How a summer in Toronto changed medicine — insulin, 1921

Before insulin: starvation as the only treatment

In the early 1920s, type 1 diabetes was a swift, terrible disease. The pancreas stopped producing insulin, blood glucose rose uncontrolled, and patients — usually children — wasted away, fell into diabetic coma, and died. The only therapeutic approach was the so-called Allen diet: extremely calorie-restricted starvation regimens that prolonged life by a few months while the children starved in their hospital beds.

That the pancreas had something to do with diabetes had been known since 1889 — Oskar Minkowski and Joseph von Mering in Strasbourg had shown that dogs became diabetic after pancreatectomy. The search for the antidiabetic factor in pancreatic extracts had been running fruitlessly for over three decades. The problem: the pancreas also contains large amounts of digestive enzymes that destroy the peptides being sought.

Banting's idea

In October 1920, Frederick Banting — a 28-year-old physician with a small practice in London, Ontario — read a review article by Moses Barron about a patient whose pancreatic ducts had been blocked by a gallstone. Barron described that the digestive acini in the pancreas had degenerated while the islets of Langerhans remained intact.

Banting jotted down an idea that same night: if one ligated the pancreatic ducts of an experimental animal, the digestive acini would die off, the islets would be preserved — and an extract from this degenerated pancreas should contain the antidiabetic substance without immediately destroying it.

The summer of 1921

Banting needed a university setting and approached J.J.R. Macleod in Toronto, a diabetes expert. Macleod was skeptical — the hypothesis was not new — but gave Banting a laboratory during his summer vacation, ten dogs, and a student assistant: Charles Best, age 22, freshly graduated in physiology and biochemistry.

On 17 May 1921, Banting and Best began their experiments. They ligated the pancreatic ducts in dogs, waited weeks for degeneration, then extracted the remaining islet tissue and injected the extract into a second dog whose pancreas had been completely removed. Blood glucose dropped — and the dog survived.

The first weeks were chaotic. Dogs died from inadequate anaesthesia, infection, or because the pancreatic ligatures failed. The team's dog Marjorie was kept alive for weeks by repeated injections — the first clear proof.

Collip's crucial contribution

The canine extract was too impure for humans. Macleod brought in James Collip, a biochemist, who developed an ethanol precipitation method to make the extract clinically usable. By January 1922 a first preparation was ready.

On 11 January 1922, 14-year-old Leonard Thompson at Toronto General Hospital received the first injection. It was a disappointment: the Banting-and-Best extract caused an allergic reaction and barely lowered blood glucose. Twelve days later, on 23 January, the team repeated treatment with Collip's purified extract. Thompson's blood glucose fell from 28.9 to 6.7 mmol/L, the ketosis disappeared, his general condition improved dramatically. It was the first successful insulin therapy in the world.

Eli Lilly and mass production

Within weeks it was clear: the University of Toronto could not meet demand. Insulin was licensed to Eli Lilly in Indianapolis — with the requirement that the patent be available free of charge for the university's own use. Lilly began industrial production in late 1922. Hundreds of thousands of patients were treated in the first years.

The contested Nobel drama

In 1923 the Nobel Prize for Medicine went to Banting and Macleod — not to Best and not to Collip. Banting was furious that Best had been passed over and shared his prize money with him. Macleod shared his with Collip. Disputes over authorship, recognition and financial share dragged on for decades and remain material for medical-history books to this day.

What we take away

• The idea alone was not decisive — it had been discussed in diabetes circles for decades.
• The convergence of several expertises was: Banting's tenacity, Best's craftsmanship, Macleod's lab and institutional protection, Collip's analytical chemistry.
• The first clinical application was almost a failure — purification made the difference. This holds for every peptide to this day: what works in animal models often fails in pharmaceutical preparation.
• The university's licensing decision to grant the patent symbolically for one dollar shaped insulin supply worldwide for a century.