Endocrinology · 1922
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 problem was that the proteolytic exocrine enzymes destroyed whatever active material was present during extraction.
Frederick Banting, a surgeon in London, Ontario, read a paper on pancreatic duct ligation 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, then completing his degree, as a research partner. Over the summer of 1921, Banting and Best worked through ten weeks of experiments in depancreatized dogs, producing an extract they called isletin that consistently lowered blood glucose.
The first human trial took place on January 11, 1922, when the extract was injected into Leonard Thompson, a 14-year-old boy admitted to Toronto General in diabetic crisis. The preparation caused a severe local inflammatory reaction and was stopped. Biochemist James Collip, who had joined the team, spent two weeks refining the purification technique. On January 23, a cleaner preparation was administered; Thompson's glucose fell from above 500 mg/dL to near-normal levels within 24 hours, and his ketonuria cleared. He was discharged and lived another 13 years, dying of pneumonia rather than diabetes.
Eli Lilly entered a licensing agreement with the University of Toronto and began large-scale production of bovine insulin by late 1922, making it available across North America before the year was out. Translation from animal work to commercial product on that timeline was unusual for the period. The Toronto team, recognizing the urgency, had deliberately kept the patent fees low to facilitate broad access.
Banting and Macleod received the Nobel Prize in Physiology or Medicine in 1923. Banting was openly hostile to Macleod's inclusion and publicly split his prize money with Best; Macleod split his with Collip. The fractured credit reflected genuine disagreements about who deserved recognition for which aspects of the work. Leonard Thompson's recovery from that January morning remained the fixed point around which all subsequent disputes turned.
Key People
- Frederick Banting — Surgeon whose concept of duct ligation led to the Toronto insulin experiments
- Charles Best — Medical student who co-conducted the dog experiments with Banting in summer 1921
- James Collip — Biochemist who purified the extract for the successful January 23, 1922 injection
- John Macleod — Toronto physiology professor who provided the laboratory and shared the 1923 Nobel
- Leonard Thompson — First human recipient of purified insulin, age 14, January 23, 1922
Banting FG, Best CH. J Lab Clin Med. 1922
Related landmarks
- 1922 · Insulin for diabetes mellitus (Endocrinology)
- 1960 · Radioimmunoassay (RIA) (Endocrinology)
- 1971 · Schally and Guillemin: Hypothalamic Releasing Hormones (Endocrinology)
- 1982 · Recombinant Human Insulin (Humulin) Approval (Endocrinology)