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

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.