Insulin: discovery and controversy.

During the first two decades of the 20th century, several investigators prepared extracts of pancreas that were often successful in lowering blood sugar and reducing glycosuria in test animals. However, they were unable to remove impurities, and toxic reactions prevented its use in humans with diabetes. In the spring of 1921, Frederick G. Banting, a young Ontario orthopedic surgeon, was given laboratory space by J.J.R. Macleod, the head of physiology at the University of Toronto, to investigate the function of the pancreatic islets. A student assistant, Charles Best, and an allotment of dogs were provided to test Banting's hypothesis that ligation of the pancreatic ducts before extraction of the pancreas, destroys the enzyme-secreting parts, whereas the islets of Langerhans, which were believed to produce an internal secretion regulating sugar metabolism, remained intact. He believed that earlier failures were attributable to the destructive action of trypsin. The name "insuline" had been introduced in 1909 for this hypothetic substance. Their experiments produced an extract of pancreas that reduced the hyperglycemia and glycosuria in dogs made diabetic by the removal of their pancreases. They next developed a procedure for extraction from the entire pancreas without the need for duct ligation. This extract, now made from whole beef pancreas, was successful for treating humans with diabetes. Facilitating their success was a development in clinical chemistry that allowed blood sugar to be frequently and accurately determined in small volumes of blood. Success with purification was largely the work of J.B. Collip. Yield and standardization were improved by cooperation with Eli Lilly and Company. When the Nobel Prize was awarded to Banting and Macleod for the discovery of insulin, it aggravated the contentious relationship that had developed between them during the course of the investigation. Banting was outraged that Macleod and not Best had been selected, and he briefly threatened to refuse the award. He immediately announced that he was giving one-half of his share of the prize money to Best and publicly acknowledged Best's contribution to the discovery of insulin. Macleod followed suit and gave one-half of his money award to Collip. Years later, the official history of the Nobel Committee admitted that Best should have been awarded a share of the prize.