Dr. Frederick Banting and the Discovery of Insulin

2023 is the 100^th anniversary of the award of the Nobel Prize in Physiology and Medicine to the man responsible for the discovery of insulin, which Canadians voted the greatest Canadian invention ever, ahead of the telephone and light bulb.                                   

Flash back to an afternoon in the mid-1930s. Several medical students are eating lunch in the University of Western Ontario Medical School cafeteria, one of them my father, a young Jewish-American medical student who had been  denied entry into American medical schools. He was demonstrating the art of catching houseflies by hand to his Canadian classmates, a skill he learned growing up in Brownsville, an impoverished section of Brooklyn, where the combination of horse-cart street peddlers and open windows in the pre-air conditioning era made flies an omnipresent nuisance in the tenements.

The Canadian students were amazed by his quick hands (the trick, he explained, was cupping your hand in front of the fly rather than attacking from behind). He was appointed goalie on their medical school hockey team, but the experiment of the American goalie with no hockey experience was short-lived because he couldn’t skate, and his quick hands were no match for the slick puck skills of semiprofessional opponents from Toronto and Montreal.  

The young men were enjoying the flycatching exhibition when a distinguished middle-aged man about to eat lunch stopped by their table briefly to compliment my dad on his dexterity. The Canadian students, star-struck, told my dad, who was unaware, that he had been singled out by the world’s then-most famous Canadian. 

The impressed gentleman was Sir Frederick Banting,  discoverer of insulin, Nobel Prize winner, and a 1923 cover subject for Time. In a 2004 nationwide poll, he was voted fourth greatest Canadian of all-time behind Tommy Douglas (father of Canadian Medicare), Terry Fox (athlete-activist) and Pierre Trudeau (prime minister and father of Justin).                                                                  

The story began in 1921 in a small, grimy laboratory at the University of Toronto. Back then, diabetes was universally fatal and worse still, the doomed patients were usually  children or young adults. The only known treatment known for diabetes was starvation,  providing patients only several hundred calories daily. Death was usually quick and particularly miserable, as patients became perpetually hungry, thirsty, and emaciated before slipping into fatal coma. Researchers from all over the world, realizing the problem had to do with a poorly functioning or nonfunctioning pancreas, sought to isolate a hormone  from the gland that might reverse the process.

Enter Frederick Banting, an unpolished boy from rural Ontario, who graduated from medical school at the University of Toronto and became a surgeon after serving in World War I. Neither his academic record nor his early surgical career distinguished him, but he was clever, curious, and interested in diabetes.  With career prospects dim, Banting left his modest surgical practice in London, Ontario, to present his ideas for isolating the pancreatic hormone to Professor J.J. R. Macleod, one of North America’s preeminent professors of physiology, in Toronto.                                                                              

When the 1921 academic year ended, Macleod planned to travel to his native Scotland to escape the hot Toronto summer. Unimpressed by Banting, he nevertheless agreed to let the itinerant surgeon have an old laboratory, unused for ten years, during his three-month absence. Banting cleaned the lab, received several dogs to operate on, and Macleod provided two students as assistants.  Since there was only funding for one, they flipped a coin to determine who would work with Banting. Charles Best, a brilliant student from Maine, won and began the project.

Through three months of stifling heat in the lab, Banting and Best achieved the unprecedented: isolating pancreatic extract, known as insulin, from dogs without having the extract destroyed by pancreatic digestive enzymes. Almost immediately, this extract controlled the blood sugars of dogs rendered diabetic by removing their pancreases. One dog, Marjorie, lived 70 days -the longest ever of any dog without a pancreas.                                                                      

A surprised MacLeod returned from Scotland realizing Banting was on to something. He allowed Banting and Best to continue their research and assigned J.B. Collip, a talented biochemist, to work with them to purify insulin. The result was one of the great discoveries in medical history.  

In December 1921, the first patient to receive insulin extract was a 14-year old boy named Leonard Thompson. He weighed 65 pounds, and was in semi-coma. The hospital staff considered him doomed. Despite early problems from the insulin injections, Thompson survived and proceeded to live a relatively normal life until he died from complications of a motorcycle accident 14 years later.                                                                                                       

The most dramatic case was that of Elizabeth Hughes. As an American, she was not on the early list of patients who could receive the scarce supply of insulin. But she was the 14-year old daughter of  Charles Evans Hughes, Secretary of State and later Supreme Court Chief Justice. Arrangements were made, and Elizabeth, weighing 60 pounds, was rushed to Toronto - days, perhaps only hours, from death.  Insulin immediately saved her life. She went on to a distinguished career at Barnard. She married, had three children and founded the Supreme Court Historical Society named in her honor, before she died at age 74. Her story is one of the true miracles of 20^th century medicine.                                                                                        

When Banting was awarded the 1923 Nobel Prize, his co-recipient was not Best, but Macleod. Relations between Banting and Macleod were never cordial, but when Macleod was selected and Best was not, Banting was furious. For a time, he considered refusing the award. Finally, he announced he would share his prize money with Best, who he noted was the actual co-discoverer of insulin. Macleod retaliated by giving one-half of his share of the money to Collip, in a feud that made international news. Years later, the official history of the Nobel Committee acknowledged that Charles Best should have received a share of the prize.                                              

What happened to the protagonists in this century-old story? Frederick Banting was knighted in 1934, and was doing research on aviation medicine for the Canadian government during World War II when he was killed in an airplane crash on a secret flight to England in 1941. A disgruntled J.J.R. Macleod left the University of Toronto five years after his Nobel Prize to return to Scotland. Hailed as a hero, he was personally embittered over the Nobel controversy and died in 1935.  His place as Professor of Physiology at the University of Toronto was taken by Charles Best. Although the Nobel eluded him, Best became a renowned academic and wrote a classic physiology textbook before he died in 1978.

The discovery of insulin turned two pharmaceutical companies into worldwide giants. Forsaking huge profits for themselves, Banting and Best gave the patent for insulin discovery to the University of Toronto and Connaught Labs, with the stipulation insulin be made available as cheaply as possible to everyone, including the poor. Connaught Labs became a major player in Canada’s pharmaceutical industry, and the company was instrumental in the development of vaccines for polio and childhood diseases. 

Demand for insulin was so great that it exceeded Connaught’s production capabilities. The company contracted with Eli Lilly in Indianapolis, which obtained some of its animal pancreases from the Chicago stockyards. Insulin helped Lilly become one of the world’s largest pharmaceutical concerns, and provided a fertile area of research, helping establish endocrinology as an important medical specialty.         

Since the discovery of insulin in that sweltering Toronto laboratory, it's amazing how far medicine has advanced in the last century and how diabetes care has changed. Sophisticated drugs that obviate the need for insulin are available for many patients, while insulin for those who need it is genetically engineered. Some patients with diabetes can be treated with pancreatic transplantation; others can be fitted with an artificial, bionic pancreas - an automated, wearable insulin pump programmed to control glucose levels. Besides this, a revolution in nanotechnology designed to deliver insulin is becoming a reality.                                  

All these developments are ultimately the result of the efforts of that extraordinary man, Sir Frederick Banting, who took a gracious moment one afternoon long ago to admire my father’s ability to catch flies.