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

Abstract

Background: Frederick Banting approached Toronto physiology professor JJR Macleod with a way to prevent pancreatic trypsin from destroying the pancreas’ internal secretion. Banting proposed to induce exocrine atrophy by ligating canine pancreatic ducts and to use extracts of islet-rich residua to treat pancreatectomized dogs. His next plan was to make extracts from fetal pancreas, which he had read was islet-rich and lacked exocrine tissue capable of making trypsin; this work has not been historically evaluated. Methods: Banting’s fetal calf pancreas story is told using primary and secondary historical sources and then critically examined using both historical and recent data on species phylogeny, islet ontogeny, fetal/neonatal islet culture/transplantation, etc. Results/Discussion: Only ruminants develop dual islets populations sequentially; fetal calf pancreata, at the gestational ages Banting used, possess numerous insulin-rich giant peri-lobular islets, which credibly explain the potency of his fetal calf insulin extract. Use of non-ruminant fetal pancreata would have failed.

The Importance of Animal Models in Biomedical Research: Current Insights and Applications

“…At least 144 species used in those animal-based studies were mammals, and 42% were rodents [ 7 ]. Dogs were the first animal model used in metabolic research on gastric secretions [ 23 ] and for discovering insulin [ 24 ]. To date, rodents are the predominant species in research ( Table 1 ) [ 9 ].…”

Whole-Organ Pancreas and Islets Transplantations in UK: An Overview and Future Directions

“…Type 1 diabetes results from the autoimmune destruction of the β-cells of the pancreatic islets and type 2 diabetes is caused from impaired insulin secretion and resistance to the action of insulin [1]. In 1921, Frederick Banting and Charles Best isolated insulin from pancreatic islets and administrated it to patients suffering from type 1 diabetes, thus inaugurating a new era in diabetes treatment [2]. Further developments, including synthetic short-and long-acting insulin, portable blood sugar monitoring and insulin pumps, have all improved diabetes management [3].…”

The discovery of insulin

“…4 Others have since written that Macleod made substantial original contributions to the research and that this information was presented to the Nobel Prize committee. 11 No one questioned Banting’s nomination, but he was so upset that Best was not nominated that he contemplated refusing the nomination. Ultimately, he opted to share his prize money with him.…”

“…Eventually, Banting realised that fetal calf pancreases would be a good source of material, as the islet cells were present in high numbers but the gastrointestinal functions had not matured. 11 This proved to be a far more promising source of insulin.…”