Canadian Inventions – Banting and Best Discover Insulin

Although diabetes is amongst the earliest documented diseases afflicting humans, an effective treatment was only available after 1921 when Sir Fredrick Banting and Charles Best successfully isolated and extracted insulin in laboratory tests. Their discovery provided respite from a disease that had a mortality rate in excess of 30% (with little hope for type 1-diabetes sufferers) and no substantiated treatment (the most successful therapy at the time was strict dieting that often resulted in starvation). While there is still no cure for diabetes and millions of people worldwide are diagnosed with the disease every year, the outlook became entirely different for diabetics after Banting and Best’s discovery. Banting was a veteran of the First World War and received the Military Cross for his service in the Canadian Army Medical Corps. On his return to Canada, he took a position as an orthopaedic surgeon at Toronto’s Hospital for Sick Children. During this period, he developed an interest in the advances of diabetes research, a subject that was largely unrelated to his work at the hospital. In 1920, Banting evolved a theory for extracting insulin from a donor pancreas. He believed that pancreatic enzymes rapidly degraded any insulin that wasn't released from the pancreas, so that insulin in an extracted pancreas would deteriorate before it could be administered to a patient (accounting for the ineffectiveness of previous experimental trials). He hoped to remove the enzyme by starving the donor pancreas prior to extraction and preserve the insulin so that it could be administered to a patient. In the spring of 1921 Banting convinced J J R Macleod, Professor of Physiology at the University of Toronto, to let him use the university facilities to investigate his theory. Macleod was sceptical of Banting’s proposal, but gave him a small laboratory, basic equipment, ten laboratory dogs and an assistant, Charles Best. Best was a medical student at the time, and neither he nor Banting had any research experience. Banting proposed inducing diabetes in one dog, while creating as a treatment an extract from the pancreas of another dog. The experiment started badly. The first dog died almost immediately from an anaesthesia overdose. Seven of the ten dogs were dead by the end of the second week, most from shock or infection. But Banting and Best persisted. Eventually, they were able to prepare a suitable pancreas extract and administer it to the diabetic dog by injection. The results were encouraging, but Macleod needed more convincing. Further experiments produced more conclusive results. The extract successfully offset the induced diabetic effects, reducing the dog's blood sugar levels. The experiments also revealed that it was unnecessary to remove enzymes from the pancreas before preparing the extract, because it was digestive enzymes in the stomach that were responsible for the degradation of insulin when the treatment was administered orally. While Banting and Best worked to advance their treatment (including a switch to bovine pancreas as a source of insulin), James Collip, a visiting biochemist from the University of Alberta, refined the extract in preparation for human trials. By early 1922, Collip had successfully purified the extract, incorporating glucose into the final preparation, to reduce the chances of an insulin overdose. Human trials began immediately, with great success. Banting, Best and Collip applied for, and were granted, a patent for the pancreatic extract. They gifted the patent rights to the University of Toronto, with the intention of making the treatment widely available to diabetes sufferers. In 1923, Banting and Macleod were awarded the Nobel Prize in Medicine. Banting was furious that Best was not recognised, and elected to share his prize money with Best in recognition of his work. Macleod split his share of the prize with Collip. Frederick Banting was elected to the Banting and Best Chair of Medical Research at the University of Toronto, where he remained until his death in a 1941 plane crash. Charles Best succeeded Macleod as Professor of Physiology in 1929, and inherited Banting’s Chair after his death. Summary by: Richard Murphy