The Discovery of Insulin

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The Discovery of Insulin Page 21

by Michael Bliss


  “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

  XII

  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

  XIII

  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 fl
uid 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

  CHAPTER SEVEN

  Resurrection

  Elizabeth Hughes’ case was particularly wonderful. Clinicians were very cautious in their early use of insulin; most were so used to diet therapy that they only gradually, even reluctantly, increased the food allotment of diabetics receiving insulin. Banting was different. Having never treated any diabetics, he had no preconceptions about the relation between insulin and diet. When he started treating Elizabeth Hughes, he took the common sense view that the main thing a young girl who weighed 45 pounds needed to do was to gain weight. So he prescribed a very liberal diet for Elizabeth, moving her rapidly up to 2,500–2,700 calories daily. “When I said she was to have bread and potato, both patient and nurse thought that I was joking and breaking faith with the gods, Joslin and Allen. The child was so delighted that she could hardly wait until the next day. The nurse thought she was breaking faith with her profession in obeying such an order and tested every single specimen separately for 24 hours and could scarcely believe it herself when there was no sugar.”1

  On her daily chart Elizabeth meticulously recorded the first piece of white bread she had eaten for three and a half years (August 25), the first time she had corn for supper (August 29), the reintroduction of macaroni and cheese to her life (September 7). Her diet was still unbalanced, with the intake of carbohydrates kept down and the extra calories supplied by fats, mostly through a daily pint of thick cream. Five weeks after coming to Toronto, Elizabeth had gained a little over ten pounds. “I declare you’d think it was a fairy tale…,” she wrote her mother,

  I look entirely different everybody says…gaining every hour it seems to me in strength and weight…it is truly miraculous…Dr. Banting considers my progress simply miraculous, none of his other patients coming near me in diet etc., and so I consider myself especially lucky. He brings all these emminent Doctors in from all over the world who come to Toronto to see for themselves the workings of this wonderful discovery, and I wish you could see the expression on their faces as they read my charts, they are so astounded in my unheard of progress….2

  Elizabeth was one of Banting’s private patients. She lived outside the hospital, and only Banting, her nurse, and Elizabeth knew the details of her diet (“I know if they did know they’d nearly roll off their seats. It’s our great big secret!… Wouldn’t Dr. Allen have ten fits if he knew what I was on now?”)3 Through the autumn of 1922 Elizabeth Hughes came back to life and health. Every week she gained two or two and a half pounds, and in October realized she was starting to grow taller. Her invalid’s routine of reading and sewing, sewing and reading, was interrupted more and more often by movies, concerts, plans to go back to school, trips to Niagara Falls, and very special nights out:

  Last night I had the loveliest time! Dr. Banting came over about quarter past seven and asked us to go out and take a drive with him. Blanche couldn’t go…so I went with him alone. Gracious I felt so grown up going out with a man alone at night!

  Well first he took me to his office where he showed me no end of interesting things about his work, clippings etc. and then he took me up to his room to see his favorite books and paintings….Well then we drove around a bit and ended up by going into the Connaught laboratory which is in the basement of the Medical Building over at the University, and seeing extract made from the first stages to the last. It was the most interesting thing I’ve seen in a long time and you must prevail on him to let you see it done when you come up. They are putting out such large quantities now that that enormous plant is running night and day with the men working in relays. Oh it certainly was one glorious evening and I shall never forget it.4

  The wonderful progress was not without complications. Every new batch of insulin was of different potency; while adjusting to it Elizabeth often had hypoglycemic reactions. They tended to be mild, though, and not very frightening, in fact led to the glorious treat of being allowed candy, for Banting arme
d her with molasses kisses to bring her blood sugar back up from hypoglycemia. The impurities in her insulin also caused pain and swelling, and the injection routine became particularly unpleasant when weak insulin had to be given in larger doses: “Imagine, I have to take 5cc. at a time. Isn’t that awful?” Elizabeth wrote on October 25,

  but it seems they have had no extract for the last few days and I suppose we were lucky to have even that poor stuff. We only have a two cc. syringe you know and so Blanche fills that and gives it to me and then unscrews it from the needle which is left sticking in to me (I feel like a pincushion) fills it again, and gives me that (am left a pincushion once more), and then have the fifth cc. It really is quite a process, and altogether takes about twenty minutes for the whole performance. My hip feels as if it would burst too, but it doesn’t, although my whole leg is numb until I walk on it a bit, then it recovers rapidly, and within an hour I would hardly know anything had been given.5

  Elizabeth’s hips, the fleshiest part of her body, were nothing more than a mass of swollen lumps from her insulin injections, she told her mother. She always added that she could endure anything for the sake of her new diet and what it was doing for her.

  I want if you can possibly find them, the links that were taken out of my little silver watch and my gold bracelet Mrs. Crozier gave me. My arm is fattening out so much you will be glad to hear that my watch is really becoming quite uncomfortable, so I need another link put in and I saved them just for this special immergency, although I must say I didn’t ever expect it to come….6

 

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