Insulin — The Hormone That Conquered Diabetes

Year: 1921-1922 | Field: Endocrinology | Impact: Transformed diabetes from a death sentence into a manageable condition

In the summer of 1921, a 14-year-old boy named Leonard Thompson lay dying in Toronto General Hospital. His body, ravaged by Type 1 diabetes, had withered to just 65 pounds. His parents watched helplessly as their son slipped toward the inevitable coma that claimed every diabetic child. But in a nearby laboratory, a young surgeon named Frederick Banting was conducting desperate experiments on dogs, convinced he could extract the mysterious substance that regulated blood sugar. Working with minimal funding and crude equipment, Banting and his student assistant Charles Best had spent months grinding up pancreases, injecting extracts into diabetic dogs, and watching some miraculously recover. On January 11, 1922, they injected their pancreatic extract into Leonard Thompson. Within hours, his blood sugar dropped and his condition stabilized. The boy who should have died became one of the first humans saved by insulin—launching a medical revolution that would rescue millions from certain death.

The Problem

Diabetes had puzzled physicians for millennia, earning the name "the pissing evil" for its characteristic symptoms of excessive urination and thirst. By 1920, doctors understood that diabetics couldn't process sugar properly, leading to a toxic buildup of glucose and ketones in the blood. The only treatment was starvation diets that prolonged life by mere months while patients wasted away. Scientists suspected the pancreas held the key—autopsies revealed that diabetics had damaged clusters of cells called the islets of Langerhans. German researcher Paul Langerhans had identified these mysterious cell clusters in 1869, and by 1901, Eugene Opie proved they were destroyed in diabetics. The challenge was extracting whatever substance these cells produced without destroying it in the process. Previous attempts had failed because digestive enzymes in the pancreas broke down the hormone before it could be isolated.

The Breakthrough

Banting's crucial insight came from reading about pancreatic duct ligation in dogs. He realized that tying off the pancreatic ducts would cause the enzyme-producing cells to wither away while leaving the insulin-producing islets intact. In May 1921, Banting and Best began their experiments in a sweltering laboratory at the University of Toronto, working with borrowed equipment and a $100 research budget. They ligated pancreatic ducts in dogs, waited for the enzyme-producing tissue to degenerate, then ground up the remaining islet tissue and injected the extract into diabetic dogs.

The results were dramatic. Dog 92, made diabetic by removing its pancreas, was near death when they injected the extract on July 30, 1921. Within hours, its blood sugar plummeted from a lethal 0.20% to a normal 0.12%. The dog lived for 70 more days on daily injections. Banting and Best had proven that pancreatic extracts could control diabetes, but their crude preparation caused severe reactions and quickly lost potency.

The breakthrough came when biochemist James Collip joined the team in December 1921. Using alcohol precipitation techniques, Collip purified the extract enough for human trials. The first injection into Leonard Thompson on January 11, 1922, caused an allergic reaction, but Collip's improved preparation given twelve days later worked perfectly. Thompson's blood sugar normalized, his ketones disappeared, and he regained strength. The boy lived 13 more years—dying not from diabetes but from pneumonia.

The Resistance

The medical establishment initially greeted insulin with skepticism. Many physicians had seen promising diabetes treatments fail before and remained cautious about this new "miracle cure." Some questioned whether the Toronto team had truly isolated a single hormone or simply created a toxic mixture that happened to lower blood sugar. The early insulin preparations were inconsistent and often contaminated, causing severe allergic reactions that reinforced doubts about safety.

More troubling was the bitter priority dispute that erupted among the discoverers themselves. Banting felt that his supervisor, J.J.R. Macleod, was stealing credit despite contributing little to the actual experiments. Collip temporarily withheld his purification methods, nearly derailing the entire project. The controversy intensified when Banting and Macleod shared the 1923 Nobel Prize, with Best and Collip excluded. Banting was so outraged that he split his prize money with Best, while Macleod shared his with Collip. The acrimonious disputes overshadowed what should have been a celebration of medical triumph.

The Revolution

Insulin's impact was immediate and profound. Within months of the first successful treatment, diabetic children who had been sent home to die were returning to school healthy and energetic. Pharmaceutical companies raced to mass-produce insulin, making it available worldwide by 1923. The Eli Lilly Company partnered with the Toronto team to scale up production, using cattle and pig pancreases from slaughterhouses to meet growing demand. Diabetic patients who had lived under death sentences suddenly faced the prospect of normal lifespans.

The discovery launched the modern pharmaceutical industry and established new standards for medical research. The Toronto team's decision to sell their insulin patent to the University of Toronto for just $1 ensured the treatment remained affordable—a stark contrast to today's drug pricing controversies. Insulin also pioneered the concept of hormone replacement therapy, paving the way for treatments using thyroid hormone, growth hormone, and other essential substances.

Today, insulin remains the cornerstone of diabetes treatment for millions worldwide. Modern synthetic insulins, produced by genetically engineered bacteria, offer precise control over blood sugar with fewer side effects than the original animal-derived preparations. Continuous glucose monitors and insulin pumps have automated much of diabetes management, while researchers work toward artificial pancreases and potential cures through stem cell therapy and immunomodulation.

Key Figures

Frederick Banting: A young orthopedic surgeon whose insight about pancreatic duct ligation launched the insulin discovery, despite having no research experience in diabetes
Charles Best: A 22-year-old medical student who became Banting's research partner and conducted most of the early dog experiments
James Collip: The biochemist whose purification techniques made insulin safe for human use and enabled mass production
J.J.R. Macleod: The University of Toronto physiology professor who provided laboratory space and supervision, though his exact contribution remains disputed
Leonard Thompson: The 14-year-old boy who became the first human successfully treated with insulin, proving the treatment's life-saving potential
Elizabeth Hughes: Daughter of U.S. Secretary of State Charles Evans Hughes, her dramatic recovery from near-death helped publicize insulin's miraculous effects

Timeline Milestones

1869: Paul Langerhans discovers pancreatic islet cells later found to produce insulin
1921: Banting and Best successfully treat diabetic dogs with pancreatic extracts
1922: First successful human insulin treatment saves Leonard Thompson's life
1923: Banting and Macleod win Nobel Prize; mass production begins
1982: First genetically engineered human insulin approved by FDA
2006: Continuous glucose monitors revolutionize diabetes management
2016: Artificial pancreas systems begin clinical trials

Part of the Discovery Chronicles collection