Discovery of Insulin (1921): Banting, Best and Diabetes

The discovery of insulin at the University of Toronto in 1921–22 turned type 1 diabetes from a fatal disease into a manageable condition. Within about eight months, a small team led by the surgeon Frederick Banting and the student Charles Best moved from experiments on dogs to saving a dying 14-year-old boy, Leonard Thompson. It was one of the fastest and most celebrated breakthroughs in the history of medicine, and also one of the most bitterly disputed.

Background: diabetes before insulin

Diabetes mellitus had been described since antiquity, but by the early 20th century doctors still had no effective treatment for its most severe form, now called type 1 diabetes. Patients, often children, lost weight rapidly, suffered extreme thirst and usually fell into a fatal coma within months or a few years. The only option was a near-starvation diet promoted by physicians such as Frederick Allen in the United States, which delayed death but could not prevent it.

Scientists had already linked the disease to the pancreas. In 1889 Oskar Minkowski and Joseph von Mering in Strasbourg showed that removing a dog’s pancreas caused diabetes. Paul Langerhans had described clusters of cells in the pancreas in 1869, later called the islets of Langerhans, and researchers suspected they produced an internal secretion that controlled blood sugar. The hypothetical substance was even given a name, insulin, from the Latin insula (“island”), before anyone had isolated it.

Several investigators came close. Georg Zuelzer in Berlin tested a pancreatic extract on patients from 1908, Ernest Scott and Israel Kleiner in the United States obtained promising results, and the Romanian physiologist Nicolae Paulescu published work on an extract he called “pancreine” in 1921. None of them produced an extract that was both effective and safe enough to be used routinely in people.

Banting’s idea

Frederick Banting was a 28-year-old surgeon with a struggling practice in London, Ontario, when, in October 1920, he read an article by Moses Barron about how blockage of the pancreatic duct caused the digestive part of the pancreas to waste away while leaving the islets intact. Banting wondered whether tying the duct in dogs, then waiting for the digestive tissue to degenerate, would allow the islet secretion to be extracted before digestive enzymes destroyed it.

He took the idea to J. J. R. Macleod, professor of physiology at the University of Toronto and an expert on carbohydrate metabolism. Macleod was sceptical of Banting’s limited research experience but agreed to give him laboratory space, experimental dogs and a student assistant over the summer of 1921, while Macleod himself was away in Scotland.

What happened in Toronto

Work began in May 1921. Charles Best, a 22-year-old graduate in physiology and biochemistry, became Banting’s assistant; a popular story says he won the job on a coin toss with another student, Clark Noble. Through a hot summer in a cramped laboratory, the two men removed the pancreas from some dogs to make them diabetic, tied the pancreatic ducts of others, and prepared crude extracts from the degenerated glands.

By late July they had evidence that injecting the extract lowered blood sugar in diabetic dogs. Results were inconsistent and many animals died, but by the autumn the pair had kept a diabetic dog alive for several weeks. They also found they could make extracts from whole fetal calf pancreas and then from ordinary beef pancreas from slaughterhouses, which made larger supplies possible. Macleod, back in Toronto, redirected more of his department towards the project.

In December 1921 the biochemist James Collip, on sabbatical from the University of Alberta, joined the team to purify the extract. Relations were already strained: Banting resented Macleod’s growing role and feared credit would be taken from him. The first public presentation of the work, at the American Physiological Society meeting in New Haven at the end of December 1921, was poorly received.

The first patient: Leonard Thompson

On 11 January 1922 Leonard Thompson, a 14-year-old boy who weighed about 65 pounds (around 29 kg), received an injection of Banting and Best’s extract at Toronto General Hospital. The result was disappointing: his blood sugar fell only slightly, and he developed an abscess at the injection site.

Collip, meanwhile, had found a way to produce a much purer extract by precipitating it with increasing concentrations of alcohol. From 23 January 1922 Thompson received Collip’s preparation. His blood sugar fell to near normal, sugar and ketones largely disappeared from his urine, and he became visibly stronger. Further patients followed within weeks, and the Toronto group adopted the name insulin for their product.

The breakthrough was tarnished by quarrelling. According to accounts collected by the historian Michael Bliss, Collip at one point refused to share his method, leading to a physical confrontation with Banting. For a time in early 1922 the team even lost the ability to make potent insulin while scaling up production.

Key people

• Frederick Banting (1891–1941): the surgeon whose idea started the project; he was knighted in 1934 and died in a plane crash in Newfoundland during the Second World War.
• Charles Best (1899–1978): Banting’s student assistant, who later succeeded him as head of the Banting and Best Department of Medical Research in Toronto.
• J. J. R. Macleod (1876–1935): the Scottish-born physiologist who provided the laboratory, guided the research design and coordinated the wider team.
• James Collip (1892–1965): the biochemist whose purification method made insulin safe enough for human use.
• Leonard Thompson (1908–1935): the first patient, who lived another 13 years on insulin before dying of pneumonia.

Production and the Nobel Prize

Making enough insulin for thousands of patients required industrial methods. The inventors assigned their patent rights to the University of Toronto’s Board of Governors for one dollar each, so that the university could license manufacturers and control quality. In 1922 it reached an agreement with Eli Lilly and Company of Indianapolis, which developed large-scale extraction from animal pancreases; production also began in Britain, Denmark and elsewhere. By 1923 insulin was widely available in North America and Europe.

Among the early patients was Elizabeth Hughes, daughter of the US Secretary of State Charles Evans Hughes, who was treated by Banting in 1922 and lived until 1981. Newspaper stories of emaciated children recovering made insulin famous almost overnight.

In October 1923 the Nobel Prize in Physiology or Medicine was awarded to Banting and Macleod. Banting, furious that Best had been passed over, announced that he would share his prize money with him; Macleod then shared his with Collip. Arguments about credit continued for decades, with partisans of Banting and Best playing down the roles of Macleod and Collip. Most historians now regard the discovery as a team effort in which all four were essential.

Consequences and legacy

Insulin did not cure diabetes, but it transformed it into a chronic condition that people could live with for decades. Children who would have died within months grew up, worked and had families. The discovery also helped establish endocrinology, the study of hormones, as a major medical field, and it demonstrated how quickly university research could be turned into a mass-produced medicine.

Insulin itself became central to later science. Frederick Sanger determined its amino-acid sequence in the early 1950s, the first protein to be fully sequenced, earning a Nobel Prize in 1958. Dorothy Hodgkin solved its three-dimensional structure in 1969. In 1982 human insulin made by genetically engineered bacteria went on sale, one of the first products of biotechnology, replacing much of the animal insulin from slaughterhouses.

The Toronto discovery belongs to a series of laboratory advances that reshaped medicine in the early 20th century, alongside the discovery of penicillin later in the decade and earlier work such as Pasteur’s rabies vaccine. It also came only a few years after the 1918 influenza pandemic, at a moment when public faith in scientific medicine was being tested and rebuilt.

Myths and facts

• Myth: Banting and Best did it alone. Their summer experiments were the starting point, but Macleod’s direction and Collip’s purification were essential for a usable drug.
• Myth: no one had tried pancreatic extracts before. Several researchers, including Zuelzer and Paulescu, had made extracts with some effect; the Toronto team was the first to produce one that worked reliably and safely in patients.
• Myth: insulin cures diabetes. Insulin replaces a missing hormone and must be taken for life; it controls the disease rather than curing it.
• Myth: the inventors gave insulin away for free. The patent was sold to the University of Toronto for a nominal sum, but insulin was still a commercial product made and sold by licensed companies.

Timeline

• 1889: Minkowski and von Mering show that removing the pancreas causes diabetes in dogs.
• 1920, October: Banting conceives his duct-ligation idea after reading Moses Barron’s article.
• 1921, May: Banting and Best begin experiments in Macleod’s Toronto laboratory.
• 1921, late July: Extracts first shown to lower blood sugar in a diabetic dog.
• 1921, December: James Collip joins the team to purify the extract.
• 1922, 11 January: Leonard Thompson receives the first, largely unsuccessful, injection.
• 1922, 23 January: Thompson responds dramatically to Collip’s purified insulin.
• 1922: Agreement with Eli Lilly; industrial production begins.
• 1923, October: Nobel Prize awarded to Banting and Macleod.
• 1982: Genetically engineered human insulin goes on sale.

Why it matters

The discovery of insulin was the first effective treatment for a deadly hormonal disease and has since kept many millions of people alive. It showed the power of laboratory physiology, the importance of teamwork and purification in drug development, and the tensions over credit and commerce that still surround medical breakthroughs today.