World Diabetes Day falls on 14 November. This date commemorates the birth of Frederick Banting in 1891. He was born in Canada and received, jointly with JJR Macleod (1876-1935), the Nobel Prize for the discovery of insulin in 1921. It is one of the myths of medical history that Macleod may have only received the Nobel Prize because he was the head of the department and did not contribute much to the discovery. This has been proven to be wrong. Macleod, trained in Aberdeen, Leipzig and London, was the leading physiologist in diabetes. In 1903, he moved to the US, since at the time the United States desperately needed biochemists. In 1918, he was nominated Professor of Physiology in Toronto. His wise decision to give a lab to Banting and Best, his continuous advice to the inexperienced young scientists and his decision to include the biochemist James Collip and others in the team to produce insulin were absolutely fundamental for the Toronto success of the discovery of insulin. Sadly, the great discovery was followed by bitter in-fighting; Banting was ferociously assertive of his own role in the discovery and Macleod, a reserved and modest man, was ill equipped to stand up to the campaign that was waged against him. He left Toronto in 1928 and died in his home country, Scotland, in 1835.

More information and a photo of Professor JJR Macleod you will find below (published in the October issue of Diabetologia, Past Masters series, written by Michael Williams, Aberdeen). Yours sincerely,

European Association for the Study of Diabetes (EASD)
Dr. Monika Grüßer
Rheindorfer Weg 3
40591 Düsseldorf, Germany
monikagruesser@easd.org

John James Rickard Macleod was born on 6 September 1876 at Clunie, Perthshire, in Scotland. His family moved to Aberdeen when he was 7 years old, and he attended Aberdeen Grammar School before studying medicine at Aberdeen University. Having decided on a future in physiology, he won a scholarship that allowed him to spend 18 months at the Physiological Institute at Leipzig, where work on the phosphorous content of muscle led to his first publication in 1899. He returned to Aberdeen as a postgraduate and in 1900 moved to London to work in the Physiology Department of the London Hospital Medical College where he proved himself to be a capable energetic researcher. In 1903 he married Mary Watson McWalter, his second cousin. They were to have no children. In the same year, he became professor of Physiology at Western Reserve University, Cleveland, Ohio, USA, at the early age of 27. There he embarked on an extensive series of investigations in which he applied new techniques to the study of carbohydrate metabolism, and tried to confirm and extend the observations of Claude Bernard on the nervous control of glucose outflow from the liver. This resulted in 12 lengthy papers in the American Journal of Physiology between 1907 and 1914, and he concluded that impaired utilisation of sugar was probably the major reason for hyperglycaemia in diabetes. This work came together in 1913 in an important monograph entitled Diabetes: its Pathological Physiology, which established his reputation as an authority in the field. In this he points out that repeated attempts to lower blood glucose by injection of pancreatic extract had been unsuccessful, and speculated that this might be either because the hormone existed as an inactive precursor in the gland or was inactivated by pancreatic enzymes in the preparations that had been used [1].

In 1918 he moved to Canada, becoming Professor of Physiology in Toronto, and continued his work on carbohydrate metabolism, and it was here, in 1921–1922, that his work, in association with Banting, Best and Collip, culminated in the discovery of insulin. This was followed by the award of the Nobel Prize for Physiology and Medicine (shared with Banting) in 1923. It was a period of frantic activity: he worked to promote the distribution of insulin around the world and co-authored a series of papers on its use and actions. Sadly, the great discovery was followed by bitter in-fighting. Banting was ferociously assertive of his own role in the discovery, and Macleod, a reserved and modest man, was ill-equipped to stand up to the campaign that was waged against him. Meanwhile, he continued an active research programme, among other things providing the conclusive demonstration that insulin comes from the pancreatic islets. In some fish, the islets form an organ separate from the exocrine pancreas, and Macleod showed that extracts from these islets produced a hypoglycaemic effect in rabbits, whereas extracts from acinar tissue were inert. His published output was phenomenal and included a leading textbook of physiology, which went through seven editions in his lifetime.

Macleod left Toronto in 1928—apparently with some relief—to become Regius Professor of Physiology at Aberdeen University, a post he held until his death. His final years were marred by ill health from progressive rheumatoid arthritis, which he endured with great patience and good humour. He died at his home on Saturday 16th March 1935, aged just 58 [2].

Macleod’s contributions to the discovery of insulin were largely forgotten following his death. Banting lacked the scientific background to appreciate the value of the advice and contributions that Macleod and Collip had made to the work, and was convinced to the end of his life that he, with Best’s help, had discovered insulin. Macleod was openly accused of stealing credit for work done by his juniors, and this did lasting harm to his reputation. The full story emerged with the publication in 1983 of Michael Bliss’ The Discovery of Insulin [3]. Macleod’s major personal contributions were finally established beyond doubt [4]. Bliss went on to show that Best had made an attempt to rewrite history in his own favour [5], behaviour that must be contrasted with the dignified silence of Collip and Macleod. Macleod himself was described by a friend as ‘immodestly modest, unassuming, social, sensitive, a born researcher and teacher’ [6], and this perhaps can serve as his epitaph. Insulin is his legacy.

Michael Williams
48, Oakhill Road
Aberdeen
Aberdeenshire AB15 5ES
UK

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