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Contributions to drug discovery from academic groups are not limited to small molecules. Biologic drugs bear tremendous promise, and significant progress has been made to use them as therapeutics. The earliest reported example is the discovery of insulin [82]. The optimization of insulin to adapt short‐ and long‐acting profiles has been described earlier in this series [83]. Interestingly, this work, albeit carried out in the laboratories of renowned pharmacologist John Macleod, was started by a rather inexperienced student, Frederick Grant Banting.

After returning from World War I, Banting worked as a lecturer in fall of 1920. Preparing for a lecture on the pancreas, a recently published article caught his attention describing the observation of surviving islets in an obstructed, atrophic pancreas. He assumed that degrading enzymes could be responsible for losing the active principle of pancreatic secrete and that these enzymes would likely be produced in acinar cells. Thus he developed the idea that by ligation of the pancreas and induction of atrophy, it may be possible to selectively destroy acinar cells and thus deplete degrading enzymes while maintaining the active blood sugar‐lowering ingredient, which could then possibly be isolated by extraction. Enthusiastically he contacted Macleod, a proven authority in the field of diabetes. Macleod was skeptical that the approach could work, as many others had failed in isolating active pancreatic extracts before. He also easily noted that Banting only possessed textbook knowledge on diabetes, was not acquainted with recent literature on the topic, and also did not have the practical surgical experience to successfully perform the complicated procedures. However, after several meetings, Macleod agreed to offer him a (non‐paid) opportunity to experiment in his laboratories and asked one of his student assistants, Charles H. Best, to assist Banting in the proposed research. They started their experimental work on 17 May 1921, but it quickly turned out that Banting overestimated his surgical skills and the dogs faded quickly. However, Banting and Best subsequently formed an experienced team, and within 2.5 months they managed to treat a pancreatectomized dog with an extract isolated from excised pancreata of other dogs, which was able to transiently reduce its blood glucose. This result caused great excitement, but provision of extracts from duct‐ligated pancreata was a laborious method with very limited throughput. In August 1921 they developed the idea to utilize fetal calf pancreata, being available from butchers, as these contained less acinar cells (which are responsible for excreting digestive enzymes and thus would lead to destruction of the – yet to be discovered – insulin). This turned out to be successful. The process was further improved significantly when they decided to use alcohol for extraction of the fetal pancreata. The alcohol extract was significantly easier to concentrate than the previously used saline solution. On 11 December 1921, they decided to use the established protocol on an adult bovine pancreas and for the first time, this extract also displayed a strong glucose‐lowering effect. At that point in time, James Bertram Collip, a talented biochemist, was included in the team to produce the required extracts and particularly to optimize its production procedure. He thoroughly reworked the experimental procedures and discovered that the active principle of the extract was still soluble at high ethanol concentrations, which enabled precipitation of other proteins. At an ethanol concentration of 90 %, the active principle itself would precipitate, which enabled an effective purification protocol. Resuspension of the precipitate yielded the desired material. He also developed a more practical activity test, which relied on injecting an aliquot into a vein in a rabbit's ear, avoiding experimentation on pancreatectomized dogs. At the time, one unit of insulin was defined as “the amount of insulin required to reduce the concentration of blood glucose in a fasting rabbit weighing 2 kg to the convulsion level of 45 mg/dL (2.5 mmol/L).” Later, after the structure and molecular weight of insulin were determined, the earlier definition was replaced by one unit of insulin being defined as the “biological equivalent” of 34.7 μg pure crystalline insulin, still relating to the pharmacological effect of insulin on the initially used rabbits. The definition of a unit of insulin is still relating to these criteria, whatever the derivative or its molecular weight is considered.

The first type I diabetic patient was treated on 11 January 1922, less than eight months after the initial research was started. Injection of 7.5 mL of extract led to a marked, but temporary decrease of blood glucose and a significant reduction of excreted urinary glucose. No reduction of ketone bodies was noted. A sterile abscess developed at site of injection, likely resulting from remaining impurities of the extract. These results, albeit clearly far from optimal, spurred further research, and the next months were characterized by extensive production of material and further clinical testing. When treating the same patient on 23 January 1922 with a new extract carefully produced by Collip, a marked drop in glucose from 520 to 120 mg/dL was observed. Ketone bodies disappeared and the physical state of the patient improved significantly. Six more patients were treated in February and in March of that year an initial report on the clinical experiments was published [84].

The scientific success was clouded by a strong argument between the researchers. Banting felt early on that the more established and experienced Macleod would try to steal his original idea and claim the discovery as his own success. He believed that Macleods' contributions were not significant and that his comments discouraged rather than encouraged Banting's research. He felt that the discovery of insulin was derived only through Best's and his own work. There was also some dispute about the value of the contributions of Collip, who, annoyed by the team atmosphere, announced that he would consider leaving the project and filing an individual patent on the purification procedure of insulin. It is reported that he and Banting even got into a physical fight over the project.

In the end, Banting and Macleod received the Nobel Prize for the discovery of insulin in 1923. Best and Collip were not included. The Prize was presented on 10 December 1923, less than 19 months after the group started their research. To this day, Banting remains the youngest Nobel laureate, being only 32 years of age when he received the Prize. Banting, upset with having to share the Prize with Macleod, initially wanted to reject the Prize but changed his mind later. He shared his monetary award with Best, as Macleod did with Collip. The decision of the Nobel committee also suffered criticism by other scientists, who had made important related discoveries before. In the case of insulin, particularly Georg Zuelzer [85], Ernest Scott [86], and Nicolas Paulescu [87] protested, but their contributions remained unacknowledged.

The discovery of insulin, albeit achieved many years ago, can still serve as a characteristic example of academic drug discovery. Clearly it began as an idea of an enthusiast, who was inspired by an ingenious thought and also clearly was not yet an expert in the research area he was about to enter. “Too much reading of the literature is inadvisable for wide diversity of opinion and confusion of thought” is a citation being connected to Banting. Also, the associated rivalry between the individual researchers is one point frequently observed particularly in academic settings. Necessarily, successful drug discovery is an interdisciplinary endeavor and calls for involvement of multiple experts willing to contribute their individual knowledge. Discussions on significance of individual contributions, e.g. reflected by debating first and last authorships, will poison the team spirit and easily compromise the joint research effort. It may even put the project as a whole at risk of a premature end. Also, decisions of the Nobel committee tend to cause criticism, particularly today, as the general research fields are broad and the selected questions are complex. Normally many scientists contributed valuable insights. With a maximal number of three laureates to be nominated for a particular topic, it is within the nature of this award that many scientists will find their contributions unconsidered.