Frederick Banting
(November 14, 1891 - February 21, 1941)
Born in Canada
Year of Discovery: 1922
Discovered the First True Miracle Drug - Insulin for Diabetes!

In the spring of 1921, Frederick Banting moved into a 7-foot by 9-foot flat in Toronto, with little more than an idea. Against the advice of his girlfriend, he left behind a struggling medical practice to pursue research at the University of Toronto - though he had absolutely no research background nor expertise. However, he was certain he had an idea that could change diabetes treatment. And, he had motivation. As a youngster, he’d watched his 14-year old friend, Jane, wither away and die from diabetes. This event shook him terribly and stayed with him as a motivator. His persistence paid off and his research idea proved to be true, leading to the discovery of insulin, the first true miracle drug. Diabetes is a disease that restricts the body’s ability to produce or to use insulin. Insulin is produced in the pancreas of healthy individuals and is critical to the regulation of blood sugar (glucose specifically) levels. In Banting's day, no one had ever heard of insulin or knew where it came from or what it did. Banting’s hypothesis was that a specific part of the pancreas produced a substance that could treat diabetes.

Banting began working in the laboratory of J.J.R. Macleod at the University of Toronto. Macleod provided the laboratory despite his skepticism of Banting’s theory. Despite everyone’s lack of belief, he set out to test his idea of deriving a secretion from a particular area of the pancreas, the Islets of Langerhans. He believed if he destroyed the rest of the pancreas, he could isolate the key substance. Banting and his assistant, Charles Best, began operating on 10 dogs. Things didn’t start out well, as seven of the dogs died in the first two weeks. Undeterred, he sold his car to fund the purchase of additional dogs. He was now “all in” and determined to beat the disease. He removed the pancreases of some of the dogs, inducing diabetes. Then, once he extracted the secretions from the dogs with altered pancreases, he was ready to test his theory. He injected the extract into a collie and waited. The results were stunning, although temporary. Banting and Best coined the term “isletin” for their extract. Excited, they added a chemist to their team and began producing more “isletin” so they could perform larger trials. The University at this point renamed it “insulin”. Banting now turned his attention toward human testing. But first, they tested it on themselves to convince themselves of its safety. In January of 1922, they tested their solution on their first human patient – a 14 year old like his childhood friend. The young boy showed immediate improvement – further testing confirmed its effectiveness, and diabetes finally had a life-saving treatment. Building on this success, Banting reached back into his childhood once again, and used his farm upbringing to switch his studies to cattle, which were readily available in great quantities. This allowed for mass production of insulin, resulting in millions of lives saved and countless lives enhanced.

When World War II broke out, Banting went to work with the Canadian Army Medical Corps. He wanted to serve on the frontlines, but Canadian officials denied his request, believing his skills were needed more on the research front. On a secret mission, while flying to England, he went down in a plane crash over Newfoundland. In a last act of service, he managed to wrap the wounds of the injured pilot before succumbing to his own injuries. His brilliant career as a lifesaving scientist ended all too soon at the age of 49.

Lives Saved:  Over 200,000,000

Read His Feature Chapter in the Book

Book Excerpts
Pre-Insulin Treatments Offered Little Hope
By the time Banting read the diabetes article on that Halloween night, the two primary treatments for diabetes were opium to make the patient oblivious to the pain and the infamous "Allen diet." The diet called for starving patients until their urine contained no sugar, then gradually reintroducing food until the ideal amount of calories to sustain the sugarless state was found. Victims often lived on rations of 400 to 600 calories a day (today you can get that in a single large order of fries from McDonalds), becoming so weak they couldn't leave their beds, so desperate for food they stole birdseed from the family canary. Years later, when pictures of World War II concentration camp survivors circled the globe, doctors were reminded of those early diabetic patients. The estimated lifespan for someone who developed type one diabetes was 12-18 months without the Allen diet, four or five years with it. But the end was always the same - death.

The Breakthrough
Twelve hours after Banting and Best gave this new extract to a diabetic collie so weak from its diabetes it could barely stand, the dog was prancing around the lab. They'd done the impossible: created an extract that reduced blood sugar! It didn't have a name, and it would be another 40 years before anyone identified the chemical structure, but Banting and Best had seen firsthand the life-giving benefits of insulin, the hormone secreted by the islets of Langerhans, the chemical every living animal needs to unlock cells and allow the energy of life - sugar - in.


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Campbell knows all about diabetes but cannot treat it; Banting knows nothing about diabetes but can treat it.
                                                           -D.E. Robertson, countering the complaints about Banting's slim research qualifications 

Credit should be apportioned 80 percent to Banting, 10 percent to Best and 5 percent each to Collip and J.J.R. Macleod.
                                                  -Bert Collip (co-creator of insulin), commenting on colleagues who argued that since Banting wasn't a diabetes expert he shouldn't get much credit

Frederick Banting and Charles Best - the beginnings of the insulin team

Key Insight
Frederick Banting had two key insights that contributed to the discovery of insulin. First, he hypothesized that manipulating the pancreas to isolate the islets of Langerhans might produce a keysubstance. His first method of isolating it by tying off the ducts to make the pancreas atrophy was only marginally successful. He then found a way to extract insulin by adding a chemical.
His second innovation has been largely overlooked. Using his farm background, he reasoned that fetal cow pancreases would produce insulin. This discovery allowed for an unlimited supply of insulin to be obtained, which meant it could finally be worked on chemically, and purified.

Insulin Bottle - 1923 Image: Univ. of Toronto

The impetus for this insight came from reading a medical article and might have been aided by being new to the subject. The second insight might be classified as a cross field analogy. He brought his knowledge of farm animals into his laboratory.

Frederick Banting's Inspiration
Frederick Banting was first introduced to diabetes during his fourth year of medical school. He attended a lecture by the leading diabetologist Frederick Allen, MD. He learned about diabetes and its only treatment: starvation. The lecture made little impact on him, however, his notes saying only: "- not dangerous to starve patients - not always best for them to maintain their own weight." October 31, 1920, preparing for a talk on diabetes and carbohydrate metabolism (about which he knew only what he had learned at the one lecture in medical school), Banting picked up the November issue of Surgery, Gynecology and Obstetrics, which had arrived the day before. He intended to use the journal's dullness to soothe him to sleep. Instead, he found himself fascinated by the lead article, "The Relation of the Islets of Langerhans to Diabetes with Special Reference to Cases of Pancreatic Lithiasis," written by Moses Barron. That one article inspired a theory that would set in motion a medical revolution!

The article described an autopsy on a patient in which a small stone had been found that was obstructing the main pancreatic duct, through which the strong pancreatic enzymes pass to the stomach to help digest food. The bulk of the pancreas had wasted away from the obstruction, but the cells in the islets of Langerhans were still healthy. Possibly, the author noted, by deliberately destroying most of the pancreas except the part containing the islets of Langerhans, one might be able to isolate that mysterious "internal" substance that played a role in diabetes. Find that substance, he wrote, and you might be able to cure diabetes. Could it be, Banting thought, that no one had been able to isolate the mysterious substance from the islets because the potent pancreatic enzymes destroyed it? Was there a way to isolate the islets from the rest of the pancreas?

Often people who have good ideas fail to act on them. Banting didn't let his idea float away. He reached for some paper and a pen and scribbled down his thoughts and made history by writing: "Diabetus (note the misspelling). Ligate (tie off) pancreatic ducts of dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate the internal secretion of these to relieve glycosurea (sugar in the urine)." As was later described in his obituary in Time magazine, Banting thought the mysterious substance secreted by these islets must act like a spark plug, providing the "juice" to help the body metabolize carbohydrates. Actually, he wasn't too far off in his metaphor. What the mysterious substance does is "unlock" cells allowing them to metabolize or "burn" blood sugar for energy!

When they gave this extract to a dog with diabetes the results were dramatic. Twelve hours later the diabetic collie, previously so weak from its diabetes it could barely stand, was prancing around the lab. They had accomplished the impossible: created an extract that reduced blood sugar!

Banting and Best named their extract "isletin." Unfortunately, the extract soon ran out and the dog died nine days later. As Banting wrote: "I have seen patients die and I have never shed a tear. But when that dog (that had been kept alive by the extract) died, I wanted to be alone for the tears would fall despite anything I could do."

Problem Solving
There were many problems to conquer before Banting could perfect his experiments. Unfortunately, the "isletin" extract was in very limited supply since their only source was the pancreases of dogs. However, when Banting learned that the pancreases of newborn and fetal animals contained more islet cells than other pancreatic cells, because animals didn't need pancreatic enzymes for digestion until they were born, he used his upbringing on a farm for a key insight. He knew that cattle were often impregnated before they were slaughtered, to make them eat more. He went to the local slaughterhouse and obtained dead fetuses. From these he was able to extract insulin and for the first time anywhere, there was a plentiful supply.

This invalidated Banting's original hypothesis - that part of the pancreas produces enzymes that destroy whatever the islets produce. However, Banting didn't mind discarding his original idea. Banting and Best had found a better supply of isletin without killing dogs. Insulin in all animals is nearly identical, so it can be used across species.

With ample supply, Banting knew they needed a biochemist to learn everything possible about insulin. Bert Collip joined the research team. He derived a method to purify insulin, using alcohol to separate out the impurities. They tested insulin on humans and it worked. There was such a flood of parents bringing sick children to Toronto that they turned over the manufacture of insulin to Eli Lilly, the pharmaceutical company. Insulin immediately became a commercial success.

Parents from all over North America raced to Toronto upon the announcement of the discovery of insulin
Those children receiving insulin quickly gained weight

Frederick Banting in the Face of Adversity
In WWI, Banting earned the Military Cross for courage under fire while he worked as a doctor to save lives. He had his arm badly damaged by an explosion. Doctors wanted to remove it, but Banting refused and nursed it back to health himself.

Twenty-eight days passed when Frederick Banting opened his own medical practice in London, Ontario before he had his first patient - his first month's income totaled $4 and came from treating that single patient.

As a young struggling doctor, Frederick Banting learned of an opening for a doctor to accompany an expedition in northern Canada as its medical director. He later wrote: "I was in desperate circumstances. The possibilities of doing research seemed remote. I tossed a coin - three out of five - heads I was to do the research, tails I was to go to the Arctic to search for oil. Tails won, and I took the next train to St. Thomas to make a personal application in the hopes of obtaining the job." A few weeks later a letter arrived with news that the arctic party had decided not to take a doctor. Banting hopped the train to Toronto to begin his diabetes research.

When Frederick Banting began researching diabetes he was only allotted 10 dogs to experiment upon.  He had to sell his car in order to buy more dogs to continue.

But as the work to isolate the active ingredient in the extract and purify it continued that spring, Banting found himself on the periphery of the action. First Macleod had renamed his discovery, then Collip refused to divulge to him his method of purifying the extract, and finally the Toronto hospital refused to put him on its medical staff, so he was barred from treating patients with the very elixir he had discovered! He began to feel his work was being appropriated, so when he and Edith broke up, he started drinking heavily, sometimes stealing the 95 percent proof alcohol used to extract insulin from the pancreases. Throughout March, he later wrote, he never once went to bed sober. He stopped going to the lab, spent his days sleeping and his nights smoking his pipe. The other boarders in the house where he rented a small room could often hear him singing "It's a Long, Long Way to Tipperary" and other old war songs. The lab, meanwhile, had encountered an insulin famine. They were having trouble making more. This prompted Best to pay a late-night call to Banting. He implored him to get off the booze and return to the lab. Banting pulled himself together and, working with Best, replicated the purification method.

Insulin was first publicly announced by Macleod at a medical conference. He received a standing ovation. Banting wasn't in attendence.

Alarmed by the rise of Nazi Germany, Banting spent the late 1930's involved in military research. In March 1941, Banting was to fly to England for military work, a precarious excursion in those days with the war going on and aircraft being a still relatively new technology. He expressed strong premonitions to several friends, but felt duty-bound to go. The bomber on which Banting was flying crashed in the wilds of Newfoundland. Banting managed to dress pilot Captain Joseph Mackey's wounds, but then began lapsing into and out of consciousness. Mackey snow-shoed out of the wilderness to find help, but by the time the rescuers arrived Frederick Banting was dead. The purpose of Banting's mission is unknown to this day. 

The Science of Diabetes and the Role of Insulin in Our Bodies
The term diabetes actually refers to a group of diseases that affects the way your body uses blood glucose (often called blood sugar). Glucose is vital to your health because it is the main source of energy that powers your brain and the cells that make up the muscles and tissues of your body. If you have diabetes, it means you have too much glucose in your bloodstream that is not able to be turned into energy.

Type 1 Diabetes is an autoimmune disease that begins in childhood. Researchers speculate that it is triggered when something, perhaps a reaction to a virus, flips a pre-existing switch in an individual's genetic code. This reaction directs the immune system to attack the pancreatic cells, which manufacture insulin.

Type 2 diabetes usually begins as an adult. Unlike type 1, people with type 2 having working islet cells on the pancreases that still manufacture insulin. However, their bodies aren't able to utilize insulin efficiently. Experts tell us that type 2 diabetes develops from the interplay between increasing insulin resistance in the muscles and liver, causing the pancreas, and even the liver, to increase the production of insulin. The strain of producing extra insulin causes the beta cells to further malfunction, ultimately causing them to "burn out" and stop producing insulin. That's why Type 2 diabetes is considered a progressive disease. Ultimately, most people with type 2 diabetes have to take supplemental insulin.

The two primary treatments for diabetes were opium, to make the patient oblivious to the pain, and the infamous "Allen diet." This diet called for starving patients until their urine contained no sugar, then gradually reintroducing food until the ideal amount of calories to sustain the sugarless state was found. Victims often lived on rations of 400 to 600 calories a day becoming so weak they couldn't leave their beds. Years later, when pictures of World War II concentration camp survivors circled the globe, doctors were reminded of those early diabetic patients. The estimated lifespan for someone who developed type 1 diabetes was one year to 18 months without the Allen diet, four to five with it. The end was always the same - death.

Later Research
In the mid-1950s, the British biologist Frederick Sanger identified insulin as a protein and revealed its chemical structure. In 1967, Dorothy Crowfoot Hodgkin determined the molecule's spatial shape (it is stored in a crystalline form in the islets of Langerhans) using x-ray diffraction. The two received the Nobel Prize for their work. Sanger later collected another Nobel Prize for his work on DNA sequencing, the core technology that enabled scientists to sequence the human genome.

Synthetic Insulin
Other researchers have found the insulin molecule is remarkably conserved from an evolutionary perspective. It is almost completely identical in all animals, from fish to fowl to worms to mammals. Pig insulin and human insulin differ by only one amino acid. Cow insulin differs from ours by three. This close molecular similarity explains why cow insulin worked for Frederick Banting just as well as dog insulin. In the decades following its discovery insulin was obtained from cows, pigs and fish for the daily shots of diabetics. Since it was very difficult to make animal extracted insulin absolutely pure, people allergic to any of these animals could have adverse reactions to the impurities. So, for decades after Banting's discovery researchers tried to create synthetic insulin. They finally reached their goal in 1978, when Herbert Boyer's laboratory, at the University of California at San Francisco, inserted a version of the human insulin gene into bacteria and turned the bacteria into little insulin factories. The following year, Genentech Corporation began producing a synthetic insulin, Humulin, the very first genetically engineered drug, using recombinant DNA technology. Humulin launched a whole new industry - biotechnology. In 1982, the Food and Drug Administration approved Humulin's use and today it is the primary form of insulin in use. Since 1982, different forms of insulin - long, short and medium-acting - have been introduced, enabling people with diabetes to fine-tune their medication depending on what they are eating and how much they are exercising on a particular day.

           Banting died in a plane crash during World War II

Scientific Discovery Timeline
1675 -- Thomas Willis first tasted urine to diagnose diabetes
1776 -- Thomas Cawley found the pancreas plays a role in the disease
1889 -- Joseph von Merring and Oskar Minkowski hypothesized something within the pancreas was responsible
1869 -- Paul Langerhans found there were two types of cells in the pancreas. Gustave-Edouard Laguesse later bestowed the name "islets of Langerhans"
1893 -- E. Hedon intimated something from within the islets of Langerhans prevented diabetes
1906 -- Georg Ludwig Zuelzer showed the right extract could bring diabetics back from the brink of death
1920 -- Frederick Banting discovers the mysterious substance secreted by isolated islets - insulin
1922 -- First human insulin trial , January 11^th,on Leonard Thompson, 14 years old 

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ca. 1925 - Elsie Needham  The first patient to recover from a coma due to insulin Image: Univ. of Toronto

Frederick Banting in His Laboratory Image: Univ. of Toronto

Banting with Charles Best, 1921 Image: Univ. of Toronto