How it began
On October 31, 1920, Frederick Banting, a surgeon in London, Ontario, wrote down an idea for isolating the internal secretion of the pancreas. J. J. R. Macleod, head of physiology at the University of Toronto, gave him a laboratory, dogs and a student assistant, Charles Best. Through the summer of 1921 their extract lowered blood sugar in dogs whose pancreas had been removed. In December 1921 the biochemist James Collip joined to purify the extract for use in people.
Before it existed
Before 1921 a diagnosis of type 1 diabetes was a death sentence. Researchers had already placed the source of the missing substance in the pancreas, and many had tried pancreatic extracts over the preceding two decades without producing a usable treatment. The Toronto group had one clear advantage: by 1921 blood sugar could be measured precisely on small samples, so they could track what their extracts did.
How it works
Collip refined an alcohol extraction so that the active substance stayed in solution while other proteins were precipitated out, and fats and salts were then removed by washing and centrifuging. He tested each batch on rabbits, which was faster than using dogs. The substance was named insulin, from the Latin for island, after the islets of the pancreas where it is made. Injected, it lowers blood sugar.
How it spread
Attempts to scale up at the university's Connaught Laboratories had failed by May 1922, and the university then made an agreement with Eli Lilly of Indianapolis to manufacture insulin. British rights went to the Medical Research Council and European rights to the nonprofit Nordisk Insulin Laboratory. Banting, Best and Collip sold their patent rights to the university for one dollar each so that no single company could control the discovery.
What changed first
On January 11, 1922, Leonard Thompson, aged 14 and close to death at Toronto General Hospital, received the first injection, with little effect. On January 23 he received Collip's purer extract. Sugar and ketones nearly vanished from his urine and his blood sugar fell by about 75 percent. He lived another 13 years. News of the trials brought requests from around the world.
What lasted
The 1923 Nobel Prize in Physiology or Medicine went to Banting and Macleod, who shared the money with Best and Collip. A review written a century later states that the Toronto four were the first to develop an insulin preparation that worked as a therapy in humans. Later work established insulin's structure and gene sequence and produced human insulin and long and rapid acting forms, which also treat many people with type 2 diabetes.