Discovery of Insulin

In 1920, type 1 diabetes was a death sentence measured in months. The standard treatment at Toronto General and elsewhere was the Allen starvation diet: caloric restriction severe enough to slow the catabolic process, which extended survival modestly at the cost of extreme wasting. Patients, often children, lived on several hundred calories per day. The underlying problem, loss of islet cell function and the resulting absence of a glucose-regulating hormone, had been theorized for decades, and researchers had attempted to extract that hormone from the pancreas without success. The likely obstacle was that the digestive enzymes of the pancreas destroyed the active material during extraction.

Frederick Banting, a surgeon in London, Ontario, read Moses Barron's paper on the islets and pancreatic duct blockage in October 1920 and proposed a solution: ligate the ducts to cause exocrine atrophy while preserving the islets, then extract from the residual tissue. He approached John Macleod, professor of physiology at the University of Toronto, who provided laboratory space and assigned Charles Best, a student, as his assistant. Beginning on May 17, 1921, Banting and Best worked through the summer on depancreatized dogs, producing an extract they called isletin that lowered blood and urine glucose.

The first human trial took place on January 11, 1922, when the extract was injected into Leonard Thompson, a 14-year-old boy at Toronto General. It lowered his blood glucose only a little, his urine still showed ketones, and he developed a sterile abscess at the injection site. Biochemist James Collip, who had joined the team, worked around the clock to purify the extract further. On January 23, Thompson received the new preparation; his blood sugar fell from 520 mg/dL to 120 mg/dL by the next day, and his ketonuria cleared. He lived another 13 years and died in 1935, aged 27.

By February 1922 six more patients in Toronto had been treated, and in April the group renamed the extract insulin. Banting, Best and Collip patented the method and sold the rights to the University of Toronto for one dollar. Eli Lilly signed a one-year exclusive agreement with the university in May 1922, achieved large-scale purified production that autumn using isoelectric precipitation, and in 1923 began selling Iletin, the first commercial insulin.

Banting and Macleod received the Nobel Prize in Physiology or Medicine in 1923. Banting was furious that Macleod had been included and Best left out, and at first refused the prize. He accepted, publicly credited Best, and gave him half his prize money; Macleod shared his with Collip.