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John Macleod (physiologist)

John James Rickard Macleod,, was a Scottish biochemist and physiologist. He devoted his career to diverse topics in physiology and biochemistry, but was chiefly interested in carbohydrate metabolism. He is noted for his role in the discovery and isolation of insulin during his tenure as a lecturer at the University of Toronto, for which he and Frederick Banting received the 1923 Nobel prize in Physiology or Medicine. Awarding the prize to Macleod was controversial at the time, because according to Banting's version of events, Macleod's role in the discovery was negligible. It was not until decades after the events that an independent review acknowledged a far greater role than was attributed to him at first.

Biography
Macleod was born in Clunie, near Dunkeld in Perthshire. Soon after he was born, his father Robert Macleod, a minister of the Free Church, was transferred to Aberdeen, where John attended Aberdeen Grammar School and enrolled in the study of medicine at the University of Aberdeen. In 1910, he delivered a lecture on various forms of experimental diabetes and their significance for diabetes mellitus at the joint meeting of the section on Pharmacology and Therapeutics and the section on Pathology and Physiology of the American Medical Association. In 1916, he was a Professor of Physiology at McGill University in Montreal, Canada. After the First World War, he went on to teach physiology at the University of Toronto, where he became director of the physiology lab and an assistant to the dean of the medical faculty. He researched various topics in physiology and biochemistry, among which were the chemism of Mycobacterium tuberculosis, electroshocks, creatinine metabolism and blood circulation in the brain. In 1905 he became interested in carbohydrate metabolism and diabetes, publishing a series of scientific papers and several monographs on the subject from then on. Additionally, Macleod was a popular lecturer and an influential contributor to the development of the six-year course in medicine at the University of Toronto. Frederick Banting and the discovery of insulin At the end of 1920, Macleod was approached by Frederick Banting, a young Canadian physician who had the idea of curing diabetes using an extract from a pancreas whose functioning had been disrupted. Macleod was not enthusiastic, because (unlike Banting) he knew about unsuccessful experiments in this direction by other researchers. He thought it more likely that the nervous system had a crucial role in regulating blood glucose concentration. Even though Banting had virtually no experience of physiology, he managed to convince Macleod to lend him laboratory space during a holiday in Scotland that summer. While Macleod was away, Banting and Best achieved a breakthrough: they isolated an internal secretion of the pancreas and succeeded in reducing the blood sugar level of another dog, whose pancreas had been surgically removed. Macleod who was "desperate to snatch victory from the jaws of defeat" stepped in and finished the presentation. From Banting's viewpoint, "this was a brazen coup by Macleod to rob him of the credit for having discovered insulin – and to rub salt into the wound, it had been done in front of the most eminent doctors in the field". Their discovery was first published in the February 1922 issue of The Journal of Laboratory and Clinical Medicine. Macleod declined co-authorship because he considered it Banting's and Best's work. Despite their success, there remained the issue of how to get enough pancreas extract to continue the experiments. Together, the three researchers developed alcohol extraction, which proved to be far more efficient than other methods. This convinced Macleod to divert the whole laboratory to insulin research and to bring in the biochemist James Collip to help with purifying the extract. The first human clinical trial was unsuccessful. Banting was insufficiently qualified to participate and felt sidelined. By the winter of 1922, he was certain that all Macleod's colleagues were conspiring against him. There was a reported physical altercation between Banting and Collip, as Banting saw Collip's breakthrough on alcohol purification as a threat, while Collip was reluctant to share the details. Collip threatened to leave because of the strained atmosphere but the encouragement of others who saw the potential of their research prevented escalation of the conflict. Later years Macleod returned to Scotland in 1928 to become Regius Professor of Physiology at the University of Aberdeen (in succession to his former teacher, John Alexander MacWilliam who retired in 1927) and later Dean of the University of Aberdeen Medical Faculty. Between 1929 and 1933 he was also a member of the Medical Research Council. Macleod did not continue to work on insulin, but he remained active as a researcher, lecturer and author. His last major contribution was a proof that the central nervous system does have an important role in maintaining carbohydrate metabolism balance, as was his original hypothesis. His theory about conversion of fats into carbohydrates remained unproven, despite his provision of several indirect proofs. despite which he remained active almost until his death. In 1933 he made a lecture tour of the US, and in 1934 he published the 7th edition of his book Physiology and Biochemistry in Modern Medicine. ==Works==
Works
Macleod was a prolific writer. His first academic article was a paper on phosphorus content in muscles published in 1899. During his career he authored or co-authored over 200 papers and eleven books. Among them are: • Practical Physiology (1903) • Recent Advances in Physiology (with Leonard E. Hill, 1905) • Diabetes: its Pathological Physiology (1913) • Physiology for dental students (with R. G. Pearce, 1915) • Physiology and Biochemistry in Modern Medicine (1st edition 1918) • Insulin and its Use in Diabetes (with W. R. Campbell, 1925) • Carbohydrate Metabolism and Insulin (1926) • The Fuel of life: Experimental Studies in Normal and Diabetic Animals (1928) ==Awards and honours==
Awards and honours
, Aberdeen John Macleod was a distinguished physiologist even before the discovery of insulin. He was elected a member of the Royal Society of Canada in 1919 and president of American Physiological Society in 1921. In 1923, Macleod was awarded the Cameron Prize for Therapeutics of the University of Edinburgh. Among the recognitions he received after 1923 were memberships of the Royal Society and the Royal Society of Edinburgh, corresponding membership of the German Academy of Sciences Leopoldina and honorary membership of the Regia Accademia Medica. His contribution to science is now recognized by the broad public, even in Canada. The auditorium of the Toronto University Medical Research Centre was named in his honour, as was Diabetes UK's award for patients who survive for 70 years with diabetes. In 2012, he was inducted into the Canadian Medical Hall of Fame. Nobel Prize The Nobel Committee reacted almost immediately to the first successful clinical trials. In the autumn of 1923, Banting and Macleod received the Nobel Prize in Physiology or Medicine, even though the long-term importance of the discovery was not yet apparent. They were nominated by the Danish physiologist and Nobel laureate August Krogh, who had a diabetic wife and had visited Macleod's laboratory and taken the method back to Denmark. Banting was furious, as he was convinced that Best should have received the other half, and he even thought of rejecting the prize. He was finally persuaded to accept it but gave half of his prize money to Best. Macleod in turn gave half of his to Collip. In 1972 the Nobel Foundation officially conceded that omitting Best was a mistake. Best publicly apologized for that mistake many years later. ==See also==
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