I
The Insulin Committee of the University of Toronto continued to administer the basic Banting, Best, and Collip patent, as well as important later patents (particularly that assigned to the university by Albert Fisher and D.A. Scott for protamine-zinc insulin) until they all expired in the 1960s. One of the important unresolved issues during the discovery period had been whether the committee would stand by its original decision to collect royalties from licensed manufacturers. In Britain and Europe, where even the decision to patent was thought highly questionable, there was intense resistance to the idea of paying royalties. Among the group at Toronto both Banting and Macleod, particularly the latter, opposed the royalties; at a proposed rate of 5 per cent of the retail selling price of insulin the University of Toronto’s share was a good return for any profit-minded inventor. The businessmen on the Insulin Committee seem to have argued that some royalty was obviously necessary to pay the committee’s costs, especially if it had to go into court to defend its patent rights, and that any surplus could properly and ethically be devoted to research in the university. While the committee finally stopped trying to collect royalties outside of North America, it always received substantial royalties from insulin sales in the United States and Canada.
Between 1923 and 1967 the University of Toronto’s royalties from insulin totalled $8 million.11 The Insulin Committee’s costs were not very high – it never had to go to court to protect the patents – so a considerable surplus was available to support research. According to an agreement worked out in 1923, half of this surplus went to research directed by Banting, Best, and Collip (Collip’s share being paid to the university that employed him), the other half to the University of Toronto’s general research funds.12 The sums involved are trivial by today’s standards, but were very substantial in the early years. Royalties averaging over $180,000 annually in the 1930s went a long way in those depression years – and the figures do not include other significant grants for research projects that came from the Lilly Company, which maintained close ties with Toronto into the 1960s. The one technically improper use of insulin profits at the university was the spending of several thousand carefully laundered insulin dollars in 1941 to help Oskar Minkowski’s widow flee from Germany to Argentina. This was one of Charles Best’s efforts to help European scientists and their families in the 1940s.
Eli Lilly and Company sold more than a million dollars’ worth of insulin in its first year of marketing, and never looked back. Insulin did more than any other single product to transform the company into a giant in the American pharmaceutical industry. The relationship with Toronto which, on balance, had worked well in the interests of everyone involved, gave the company a dominance in American insulin production which it easily maintained into the twenty-first century and the age of insulin manufacture by genetic engineering. The introduction of insulin, using extensive clinical testing and physician education in an age before government regulation, had been a great credit to both the company and the university. As well, insulin had established the scientific credentials of the company and given it a reputation as a pioneer in collaborative work with university researchers, many of whom, including the American discoverers of the treatment for pernicious anemia and Canadians experimenting with vincristine derivatives to treat leukemia, came to Lilly with their ideas.
Canada’s insulin was supplied by the Connaught Laboratories, wholly owned by the University of Toronto, and was the staple of the company’s development into a major pharmaceutical house in its own right, the largest Canadian-owned drug company. In 1972 the University sold Con-naught Laboratories, putting the proceeds into a special fund to support research.13 Connaught’s insulin division was eventually sold to Novo-Nordisk, the Danish-based insulin company that had evolved out from August Krogh’s visit to Toronto in 1922 and was now competing around the world with Eli Lilly.
Talk of honouring the insulin discovery by raising a private endowment to fund research became a reality in Toronto in 1925 when the university’s prominent governors, led by Sir William Mulock, launched the Banting Research Foundation. In a whirlwind fund-raising campaign, characterized by the raising of extravagant expectations about the possibility of curing cancer and other dread diseases, the foundation’s capital goal of $500,000 was easily met.14
There was considerable hope in the early years that the Banting-to-insulin progress could be repeated. Several practising physicians brought their bright ideas to Toronto, where, thanks to the Banting Research Foundation, and Banting himself, they received more generous support than Professor Macleod had ever given Fred Banting. But Fred’s classmate, Beaumont Cornell, did not solve the riddle of pernicious anemia and the liver extract proposed by Dr. MacDonald of St. Catharines to reduce high blood pressure also failed to work, dashing everyone’s early high hopes. That matter also created some embarrassment and nearly ended up in the courts when a professor from the University of Western Ontario accused MacDonald of stealing his ideas. Medical history, too, has a tendency to repeat itself as farce.
Through the years many other more qualified researchers received valuable aid financial aid from the Banting Research Foundation. It lives on as a small, but historic and proudly independent granting agency. Organized support for scientific research in Canada, from both public and private sources (mostly the big American foundations) was still so primitive before World War II that the money generated by insulin was probably the largest pool of Canadian capital supporting medical research.
Insulin had given such prominence to the University of Toronto, particularly in the field of diabetes work, and created so much support for more research in Toronto, that it was later wondered why the city did not become a world centre of diabetes research and treatment. There were several reasons. Macleod’s departure crippled the university’s insulin research capacity. The one trained clinician on hand when insulin was discovered, Walter Campbell, ironically nicknamed “Dynamite,” was slow-talking, slow-moving, fundamentally unenterprising. The clinician who took over the limelight in Toronto during the discovery period, Banting, was not a good diabetologist, and in any case decided his future lay in developing great ideas to cure other diseases. Generally, discoverers and clinicians alike shared the view that insulin had licked diabetes. When insulin became widely available, the special diabetes clinic at Toronto General Hospital closed down. You gave insulin to the world and went on to some other great thing. It happened that the next product given to the world by Toronto medical researchers was pablum, invented at the Hospital for Sick Children. More than 85 years after the discovery of insulin Canadian medical researchers had not won a second Nobel Prize.
By contrast, Elliott Joslin had devoted his life to the treatment of diabetes. He also realized that the disease was far from conquered by insulin. He considered insulin the end of one era in diabetes management, not the end of diabetes. With boundless energy, a deep sense of mission, and considerable public relations skill, Joslin continued to expand his facilities and his staff in Boston, becoming the ‘master clinician’ of diabetes,15 leaving at his death in 1962 a major establishment, the Joslin Clinic of ongoing national and international significance. It was the kind of legacy Frederick M. Allen had hoped to create through his Physiatric Institute and that the Toronto discovers of insulin did not think it was necessary for them to create. In the 1950s Charles Best did encourage diabetes research, and in the late 1970s the University of Toronto decided to concentrate its expertise, build on its traditions, increase its research effort, and honour Banting and Best, by creating the Banting and Best Diabetes Centre. Toronto once again became a major player on the diabetes field.
II
Leonard Thompson, the first person brought back from the edge of the grave by insulin, died on Easter Monday, April 20, 1935, in Toronto General Hospital. Thompson was twenty-seven years old. He had lived a more or less normal life, holding down a steady job as an assistant in a drug and chemical factory, taking eighty-five units of insul
in daily. He was not a very well-controlled diabetic, and was in particular difficulty during the tenth anniversary of the discovery, apparently from excessive celebration. Once in 1932 he was brought into Toronto General in a coma and only barely survived.
The story that Thompson’s death was caused by a motorcycle accident is incorrect. In his final illness a bout of influenza led to pneumonia complicated by severe acidosis. He died in a coma in an oxygen tent. Leonard Thompson’s pancreas was small and partly atrophied, with few islet cells. The irreverent young staff at the hospital suggested that it should be mounted over the front door of the Banting Institute. When Fred Banting met the medical student who had done the autopsy, Burns Plewes, he asked, “Did that poor boy remain on a high-fat low carbohydrate diet all these years?”
“Yes,” Plewes answered.
“Did he have any fun?”
“Yes, he had some fun. He used to get drunk nearly every weekend.”
“Well, I’m glad he had some fun.”
Leonard Thompson’s pancreas was preserved and is displayed as item 3030 in the anatomical museum at the Banting Institute.
Jim Havens, the first American to receive insulin, became an artist. He specialized in woodcuts, his work was widely exhibited, and he was eventually elected to membership in the National Academy of Design. He married in 1927, had two children, and worked closely with Elliott Joslin on experiments with insulin. Havens had more than his share of illness, but controlled his diet and insulin well and lived a fairly normal life. He was beginning to experience some of the complications of his condition when he died of cancer in 1960 at age fifty-nine.
Elizabeth Hughes graduated from Barnard College in 1929 and the next year married William T. Gossett, a talented young lawyer. The couple moved to Michigan where Gossett rose through the legal department of the Ford Motor Company, becoming vice-president and general counsel and serving a term as president of the American Bar Association. Elizabeth was prominent in civic affairs and voluntary work in the Detroit area, while raising three children, all born by caesarian section. She was overweight for several years in the late 1920s, took up smoking, and would have the occasional cocktail, but in fact controlled her diet rigidly, eventually dropping back to a bit below normal weight and giving up smoking. She was athletic and an indefatigable world traveller, but never went anywhere, of course, without her insulin.
Elizabeth remembered the years of starvation before insulin as a “nightmare” from which she had awakened in Toronto to lead a normal life. She put the nightmare years behind her, and made her life as normal as possible, telling no one of her diabetes and insulin dependence. Even William Gossett did not learn her secret until a week after they had become engaged.
After first studying Elizabeth Hughes’ medical records in the Banting Papers, and then finding him through biographies of Charles Evans Hughes and Who’s Who, I wrote to W.T. Gossett asking, in effect, when his wife had died and of the later course of her diabetes. The reply came from Elizabeth Hughes Gossett herself, alive and in good health fifty-eight years and some 43,000 injections after first receiving insulin in Toronto.
She was distressed that I had been able to locate her and discover her secret. She agreed to see me only after I promised to give her a pseudonym and disguise her identity in this book. In November 1980, we spent a Saturday together at the Gossett home in Birmingham, Michigan. Elizabeth was a slim, attractive, husky-voiced lady, somewhat wizened, and grey-haired, of course, but with none of the debilities of the legs or eyes that often plague diabetics in their old age. She was perfectly alert mentally, rather more intellectually supple and wide-ranging than many people half her age. She was just back from a six weeks’ tour of China. In the 1970s, concerned to perpetuate her father’s greatest work, she had been the guiding spirit founding the Supreme Court Historical Society.
At the end of our day together Elizabeth loaned me the letters she had written to her mother from Toronto in 1922. As agreed, I disguised her identity in the early drafts of this book, inventing “Katharine Lonsdale,” the diabetic daughter of a prominent American political figure. On April 25, 1981, Elizabeth Hughes Gossett died suddenly of a heart attack, the condition perhaps brought on by sixty years of diabetes. She had said she would have no objection to my writing freely about her after her death.
Several months after the publication of the first edition of this book I learned that one of the “living skeletons” brought to Toronto in July 1922 (see p. 144) was still alive. Teddy Ryder, the five-year-old son of a New Jersey engineer, received his first insulin from Banting in Toronto on July 10, 1922. He weighed 26 pounds. In 1983 Ted Ryder lived quietly in retirement in Hartford, Connecticut, still taking his insulin, suffering no major problems from his diabetes. His mother, Mildred Ryder, alert and healthy at 92, had vivid memories of their trip to Toronto in the summer of 1922, including someone’s comment at the station in New York: “I feel so sorry for Mildred; you know she’ll never bring that child back alive.”
In 1990 Ted Ryder, age 73, returned to Toronto for the launch of a display about the discovery of insulin and the naming of the J. J.R. Macleod Auditorium on the site of the old medical building. Ted and his girlfriend (after the death of his over-protective mother he was having a wonderful late-life romance) came to dinner at our home. In July 1992 Ted became the first diabetic to live seventy years on insulin, having taken some 60,000 injections. He died of old age and complications in April, 1993, giving the residue of his estate to the University of Toronto to be used for medical research. While Ted was the last of the original Toronto patients (he and Elizabeth Hughes outlived all of the discoverers of insulin), remarkable, inspiring stories of the longevity of insulin-dependent diabetes have continued to multiply. The early years of the current century witnessed the honouring of the first 75- and then 80-year veterans of insulin use.
III
But those stories could be misleading. The discovery of insulin did not lead to more than a few medical miracles like the cases of Elizabeth Hughes and Ted Ryder. The prosaic reality was that diabetics’ cup was still half-empty. For all the diabetics to whom insulin became the staff of life itself, there were others who could not afford it or were too proud to take means tests to get it as charity. There were diabetics in the 1920s whose doctors had yet to learn about insulin or were too conservative to use it. There were, and in parts of the world still are, diabetics who never knew they were diabetic, having access to no doctor at all.
Some of those who were given insulin used it recklessly, assuming they could eat and drink all they wanted, so long as they covered themselves by upping the dose. The type of doctor who came to specialize in pills and bills probably contributed to this attitude, finding that prescribing insulin was the fastest way of processing his diabetic patients (many of whom, with type 2 diabetes, would not need insulin and might be better off without it). Insulin’s influence on medical practice in that respect could be harmful. It was one of the first of the truly powerful and effective weapons in the ordinary physician’s “arsenal” against disease. The filling-up of that arsenal, with the sulfonamides in the 1930s, then penicillin and the other antibiotics in the 1940s and 1950s, then drug upon drug, made many physicians too confident of their powers, and many laymen too certain that their doctors had a quick fix for every sickness. The trouble with being able to work miracles, virtually raising people from the dead, is that it tends to replace one kind of religion with another, one set of priests with another.
As a research achievement, the discovery of insulin was almost too perfect. The appearance of insulin out of nowhere, it seemed, as the “cure” for diabetes may have fostered, as it certainly did in Toronto, a belief that next week or next year – or, as a friend wrote to Banting, “every few minutes”16 – the doctors would come up with another cure. Surely it was just a matter of a little more time and a little more money before Banting or somebody else unlocked the secrets of heart disease or cancer. It was only gradually realized that
the discovery of insulin was not a model of how medical research would develop. On the other hand, if you looked at the discovery not as the overnight achievement of unsung genius, but as the culmination of a world-wide, thirty-year search involving hundreds of researchers spending millions of dollars and sacrificing thousands of animals, perhaps it was more typical. The problem was that hardly anyone looked at the discovery of insulin in this way.
It was gradually realized that insulin had not solved the problem of diabetes. Diabetics who got the insulin they needed and then balanced their diets and their insulin as carefully as possible could not regain physiological normality. Artificially supplied insulin, the need for which could only be estimated by crude, inaccurate urine and blood tests, could not truly compensate for the missing pancreatic function. In the years after insulin, as Chris Feudtner shows poignantly in his 2003 book Bittersweet: Diabetes, Insulin, and the Transformation of Illness, diabetes took a heavy toll in impaired vision, kidney disease, hardening of the arteries with a variety of circulatory problems, and other so-called degenerative complications. As Joslin once put it, the era of coma as the central problem of diabetes had given way to the era of complications. The “miracle” of insulin had been to multiply the life expectancy of an early-onset or type 1 diabetic twenty-five fold. The statistical reality was that this total life expectancy remained considerably less than that of people whose pancreas functions normally.
The Discovery of Insulin Page 34