There are two names that almost always come to mind when people reflect on the landmark discovery of insulin in 1922: Dr. Frederick Banting, the headstrong surgeon who conceived the idea, and Charles Best, the dedicated student assistant who tested it in the laboratory. The story of their efforts to lower experimental dogs’ blood sugar levels has become legendary due to their perseverance through a sweltering Toronto summer.
There is, however, one piece of that historical puzzle that is often overlooked.
It was a dark, murky, and highly impure liquid that Banting and Best produced in the early days. It routinely caused painful local abscesses, severe allergic reactions, and violent fevers when injected into living tissue. Human life could simply not be saved by their extract in its original form.
Dr. James Bertram Collip enters the scene.
He joined the Toronto team at a time of crisis and was a brilliant, quiet biochemist. Using alcohol solutions and test tubes, he discovered the exact chemical process needed to separate pure, life-saving insulin from dangerous cellular debris. Despite Collip’s technical genius, insulin might have remained a laboratory experiment rather than a safe, global treatment.
James Collip is the untold story of the insulin team, his breakthroughs in the lab, and his lasting legacy as a pioneer of modern endocrinology.
An Early Life in Biochemistry and a Rising Star
Originally from Belleville, Ontario, Canada, James Bertram Collip was born in 1892. Despite his young age, he showed an exceptional aptitude for academics, enrolling at the University of Toronto at fifteen to study physiology and biochemistry.
The chemical structures in Collip’s chemistry were especially well remembered because he was quiet, attentive, and deeply focused. It is remarkably young for someone with such an advanced degree to have earned their doctorate in biochemistry in 1916.
After graduating, Collip accepted a lecturer’s position at the University of Alberta’s Department of Physiology and Biochemistry. After publishing well-regarded papers on blood chemistry and metabolic processes, he quickly earned a reputation as a meticulous researcher who excelled at tissue extraction and chemical purification.
During the spring of 1921, Collip was awarded a traveling fellowship to conduct advanced research with Dr. John Macleod, head of the physiology department, at the University of Toronto. A medical history chapter that was about to explode coincided with his sabbatical.
A Crisis of Crude Extracts
At the time Collip arrived in Toronto, Banting and Best had already achieved their baseline breakthrough: they had successfully reduced blood sugar levels in diabetic dogs with pancreatic extracts.
Transitioning from animal testing to human application proved to be a major obstacle for the team.
Raw extract, which was prepared by grinding pancreatic tissue and filtering it through paper, contained digestive enzymes, foreign proteins, and bacteria. At Toronto General Hospital, the team conducted their very first human trial in January 1922 on 14-year-old Leonard Thompson. It caused severe inflammatory reactions and sterile abscesses at the injection site, but only marginally affected his blood sugar levels.
Trial was halted. In terms of surgical and laboratory skills, Banting and Best had reached the limits of their abilities. The hormone could be harvested, but it could not be cleaned because of their lack of advanced chemical knowledge.
James Collip was formally asked by Professor Macleod to pause his own research projects to focus exclusively on the purification of pancreatic extract.
Alcohol Breakthrough in the Laboratory
He threw himself into the problem with a relentless intensity. The process of purifying a delicate protein hormone was like finding a needle in a haystack, except that if exposed to the wrong chemical conditions, the needle would break.
In his experiments, he focused on using alcohol at varying concentrations as a solvent. There is a precise scientific logic to the results: differently soluble proteins and impurities precipitate at different levels of alcohol. As long as Collip could find the right “sweet spot” of alcohol concentration, all of the toxic impurities would settle to the bottom of the flask, but the insulin hormone would remain dissolved.
While working late into the night in January 1922, Collip systematically tested dozens of subtle variation ratios:
- Concentration below 50% alcohol: The heaviest tissue debris and enzymes are filtered out.
- Concentration (around 80% alcohol): The active insulin hormone remained dissolved in the liquid, separated from larger molecules.
- A high concentration of alcohol (above 90%) causes the pure insulin itself to precipitate out of the liquid as a clean, white powder.
The world’s first pure, non-toxic, injectable insulin solution was made by re-dissolving that clean powder in sterile water.
Leonard Thompson’s transformation was instantaneous after receiving the second injection of Collip’s newly purified extract on January 23, 1922. Blood sugar levels plummeted, urine cleared of ketones, and the boy’s energy returned—without any sign of the severe allergic reactions or abscesses caused by the previous batch.
Having bridged the gap between a laboratory concept and a viable medicine, Collip had made a significant contribution to medicine.
Memory Loss in the Laboratory: The Secret Forgotten
After the team had accomplished their miracle, disaster struck again-this time inside Collip’s head.
As soon as Collip made his discovery, he tried scaling up his purification process to produce larger quantities of insulin. Despite his best efforts, the new batches failed completely. The insulin either lost its potency entirely or remained contaminated with toxic impurities.
Collip realized he couldn’t duplicate his exact original formula due to his exhaustion and stress from running dozens of quick variations without meticulously recording ambient temperature and pH balance adjustments.
Chaos reigned in the lab. There was a dramatic flare-up in tension between team members when patients were running out of pure insulin. According to Banting, who was notorious for his volatile temper, Collip had withheld the secret formula so that he could profit from it independently. Collip and Banting got into a physical confrontation in the lab, where Banting grabbed him before colleagues intervened.
Knowing that human lives were at stake, Collip swallowed his pride, retreated to his bench, and spent weeks retracing his steps. Eventually, he rediscovered the pH balances and temperature thresholds required for mass purification by working with Best and Macleod.
After the crisis had passed, steady production resumed in North America, allowing widespread production to take place.
A One-Dollar Patent and the Nobel Divide
As part of the team’s efforts to ensure international patents for insulin to prevent predatory commercial exploitation, Collip signed over all patent rights to the University of Toronto for just one dollar.
The invention designed to save dying children was not intended for Collip to enrich himself, as he believed that life-saving medicine belongs to humanity.
In 1923, Frederick Banting and John Macleod shared the Nobel Prize in Physiology or Medicine, omitting Collip and Best. Charles Best and Banting split Banting’s prize money to protest exclusion.
Macleod publicly announced that he would share his half of the Nobel Prize monetary award equally with James Collip, formally acknowledging that Collip’s biochemistry led to the clinical breakthrough.
A Giant of Endocrinology: Life Beyond Insulin
Scientists who participate in a world-changing discovery early in their careers often live in its shadow for the rest of their careers. A notable exception was James Collip.
As a result of his work on insulin, Collip returned to the University of Alberta and later accepted prestigious positions at McGill University and the University of Western Ontario. Over the next four decades, he established himself as one of the most prolific endocrinologists in medical history:
1. Determination of the Parathyroid Hormone (PTH)
Collip isolated parathyroid hormone (PTH) in 1925, proving that calcium levels in the blood and bone tissues are controlled by the parathyroid glands in the neck. Metabolism-related bone diseases have been better understood thanks to this breakthrough.
2. Extraction of ACTH and pituitary hormones
The pituitary gland is regarded as one of the master glands of the human body, and Collip was a pioneer in studying it. Adrenocorticotropic hormone (ACTH) plays a key role in regulating inflammation and responding to stress, and his laboratory was one of the very first to isolate and purify it.
3. The role of medical leadership during wartime
The National Research Council’s Medical Research Division was headed by Collip during World War II, where he coordinated blood transfusions, shock treatments, and pilot survival systems.
During the last two decades of his career, he mentored generations of medical researchers and physicians at the University of Western Ontario.
At the age of seventy-two, James Collip passed away in June 1965, leaving behind a legacy of scientific achievements that went far beyond the summer of 1921.
James Collip’s Journey: Key Takeaways
There are several timeless lessons for science, medicine, and society to be learned from the life and work of James Collip:
- A Safe, Effective Cure Wholly Depends on Specialization: Banting had the original medical vision, but it took Collip’s specialty in biochemistry to make that vision a reality.
- A willingness to work through exhaustion: Despite his early purification steps failing to reproduce, Collip remained disciplined.
- An example of true altruism: Collip traded his multi-million dollar patent rights for a single dollar, sacrificing his personal fortune for the sake of public health.
- A lifetime of lasting excellence: Having isolated parathyroid hormone and advanced hormone research for decades, Collip proved that true science is not a one-time occurrence.
Lastly,
Neither James Bertram Collip nor his work sought public acclaim or dramatic headlines. Scientists like him prefer the calm environment of their laboratories to public rivalries and media attention.
Without his precise chemical breakthroughs in early 1922, insulin’s story might have ended in tragedy rather than triumph. With his discovery of the secret to purifying raw pancreatic extracts, James Collip saved Leonard Thompson and helped millions of diabetics around the world live long, healthy lives. With Banting, Best, and Macleod, he stands as an equal partner in one of mankind’s greatest medical achievements.
