Setting the Scene: Canada in 1920
In 1920, on the eve of the discovery of insulin, Canada was hesitantly emerging from four tumultuous years of war. The final months of World War I, which ended on November 11, 1918, coincided at home with the enormous suffering caused by the global influenza pandemic of 1918-19. Emerging from the pandemic, the federal government set up a national department of health in 1919. At the same time, significant labour unrest erupted, most dramatically in the Winnipeg General Strike.
As 1920 began, so did a period of relief after many years of economic sacrifice and anxiety, and the start of what many Canadians hoped would be a bold new age. The telephone and the radio had become standard technologies in most Canadian homes. People flocked to movie theatres to watch films, which, as of 1927, also had sound. The members of the “Group of Seven” held their first exhibit of iconic Canadian paintings in May 1920. On July 1, 1920, the Dominion Elections Act came into effect, granting women the right to vote and run in federal elections. The start of the 1920s also saw growing consumer interest in the automobile and the expansion of aviation across the country. Indeed, the first airplane flight across Canada, from Halifax, N.S. to Richmond, B.C., was completed on October 17, 1920, which happened to be two weeks before Dr. Frederick G. Banting was struck by a unique idea in the middle of the night — an idea that led to the discovery of insulin.
Diabetes in 1920: Personal Context
In 1920, a diagnosis of diabetes was essentially a death sentence, especially for a child with rapid onset of what later was defined as Type 1. Life expectancy was generally less than a year from diagnosis. Slower onset diabetes, mostly among adults and later defined as Type 2, was more manageable, yet still deadly in many cases.
At the time there was no exact definition of diabetes as diagnostic methods were uncertain and changing, as were statistical methods. Thus, it was impossible to know just how many diabetics there were in Canada, or anywhere else. The best estimate was that between 0.5 and 2.0% of the residents of industrialized countries had diabetes in 1920. In more prosperous and well-nourished societies, the disease seemed more prevalent. In fact, by 1920, diabetes was most visible in the richest countries, notably the United States and Germany, as well as Canada. The prevalence of diabetes became more apparent as people became better nourished and were able to fend off often lethal infectious diseases due to improved hygiene and the wider use of antitoxins and vaccines.
Diabetes develops when the body starts to lose the ability to utilize fuel. Food is not fully metabolized or transformed into energy. Instead, the nutrients pass through the body and are expelled. The term “diabetes” derives from the Greek word for “siphon” or “pipe-like.” A 17th century physician described diabetes as “the pissing evile.” The key symptoms of severe diabetes included frequent and voluminous urination — up to 15 litres per day — and unquenchable thirst.
Another distinctive diagnostic test was that the urine was sweet to the taste, as it was heavy with sugar. The full name, “diabetes mellitus,” originated from the Latin term “mellitus,” which means honey or sweet. (This characteristic distinguishes diabetes from another condition that leads to large amounts of sugar-free urination.) In the diabetic, glucose (sugar) remains in the bloodstream instead of being absorbed into cells. The kidneys normally remove sugar from the body’s waste water. But with elevated blood sugar levels, the glucose spills into the urine. As the body loses fluid, the sufferer develops a terrible thirst, a craving for sugar and ultimately intense hunger.
Without treatment, diabetes invariably worsens, and its effects become much more wide-ranging than just weight loss and weakness. Cataracts, blindness, severe foot and leg infections (especially gangrene) were common secondary effects of diabetes, particularly Type 2. For juvenile diabetics suffering from Type 1, the disease effectively destroyed the body. As the victim struggled to assimilate fats in place of carbohydrates, her system became clogged with partially burned fatty acids (ketone bodies). When doctors found an abundance of ketones in urine, they could be quite sure that diabetes had entered its final and fatal stages. The ketones also left a tell-tale breath odor — sickly-sweet, like rotten apples, which often pervaded whole rooms and hospital wards. At this stage, the sufferer experiences a restless drowsiness, which fades into semi-consciousness followed by a desperate “air hunger” and a deep diabetic coma, from which there was no hope of recovery.
Diabetes, 1920: Hopeful Treatments
In 1920, physicians treating diabetes invested hope in the “starvation diet” pioneered by Dr. Frederick M. Allen in 1915 and promoted by Dr. Elliott P. Joslin. Dr. Allen trained in medicine in California and began working on problems of sugar consumption while he held a fellowship at Harvard Medical School. This work led to intensive research on diabetes, especially while at the Rockefeller Institute from 1914 onwards. In April 1921, Allen opened the world’s first diabetes clinic in Morriston, N.J. Dr. Joslin was the most prominent American specialist in diabetes. He studied medicine at Yale and Harvard universities, and gradually narrowed his Boston medical practice to specialize in diabetes. Joslin was a prolific writer whose work was aimed at both physicians and diabetics themselves, and always trying to put the best face on the diabetic’s situation. Prior to 1915, doctors tried many diabetes treatments, among them bleeding, blistering and doping, including with opium. They also encouraged patients to eat as much as possible, and especially sugar, based on the idea that they needed extra nourishment to compensate for the losses through excessive urination.
However, other doctors began to take the opposite approach, realizing that the extra food diabetics consumed to sate their urgent hunger actually increased the strain on their systems and made things worse. These physicians felt carbohydrates were especially problematic. If the body couldn’t metabolize carbohydrates, perhaps diabetics should be given a low carb diet. Some practitioners further noticed that prescribing periodic fasting days had the effect of reducing or removing sugar from the urine. They recommended strict low carb-high fat diets, with close monitoring of diet and sugar levels in urine. But it soon became apparent that diabetics were often unwilling to follow strict diets.
Diabetes: Locating its Cause in the Pancreas
During the latter half of the 19th century, scientists gradually developed a clearer understanding of the cause of diabetes by focusing attention on the pancreas and its role in regulating metabolism. In 1869, Paul Langerhans, a German medical student, first differentiated two systems of cells in the pancreas: “acini” cells, which secrete normal digestive juices that flow into the intestine; and the mysterious “islet” cells that appeared scattered through the pancreas like islands, unconnected to the acini cells. The islet cells were later named Islets of Langerhans, but their function remained unclear.
In 1889, Dr. Oscar Minkowski, a German physician and physiologist, induced diabetes in a dog after removing its pancreas. The use of animals in medical research (vivisection) became controversial in Europe during the 19thcentury, prompting some regulation, especially in England, but not in Germany. However, greater awareness of animal welfare, the development of anesthesia to control pain, and significant advancements in understanding physiology, based on animal research, applicable to treating and preventing disease in humans, enabled, yet constrained, the use of animals in medical research. National regulation of the use of animals in research and testing was implemented in the United States in 1966 and in Canada in 1968.
Minkowski’s discovery prompted other researchers to later show that the islet cells were the source of a chemical — or an internal secretion later defined as a “hormone” — that somehow regulated blood sugar. At the time, scientists focused their efforts on the pancreas by trying to prepare pancreatic extracts from the whole pancreas and then measuring their effects on sugar levels in urine after injections into diabetic dogs. Starting in 1906, Georg Ludwig Zuelzer, a physician based in Berlin, prepared an alcohol-based extract from calf pancreas and boldly conducted a series of human tests with severe or otherwise hopeless diabetic cases. Such patients were in a diabetic coma and it seemed that little could be lost in trying the extract on them. While the results were encouraging, with clear, but temporary improvement in their condition — the patient seemed to be coming back from the edge of his grave — limited supply of extract and serious toxic reactions, limited progress. Still, to Zuelzer, watching a patient being pulled out of a diabetic coma, albeit only briefly, was unforgettable.
Following other failed efforts to prepare effective pancreatic extracts, Dr. Allen, in 1913, began more focused studies of this organ. He removed 90% of the pancreas in dogs used for experiments to study the effects of diet controls — specifically with carbohydrates, fats and proteins — on diabetic symptoms in those animals. He then applied those findings to treating human diabetics. At the time, there was no regulation of human experimentation: such bioethical regulations didn’t emerge until the 1950s. Allen’s goal was to find the optimal course of fasting, followed by a degree of careful under-nourishment, that would enable a diabetic to live sugar- and symptom-free. For severe diabetics, especially children, such a course of treatment required close supervision in a hospital setting. Unfortunately, in most cases, these treatments ultimately led to a Catch-22: the patients either died from diabetes or starvation.
By 1920, however, the limits of the Allen treatment had become more apparent, including to Allen himself. Concurrent advancements in more easily and precisely measured blood sugar levels prompted some scientists to renew their efforts to prepare pancreatic extracts and test their effects on diabetic animals. This work was led by Israel Kleiner in the U.S., and Nicolas Paulesco in Romania. Their results clearly demonstrated that pancreatic extracts could reduce blood sugar levels, although they only tried them in diabetic dogs. Their pancreatic extracts were prepared from either whole or partial pancreases. Alongside the elusive internal secretion from Islet cells, the extracts invariably contained some of the external secretion cells, along with other pancreatic substances, which could prompt toxic reactions in the lab animals. Thus, there was a clear hesitation to try such extracts on human diabetics.
October 30-31, 1920: Frederick Banting’s Idea
In the early hours of October 31, 1920, in London, Ontario, 28-year-old Dr. Frederick G. Banting woke up suddenly. He had had a flash of insight for a novel experiment to isolate the elusive internal secretion of the pancreas as a means of treating diabetes.
Banting’s idea can be traced to various disparate factors: his training as a physician and surgeon at the University of Toronto; his medical and surgical service during the First World War; and his desire to establish a medical practice. Banting opened his practice in London on July 1, 1920. But after attracting very few patients, in early October, he found part-time work as a demonstrator in surgery and anatomy at the University of Western Ontario. He worked for Dr. F.R. Miller, professor of physiology.
Miller had asked Banting to prepare a lecture for physiology students on carbohydrate metabolism scheduled for November 1st. Although he had no particular interest in the subject, nor the disease most closely associated with it, diabetes, Banting threw himself into the necessary background research. On Sunday, October 30th, he spent several hours preparing his talk. He happened to have just received the November, 1920, issue of Surgery, Gynecology and Obstetrics. The journal’s leading article for that issue was entitled, “The Relation of the Islet of Langerhans to Diabetes with Special Reference to Cases of Pancreatic Lithiasis,” by Moses Barron, an American pathologist. Banting took the journal with him to bed and read the article with particular interest.
The paper was not particularly noteworthy, but it did discuss a rare case of formation of a pancreatic stone (pancreatic lithiasis), similar to a gall stone, that completely obstructed the main pancreatic duct. Barron came across the case while doing routine autopsies. When he examined the pancreas, he found that, while all the acinar cells had disappeared after atrophy due to the pancreatic stone, most of the islet cells appeared to have survived intact. Barron further realized that his observations were similar to what others had shown when pancreatic ducts were blocked experimentally by ligation, or the tying off of the ducts. His observations thus seemed to support the hypothesis that the health of the islet cells was the key factor in the development of diabetes.
Banting, who had also been reading about carbohydrate metabolism and diabetes, fell asleep soon after reading Barron’s article. After a few hours of disturbed sleep, he awoke with a compelling idea that he quickly jotted down in a notebook:
“Diabetus – Ligate pancreatic ducts of dog – Keep dogs alive till acini degenerate leaving Islets – Try to insolate the internal secretion of these to relieve glycosuria”
While his handwriting and spelling may have been a bit off, the idea seemed original as far as he could determine. It pointed to a novel surgical method to isolate the islet cells and possibly enable the extraction of the internal secretion of the pancreas, which could then be used to relieve “glycosuria,” i.e. the distinctive sweet “pissing evil” of diabetes. Banting envisioned that, after ligating the pancreatic duct of one dog and letting the pancreas degenerate while still inside the animal, another dog would be experimentally made diabetic by fully removing its pancreas. After several weeks, the ligated, degenerated pancreas could be removed from the first dog, an extract prepared from it, which would then be administered to the second, diabetic dog, to see if it lowered levels of sugar in its blood and urine.
The next morning, Banting presented his idea to Miller, who was intrigued. But as there were no appropriate research facilities at UWO, Miller suggested Banting consult with Dr. John J.R. Macleod, U of T’s head of physiology and a leading authority on diabetes. Banting already had plans to visit Toronto the following weekend to attend a wedding and hesitantly asked for a meeting with Macleod on Monday, November 7th. As a courtesy to a U of T medicine graduate, Macleod agreed to meet with an excited, though quite nervous, Banting. Needless to say, it turned out to be a significant meeting.