Banting | Best & Insulin #1

In October 1920, Canadian Frederick Banting concluded that it was the very digestive secretions that Minkowski had originally studied that were breaking down the islet secretion(s), thereby making it impossible to extract successfully. He jotted a note to himself: "Ligate pancreatic ducts of the dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate internal secretion of these and relieve glycosurea."  The idea was the pancreas's internal secretion, which, it was supposed, regulates sugar in the bloodstream, might hold the key to the treatment of diabetes. A surgeon by training, Banting knew certain arteries could be tied off that would lead to atrophy of most of the pancreas, while leaving the islets of Langerhans intact. He theorized a relatively pure extract could be made from the islets once most of the rest of the pancreas was gone. In the spring of 1921, Banting traveled to Toronto to explain his idea to J.J.R. Macleod, who was Professor of Physiology at the University of Toronto, and asked Prof. Macleod if he could use his lab space to test the idea. Prof. Macleod was initially skeptical, but why not & eventually agreed to let Banting use his lab space while he was on holiday for the summer. He also supplied Banting with ten dogs on which to experiment, and two medical students, Charles Best and Clark Noble, to use as lab assistants, before leaving for Scotland (going on holidays? He had something big coming up knowing that he too was a big Research Icon around Toronto).  Since Banting required only one lab assistant, Best and Noble flipped a coin to decide who would assist Banting for the first half of the summer. Reluctantly, Best had agreed that Noble take the first half but Noble insisted the coin decide their fate whilst Banting just watched. Best won the coin toss, and took the first shift as Banting's assistant. Loss of the coin toss may have proved unfortunate for Noble, given that Banting decided to keep Best for the entire summer, and eventually shared half his Nobel Prize money and a large part of the credit for the discovery of insulin with the winner of the toss. Had Noble won the toss, his career might have taken a different path. [ true... ] Banting's method was to tie a ligature around the pancreatic duct; when examined several weeks later, the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets. They then isolated an extract from these islets, producing what they called "isletin" (what we now know as insulin), and tested this extract on the dogs starting July 27. Banting and Best were then able to keep a pancreatectomized dog named *Marjorie* alive for the rest of the summer by injecting her with the crude extract they had prepared. Removal of the pancreas in test animals in essence mimics diabetes, leading to elevated blood glucose levels. Marjorie was able to remain alive because the extracts, containing isletin, were able to lower her blood glucose levels.

 Banting and Best presented their results to Prof. Macleod on his return to Toronto in the fall of 1921, but Prof. Macleod pointed out flaws with the experimental design, and suggested the experiments be repeated with more dogs and better equipments. He then supplied Banting and Best with a better laboratory, and began paying Banting a salary from his research grants. Several weeks later, the second round of experiments was also a success; and Prof. Macleod helped publish their results privately in Toronto that November. However, they needed six weeks to extract the isletin, which forced considerable delays. Banting suggested they try to use fetal calf pancreas, which had not yet developed digestive glands; he was relieved with a satisfactory smile to find this method worked well. With the supply problem solved, the next major effort was to purify the extract. In December 1921, Prof. Macleod invited the biochemist James Collipto help with this task, and, within a month, the team felt ready for a clinical test....