Essential Contributions of Pathologists and Laboratory Physicians Leading to the Discovery of Insulin

Abstract

Context.— Frederick Banting, Charles Best, J. Bertrand Collip, and J. J. R. Macleod contributed to the discovery of insulin in 1921–1922. Recent advances in anatomic pathology, experimental pathology, and clinical pathology were necessary for the research in Toronto, Ontario, Canada, to begin and to succeed. Objective.— To explore the role of pathology and laboratory medicine in laying the foundation for the discovery of insulin. Design.— Available primary and secondary historical sources were reviewed. Results.— During a 3-decade period, pathologists, through autopsy pathology and experimental animal studies, were able to provide solid evidence that the pancreatic islets were the source of the internal secretion responsible for proper carbohydrate metabolism. Banting, a surgeon with no previous research experience, read about these studies in a case report with an extensive literature review by pathologist Moses Barron; this piqued Banting's interest and caused him to approach Macleod, a Toronto physiology professor, with an idea that initiated the research. Advances in clinical laboratory medicine, which allowed them to measure blood glucose levels using small blood volumes, were critical to their success. Conclusions.— By 1921–1922, the pieces necessary to solve the puzzle were available. The primary reason that the time was ripe for the discovery was the contributions of pathologists and laboratory physicians in the preceding 3 decades. As the 100th anniversary approaches, our profession can take pride in its important contributions to the discovery of insulin, which is broadly recognized as one of the most important medical research advances of the 20th century.

Frederick Banting’s actual great idea: The role of fetal bovine islets in the discovery of insulin

“… 10 As for Ibrahim’s study, the importance to Banting of not having to deal with trypsin in fetuses up to 4 months gestation is obvious. Carlson and Drennan had found that pregnant dogs undergoing pancreatectomies near term did not become diabetic and speculated: “the internal secretion of the fetal pancreas passes through the uterine membranes in sufficient quantity to prevent diabetes in the mother” 22 p393 However, it should be noted that this conclusion was highly tenuous as it was based on a small number of dogs and, since it had been performed in 1910 before blood glucose measurements were practical, 23 only a few urine sugar measurements over 2–3 d. Banting and Best wrote: “The most natural interpretation of Carlson’s result is that the pancreas of the fetus furnishes to the mother an internal secretion which is necessary for the metabolism of sugar.” 10 p464 However, they cautiously noted that another investigator had been unable to replicate Carlson’s study. 10 …”

“…But is the idea even biologically plausible – is it compatible with what we know today? Because of my 20 y interest in the history of insulin 4 , 5 , 23 , 24 , 26 and my 30+ y career as a pediatric-perinatal pathologist clinician-scientist running an islet xenotransplantation laboratory, 27–32 I decided to use the approaching 100 th anniversary of the discovery of insulin as an excuse to address this perplexing, unanswered historical-biological question. In reading primary and secondary historical sources on Banting’s second great idea, it appears to have been based upon his and Best’s readings about both human and livestock fetal pancreata.…”

“…Additional details about early islet histology and histopathology critical to the discovery of insulin have been reviewed in detail elsewhere. 23 …”

Winner's curse: The sad aftermath of the discovery of insulin

“…Their success was made possible by recent advances in biochemical testing made elsewhere. 5 Best had been trained by Macleod to perform state-of-the-art blood glucose and other biochemical tests, but neither Banting nor Best had the expertise to purify an extract for human use. This became manifest when their preparation failed to help Leonard Thompson on January 11th 1922, and it took the chemistry skills of James Bertram Collip to rescue the situation.…”

Pancreas preservation with amphotericin B deteriorates islet yield for porcine islet isolation

“…Since the discovery of insulin by Banting and Best in 1921, the prognosis and treatment options for individuals with diabetes have improved 1‐3 . However, the current need for frequent blood glucose monitoring necessitated by multiple daily insulin injections has resulted in significant lifestyle challenges for individuals afflicted with Type 1 diabetes.…”