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Week8_Banting2

Week8_Banting2 - TEXTS AN D DOC UMEN TS BANTING’S...

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Unformatted text preview: TEXTS AN D DOC UMEN TS BANTING’S, BEST’S, and COLLIP’S ACCOUNTS OF THE DISCOVERY OF INSULIN With an Introduction by Michael Bliss In the Fall 1978 issue of the Bulletin (52: 29S~515‘), Lloyd Stevenson " 'ntroduced i]. R. Macleod’s “History of the Researches Leading to the Discovery of Insulin.” This document, which had been written in Septem— ber 1922 at the request of Colonel Albert Gooderham and never previously published, was obviously of great historical interest, being a contemporary account of the discovery of insulin by one of the members of the discovery team. The following documents are the contemporary accounts of the dis— covery written by the other three members of the team. Like Macleod's, these accounts have not been previously published. They are preceded by the letter Gooderham wrote to Macleod, Banting, and Best on 16 September 1922, which resulted in the preparation of three of the four manuscripts. manuscripts. Albert Gooderham wrote his letter in his capacity as Chairman of the Insulin Committee which had been established by the Board of Governors of the University of Toronto to handle all matters relating to the patenting and other use of insulin. In his introduction to the Macleod document, Stevenson commented on the impossibility, past and possibly present, of locating a copy of the Macleod manuscript in “the gothic vaults of the University of Toronto." Instead he used a copy which had been kept by Macleod and was found among his personal papers long after his death. While the University of Toronto no longer stores its documents in anything resembling “gothic vaults,” and while the voluminous records of the Insulin Committee have recently been recovered for the University, it is still impos— sible to locate the copies of Macleod’s, Banting’s, or Best's accounts that were given to Gooderham. They seem to have disappeared, perhaps in the dis- posal of his personal papers by his family or in one of the periodic house- cleanings of University records over the years. The copy of Banting’s account published here is from a typescript contained in his papers at the Thomas Fisher Rare Book Library of the University. Identical copies of C. H. Best’s account are in his papers, recently donated to the Fisher Library; on deposit in the library of the Wellcome Institute in London, England; and in the papers of his would-be biographer, the late W. R. Feasby, at the Canadian Diabetes Association in Toronto. 'wfivnv\vr‘ “J w/ “A rrK sin 1 l ll'irj iiist‘t’n'r'r} oi insulin “7*? By the time of (Z‘rooderham's lfilt‘l‘d. B. Collip had left the University oi Toronto, where he had worked during his 1921 22 sabbatical year, to reSume his duties at the University of Alberta in Edmonton. (io<’>derhani chose not to write Collip, but instead asked each of the others to outline (lollip’s contribution to the discovery When Macleod wrote Collip about this procedure, Collip drew tip an itemized list of his contributions to the insulin research 'I'wn drafts of it exist in fragments oi t rillip's correstmnrlenre the version printed here is the text ol an undated, signed statement by Collip. prepared from the earlier dratts. which is preserved in his papers in the library ofthe Faculty of Medicine ofthe University of Western Ontario While very different from the other documents, it deserves publication along with them, particularly because so much of the controversy at the time (and later) swirled around the work done by Collip after he joined the team in December 1921. Stevenson’s introduction to the Macleod document raises the question of why these histories were treated so gingerly by the University of Toronto for so many years. At one time, Stevenson writes, a president of the Univer— sity, Sydney Smith, threatened him with legal action if he persisted with his interest in quoting from Macleod’s account. Of course Smith’s action, taken in the mid—19505, was improper. It was also a blufi, for the University in no way controlled the copyright to i]. R. Macleod’s work. Presidential corre spondence in the University Archives and in the C. H. Best papers indicates that Smith’s interest in the matter was caused by the knowledge that publica tion of Macleod’s account would cause Best, one of the most distinguished members of the University’s faculty, to insist that his own and Banting’s accounts also be published. Collip, at that time Dean of Medicine at Western, would inevitably have become embroiled in the controversy because of the extremely serious (and only partly justified) charges levelled at him in Banting‘s account. Banting, of course, had died in 1941. Taking counsel with Western’s president, G. E. Hall, and worrying that a full-scale rehashing of the insulin controversy would not be good for Best’s uncertain health, Smith decided to use his influence to keep the lid on all of these documents. As Collip had predicted and believed proper, the “hid— den” history of the discovery of insulin would not emerge until all of the principals were dead. Best was the last to die, in 1978. When I decided in 1979 to attempt to write a history of the discovery of insulin I knew nothing of these matters; no one did at the University of Toronto, which has a minimal institutional memory. The only document still being deliberately “suppressed” was Banting’s account, kept in a section of his papers restricted at the discretion of the head of the Fisher Library, who was respecting a decision taken years earlier by a (now—defunct) university committee on the Banting Collection. When I explained my interest in Banting it was immediately decided to make the account available to me and 2.: \III ii, t“ 1H: “llité‘gl Vii. to any other qualified researcher interested in the discovery of insulin Publication, it was agreed, would follow as soon as enough research was availal‘ile to make possible an appreciation otthe strengths and weaknessci oi Banting s viewpoint in the contevt oi the events of 19A) 22 at loronto in the winter of l939~~40, a year before his death, Banting drafted a much longer account which he provisionally entitled "The Story of Insulin. .~\pproxiinately one hundred pages in typescript, never revised from Bani ing's first draft, the document is an invaluable source for tlte historian or biographer, but does not easily lend itself to publication. it is rambling. often poorly-written, unreliable, and difficult to excerpt. Access to it has been on the same principles as to Banting’s 1922 account. I am currently attempting to arrange single-volume publication of all of the basic documents relating to the discovery of insulin; this would include “The Story of insulin” as well as Banting and Best’s notebooks, also available at the Fisher library Albert Gooderham wrote to Banting, Best, and Macleod in the hope that the differences in their versions of events could be reconciled and one authoritative history ofthe discovery agreed upon. C. H. Riches, the Universi ty’s patent attorney, was pressing him for such a unified account, and imporv tant discussions were about to take place with G. H. A. Clowes, research director of Eli Lilly and Company (which was by then collaborating with the University in the development of insulin) and two representatives of the Medical Research Council of Great Britain, H. H. Dale and Harold Dudley. Anyone who reads the following documents, combined with the Macleod account, will realize how great and bitter the differences were that had to be reconciled. Between Banting and Macleod, in particular, there had been a complete clash of temperaments and breakdown in personal relations. Bant- ing had also quarrelled bitterly with Collip, so much so that the January 1922 confrontation between them over methods of preparing insulin, was in facr violent. Banting’s extreme dislike of both Macleod and Collip in 1922, as well as his oppressive fear of losing credit for the discovery he felt followed from his great idea, makes his account of events the most passionate and least reliable of these documents. I had originally hoped to present these accounts with detailed editorial annotation to correct errors, highlight points of disagreement, etcetemi It was soon realized that such footnoting would take up more space than the documents themselves, and would lead to a complete re—telling of the his tory of the discovery. Therefore I have followed Stevenson’s practice with Macleod’s account and present the documents exactly as they were written. For a reconciliation of their authors’ differences, biases, distortions, errors, and other unclear points, a task which Colonel Gooderham abandoned in 1922, readers should consult my book, The Discovery of Insulin, published in Canada by McClelland 8: Stewart and in the United States by the University of Chicago Press. l . i.,.,.i-,. x, iildkull: ALBERI MUDDERHAMS lFl l‘lilt 'I‘oronto, (.rinatla it» Sept l‘L’Z My dear Dr. Banting: lMat‘leod, Bestj In view of the articles which have appearcd in the press regarding tht discovery of “insulin and or the t.insatistactor'v relationships which seem tc exist between l’rof tVlaclcod. Di Banting and Mr Best. regarding the contri bution which each has made towards this discover}, 1 ant rnr‘ist atixtous tr, restore the harmony of our Committee, that we may all work together in the future unitedly. in order to bring this about, it would be desirable to give, me a typewrit ten statement of your understanding of the discovery of “Insulin” right from the very start and its production to date. I am asking the others to do the same. In the absence of Prof. Collip I would appreciate if you would incor— porate in your statement an outline of his contribution to this work. I would then compare these statements and see wherein they differ, and ask you three gentlemen to meet at any early date with a view to harmonizing these statements with me. I feel that we should have as a result a connected account of the work from the very start, which would be available to anyone desiring information and which would be agreed upon by each member. This would, in my opinion, clear up all our misunderstandings and we would adjust this matter between ourselves before Dr. Clowes, and the gentlemen from England arrive. This understanding is urgent, as Mr. Riches requires me to give him such a statement in order that the question of the patents and of amended patents which are now necessary, may be proceeded with at once, Please be good enough to think this over carefully as I feel that this is the only way in which a satisfactory settlement of our difficulties can be made. I will be at your service almost anytime to do what I can to get everything working in harmony. Yours sincerely, ALBERT GOODERHAM F. G. BANTING [THE DISCOVERY OF INSULIN] Early in November 1920 while reading an article by Moses Barron in Surgery, Gynaecology and Obstetrics, on the Islets of Langerhans in relation to diabetes, the idea presented itself to me that since the ascinous but nor the insular tissue degenerates after the pancreatic ducts are tied, by this means ggfi .‘tlltllAlzl. 35H??? an extract of the islet tissue might be obtained, without the destroying influence of the pancreatic juice T he idea above mentioned occurred to me about 2 am. The next morning I went to see Dr. Miller. Professor of Physioli ogy, Western University, Iondon, with whom I was then working. He said that the idea had not been worked out so far as he knew. Dr. Crane, Profes sor of Pharmacology, did not know of any work on the subiect I next looked up every available reference in the library of the medical school, but found no work pertaining to the subject. I went to 'loronto and talked the matter over with Dr Starr, then with Professor Macleod. on November 6th My interview with Professor Macleod lasted about an hour. I told llllll carefully what I had planned, and to my disappointment he did not seem at all interested, and put me off by saying that many men had worked for years in well—equipped laboratories and had not proved that there was even an internal secretion of the pancreas. I then repeated my ideas to him, and he sat back in his chair with closed eyes for some time. Then he began to talk. He thought that “this might be the means of getting rid of the external secretion.” As far as he knew this had never been tried before “It was worth trying" and “negative results would be of great physiological value.” This latter phrase he repeated at least three times. This was not very encouraging, for I was not inclined to give up ap— pointments in Surgery and Physiology in London to get “negative results of great Physiological importance.“ I told him that there were no facilities in London, and that I would come to his laboratory to work if he would allow it. This he consented to do. I wanted to sell out in London, but Dr. Starr would not hear of it. He said that he would talk with Prof. Macleod and let me know. I do not know the trend of the conversation, but Dr, Starr strongly advised me to keep to surgery till the school term was over, and then to try out my idea if I still desired to doit. I left London on conclusion of the term, May 14th. When I arrived at the Physiological Department the work was discussed. Mr. C. H. Best was to assist me for three weeks, and Mr. Noble for three weeks, thus giving me six weeks. Professor Macleod apologized to Best and Noble, telling them that “it would likely all go up in smoke but would be a good operative training, and we must leave no sod unturned.” He instructed me how to do the first operation (the Hedon method of Pancreatectomy); the only time I have ever seen him in the operating room. Best was to be my assistant for the first three weeks, having tossed with Noble for who would be firsr. We arranged to do blood sugar, total sugar excreted, total nitrogen, and record the diets, etcetera. Early in june the professor sailed for Scotland. During June and July Best and myself (for Noble had decided that he would let Best do his share of the work) tied the pancreatic ducts on about six dogs, and had run a number of controls on the Hedon operation. Finally on July 3lst, 1921, we had both a diabetic dog and a dog on which the ducts The lustmerx mt Insulin get; had been tied for seven weeks. The duo. tied dog was killed with an over dose of chloroform and the pancreas removed, and mascerated in ice cold Ringersol. The blood sugar dropped after the injection, and our positive results Were commenced. Various things Were tried with the extract, as shown in the articles on the work at this time (In this history I do not wish to give a detail of the findings so much as 1 do as to how the findings came about). All went merrily till the latter part ol September. when the prolessoi returned. We had been waiting all Summer to tell him of our results, and to get things that we needed for the laboratory. The place where we were operating was not fit to be called an operating room. Aseptic work had not been done in it for some years. The floor could not be scrubbed properly, or the water would go through on the laboratories below. The walls could not be washed for they were papered and then yellow washed. There were dirty windows above the unsterilizable wooden operating table. The operat ing linen consisted of towels with holes 'in them. It was made more difficult to get things because I had been given six weeks to get results, and overtime was not in any person‘s line, and, worst of all, no one took me seriously, since the professor had said that “it would likely go up in smoke,” We had a number of dogs die of infection despite our utmost care, and finally we were compelled to operate in the research operating room of the Pathology Building. Shortly after Professor Macleod’s return (the last week in September) I asked him for four things: 1. A salary, because I was already deeply in debt and could not borrow more money; 2. A room to work in, for we had been working in a room which was not private; 5. A boy to look after the dogs, for we frequently had to clean the cages and operating room ourselves; 4. The floor of the operating room repaired. Professor Macleod was not inclined to give us these demands and said that if he gave us these things some other research would suffer. I told him that if the University of Toronto did not think that the results obtained were of sufficient importance to warrant the provision of the aforementioned requirements I would have to go some place where they would. His reply was “As far as you are concerned, I am the University of Toronto." He told me that this research was “no more important than any other research in the department.” I told him that I had given up everything I had in the World to do the research, and that I was going to do it, and that if he did not provide what I asked I would go some place where they would. He said that I “had better go." I rose to go, but the professor softened a little and finally decided that he could get a boy and a room and that the operating room might be made waterproof by tarring the floor. €60 ,XlltiiALl ESE l‘.~'~ I would have left the University of lUl’Lnlit) at this time had not Professor Henderson secured for me an appointment in Pharmacology, and had l not promised Professor Fitzgerald that I would HO! leave Toronto without con- sulting him. (I told the results of experiments trout time to tune during the “summer to i—‘rotessors Henderson and Fitzgerald) it might be pointed out here that l have never at any time held an llppi?ll7.f111t,‘l'tl in the l‘trépartment oi Physiology of the l‘i’llVBI'Sll} of loronto. During the Summer the work, for the most part. was done in the De partment of Physiology, but total nitrogen estimations were done in the Department of Biochemistry. Some operations were done in the surgical research operating room, Histological sections were made for us in the Department of Pathology. and the Connaught Laboratory gave us the facilities of the operating room at the farm, and three calves for exhausted gland experiments. At the Physiological Journal Club Meeting of November 14th, it was arranged that Best show the charts and that 1 give a resume of the work of other investigators, and the development of our research. Professor Macleod in his remarks gave everything that I was going to say and used the pro» noun “we” throughout The following day students were talking about the remarkable work of Professor Macleod. Very little progress was made between October lst and the middle of November. At this time a new era was introduced by the discovery that the pancreas removed from foetal calves contained the antiidiabetic principal, and that the subStance could be extracted with saline. The idea came to me in the following manner: Laguesse found that the Islets were more plentiful in foetus and newborn, hence there should be more internal secretion in the newborn. I thought first of using pancreas of newborn, then I thought of producing abortion in dogs and u'sing the pancreases thus obtained. Then it occurred to me that there might be a time in development when the internal but not the external secretion would be present. This idea finally presented itself about 2 am. November 16, 1921. The next day Best and I went to the Davies Abbattoir and secured a number of pancreases of foetal calves, made an extract, injected it into a diabetic dog, and the blood sugar fell. 1 later found that Ibraham had shown that the foetal pancreas of under four months development did not contain proteolytic enzymes. On December 6, 1921, some mascerated foetal pancreases were placed in alcohol and allowed to stand. The alcohol was filtered till clear and then evaporated to dryness in a warm air current. The residue was dissolved in saline and injected into a diabetic dog, #23. The blood sugar fell from .26 to .11 in five hours. This was the first positive result of extract made by al- coho...
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