Insulin: A Canadian Medical Miracle Of The 20th Century

This discovery of insulin in 1921 has saved millions of lives around the world.  Life and hope was given to diabetics and this is ongoing today.  Insulin is a hormone secreted by the beta cells of the islets of Langerhans, specific groups of cells in the pancreas. A shortage of insulin in the body results in diabetes. The word insulin comes from the Latin word for island. Canadians, Frederick Grant Banting and Charles Herbert Best were the first to obtain insulin, from extracts of pancreas, a preparation of insulin, which could serve to replace a deficiency of the hormone in the human body.

In the days before insulin, diabetes was a slow but sure death sentence that typically struck children and adults under 30. Victims had constant thirst and voracious appetites, but wasted away when they could not process their food. Hospital diabetic wards were full of living skeletons. In time, all of these patients died.

At the time of the discovery of insulin, the only way to manage diabetes was through a diet low in carbohydrate and sugar, and high in fat and protein. Instead of dying shortly after diagnosis, this diet allowed diabetics to live but only for a few years at most. Victims eventually fell into a coma and died, frequently within months of a diagnosis.

Diabetes Mellitus is a medical condition known to physicians for thousands of years. References to this disease can be found in many ancient writings. Diabetes was given its name by the Greeks after their word for siphon. The term “Mellitus,” Latin for honey or sweet, was added after doctors realized the urine of a diabetic person was loaded with sugar. A taste test was the original means of diagnosing diabetes mellitus. It was often called the sugar disease or later sugar diabetes. However, the cause of diabetes remained a mystery until recent times. In the early 1920s, researchers strongly suspected that diabetes was caused by a malfunction in the digestive system related to the pancreas gland, a small organ that sits behind the stomach more on the left side of the body.

Significant breakthroughs have only surfaced in the last century. In 1889 a German scientist called Paul Langerhans discovered that damage to specific cells caused diabetes to develop, hence these cells became known as the Islets of Langerhans. Two Austrians Von Mering and Minkowski further supported this. They determined that on removal of the pancreas diabetes occurred. As with most major scientific discoveries, the groundwork for the discovery of insulin had been laid by several others (covered later in the website) before the Canadian researchers isolated it.

Insulin was discovered at the University of Toronto, Canada, in the summer of 1921. Frederick Grant Banting and Charles Herbert Best discovered it. Starting with Fred Banting’s orginal idea a search for a cure for diabetes began in the late spring of 1921; insulin was discovered 4 months later. During the discovery phase, Dr. Banting and Charles Best worked alone in the lab to produce and test the drug on dogs. Dr. Bertram Collip and John J. R. MacLeod joined the team when insulin tests worked and the purification stage started.

His idea gripped young Fred Banting’s mind in the fall of 1920. But we must go back to the time when Banting was born on a farm in Essa Township, just outside the small town of Alliston, Ontario on Nov. 14, 1891. The farm is not far from Toronto. On the farm he learned a lot about animals, hard work and good family values.  Fred Banting was always curious to find out why some of these creatures died.  Some of his first investigations were done in the Banting barn. At age 14, he watched a close friend and neighbour, waste away and die as a result of the dreaded diabetes..

Fred graduated from medical school in 1917 and went off to the Great War. He was repairing and dressing wounds in France as a battalion medical officer. The field station conditions were horrid. At the height of a battle, as he tended to the injured Banting’s right forearm was hit by shrapnel from a shell. He ignored orders to leave the area and seek medical help and continued to help the wounded. When he was eventually evacuated behind the front lines it was almost too late. His wound was bad and was not healing properly. Because the doctors suggested amputation the stubborn Banting took over the corrective medicine. His arm was saved. He was awarded the Military Cross for courage under fire.

He returned to Canada a war hero and served as an intern at Children’s Hospital (Sick Kids). He specialized in orthopedics. By the fall of 1920, Banting was a struggling young physician trying to build a practice in London, Ontario. He was completely broke and owed money to his father. Business was so slow that he took a job at London’s Western University as a demonstrator in surgery and anatomy. The position required him to give a lecture on the pancreas on Nov. 1, 1920. It was a fateful assignment. Banting’s research for the lecture covered the fuzzy area of how the pancreas released an internal secretion that was key to preventing diabetes mellitus.

After writing up the lecture, he settled in to read a freshly published article called The Relation of the Islets of Langerhans to Diabetes by Dr. Moses Barron. He reported that blocked pancreatic ducts would make the pancreas shrivel, but its cell system the islets of Langerhans did not. He also noted that diabetes didn’t appear to develop unless the islets were damaged. Could the islets carry the secret of the mysterious internal secretion? The question kept Banting awake. Finally, at about 2 a.m., he got out of bed and scribbled the following words on a small sheet of notebook paper dated Oct. 31, 1920.

“Diabetus; Ligate pancreatic ducts of dogs. Keep dogs alive till acini degenerate leaving Islets; try to isolate the internal secretion of these to relieve glycosurea.” Note the spelling errors. In other words the cells that controlled the digestive juices, when tied up atrophied and died. The digestive fluid could not destroy the islets. Once Banting knew this he wrote, “Tie off the pancreatic duct of dogs. Wait six to eight weeks for degeneration. Remove residue and extract.”

The following day he discussed his idea with Dr. Miller at Western University. Miller suggested that Banting talk to J. J. R. Macleod. At the time Western did not have the capacity to conduct this type of work. Macleod was an expert on carbohydrate metabolism. At first, MacLeod was not the least bit interested in Banting’s idea. But J.J.R. Macleod, a University of Toronto professor of physiology, eventually heard the always-stubborn Banting out when he presented his idea again on Nov. 8, 1920. The following spring, MacLeod offered Banting the use of an aging unused lab located in the old medical building. This building has long since been replaced with modern facilities. Macleod included the help of two summer assistants. A coin toss decided that Charles Best, who had just completed a degree in biochemistry and physiology, would work with Banting first. He later stayed on because the work was going well.

Macleod gave them some technical direction then left for his summer vacation. Banting and Best’s experiments made dogs diabetic by removing their pancreases. Banting performed the surgery and Best measured urinary and blood sugars, as well as performing other tests. It was hard work and they had no salary. Banting sold his car and they scrounged meals wherever they could. Fred Banting got loans from his father and brothers so he could continue the work. After several false starts during that sweltering summer, the pair eventually managed to obtain an anti-diabetic pancreatic extract. They got the first positive results on July 30, 1921. In August work progressed well. They showed that removing the pancreas from dogs made them diabetic. Then they went a step further and painstakingly took fluid from healthy dogs’ Islets of Langerhans, injected it into the diabetic dogs and restored them to normalcy. They were able to keep diabetics dogs alive. One dog and lab pet Marjorie, referred to in Banting’s lab notes as Dog 33, was kept alive with pancreatic extract injections for 70 days. However, a constant supply on potent insulin was a huge problem.

On his return from vacation, Macleod realized that something great had happened while he was away. He provided guidance to Banting and Best who along with expert biochemist J.B. Collip worked feverishly in the fall of 1921 to purify insulin or isletin as they called it at the time. With the help of James Bertram Collip, they were then able to extract a reasonably pure formula of insulin.

They moved on to extract insulin from the pancreas of cattle from slaughterhouses. The idea of using the pancreas from a calf fetus was Banting’s. His father raised Shorthorn cattle and Fred often helped slaughter the Shorthorns for family food and local markets.  At this point Fred Banting was completely broke.  He was not given a salary to do this work.   His family rallied to help him and provided the much needed money to fund the research work in Toronto.

In January 1922, a diabetic teenager in a Toronto hospital named Leonard Thompson became the first documented person to receive an injection of insulin. It was the first time in recorded history that an extract of pancreas had what has been described as an undeniably “anti-diabetic” effect on a human. Thompson was observably more alert and aware, and the stunning effect was repeated on other diabetic persons. Leonard improved dramatically, and the news about insulin spread around the world like wildfire.

An insulin famine followed. The team worked furiously on the mass production of the new drug. It was patented by the discoverers and sold for a dollar. The University of Toronto immediately gave pharmaceutical companies license to produce insulin free of royalties. In early 1923, about one year after the first test injection, insulin became widely available, and saved countless lives.

For 60 years after Banting’s group isolated insulin, diabetics relied on hormone purified from animals, primarily cattle and pigs. The discoverers did not know how lucky they were. It turns out that the amino acid sequence of insulin is almost exactly the same in different animal species, so insulin from cows and pigs also works in humans.

Since insulin was discovered in 1921, it has become one of the most thoroughly studied molecules in scientific history. Much of the insulin science and delivery technology has changed since 1921. However, one thing remains constant. In Sir Frederick Banting’s own words. “Insulin is not a cure” More work still needs to be done!

The discovery of insulin in 1921 at the University of Toronto quickly made celebrated heroes of Banting and Best and later Collip and Macleod. Hundreds of stories about diabetics were near resurrections. Many who had picked their final resting place lived on for many years. It was no longer a question how quickly will they die. Doctors could fight the ghastly disease that had stymied researchers for generations. Diabetic persons could look forward to a near normal quality of life.

Relations within the discovery team were far from perfect. Banting thought Macleod stole all the glory. After all Macleod was not in the country during the hot summer of 1921 when Banting and Best isolated insulin. Banting had to do the work without any compensation. Macleod doubted that Banting, who was not an experienced scientist, could obtain positive results. He had to force his way past Macleod to get his idea off the ground. They were never on good terms. Collip was close to Macleod so his relationship with Banting was strained for some time.  But in later years, Banting and Collip developed a close bond. The discovery of insulin is a remarkable story of youthful idealism, dueling egos and miraculous recoveries. It was a world-class achievement in this century that sent ripples around the globe. It put Canada on the medical map.

The fame of the discoverers rose in meteoric fashion. On February 26, 1923, when the Nobel Prize for medicine and physiology was jointly awarded to Banting and Macleod. It was the first for a Canadian. But the celebration was marred by egos and infighting as Banting, furious with how much credit Macleod had received, announced that he would share his half of the prize with Best. A few days after Banting’s announcement, Macleod split his honours with Collip. But the work of Banting and Best, along with that of Macleod and Collip, carries on in the children and grandchildren of those first insulin recipients, and in everyone who lives today because it was discovered.

Banting was honoured in 1930 when dedicated to him was the Banting Institute by the University of Toronto. From this new institute he carried on his research in medicine and in 1934 was knighted. The Sir Frederick Banting Foundation was formed to fund start up research and still survives today. Other awards and historic recognition for all the discoverers followed.

Fred Banting died in the crash of a warplane in Newfoundland.  He was on his way to England to do research work intended to shorten WWII. He died on February 21, 1941