James Collip in his office at McGill University circa 1930.
Dr. James Bertram Collip was a precocious young man. He obtained his undergraduate degree in Physiology and Biochemistry from the University of Toronto at age 15 — too young, apparently, to take on the medical courses that he initially wanted — and a PhD in Biochemistry from the University of Toronto at 24. He was an experienced researcher and had already worked for seven years at the University of Alberta as a lecturer when he returned to his alma mater and became part of the historic insulin discovery team.
In the spring of 1921, Collip took a 6 month sabbatical with a Rockefeller Travelling Scholarship to work with J.J.R. MacLeod in Toronto, examining the effect of pH on sugar concentration in the blood. With this funding, he travelled to marine biological stations in Woods Hole in Massachusetts and St. Andrews in Nova Scotia. Upon his return to Toronto later that year, it became clear that his expertise was in demand on the insulin project as both Dr. Frederick Banting and his student Charles Best were having difficulties preparing a pure extraction of insulin that was suitable for clinical use. The impurities in their crude preparation caused sterile abscesses at the site of injection and other side effects. Collip achieved quick success by increasing concentrations of alcohol in the purification process. In January 1922, Collip readied an extract that successfully treated a young boy living with diabetes named Leonard Thompson.
In addition to technical assistance, Collip contributed physiological discoveries to the project. He showed that too high a dose of the insulin extract caused dangerously low blood sugar levels (hypoglycemia) in rabbits. He also developed a way of measuring the insulin extract’s effect on blood sugar in rabbits so that they had an easier and cheaper way of standardizing the preparation. Additionally, he was able to show that the extract, once administered, caused glucose in the blood to be converted to glycogen in the liver — an essential metabolic function that is deficient in people living with diabetes. This, coupled with the elimination of abnormal ketone concentrations in the blood and urine, demonstrated the effectiveness of his insulin extract in treating the condition.
Despite the success, Collip’s preparation method only produced small quantities of insulin and could not sustain scale-up to meet the demand of treatment. The operation was taken over by the University of Toronto’s Connaught Antitoxin Laboratories, with help from the Indianapolis-based Eli Lilly and Company. A patent was filed in 1922 under Banting, Best and Collip, and was sold to the University for $1. Royalties were divided, with half funding the University’s research activities and the other half supporting the three researchers with their own work in Canada.
Every story has its tensions, and the tale of insulin discovery is no different. Angry confrontations broke out as Collip at one point refused to divulge his methods for extraction, claiming it was MacLeod’s instruction that everything remain confidential until it is tested and proven effective, and Banting became increasingly agitated over suspicions of MacLeod and Collip taking credit for his work. In 1923, the Nobel Prize in Physiology or Medicine in 1923 was awarded jointly to Banting and MacLeod for the discovery of insulin. MacLeod shared his half of the prize money with Collip, while Banting did the same for Best.
After his time in Toronto, Collip returned to Edmonton where he became a Professor and Head of the Biochemistry Department in 1922. He also obtained his MD in 1926 before being recruited to McGill University in 1928 where he served as Chair of the Department of Biochemistry. In 1947, he was appointed Dean of Medicine at the University of Western Ontario. He continued working on endocrinology throughout his career, notably becoming a leader in the study of pituitary hormones and one of the first researchers ever to isolate the parathyroid hormone.
— Written by Angela Zhou