Insulin isolated in Toronto
At the University of Toronto, Canadian scientists Frederick Banting and Charles Best successfully isolate insulin--a hormone they believe could prevent diabetes--for the first time. Within a year, the first human sufferers of diabetes were receiving insulin treatments, and countless lives were saved from what was previously regarded as a fatal disease.
Diabetes has been recognized as a distinct medical condition for more than 3,000 years, but its exact cause was a mystery until the 20th century. By the early 1920s, many researchers strongly suspected that diabetes was caused by a malfunction in the digestive system related to the pancreas gland, a small organ that sits on top of the liver. At that time, the only way to treat the fatal disease was through a diet low in carbohydrates and sugar and high in fat and protein. Instead of dying shortly after diagnosis, this diet allowed diabetics to live--for about a year.
A breakthrough came at the University of Toronto in the summer of 1921, when Canadians Frederick Banting and Charles Best successfully isolated insulin from canine test subjects, produced diabetic symptoms in the animals, and then began a program of insulin injections that returned the dogs to normalcy. On November 14, the discovery was announced to the world.
Two months later, with the support of J.J.R. MacLeod of the University of Toronto, the two scientists began preparations for an insulin treatment of a human subject. Enlisting the aid of biochemist J.B. Collip, they were able to extract a reasonably pure formula of insulin from the pancreases of cattle from slaughterhouses. On January 23, 1921, they began treating 14-year-old Leonard Thompson with insulin injections. The diabetic teenager improved dramatically, and the University of Toronto immediately gave pharmaceutical companies license to produce insulin, free of royalties. By 1923, insulin had become widely available, and Banting and Macleod were awarded the Nobel Prize in medicine.
source: This Day in History
The Discovery of Insulin: the Work of Frederick Banting and Charles Best
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 (1). Virtually all of the information in this Introduction is from Ref.2.
Frederick G. Banting. Photo courtesy of the National Library of Medicine.
Charles H. Best. Photo courtesy of the National Library of Medicine.
Footnotes
- The American Society for Biochemistry and Molecular Biology, Inc.
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