John James Rickard Macleod Biography (1876-1935)


John James Rickard Macleod was born in Cluny, near Dunkeld, Scotland, on September 6, 1876, the son of the Reverend Robert Macleod. Soon after his birth,the family moved to Abderdeen. Macleod attended Aberdeen Grammar School and Aberdeen University. He went on to study medicine at Marischal College, wherehe graduated with honors in 1898. With an Anderson traveling scholarship, Macleod continued his education at Leipzig's Physiology Institute where he studied biochemistry for a year. In 1900 he returned to London to become a demonstrator in physiology at the London Hospital Medical College, and the followingyear became a biochemistry lecturer there. The same year he was named a Mackinnon research scholar by the Royal Society. During this period, Macleod published his experiments on intracranial circulation and caisson's disease. In 1902 he attended Cambridge University and obtained a diploma in public health.He married Mary Watson in 1903, and journeyed to America to become professorof physiology at Western Reserve University in Cleveland, where he stayed for 15 years. The same year he arrived at Western Reserve, his text, Practical Physiology, was published.

Macleod began his investigations into the human body's carbohydrate metabolism during his early years at Western Reserve, studying salt and urea metabolism. Studies of the breakdown of liver glycogen followed, and in 1913, he published Diabetes: Its Physiological Pathology. In 1918, Macleod went to the University of Toronto to become a professor of physiology and associate dean of the faculty of medicine. Macleod's major areas of interest at this time were the effects of oxygen excess and deprivation. He also studied respiration in animals whose brains had been removed or spines cut. During this period, he wrote Physiology and Biochemistry in Modern Medicine. The 1,000-page book went through seven editions and became a standard text in the field.

In 1921 Macleod returned to his work on carbohydrate metabolism, comparing the blood-sugar level in normal animals with that of animals with their pancreas removed. At the time it was known that diabetes was caused by the failure of the pancreas to secrete a substance that regulates sugar metabolism, causing an abnormally high concentration of glucose in the blood and an excretion of sugar into the urine. It was also understood that the unidentified substance sped the passage of sugar in the form of glucose through the body to be oxidized as a source of energy or converted the sugar into glycogen for storagefor later use as glucose. Macleod appointed Frederick Grant Banting, a Canadian orthopedic surgeon, to specifically investigate the function of a clusterof cells in the pancreas known as the islet of Langerhans. Macleod chose Charles Herbert Best, one of his senior medical students, to be Banting's chief laboratory assistant. Together the three men planned how they would separate the islet from the pancreas to isolate the substance secreted by the cell cluster. This substance, Macleod believed, was the sugar regulator they were seeking.

When Banting and Best tied the ducts of the pancreas so that it would atrophy, they were able to isolate a residue in the islet. They injected this extract into dogs and found that it did indeed lower blood glucose. The problem ofhow to obtain larger quantities of the extract, named insulin, remained. Forhelp, Banting turned to James Bertram Collip, a young Canadian biochemist. Collip used pancreas glands bought from a butcher as a source of insulin. To demonstrate how safe the extract was, Banting and Best injected themselves withinsulin. By January, 1922, they had begun clinical trials. A youngster namedLeonard Thompson was the first diabetic to receive insulin injections. The results proved that the new treatment controlled the debilitating disease. Solving the final problem of making insulin therapy available to the general public, an American biochemist, John Jacob Abel, converted insulin into a crystalline form in 1926, so that it could be given in precise dosages. Today insulin is prepared from the pancreatic tissue of domestic animals.

The Nobel Prize committee acted with remarkable swiftness to recognize the achievement. Macleod and Banting were given the Nobel Prize in 1923, only a year after their discovery. Collip later noted that Macleod's outstanding position in the field of carbohydrate metabolism had made it appropriate and fortunate that the discovery of insulin had been made in his laboratory. Macleod, for his part, maintained that it was only through team work that insulin couldbe isolated. He shared his prize money with Collip, while Banting divided his with Best.

In 1928 Macleod returned to Scotland to become chairman of the physiology department at the University of Aberdeen. He continued his research into carbohydrate metabolism there and at the Rowett Institute, publishing numerous papers on insulin, experimental glycosuria--the presence of sugar in the urine--respiration and lactic acid metabolism. Arthritis forced him to discontinue hislaboratory work, but he continued supervising the work of the physiology department. He died on March 16, 1935, at the age of 58.

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