The Scientists Who Discovered Insulin Sold the Patent for Just One Dollar
Until 1921, receiving a diagnosis of Type 1 diabetes was an agonizing death sentence, with patients surviving only months on extreme starvation diets. At the University of Toronto, Frederick Banting, Charles Best, James Collip, and J.J.R. Macleod successfully isolated and purified insulin from animal pancreases. Within months, comatose diabetic children awoke and recovered. Believing life-saving medicine belonged to humanity, the researchers sold their patent to the university for just one dollar each.
The Death Sentence of Type 1 Diabetes
In the early decades of the twentieth century, a diagnosis of severe juvenile diabetes—what is recognized today as Type 1 diabetes—was almost universally fatal. The disease manifested rapidly: the body lost the ability to process glucose, resulting in severe weight loss, unquenchable thirst, extreme lethargy, and eventual diabetic ketoacidosis. Once ketoacidosis set in, patients slipped into deep comas and typically died within days. For parents and physicians, watching a child succumb to the illness was a protracted and harrowing experience, as modern medicine possessed no means to replace the missing internal secretion responsible for metabolizing sugar.
The sole therapeutic intervention available at the time was the strict starvation diet pioneered by physicians such as Frederick Madison Allen and Elliott Joslin. Under this regimen, patients were restricted to minimal daily caloric intakes, sometimes subsisting on fewer than five hundred calories a day while eliminating nearly all carbohydrates. While this extreme dietary restriction lowered blood sugar levels and reduced sugar excretion in urine, it did not cure the disease. Instead, it traded death from diabetic coma for death by severe malnutrition. Patients were reduced to living skeletons, often surviving for only a few painful months or an extra year or two under constant institutional supervision.
Banting's Hypothesis and the Toronto Collaboration
The pancreas had been linked to carbohydrate metabolism decades earlier. In 1889, German researchers Oskar Minkowski and Joseph von Mering demonstrated that surgically removing the pancreas of a dog induced immediate, severe diabetes. Pathologists had also identified tiny clusters of cells throughout the pancreas, known as the islets of Langerhans, and suspected they produced an internal hormone essential for regulating sugar. However, attempts to extract this substance consistently failed. Whenever scientists crushed pancreatic tissue to extract the hormone, the organ's powerful digestive enzymes—trypsin and other proteolytic juices produced by the acinar cells—degraded the delicate internal secretion before it could be isolated.
In late October 1920, Frederick Banting, an orthopedic surgeon and general practitioner in London, Ontario, formulated an alternative approach after reading an article by pathologist Moses Barron. Barron observed that when the pancreatic duct was blocked by stones, the digestive enzyme-producing acinar cells atrophied, while the islets of Langerhans remained largely intact. Banting hypothesized that by surgically ligating the pancreatic ducts in living animals and waiting for the digestive tissue to degenerate, researchers could harvest the remaining islets free from destructive digestive enzymes. In the spring of 1921, Banting presented his idea to John James Rickard Macleod, a prominent professor of physiology at the University of Toronto who possessed extensive expertise in carbohydrate metabolism.
Macleod was initially skeptical of Banting's surgical plan, as numerous experienced physiologists across Europe and North America had tried and failed to isolate the internal secretion. Nevertheless, Macleod agreed to provide Banting with laboratory facilities, experimental animals, and physiological guidance during the summer of 1921 while Macleod traveled to Scotland. To assist with chemical assays, blood sugar measurements, and physiological tests, Macleod assigned Charles Best, a young physiology and biochemistry graduate student who had recently completed his degree.
From Animal Extracts to Whole Pancreas Harvesting
Beginning their laboratory work in May 1921, Banting and Best operated on dogs, tying off their pancreatic ducts and waiting several weeks for the acinar tissue to wither. They then removed the atrophied organs, chilled them in saline, macerated the tissue, and filtered the fluid. Injecting this crude extract—which they initially called 'isletin'—into dogs made diabetic by pancreatectomy yielded dramatic results. The animals' elevated blood glucose concentrations dropped significantly, and their general clinical conditions showed temporary improvement.
While duct ligation proved that the islet tissue held the active compound, the surgical process was slow, labor-intensive, and resulted in high animal mortality. Realizing that a practical supply was necessary for broader testing, Banting and Best altered their methodology. They discovered that fetal calf pancreases, obtained from local slaughterhouses, did not yet produce active digestive enzymes and yielded potent extracts without requiring surgical ligation. Shortly thereafter, they refined the method further, using an acidified alcohol solution to extract the active secretion directly from whole adult cattle pancreases. The alcohol prevented digestive enzymes from degrading the hormone, bypassing the need for duct ligation altogether and unlocking an abundant commercial source of raw material.
Purification and the First Human Trials
Despite their laboratory success in lowering blood sugar in diabetic dogs, the crude extract remained too impure for safe human administration. Early preparations contained foreign proteins and contaminants that produced painful local swelling, sterile abscesses, and systemic fevers in test animals. Upon Macleod's return, he redirected the resources of his department toward the project and invited James Bertram Collip, an experienced biochemist on sabbatical from the University of Alberta, to join the research group in December 1921. Collip was tasked with purifying the active hormone so it could be administered safely to human patients.
Collip systematically tested varying concentrations of ethyl alcohol to precipitate unwanted proteins out of the extract while keeping the active anti-diabetic principle in solution. The team faced urgent clinical stakes: on January 11, 1922, a fourteen-year-old boy named Leonard Thompson, who was severely malnourished and dying of Type 1 diabetes at Toronto General Hospital, received the first clinical injection of Banting and Best's extract. The initial trial was a failure; the crude fluid produced an allergic reaction and an abscess, with only a minor effect on his blood sugar. Clinical testing was immediately paused while Collip refined his precipitation technique.
On January 23, 1922, Thompson received an injection of Collip's newly purified extract. The outcome was transformative. The boy's blood sugar dropped from dangerously elevated levels into the normal range, the sugar and ketones disappeared from his urine, and his vitality rapidly returned. Over the subsequent weeks, the Toronto team administered the purified substance—officially named 'insulin,' from the Latin 'insula' for island—to other terminal patients. Children who had been comatose awoke, regained their appetites, and began gaining weight, marking one of the most astonishing turnarounds in modern clinical history.
The One-Dollar Patent and Public Service
With insulin's therapeutic value established, the researchers confronted the question of intellectual property. Under the prevailing medical ethics of the era, profiting directly from life-saving medicines was widely viewed with skepticism by academic physicians. Banting strongly maintained that medical discoveries belonged to the public and that seeking personal wealth from a treatment essential for human survival was unethical. However, the university and the researchers recognized a practical danger: if they did not secure a patent, an outside commercial entity might patent a minor variation of the extraction process, monopolize production, and restrict public access or inflate prices.
To protect the integrity of the treatment and ensure widespread availability, Banting, Best, and Collip applied for patents on insulin and its method of manufacture in late 1922 and early 1923. Upon the granting of the patents, the three researchers assigned all rights to the Board of Governors of the University of Toronto for a token payment of one dollar each. Macleod chose not to have his name on the patent application due to his academic standing and principles regarding medical patents.
The University of Toronto established the Insulin Committee to oversee production standards and licensing. Recognizing that the university lacked the industrial capacity to meet global demand, the committee entered into an agreement with the American pharmaceutical firm Eli Lilly and Company. Under this arrangement, Lilly was granted temporary exclusive manufacturing rights in the United States in exchange for developing large-scale purification methods and supplying the hormone at reasonable prices, after which the process was licensed widely to other manufacturers around the world.
Credit, Discord, and the Nobel Prize
The triumph of insulin was accompanied by fierce internal friction. Banting, an outsider to elite academia, harbored deep distrust toward Macleod, suspecting that the senior professor was attempting to claim undue credit for experiments he had not directly conducted. Best and Collip also experienced bitter professional disagreements, at one point nearly coming to physical blows in the laboratory over the details of the purification process. The intense race to publish results and claim priority strained personal relationships throughout the Toronto department.
In the autumn of 1923, the Nobel Committee for Physiology or Medicine awarded the Nobel Prize jointly to Frederick Banting and J.J.R. Macleod. Banting was incensed that the award omitted Best, his original partner through the grueling summer of 1921, and initially threatened to refuse the prize. Convinced by colleagues to accept, Banting immediately announced that he would share half of his monetary prize with Charles Best. Macleod followed suit, publicly announcing that he would divide his portion of the prize money with James Collip. While the shared prize money acknowledged the essential contributions of all four men, the collaborative dispute highlighted how modern medical breakthroughs increasingly relied on interdisciplinary teamwork rather than solitary inventors.
Key takeaways
•Before 1921, Type 1 diabetes was fatal; the only treatment was an extreme starvation diet that postponed death by months or a few years through severe malnutrition.
•Banting and Best initially isolated crude pancreatic extracts in 1921, but it was biochemist James Collip's fractional alcohol precipitation method that made the extract safe and effective for human use.
•To prevent commercial monopolies and ensure quality, Banting, Best, and Collip patented insulin and assigned the patent rights to the University of Toronto for one dollar each.
•The 1923 Nobel Prize was awarded to Banting and Macleod, who subsequently divided their prize money with Best and Collip to recognize the essential four-person team behind the discovery.