The Discovery of Insulin Read online

  Roberts was immediately rebuked for the intemperance of his letter, indeed for writing the letter at all, by Dr. Henry H. Dale, a leading figure in British research who had recently been in Toronto studying insulin at first hand. Roberts’ review, Dale wrote, was “armchair criticism,” the kind of destructive comment that “seldom leads to anything but verbal controversy.” Whatever might or might not finally be decided about Banting and Best’s experiments, nobody could deny that a first-rate discovery had been made. “It is a poor thing,” Dale scolded, “to attempt belittlement of a great achievement by scornful exposure of errors in its inception.”2

  Dale’s view that critical discussion of Banting and Best’s work amounted to belittlement of a great achievement prevailed in medical and historical circles for the next three decades. There was no point to be served, it was believed, in discussing the issues raised by Roberts, who himself immediately lapsed into silence and was not heard from again; or, for that matter, in discussing the controversy about credit and the Nobel Prize. Most accounts of the discovery of insulin tended to slide over matters that might impair the dignity of science or the glory of the achievement. Yes, it could be revealed that Banting had been extremely bitter about Macleod and the Nobel Prize, and had spoken of the professor in the harshest terms. But why describe the nature of their quarrels in print, let alone print the vulgar terms Banting had actually used about Macleod? As for the technical but extremely important points raised by Roberts about the experiments, some of these could be mentioned in footnotes without appearing to belittle the great discoverers. The one serious biography of Banting, by Lloyd Stevenson, published in 1946, handles the issues this way. For the time Stevenson showed remarkable candour: Banting and Macleod were dead, but the other participants and their colleagues were alive and influential.

  Well into the 1950s the oral history of the discovery of insulin was more interesting than the written history. There was a kind of underground of gossip, centring in Toronto medical circles and usually becoming more interesting after each round of drinks. Everybody who had been on the spot in 1921 and 1922 – professors in the university, medical students, residents and nurses in the hospital, friends of those involved – had stories to tell about what had really happened in those days, what the discoverers were really like, what their fights had been really about. The best stories were the ones the discoverers themselves told. Banting, who died in 1941, and Best, who lived until 1978, tended to be the most talkative. J.J.R. Macleod, who left Toronto in 1928 and died in 1935, had let slip an occasional bitter remark. J.B. Collip, who was never employed in Toronto after 1922, was a very discreet professor at McGill University and then dean of medicine at the University of Western Ontario before his death in 1965. But even Collip would sometimes get talking about the insulin days. For all of them, after all, it was the greatest event of their lives.

  Outsiders and insiders alike assumed that the truth about the birth of insulin would eventually come out after all the principals had died. A few insiders knew, and a few others guessed, of the existence of important unpublished documents. A verbal reference to these documents made about 1967 by my older brother, at that time a professor of physiology at McGill, first interested me in the possibility of some day writing a book on the discovery of insulin. This would be a much better book if he had lived to help write it.

  The critical silence had meanwhile been broken by an American doctor, Joseph H. Pratt, whose lifelong interest in the pancreas and diabetes went back well before the discovery. In his eighties in 1954, Pratt published in the Journal of the History of Medicine a thirty-five-hundred-word article entitled “A Reappraisal of Researches Leading to the Discovery of Insulin.” It was actually a condensed version of a much longer article Pratt had been circulating for some years and agreed to tone down under repeated pressure not to reopen old wounds. Even so, Pratt’s publication was a major critical review of the insulin work. He repeated and expanded upon Roberts’ old criticisms, and made a special point of drawing attention to the contribution Macleod and Collip had made in refining both Banting and Best’s flawed experiments and their crude pancreatic extract. “Credit for the discovery of a preparation of insulin that could be used in treatment,” Pratt wrote, “belongs to the Toronto investigators Banting, Best, Collip, and Macleod working as a team. Each of these men made an important contribution.”3

  Pratt’s attempt to rewrite the history of the discovery of insulin prompted a sharp reply from a medical historian in Toronto, Dr. W.R. Feasby, who was also an ardent admirer of C.H. Best. The burden of Feasby’s 1958 article, “The Discovery of Insulin,” in the Journal of the History of Medicine, was that the conventional history of the discovery was correct in all important particulars. “The published and unpublished records of Banting and Best’s work establish the fact that convincing proof of the presence of insulin was available in the summer of 1921, when they were working alone…” Banting and Best discovered insulin, Feasby reiterated; the others helped somewhat in its development.4

  Pratt had died. Feasby died before finishing the biography of Best on which he worked for several years. Frederick Banting’s second wife, Henrietta, died before making any significant progress on the biography she planned to write of her husband. The Toronto doctor who took over her work, Ian Urquhart, also died. In the meantime medical historians in other countries were beginning to consider the discovery of insulin from the point of view of other people besides the Torontonians who had been working on pancreatic extracts.

  Before his death (the death rate among those trying to write about the discovery of insulin sometimes seems higher than it is among diabetics), a Scots medical historian, Ian Murray, published several articles in the late 1960s and early 1970s on the search for insulin. His aim was to show how the Toronto work related to half a century of earlier investigation of the pancreas and diabetes. Insulin had not emerged out of a vacuum, but was the culmination of years of work by dozens of scientists in many countries. Murray was particularly interested in a Romanian scientist, Nicolas Paulesco, who in 1921, just as Banting and Best were starting to work, published very important papers describing successful experiments with pancreatic extracts. Unfortunately for Paulesco, the North Americans moved so quickly into the testing and production of insulin that he never got serious clinical tests of the material he called “pancréine” under way. Paulesco and his work disappeared from history.

  Now they were resurrected. “Banting and Best are commonly believed to have been the first to have succeeded in isolating insulin,” Ian Murray wrote. “They have been hailed as its ‘discoverers’. Their work, however, may more accurately be construed as confirmation of Paulesco’s findings.”5

  Murray’s work revived Romanian interest in a countryman who had apparently achieved so much and been so little honoured. Influenced by the impending fiftieth anniversary of the discovery, members of the Romanian School of Medicine in Bucharest launched a campaign to have Paulesco given his due. As a result of their agitation, the International Diabetes Federation decided to establish a special blue-ribbon committee to prepare a factual account of the various researches leading to the discovery of insulin. The report, published in 1971, was a careful, tightly written summary of historical knowledge about the discovery. Its conclusions, difficult to simplify because of the subtlety of the argument, were to the effect that Paulesco might indeed have discovered insulin as a therapy for diabetes had not the North Americans been able to move so swiftly and successfully to develop the results of Banting and Best’s research. Pancréine probably contained insulin – so did the pancreatic extracts prepared by several earlier researchers, especially a German named Zuelzer – but it was the Canadians who made insulin suitable for the treatment of diabetes.6

  The Romanians were not satisfied. Their continued complaints about the composition and work of that committee were secondary to their deep anger at an egregious error Banting and Best had made in their first paper, published in February 1922. In t
heir only reference to Paulesco’s work, published before theirs, Banting and Best imply quite wrongly that his results were negative. It is such an odd error, with apparently such devastating consequences for Paulesco’s reputation. Was this why the Nobel people neglected him? the Romanians asked. The leading Romanians interested in Paulesco’s rehabilitation decided that Banting and Best’s misrepresentation of his work was too suspicious to explain away as a simple mistake. It was a deliberate distortion of Paulesco’s work by Banting, wrote Dr. Constantin Bart in a 1976 article entitled “Paulesco Redivivus.” Bart went on to deduce what he thought was the real truth behind Macleod getting half of the Nobel Prize: Macleod, well versed in the literature, must have found out about Banting’s falsification and threatened him with public exposure unless Banting shared the credit and glory with him, Macleod. The history of the discovery of insulin seems to have included scientific blackmail and a vicious conspiracy to cheat Paulesco out of his rightful share of honour and prizes. Truth indeed stranger than fiction.7

  Fanciful as their speculations were, the Romanians had a point in wondering why more had not been written about the events at Toronto. Their reviews of the literature on the history of the discovery alerted them to the quarrelling among the discoverers and to all the unresolved historical controversies about Banting and Best’s research. With European authorities writing almost jeeringly about the “vrai panier de crabes” at Toronto in 1921–22,8 it was surely time to find out what had really happened.

  There was one more important publication in the late 1970s. J.J.R. Macleod had died in Scotland in 1935. Thirteen years later a copy of a document found among his papers reached North America. Dated September 1922, it was entitled “A History of the Researches Leading to the Discovery of Insulin,” and was Macleod’s personal account of the events at Toronto. From 1948 to 1978 the Macleod manuscript had had an underground circulation among a small circle of scholars. Fearful of reopening a controversy that might do no one any good, the president of the University of Toronto in the mid-1950s had quite improperly used his influence to prevent its publication.9 Lloyd Stevenson, who had written Banting’s biography many years earlier, finally published the Macleod document in the Bulletin of the History of Medicine in 1978.

  As the research for my book developed, Macleod’s account turned out to be only one of many new documents shedding light on the discovery. It was clear from a careful reading of Macleod that Banting and Best had prepared similar accounts at the same time in 1922. Manuscripts of these were found. In the Banting Papers was a second long account that Banting had written in 1940. So was the correspondence Banting and Best had had with Macleod in the summer of 1921. So were the original index cards on which Banting and Best had recorded the notes taken from their reading, including their note on Paulesco’s prior article. Banting’s original notebook, in which he recorded his first idea and the first series of experiments, was discovered. So were many other documents. Some of them were coming to light in the natural course of events, as when the University of Toronto made the Banting Papers available for scholarly research, and when the Nobel Committee of the Caroline Institute in Stockholm agreed to open its archives to qualified researchers. Others emerged because of this project. At the outset I decided to make a more determined and careful search for documents than anyone had previously undertaken, and that search was rewarding.

  My aim was to carry out the historian’s job of re-creating the discovery of insulin. As far as possible I wanted to work from contemporary sources. I wanted to ignore the judgments of later writers and put aside the partisan recollections of the discoverers themselves, at least until I had found out from the documents generated at the time – laboratory notebooks, correspondence, published articles, etc. – exactly what had happened. I wanted to reconstruct the insulin research dog by dog, day by day, experiment by experiment. After that it would be proper to reflect on the fallibility of the participants’ memories and the validity of the scientists’ claims and counter-claims.

  More documents were found than I had expected. They include the voluminous records of the University of Toronto’s Insulin Committee, complete with the droppings deposited by experimental mice; every scrap of paper relating to the introduction of insulin into Britain, preserved by the Medical Research Council in London; and the priceless letters a diabetic child wrote to her mother from Toronto in 1922, which were handed to me by their author. I have been able to reconstruct the events in far more detail than I first thought possible. Even so, it will be seen that aspects of the discovery of insulin are still unclear. In some places gaps in the record have to be acknowledged. Some of them are small or insignificant enough to permit a careful, explicit speculative leap. More often than a purist would wish, I have to fall back on memories, on the written accounts generated and distorted by the sensation of the discovery, and on the sixty-year-old recollections of the many people who talked to me out of their concern that the truth be recorded, but who well understood that the truth might not be exactly as they remembered it. These interviews, with everyone I could find who had something to say and was willing to say it (there were more of these people alive than I or anyone else had imagined), were invaluable in conveying colour, anecdotes, and the appreciation of personality absolutely crucial to understanding the men and the events.

  Historians who want their books to be widely read often aim at producing seamless narratives. They weave the material spun from their sources so skilfully that readers are not distracted or bothered by signs of the documentary origins. For this book, however, I decided not to go out of my way to cover up the references to the sources. At times the controversial nature of both the subject and the sources absolutely requires that they be noticed and quoted from at length. At other times the documents are so eloquent that summarizing and paraphrasing destroyed their impact. Changing metaphors, the job is always to build as carefully and finally as one can, but this is the kind of architectural situation where it is best not to try to hide the pipes or disguise the cementwork.

  The book is aimed at any intelligent reader. So all readers will have to put up with minor inconvenience. Laymen will have to learn a few not very difficult medical terms. Medical men must understand that I cannot use their shorthand and am sometimes forced to simplify or ignore some very complex issues – without ever, I hope, doing so to the point of distortion. The extensive documentation in the end notes and bibliography is designed to satisfy scholars without intruding upon the normal reader.

  My aim has been to write a readable and definitive history of the discovery of insulin. I have tried to make the book definitive in two senses: first, that readers who disagree with my conclusions will agree that the book contains a full and fair presentation of all the evidence; second, that the research has been thorough enough to guarantee that any new documents found after publication will not significantly change the account.

  The history of the discovery of insulin, as it emerges in the following pages, is a much more intricate, complex event than our conventional accounts have suggested. It is also a richly dramatic event, and I have tried to present every facet of that drama – the tension, interludes, crises, climaxes, ironies, and occasional absurdities – exactly as it happened. In offering this history, I reject the view that the truth will lead to a belittlement of the discovery of insulin or of the discoverers. This is a book about life, disease, death, salvation, and immortality. It is a wonderful thing to be a witness to the struggles of men, weighed down with all the burdens manhood bears, to find a way of enlarging the possibilities of our human condition.

  CHAPTER ONE

  A Long Prelude

  A person becomes diabetic when the body starts losing the ability to utilize its fuel. The food taken in is no longer fully transformed, or metabolized, into energy. Instead, nutrients begin passing through the system; hence the origin of “diabetes,” from the Greek word meaning siphon or pipe-like.

  A seventeenth-century English surgeon called di
abetes “the pissing evile.” The frequent and voluminous urination by severe diabetics (as much as ten to fifteen quarts a day), accompanied by their unquenchable thirst, had caused the disease to be recognized thousands of years before by the Egyptians and Greeks. In the first century A.D., Arataeus described the disease as “a melting down of the flesh and limbs into urine.” When early physicians found that the urine of diabetics was sweet to the taste, they realized it was heavy with sugar. Gradually the Latin word for honey/sweet, “mellitus,” was added to distinguish the disease from diabetes insipidus, a pituitary disorder in which a large volume of sugar-free urine is passed (containing no sugar, the urine is insipid to the taste). Diabetes mellitus was also called the sugar disease or the sugar sickness. That was a fair description, for the most obvious problem in diabetes mellitus is the body’s failure to be able to burn much of the simple glucose made from its food, especially from carbohydrates. Instead of being absorbed into the cells, the glucose remains in the bloodstream. The kidneys normally remove sugar from the body’s waste water, but in a diabetic’s system the sugar overload is too great. Glucose spills into the urine; the quantities of urine greatly increase; and as the body loses liquids a terrible thirst develops as the system craves renewal. Its craving for sugar leads to a terrible hunger, especially for carbohydrates.

  Frequent urination (polyuria), constant thirst (polydipsia), and excessive hunger (polyphagia) are the classic symptoms of diabetes. They are often accompanied by fatigue or weakness, and then rapid weight loss as the body begins to fail from lack of nourishment.

  Diabetes seems to be brought on by a variety of factors. It is most commonly found in people over forty whose metabolic system has had to work hard during their lives to cope with over-nourishment leading to obesity. That kind of “maturity-onset” (or type 2) diabetes often develops gradually over many years, and the early symptoms are hardly noticeable. In younger people, however, the system’s failure is more commonly sudden and serious. “Juvenile-onset” (type 1) diabetes may in some instances have a viral cause. In both types, however, there is often an hereditary predisposition to diabetes, an inherited genetic or systemic weakness that worsens, either gradually or suddenly, under the influence of other factors.