The Conquest Of Diabetes
In 1920 scientists all around the world were searching for a treatment for diabetes, a heart-rending disease that had been growing steadily in incidence. Dr. Frederick G. Banting was not one of them. He was a lonely surgeon stranded in London, Ontario, where he spent his days waiting in vain for patients and his nights scheming to get out of London, Ontario, as soon as possible. At one point he applied to be a doctor in the Arctic. At another he tried to join the British Army in India. After six months, however, the most exciting offer he’d had was the chance to give a weekly lecture in internal medicine at the local university. Then late one night, after reading an article in preparation for a lecture on the pancreas and carbohydrate metabolism, subjects about which he knew almost nothing, he came up with a single idea that led within months to the isolation of insulin and the first longterm treatment for diabetes.
Banting’s miracle, as it was commonly called, brought the awkward young doctor much more adventure than he could ever have found in the Arctic or anywhere else. Within two years he was internationally famous; within three he was sharing the Nobel Prize in Physiology or Medicine; fourteen years after that he was Sir Frederick, a Knight Commander of the British Empire. Throughout the rest of his career, Banting was regarded as a genius, yet no one was more aware than he that he was nothing of the kind. In the mid-1930s he was asked to deliver a lecture on diabetes, and he responded by asking how long the lecture was supposed to last. “Hell, for all I know about it, fifteen minutes would be enough,” he explained.
Banting seemed to know that ignorance had been on his side during his moment of inspiration in 1920. He had been brilliant enough to think of a solution to diabetes’s most frustrating problem largely because he had been ignorant enough to view it as a simple problem. But even if it was the only idea he ever really had, it was enough to transform his life and save millions and millions of others.
Frederick Banting’s parents, who owned a farm north of Toronto, had enough money to send only one of their five children to college, and they gave it to Fred on the understanding that he would become a Methodist minister. But he was not pious by nature; rather, he was a fighter, and when he lost his temper, he was likely to use his fists. He delighted in dances, theaters, and the company of pretty girls. If he needed an outlet for his spiritual side, he may have found it in landscape painting, a hobby he took up in his thirties (today Banting’s paintings bring hefty prices at auctions). When he switched to medical study in 1912, his family was less than pleased, but they continued to support him.
At the outset of World War I, Canada found itself in sudden need of doctors to serve with the soldiers overseas. Medical school courses were accelerated so that students learned as much as a year’s worth of medicine in a single semester, or at least they were supposed to; some of them later joked about the gaps left by such a schedule. Banting graduated from the University of Toronto in one of several classes of 1917, a class so accelerated that he actually graduated in December 1916. In 1918, serving at the front in Cambrai, France, he was wounded in the arm. By the time he recuperated and received his discharge, in September 1919, the war was long over and Canada was glutted with doctors.
Banting was a hard worker and threw himself into any calling that might be considered his duty. However, duty was not all. In 1920 he moved to London, Ontario, mostly because it was near a town where his fiancée was teaching school.
He bought a substantial house in London, with an office attached, and a secondhand Ford. He invested in equipment for the office and informed his fiancée that in only two years or so he would be established. Then they could be married. She had already waited through the second half of World War I and a couple of years beyond that, so she began to take a new look at the situation and also at Banting.
After Banting officially opened his doctor’s office, he sat at his desk for 29 days before the first patient walked in. Not many more followed. If Banting had been diffident yet quick-tempered before serving in France, he developed a remoteness after returning home from the war; such a person could not possibly attract patients in a town where he wasn’t known and barely circulated. He even managed to repel his fiancée, who suddenly returned his engagement ring by mail. Just six months after arriving in London, he was already stuck there. To keep up the payments on his house, he had no choice but to borrow a large sum from one of his brothers (who had not had the benefit of a college education). It was at that time that he applied to a group of oil workers leaving for the Arctic and to the British Army, which did not want his services in India.
A businessman from Michigan who had received a diagnosis of diabetes in 1907 called it a hole inside him. No matter how much he ate, he lost weight just as though the food were dropping through an opening in his stomach. He became a shadow of himself, in stature, strength, and coloring, and he died in 1917. At the time, the most informed treatment for diabetes was a low-calorie diet. The hope was that the fewer calories ingested, the more would be absorbed, because when diabetics ate freely, their systems were so overburdened that almost no calories could be absorbed. That disbalance, accompanied by alarmingly high blood-sugar rates and discharge of sugar, was called glycosuria.
The low-calorie diet was itself a tribulation, setting ceilings of 1,000 or even 500 calories per day for patients already emaciated from the disease. In most cases patients suffering from glycosuria were ultimately faced with a harrowing choice: either starve themselves to death slowly through the diet or be starved to death through the ravages of the diabetes. According to one study, the more painful course was to eat freely and let the disease take its toll.
During the last half of the nineteenth century, researchers had learned that diabetes was a disease of the pancreas, a gland nestled against the stomach and composed of loosely connected clumps of tissue. The pancreas produces a watery but very potent juice that it delivers to the small intestine, where it breaks down different foods into usable nutrients. The fact that the pancreatic juice is an extremely powerful mixture was to frustrate many attempts at isolating a treatment for diabetes.
By 1900 doctors were well aware that the pancreas had a second function: emitting a substance directly into the bloodstream to break down carbohydrates and sugars into absorbable glucose. A German medical student named Paul Langerhans discovered in 1869 that there was a second cell system, in addition to the clusters of cells that secrete pancreatic enzymes, dispersed throughout the pancreas. These were later named the islets of Langerhans, and in 1901 they were identified as the potential source of the mysterious secretion that regulated carbohydrates right in the bloodstream. It was commonly identified as the pancreas’s “internal secretion.” For the next 20 years diabetes researchers kept coming up with the same idea: Make an injectable solution from a healthy pancreas (cut up and liquefied in some manner) that would contain the internal secretion and compensate for diabetes.
When this was tried, the pancreatic extract sometimes did nothing at all. Other times it caused violent side effects without affecting the glycosuria. The leading figures in the field of diabetic medicine rejected the treatment and looked for other answers. Dr. J. J. R. Macleod, of the University of Toronto’s Physiology Department, was especially adamant that pancreatic extracts were hopeless. He pointed out in 1913 that the enzymes of the pancreatic juice would tend to destroy whatever other agent was present in the organ when it was cut up and liquefied. As for removing the islets of Langerhans separately, that was impossible because they were so tiny, and, he theorized, they might not always contain the vital substance anyway. Attempts to extract the internal secretion were useless, Dr. Macleod concluded.
On the evening of October 30, 1920, Banting felt prepared for his upcoming lecture on the pancreas, having visited the medical college’s library several times. He was sitting around his house with, of course, nothing to do when he picked up a magazine that had just arrived, Surgery, Gynecology and Obstetrics . The lead article was about the pancreas, so Banting read it carefully: “The Relation of the Islets of Langerhans to Diabetes with Special Reference to Cases of Pancreatic Lithiasis” [lithiasis is the formation of mineral deposits in the body]. The author, Moses Barren, M.D., described a rare condition in which pancreatic stones (akin to gallstones) block the flow of juices out of the pancreas and into the small intestine. When that happens, the pancreas’s functions cease and most of its tissue shrivels up, but the islets of Langerhans remain healthy. Dr. Barron had found that if he simulated the condition experimentally by tying off the ducts leading out of the pancreas, the same atrophying occurred, again without affecting the islets.
Banting went to bed that night worrying, as he later said, his usual worries, mainly how to get out of debt. However, as he lay there, his mind returned to the article he had just read and started to build a bridge, as he later called it, between various of the facts he had learned regarding diabetes. Finally he got up and made a comment in his notebook: “Ligate pancreatic ducts of dogs. Keep dogs alive till acini [the more common pancreatic cells] degenerate leaving Islets. Try to isolate the internal secretion of these to relieve glycosuria.”
Eight days later Banting was on his way to the medical school at the University of Toronto, to apply to Dr. J. J. R. Macleod for funding and facilities to test his idea. The meeting was short. Macleod, eminent but overbearing, had heard most of the theories about diabetes many times before, and he rejected Banting’s with dispatch. Banting, for his part, was growing used to failure, and he accepted Macleod’s verdict without protest. He wasn’t the fighter he had once been.
However, he couldn’t forget the idea of tying off the ducts to remove the potent enzymes from the pancreas. It seemed violently wrong that Macleod was rejecting a promising idea that would be relatively easy to test. Accompanied by a few colleagues, Banting made a second appeal to Macleod in the winter of 1921. The professor took the time on that occasion to explain that not only would he not waste resources on Banting’s idea, but he wouldn’t waste them on Banting, a man with negligible credentials as a research physician and none whatever in the field of diabetes.
The Macleod-Banting impasse became something of a cause célèbre at the medical schools of Toronto and nearby London. Some established researchers resented Banting as an upstart, but those who had worked with him vouched for the fact that he was at least sincere. Macleod could (and did) label him as a country bumpkin but certainly not as foolish or flighty.
The University of Toronto, though still out of reach, remained Banting’s only real hope. It was one of the world’s leading centers of diabetes research, and as an alumnus he had a better chance of finding a place there than at any other institution. Diabetes, meanwhile, was in the midst of a quiet rise in the ranks of fatal diseases: It was the twenty-eighth leading cause of death in 1900, the twelfth in 1920, and the seventh in 1940. Today it is the third most common cause of death. One reason for this trend is success against other illnesses. People who might once have succumbed to tuberculosis, typhoid fever, or pneumonia now live long enough to develop diabetes. Another reason has had to do with eating habits in Europe and North America. People who consume inordinate amounts of candy and desserts put stress on their ability to control their blood-sugar levels, as do heavy drinkers, since alcohol is regulated in the bloodstream by the same internal secretion of the pancreas. Moreover, susceptibility to diabetes is hereditary, so there are also genetic reasons why diabetes has become ever more common throughout the twentieth century. Juvenile-onset diabetes is different in origin, being brought on through heredity or, in some cases, a virus, and it is typically more virulent than adult-onset diabetes. It usually kills quickly if there is no immediate treatment.
In either form of diabetes the bloodstream takes in carbohydrates without any means of breaking them down into usable form. Patients grow tired because they can’t get energy value out of their food and thirsty because they are struggling to flush out the useless carbohydrates. Because processing food so inefficiently takes more energy than it provides, before insulin the inevitable conclusion of the disease was a drastic loss of weight and, just as in cases of famine, a final coma.
In the spring of 1921 a professor who knew both Macleod and Banting negotiated a compromise by which Banting would be given a laboratory and a group of dogs on which to experiment so long as he completed most of his work while Macleod was away for the summer. The time limit was eight weeks, and Banting was to arrive in early May to begin planning the experiments in consultation with Macleod. Since there was considerable truth to the accusation that Banting knew almost nothing about pancreatic functions and carbohydrate metabolism, he started preparing by looking for an assistant with greater expertise than he had himself. The candidate also had to be willing to work free. Professor Macleod recommended Charles Best, a 21-year-old who would turn out to be crucial to the isolation of insulin.
Best, who had been raised in upper-class surroundings, had only just earned his undergraduate degree, but his education was already more thorough than that of Banting. Best was a neophyte researcher, but he had made a specialty of carbohydrate chemistry. Just as important, he was easygoing and optimistic, unlike Banting, yet determined to find success, exactly like Banting. Although Best had intended to spend the summer playing professional baseball, he decided instead to join the effort. He soon became, in Banting’s view, an equal partner in the research.
On May 16 Banting began the project by scrubbing the garret laboratory to which he’d been assigned. Less than six weeks later he had his first success with the new treatment. In between, he and Best killed an unfortunately large number of dogs, through fumbling surgery and imperfect procedures. Even in successful experiments they killed dozens of dogs, a distressing necessity mitigated by the fact that dogs, too, suffer from diabetes, so Banting’s work would prolong millions of animal lives as well as human ones. By August 3, with mistakes having taken the lives of 17 dogs, the two researchers, intent but bumbling, finally achieved promising results.
The animal known as Dog 408 was a yellow collie that had had her pancreas entirely removed the day before, bringing on diabetes-like symptoms almost immediately. She was listless and unnaturally thirsty. Banting had started preparing another dog six weeks before, performing an operation to tie off the ducts leading from his pancreas to his small intestine. According to the theory, the only healthy tissue left after that span of time would be the islets of Langerhans. The rest of the organ, emptied of strong enzymes, would be inert. Banting now removed the pancreas from that dog’s body, cut it up, and liquefied it. He then injected it directly into a vein in the collie’s neck. She had been lying quite still, but a moment after the shot she perked up. Moreover, her blood-sugar level went down with each new injection of the extract.
The collie proved Frederick Banting right. The substance in the islets of Langerhans (later called insulin, from the Latin for “island” or “islet”) could indeed be isolated from the rest of the enzymes and agents in the pancreas via the duct-tying procedure. It could keep a diabetic dog alive. However, the collie also proved that Banting was ill equipped for the job of developing his idea into a true treatment. On August 6 he gave the dog an increased dose of the extract, and she lapsed into a coma and died within hours.
To become a treatment for diabetes, insulin would have to work within an intricate web of substances as part of a formula no less complicated than the very chemistry of the bloodstream. The insulin supply would have to be as pure as possible and utterly predictable in potency. As long as the specific properties of insulin remained unknown, with their measurement in the realm of guesswork, an injection could easily be tantamount to poison. Banting had succeeded in isolating insulin, amazingly quickly, but other scientists would have to work out a framework for standardizing it, one that could allow minute adjustments.
By the time J. J. R. Macleod returned in September, Banting was enjoying his triumph. It had not gone much farther than his own tiny laboratory yet, but the lab was alive with dogs—dogs with no pancreases. Nonetheless, Dr. Macleod swept aside Banting’s results and suggested other possible reasons for the dogs’ survival. He intimated that he would discontinue his support of the research in favor of other, more promising avenues.
Later that month Banting presented himself in Macleod’s office for a confrontation. Unlike their first interview, about ten months before, the conversation was neither short nor perfunctory. Personally, Banting was even more desperate than before; he told an associate at about that time that he had only seven cents left to his name, and it wasn’t much of an exaggeration. Professionally, though, he now considered himself Macleod’s equal, if not his superior. “I told him I had given up everything I had in the world to do the research,” Banting later recalled, “and that I was going to do it, and that if he did not provide what I asked, I would go someplace where they would.”
At that suggestion, Macleod laughed. However, he eventually agreed to Banting’s requests. And after seeing the results of a series of new tests that fall, Macleod suddenly dropped nearly all his department’s other research activities so as to devote as many resources as possible to the further development of insulin. He organized the effort in a way that would have been foreign to Banting, who was in the throes of soaring enthusiasm and wanted to go in every direction at once.
The most important contribution Macleod made was the recruitment of an accomplished chemist from western Canada, James B. Collip, to work out ways to purify insulin and to measure it.
At the same time, Banting addressed the dire problem of supply. It cost two dogs’ lives to keep a third dog alive for three days. That did not bode well for the treatment of a disease with many thousands of victims. Banting had learned from his reading that the pancreas of an unborn puppy possessed the same characteristics as a duct-tied one, in that it had healthy islets but no digestive enzymes. He wondered if the same might be true of unborn calves. As a farmer’s son he knew that slaughterhouses commonly left the carcasses of unborn calves for waste. After a couple of tests he pioneered the use of slaughterhouses as a source for pancreatic material. The stray dogs of Toronto had done their part. Soon Best developed a method by which the pancreases of slaughtered full-grown cows could yield insulin.
Other, more insidious problems faced Banting as the insulin treatment began to be publicized around Toronto. In the first place, Dr. Macleod on at least one occasion used the pronoun “we” in describing the effort to isolate insulin. That irked Banting no end. And then Banting heard that insulin was being called Collip’s extract, in honor of the diligent chemist who was making it practical for general use. Banting sought out his colleague at the university. Without any preliminaries he jumped on Collip and tackled him. Hitting Collip’s head against the floor, Banting growled, “So, you will call this Collip’s extract, will you?” He was losing control of his idea, and he handled that fact badly.
Banting and Best presided over insulin’s first human trial in the winter of 1922. The patient was a teenage boy who, declining into the final stages of diabetes, weighed only 65 pounds. His father, who had carried him into a Toronto hospital, gave permission for the experimental treatment. The first insulin injections, prepared by Banting and Best themselves, were failures, but a few weeks later Collip supplied an improved version. Collip’s extract reversed the symptoms. The boy eventually resumed a normal life, and he lived for 15 more years.
Dr. Macleod made the first major public announcement regarding insulin treatment at a physicians’ conference in Washington, D.C., on May 3, 1922—less than a year after Banting had begun his research alone in the attic lab. Many diabetics in Toronto were already leading normal lives by the summer of 1922. However, a lag in the mass production of insulin delayed its general availability until the beginning of 1923. None of the pioneers in insulin research showed interest in the money to be gained from it. Long before it was commercialized, they each assigned their patent rights to the University of Toronto.
Throughout the first half of the twentieth century, one of the leading figures in diabetes research in the United States was a kindhearted doctor named Elliott P. Joslin, the founder of the institute in Boston that bears his name. “All that I could give to the 3,050 diabetics I have treated in the last 25 years,” he said in 1923, “has been hope that if they deny themselves and live like Spartans, someday a genius would come along with a remedy that would give them life.” Joslin then named Banting as having given diabetics just that: life. It was high praise. But it wasn’t enough.
Banting had been stranded by the events of the previous three years. Praise for his accomplishments didn’t especially please him. He craved the reverse: public acknowledgment that J. J. R. Macleod had done nothing other than obstruct the effort at its most vulnerable point—and mock it and mock Banting. In Banting’s mind, insulin had been isolated despite Macleod, not because of him.
In 1923 the Nobel Committee awarded its Prize in Physiology or Medicine to Frederick Banting and J. J. R. Macleod. When Banting heard about the dual award, he flew into a rage. Back in 1920 he had been a forgotten man in a backwater neighborhood of London, Ontario. Three years later the worst thing that had ever happened to him was winning the Nobel Prize. Too much had occurred, exploding out of a single moment on October 30, 1920. That moment had distorted all that came after it, because it was a moment so unlike any other in Frederick Banting’s life.
After leaving insulin research to others, Banting moved on to various opportunities at several research institutions, including two that were named for him. However, comparatively little came of his efforts. He tended to shift from one major area of research to another, leaving behind neither detailed observations nor inspired breakthroughs. For a time his personal life fitted something of the same pattern. After he became famous, he had the satisfaction of receiving new attentions from his former fiancée and evincing absolutely no interest in them. He married in 1924, at the age of 32, and divorced eight years later, after a long separation. His second marriage appeared more stable, but he died only two years into it.
Sir Frederick Banting was killed in an airplane crash in 1941. As a major serving in the Canadian Army’s Medical Corps, he was bound for Europe on an army transport plane that went down over Newfoundland. He survived the initial impact and was found about an hour later by the only other survivor, the pilot. When he died, he was mumbling medical ideas and insisting that the pilot write them down.