Читать книгу Unveiling Diabetes - Historical Milestones in Diabetology - Группа авторов - Страница 61

In 1910, Zülzer negotiated with the Hoechst Company, but they refused to cooperate. Zülzer had to continue working with his limited private means. In 1911, Hoffmann La Roche became interested in his work. With this support, Zülzer was able to set up a laboratory in the Hasenheide hospital and to collaborate with the chemist Dr. Camille Reuter (1886–1974), an employee of Roche working in the company’s laboratory in Grenzach, and pupil of Prof. Richard Martin Willstädter (who received the Nobel Prize for his work on chlorophyll in 1915 and had to emigrate to Switzerland in 1939). In 1914, Reuter continued to produce extracts in the Roche laboratories in Grenzach in Germany, located near Basel in Switzerland. Camille Reuter even processed over 100 kg of pancreata. In August 1914, these extracts very often led to severe cramps or death in experimental animals. The results of this research performed by Reuter in the Roche laboratories were not published. Nevertheless, following the discoveries in Toronto, Camille Reuter reported on this work in a scientific meeting in Luxembourg on January 13, 1924 [10]. Reuter reported that he had started to evaluate the effect of the extracts by measuring glycemia in dogs, it happened that glycemia dropped down to 0.017% in an animal. He even treated a patient with severe diabetes, stating that glycemia dropped and glucosuria disappeared [10].

Reuter, who was the head of the laboratories of Roche at the time, discussed the findings with his board. The board decided to abandon this research. The Hoffmann la Roche board members thought that the action of the intravenously injected extract was far too short and that nobody would ever consider injecting an antidiabetic agent multiple times per day for many years. They decided to focus on the development of oral agents to treat diabetes. Reuter filed the results of his work in the archives of Roche in November 1914, they were not available to the public. In 1924 he published the details of the research he had carried out in the Roche laboratories in 1914 [11]. Camille Reuter left Roche and returned to Luxembourg. He died in his home country Luxembourg in 1974.

If Zülzer had frequently measured the blood glucose concentration of his animals it would have been a direct path to the Nobel Prize – but he never did. Blood glucose measurements were still very complex in those days: a lot of blood was needed. Later, new methods required less blood and made more frequent measurements possible, like the method published by Hagedon and Jensen in 1918 [12]. Perhaps Zülzer did not even think about the possibility of hypoglycemia – he was convinced that insulin simply acted as an antagonist to adrenaline – how could hypoglycemia occur? At this crucial period, just when Zülzer had very effective extracts available with Roche, he had to go to the front and the Hasenheide Clinic became a military hospital. Zülzer’s attempts to find support for his work after the end of the First World War were unsuccessful.

Fig. 3. Tomb of George Zülzer, White Chapel Cemetery in Troy, Michigan. Thanks to Alejandra de Leiva Pérez for the picture.

Following the discovery of Insulin in Toronto the first US patent application was refused on November 10, 1922. The problem was Zülzer’s US patent dating from 1912. However, it was possible to pursue the patent application to a higher level. The Toronto team, supported by Eli Lilly, had to present more evidence about the effective treatment with insulin and their method to produce it. The famous US diabetologists Joslin and Allan, and even the US politician Charles Evans Hughes – whose daughter was one of the first patients successfully treated with insulin, supported the application, which was finally granted by the US patent office to the discoverers of insulin as well as for the method to produce it on January 23, 1923 [13].

In 1933 the Nazis revoked Zülzer’s title as a lecturer. Subsequently, he emigrated in early 1934 and established a successful internist practice in New York. He died on October 15, 1949 – 3 years after giving up his practice at the age of 79 years [1]. He is buried in Troy, Michigan. On the tombstone one can read: “Dr. Georg Ludwig Zülzer, the first physician to bring diabetic patients out of coma with his extracted pancreas preparation” (Fig. 3). Several members of his family could not escape the holocaust, including his cousin, the biologist Dr. Margarete Zülzer, who was killed by the Nazis in Westerbork in the Netherlands in 1943.