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Frederick Banting - Insulin:
According to data published by the U.S. Census Bureau, International Diabetes Federation and the National Diabetes Surveillance System, between 10 and 20 million people worldwide are believed to have Type 1 diabetes. Using population growth estimates from 1950-2008 and an intermediate incidence rate of 6/100,000 new cases per year, over 16 million lives have been saved. There was no effort to determine the number of lives saved for type 2 diabetes (adult onset diabetes), although insulin definitely saves some lives with it as well.
--Amy R. Pearce, PhD
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Frederick Banting, MD
(November 14, 1891 - February 21, 1941)
Born in Canada
Year of Discovery: 1922
Discovered the First True Miracle Drug!
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. He 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.
Introduction by Tim Anderson
Main Content by Maury M. Breecher
Table of Contents
Key Experiment or Research
Quotes by Frederick Banting
Quotes About Banting and Insulin
Excerpt from Scientists Greater than Einstein
The Science Behind the Discovery of Insulin
Scientific Discovery Timeline
Recommended Books About the Science
Books by Frederick Banting
Books About Banting
Major Academic Papers
Links to Science and Related Information on the Subject
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.
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!
Key Experiments or Research
Medical Discovery Research
Banting needed facilities and sponsorship to do his research. After months of pleading to an at first reluctant professor, he was allowed to begin his research in a laboratory under the sponsorship of University of Toronto professor of physiology, John James Richard Macleod, one of the world's foremost experts on carbohydrate metabolism. Macleod was going away for the summer, but provided Banting with ten dogs, a filthy laboratory on the top floor of the university's medical building, and a fourth-year student willing to help. That student was Charlie Best, who won the right to work with Banting on a coin flip.
The plan was to anesthetize the dogs, cut them open, pull out their pancreas, tie off the pancreatic ducts, and close the incision. Then, the main part of the pancreas would shrivel up, or atrophy, leaving the precious islets of Langerhans and their mysterious substance isolated. Other dogs would have their whole pancreas removed, giving them type 1 diabetes, they would be available to test the
One reason the dogs had died was that the catgut used in the surgery to tie off the pancreatic ducts would loosen. Banting adjusted his experiment by using surgical silk for the ligatures instead of catgut. After many setbacks, Banting finally had an extract and amazingly, it seemed to work. Banting wrote Macleod a letter, saying, "I have so much to tell you and ask you about that I scarcely know where to begin. I think you will be pleased when you see how the problem is unrolling from one end and rolling up at the other. At present I can honestly state my opinion that:
(1) The extract invariably causes a decrease in the percentage of blood sugar and in the excretion of sugar in diabetic dogs.
(2) That it is active at least for four days if kept cold.
(3) That it is destroyed by boiling.
(4) That extracts of spleen and liver at least, prepared under similar conditions, have no such action.
(5) The clinical aspects of the animals are improved by the extract.
The number of problems that are presenting themselves is becoming greater and greater. Some of them I would wish to present for your approval...."
A significant advance came when Banting figured out a new way to deplete the pancreas of the external secretion by stimulating it with the hormone secretin. This caused the pancreas to release its enzymes until it was empty. To make their extract, they ground up the remaining pancreas, with its islets of Langerhans. Now they no longer had to wait for the pancreas to atrophy.
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."
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.
-Frederick Banting, on the necessity of hands on experimentation.
Published Quotes about Frederick Banting and Insulin
"No single event in the history of medicine had changed the lives of so many people, so suddenly."-Stephen Hume, Biographer of Banting
"This was the first time in medical history that a diabetic child had been restored to health."
-Gayle M. Herrington, in a 1995 article.
"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 by comparing him to Walter Campbell, the young doctor who handled the diabetic patients at Toronto General Hospital.
"The era of coma as the central problem of diabetes gave way to the era of complications."
-Dr. Elliott P Joslin, founder of the world famous Joslin (diabetes) Clinic.
"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, commenting when people argued that the specialists in the lab should have gotten more credit than Banting.
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.
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.
Macleod was going away for the summer, but provided Banting with ten dogs, a filthy laboratory on the top floor of the university's medical building, and a fourth-year student willing to help. That student was Charlie Best. Macleod had chosen him and another student, Clark Noble, to help Banting through the summer. The idea was that they would each work a month and vacation a month. To see who would get to vacation first, they flipped a coin. Best "lost" the coin toss, but his work earned him a place in history.
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.
On October 26, 1923, the Nobel Prize in medicine was awarded to Banting and Macleod, the fastest the Nobel committee has ever awarded a prize after an initial discovery. Upon hearing that he was to share the prize with Macleod, however, Banting became very upset that Best was not included, swearing that he wouldn't accept the award. Banting's friends and colleagues converged, calming him down and reminding him that he would be the first Canadian to receive the Prize - an honor and major achievement for both him and his country. Banting grudgingly agreed with his friends that he should not refuse the prize. One thing he could do, however, was split his share of the $30,000 monetary prize with Best. Fifteen thousand dollars was a lot of money in those days, more than most people made in a year, enough to buy a house and have enough left over for a car. Banting immediately cabled Best, who was presenting an academic paper that night at Harvard Medical School, telling him in the truncated language of the wire medium:
"I ascribe to Best equal share in the discovery stop
Hurt that he is not so acknowledged by Nobel trustees stop
Will share with him."
A few days later, Macleod, not to be outdone, announced he would share his portion of the prize with Collip. However, the exclusion of Charles Best remains, as one historian writes, "one of the worst mistakes made by a Nobel committee."
Banting married in 1924 and had a child, William, in 1928. He married again in 1937.
Banting was an avid amateur painter and cultivated a relationship with the Canadian painters' society known as the Group of Seven
After developing insulin, Banting worked with the British Royal Air Force Research and Development, helping to develop and test the G-Suit.
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.
Excerpt from Scientists Greater Than Einstein: The Biggest Life Savers of the Twentieth Century
Buy a copy in the online store
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.
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 died I wanted to be alone for the tears would fall despite anything I could do."
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 a year to 18 months without the Allen diet, four or five with it. But the end was always the same - death.
Diabetic "Shockers" -
Until the 20th Century, tasting urine was the primary test for diabetes diagnosis. Many doctors tried to get their patients to perform the test.
Before the discovery of insulin in 1922, type 1 diabetes, then known as juvenile diabetes, had a 100% death rate.
Before insulin, the only treatment for type 1 diabetes was starvation - extending life only a few years.
Frederick Banting was unimpressive in high school and was an extremely poor speller; he first spelled diabetes as "diabetus."
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.
Collip "lost" the secret for purifying the extract (he might not have written it down) creating an insulin famine.
Banting and Best named their extract isletin. Macleod overruled them and renamed it insulin.
Insulin was first publicly announced by Macleod at a medical conference. He received a standing ovation. Banting did not attend.
When Frederick Banting was researching diabetes he had to sell his car in order to buy more dogs to continue.
The first people to ever receive insulin were Frederick Banting and Charles Best - they injected insulin into each other's arms to see if it was safe on humans.
Banting was offered $1 million and royalties by an American financier - but turned it down and never profited from insulin.
Only about five grams of insulin is circulating in a human's blood at any given time - about the amount contained in a sugar packet.
Insulin in all animals is nearly identical and can be used across species.
Basic Science of Diabetes and the Role of Insulin
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 - no matter what type -- it means you have too much glucose in your bloodstream, although the reasons why may differ. Type 1 Diabetes is an autoimmune disease. Its exact cause is unknown. Researchers speculate that it is triggered when something -- such as 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 -- called islet or beta cells -- which manufacture insulin. Type 2 diabetes is the second main type of disease. 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 as efficiently as when their bodies were healthy. This inability to utilize insulin efficiently is called insulin resistance. 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.
What triggers the release of insulin in a healthy person? That occurs when carbohydrates ingested during a meal are digested. The resulting blood sugar increase triggers the release of insulin from the pancreatic beta cells. Insulin makes the level of glucose in the bloodstream go down by opening the doors of the cells to glucose, allowing blood sugar to be used as fuel. Insulin does this by attaching, or binding, to spots on the surface cells called receptors. Only when this binding process occurs are the cells "unlocked," allowing glucose to pass through the cell membrane into the cells where it is burned for energy. Insulin can be thought of as the keys that unlock the "doors" of the cells. However, in type 1 diabetes something has stolen those keys (no insulin is created by the islet cells of the pancreases. In type 2 diabetes, insulin is manufactured by the beta cells; however, insulin resistance interferes with the unlocking process, the binding of glucose to the insulin receptors (the keyholes). Though some insulin is able to get through, people with type 2 diabetes experience a very inefficient use of insulin.
Insulin is also a hormone with multiple other functions. It increases the rates of DNA replication and protein synthesis in cells by encouraging the uptake of amino acids from the bloodstream into muscles and other tissues. It also causes arterial wall muscles to relax, thereby increasing blood flow. However, its best-known function is to regulate sugar metabolism. In fat cells insulin converts glucose into triglycerides for storage. In muscles (and the liver) it converts glucose into glycogen. Type 1 diabetics don't have this storage benefit, so their bodies run out of fuel. That's why they need supplemental insulin to survive. The insulin carries blood glucose into cells where it can be burned for fuel, or stored as glycogen or triglycerides for later use. In contrast, about four hours after a meal, glycogen begins to break down into glucose in the liver of nondiabetics, providing fuel to the body. The body can also break triglycerides down into glucose to use as fuel. Normally, there is remarkably little sugar (glucose) in a person's blood stream. A typical grown man has five grams of glucose - about the weight of a restaurant sugar pack - in his whole bloodstream, which carries around five liters of blood - this corresponds to a blood glucose level of 100 mg/dl (milligrams per deciliter) when fasting. Since people with type 1 diabetes make no insulin, their livers cannot store glucose as glycogen, and consequently their blood streams become flooded with sugar-as much as 20 times the normal level. This puts them at risk of diabetic coma after every meal. One of the roles of the kidneys is to filter out excess sugar and expel it in the urine. In people with uncontrolled diabetes, the excess sugar is so concentrated that doctors from the times of Hippocrates noticed that flies would congregate around the chamber pots of people with diabetes.
The History of Diabetes and Insulin and Other Scientists Who Contributed to the Treatment of Diabetes
In 1675, the British physician Thomas Willis tasted the urine of several people with diabetes and found it uniformly sweet and, for nearly two centuries after, tasting urine was the primary test for a diabetes diagnosis. Today we know the reason diabetics' urine is so sweet is that their bodies are unable to process glucose, the sugar molecule that provides the energy cells need to power every aspect of human life.
In 1776, Matthew Dobson discovered sugar in the blood of patients, which confirmed diabetes was a systemic disease, not simply one of the urinary tract. A few years later, the researcher Thomas Cawley performed an autopsy on a patient who had died from diabetes and found the pancreas, a small, jelly-like gland that sits atop the liver, had shriveled up. That was the first intimation that this gland plays a role in the disease.
It wasn't until 1889 that German scientists Joseph von Merring and Oskar Minkowski discovered diabetic-like symptoms in dogs whose pancreases had been removed. They were the first to hypothesize that something within the pancreas was responsible for the terrible sugar disease. To test that hypothesis, Minkowski removed a dog's pancreas and suddenly found the previously housebroken dog peeing everywhere. Upon testing the dog's urine, he found it filled with sugar. Minkowski had become the first person to induce diabetes in another living being. So, what was it about the pancreas that prevented diabetes? Minkowski determined that when he cut the pancreatic duct leading to the dog's intestine, it released pancreatic enzymes known to assist in digestion, but that did not induce diabetes. Some still unknown part of the pancreas was at work.
That other part had actually first been described in 1869 by a German medical student, Paul Langerhans. Langerhans found the pancreas contained two types of cells: the acini, which are clusters of cells that secrete the pancreatic enzymes, and another type of cell unconnected to the acini. In 1893, the French researcher Gustave-Edouard Laguesse bestowed the name "islets of Langerhans" on those "other" cells, in honor of the man who originally identified them. He called them "islets" because, when looking at the cells through a microscope, they looked like islands floating in the pancreas. There are from one to three million of these islet cells in a normal pancreas, constituting about 2 percent of its mass.
Later that year, the French researcher E. Hédon removed nearly the entire pancreas from a dog, including the part that secreted the digestive enzyme, leaving only a small portion with the islets of Langerhans. This he grafted under the dog's skin so that it continued functioning. The dog didn't develop diabetes. When Hédon cut off the remaining pancreas.. . . Voila! Diabetes.
Clearly, something within the islets of Langerhans prevented diabetes. Over the next few years more than 400 researchers set to work trying to find that mysterious "something." Diabetes researcher Lydia Dewitt estimated at the turn of the century: "More thought and investigation was going into the islets of Langerhans than any other organ or tissue of the body." On June 20, 1906, a German internist named Georg Ludwig Zuelzer injected an extract of beef pancreas and adrenalin into a man in a diabetic coma. The man came out of the coma hungry, dying 12 days later when the extract ran out. Zuelzer later wrote: "Whoever has seen how a patient lying in agony soon recovers from certain death and is restored to actual health will never forget it." Zuelzer's was just the first of many such accounts of the miraculous recovery the right extract could bring to diabetics on the brink of death. Unfortunately, the recovery never lasted and inevitably the patients had severe reactions, including vomiting, high fevers, and convulsions. In 1913, diabetologist Frederick Allen declared: "All authorities are agreed upon the failure of pancreatic opotherapy (pancreatic juice therapy) in diabetes . . . injections of pancreatic preparations have proved both useless and harmful."
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.
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.
A year after the introduction of Humulin the first insulin pump was introduced. About the size of a pager, it was connected to the body via a catheter that had to be changed every few days. Since then, the technology has improved to the point the pump is now implanted, delivering insulin as needed and eliminating the need for shots and careful measuring of blood sugar levels. About 20 percent of type 1 diabetics use a pump. Recently, in 2006, the first non-injected insulin was approved by the FDA -- Exubera, an inhaled therapy.
A cure for diabetes is still being sought. Researchers have had some success with kidney-pancreatic transplants and with implants of islets of Langerhans. But there is a shortage of organ donors, and transplants often cause immune rejection, so some researchers have tried to clone a patient's own islets before they stop producing insulin entirely, with the goal of reinserting them back into the pancreas. Other scientists are trying to use embryonic stem cells - cells capable of differentiating into any type of cell - to "grow" new islet cells identical to an individuals' own.
Types of Diabetes
There are three types of diabetes: gestational, which only strikes a small percentage of pregnant women; type 1, once called "juvenile" or "childhood" diabetes, which occurs mainly in children; and, type 2, a form that once was called "adult" diabetes, because it usually develops in mid-life or later. Today, however, even children (generally obese children) can develop type 2 diabetes. About 21 million people are estimated to have types 1 and 2 diabetes. Only about 5 percent of all people with diabetes have type 1. However, before the discovery of insulin the type 1 form was deadly, striking suddenly with symptoms of great thirst and urine output, tremendous hunger, and frightening weight loss. The 100 percent mortality rate of type 1 diabetes defied hundreds of years of efforts to find a way to arrest this dreadful disease.
Frederick Banting's Life: A Timeline
1891 born on his family's small farm in Ontario, Canada, the youngest of five children
1910 accepted into Victoria College in Toronto
1912 enrolled in the University of Toronto's five-year medical program
1916 graduated with medical degree and the following day reported for military duty in WWI
1917 shipped out to Kent, England to treat patients and consequently injured during battle
1918 transferred to the war's front for battlefield medicine and consequently injured
1919 formally discharged, 28 years old, a smoker and heavy drinker, engaged to Edith
1919 spent a year at Toronto's Hospital for Sick Children performing 100 surgeries
1920 opened a home/doctor's office, making just $4 his first month
1920 taught at London's West University, and was first inspired by a diabetes article written by Moses Barron
1920 approached Macleod about his theory of isolating the mysterious substance from the pancreas
1921 started researching his theory under Macleod at the University of Toronto
1922 first human insulin trial on 14-year-old Leonard Thompson
1923 the Nobel Prize was awarded to Banting and Macleod
1928 had a son named him William, and became an accomplished amateur painter
1932 marriage ended
1941 died after a military flight crash in Newfoundland - before he died of his own injuries, he treated wounds of the pilot, thereby saving that person's life
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 11th,on Leonard Thompson, 14 years old
Recommended Books about the Science of Diabetes
Kereiakes, J. Dean, Wetherill, L. Douglas. Diabetes: What You Should Know. Blackwell Science, Inc., 2001
Roith, D Le; Taylor, S; Olefsky, J M editors. Diabetes Mellitus. A Fundamental and Clinical Text. Philadelphia, PA: Lippincott-Raven, 1996
Stewart, B. Gail. Diabetes (Board Book). Kidhaven Press, December 2002
Zaidi, Sarfraz M.D. Take Charge of Your Diabetes: A revolutionary Plan for Treating Your Diabetes and Preventing its Complications. Philadelphia, PA: Perseus Books Group, 2007
A.Y. Jackson. The Far North. Book of drawings with an introduction by F.G. Banting. Toronto: Rous & Mann., 1927
Bliss M. The Discovery of Insulin. Chicago: University of Chicago Press; 1982
Bliss, Michael. Banting: A Biography. University of Toronto Press. 1993
Mayer, Margaret Ann and Henriksen, Harold. Sir Frederick Banting, Doctor Against Diabetes. Chicago: Children's Press, 1974
Hume SE. Frederick Banting: Hero, Healer, Artist. Montreal: XYZ Publishing; 2001
Stevenson, Lloyd. Sir Frederick Banting. Toronto: The Ryerson Press, 1947
Woodward, Billy, Shurkin, Joel and Gordon, Debra. Scientists Greater than Einstein: The Biggest Lifesavers of the Twentith Century. Linden Publishing, 2009.
Nobel Prize in Physiology (1923) - Banting and Macleod
Reeve Prize of the University of Toronto (1922)
Lifetime Research Grant from Canadian Government, including a Life Annuity of $7,500 (1923)
Administrator at the University of Toronto
Banting and Best Chair of Medical Research endowed by the Legislature of the Province of Ontario (1923)
LL.D. Degree (Queens) and the D.Sc. Degree (Toronto) (1923)
Knighthood in the British Court (1934)
Major Academic Papers
Reviews and Notices of Books
The Lancet, 203 (5261), p.1318-1320, Jun 1924
...Insulin. By J. J. R. MACLEOD, Professor of...Toronto and F. G. BANTING, Research Professor...given by Prof. Macleod and one by Prof. Banting in January, 1923...description given by Macleod is most instructive...ments by Dr. Banting with Dr. C. H...
...Insulin. Macleod, J.J.R. , The Lancet, 202 (5213), p.198-204, Jul 1923
...July 24th. INSULIN. J.J.R. Macleod F.R.S., M.B., CH.B. ABERD...UNIVERSITY OF TORONTO. [Prof. Macleod gave an historical survey of...the pancreas furnished by Banting and Best, their experiments...know also from the work of Banting and Best on depancreated dogs...
Canadian Diabetes Association's timeline of the History of Diabetes
Contributions of the American Journal of Physiology to the discovery of insulin
American Diabetes Association
Wikipedia article on diabetes
Library and Archives of Famous Canadian Physicians: Frederick Banting
Bitter Facts of Diabetes and Blood Sugar - lots of facts
Article about the tension between Banting and Macleod
Preventing and managing the different types of diabetes
Exercise can help manage symptoms
How diabetes affects your blood sugar
New Yorkers living and coping with type 2 diabetes. A widespread epidemic: parts 1,2,3
Written Media Links
Dobson, M. Nature of the Urine in Diabetes. Med. Obs. Inqu. 5: 298-310, 1776
Hsueh, W. A., Moore, L., and Bryer-Ash, M. Contemporary Diagnosis and Management of Type 2 Diabetes (2nd Ed). Newtown, PA: Handbooks in Health Care Co., 2003
Krall, L.P. & Beaser, R. S. Joslin Diabetes Manual. Philadelphia: Lea & Febiger, 1989
Saudek, C. D., Rubin, R. R., and Shump, C.S. The Johns Hopkins Guide to Diabetes for Today and Tomorrow. Baltimore: Johns Hopkins University Press, 1997
Chapter 9: Frederick Banting - The First True Miracle Drug - Insulin
Written by Billy Woodward and Debra Gordon
1. Bliss M. The Discovery of Insulin. Chicago: University of Chicago Press; 1982.
2. Bliss M. Resurrections in Toronto: the emergence of insulin. Horm Res. 2005;64 Suppl 2:98-102.
3. Majumdar S. Glimpses of the history of insulin. Bull Ind Inst Hist Med. 2001;31:57-70.
4. Bliss M. Banting: A biography. Toronto: University of Toronto Press; 1984.
5. Gale EA. The rise of childhood type 1 diabetes in the 20th century. Diabetes. Dec 2002;51(12):3353-3361.
6. Gidney RD, Millar WPJ. Quantity and Quality: The Problem of Admissions in Medicine at the University of Toronto, 1910-51. Historical Studies in Education. Fall 1997 1997;9(2).
7. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. CMAJ. July 18, 2006 2006;175(2):165-170.
8. Herrington GM. The discovery of insulin. Ala Med. 1995 Jun; 64(12):6-12.
9. Hodges B. The many and conflicting histories of medical education in Canada and the USA: an introduction to the paradigm wars. Medical Education. 2005;39(6):613-621.
10. Hume SE. Frederick Banting: Hero, Healer, Artist. Montreal: XYZ Publishing; 2001.
11. Jain KM, Swan KG, Casey KF. Nobel prize winners in surgery. Part 3. (Frederick Grant Banting, Walter Rudolph Hess). Am Surg. Jul 1982;48(7):287-290.
12. King KM, Rubin G. A history of diabetes: from antiquity to discovering insulin. British Journal of Nursing. 2003;12(18):1091-1095.
13. Rafter GW. Banting and Best and the sources of useful knowledge. Perspect Biol Med. Winter 1983;26(2):281-286.
14. Rosenfeld L. Insulin: Discovery and Controversy. Clinical Chemistry. 2002;48(12):2270-2288.
15. Spark-Plug Man. Time; 1941.
16. Tattersall RB. A force of magical activity: the introduction of insulin treatment in Britain 1922-1926. Diabet Med. Sep 1995;12(9):739-755.
17. Welbourn R. The emergence of endocrinology. Gesnerus. 1992;49:137-150.
18. 2003. The Discovery and Early Development of Insulin. University of Toronto Libraries, Fisher Library Digital Collections. http://link.library.utoronto.ca/insulin/index.html
19. 2006. 2005 Annual Report, Eli Lilly, Corp.
20. 2006. Novo Nordisk Is Changing Diabetes. Nov Nordisk. http://www.novonordisk.com/about_us/facts_and_figures/facts.asp. Accessed July 3, 2006.
21. Diabetes Fact Sheet. World Health Organization. http://www.who.int/mediacentre/factsheets/fs312/en/