Macleod welcomed the opportunity to say all of these things in writing, “If by so doing I can help to retain for the University of Toronto the reputation which it has already acquired, through the publications on Insulin, as a place where collaborative investigation among diverse groups has been successful in giving to medical science a finished piece of work within a few months’ time.”22
Fred Banting knew that he – he alone – had had the Idea that led to the discovery of insulin. He knew and would never forget that Macleod had been critical and discouraging of his work at every turn. Macleod had not believed in him or his Idea. As Banting remembered the events of 1921, Macleod had been part of his problem, not an aid to its solution. Discovering insulin was a matter of pursuing the Idea in the face of a long series of obstacles. That September 1921 interview, when Macleod told him “As far as you are concerned, I am the University of Toronto”, had been particularly devastating. He had only stayed at Toronto, Banting now believed, because of Velyien Henderson. Henderson was the one person who had encouraged and stood by him when he needed help. Henderson was barely getting any credit at all. Banting tended not to remember any of Macleod’s specific suggestions, or remember them as being of any value, only that Macleod had not done any of the experiments, not a single one.
In Banting’s history, Collip had started work only after the important advances had been made. (Without quite realizing the implications of what he was saying, Banting used Macleod’s reluctance to let Collip start work as further evidence of the professor’s lack of helpfulness.) Macleod had treated Banting unfairly at New Haven, then Collip had broken the gentlemen’s agreement by refusing to tell Banting and Best his methods, which Banting accused him of wanting to patent. Macleod had allowed the impression to be spread throughout the United States and England that he, Macleod, had originated the work. Banting was willing to credit Macleod with a “most admirable” execution of the investigation of insulin’s physiological action, beginning – in Banting’s mind – about February 1, 1922. Well before that date, Banting believed, he and Best had discovered insulin. In an appendix to his account Banting catalogued another half-dozen examples of Macleod showing “a lack of trust and co-operation” to him, ranging from a squabble over summer research funds to derogatory remarks Macleod had apparently made to another doctor. Banting concluded, a little hesitantly perhaps, that “All these points of difference might have been reasonably and easily explained to me had Professor Macleod wished to do so.”23
As Macleod’s student and Banting’s co-worker, Best had been more or less caught between the two of them in their running quarrels. He had tended to mind his business, spend his spare time with Margaret, and take little part in the fighting. Of the three accounts of the discovery Best’s was the shortest, only about a thousand words, but perhaps the most objective. It was a straightforward, sometimes almost point form, statement of who had done what. Best gave much more credit to Macleod than Banting did, confirming, for example, Macleod’s claim to have suggested the use of alcohol as an extractive. He also gave more credit to Collip than Banting did, though not on the key point of methods of purification. (“In my opinion the principal work which Dr. Collip performed was to determine the highest concentration of alcohol [in] which the active principle was soluble.”) There was no rehearsal of injustices in Best’s account, or any of the sense of grievance that echoed through both Banting’s and Macleod’s documents.
Best was the only one of the three to comment directly on what, in retrospect, appears to be a vital point in the dispute. Could it be said that Macleod and Collip, seeing how promising the junior men’s work was going to be, had stepped in and taken over, getting the good results and trying to get the credit, without having given Banting and Best a fair chance to do it themselves? “The work during the fall months reported in our two papers was performed entirely by Banting and myself,” Best wrote. “We had the benefit of Dr. Macleod’s advice, but as he states, we were given the opportunity to conclusively prove the efficiency of our extract upon diabetic animals, and as will be stated subsequently, diabetic patients, before the other members of the Physiological Staff participated in this work.”
Unfortunately, neither Best’s nor Banting’s accounts discusses that first testing of their extract on diabetic patients. Best concluded his history by saying that he was going into less detail than he intended to; he wrote it under a momentary misapprehension that Banting and Macleod had managed to reconcile most of the details in their versions.24
There was no reconciliation, then or later. The meeting Gooderham had suggested was not held. It is not known how Gooderham reacted to these documents, except that he realized that they disagreed.25 No comprehensive account of the discovery of insulin was ever prepared at Toronto. The documents were not made public (Gooderham’s original copies still cannot be found), of course, and the discoverers gave no more statements to the press about credit in 1922.
IV
Relations among the principals at Toronto continued to be tense. Whenever Banting and Macleod had to settle anything together the atmosphere was either frigid or heated, nothing in between. After the summer of 1922 the only significant written communication is a long formal letter from Banting to Macleod written at the end of September, setting out the arrangements that the two of them and Velyien Henderson had reached governing Banting’s resumption of research. Banting had not been able to get satisfactory space in any of the laboratory departments, he claimed, and had finally threatened to start a private laboratory outside of the university on his own initiative. Henderson stepped in and offered to give Banting space in the Pharmacology Department if Macleod would surrender a share of the Carnegie grant that had been awarded to Physiology for insulin research. Macleod went along with the proposal.26
While feuding with Macleod over lab space, Banting was also quarrelling constantly with Duncan Graham about the management of the Diabetes Clinic at Toronto General Hospital. He complained that Campbell and Fletcher were getting all the patients, that he was not getting paid, that his colleagues were not treating patients properly, that he did not have enough lab space. The clinic did not work well, Banting wrote in 1940: “Graham was a close personal friend of Macleod’s. I could tolerate Fletcher but I could not tolerate Campbell. Graham was always absolutely fair and unselfish and I respected him because of this unselfishness and absolute honesty. But we were not friends. I could not talk to him. We did not then understand each other. I hated him, and he hated me.” According to Banting, Graham at one point lost patience with him entirely, and suggested he leave Toronto and go to New York. Graham himself was having anything but an easy time directing a clinic using a spectacular new treatment that hundreds of patients were clamouring to obtain. Banting was a perpetual thorn in his side.* And in the side of his secretary, Stella Clutton, to whom Banting often complained about her boss. Reaching the end of her patience one day, she said to him, “Fred Banting, you’re acting like a fifteen-year old; why don’t you grow up?”27
Macleod and Banting continued the dispute about credit in front of their fellow scientists and by proxy. Both were in demand as speakers at gatherings of medical men. Banting’s talks centred on how he got his idea and how he and Best got their first results that summer of 1921. Macleod and Collip would be mentioned, briefly, as having done valuable work in the development of the discovery. Macleod’s talks always began with Banting, Best, and duct ligation, but gave much attention to glycogen and respiratory quotient experiments, the purification problem, Collip, and the rest of the team. On occasions when they both spoke, each giving his complete version, it was a long evening. People who knew what was going on did not know whether to be amused or angry.28
They talked and wrote privately to friends who they knew would make use of what they learned. When Macleod wrote Bayliss explaining the difficulty his letter had caused, for example, he sketched the history as he saw it, and mentioned how “greatly relieved” he was “that there are those in
England who will see to it that due credit is given to all who have participated in our joint endeavours.” Bayliss later published a letter in Nature which Macleod told Collip “puts things pretty straight.”29† Banting had always talked freely to his friends; they in turn talked fairly freely to reporters, especially Greenaway of the Star, leaking details of Banting’s hardships, the difficulty he had getting adequate working space, and other injustices done to him.
Banting’s written statements are franker, cruder, more accusatory, and more bludgeoning than Macleod’s cool, scientific prose, self-justifying as it, too, could be. Banting now hated Macleod with a passion, an attitude he never abandoned. His most violent written expression of his feelings was in 1940, at a time in life when many of his friends thought he had mellowed. In some ways he had, but not when he was writing about the discovery of insulin and remembering those fights he had had with Macleod in 1921 and 1922:
MacLeod…was never to be trusted. He was the most selfish man I have ever known. He sought at every possible opportunity to advance himself. If you told Macleod anything in the morning, it was in print or in a lecture under his name by evening. He was grasping, selfish, deceptive, self-seeking and empty of truth, yet he was clever as a speaker and writer. He never produced a physiologist for he took all that anyone had for his own purpose. He loved acclaim and applause. He had a selfish, over-powering ambition. He was unscrupulous and would steal an idea or credit for work from any possible source. Like all bullies, MacLeod was a coward and a skulking weakling if things did not go his way.30
The invective, which continues for another several hundred words, ending with “simpering coward,” says more about Banting than it does about Macleod. Everyone I have talked with who knew Macleod personally-friends, students, colleagues, his former secretary – considers Banting’s view of him absurd or worse. J.J.R. Macleod was a gentle, honest, dedicated scientist. He was perhaps a little shy and reserved, particularly with students and strangers, perhaps a little vain. He was by temperament a cautious scientist, not brilliant or imaginative, but sound and plodding. He liked to quote Pasteur’s remark that in science chance favours the prepared mind. He was an urbane, cultivated, and dapper member of the professoriat. A common view of him as having been very authoritarian, on the German model of the “Herr Geheimrat” professor, is flatly denied by everyone who knew him, including former students, employees, and colleagues who worked with truly authoritarian German professors.
Macleod was bewildered by Banting and his ferocity. The quarrelling seems to have been deeply troubling to him. He never put his deepest feelings about Banting on paper or talked frankly to friends about Banting and the discovery period. In later years it was Mrs. Macleod who would drop the occasional remark about “that horrible Doctor Banting who made our life so miserable in Toronto.” After studying Macleod’s correspondence and talking to people who knew him, I believe that at bottom Macleod was contemptuous of Banting for his ignorance as a researcher and for the crudeness of his manners, dress, and language. Macleod believed, I think, that Banting and Best would not have come close to insulin without his and then Collip’s help.
It is remarkable, in a way, that Macleod seldom did more than hint at this attitude in his letters and articles. He never said nearly as much as he could have about Banting’s scientific ignorance, the weaknesses of Banting and Best’s experiments, the problems with the first clinical tests, and, above all, the fact that when Banting had an open field in front of him to develop his extract in the fall of 1921, the best suggestion he had been able to produce was the idea of pancreatic grafts. Macleod slid over so much of this in his many accounts of the discovery that it is possible to read them as giving more credit to Banting and Best than was either necessary or Macleod believed they deserved. It is almost as though he was protecting his younger researchers from the full glare of critical scrutiny of their work. I have found only one instance of Macleod telling a fellow scientist that Banting and Best would have gone off on the wrong track in 1921 without his advice. He said as much to August Krogh, the Danish Nobel laureate, on Krogh’s visit to Toronto in November 1922. The importance of that conversation will be discussed in the next chapter.
V
The devastating criticism of Banting and Best’s work came from England, in the letter that Dr. Ffrangcon Roberts published in the December 16, 1922, issue of the British Medical Journal. Having studied Banting and Best’s first two substantial papers (those in the Journal of Laboratory and Clinical Medicine), Roberts set out to review the steps leading up to the production of insulin in Toronto. The work began there with Banting’s hypothesis that it was necessary to protect the internal secretion of the pancreas from the powerful external secretion, the proteolytic enzyme trypsin, by ligating the pancreatic ducts to cause the trypsin-producing cells to atrophy. Roberts declared that the hypothesis was simply false. “Now it is one of the best established facts in physiology,” he wrote, “that the proteolytic enzyme exists in the pancreas in an inactive form – trypsinogen-which is activated normally on contact with another ferment, enterokinase, secreted by the small intestine.” Roberts allowed that trypsinogen is also activated when a pancreas is cut out and begins to deteriorate, but this happens only slowly and can easily be prevented by chilling. Given these facts, there was no physiological basis at all for Banting and Best’s duct-ligation experiment. They had undertaken a cumbersome, time-consuming process to forestall enzyme action which would never take place.
Keeping that in mind, as well as the possibility that the good results obtained in Toronto may have disproved “established facts” about trypsinogen (i.e., proved that active trypsin is found in the pancreas), Roberts examined Banting and Best’s experiments carefully and critically. In passing, he pointed out some of the factual disparities between the charts and text in the first paper, as well as the apparently abnormal condition of some of the dogs. His main target, though, was the experiment Banting and Best had run on August 17 and 18 using whole gland pancreas. Using their published figures, Roberts showed that the experiment (discussed earlier on p. 76) demonstrated that extracts made from whole pancreas were more effective and more lasting than those made from degenerated pancreas. Banting and Best’s own evidence showed the incorrectness of their working hypothesis. Instead of realizing this, they had drawn the “astonishing conclusion” that the whole gland extract was weaker, and believed that the experiment reinforced their hypothesis.
Their attempts to exhaust glands of the external secretion by means of secretin-stimulation were meaningless, Roberts argued, because they had no means of showing that exhaustion had actually taken place. “To establish their point Banting and Best have to show that the gland which they say is exhausted really is exhausted. This can only be done by demonstrating the absence of the three ferments by the ordinary methods. This they have neglected to do.” If anything, their secretin experiment also disproved the main hypothesis, for, without realizing it, they were again showing that extracts of whole pancreas were potent. The one thing Banting and Best had not directly tried was the crucial experiment that would have verified or nullified their hypothesis: instead of assuming it, they should have tried to prove that there was no active principle in extracts made from a normal pancreas.
Roberts drew attention to more problems with the experiments, such as inadequate data on blood sugar patterns after pancreatectomy but before injection, and summarized Banting and Best’s situation:
Having therefore failed to establish their main thesis, but encouraged by a complete misreading of their results (I challenge any unbiased person to read the paper carefully and come to any other conclusion), Banting and Best then proceed to investigate further methods of preparing a hormone free from the destructive action of ferments. They tried foetal pancreas…no comparison has been made between foetal and normal adult pancreases.
Then they had completely changed their methods, adopting alcohol as an extractive and suddenly moving from foetal to normal
pancreas. Perhaps they had concluded that alcohol did the job of destroying the (non-existent) proteolytic enzymes, but they never proved this by comparing alcohol with aqueous extracts. Instead, they had turned to a totally different aspect of the problem, concentrating on how to produce a non-toxic rather than a non-inactive extract. This problem had been solved, but, Roberts pointed out, “What Banting and Best have failed to realize is that in so radically changing their method they have abandoned the principle from which they started and which they never proved.”
What did this set of experiments, for which Roberts had not one word of commendation, amount to? The experiments led eventually to insulin. But,
The production of insulin originated in a wrongly conceived, wrongly conducted, and wrongly interpreted series of experiments. Through gross misreading of these experiments interest in the pancreatic carbohydrate function has been revived, with the result that apparently beneficial results have been obtained in certain cases of human diabetes…whatever success the remedy will have will be found to be due to the fact that the hormone has been obtained free from anaphylaxis-producing and other toxic substances. The experiments of Banting and Best show conclusively that trypsin qua ferment has nothing whatever to do with it.31
Macleod’s British correspondents apologetically alerted him to the critical article. In mid-January he wrote Dale that Roberts’ letter “has, I think, been overlooked by Banting and Best, and I see no object in calling it to their attention at present.” The next summer, in a major lecture on insulin, Macleod himself answered Roberts:
The Discovery of Insulin Page 28