History of Diabetes and Insulin

One of the earliest detailed surviving clinical accounts is by the Greek physician Aretaeus of Cappadocia, writing in the second century CE. He used "diabetes" — from the Greek word for a siphon, or passing through — for a condition of unquenchable thirst and excessive urination, and described the wasting, the sweet-smelling breath, and the usually fatal course. In the Indian medical tradition, the Charaka Samhita, compiled in the early centuries CE, described madhumeha, "honey urine," as a form of swelling, considered hereditary and associated with obesity, and recommended bitter gourd and other plants as remedies.

The modifier "mellitus" (honey-sweet) was added much later. In the seventeenth century the English physician Thomas Willis emphasized the sweet taste of diabetic urine, helping distinguish diabetes mellitus from other conditions that also caused excessive urination.

Before insulin, treatment was largely dietary. In 1797 the Scottish physician John Rollo published a regimen centered on animal foods and restricting bread and other carbohydrates. Later severe calorie-restriction or "starvation" diets could sometimes prolong life, but they were harsh, often ineffective, and left patients weak and hungry.

1. 2nd century CE: Aretaeus of Cappadocia describes "diabetes," the "siphon" disease of thirst and wasting.
2. Early centuries CE: The Charaka Samhita describes madhumeha, "honey urine."
3. 17th century: Thomas Willis emphasizes the sweet urine of people with diabetes mellitus.
4. 1797: John Rollo publishes a carbohydrate-restricted dietary treatment.
5. 1910: E. P. Sharpey-Schafer proposes the name "insulin" for the hormone he attributes to the islets.

Nineteenth-century chemistry made sugar in urine and blood increasingly measurable. In 1869 the German medical student Paul Langerhans described small clusters of cells scattered through the pancreas, later called the islets of Langerhans. In 1889 the German physiologists Oskar Minkowski and Joseph von Mering showed that removing the pancreas from a dog produced severe diabetes, helping researchers locate metabolic control in an organ rather than in the kidneys alone.

The hypothesis that the islets released an internal secretion encouraged repeated attempts to prepare a pancreatic extract without the digestive enzymes destroying or contaminating it. Between 1906 and 1908 the Berlin physician Georg Zülzer tested a pancreatic extract in patients; it produced some improvement but also serious adverse effects and could not become a dependable treatment. In 1910 the British physiologist E. P. Sharpey-Schafer proposed the name "insulin" for the hormone he attributed to the islets. The Romanian physiologist Nicolae Paulescu conducted experiments before and after the First World War and published in 1921 that a pancreatic extract lowered blood sugar in dogs. His priority claim was later disputed, and he was not included when the Nobel Prize was awarded in 1923.

Toronto's achievement was therefore both new and cumulative. Banting's experimental idea, Best's laboratory work, Macleod's facilities and physiological direction, Collip's purification, animal labour, clinical judgement, and patient participation all contributed. Disputes over the Nobel Prize reveal how institutions compress collaboration into a few names.

On 6 November 1920 the surgeon Frederick Banting, then working in London, Ontario, visited the physiologist J.J.R. Macleod at the University of Toronto with the idea of isolating an islet secretion. Macleod gave him a room, two students, and some dogs. In the summer of 1921 Banting and the medical student Charles Best began experiments in a physiology laboratory at the University of Toronto, and in August their extract, which they called "isletin," lowered the blood sugar of a dog whose pancreas had been removed.

The team switched to calf pancreas in November 1921, and in early December the biochemist James Collip joined to solve the purification problem. On 11 January 1922 the 14-year-old Leonard Thompson, admitted to Toronto General Hospital in a serious condition, received the first human injection. The early extracts were impure and produced local reactions. On 23 January 1922 Thompson received Collip's more purified preparation, which produced clear clinical improvement. The University of Toronto began collaborating with Eli Lilly in May 1922 to scale up production, and the inventors assigned the insulin patents to the university for one dollar each in December 1922. Commercial supply expanded in 1923. The insulin therapy timeline entry marks 1921 as a turning point, and Leonard Thompson's treatment in 1922 became one of the emblematic moments of twentieth-century therapeutic medicine.

Insulin also belongs to the history of medical infrastructure. It required animal pancreases, purification, standardization, commercial manufacture, refrigerated supply, clinical supervision, and later home monitoring. The therapy was life-saving, but never simple.

1. 6 November 1920: Banting secures Macleod's support at the University of Toronto.
2. August 1921: "Isletin" lowers the blood sugar of an experimental dog.
3. December 1921: James Collip joins to solve the purification problem.
4. 11 January 1922: Leonard Thompson receives the Toronto team's first clinical injection.
5. 23 January 1922: Collip's purified extract produces the first clear clinical improvement.
6. 1923: The Nobel Prize in Physiology or Medicine goes to Banting and Macleod.

In 1923 the Nobel Prize in Physiology or Medicine went to Banting and Macleod "for the discovery of insulin." Best and Collip were not included — an omission that has remained controversial — and each laureate divided his half of the prize with the other. The exclusion of Paulescu, whose experiments published in 1921 had lowered blood sugar with a pancreatic extract, added to the dispute over who deserved priority.

While insulin was being manufactured, the mainstay of treatment elsewhere remained the starvation diet. The American physician Frederick M. Allen promoted a strict low-calorie regimen before insulin became available; insulin transformed that practice from a desperate restriction into one component of a broader therapy.

Patients also organized. In the late 1940s Charles Best helped found the Diabetic Association of Ontario, and in 1953 the provincial associations amalgamated as the Canadian Diabetes Association, which provided advocacy, education, and research funding. Insulin remained the only effective treatment until oral hypoglycaemic agents appeared in the 1950s.

Early extracts varied in strength and purity. David Scott's acetone method and Peter Moloney's benzoic-acid adsorption process, developed at the University of Toronto in 1922, made larger and more consistent batches possible; by November 1922 Connaught was producing about a litre of insulin per week. Connaught Laboratories and pharmaceutical manufacturers such as Eli Lilly then developed larger-scale production, testing, and dosage standards. Patents and licensing were intended to supervise quality while industrial collaboration supplied far more patients.

Longer-acting preparations, disposable syringes, portable glucose meters, pumps, recombinant human insulin, and continuous monitors repeatedly changed self-care. Each technology offered flexibility while adding new requirements for education, supplies, interpretation, and maintenance.

Insulin did not eliminate diet, exercise, or the risk of complications. It created a lifetime relationship among patients, families, clinicians, manufacturers, pharmacies, laboratories, and health systems. Cost and interrupted supply can turn a treatable condition back into an emergency.