minkowski’s clinic with less favorable results, and the investigation was abandoned by this group of workers” (www.nobelprize.org/prizes/medicine). In the first publications on insulin, the team in Toronto did not quote Zülzer, only mentioning him after the patent issue.

Unveiling Diabetes - Historical Milestones in Diabetology

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