What If Insulin Was Never Isolated?

Before insulin's isolation, type 1 diabetes — in which the pancreas produces little or no insulin, the hormone that regulates blood sugar — was uniformly fatal, typically within one to two years of diagnosis for adults and considerably faster for children. The only available treatment, developed by Frederick Allen in the 1910s, was severe caloric restriction, sometimes down to as little as 400-600 calories a day, which could extend survival by managing blood sugar through near-starvation but left patients severely malnourished and still, ultimately, facing death from the disease — a treatment widely and grimly described by physicians of the era as essentially starving patients to gain a small amount of additional time.

Frederick Banting, a young Canadian surgeon with an idea about isolating the pancreatic secretion responsible for blood sugar regulation, approached University of Toronto physiologist John Macleod in 1921 and was given laboratory space and a medical student assistant, Charles Best, along with access to dogs for experimentation over the summer. Working through repeated failures, Banting and Best successfully isolated a pancreatic extract that lowered blood sugar in diabetic dogs by that autumn. Biochemist James Collip, added to the team, then developed a purification process that made the extract safe and effective for human use. In January 1922, the team administered purified insulin to Leonard Thompson, a 14-year-old dying of diabetes at Toronto General Hospital — his condition improved dramatically within days. Banting and Macleod received the 1923 Nobel Prize in Physiology or Medicine for the discovery, an award that generated lasting controversy since both Best and Collip, whose contributions were widely considered essential, were excluded.

Insulin's isolation depended on a specific, relatively narrow set of institutional circumstances: Banting's idea, Macleod's willingness to provide laboratory resources and a research assistant despite reported early skepticism about Banting's specific approach, and the compressed timeline — the entire breakthrough, from Banting's initial proposal to successful human treatment, spanned less than a year. A meaningfully plausible divergence imagines Macleod declining to support Banting's project at all, a real possibility given Banting had no formal research background and Macleod was, by most historical accounts, not initially convinced the approach would work.

Given that other researchers internationally — including Romanian physiologist Nicolae Paulescu, who published research on a similar pancreatic extract in 1921, shortly before the Toronto team's work, though without achieving a clinically usable, purified product for human treatment — were pursuing related research directions, a complete, permanent non-discovery is less plausible than a meaningful delay: imagine the Toronto team's specific combination of resources and rapid progress not coming together, pushing successful isolation and purification back by five to fifteen years to whichever research group or country eventually achieved what Paulescu's and others' related but incomplete work suggests may otherwise have converged on a working treatment eventually regardless.

In the years immediately following a delayed discovery, children and adults diagnosed with type 1 diabetes continue facing the same near-certain death sentence, managed at best by Allen's severe starvation diet, which could extend survival modestly but at severe physical cost and without any prospect of a normal life expectancy or quality of life. Leonard Thompson, the first patient successfully treated with insulin in January 1922, would instead have been among the diabetic patients who, absent this breakthrough, died from the disease within the following year or two, a fate that actually befell an enormous number of diabetic children and young adults throughout the pre-insulin era.

The broader medical and scientific community's understanding of hormones and endocrine function more generally, still a relatively young field in the early 1920s, would develop somewhat differently without insulin's discovery serving as one of the era's most dramatic and clinically consequential demonstrations of hormone-based treatment — a landmark success that helped establish endocrinology's credibility and attracted further research investment and interest into other hormonal treatments through the following decades.

For individual families with a diabetic child or young adult, the absence of insulin means continuing to face what was, before 1922, one of medicine's most agonizing and hopeless diagnoses — physicians of the era have left extensive documented accounts of the psychological toll of treating dying diabetic children with only the starvation diet available, describing wards of visibly emaciated young patients for whom there was, prior to insulin, genuinely no other option to offer.

Once insulin did become available, its impact was felt with striking speed and visibility — patients who'd been near death recovered dramatically within days of treatment, and photographs and case reports of this recovery became some of the era's most widely circulated and celebrated medical stories. A world without this specific, visible, rapid transformation available to point to would mean diabetic patients and their families continuing to experience the disease as an inevitable, unstoppable decline, with the specific hope and relief insulin's availability actually provided simply not existing for a longer stretch of the twentieth century.

At the broadest scale, insulin's discovery and subsequent industrial-scale production — Eli Lilly and Company began large-scale commercial insulin production within about a year of the Toronto team's discovery, making the treatment widely available with remarkable speed for a novel medical breakthrough of that era — transformed type 1 diabetes from a death sentence into a manageable chronic condition for an enormous and steadily growing global population of patients over the following century. A world where this discovery is delayed by even a decade plausibly means an entire additional generation of diabetic patients worldwide facing the disease without any effective treatment, a genuinely significant global mortality difference given how uniformly fatal the condition was beforehand.

Insulin's discovery and rapid commercialization also helped establish an influential early template for how a major medical breakthrough could move from laboratory discovery to widespread industrial production and global distribution within just a few years — a pattern that later, larger-scale medical and pharmaceutical development efforts, including much of twentieth-century vaccine and antibiotic production, would follow and build institutional and industrial capacity around. A world without this specific, unusually rapid nineteen-twenties precedent plausibly means the broader pharmaceutical industry's capacity and institutional expectations for translating major discoveries into mass production develop somewhat differently and more slowly.