The Insulin Story: Part 1 - The Discovery of Insulin
The discovery of insulin is one of the most celebrated breakthroughs in the history of medicine. Though its fame comes largely from insulin’s immense clinical value, part of the spectacle was its ”miraculous” ability to bring extremely sick people back to health extremely quickly. But the insulin story is particularly interesting for its relevance to the present day. Aside from the genius of the co-discoverers, it shows the importance of a number of institutional structures which may have tipped the balance toward insulin’s discovery in Toronto, rather than by researchers elsewhere. Specifically, the discovery and rapid development of insulin for commercial use was the product of a broad and diverse collaborative network--one that provides a clear historical touchstone for MaRS and the convergence innovation paradigm.
The article powerfully inspired Banting. Unable to sleep, he arose in the middle of night to write himself the following note:
As the pancreas contains corrosive digestive juices, researchers had found it impossible to isolate the ”internal secretion,“ whose existence was only hypothetical. Banting’s plan was to seal dogs’ pancreatic ducts shut, causing all of the pancreas but the islets of Langerhans to degenerate. This made the business of extracting the ”internal secretion”—if it existed—much more promising.
On November 8, 1920, Banting pitched his idea to J.J.R. Macleod, a University of Toronto physiology professor and an internationally respected authority on carbohydrate metabolism. Macleod was not particularly impressed; Banting was a surgeon by training, not a researcher, and had only a cursory knowledge of the pancreas and diabetes. (You may have noticed that in the above note, Banting misspelled both ”diabetes” and ”glycosuria.”) But Banting’s approach was novel and Macleod had extra lab space, so he made arrangements for Banting to start in the upcoming summer. He assigned Charles Best, a recent Honours Physiology and Biochemistry graduate, as an assistant.
In January 1922, the group decided to move to human trials. Before insulin, the only means of controlling diabetics’ symptoms was by severely limiting their diet—so called ”starvation therapy.“ Most often, this treatment replaced a quick death from diabetes with a slow, painful wasting away over several months or years. Such was the case with Leonard Thompson, a weak, haggard boy of 14 whose hair was falling out and who weighed only 29 kilograms when he was admitted to the Toronto General Hospital. It was clear that his diabetes was too severe for starvation therapy and he was deemed a hopeless case. In Ward H of the Heritage Building’s Medical Wing (the approximate location of the Phase II tower), Banting gave Thompson a shot of the extract in each buttock on January 11, 1922. The extract was clearly rife with impurities (Chief Clinician Walter Campbell described it as a “thick brown muck”); although there was a mild reduction in Thompson’s blood and urine sugar content, it caused a sterile abscess to form at one of the injection sites. Campbell decided that the extract was more dangerous than beneficial and did not justify further testing.
But the Toronto group was not stumped for long. On January 19, Collip made an ingenious improvement to his purification method, purging the extract of the toxic brown muck. On January 23, the refined extract was tried again on Thompson. This time his blood sugar dropped dramatically, sugar nearly disappeared from his urine and ketones—a symptom of diabetes caused by the incomplete metabolization of lipids—disappeared completely. Miraculously, Thompson became visibly brighter and stronger. When these incredible results proved repeatable over several weeks with Thompson and six other patients, the group published its findings in the Canadian Medical Association Journal. On March 22, the day that the CMAJ was mailed out, the Toronto Star’s headlines proclaimed “Toronto Doctors On Track Of Diabetes Cure.”
Frederick Banting
BANTING’S INSPIRATION
Frederick Banting graduated from the University of Toronto Medical School in 1916, and after serving in World War One, he set up a practice in London, Ontario, and took up a lecturing position in surgery and anatomy at the University of Western Ontario. On October 30, 1920, he came across an article in the periodical Surgery, Gynaecology and Obstetrics while preparing for a lecture on the pancreas. Dr. Moses Barron, the author, had found a living subject whose pancreatic ducts were blocked. The pancreas completely shrivelled except for pockets of tissue known as the islets of Langerhans. Although the pancreas’ only known function at the time was the secretion of digestive juices, it had long been suspected that it was associated with diabetes. As diabetes did not ensue in the patient, Barron’s findings suggested that the islets of Langerhans were the source of an anti-diabetes ”internal secretion.”The article powerfully inspired Banting. Unable to sleep, he arose in the middle of night to write himself the following note:
Diabetus
Ligate pancreatic ducts of dogs. Keep dogs alive till acini degenerate leaving Islets.
Try to isolate the internal secretion of these to relieve glycosurea
As the pancreas contains corrosive digestive juices, researchers had found it impossible to isolate the ”internal secretion,“ whose existence was only hypothetical. Banting’s plan was to seal dogs’ pancreatic ducts shut, causing all of the pancreas but the islets of Langerhans to degenerate. This made the business of extracting the ”internal secretion”—if it existed—much more promising.
J.J.R. Macleod
Banting, Best and one of their ill-fated dogs.
LABORATORY TRIALS AND TRIBULATIONS
In May 1921, Banting and Best began their experiments under MacLeod’s supervision, ligating dogs’ pancreatic ducts and testing the resulting extracts on de-pancreaticized, severely diabetic dogs. The surgical procedures were awkward, causing a high attrition rate among the dogs. Conscious of their limited funds, Banting and Best took to the streets of Toronto, buying new dogs en masse for one to three dollars, ”no questions asked.“ By December 1921, the two had gathered some moderately promising results and were relieved to abandon dogs in favour of pork and beef foetus (available in large supply from nearby farms) as a source of pancreatic tissue. Better yet, they attracted the talents of J.B. Collip, a PhD in Biochemistry and an expert on endocrine secretions and tissue extracts.In January 1922, the group decided to move to human trials. Before insulin, the only means of controlling diabetics’ symptoms was by severely limiting their diet—so called ”starvation therapy.“ Most often, this treatment replaced a quick death from diabetes with a slow, painful wasting away over several months or years. Such was the case with Leonard Thompson, a weak, haggard boy of 14 whose hair was falling out and who weighed only 29 kilograms when he was admitted to the Toronto General Hospital. It was clear that his diabetes was too severe for starvation therapy and he was deemed a hopeless case. In Ward H of the Heritage Building’s Medical Wing (the approximate location of the Phase II tower), Banting gave Thompson a shot of the extract in each buttock on January 11, 1922. The extract was clearly rife with impurities (Chief Clinician Walter Campbell described it as a “thick brown muck”); although there was a mild reduction in Thompson’s blood and urine sugar content, it caused a sterile abscess to form at one of the injection sites. Campbell decided that the extract was more dangerous than beneficial and did not justify further testing.
J.B. Collip