What was known before 1921
Diabetes had been recognized as a wasting illness for centuries, but its cause was unclear for most of that time. A few pieces of the puzzle came together in the nineteenth century. In 1869, the German medical student Paul Langerhans described clusters of cells in the pancreas that were later named the islets of Langerhans. In 1889, Oskar Minkowski and Joseph von Mering found that removing a dog’s pancreas caused a condition resembling severe diabetes. That pointed to the pancreas as the source of something the body needed to control blood sugar.
Early in the twentieth century, researchers in several countries tried to prepare extracts from the pancreas and give them to diabetic animals or people. Some of these experiments lowered blood sugar, but the extracts were impure and often caused harmful side effects, so the work was not turned into a usable treatment. Several people, including the Romanian physiologist Nicolae Paulescu, reported results of this kind around the same period as the Toronto team. Historians still discuss how much weight these earlier and parallel efforts deserve.
The only treatment available to doctors was dietary. Strict, very low-calorie diets could extend the lives of some patients with severe, childhood-onset diabetes by months or a few years, but they left patients extremely thin and weak, and the disease usually won in the end.
The Toronto experiments of 1921
The central story begins in the spring of 1921. Frederick Banting, a young surgeon with limited research experience, had an idea about isolating the pancreas’s internal secretion. He took it to John Macleod, a professor of physiology at the University of Toronto. Macleod provided laboratory space for the summer, along with dogs, and assigned two medical students, Charles Best and Clark Noble, to help. Best ended up continuing the work with Banting.
The team removed the pancreas from some dogs to make them diabetic and prepared extracts from the pancreas of other animals. They reported that injecting the extract lowered blood sugar in the diabetic dogs and improved their condition. Macleod was away for part of that summer and, on his return, helped expand and test the work more rigorously. The early extract was crude, and results were uneven.
Collip and purification
In late 1921, the biochemist James Collip joined the group. His job was to develop a purer extract that could be given safely to humans. Working in the winter of 1921-22, he developed a method of purification using alcohol that produced a more reliable preparation. Without this step, the discovery probably would not have become a practical medicine. This is why many historians see the achievement as a team effort rather than the work of one or two people.
The first patients
The first human recipient was Leonard Thompson, a 14-year-old boy who was seriously ill with diabetes at Toronto General Hospital. He received his first injection on January 11, 1922. That first dose, made with the earlier, less pure extract, produced only a modest drop in blood sugar and caused a reaction at the injection site. After Collip improved the preparation, Thompson received a second series of injections in late January, and his blood sugar and general condition improved markedly. He lived for more than a decade afterward, though his long-term outcome was shaped by the limited knowledge and tools of the time.
Other patients soon followed, and accounts from the period describe starving children regaining weight and strength within weeks. Such stories helped make insulin one of the most dramatic medical turnarounds of the century. At the same time, early insulin was not a cure. It replaced a missing hormone and had to be injected for life, and the right dose was hard to judge. Too much insulin could lower blood sugar dangerously, so early treatment involved a great deal of trial and error.
Naming, patents and production
The substance was first referred to by names such as “isletin” before the name insulin, from the Latin word for island, became standard. The Toronto researchers assigned their patent rights to the University of Toronto for a nominal sum, reportedly one dollar each, because they wanted the treatment to be widely available rather than controlled by an individual.
Making enough insulin was a serious challenge. The university partnered with the pharmaceutical company Eli Lilly and Company in the United States, and other producers followed in other countries. Over the next few years, manufacturers improved yields and standardized strength, which was important because early batches varied. This was an early case of what later became industrial chemistry applied to medicine, in which a biological substance had to be extracted, purified and measured consistently at scale. Insulin was injected with a hypodermic syringe, so the history of the drug is tied to the history of the tools that delivered it.
Who gets the credit?
The 1923 Nobel Prize in Physiology or Medicine was awarded to Banting and Macleod. Banting was reportedly upset that Best had not been included, and he publicly shared his prize money with Best. Macleod in turn shared his with Collip. That arrangement shows how unsettled the question of credit was, even among the people involved.
Several points are well documented. Banting had the original idea and drove the early experiments. Best did much of the practical laboratory work. Macleod provided the facilities, scientific guidance and critical evaluation. Collip made the purification that allowed human use. Other points remain debated, including how much the earlier pancreatic extract work, including that of Paulescu, contributed, and how Macleod’s role should be weighed against that of the younger researchers. Different biographers have reached different conclusions, and it is safest to describe the discovery as the product of a group whose members later disagreed.
What came after
Insulin extracted from animal pancreases, mostly from cattle and pigs, was the standard for decades. Longer-acting forms appeared in the 1930s and later, allowing fewer injections. In the 1950s, the British biochemist Frederick Sanger worked out the amino acid sequence of insulin, a landmark result that earned him a Nobel Prize in 1958 and was an early demonstration that a protein has a defined structure. Later in the twentieth century, human insulin was produced using genetically engineered bacteria, reducing reliance on animal sources.
Insulin’s story also sits alongside other major medical advances of the era, such as the penicillin discovery, which transformed the treatment of infections. The two share a pattern: a laboratory finding, a difficult period of purification and scale-up, then rapid adoption. Insulin did not remove the challenges of living with diabetes, and later technology, from pumps to sensors, has continued to build on the 1922 breakthrough. Outcomes for any individual patient depend on many factors, and this account is history, not medical guidance.