Discovery of Insulin (1921-1922)

Summary

In the summer of 1921, a one-armed Ontario country doctor named Frederick Banting persuaded a University of Toronto physiologist to lend him a lab, some dogs, and a medical student. The idea Banting was chasing was not entirely sound, but it led somewhere nobody had reached before. On January 23, 1922, a purified extract from the pancreas was injected into Leonard Thompson, a fourteen-year-old boy dying of diabetes at Toronto General Hospital. His blood sugar fell almost immediately. Within weeks, comatose patients across North America were sitting up and asking for food. Physicians and families reached for religious language — resurrection, Lazarus — because nothing in the ordinary vocabulary of medicine fit what they were watching. The discovery did not cure diabetes, and the team that made it fractured badly over credit. But it ended the era in which a diagnosis of childhood diabetes was a death sentence measured in months.

Background

A Disease Without a Bottom

Diabetes mellitus had been described for millennia as a melting of the flesh — flesh dissolving into urine — but its mechanism remained obscure until 1889, when the German physiologist Oskar Minkowski established that the disorder originated in the pancreas, not in the liver or stomach as had long been assumed. (Bliss, 2011) Minkowski’s finding generated two decades of endocrinological optimism: if a pancreatic secretion regulated metabolism, perhaps it could be isolated and replaced. That optimism largely collapsed. By 1919, even Harvey Cushing — Osler’s most distinguished pupil — had grown so disgusted with the field that he took to calling it “endo-criminology,” and his presidential address to the Association for the Study of Internal Secretions was mostly an attack on the quackery its founders had promoted. (Bliss, 2011)

The Starvation Regimen

The best medicine could offer a type 1 diabetic patient in 1920 was Frederick Allen’s “under-nutrition” regimen: systematic caloric restriction designed to reduce the metabolic burden on a pancreas that could no longer do its job. “Under-nutrition” was a euphemism. The actual therapy was starvation — a managed, medically supervised starvation that prolonged life by months or, in rare cases, a few years, at the cost of profound physical deterioration and near-continuous hunger. (Bliss, 2011)

William Osler, writing in the 1918 edition of The Principles and Practice of Medicine — four years before insulin — noted flatly that he had never personally known a single instance of recovery in a diabetic child. (Bliss, 2011) That was not pessimism; it was observation.

The human cost of the Allen regimen was visible in James Havens of Rochester, New York, who survived on it longer than almost anyone: six years, from 1915 to 1921, before becoming bedridden and near death at twenty-one. His hospital chart in spring 1922 recorded that he was crying much of the time and was “anxious to die and end his misery.” (Bliss, 2011) His father had already written to the treating physician in fatalistic acceptance that no hope remained.

The Event

Banting’s Idea and Its Institutional Luck

Frederick Banting was not a research physiologist. He was a twenty-nine-year-old surgeon from rural Ontario who had just failed to establish a general practice in London, Ontario, and was supplementing his meager income by teaching anatomy part-time at Western University. In October 1920, reading a journal article before a lecture he was supposed to give on the pancreas, he scribbled a research idea in a notebook. The idea — that ligating the pancreatic duct would cause the exocrine cells to degenerate while leaving the insulin-secreting islet cells intact, making extraction simpler — was, as the historian Michael Bliss established, physiologically unsound. Duct-ligated pancreases do not atrophy differentially in the way Banting supposed. (Bliss, 2011)

He was advised to take the idea to J. J. R. Macleod, the Scottish-born professor of physiology at the University of Toronto and one of the leading figures in carbohydrate metabolism research. Macleod was skeptical, but he offered Banting something invaluable for his eight weeks of summer vacation: a laboratory, ten dogs, the use of an operating room, and Charles Best, a twenty-two-year-old graduate student who happened to know how to measure blood sugar. That surplus of institutional resources — the dogs, the student, the room — was, in Bliss’s assessment, indispensable. Nothing would have come of Banting’s idea without it. (Bliss, 2011)

The Extract, the Purification, the Patient

By December 1921, Banting and Best had produced a crude pancreatic extract that reduced blood sugar in diabetic dogs. What they could not do was purify it sufficiently to use in humans: the impurities caused severe reactions. James B. Collip, a thirty-year-old biochemist from the University of Alberta who had joined the team, worked alone on the purification problem. On January 19, 1922, he succeeded. (Bliss, 2011)

Four days later, on January 23, the purified extract was administered to Leonard Thompson, a fourteen-year-old boy who had been admitted to Toronto General Hospital with severe diabetes and was near death. His blood sugar fell almost immediately. Within days he was out of bed. Porter, writing from outside Bliss’s level of detail, records the same compressed version that entered popular memory: the injections given to a dying boy, the blood sugar that fell at once. (Porter, 1997) The Toronto team recognized what it had. The researchers, in Bliss’s phrase, understood they were making one of the great breakthroughs in the history of modern medicine. (Bliss, 2011)

Elizabeth Hughes, the fifteen-year-old daughter of U.S. Secretary of State Charles Evans Hughes, was perhaps the most famous early case. She had been starved down to forty-five pounds and was within hours of death when she arrived in Toronto in August 1922. Banting treated her. Her blood sugar normalized. She wrote her mother that autumn that the effect was “unspeakably wonderful.” Fifty-eight years later, Elizabeth Evans Hughes Gossett — mother of three, celebrating her fiftieth wedding anniversary — was still alive on insulin. (Bliss, 2011)

Religious Language in a Scientific Ward

The physicians and families watching these recoveries did not reach for the neutral terminology of clinical improvement. They reached for the language of their Christian heritage: miracle, resurrection, Lazarus, being born again. Some patients described the sensation of their first insulin injection as comparable to the experience of being born again by the Holy Spirit at Pentecost. To witness a patient brought out of diabetic coma by a single injection was, for observers still formed by that tradition, to watch something that resembled the raising of Lazarus. (Bliss, 2011) The language was not metaphor to the people using it; it was the only vocabulary available for events that had no clinical precedent.

Aftermath and Contests

The Team That Fractured

The collaboration that produced insulin was not harmonious. Banting, who was intensely suspicious and deeply insecure about his lack of formal research training, came to believe that Macleod was stealing credit. When Collip refused to share the details of his purification method — concerned, with some reason, that Banting might damage the work — Banting physically attacked him in the laboratory. Best had to separate them. (Bliss, 2011) The episode left the team’s personal relationships permanently fractured even as they continued to work together.

Charles Best, who would spend decades afterward seeking recognition as the co-discoverer, produced multiple later accounts of the insulin research that Bliss describes as distorted attempts to rewrite history — accounts most charitably explained, in Bliss’s assessment, by the effects of clinical depression. (Bliss, 2011)

The Nobel Prize and Its Awkward Distribution

The Nobel Prize in Physiology or Medicine was awarded for insulin in 1923, less than two years after the discovery — an unusually fast recognition. The committee gave it to Banting and Macleod, who intensely disliked each other. Both laureates immediately divided their prize money: Banting shared his with Best; Macleod shared his with Collip. Llewellys Barker, who had succeeded Osler as professor of medicine at Johns Hopkins, offered the most diplomatic summary at Toronto’s Nobel dinner: “In insulin there is glory enough for all.” (Bliss, 2011)

Medicine as Secular Faith

The broader cultural consequences of insulin took a generation to become visible. After 1922, Banting was the most famous person in Canada, expected by a credulous public to conquer a new disease every few months. Medical schools began turning away applicants in large numbers for the first time. By the end of the 1920s, the elite medical profession had surpassed the mainstream Christian clergy in social prestige, just as the clergy were losing ground to postwar disillusionment and declining church attendance. The transfer of faith was not incidental. (Bliss, 2011)

Bliss’s analysis of this transfer is unsentimental. Insulin was not a cure; it was a maintenance therapy, and an imperfect one. Since its discovery, total diabetes in the human population has grown enormously, driven primarily by the epidemic of type 2 diabetes associated with affluence and sedentary life. In its various forms, diabetes now represents a greater burden of disease than it did in Banting’s time. There is still, strictly speaking, no cure. (Bliss, 2011)

Human Notes

See Also

• diabetes-mellitus
• endocrinology
• therapeutic-nihilism
• frederick-banting
• charles-best
• james-j-r-macleod
• secularization-of-medicine
• starvation-therapy
• founding-of-johns-hopkins-medical-school-1893

Sources

• Bliss, Michael (2011). The Making of Modern Medicine: Turning Points in the Treatment of Disease. University of Chicago Press. (source_id: bliss-making-modern-medicine-2011)
• Porter, Roy (1997). The Greatest Benefit to Mankind: A Medical History of Humanity. W. W. Norton. (source_id: porter-greatestbenefit-1997)