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.
Ernest Lyman Scott: The Case of the Murdered Manuscript
Ernest Lyman Scott (Fig. 4) was born on August 18, 1877 in the small town of Kinsman in northeastern Ohio. He grew up on the farm of his parents – his great grandfather had been granted the equity soon after the Western Reserve was opened for settlement in 1802. Their farm was not running very well and, as a result, his father could not afford to pay for the Ernest’s education. Luckily a prosperous Kinsman citizen offered a free loan of USD 1,000 with no limit on the time to repay it. Ernest studied natural sciences at Ohio Wesleyan University, finishing his BA in 1902. His first job was working for the US Coast and Geodetic Survey (1902–1903). Later he worked as a teacher of natural science in West Bay City until 1909 [14]. One of his students, a 17-year-old boy, developed diabetes – he was told by the doctors that all he could do was die [14]. This sad experience led Scott to pursue a scientific career in physiological research. In spring 1909 he was employed as an instructor in the Department of Physiology in the Medical School in Chicago. His stipend was only USD 750 per year and tuition fees, laboratory fees, and living expenses for 2 had to be paid from this. He presented to his boss, Prof. Anton Julius Carlson, a topic for his MA thesis: to find a blood glucose-lowering substance in the pancreas. Carlson was not enthusiastic – this topic was not in his main research interests – but he agreed. The research had to be carried out in the department of chemistry. This laboratory had excellent equipment thanks to donations by the Rockefellers. The interim head of department was Prof. Waldemar Koch, who chaired the department of pharmacology. Koch was a nephew of the Noble Prize winner Robert Koch. Initially, Scott consulted carefully all the published literature on the topic. In contrast to Zülzer, Scott believed that the hormone was a protein. He ground pancreas with sand and alcohol made to 85%. This was also the method Banting and Best used following their initial extractions of insulin. After his work on the extraction of insulin Scott carried out experiments on pancreatectomized dogs in 1911. The results were quite positive and glucosuria decreased after the injection of the extract (Fig. 5). Sadly, the convincing synopsis of the experiments from the thesis was not included in the publication by Prof. Carlson. (Fig. 6).
Fig. 4. Ernest Lyman Scott serving in the US Army in France [14].
In summer 1911 Scott wrote his thesis and gave three copies to Prof. Carlson. Carlson offered Scott a renewal of his position with the same – very low – salary. But Scott needed more money as he and his wife were expecting their second child. Scott instead accepted a position at the University of Kansas and left Chicago at the end of September 1911.
Carlson submitted Scott’s work to the American Journal of Physiology [15] without any consultation with Scott. He never read the paper before it was printed [14] and it was published in the name of one single author: E.L. Scott! The thesis was changed substantially. The discussion of previous research was drastically shortened, half of the references were omitted (5 of 10, Zülzer and Forschbach were not quoted any more). In one of the citations a mistake was introduced: Cohnheim should not be referenced as 1904 but rather 1906, as mentioned correctly in the thesis. However, the worst was the summary of the article. Scott’s thesis ends with the following (reprint of the thesis in Scott [14]):
Conclusions
1st. There is an internal