How Toronto’s street dogs powered one of medicine’s greatest breakthroughs—the discovery of insulin

Back in 1889, two German researchers, Oskar Minkowski and Joseph von Mering, discovered something striking while performing a vivisection—the practice of operating on live animals for scientific study—on dogs.

They observed that when the pancreas was removed, the animals developed severe symptoms of diabetes and died soon afterward. At the time, diabetes was not survivable, and it remained so until almost three decades later, when a young surgeon, Frederick Banting, and his assistant, Charles Best, succeeded in extracting insulin in physiologist John Macleod’s laboratory in 1921.

Two years later, Banting and Macleod were awarded the Nobel Prize in Physiology or Medicine for the discovery of insulin. Banting shared the award with Best, and Macleod shared his prize money with James Collip, who played a crucial role in purifying the extract. But the inadvertent contributors who made the ultimate sacrifice for the discovery of insulin were a group of street dogs in Toronto.

Dreamy idea

Frederick G. Banting was trained as a physician and surgeon at the University of Toronto. During World War 1, he served in the army. After the war, he opened a medical practice in London in July 1920, but he struggled to attract patients. By early October 1920, he found part-time work as a demonstrator in surgery and anatomy at the University of Western Ontario, working under Dr F. R. Miller, a professor of physiology. Miller asked Banting to prepare a lecture for physiology students on carbohydrate metabolism—a topic in which Banting had little interest. Until then, he had also given very little thought to the disease most closely linked to carbohydrate metabolism: diabetes.

Still, Banting spent several hours preparing his lecture. As part of his research, he read the November 1920 issue of Surgery, Gynecology and Obstetrics, which had just arrived from the press. The lead article in that issue was “The Relation of the Islet of Langerhans to Diabetes with Special Reference to Cases of Pancreatic Lithiasis,” by American pathologist Moses Barron. Banting took the journal to bed and read the paper carefully. It described a rare case in which a pancreatic stone had completely blocked the main pancreatic duct—a case Barron had encountered during routine autopsies. Because of the blockage, almost all the acinar cells, which produce digestive enzymes, had wasted away, while most of the insulin-producing islet cells remained intact.

This matched what earlier laboratory experiments had shown when scientists deliberately blocked pancreatic ducts in animals. The case suggested that diabetes might not be caused by damage to the whole pancreas but rather by the destruction or failure of the insulin-producing islet cells. Barron’s observations supported the idea that the condition of the islet cells was central to the development of diabetes.

That night, Banting went to sleep with these ideas on his mind. In the middle of the night, he woke suddenly with a flash of insight, and he jotted it down in his notebook: “Diabetus—Ligate pancreatic ducts of dog—Keep dogs alive till acini degenerate, leaving Islets—Try to isolate the internal secretion of these to relieve glycosuria.” In other words, he believed he had found a way to remove insulin from the pancreas without destroying it.

His plan involved two dogs. In the first dog, Banting would tie off the pancreatic duct so that most of the pancreas would gradually shrink and die, except for the islet cells. In the second dog, he would induce diabetes by removing the pancreas entirely. After several weeks, he would remove the shrunken pancreas from the first dog, make an extract from it, and inject that extract into the diabetic second dog. If the sugar levels in the dog’s blood and urine fell, the extract would be proven effective.

The next morning, Banting presented the idea to Miller. However, the University of Western Ontario lacked appropriate proper research facilities to test the hypothesis. Incidentally, Miller suggested Banting consult with Macleod, the University of Toronto’s head of physiology and a leading authority on diabetes. Soon, the duo met, and by March 1921, McLeod wrote to Banting that he could come to Toronto and use the facilities to test his vision.

However, by then Banting had been indecisive as his practice picked up in London and his fiancée pressed him to stay. Banting soon called off the engagement, and he wished to leave London.

Though McLeod had given the offer, there was another offer in front of him: to serve as a medical officer on an Arctic oil expedition. The young surgeon then tossed a coin to decide whether to go to Toronto or on an Arctic expedition. The coin toss gave the verdict in favour of the Arctic expedition, but Banting decided to head to Toronto itself, finally.

Street to lab

Soon, Banting got Best to assist him, and they started work at the University of Toronto’s Medical Building. Their first task was to operate on dogs supplied by Macleod’s team and remove their pancreases to trigger diabetes. Although Banting was a surgeon, he had little experience performing a pancreatectomy on dogs. The first operation took about 80 minutes, but the dog recovered. It was done in two stages, leaving a small part of the pancreas behind. A week later, they removed the remaining piece and saw clear signs of diabetes.

They operated on two more dogs, but both died—one from an overdose of anesthetic and the other from bleeding. A third dog survived the surgery but died soon afterward. The first dog had died by then as well.

Their luck changed with a dog labelled #387. This time, the surgery worked. Banting began regular tests, and he removed the last portion of the dog’s pancreas. As expected, the dog soon showed classic diabetic symptoms: high blood sugar and sugar in its urine.

The next phase of the research was even more delicate. Following Banting’s idea, they needed to tie off the pancreatic duct in a dog and let the pancreas slowly shrink over several weeks. The first dog to undergo this procedure died three days after surgery. The second survived, but Banting wasn’t sure he had actually tied the duct correctly. A third dog lived only two days before dying from an infection.

After two weeks, seven of the ten dogs they had operated on were dead. Running short of dogs to experiment on and frustrated with the rate at which they were going through the university’s supply of experimental dogs, Banting then decided to do something, to the horror of McLeod. He went to the streets of Toronto and bought dogs for $1–$3 each to replenish supplies. Notably, the future Nobel laureate led them back to the lab with his tie.

Toronto had a vocal anti-vivisectionist community that opposed the use of animals in medical research. And Macleod was worried that Banting and Best might be accused of dog-napping, so he urged them to avoid anything that could give that impression.

By mid-June, after four weeks of work, things finally looked hopeful. By then, several dogs they had procured from the streets had undergone life-threatening surgeries. By the end of July, Banting surgically removed the shrunken pancreas from Dog #391—a key “helper dog” in the breakthrough experiments of the summer of 1921. Its pancreas had fully degenerated after the duct-ligation procedure done around mid-July. And Best and Banting proceeded to prepare their first pancreatic extract based on the detailed instructions left to them by Macleod, who had gone for a summer vacation. Once prepared, the extract was injected into Dog #410, a diabetic dog, but the results were disappointing: the animal slipped into a coma and died. A second dog showed brief improvement after an 8 cc dose, then also died.

Three days later, they tried again with Dog #408. This time, the dog’s blood sugar dropped sharply—and the animal stayed in good condition. Encouraged, Banting and Best began adjusting the dosage. By August 9, Banting wrote to Macleod that the extract “invariably” lowered blood sugar.

In one remarkable case, they kept a severely diabetic dog alive for 70 days—it died only when their supply of extract ran out. Within months of this breakthrough, the first human patient received an injection. Leonard Thompson, a 14-year-old boy dying of diabetes in a Toronto hospital, became the first person to receive insulin. Within 24 hours, his dangerously high blood sugar fell to near-normal levels, and news of the success spread around the world. By 1923, Eli Lilly started mass-producing insulin—and for the first time, it was clear that people could live with diabetes!