The Prize:
The Nobel Prize in Medicine or Physiology in 1923 to Frederick G. Banting and John J. R. Macleod “for the discovery of insulin.”
The Science:
Diabetes is a disease affecting over 171 million people worldwide, and this number is expected to double by 2030. It was originally described by the Greeks in the first century CE and named for the excessive urination that untreated diabetics suffer from. Prognosis for sufferers has changed a lot since the discovery of insulin. Those with access to this life-saving hormonal treatment, can manage their diabetes and lead long, full lives.
Diabetes is the result of elevated blood sugar levels. The disease can be divided into two subtypes: I and II. Type I diabetes is normally diagnosed in childhood or early adulthood. It’s caused by an auto-immune reaction that destroys the insulin-producing cells of the pancreas. Without the hormone insulin, the body is unable to take up sugar from the blood after a meal. Instead, sugar builds within the bloodstream unused by the cells that need its energy. Eventually, the sugar “spills over” into the urine, making urine sweet-tasting—one of the historical methods for diagnosis. Left untreated, these elevated sugar levels can cause damage to the heart, eyes, kidneys, and nerves.
Type II diabetes is the result of low insulin production or a reduced cellular response to insulin. This is the most common form of diabetes in North America. It normally develops slowly with age and is correlated with obesity and a sedentary lifestyle. Type II diabetes can usually be managed with lifestyle changes and medication if caught in the early “pre-diabetes” stage of slightly elevated blood sugar levels.
In 1889, Joseph von Mering and Oskar Minkowski discovered that when dogs have their pancreas removed, they develop diabetes symptoms similar to those that humans experience. At the beginning of the 20th century, it was proposed that the difference between healthy and diabetic individuals lay in a single chemical called insulin, for the Latin word insula which means “island,” because it is produced in the b-cell islets of the pancreas.
Prognosis for Type I diabetes’ patients in the early 1900s was a slow, painful death that could only be staved off for a short time post-diagnosis by adherence to a rigorous low-sugar diet. Hospital wards of the time were filled with diabetic sufferers slowly wasting away to their deaths.
Despite the knowledge that insulin could be found in the pancreas, treating diabetic patients with extracts of this tissue had no effect on the disease. This is because the pancreas also makes important digestive enzymes that were breaking down the pancreatic stores of insulin before it was given to patients.
A major leap forward came when Frederick Banting read the work of Moses Barron. Barron had shown that tying the pancreatic duct that delivers the digestive enzymes to the intestine can protect the insulin-producing b-cell islets, and therefore the insulin they store, from digestion. Banting hypothesized that if the pancreatic duct is tied and enough time passes to allow the amount of pancreatic enzymes to drop, insulin could be successfully isolated from healthy animal pancreases for therapeutic use.
Banting, then a doctor and lecturer at the University of Western Ontario, was given permission by a senior faculty member at the University of Toronto, J.J.R. Macleod, to pursue his idea at U of T in 1921. Macleod gave Banting lab space to conduct his work, some technical advice, and the aid of a recent biochemistry graduate, Charles Best. Macleod then left for a summer-long vacation.
That summer, Banting and Best were able to create diabetic test dogs by removing their pancreases, but took their work one step further: they injected pancreas islet juices into test dogs that amazingly relieved the dogs’ diabetic symptoms. The first dog who survived pancreas removal was at the brink of death when suddenly, after an injection of the pancreatic islet isolate, raised its head and started wagging its tail. The injections reduced blood sugar levels in the test dogs and kept them alive.
When Macleod returned from vacation to these miraculous results, he put the biochemist J.P. Collip (on sabbatical from the University of Alberta) on the project to help Banting and Best optimize insulin purification from cow pancreas. Macleod also found the experimental methods of Banting and Best questionable, and made suggestions for repeating their experiments with better lab equipment and added experimental controls.
By January 1922, armed with a pure and abundant source of insulin isolated from cows, the first diabetic patient received an injection of life-saving insulin. Teenager Leonard Thompson’s health improved dramatically almost right away. Similar results were seen in more and more patients. Elizabeth Hughes, the 14-year-old daughter of the American Secretary of State, weighed only 45 lbs before receiving her first dose of insulin. Within months she gained a healthy weight and lived to the age of 73.
To make insulin available cheaply and quickly worldwide, Banting and Best made a noble gesture and sold their rights to insulin to U of T for one dollar. U of T allowed pharmaceutical companies to produce insulin without royalty payments, making insulin widely available within the year.
In 1923, Macleod and Banting were jointly awarded the Nobel—after only their first nomination and only a year and a half after the discovery. This also marked the first Canadian Nobel Prize, putting Canadian research on the map and Canadian researchers into the spotlight.
Today, insulin still saves lives, but diabetes remains without a cure (insulin is only a therapeutic). Diabetics must be vigilant in monitoring their blood sugar levels, eating a balanced diet, and exercising.
What you may not know:
When Banting discovered that he had co-won the Nobel prize with Macleod, he was furious and planned to refuse the award. Banting felt that the summer of hard work that he and Best had shared working on Banting’s hypothesis was not at all aided by Macleod. While Macleod was on vacation, they worked in a swelteringly hot lab, often sleeping and eating there in order to work longer hours. Banting even resorted to selling his car to pay for the work.
However, supporters of Macleod suggest that the poor experimental methods of Banting and Best required his advice and supervision and that Macleod’s connections are what allowed the discovery of insulin to gain widespread recognition so quickly.
Banting changed his mind about refusing the Nobel Prize and instead chose to share his portion of the award with Best. Shortly afterwards, Macleod announced that he would share his portion with Collip. The relationship between Macleod and Banting never recovered, eventually reducing itself to petty politics within the U of T Physiology Department.
The controversy over the awardees does not end at U of T: another scientist, Nicolae Paulesco, working in Romania, has credible claims to discovering insulin under another name, “pancreatine,” a year before the Toronto group.
Today you can find monuments to the discovery of insulin on campus: the Banting and Best Institutes on College Street, and the Macleod auditorium in the Medical Sciences Building. Nov. 14, Banting’s birthday, is honoured around the world as World Diabetes Day.
