John J. R. Macleod

Scottish physiologist

• Born: September 6, 1876; Cluny, Scotland
• Died: March 16, 1935; Aberdeen, Scotland

As the leader of a physiology research laboratory at the University of Toronto in Canada, Macleod shared the 1923 Nobel Prize in Physiology or Medicine with Frederick G. Banting for the discovery of insulin as a treatment for diabetes.

Primary fields: Biology; medicine

Specialties: Physiology; biochemistry

Early Life

John J. R. Macleod was born in Cluny, a village in Perthshire, Scotland. His father served as a minister to a church in the area but soon after Macleod’s birth received a call to serve in Aberdeen. It was in Aberdeen that Macleod attended Marischal College, Aberdeen University, to study medicine. He graduated with distinction in 1898.

In 1900, he accepted a teaching position at the London Hospital Medical College. Macleod’s reputation as a teacher and researcher attained international status, and in 1903, with his new wife, Mary Watson McWalter, he traveled to Cleveland, Ohio, where he was appointed professor of physiology at what is now Case Western Reserve University. In 1918, he moved to Canada to accept a position as professor of physiology at the University of Toronto.

While he was at Toronto, Macleod published a book on diabetes and how it functions as a human disease. In the text he suggested that the disease was brought about by mental stress, such as that experienced by locomotive engineers, captains of ocean liners, and workers who are frequently under severe strain. He also recognized that individuals with diabetes showed high levels of sugar in their blood (hyperglycemia), high levels of sugar in the urine (glycosuria), and sometimes both. This was a manifestation of carbohydrate metabolism, one of Macleod’s longtime research interests.

Life’s Work

Frederick G. Banting, a Canadian surgeon with private practice in London, Ontario, had an idea for a possible treatment for diabetes. An article in medical literature suggested a link between the pancreas gland and the onset of the disease. His idea was to surgically interfere with the pancreas of laboratory dogs and study the effects on the animals’ metabolism of sugar. Because his experience had largely been as a clinician, Banting sought a mentor and laboratory space in which to carry out his research and sought out Macleod’s counsel as a respected scientist.

Macleod was not thoroughly convinced that Banting was on the right track but evidently thought enough of the concept to give the younger man some degree of support. He provided laboratory space, an assistant, and ten dogs as experimental animals. The procedure Banting proposed was to surgically interfere with the functioning of a dog’s pancreas and isolate the precise pancreatic function that induced diabetes. Macleod offered Banting one of two recent graduates to serve as an assistant. The choice was actually made by the candidates, according to legend, on the basis of a coin toss. The assistant was to be Charles H. Best, a recent graduate in physiology and chemistry.

Macleod left Canada for a summer in Scotland, leaving the two junior workers to carry on the research. Evidently, Macleod was impressed by what he found on his return to Canada. After evaluating the success of what Banting and Best had discovered, Macleod abandoned his own research and applied all the resources of his laboratory to the new work. In addition, Macleod invited another researcher to join the team, and James Bertram Collip, a biochemist on leave from the University of Alberta, arrived in December 1921.

Their first patient was a fourteen-year-old boy named Leonard Thompson, whose physician expected him to live only a few weeks more. The initial treatment of Thompson with insulin extract on January 11, 1922, proved inconclusive. Apparently, there were impurities in the extract. More purified preparations were made available, and Thompson underwent a series of treatments. His condition soon improved. He gained weight and began to act like a healthy boy his age. (Thompson died eleven years later from complications following a motorcycle accident.) News of the discovery spread in the scientific literature as well as in newspapers and popular magazines. Diabetics who formerly faced certain death from the disease clamored for treatment with this new, miraculous cure.

More patients were successfully treated with the revolutionary medication. The production of insulin improved, and soon commercial quantities were available. It became obvious that the injections of insulin did not cure diabetes, but rather controlled it. With daily injections of the substance, diabetic patients were able to live a reasonably active lifestyle and enjoy a more or less average life span. The discovery of insulin and its application to what had previously been a fatal disease seemed miraculous. The crowning recognition for the discovery of insulin came in 1923 when Macleod and Banting were nominated for the Nobel Prize in Physiology or Medicine. The nominating committee recommended a joint award based on the respective roles of the two scientists. The committee noted that whereas Banting had the basic idea and the initiative to carry out the research, Macleod had been the adviser and senior leader of the project.

Banting was furious at having to share the prize with Macleod. According to Banting, Macleod’s only contribution was to provide laboratory space. He wrote that his young assistant, Charles Best, was more deserving of a share. Accordingly, Banting shared his prize money with Best. In similar fashion, Macleod elected to share his portion of the prize money with Collip, the chemist.

The research team soon disbanded. Macleod was made a fellow of the Royal Society and received honorary degrees from the University of Toronto, Case Western Reserve, and other universities. After returning to Scotland in 1928, he was appointed Regius Professor of Physiology at Aberdeen University. He retired from active laboratory research because of his struggles with arthritis and died in Aberdeen on March 16, 1935.

Impact

In a world grown accustomed to antibiotics and immunization, it may be difficult to imagine the impact of the discovery of insulin. Diabetes has been recognized since antiquity, and up until the time of Macleod and his colleagues, near starvation of the diabetic was a common approach, as was forcing fluids or withholding fluids. In almost all cases, however, a person who was diabetic ultimately died from the disease.

The global impact of diabetes is severe: as of the year 2000, according to the World Health Organization, an estimated 171 million people worldwide had the disease, a number expected to more than double by 2030. In the first five years of the twenty-first century, according to the Centers for Disease Control and Prevention, there were an estimated 14.5 million diagnosed cases in the United States (21 million total) and millions of cases in Canada.

The work that came out of Macleod’s laboratory paved the way for more diabetes research. Later workers recognized three forms of diabetes: type 1 (insulin dependent), sometimes called juvenile-onset diabetes because it most often appears during childhood, adolescence, or young adulthood; type 2, often called adult-onset diabetes, in which the disease symptoms often can be controlled by diet and exercise alone but also, in many cases, with insulin; and secondary diabetes, resulting from diseases that destroy the pancreas gland or otherwise interfere with its functioning. The results of the work of Macleod and colleagues have given hope to the millions of diabetics in the world that theirs was a chronic but treatable disease, not a death sentence.

Bibliography

Bliss, Michael. The Discovery of Insulin. Toronto: U of Toronto P, 2000. Print. Discusses the history of diabetes and the search for a cure, the medical research that culminated in the discovery of insulin by Macleod and his colleagues, and the personal and professional conflicts among members of the research team.

Howard, John M., and Walter Hess. History of the Pancreas: Mysteries of the Hidden Organ. New York: Kluwer Academic, 2002. Print. Written by two academic pancreatic surgeons, this history of studies of the pancreas covering antiquity to contemporary times includes information about Macleod and the discovery of insulin.

Shampo, Marc A., and Robert A. Kyle. “John J. R. Macleod: Nobel Prize for Discovery of Insulin.” Mayo Clinic Proceedings 81.8 (Aug. 2006): 1006. Print. Discusses the life and work of Macleod, focusing on his participation in and support of research that culminated in the discovery of insulin as a diabetes treatment.