Insulin: 100th anniversary

Community Featured

By Dr. Jock Murray and Janet Murray

For The Advocate

We mentioned before that we all like our stories that are often more myths than truth, as the myths are like Hollywood scripts, even though the truth is often more interesting. This is the case with one of Canada’s greatest medical triumphs, as we celebrate this year the 100th anniversary of the discovery of insulin.

The popular story is that surgeon Frederick Banting, who was searching for the mysterious secretion in the pancreas that could control glucose metabolism, awoke at night in October 1920, and scribbled a surgical solution on a notepad. His idea was to tie off the pancreatic ducts of dogs to isolate the internal secretion that reduced glucose levels. He and his medical student assistant, Charles Best, isolated the secretion, tried it on a young diabetic near death and suddenly the world had changed.

In this year, 100 years later, we should recognize that millions of people with diabetes have benefited from the work of all four of these men, and the team around them.
(Banting House, University of Western Ontario)

The history is more complex and messier, as clearly told by Michael Bliss in his two award winning books (The Discovery of Insulin, 1982; and Banting: a biography, 1984). In the 1920s it was known that removing the pancreas in animals led to fatal diabetes, so there was something in the pancreas that controlled glucose metabolism. Many before Banting had been searching for the pancreatic secretion, but after many failures, most gave up.

Banting had been preparing a talk to medical students at the University of Western Ontario on the pancreas on the fateful night when he jotted down an experiment to try. He had little experience in research or diabetes (which he mis-spelled on his scribbled note). Banting took his idea to Dr. J.J.R. Macleod, a well-respected expert on carbohydrate metabolism, and with good research facilities at the University of Toronto. Macleod was concerned about Banting’s inexperience in research and knew many had failed in this pursuit before, but he gave him the animals, and lab resources. A 22 year-old medical student, Charles Best, won a coin toss with another student to assist in the experiments. They started work on 17 May 1921 with Macleod’s giving detailed direction on how to do the experiments and prepare extracts for injection.

On 30 July they began injecting dogs with the extract and noted a drop in blood sugar. They called the extract “isletin”. Macleod suggested the extract should be called “insulin”.

Banting’s initial idea of using depancreatized dogs was useful in starting the experiments but they soon found they could get the extract from fresh beef or pork pancreas at local abattoirs. Macleod insisted they repeat and verify their experiments and he and Banting, who never got along, increasingly got into conflict.

James Collip, a talented biochemist from the University of Alberta, but a Toronto graduate, arrived to spend some time doing research with Macleod and was assigned to help purify the crude extract prepared by Banting and Best, which he did. The first presentation of their animal experiments to the American Physiological Society in December 1921 was underwhelming, as they had heard many claims before. Undeterred, they felt ready to try it on humans with diabetes. In January 1922 they injected a 14-year-old boy, Leonard Thompson, who was near death with diabetes. The result was disappointing. Twelve days later they tried again, and Thompson’s blood sugar had a dramatic drop and his tests and symptoms were reversed. They knew they had done something that could change the course of a disease that killed so many.

The key to the breakthrough on Thompson was that Collip, working furiously, had been able to develop an improved extraction process to remove toxic contaminants from Banting and Best’s extract. His purer extract worked consistently and effectively, suggesting very powerfully that the Toronto team had indeed discovered the internal secretion of the pancreas. Over the next weeks they rushed to verify the results and in March reported the results in other patients. Macleod reported the results at the Association of American Physicians in March, first using the word “insulin”. Co-authors on the paper were F.G. Banting, C.H. Best, J.B. Collip, W.R. Campbell, A.A. Fletcher, J.J.R. Macleod and E.C. Noble. Campbell and Fletcher had administered insulin to their patients and Noble was a young physiologist. This time the reception was a standing ovation, unusual for an academic paper at a medial meeting, but the audience recognized they were witnessing what would be one of the great medical discoveries of the 20th century.

The patent for insulin was given by the team to the University of Toronto. Now forgotten, Peter Moloney, a chemist, joined the team in 1922 and developed a way to purify insulin further and produce it in mass quantities, so by the end of 1923 it was available for diabetics around the world.

The excitement was at a high pitch and it was expected there would be accolades, even the Nobel Prize. Although it is clear that the discovery could not have happened as it did without the four major players and the team, Banting had his own view. He felt the discovery was entirely the result of his idea and his work with Best. He was always in conflict with Macleod, and even had a physical fight with Collip. He dismissed the work of others suggesting Macleod just provided research space, and Collip just did some chemical work.

In 1923 the Nobel committee made the most rapid award in their history. The committee recognized the discovery of Banting, and the research guidance of Macleod. Best and Collip were not mentioned. Infuriated, Banting announced he would share his award with Best, and Macleod said he would share his with Collip. The Nobel decision has been a controversy since, and hindsight would suggest all four should have been recognized. Banting’s admirers, joined by Best and his friends, insisted that Macleod was improperly recognized, and that the award should have gone to Banting and Best. Years of propaganda, involving extensive distortion of history, established in the popular mind, especially in Canada, the view that insulin had been discovered by Banting and Best. Macleod and Collip became forgotten men.

Dr. T. Jock Murray is a graduate of Pictou Academy and former Dean of Medicine at Dalhousie University. Janet Murray is a graduate of Mount Saint Vincent, majoring in philosophy and a diploma in journalism. She is the former Chair of the Board of Governors of Mount Saint Vincent University.