“Unspeakably Wonderful”
A totally unexpected, almost incredible disaster in insulin production took place sometime between late February and the end of March. Certain of the fact of their discovery and of its therapeutic benefit for human diabetics, the Toronto group had gone ahead with plans to manufacture insulin in large quantities. The Connaught Anti-Toxin Laboratories was to finance and administer production. Collip was to direct insulin manufacture.1 Special equipment was installed in the basement of the medical building. Everything seemed set for smooth progress. All the problems with purification, the fights about credit, and the rest of the strains, were surely in the past.
Then, to his and everyone’s surprise, Collip found that he could not make insulin. First he could not make it in large batches using the apparatus set up in the special manufacturing area. Then he started to have trouble making it by any method, even in his own lab, apparently being unable to duplicate his own successful procedures of January and February. The result of Collip’s failure was an insulin famine in Toronto during the spring of 1922, a frantic struggle by everyone on the team to find some way of regaining the knack of making insulin, and fundamental changes in policy regarding the handling and development of the frighteningly elusive discovery.2
It was one of the most trying periods in Collip’s life: brilliant success in the winter; failure after failure, with more and more serious consequences, all through the spring; endless hours in the lab trying to make insulin. Everything was complicated by a serious attack of flu in the Collip household, while at the lab the breakdown in relations with Banting was total, apparently not having been restored since the fight in January. Banting and Collip probably did not speak.5 Collip may not have been physically safe in Banting’s presence: so many of the stories about the Banting-Collip fight have it taking place in public, or centre it on the loss of insulin production, that there is a reasonable possibility of a second violent incident of some kind having taken place. He was unquestionably vulnerable to Banting’s angry scorn. How could Collip have possibly lost the secret? How the hell could he have done it? Obviously, according to Banting, by being so secretive. If not secretive, or as well as being secretive, by being inexcusably sloppy.4 Collip had known the pure joy of discovery in January. Now he knew dark nights of despair.
People who understand biochemistry tend to be more charitable than Banting was in understanding Collip’s situation. Failures like these were not uncommon in primitive extractions working with unknown substances. Before and during Toronto’s agony with insulin, for example, years of effort and hundreds of thousands of dollars were going into the still unsatisfactory effort to purify thyroxin, insulin’s predecessor as a hormone with great therapeutic possibilities.5 Pioneering chemists were working with delicate procedures, crude and unreliable equipment, and such frustrating unknowns as the chemical composition of the substance they were trying to produce. In Collip’s case, as well, Banting’s belief that his records left much to be desired was probably right. Collip’s only surviving comment on the problem is a laconic statement that “great difficulties were encountered chiefly because the conditions of time and temperature which were adhered to in the original method could not be obtained in a large scale process with the facilities then at hand.”6
A few humans had been given insulin, all at Toronto General Hospital. There are few records of how they were dealt with when the supply failed. Some of them, having regained enough weight and strength to carry on starving for a few more months, were put back on their diets. Leonard Thompson, for example, was sent home in May without insulin. The most needy cases received whatever small amounts of insulin Collip could produce. The neediest of these was a young girl, a friend of Best’s from a Toronto suburb, who was admitted in February suffering from emaciation, dehydration, and severe acidosis. She was given insulin as supplies permitted. The injections eliminated the acidosis. There was no more insulin to inject. The acidosis returned. The girl gradually slipped into a coma. The doctors gave her massive doses of weak, only partially prepared extract, and were able to bring her back to consciousness. This was the first “recovery” from coma at Toronto. It was only temporary. “Collip gave us the last bit of partially completed extract at two o’clock one morning,” Campbell recalled, “and then no more could be completed for days. It was not enough.” The little girl’s death in April 1922 was the one time in Toronto that a patient who had been treated with the extract died for lack of it.7 Some years later in England, the first patient to receive penicillin suffered a similar fate.
It was a season for real-life melodrama. Banting, it will be remembered, spent most evenings in March drinking himself comatose to get his mind off his troubles. Charley Best came to his room on the night of March 31, Banting wrote later. The young man found the boarding-house room blue with smoke and Dr. Banting half drunk. Best proceeded to give Banting a bawling-out. In passing, he mentioned the situation at the lab and the opportunity they had to go back to work together trying to make an effective extract.
Banting said he wasn’t interested. They could have the whole damn thing. He was going to finish the teaching term with Henderson and then get out of Toronto and find a place where there were decent people to live with.
“Then Best said probably the only thing that would have changed my attitude, ‘What will happen to me?’“
‘“Your friend Macleod will look after you’, I said.”
“Best replied, ‘If you get out I get out’.”
“There was silence for some moments. I thought of all the joy of the early experiments which we had known together. Here was loyalty. I emptied my glass. ‘That is the last drink which I will ever take until insulin circulates in diabetic veins. Shake on it, Charley. We start in tomorrow morning at nine o’clock where we left off.’“
“Best was pleased. We sat down and as we had done hundreds of times, planned experiments.”8
While these larger-than-life events were taking place among his associates, J.J.R. Macleod was worrying about the future of their work. Toronto had announced to the world its discovery that certain extracts of pancreas were effective in the treatment of diabetes. Toronto knew how to make these extracts… in theory. In reality Toronto could not make effective extracts in large quantities, sometimes not in any quantities. The researchers were sure it could be done, but they had no idea when they themselves would be able to do it again.
Suppose someone else set to work and learned how to make effective pancreatic extracts. The ugly question of patenting had already been raised within the Toronto group. Surely it was a much more pressing question when outsiders were considered. Suppose some enterprising drug company, or even an enterprising chemist, took up the pancreatic extract problem now, either found out the basic details of the Toronto people’s methods, or, knowing success was possible, worked out some successful variation, and then took out a patent on the discovery?
Drug companies were certainly interested. Late in March, Clowes of Eli Lilly and Company wrote Macleod about his firm’s continuing interest in developing the new extract. He urged a reconsideration of the decision not to work with a major manufacturing firm:
Public interest in this work will naturally be very great and the demand for the product will be such as to lead to attempts on the part of unprincipled individuals to victimize the public unless some steps are taken to arrange for the manufacture of the product by the procedures recommended by Dr. Collip and the control of the product by means of such tests as you and your associates would consider necessary.
If Clowes knew about the researchers’ collaboration with the very small Connaught Laboratories, he dismissed it as inconsequential. The Lilly company would be delighted to work with Toronto, Clowes wrote, and hinted, perhaps intentionally, perhaps not, that Toronto could be bypassed: “I have thus far refrained from starting work in our laboratories on this question as I was anxious to avoid in any way intruding on the field of yourself and your associates until you had published your results. I feel, however, that the matter is now one of such immediate importance that we should take up the experimental end of the question without delay, preferably cooperating with you and your associates…. “9
Macleod replied that Clowes’ firm would have first consideration if Toronto decided it needed help, but that for the next month or two the group would continue on its own. Toronto hoped to publish its method for everyone to use, and would try to protect the public by publishing specifications for the determination of insulin’s toxicity.10 Actually, Macleod was not so sure of his course and in early April began seeking other advice. He approached the deputy minister of health for Canada, who consulted with the commissioner of patents and confirmed the unhappy possibility that a competitor’s patent could interfere with Toronto’s work, even bring it to a complete halt. At best, the litigation necessary to frustrate such competition, on the ground of Toronto’s announced priority, would be lengthy and expensive.11
Macleod also wrote to at least one other discoverer, E.C. Kendall, who had isolated thyroxin at the Mayo Clinic in 1914. Kendall had patented his process of isolating thyroxin, and enthusiastically recommended that the Toronto group do the same with their pancreatic extract. He explained to Macleod the arrangement between himself, the brothers Mayo, and the University of Minnesota, by which the patent had been given to the university. It had then established a special committee to license manufacturers of the product.12
Macleod was more cautious than Kendall about patenting. Chemists and drug companies had few qualms about taking out patents on their processes or products (Kendall wrote of the Toronto situation, for example, “I can see no more reason why the man that separates the active constituent of the pancreas should not share financially as much as the man that makes a new wireless telephone”). But medical men, such as Macleod and Banting, were bound by their profession’s code to make all advances in health care freely available to humanity. If nothing else, it would violate a physician’s Hippocratic oath to engage in the profiting from a discovery that patenting normally implied. During preliminary discussions of this problem in Toronto, Banting was apparently particularly reluctant to be in any way associated with patenting.13
The possibility of losing the discovery seemed so real, however, that the group decided Toronto had to have the insurance patenting offered. On April 12, Banting, Best, Collip, Macleod, and Fitzgerald wrote jointly to the president of the University of Toronto, Sir Robert Falconer, explaining the situation. They proposed that a patent on the process be taken out in the names of the two “lay members” of the group, Best and Collip, and then immediately assigned to the Board of Governors of the University of Toronto. It was to be a purely defensive manoeuvre, one which would never stop anyone else from making the extract. In fact the point was to stop anyone from ever being in a position to stop anyone else:
The patent would not be used for any other purpose than to prevent the taking out of a patent by other persons. When the details of the method of preparation are published anyone would be free to prepare the extract, but no one could secure a profitable monopoly.14
The Board of Governors of the university agreed to the arrangement. An application was filed for a Canadian patent in the names of Collip and Best.
All four of the principal researchers worked long hours in April and May trying to regain the secret of making insulin. Although their later accounts tend to disagree on credit for important suggestions, it seems that the research was more than ever effectively a team effort, with at least three of the four making vital contributions.15
They gradually became convinced that the crux of the problem was in the heating that the extract experienced as part of the process of evaporating off the alcohol. Best discovered significant variations in the pressure of the water being supplied to the crude vacuum pumps they were using. These caused significant variations in temperature and distilling time. (A similar problem twenty years later frustrated early attempts to purify penicillin.)16 Macleod, who had been investigating different grades of alcohol, as well as the influence of different degrees of acidity, then turned his attention to what was happening in the evaporation. He found that the high temperature was causing some of the proteins in the solution to break down, an observation which seemed to reinforce previous experience that heat somehow neutralized the active principle. Macleod suggested abandoning the use of vacuum stills, and going back to the warm-air current method of evaporation that Banting and Best had used earlier at his urging. Collip, too, had decided the temperature had to be kept down, and to do this had experimented with acetone rather than alcohol as the principal extractive.17
By mid-May the group had recovered the ability to make insulin. The method involved using acetone with slight acidification. (The degree of acidity was the other variable that was constantly tinkered with; the solubility of elements in the mixtures varied according to the degree of acidity as measured by pH determinations. As was realized later, adjustments in the pH range of the solutions were in fact far more important than the temperature of distillation.) The pancreas-acetone mixture was filtered and then set out in enamel-lined trays placed in a make-shift wooden tunnel. A big old exhaust fan, formerly used in the medical building’s heating system, supplied the wind. Coils in the roof of the tunnel heated the air as it passed over the trays. After an hour in the tunnel, five hundred cc. of solution in a tray would be reduced to fifty cc, the temperature never exceeding 35C. The rest of the process, involving Collip’s method of “trapping” the active principle in various percentages of alcohol, was fairly straightforward, though it took several days before the final product emerged.
The method produced a few cubic centimetres of insulin solution. It was expensive, mainly because of the cost of alcohol, and hazardous. “You can’t imagine a more dangerous set-up,” Peter Moloney told me. He was the first chemist added to the production facility to work on insulin in that spring of 1922. In 1980, when we talked in his room in St. Michael’s College, the distinguished, white-haired, chuckling old man, still an active chemist as he approached his ninetieth birthday, brought back vividly the reek of acetone that spring and summer, the rattling of the motor driving the big fan, and his horror when a bottle of picturic acid was shaken off its shelf, fell to the floor, and shattered. Only the placing of its cork stopper, Moloney thought, saved an explosion that would have ignited the acetone, causing a dreadful fire. Toronto would have sacrificed its medical building and several chemists in its haste to make insulin.18
The rediscovery of a way to make insulin made it possible to consider resuming clinical tests. Banting, as we have seen, had played little part in the clinical work at Toronto General Hospital, for he had been denied an appointment to the hospital’s staff. In February and March it had seemed to Banting as though he had no further role to play in the development of the discovery. As he pulled himself together that spring, however, probably relying heavily on such friends as Velyien Henderson for advice, Banting must have realized that he had an unchallengeable claim to use the extract. A very large number of people, including Banting himself, believed that he had discovered it. It would be unthinkable to deny Dr. Frederick Banting, a licensed physician in good standing, priority in the clinical use of insulin. If Banting did not get his way the amount of trouble and bad publicity he and his friends could cause was practically unlimited.
The fact that Duncan Graham would not give Banting an appointment at Toronto General Hospital was not the barrier it had first seemed. Why should TGH have a monopoly of the clinical tests of insulin simply by virtue of being the university’s chief teaching hospital? In the spring of 1922, Dr. F.G. Banting established an office at 160 Bloor Street West in Toronto and began the private practice of medicine. This one step instantly gave him the right to use the facilities of TGH’s private patients’ pavilion for his private patients. Then, early in April, Banting was interviewed about the discovery by the Director of Medical Services for the Canadian Department of Soldiers Civil Re-Establishment, which handled the affairs of war veterans; several weeks later Banting was appointed head of a new diabetes clinic at Toronto’s Christie Street Military Hospital, where he had worked briefly in 1918–1919. Now he had all the facilities he needed.19 About the same time, an agreement was reached with the Connaught Laboratories on the distribution of insulin for clinical use. One-third of the production was to go to Banting for his private practice, one-third was to be used in Banting’s Christie Street clinic, and one-third would be available for work at Toronto General and the Hospital for Sick Children.20 Macleod began referring all the inquiries he received from diabetics to Dr. Banting, “my clinical associate.”
By mid-May enough insulin was being produced by the new method to permit resumption of limited clinical testing. Dr. Joe Gilchrist received his second injection on May 15. Gilchrist had agreed to work at the Christie Street clinic under Banting, and so served as both physician and patient. In the early months of sporadic production and frequent impurities, Gilchrist became Toronto’s self-proclaimed “human rabbit,” testing each new batch on himself after it had been tried on the rabbits.21
There was also enough insulin in mid-May to allow Banting to meet the urgent request of Dr. John R. Williams, who had come to Toronto from Rochester, New York, some miles away on the other side of Lake Ontario, to see if he could get some insulin to try on his most desperately ill patient. Jim Havens, son of a vice-president of Eastman Kodak, had been diagnosed as diabetic seven years earlier at age fifteen. He did fairly well on an Allen diet until 1920 when his capacity began a sharp decline. The boy was treated by Allen, and his father supported Allen’s “heroic efforts” to get research going at the Physiatric Institute. By early 1921, however, James Havens, Sr., had given up hope that Allen or anyone could help young Jim.22 When news came of the discovery in Toronto a year later, James Havens, Jr., was a 73½-pound skeleton, living on 820 calories a day, barely able to lift his head from his pillow, crying most of the time from pain, hunger, and despair. According to Williams, he was
a most pitiable spectacle. Blood sugar 450 mgs. Plasma bicarbonate [a measure of acidosis] 24.9 volumes per cent. For weeks the patient had suffered severely from pains in his legs, which made the constant use of codeine necessary. The edema and profound weakness confined him to bed and he was rapidly approaching death, when through the great kindness of Doctors Banting and Macleod, extract was supplied for his treatment.23
Havens got his first insulin on the evening of May 21, 1922. He was the first person treated with it in the United States.24 The first injections of one or two cubic centimetres (throughout this period one rabbit “unit” of insulin, roughly defined as the amount necessary to send a rabbit into hypoglycemic convulsions, was usually about one cubic centimetre in volume) were very painful and had no effect, confirming, it is said, Williams’ hesitancy about trying the new cure in the first place.25 On May 26 Banting went to Rochester to examine Havens. He advised doubling and then tripling the dosage. Within a day or so Havens’ urine was sugar-free, his blood sugar was down to normal, and his clinical condition greatly improved. Banting agreed to have fresh supplies of insulin sent by train from Toronto.* Two weeks after first receiving insulin, Jim Havens was able to rise from his bed and walk. “The patient is very much better,” Williams wrote Banting. “His appearance indicates much greater improvement than the laboratory studies suggest. Dr. Joslin made the statement to me one time, that of all the ways of measuring the condition of a diabetic, he thought the clinical appearance to be one of the best and that is my experience…The greatest advance noted is in his state of mind.”27
Williams had come to Toronto personally to plead for insulin. Others, alerted by the May 3 paper in Washington, were beginning to do the same or to write Banting or Macleod asking when the new treatment would be available. “I have some really heart-breaking cases under my care at the present time,” the chief pediatrician from the Johns Hopkins Hospital in Baltimore wrote in a typical appeal, “two of them lone children of different families whose carbohydrate tolerance is gradually going down. They know of your work and are pestering me to get some of the material if I can. I do not wish to pester you, but only to let you know how anxious I am to use some of the ‘insulin’ if I can get it.”28 But Toronto had no extra insulin to give to him or anyone else. For several weeks Jim Havens was the only diabetic outside of Toronto who was being treated with insulin.
The pressure to produce more insulin was mounting daily. All attempts to produce the hormone in large quantities continued to fail. Toronto’s recovery of a method in mid-May was accompanied by a realization that the group had to have help. The ubiquitous George Clowes had spoken to Macleod again at the Washington meeting at the beginning of May, had written offering advice on the American patent situation, and continued to urge Toronto to collaborate with his firm. The Torontonians finally came around and invited Clowes to come to Toronto on May 22. (They also invited Rollin Woodyatt of Chicago, who was offering an informal collaboration that would put his expert staff, financial backing, and the pancreas resources of the Chicago stockyards at Toronto’s disposal. Woodyatt, however, was unable to come to Toronto at the time specified.)29 Clowes brought with him a chemist, a patent attorney, and the vice-president of Eli Lilly and Company, Mr. Eli Lilly. In two or three days of meetings at the King Edward Hotel, the Americans and Canadians worked out an agreement for the development of insulin.
The proposed collaboration was explained in another formal letter, written on May 25 to Falconer from the research team plus Fitzgerald of the Connaught. They now recommended that the University of Toronto Board of Governors accept from Collip and Best a United States patent on the process, for which they were applying. The Board would eventually license North American firms making insulin for sale and collect royalties from them to support research in the university. For now, however, the group recommended that a temporary exclusive licence be given to Eli Lilly and Company of Indianapolis. The explanation of the recommendation was as follows:
Experience on production of “insulin” on a moderately large scale in the Connaught Laboratories has shown that this is fraught with many difficulties not encountered in the small laboratory scale, and we do not believe that production in amounts that are adequate to supply the demands for it can be accomplished without further experimentation in its preparation on a much larger scale than is possible here. To make this further step possible it will be necessary for us to collaborate with some well equipped and properly staffed commercial house engaged in this work. After careful consideration we have decided that it is much better to arrange to deal with one firm rather than several, partly because concentrated effort is likely to be more efficient than divided effort, and partly because we could not act as consultants to several establishments at the same time….
We have chosen to collaborate with [Eli Lilly and Company]. We recognize this firm will be placed at an advantage over its competitors through this collaboration with us, but we believe that it is much less serious than there should be further delay in proceeding intensively with production on a large scale, and, moreover, we propose to give other firms, as well as hospitals and other non-commercial concerns, every chance to do the best they can by publishing the details of the method as at present used by us in the Connaught Laboratories in full at an early date (within three months). By this step, our proposed co-operation with the Lilly Co. cannot be criticized as unethical or unfair or as in any way prejudicial to the free manufacture of “insulin.”30
Toronto’s decision to collaborate with his company was a triumph for and testimony to the persistence of G.H.A. Clowes. It also reflected a vote of confidence in both Clowes and his company by the Toronto researchers, who had not acted impulsively or without consideration of their several alternatives.
In 1922 Eli Lilly and Company had been making and selling pharmaceuticals for forty-six years from their base in Indianapolis, Indiana. It was a family-owned “ethical” drug company (no patent medicines, no extravagant claims, and advertising and sales to doctors and pharmacists only), which had grown to become a major, though not dominant factor in the industry. In 1921 Lilly employed about eleven hundred people and did just over $5 million worth of business. The firm was managed, according to the founder’s son and president, J.K. Lilly (whose own son, Eli, had been the family man in Toronto), with the aim of being “conservatively progressive.” Part of the house’s progressiveness in the early 1900s had been the creation of a substantial research facility. At the end of the First World War the Lilly family had decided to strengthen further the firm’s links with the scientific community, even though the short-term returns from such ventures might be minimal. As part of this continuing policy G.H.A. Clowes was hired as a special research chemist in 1919 and appointed director of research the next year.
George Clowes (pronounced clews) was an Englishman in his mid-forties, a minister’s son who had taken a Ph.D. in chemistry in Germany, done post-doctoral studies in England and France, and then emigrated to America as a land of greater opportunities than Britain. Before moving to Lilly, Clowes had spent many years at a state research institute in Buffalo, New York, ninety miles from Toronto. He was a serious researcher in his own right, most interested in problems relating to cancer, but with a restless curiosity about all kinds of knowledge. His job with Lilly was almost unprecedented in a commercial organization, Clowes wrote, in giving him virtually free reign. During the summers, for example, he worked at the Marine Biological Laboratories at Woods Hole, Massachusetts, where he had his own lab, assistants, and no commençai responsibilities. His research reports emphasized the absolute necessity of continuing to strengthen the firm’s links with the scientific community, including the universities, and raising its prestige and authority among researchers. Few broad corporate strategies have ever paid off as quickly and magnificently as this did for Eli Lilly and Company.31
Macleod had known Clowes for some years, was impressed by his stature as a scientist, and by his company’s enlightened support of research. He and the other Torontonians were probably also impressed by the plans Clowes outlined to them for the development of insulin. The firm had recently been very active in work on glandular products, and had a good team of chemists ready to work on insulin. It wanted an exclusive licence for an “experimental period” of one year, during which there would be a complete pooling of knowledge between Toronto and Indianapolis. There would be a several-stage development of the product involving large-scale clinical tests in Toronto and the United States, with Lilly supplying extract free of charge in the initial stages and then selling it at cost. Lilly would share any improvements it made in the manufacturing process with Toronto, and if any improvements were patentable would pool the patent rights for all territory outside of the United States. At the end of the experimental period, Lilly wanted a licence to manufacture insulin on the same terms as Toronto would license other manufacturers. As Clowes had proposed in earlier letters, the firm thought it would be appropriate for insulin licensees to pay Toronto royalties on all insulin sold.
The collaboration was formally established in an “Indenture,” dated May 30, 1922, between the Board of Governors of the University of Toronto and Eli Lilly and Company. It was intended to be a close, but not necessarily exclusive, relationship. The Lilly company was prohibited from divulging details of the process to other parties, for example, but Toronto was not. As they had told Falconer, the Toronto team still intended to publish their method in order to make sure others would know how to make insulin when Lilly’s exclusive rights expired and to protect themselves from charges of unethical secrecy. As well, the Lilly agreement limited the company’s territorial rights to the United States, Central and South America. To handle insulin in Britain and the rest of the Empire, perhaps Europe too, the Torontonians had decided to offer the patent rights to the British Medical Research Council, for administration in a way parallel to the University of Toronto’s handling of the Americas. At the end of May, Macleod wrote the Medical Research Council conveying the offer. On its part, the Board of Governors appointed a small committee to work with the discovery group in carrying out the licensing and development arrangements. These bodies soon evolved into Toronto’s Insulin Committee.32
The Toronto group was anxious to get policies for developing insulin in place during May, not only because of the demand from doctors and diabetics, but also because of the imminent break-up of the group. Collip’s appointment at Toronto expired on May 31. Such negotiations as there may have been about his staying on seem to have dissolved in the quarrels with Banting and then the difficulties making insulin. Whether or not Collip wanted to stay on but was not wanted, or was wanted but was fed up with the fighting, is not known.
At the end of May the Toronto researchers read six short papers on their work at a session of the annual meeting of the Royal Society of Canada. The first two of these, scheduled to be published several months later, contained methods for making insulin as developed by Banting, Best, and Collip. There were two recipes – “The Preparation of the Earlier Extracts,” by Banting and Best, and “The Preparation of the Extracts as used in the first Clinical Cases,” by Collip – an indication for the record of who had done what by members of a team that had fallen apart.33 Best and Collip then travelled to Indianapolis. On June 2 and 3 they told the Lilly chemists all they knew about making insulin and helped with the first attempt to extract it. The process worked.34 His time in Toronto over, J.B. Collip went back to his job at the University of Alberta.
Beginning work immediately, the Lilly company poured men and money into insulin production. But they were not the first to make insulin in the United States. Dr. W.D. Sansum of the Potter Metabolic Clinic in Santa Barbara, California, had noticed Banting and Best’s first publication and in April had written Banting to ask about progress. When Banting told him of the delays, Sansum decided to try making pancreatic extract himself. He and his associates tried various methods. As soon as they learned to use alcohol as an extractive and normal rabbits for testing (from Banting and Best’s May article, combined with a letter Joslin had published immediately after the May 3 meeting), the Potter group found they could make potent extracts. On May 31 they began administering insulin to an adult male patient, and soon succeeded in making him sugar free. They tried to increase their supply of the extract early in June, collecting the pancreases from sixteen hundred sheep. Just as had happened in Toronto, they found that the attempt to scale up production failed completely. Macleod learned of the California work in mid-June when Sansum wrote to him asking for advice.35
Macleod had expected some such development. It was only through professional courtesy that Rollin Woodyatt was delaying trying to make extracts and other diabetologists, including Allen, were starting to become impatient. They all had dying diabetics on their hands, patients they had encouraged to carry on in the faint hope that some treatment would be discovered. Now the announcement of the treatment had come out of Toronto, but no treatment. Some of the patients’ life expectancy was a matter of weeks.36
To meet the clinicians’ demand, while at the same time usefully spreading out the research job, Toronto and Lilly had agreed that a select group of physicians and institutions would be given the extract for testing purposes as soon as it became available. Until then, the Torontonians saw no reason why other researchers should not be able to make insulin. Macleod sent both Sansum and Woodyatt details of the method. To honour the Lilly agreement, he required them not to divulge the method to anyone likely to produce the extract commercially.37
Of course experimental and clinical work would continue in Toronto, with the Connaught Laboratories, small and makeshift as its facility was, doing everything possible to increase insulin production for the city and for Canada. After Collip left, Best was placed in charge of Connaught’s insulin manufacture. Banting handled the clinical work through his private practice and his Christie Street patients. Macleod was to carry on experimental development. To finance the research, Macleod applied for and was awarded an $8,000 grant from the Carnegie Corporation. Part of it was to be shared with Collip, who fully intended to carry on research into insulin at the University of Alberta. Macleod himself was travelling east, to spend the summer of 1922 at the Marine Biological Station in St. Andrew’s, New Brunswick. He was intrigued by the thought that insulin ought to be easily procurable from those species of fish in which the islets of Langerhans were anatomically separate from the rest of the pancreas. Perhaps fish insulin would be easier and cheaper to produce than the dribs and drabs of semi-pure beef insulin they were struggling so hard to make in Toronto.
The University of Toronto was awakening to the importance of the discovery made in its Physiology Department and first tested at its teaching hospital. Part of the institution’s consciousness involved realizing how curious it must appear to outsiders that Banting had no university appointment (his job in the Pharmacology Department had expired) and no position at Toronto General Hospital. How strange, too, that no further clinical testing was going on at Toronto General. (According to Banting, this fact was driven home to the chairman of the hospital’s Board of Trustees, C.W. Blackwell, when on a trip visiting American hospitals he was asked everywhere about insulin and had to admit nothing was happening at his hospital and he knew nothing about insulin. Blackwell broke off his trip, came back to Toronto, and began discussing with Falconer how to get Banting at work treating diabetics at the hospital.)38
Unless something was done quickly, the university and hospital faced the prospect of losing much of the prestige attaching to what was starting to look like a very great discovery. Banting was completely outside the university. Suppose he went even further outside, and, as he had threatened at least once in the past, left Toronto entirely. He was beginning to get offers, some of them princely.*39 What an embarrassment if the principal discoverer of insulin, as most people saw him, left Canada. Even if Banting stayed in Toronto, his non-relationship with the university would be embarrassing. On the other hand, those who knew Banting’s limitations might also have realized that he was not in fact competent to direct major clinical experiments on diabetics. The clinical reports Banting was likely to produce on his own would very likely pale in comparison with those of the first-class American diabetologists. This, too, would be embarrassing. Banting may have realized it himself. As his friend Dr. D.E. Robertson put the situation to Duncan Graham, “Campbell knows all about diabetes but can not treat it and Banting knows nothing about diabetes and can treat it.” Finally, if the enterprising American clinicians got ahead of Toronto, making it possible for American diabetics to get insulin in preference to Canadians, the result might be a national outcry. Altogether it was a very delicate situation.40
Even after the insulin famine eased in May, Walter Campbell appears not to have been getting supplies of insulin for his patients. Perhaps there was too little available. Perhaps Banting, as he himself implied in 1940, was conspiring to withhold insulin from the hospital until he was given a clinical position.41 In any case, an ad hoc university committee, chaired by Falconer, met in mid-June to resolve the doctors’ conflicts. Agreement was reached on the conditions by which Banting, collaborating with Duncan Graham, Walter Campbell, and A. A. Fletcher, would have clinical facilities at Toronto General Hospital. These would also entail a university appointment for Banting. The slow grinding of the university and hospital bureaucracies, combined with Banting’s heavy schedule that summer, made it impossible, however, to get the clinic started before the latter part of August.42
During July Macleod was working in New Brunswick. Best was spending a few weeks with his family in Maine. Banting was alone in Toronto. He was being deluged with requests for insulin from physicians, diabetics, diabetics’ families, people who had come to Toronto, people wondering if they should come to Toronto, people wondering if insulin could come to them. July heat in Toronto was oppressive again this year, Fred wrote Charley, “and even worse than the heat as a disturbance is that diabetics swarm around from all over and think that we can conjure the extract from the ground.” Diabetics were literally camping at the doors of the lab trying to get insulin.43
The standard reply to all inquiries was that insulin was still in the experimental stage, supplies were severely limited, and the inquirer would be informed when the situation changed. All available production was going to Jim Havens in Rochester and to Gilchrist and a handful of diabetic soldiers at Christie Street Hospital. Thinking the supply situation was improving, Banting gave in to some of the most desperate pleas; in mid-June and early July he agreed to treat a few private patients who were otherwise about to die. Four living skeletons, three children and one adult, were brought to Toronto from points in the United States and Canada.
Elizabeth Hughes was not among them. The fourteen-year-old diabetic had clung to life through the winter of 1921–22, a pathetically starved little girl, five feet tall but weighing no more than 52 to 54 pounds. In the spring of 1922 she was taken to Bermuda with her nurse to enjoy the climate. She contracted the diarrhoea epidemic on the island. Both her weight and her carbohydrate tolerance slipped further. From May 19 to June 2, 1922, Elizabeth received less than 300 calories of nourishment a day. Her weight, fully clothed, fell below 50 pounds. As indomitable a girl as ever existed, a kind of real-life duplicate of the heroines of girls’ literature, Elizabeth fought off the lassitude and despair that overtook most diabetics in the final stages of their sickness. She continued to exercise every day and made it a personal triumph to walk up the ramp to the ship that brought her home from Bermuda.
Elizabeth’s mother, Antoinette Hughes, had learned about the discovery in Toronto. Allen and other doctors told her that in this case the newspapers were right; there was something to it. On July 3 she wrote Banting to ask whether anything could be done for her “pitifully depleted and reduced” daughter. Banting’s answer on July 10 was the standard discouragement. All the Hughes family could do was try to keep Elizabeth going, hoping she would last until insulin was beyond the experimental stage. In fact it was impossible to build up her tolerance, and Elizabeth continued her drift towards death from starvation. A friend of J. J. R. Macleod’s, whose moving appeal on behalf of a poor fisherman on Prince Edward Island had met with the same response, wrote, “It is pitiful that so great a boon should be in sight, yet not in reach.”44
The insulin situation was a nightmare. Every attempt to increase the quantity of extract being produced in Toronto failed. When Best left on holidays, there were problems procuring pancreas. Then there was a shortage of acetone. Worse still, the quality of extract that was being produced was not good. Protein impurities caused abscesses in many of the patients; salts still in the solution made many injections excruciatingly painful.45 Strong extract seemed to have the worst side-effects, but weak extract had to be injected in painfully large doses to do any good. Banting resorted to rectal administration of extract to try to minimize the pain. There was fleeting optimism, then realization that the insulin was having no effect.46
By the end of June it seemed that the optimism after the first success with Jim Havens had also been premature. Dr. Williams was still enthusiastic about Havens’ subjective improvement and his weight gain, but wrote Banting that there was little laboratory evidence of progress. On a steady regime of eight cc. of extract a day, Havens was still excreting 200 grams of sugar and showing a blood sugar averaging .350. The boy was beginning to complain about the severe pain caused by the injections, suffered from an abscess, and his morale was starting to weaken. From time to time he had to be given a day of “rest” from his suffering.
As he pondered Havens’ case, Williams became more and more interested in the possibility that a Rochester colleague, Dr. John R. Murlin, might have an alternative worth trying. Murlin was noticed in chapter one as one of the researchers who had continued work on pancreatic extracts despite the disparagement of them in the years before the war. Before being ended by the war, Murlin and Kramer’s research, which had started well, had led them into a long blind alley.47 Murlin left the pancreatic extract problem until October 1921, when Paulesco’s results encouraged him to start up again. He was making interesting progress with respiratory quotient experiments on animals when Banting came to Rochester at the end of May to give insulin to Havens. Murlin met Banting, learned more about Toronto’s methods, and, with his colleagues at the University of Rochester, launched a feverish program of extract preparation and testing. He found that extract made by Banting and Best’s methods had fatally toxic side-effects. So he worked on a wide range of alternatives, and towards the end of June told Williams he believed he had an extract that could be taken by mouth through a duodenal tube.
Williams and James Havens Sr. hesitated to have yet another experimental remedy tried on poor Jim, but the Toronto extract finally became so painful they saw little to lose in Murlin’s alternative. On July 9 and 10 Jim Havens was given massive doses of Murlin’s pancreatic potion (a hydrochloric acid perfusate). Its only effect was to make the boy violently ill. Later in the day on the 10th, Williams thought Havens was heading for coma. He quickly went back to Toronto’s less unsatisfactory extract:
I injected 8 cc. of the extract into the buttocks. He immediately complained of a sensation all over his body as though he had been poisoned, and of a profound burning in the stomach. I at once gave him by mouth a dram of soda bicarb in 12 ounces of water. This did not relieve the burning or apparently ease the symptoms, but in a few minutes he vomited more than 2 quarts of undigested food and fluid. Shortly after that intensely itching wheels [sic] broke out on his body. I thought he would die but he came out of it all right.
Havens’ father wrote to Banting that they had now backslid to just about where they had started with Jim almost two months earlier.48
Progress or not, the pressure on Banting to take more patients continued to grow. Early in July he was phoned by Dr. L.C. Palmer, a local surgeon who had been a fellow medical officer at Cambrai in 1918. Palmer had a fifty-seven-year-old, severely diabetic patient, Mrs. Charlotte Clarke, who was suffering from a gangrenous infection in her right ankle. She seemed to be under a death sentence, for only amputation could stop the spread of the infection. Severe diabetics rarely survived amputations, and in a case like this most surgeons would not even try.
Banting could not turn down a fellow soldier’s request for consultation. He decided that they should go ahead and try the amputation, using insulin. What the hell, why not? On July 10, Charlotte Clarke, who was nearly comatose, was given her first insulin. On the 11th, Palmer amputated her right leg above the knee, using a general anesthetic which he had not thought she would have been able to stand without insulin. After the operation he was still skeptical: “I did not feel that wound would heal and looked for the worst possible results,” he wrote in his summary of the case. Mrs. Clarke came out of the operation showing large quantities of acetone in her urine. Banting injected insulin to control it. “It did not seem possible that she could get better,” Palmer wrote. This was the first major operation performed on a diabetic with the help of insulin.49
It may have been responsible for precipitating yet another round in Toronto’s continuing insulin crisis. Banting wrote afterwards that he had taken five other patients off insulin to supply Mrs. Clarke. It was poor quality insulin, in any case, and there was very little of it. By mid-July, production at the Connaught Laboratories was apparently at the point of failing completely once again. Williams, who had come to Toronto in desperation to get something pure enough to use on Havens, later wrote that “Toronto insulin had become intolerable.” Banting was beside himself, Peter Moloney remembered, to get insulin to keep his patients alive.50
Could Eli Lilly and Company come to the rescue? When the firm’s work on insulin began early in June, Clowes planned to run ongoing small-scale experimental programs in tandem with a series of factory-scale attempts at mass production. A team of chemists, headed by George Walden, devoted their full time to the insulin work. The schedule called for fairly large quantities of insulin to be on hand by October.51
Lilly’s preparations, made from pork pancreas, were potent from the beginning. As always, however, it proved painfully difficult to increase the yield. The first shipment of Lilly insulin, ten five-cc. bottles labelled “Iletin,” had arrived at the physiology department in Toronto on July 3. Best, who was about to leave for holidays, immediately took four bottles of it for Banting’s clinic. George Eadie, who was doing rabbit tests on the extract in the department, reported to Macleod that he later gave Banting two more bottles because the clinic was so short of insulin.
(In New Brunswick, Macleod was distressed to learn from Eadie that R.D. Defries, acting director of the Connaught Laboratories, had written Lilly asking that future shipments be sent directly to Banting. Macleod wrote Defries to make sure the physiology department got some of the extract for testing. “Please do not misunderstand my attitude in this matter,” he told Defries, “but you must know how disagreeable and upsetting things were last winter and to avoid this I am trying in the future to have every thing work strictly according to prearranged agreements.” On his part, Banting was upset that Macleod had in the first place, “on his own initiative,” instructed Lilly to send its extract to Eadie. He also found that Macleod’s technicians had taken over the little room he and Best had used, leaving him with no lab space – or, after yet another quarrel, research money – in the medical building.)52
Clowes came to Toronto on July 16 to go over the results of Banting’s first clinical tests of “Iletin” and plan the future testing program. He was surprised to learn of Connaught’s production problems and the severe shortage in Toronto. Clowes wired Indianapolis to ship more insulin. He suggested to the Connaught chemists that they try evaporating the alcohol at still lower temperatures as well as getting a more complete separation of fats. The Lilly people had been skeptical of Toronto’s makeshift wind tunnel evaporation method from the beginning, Clowes wrote Banting after his visit. Lilly had always used vacuum distillation, and Clowes thought Toronto would be wise to scrap its system and get new vacuum equipment.53
Banting decided to go to Indianapolis to study Lilly’s method for himself. “I have a hunch that Clowes is holding out on us since he would not tell us how that [first Lilly] batch was made,” Banting wrote to Best. “And furthermore since the extract we’re making here is ‘pretty rough’, I think they might supply us with some for the patients are needing it very badly.”54 On the 23rd he went to Indianapolis with D.A. Scott, Con-naught’s latest addition to its insulin team.
Banting’s suspicions about Clowes were groundless, for the Lilly group went out of their way to help the Canadians. In fact Clowes and the Lilly family took an instant liking to Fred Banting and decided to support him every way they could. Banting and Scott were shown complete details of the production facility, and the insulin supplies Clowes had promised were waiting for Banting. J.K. Lilly described the visit in a letter to his son, Eli:
When they left Toronto, there was not a single unit left in the city. Banting…has a large number of patients, and he certainly was in trouble. We had 150 units ready for him, and when I told him he could take it back with him, he fell on my shoulder and wept, and when I told him that the next evening we would send him 150 units, he was transported into the realms of bliss. Banting is really a fine chap and we must back him to the limit.55
Probably because supplies were so limited, Charlotte Clarke, the diabetic amputee, had been given no insulin after the seventh day of her post-operative period. Initially it seemed as though the insulin had done its job, for Palmer was able to remove the stitches from her wound and report nearly perfect healing. On July 25, however, the wound broke completely open. “The outlook was most discouraging,” Palmer wrote. “It did not seem possible to ever get the wound to heal again.” Two days later Banting was back in Toronto with his fresh supply of Lilly insulin. The wound immediately began healing again.56
Banting came home convinced that Toronto had to have vacuum stills like those being used to make insulin in Indianapolis. It was expensive apparatus, costing several thousands of dollars that the Connaught Laboratories did not have. Banting decided to get the money. Most of the university’s senior administrators were out of town, so he went directly to the chairman of the Board of Governors, Sir Edmund Walker. Walker was past president of the Canadian Bank of Commerce and a commanding patron of the arts and sciences in Toronto. He agreed to see Banting in his splendid downtown office. Banting explained to Walker that $10,000 was needed immediately for better equipment in the insulin plant. Walker replied that it was quite impossible to get that amount so quickly. Such an expenditure would have to be approved by the Board of Governors. The Board would not be meeting again until the university year began in September.
Banting was furious. Several offers of financial help from wealthy Americans had been transmitted to Toronto through American doctors. One of these doctors, H. Rawle Geyelin of New York City, had particularly impressed Banting during a visit to Toronto earlier in the month. “Now Banting, I am going home to put my most severe diabetics to bed so that they will live long enough to get insulin,” Geyelin told him as they parted at the station. “Let me have some as soon as possible…and by-the-way if you need money for your research I might be able to help you.” Listening to Walker’s explanation of why the University of Toronto could not meet his request, Banting thought of Geyelin, got to his feet, and, as he remembered it in 1940, said to Walker:
“Mr. Chairman, we got to get this still and I want to know if you damned Board of Governors will or will not accept the money if I get it for them.”
The dignified old gentleman was amazed and completely nonplussed at my boldness. He gasped and stared and stammered. “I could see no objection.”
“Thanks,” said I, turned on my heel, and left without further word.
Banting took the train to New York a day or two later to ask Geyelin for the $10,000. Geyelin phoned one Robert Bacon, who had a very sick diabetic child. After a few minutes’ conversation Geyelin turned to Banting and asked how the cheque was to be made out. Banting wired Defries in Toronto to go ahead and order the first small vacuum still. He also wired Indianapolis to add Geyelin’s name to the list of clinicians who would receive insulin when it was ready.57
Banting went on from New York to visit Allen at his Physiatric Institute in Morristown, and Clowes at Woods Hole; he and Clowes then saw Joslin in Boston. Lilly was ready to begin supplying Joslin, Allen, and other leading diabetologists with insulin. (Sansum in California, it will be remembered, was using his own insulin clinically; Woodyatt in Chicago had also begun making insulin and first used it on patients in June.) Clowes and Banting discussed how to go about this in a way that would protect Toronto’s – and Banting’s – priority in the work. Clowes’ idea, consistent with his original plan, was to form a small co-ordinating committee to plan the course of the testing, with a view to the results being published in a special issue of Allen’s Journal of Metabolic Research. Banting would be a member of the committee, an editor of the journal, and at the head of the list of authors in the special issue. Clowes thought the issue could be published by the end of 1922; Lilly would bear the expense of distributing it throughout the United States. “And if this were done,” Clowes wrote Banting on August 11, 1922, “you would not only get full credit for your work but it would be the first step toward securing the Nobel Prize in medicine for you and your associates.”58
Clowes and the Lilly family had begun to grasp the full significance of what they were doing. “I am almost overwhelmed with this tremendous situation,” J.K. Lilly wrote Clowes, “and experience some difficulty in keeping my feet on the ground and my brain in normal operation….Macdonald [one of the Indianapolis clinicians] says it looks to him like the biggest thing that ever happened in medicine, and that is saying a good deal for some very big things have happened in medicine.” “You have certainly entered the holy of holies,” he added a few days later, “and are sitting on the throne with the elect. It is a marvellous development and I rejoice in it.”59
But insulin did not come easily to the Lilly company either. Just as the Americans thought they had mastered the process and were proceeding in a straight line towards commercial production, unforeseen problems started to develop. Every lot was not coming out at full strength. In early August several lots were not successful at all, apparently because the United States government had forced a change in the kind of alcohol the company was allowed to use. Having just made a commitment to supply the clinicians with more than seven hundred and fifty units of insulin a week (of which Banting was to get five hundred), Lilly found itself “right on the ragged edge” of a serious supply problem.60 The experimental program, aimed at developing better manufacturing processes, had to be suspended to meet the promise to the clinicians. This greatly distressed Clowes, who persuaded Banting to cut back his allotment from five hundred to three hundred and fifty. Joslin and Allen had agreed to give Banting advice on his patients’ dietary regime, and Clowes hoped this would enable him to stretch his insulin just as far. Banting’s cutback enabled Williams in Rochester to begin receiving Lilly “Iletin” to use on Jim Havens instead of the painful Toronto stuff.61
Clinical tests began at the Methodist Hospital in Indianapolis on August 3.62 In Boston, Elliott Joslin received his first insulin on August 6. Thinking about the trials he would begin the next day, Joslin was too excited to sleep that night. It is said he was too nervous to make the first injection himself, so it was given by his associate, Dr. Howard Root. The patient was a forty-two-year-old former nurse, Miss Mudge, who in five years of diabetes had starved herself down to 69 pounds – “just about the weight of her bones and a human soul,” Joslin put it.63 Miss Mudge was an invalid from her diabetes; only once in the past nine months had she found strength to go out on the street. The immediate effect of her first injection of insulin was not that dramatic, Joslin remembered. But six weeks later Miss Mudge was walking four miles daily.64
Dr. Frederick Allen made his planned visit to Toronto on August 8 (partly to give Banting help) before beginning to use insulin in Morris-town. While he was away, rumours spread among the patients at his Physiatric Institute that something momentous was about to happen. One of the nurses, Margate Kienast, later described their reaction:
… the mere illusion of new hope cajoled patient after patient into new life. Diabetics who had not been out of bed for weeks began to trail weakly about, clinging to walls and furniture. Big stomachs, skin-and-bone necks, skull-like faces, feeble movements, all ages, both sexes – they looked like an old Flemish painter’s depiction of a resurrection after famine. It was a resurrection, a crawling stirring, as of some vague springtime.
She remembered the scene when the patients heard that Dr. Allen had come back:
Bed immediately after dinner was the rule for our patients. But not that evening. My office opened on the big center hallways. I could see them drifting in, silent as the bloated ghosts they looked like. Even to look at one another would have painfully betrayed some of the intolerable hope that had brought them. So they just sat and waited, eyes on the ground.
It was growing dark outside. Nobody had yet seen Doctor Allen. His first appearance would be at his dinner, which followed the patients’ dinner hour. We all heard his step coming along the covered walk, past the entrance to the main hallways. His wife was with him, her quick tapping pace making a queer rhythm with his. The patients’ silence concentrated on that sound. When he appeared through the open doorway, he caught the full beseeching of a hundred pairs of eyes. It stopped him dead. Even now I am sure it was minutes before he spoke to them, his voice curiously mingling concern for his patients with an excitement that he tried his best not to betray.
“I think,” he said, – “I think we have something for you.”65
On August 10 Allen began administering insulin to six of his most critically ill patients. Their first doses were minuscule, half a unit or less per injection, partly to spread out the supply, partly for fear of hypoglycemic reaction. Even so, the effects were striking. “Our first results with your pancreatic extract have been marvellously good,” Allen wrote Banting on the 16th. “We have cleared up both sugar and acetone in some of the most hopelessly severe cases of diabetes I have ever seen. No bad results have been encountered either generally or locally. We have been able to increase diets, and already an effect seems evident in the form of increased strength….I only wish that we could have several times as much extract as is available just now.”66
Allen’s most desperately ill patient had been Elizabeth Hughes. She still clung to life, but her only progress was downwards. It may have been while talking with Allen in Toronto that Banting agreed to add the child to his list of patients. Or there may have been one final appeal to him from the family, possibly through Dr. Lewellys Barker, who was once again on hand and was in touch with the Hughes family. By August 12 it had been decided to bring Elizabeth to Toronto. Allen told Banting he would find her a model patient for treatment. “There could not be a child, who for her own self deserved your care more than Elizabeth, in addition to any consideration due on account of her family.” Allen must have offered to take Elizabeth as one of his first insulin patients at Morristown; the family seems to have been influenced by the prospect of going right to “the fountainhead” for insulin (where, it should be added, supplies of the fluid were far more plentiful). Elizabeth, her mother, and her nurse came to Toronto on August 15.67
When Banting examined Elizabeth Hughes on the 16th, he must have marvelled that she was still alive. The pathetic child would turn fifteen in three days. Banting’s handwritten notes of his examination of Elizabeth survive in his papers:
wt 45 lbs. height 5 ft. patient extremely emaciated, slight aedema of ankles, skin dry & scaly, hair brittle & thin, abdomen prommt, shoulders drooped, muscles extremely wasted, subcutaneous tissues almost completely absorbed. She was scarcely able to walk on account of weakness. Respiratory, digestive & cardio-vascular systems normal.68
He began insulin treatment at once. The first injections, one cc. twice a day, cleared the sugar from Elizabeth’s urine. Banting immediately began increasing her diet. It had been 889 calories (actually 789 through July, but on the 29th Allen had allowed an extra 100 calories of fat daily, probably to hold off death from starvation). At the end of the first week’s treatment Banting had Elizabeth up to 1,220 calories; another week and she was on a normal girl’s diet of 2,200 to 2,400 calories.
Antoinette Hughes had had to go back to Washington. In long, chatty letters Elizabeth kept her mother informed of her progress. Elizabeth realized from the beginning that insulin was going to bring her back to health. She was an extraordinarily fluent writer, but had trouble finding words to describe what this experience meant to her. “To think that I’ll be leading a normal, healthy existence is beyond all comprehension,” she told her mother in her first letter. “Oh, it is simply too wonderful for words this stuff,” she burst out a few weeks later.69
The day Fred Banting examined Elizabeth Hughes he met his friend Dr. D.E. Robertson at lunch at the university’s faculty club. The newspapers had found out about Elizabeth; her trip to Toronto to get insulin from Dr. Banting was reported throughout North America. During lunch Robertson looked carefully at Banting and then asked whether he had worn the suit he had on now when he had met the Hugheses. Yes, Banting said, it was the only suit he owned.
“You are coming with me,” Robertson told Banting at the end of their meal.
“I asked no questions. He took me to the most expensive tailor in Toronto and said, ‘make this man a suit,’ ‘let me see your blues’. I was measured while he selected the cloth. Then he said ‘better make him an overcoat’ & he selected the cloth & directed how it was to be made. ‘I don’t know when he’ll have enough money to pay you, but I vouch for him.’ “70
It was a time for new suits and celebrations. On August 19 Clowes wired that the process was now working splendidly and Toronto’s quota could be restored. On the 21st the diabetes clinic at Toronto General Hospital finally opened for business. As an attending physician under Duncan Graham’s direction, Banting was to be paid the then princely salary of $6,000 annually (much more than his associates, Campbell and Fletcher, were allowed).* His clinic at Christie Street had not gone well, for the first patients had been plagued by pain and abscesses, reactions which discouraged other diabetic veterans from volunteering. But the situation suddenly changed dramatically. One of the “faithful” asked for a weekend’s leave and permission to take his insulin supplies with him, Banting remembered. The doctors consented. The soldier returned to the hospital on Monday all smiles. “For the first time in three years I am a man again.” Insulin had restored his sexual desire and potency. “By night,” Banting wrote, “every diabetic in the hospital was asking for insulin.”71 It was mostly Lilly insulin they were getting, but by the 22nd the Connaught facility, newly equipped with the special vacuum apparatus, was about to produce its first substantial batch of truly potent insulin.72
In Rochester Jim Havens had already been switched to the American product. In Toronto Mrs. Charlotte Clarke was learning how to use her new artificial leg. In her rooms at the Athelma Apartments, on Grosvenor Street just next to Toronto General Hospital, little Elizabeth Hughes found herself slowly awakening from her nightmare of diabetes, diet, and starvation. “Isn’t that unspeakably wonderful?” she exclaimed to her mother.73