The Discovery of Insulin

by Michael Bliss

  Banting’s acceptance of the situation was realistic, for he knew that the Nobel award was immutable. Stockholm never explained, changed, or apologized. Consequently the Nobel Committee heard nothing about the outrage their award had caused among Banting and his friends. There is no comment in the Nobel records about the division of the cash (which turned out to be about $24,000). This was the prize winners’ business. The 1923 prize had gone to Banting and Macleod. There is no foundation for stories that Banting had somehow ordered Sweden to put his name before Macleod’s.

  The Nobel Committee did receive furious letters of protest from other quarters. From Berlin, Georg Zuelzer, knowing he would never have success or fame, made a pathetic plea for some recognition of his priority. From Bucharest, Nicolas Paulesco, outraged at what he believed was Toronto’s theft of his work, demanded justice from the Nobel Committee. The protests were ignored.44

  VI

  The University of Toronto recognized its Nobel laureates with a special convocation on November 26, at which Banting and Macleod were each awarded the honorary degree of Doctor of Science. The ceremony was followed by a glittering banquet for four hundred people in the Great Hall of Hart House. The after-dinner speeches were glowing tributes to insulin, Banting, Macleod, sometimes Best, and to the university whose facilities had made it all possible. There were pleas to the public and to governments for more money to support research, and to Canadians and the university to be worthy of their inheritance. It was an evening of self-congratulation and harmony, punctuated only by the class yells of the members of Meds 1 T7 and the music of the jazz orchestra hired for the occasion.

  Some of the insiders must have smiled to themselves as Banting gave his most generous thanks to Best and Velyien Henderson, while Macleod spoke as the representative of all the co-workers in the army that had conquered diabetes. Lewellys Barker, who almost exactly two years earlier had been the first person outside of Toronto to hear of the work, summarized what most reasonable men felt when he said, “There is in insulin glory enough for all.”45

  CHAPTER TEN

  A Continuing Epilogue

  J.J.R. Macleod left the University of Toronto in 1928 to go home as Regius Professor at the University of Aberdeen. People who knew him give conflicting accounts of his reasons for returning to Scotland. In many ways it was a natural move, but there are also stories about how unpleasant Macleod’s life was made in Toronto as a result of Banting’s unrelenting hatred. In one version, Macleod is said to have felt he had to leave or take legal action against Banting. When the university held a farewell dinner for Macleod, Banting not only refused to attend, but is said to have requested that there be an empty place set for him at the table. A friend of the Macleods who went to the train with them the day they left Toronto noticed that the professor was shuffling his feet. Asked why he was doing that, J.J.R. Macleod said, “I’m wiping away the dirt of this city.”1

  Macleod was received in Aberdeen as a great physiologist, the man who had, with his associates, discovered insulin. While it was known that there had been “troubles” in Toronto over insulin, there was no first-hand local knowledge of the details, and the professor himself politely turned aside inquiries from curious students and colleagues. He built a beautiful home, its walls lined with the Canadian paintings the Macleods had collected. But he never talked about the Toronto days. Most of Macleod’s Aberdeen days were spent in nagging pain from a severe arthritic condition. He died in 1935 at age fifty-nine.

  Macleod’s replacement as Professor of Physiology at Toronto was twenty-nine-year old Charles Best. Best had sped through the medical course at Toronto, graduating near the top of his class in 1925. He had married Margaret Mahon in 1924 and the beautiful couple sailed to England, where H.H. Dale was waiting for the young Canadian to do postgraduate work with him at the National Institute for Medical Research. When Dale had first visited Toronto in September 1922, he had been favourably impressed by Best’s work on insulin production and his potential as a scientist. Dale’s advice to Best had been to get out of the limelight and adulation in Toronto and get the thorough training he needed to supplement the insulin adventure. When Toronto was canvassing for a successor to Macleod, Dale and others, including Macleod, recommended Best as one of the most promising physiologists anywhere.

  Fred Banting was able to get back to his lab in 1923, but he never really got out of the limelight. He was barely at work that fall when the Ontario Minister of Health created an enormous newspaper fuss by announcing that Banting was on the verge of discovering something greater than insulin. Banting never got the advanced training or the wise advice that might have guided him into fruitful scientific work after insulin. He should have spent the rest of his life practising medicine. Instead, he was a well-to-do research professor (his annuity and professorial salary totalling $13,500) with no teaching obligations and all the research funding he needed. As students clustered around him, the Banting and Best Chair grew into the Banting and Best Department of Medical Research, a unit separate from the rest of the university. It was Banting’s own little kingdom, a happy land peopled by colourful, often hard-drinking, students and cronies of Banting’s, some of whom were adept scientific tinkerers. All the unpleasant administrative work was handled by the faithful Miss Sadie Gairns, who had become Banting’s first research assistant in 1922. In 1930 the university named a new medical building the Banting Institute. While the Banting and Best Department was housed on one floor, the “Institute” had no real existence at all, a situation causing no end of confusion both inside and outside the university.

  Most of Banting’s research after insulin was directed at finding a cure for cancer, mainly by way of experiments trying to produce resistance to Rous’s sarcoma (a virally induced tumour). Banting tried very hard to duplicate what he thought was the insulin experience: viz, the having of a great idea, thinking up the ingenious approach that would solve everything. In his many talks on medical research he always emphasized the ideas, not the training, that researchers brought to their work. Except for some interesting and now controversial work on silicosis, Banting’s ideas did not pan out. Throughout his life, of course, the press and the public continued to hope that Banting would repeat the triumph of insulin. H.H. Dale, later Sir Henry Dale, told the story of a reporter who called to confirm a story about a great discovery by Banting in Canada: “Is it possible that Dr. Banting has found a cure for metabolism?” the reporter asked Dale.

  Fred’s love for Edith Roach suffered several more tempestuous episodes. According to those who liked Fred but not Edith, she was all too willing to marry him now that he was the discoverer of insulin. Those who knew Edith well remember that she demurred all the more strongly, saying that everyone would think she was only marrying him for his fame. In 1924 Canada’s most eligible bachelor was suddenly swept off his feet and married by a doctor’s daughter from Elora, Ontario, the attractive and very sociable Marion Robertson. Edith married many years later. The Banting marriage was a disaster, ending in 1932 in a sensational, some said scandalous, divorce. This aspect of his life, his attempts to cope with his notoriety, his growing interest in painting and the arts, his travels, and his professional adventures, are dealt with in my forthcoming biography of Banting. Fred Banting was more interesting and more successful as a man than as a scientist. He was the kind of person who fulfills Joan Didion’s definition of a literary character – “ambiguous and driven and revealing of his time and place.”2

  Banting matured and mellowed in the 1930s. He grew out of many of the hatreds of the insulin days, becoming close friends with Bert Collip and coming to revere Duncan Graham as a father-substitute. His hatred for Macleod did not diminish. To it was added a dislike of Best. It grew out of the friction naturally resulting from the two of them having to share power and influence in the hothouse worlds of the University of Toronto and Canadian medical research. Banting disliked Best’s ambition; Best could not respect Banting as a scientist.

  When a Co
nservative government of Canada briefly resumed accepting titles for Canadians in 1934, Banting was honoured with a knighthood, becoming Sir Frederick Banting, K.B.E. It was the most incongruous of all his honours, and he knew it. “Next person who calls me ‘Sir’ will get his ass kicked,” he once said at a meeting of medical men in England. Fred Banting was nothing if not one of the boys.

  When war resumed in 1939, Banting had just married again, to a technician in his department, Henrietta Ball. He tried to enlist as an ordinary medical officer, but was pressured to serve as co-ordinating chairman of Canada’s wartime medical research effort, and appears to have done this job well. While in London in the winter of 1939–40, consulting with his British counterparts, he filled in weekend hours writing the long account of the discovery of insulin referred to so often in these pages. It contains some excellent passages, but Banting’s history is rambling, unpolished, and was never checked for accuracy – more a documentary source than a history in its own right.

  Banting returned to Canada in the spring of 1940. On February 20, 1941, he took off from Gander, Newfoundland, aboard a Hudson bomber, en route to England for a second time. The plane crashed in Newfoundland. Banting died in the wreck. There was much speculation about the reason for his embarking on such a hazardous mission, and on the cause of the crash. Was Banting carrying vital military intelligence? Was his plane sabotaged by Nazi agents? An accurate account of Banting’s last mission will be found in the biography.

  Best and Collip were the two members of the insulin team who went on to long careers as productive researchers. Best, his associates, and his students at Toronto, continued Macleod’s work on the properties of insulin, did basic studies of the dietary factor choline, and developed the important anti-coagulant, heparin. After Banting died, Best inherited his mantle as the most prominent living discoverer of insulin. He also took charge of the Banting and Best Department, which was eventually integrated into the faculty of medicine. In 1953 the university erected the Best Institute next door to the Banting Institute, doubling the confusion caused by naming buildings institutes. In the later years of his life Best was showered with honours by grateful diabetic associations, medical bodies, and universities. The Nobel Prize, which he felt he ought to have shared in 1923, eluded him.3 Bouts of serious depression appear to have accentuated an obsessive concern for credit and glory. Charles Best retired in 1967. He died in 1978 of an illness brought on by hearing the news of the death of his oldest son.

  J.B. Collip recovered from the dead end of glucokinin to do intensive pioneering work on the isolation of the parathyroid hormone, in his spare time adding a medical degree to his list of letters. In 1927 he almost went to the Mayo Clinic in the United States, but changed his mind – turning down what is said to have been a “staggering” salary4 – and the next year accepted the chair of biochemistry at McGill University. Collip’s McGill years were a whirlwind of endocrinological research as he and his students were in the forefront of the isolation and study of the ovarian and gonadotrophic and adenocorticotrophic hormones. Just as Banting always hoped he would repeat his great Idea, Collip always hoped he could isolate another magic hormone, and there was a long succession of products produced in co-operation with drug companies – parathormone, then Emmenin, Premarin, and brands of ACTH. None of them came close to insulin, of course, but in trying so hard and so variously (with a fairly high degree of failure and error, as well, as in the glucokinin affair), and by concentrating his restless energy in one field, Collip made himself by far the dominant figure in the history of endocrinology in Canada. Endocrinological research generally had received an enormous stimulus everywhere by the discovery of insulin. The next spectacular therapeutic advance in the 1920s after insulin, the use of liver extracts for pernicious anemia, came out of the heightened interest in organ therapy caused by insulin and was also insulin-dependent in the sense that one of the discoverers, George Minot of Harvard, was a severe diabetic.

  Fred Banting spent his last night in Montreal with Collip before going on to Gander. Collip was deeply shaken by the news of his death. In an obituary tribute to Banting a few months later he made his last statement about his own role in the discovery of insulin, writing that his contribution to the team was “only that which any well-trained biochemist could be expected to contribute, and was indeed very trivial by comparison with Banting’s contribution.” Banting in those last years had told friends that he and Best wouldn’t have achieved a damned thing without Collip.5

  In 1947 Collip became dean of medicine at the University of Western Ontario, by then a considerably better medical school than in the days of Banting’s demonstratorship a quarter-century earlier. Collip served as dean for fourteen years and then continued as head of the Department of Medical Research at Western. He died in 1965 at age seventy-two, just after finishing another of his marathon drives across the North American continent. In later years Collip was very reluctant to talk or write about the discovery of insulin, saying that the truth was to be found in the scientific publications and might emerge after they were all dead.

  Others were not so reticent about claiming credit for the discovery. Georg Zuelzer, for example, often referred to himself in public as the discoverer of insulin. A refugee from Nazism, he emigrated to the United States in 1934 and spent the last years of his life practising medicine there. According to Best, Zuelzer once came to Toronto and insisted on his priority to those who would listen to him. Years earlier in Germany, Minkowski had publicly disposed of his claims by saying, after listening to Zuelzer, “I too share with Doctor Zuelzer the regret that I did not discover insulin.”6 Zuelzer died in a home for the aged in New York in 1952.

  Late in 1923 E.L. Scott published a brief claim to priority in the discovery of a method of extracting the active principle of the pancreas (“the discovery of the curative power of ‘insulin’ has been open from January, 1912, to any one who cared to repeat and extend my work”). At the same time, however, he wrote Banting congratulating him and Macleod as the “logical recipients” of the Nobel Prize, and stating that they had always given him, Scott, “all the credit that was coming to me.” Scott had made his claim, he wrote, because “I was after another man who I have very good reason to believe is perfectly willing to accept credit due not only to me but others including yourself.”7

  That man, Murlin, had applied for a patent on his anti-diabetic pancreatic substance in July 1923. When it was finally granted in 1925, the patent protected as “discovery” of no use to anyone. Murlin, who never did understand how Toronto had beaten him to insulin, continued to work furiously to discover something better than insulin, and did have at least the satisfaction of discovering the second (but far less significant) islet-cell hormone, glucagon. In the late 1950s Murlin and Kramer joined the discussion Pratt had sparked about the insulin research by publishing an account of their work, claiming a place in the history books.8 To the end of his life, I was told by acquaintances, Murlin believed that the people in Toronto had somehow stolen his work. E.L. Scott’s widow, and the Romanian friends of Paulesco, also claimed that credit had not been given to those who had really done the work. Paulesco himself gravitated to proto-Nazi, anti-Semitic politics before his death in 1931. Israel Kleiner, who in 1919 was closer to success than any of them, made no claims at all.

  The outsider whose life’s work and reputation was most affected by the discovery was Frederick M. Allen. Before insulin, Allen was the man to reckon with in diabetes, his work and methods dominating his field to an extent seldom equalled in therapeutics. After insulin, Allen was just another diabetologist, the proprietor of a high-cost institute many of whose patients no longer needed its services. Allen was also a man with few friends, many enemies, and no university or foundation support.

  He turned much of his attention to hypertension, becoming one of the first to prescribe low-salt diets for high blood pressure. But he also kept on with diabetes research, and in 1927 announced the discovery of a new treatment
for diabetes. It was a preparation made from mulberry or blueberry leaves, a refinement of an old Austrian folk remedy which had been brought to Morristown by a visiting Austrian scientist, one Dr. Wagner. It had the advantage over insulin of being able to be given orally. Allen named his preparation “Myrtillin,” applied for a patent on it, an d entered into an agreement with E.R. Squibb & Son to develop it.

  Myrtillin went the way of glucokinin and other vegetable-derived hypoglycemic agents discovered in the 1920s. The action of the chocolate-coated anti-diabetic pills was too slow, erratic, and toxic to be suitable for humans. The Myrtillin failure left Allen deeply in debt to Squibb’s, who in 1930 brought suit to recover the money they had loaned him.9 They were among a host of Dr. Allen’s creditors that depression year. He waged a heroic struggle to keep his half-empty Physiatric Institute going, only to be finally evicted in 1936.

  Frederick Allen drifted from one little-known hospital to another, carrying on his animal experiments in basements, outbuildings, once in rented space in a public stable. A fanatical researcher to the end, he had gone on from hypertension to studies of the use of refrigeration in surgery and then to cancer research, never having adequate funding, becoming increasingly isolated, bitter and paranoic about his treatment at the hands of the medical Establishment. Allen’s life, like Captain Ahab’s, was a tragedy of American individualism. His pathetic unpublished autobiography ends as he is meditating on how fortunate another outsider, Frederick Banting, was, to have his work accepted and his later research so well supported. When he had first ment Banting in the summer of 1922 and heard his story, Allen had offered him a job at the Physiatric Institute. Frederick Allen was pursuing his research in the basement of the Pondville State Hospital in Massachusetts when he died in 1964 in his eighty-eighth year. The last word as his autobiography breaks off is “independent.”10