The Pre-Insulin Era: A Death Sentence
For centuries, diabetes was a dreaded diagnosis. Before the discovery of insulin, treatment primarily involved severe, calorie-restricted diets. While these diets could temporarily manage blood sugar, they often led to a state of slow starvation. The life expectancy for a child diagnosed with diabetes was typically no more than a year.
Late 19th and early 20th-century research began to highlight the pancreas's role in diabetes. Experiments in 1889 by Oskar Minkowski and Joseph von Mering showed that removing a dog's pancreas caused diabetes. In 1901, Eugene Opie linked diabetes to the destruction of the pancreatic islets of Langerhans. However, previous attempts to create usable pancreatic extracts failed due to digestive enzymes destroying the active substance or resulting in toxic extracts.
Frederick Banting's Idea and the Start of the Team
The catalyst for the breakthrough came from Frederick Banting, a Canadian surgeon. In October 1920, inspired by an article, Banting conceived an experimental approach: ligate the pancreatic ducts of a dog to eliminate the digestive tissue (acini) while preserving the insulin-producing islets of Langerhans. This would allow extraction of the "internal secretion" without its destruction.
Needing research expertise, Banting approached Professor John Macleod at the University of Toronto. Macleod provided Banting with lab space, experimental dogs, and assigned medical student Charles Best to assist him. A coin toss determined Best would be Banting's partner.
The Crucial Summer of 1921
Banting and Best began their experiments in May 1921. They ligated pancreatic ducts, waited for acini to atrophy, and then extracted the islet tissue. This extract, initially called "isletin," was injected into diabetic dogs. In August 1921, they achieved success: injecting the extract into a severely diabetic dog resulted in a dramatic drop in blood sugar. This dog, Marjorie, survived for 70 days with regular injections.
Upon his return, Macleod, initially skeptical, was impressed but insisted on rigorous testing. His scientific approach often led to clashes with Banting's intense personality.
James Collip's Purification Breakthrough
By December 1921, human trials were considered, but the crude extract caused side effects. Macleod enlisted biochemist James Collip to purify it. Collip developed an alcohol extraction method that removed toxic impurities while preserving insulin, making it safe for human use.
The First Human Trial and Immediate Impact
On January 11, 1922, the extract was first administered to 14-year-old Leonard Thompson, who was dying from type 1 diabetes. The initial injection had limited success and caused a sterile abscess. However, after Collip refined the purification, a second injection on January 23 led to remarkable results: Thompson's blood sugar dropped, and his condition significantly improved.
The immediate success led to high demand. The University of Toronto partnered with Eli Lilly for production, and the patent was sold to the university for just $1. Banting famously stated that insulin belonged “to the world”.
The Nobel Prize Controversy and Legacy
The discovery's importance was quickly recognized. In 1923, Banting and Macleod received the Nobel Prize in Physiology or Medicine. This sparked controversy as Best and Collip were not initially included. Banting announced he would share his prize with Best, and Macleod shared his with Collip, ensuring all four were financially acknowledged. The Nobel Committee later acknowledged Best's significant contribution.
Evolution of Insulin: From Animal Extracts to Recombinant Technology
Early insulin production involved purifying it from animal pancreases, primarily cattle and pigs. This method had drawbacks:
- Allergic Reactions: Animal insulin differed from human insulin, potentially causing allergies.
- Limited Supply: Production was restricted by the availability of animal sources.
- Inconsistent Purity: Early methods resulted in variable insulin quality.
The next major advance was recombinant DNA technology in the 1970s.
| Feature | Animal-Derived Insulin (Historical) | Recombinant Human Insulin (Modern) |
|---|---|---|
| Source | Pancreases of cattle and pigs | Genetically modified E. coli bacteria or yeast |
| Purity | Less pure, with minor protein impurities | High purity; virtually identical to human insulin |
| Supply | Limited by the availability of animal sources | Unlimited and can be mass-produced |
| Cost | Less expensive to produce, but higher risk of side effects | Initially more expensive, but scalable production and technological advancements make it more reliable |
| Allergic Reactions | Higher risk due to non-human protein content | Significantly lower risk of allergic reactions |
| Formulations | Often slower-acting and less consistent | A wide range of rapid-, short-, intermediate-, and ultra-long-acting versions available |
This genetic engineering allowed for mass production of synthetic human insulin, which is purer and less allergenic. Ongoing advancements in formulations and delivery systems have significantly improved the lives of millions with diabetes.
The Collective Achievement
The invention of insulin was a collective achievement, requiring Banting's drive, Best's lab work, Collip's biochemical expertise, and Macleod's scientific oversight. It is a powerful example of how scientific collaboration and an ethical commitment to accessibility can have a global impact. For those interested in a deeper dive, the book The Discovery of Insulin by Michael Bliss provides a comprehensive account of this fascinating history.
Conclusion
The discovery of insulin was a collaborative effort involving Frederick Banting, Charles Best, James Collip, and John Macleod. Their work transformed diabetes from a fatal disease into a manageable condition. Despite initial controversy over the Nobel Prize, their decision to share the prize and patent underscored their commitment to making this treatment accessible. The story of the discovery of insulin demonstrates the power of teamwork and integrity in medical science, with its legacy evolving through modern technology.
