The Discovery of Insulin: the Work of Frederick Banting and Charles Best

Abstract

The Preparation of Insulin (Best, C. H., and Scott, D. A. (1923) J. Biol. Chem. 57, 709–723) The story of the discovery of insulin has been well chronicled beginning with a young physician, Frederick Banting, in London, Ontario, imagining that it might be possible to isolate the internal secretions of the pancreas by ligating the pancreatic ducts to induce atrophy of the acinar cells and thereby minimize contamination of the tissue extract with digestive enzymes. Banting presented his suggestion to J. J. R. Macleod, a distinguished physiologist at the University of Toronto who provided Banting with a laboratory for the summer and some dogs for the experiments. Macleod also assigned Charles Best, a young student, to work as Banting's assistant for the summer. During the summer of 1921, Banting and Best made remarkable progress, and by fall they had isolated material from pancreas extracts that dramatically prolonged the lives of dogs made diabetic by removal of the pancreas. In the winter of 1922, Banting and Best treated their first human patient, a young boy, who's life was saved by the treatment. This was a stunning accomplishment. Consider that from the start of the research in the summer of 1921 to treating a human patient successfully in the winter of 1922, the pace, especially by current standards for clinical treatments, was remarkable. With that achievement, Macleod, who had been initially unenthusiastic about the work, assigned his entire laboratory to the insulin project. He also enlisted the Eli Lilly Company to aid in the large scale, commercial preparation of insulin although the University of Toronto received the patent for insulin production. By 1923, insulin was available in quantities adequate for relatively widespread treatment of diabetes. Although the success of the insulin project was remarkable, the rewards for the research workers were, it seems, quite controversial. The 1923 Noble Prize in Physiology or Medicine was awarded to Banting and Macleod. Apparently, Banting was annoyed at the omission of Best and gave him half of his share of the prize. There was also, perhaps, the feeling that Macleod had done little in the initial stages of the work and was an undeserving recipient. Macleod split his share of the Prize with J. B. Collip who had made contributions to the later stages of the work on insulin purification. After the spectacular events of 1921–1923, the University of Toronto established the Banting and Best Department of Medical Research separate from the University. Banting accomplished little during the rest of his career and died in a plane crash in 1940. Best, however, had a long successful tenure at the University of Toronto working on insulin and subsequently other important topics including the importance of dietary choline and the development of heparin as an anticoagulant. The paper selected as this Journal of Biological Chemistry Classic is not itself “classic” in the usual sense. It reviews very well, however, a remarkable body of classic work. The information regarding various procedures that had been developed quickly and compared in attempts to improve the yield and purity of insulin also contains clues to some special properties of the protein, although so little was known at that time about the structure of insulin (or any protein) that there seemed little rationale for its purification. Insulin was crystallized in 1926 by John J. Abel (1Abel J.J. Crystalline insulin..Proc. Natl. Acad. Sci. U. S. A. 1926; 12: 132-136Crossref PubMed Google Scholar). Virtually all of the information in this Introduction is from Ref. 2Bliss M. The Discovery of Insulin. The University of Chicago Press, Chicago, IL1982Crossref Google Scholar.

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