The Amazing Story of the Discovery of Insulin by Banting and Best | The History of Nobel Prize for the Discovery of Insulin
Prologue
The name diabetes comes from the ancient Greek phrase meaning "to flow," which refers to one of its most common symptoms. Thomas Willis, an English physician who lived from 1625 to 75 in the 17th century, gave diabetes the much more memorable moniker "the pissing evil." However, frequent toilet trips were the least of a patient's concerns!
Diabetes was a death sentence prior to the discovery of insulin in 1921. The most common treatment was to put patients with "sweet urine" on very strict diets with minimal carbohydrates. This bought them a few more years but couldn’t save them. In some cases, patients died from starvation as a result of strict diets. Therefore, the discovery of insulin in Toronto by Canadian physician Sir Frederick Banting and his American medical assistant Dr. Charles Best completely changed the way the condition was treated, probably saving tens of thousands of lives.
Although insulin has been called "arguably the greatest medical miracle of this century," few are aware of the epic tale of its discovery which involves luck, friendship, animosity, ego, injustice, and the fragile nature of human endeavor. Today, I’m going to tell you that story!
What is diabetes?
Glucose (sugar) is the main source of energy for our body. The body breaks down the food (carbohydrate) we eat into glucose. The glucose is then absorbed in the blood that carries it to all the cells of our body to use it to produce energy. The pancreas produces the hormone insulin, which facilitates the body's cells' absorption of glucose for use in energy production. If your body doesn’t make enough insulin or doesn’t use insulin properly, glucose stays in your blood and doesn’t reach your cells, causing high blood sugar (hyperglycemia). This is called diabetes. Over time, having consistently high blood glucose can cause health problems, such as heart, kidney, nerves, and eye damage.
What are the 3 main types of diabetes?
Type 1 diabetes
Type 1 diabetes is a chronic autoimmune disease in which your immune system targets and kills the insulin-producing cells in your pancreas for unclear reasons. Type 1 diabetes comprises 10% of patients with diabetes. Although it can appear at any age, children and young people are typically diagnosed with it.
Type 2 diabetes
In Type 2 diabetes, your body doesn’t make enough insulin, and/or your body’s cells don’t respond normally to the insulin (also known as insulin resistance). It is the most common type of diabetes. Although it primarily affects adults, children can also have it. If you have a family history of Type 2 diabetes and risk factors including being overweight or obese, you are more likely to have the condition. Understanding the risk factors and adopting healthy lifestyle choices, like reducing or avoiding weight gain, can help postpone or prevent Type 2 diabetes.
Gestational diabetes
Some people develop this type during pregnancy. After pregnancy, gestational diabetes normally disappears. On the other hand, having gestational diabetes increases your chance of getting Type 2 diabetes in the future.
The race to discover insulin kicks off in 1770
The race to discover insulin began in the 1770s when Dr. Matthew Hobson, an English physician, demonstrated that sugar was the cause of "sweet urine," which "preceded and accompanied by sugar in the blood."
In 1889, two German researchers Oscar Minkowski and Joseph von Mering, discovered that dogs that had their pancreas gland removed experienced diabetes symptoms and eventually passed away. This gave rise to the theory that some "pancreatic substance" could control diabetes.
In 1910, British physiologist Sir Edward Albert Sharpey-Schafer suggested only one chemical was missing from the pancreas in people with diabetes. He decided to name this chemical insulin after the Latin word “insula,” meaning “island” since it was secreted from the islets of Langerhans, which are groups of specialized cells in the pancreas.
In 1889, Oscar Minkowski and Joseph von Mering discovered that diabetes is a pancreatic disease
In 1910, Sir Edward Albert Sharpey-Schafer coined the term “Insulin”
Georg Zuelzer starts experiments in Germany in 1908 but ends tragically
In 1908, German doctor Georg Zuelzer showed that pancreatic extracts could reduce the sugars in the urine of diabetic patients. Calling his preparation “Acomatol”, Zuelzer filed a patent on it. However, he struggled with impurities in his extract that caused fever, shivering, and vomiting in patients. When he used alcohol to purify the extract, he observed some new and serious side effects - test animals became convulsive and sometimes slipped into a coma. So, he thought his extract was still not pure enough for clinical usage. Little did he realize that the new side effects of convulsion and coma were not due to impurities, but rather because his preparation was now so pure, that it was lowering the blood sugar level dramatically thereby plunging the animals into hypoglycaemic shock. So, he had a potent version of insulin in his hand, but he did not realize it and hence did not release it to the world thereby missing the Nobel prize.
By 1914, when things started looking hopeful and Zuelzer had the support of Swiss pharmaceutical Hoffman La Roche, the First World War broke out, and Zuelzer’s research was brought to an abrupt halt from which it never recovered.
In 1914, Georg Zuelzer was on the verge of discovering insulin which was abandoned due to World War I
Frederick Banting and John Macleod starts experiments in Canada in 1920
The son of a Canadian farmer, Frederick Grant Banting graduated in medicine from the University of Toronto in 1916. He enlisted in the Canadian Army shortly after, serving in World War I as a medical officer. After the war, he established a practice in London (a Canadian city), Ontario, which is roughly 150 kilometers west of Toronto. Due to the practice's poor performance, Banting was forced to teach anatomy and surgery to medical students as a demonstrator at Western Ontario University in London (the Canadian city).
One day, while reading a paper on the subject in 1920, Banting had an inspiration. He realized that as soon as the islets of Langerhans in the pancreas were secreting insulin, the pancreas' digestive juice was destroying it before it could be isolated. If he could stop the pancreas juices from working, but keep the islets of Langerhans going, he should be able to find the “stuff!” John J.R. Macleod, the recently appointed head of the Department of Physiology, initially laughed at this idea when he presented it to him. Banting persuaded him till Macleod gave him money and gave him ten experimental dogs and a well-equipped lab.
Frederick Banting
John Macleod
Best joins Banting via a “coin flip” in 1921
Although Banting had the idea for the work, Macleod was worried that he didn’t have the specialized surgical abilities necessary to complete it. So, before leaving for vacation to his home country of Scotland in May 1921, Macleod assigned two undergraduates Clark Noble and Charles Best to work as Banting's lab assistants that summer. Since Banting only needed one lab helper, Noble and Best flipped a coin and Best was chosen!
This “historic collaboration” began with some personality clashes but they had the first definitive results in August 1921 after extracting a "thick brown muck" looking substance from the islets of Langerhans of healthy dogs and injecting it into diabetic dogs to lower their abnormally high blood sugar levels. After returning from vacation, Macleod urged them to keep experimenting since the results were not consistent due to impurities in the insulin extract. Sometimes injecting the pancreatic extract even resulted in toxic reactions like eruption of abscesses at the injection site.
Charles Best and Frederick Banting with the first experimental dog to receive an insulin injection
Banting and Best’s laboratory arranged by Macleod where insulin was discovered
Banting and Best present findings disastrously and Macleod rescues in 1921
Banting and Best presented their findings at the American Physiological Society conference held at Yale University on December 30, 1921. Due to his nervousness and lack of experience in presenting, Banting delivered the paper poorly, and the audience was very critical of the results. As the session's chair, Macleod entered the conversation to try and save Banting from the harsh criticism. Following this disaster, Banting started to believe that Macleod had taken the credit away from him and Best, and their relationship started to suffer.
Best and Banting
Nicolae Paulescu starts experiments in Romania but gets shunned in 1921
Meanwhile, during the summer of 1921, just as Banting and Best were commencing on their own research, a Romanian scientist called Nicolae Paulescu reported comparable findings in a European scientific publication. But Paulescu’s scientific work was eclipsed by the horrific disclosure of his anti-Semitic views and the part that he played in initiating the Holocaust in Romania.
Nicolae Paulescu
James Collip joins Banting and Best in 1922
Macleod assigned a Canadian biochemist James Bertram Collip to the group to help with the purification. Collip cracked the method of using alcohol to purify the extract to avoid toxic reactions in the patients. Additionally, he realized that while insulin may save lives, it could also kill them. Collip's pure preparation caused healthy animals to become convulsive, comatose, and ultimately die when he injected it into them. This was because Collip’s preparation was now so pure, that it was lowering the blood sugar level dramatically thereby plunging the animals into hypoglycaemic shock just like Georg Zuelzer in 1908. In such cases, he proposed to remedy it with some quick-acting sugar.
James Collip
First human clinical application in 1922
January 11, 1922 is a day to be remembered because on that day a boy of 14 named Leonard Thompson who was admitted to Toronto Hospital and about to die due to Type 1 diabetes received the first injection of insulin purified by Collip and within 24 hours his highly elevated blood sugar level became near normal and he escaped death. News about insulin spread like wildfire across the globe.
Leonard Thompson, the first human to receive insulin injection along with the image of Collip purifying the insulin extract
Banting and MacLeod gets Nobel Prize for Insulin in 1923
In 1923, Banting and Macleod were conferred the Nobel Prize for the discovery of insulin. Best and Collip got nothing. Banting was upset that Best had not been nominated and decided not to accept the prize. He believed that Macleod had no right to claim anything on the discovery of insulin, as this 1940 diary note makes extremely evident: “He was the most selfish man I have ever known. He sought at every possible opportunity to advance himself. If you told Macleod anything in the morning it was in print or in a lecture in his name by evening … He was unscrupulous and would steal an idea or credit for work from any possible source.”
Ironically, though, Banting might not have received the prize at all and would most likely still be a struggling general practitioner in provincial Ontario if it weren't for Macleod. A few days later, Banting declared that he and Best would divide the prize money. Under pressure, Macleod eventually said that he would give Collip a portion of his award money.
Excerpt from Outlook magazine highlighting the news of Banting and Macleod winning the Nobel Prize
The Nobel Prize diploma and medal received by Frederick Banting and John MacLeod
Best claims credit for Insulin in post-Nobel aftermath
However, despite Banting sharing his prize money, Best wasn’t happy which began to irritate Banting. In 1941, before he boarded a flight on a secret war-time mission to the UK, Banting proclaimed - “This mission is risky. If I don’t come back and they give my [Professorial] Chair to that son-of-a-bitch Best, I’ll never rest in my grave.” Tragically, his words turned out to be prophetic. His plane crashed shortly after takeoff and he unfortunately passed away. As Macleod had already passed away in 1935, Best and Collip were now the only members of the original Toronto research team that had discovered insulin. Best was also adamant that people would remember him.
Best started giving interviews and publishing papers mentioning that the pivotal moment in the story of insulin had been when Leonard Thompson was injected for the first time on January 11, 1922 with an extract made by himself and Banting. He also claimed that the crucial innovation of using alcohol to remove impurities was his idea conveniently downplaying Collip’s contribution. Collip never made a comment on these claims.
Charles Best in later life in a reconstructed lab
Mass production of insulin
In 1923, the pharmaceutical company Eli Lilly began mass production of insulin. Manufacturers created a range of slower-acting insulins in the ensuing decades, with Novo Nordisk Pharmaceuticals, Inc. launching the first one in 1936. In 1969, Dorothy Hodgkin discovered the chemical structure of porcine (derived from pork) insulin. Prior to that, she became a Nobel Laureate in 1964 for her work on structural chemistry. Using E. coli bacteria, the first synthetic, genetically modified "human" insulin was created in 1978. In 1982, Eli Lilly introduced the first synthesized human insulin for sale under the ‘Humulin’ brand.
Insulin vial produced by Connaught Laboratories, Toronto (1923)
Epilogue
So that brings us to the end of Banting and Best’s story of the discovery of insulin. The discovery of insulin is considered as one of the most important medical achievements of the 20th century. Today, more than 15 million diabetics are alive due to insulin!
This article is authored by my father Dr. Kamal Kumar Sengupta. He is a retired doctor with a five-decade-long career as an eye surgeon, a patented inventor of ophthalmic surgical instruments, and an author of ocular pharmacology textbooks. Post-retirement, he decided to invest his time in writing motivational stories from across the globe that will inspire future generations to experience the world, explore ideas, and follow their dreams. I hope you liked this article and if you did, don’t forget to let us know in the comments below!
All images in the article are royalty-free images from jstor.org and fisher.library.utoronto.ca used for visualization purposes only. We hold no copyright on the images.
Stamp commemorating the discovery of insulin © Canada Post Corporation, 1971
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