The Discovery of Insulin
Page 40
93 Collip 1923C.
94 Collip 1923E.
95 Collip 1923D, pp. 526f.
96 IC, clippings file; BP, 47, p. 74.
97 MP, folder 342, Collip to Macleod, April 21, 1923.
98 Collip 1923F, H.
99 Best and Scott 1923B.
100 MP, Macleod to Scott, April 23, 1923; Macleod 1926, pp. 292–3; Macleod and Campbell 1925, pp. 17–18; Macleod 1924B, p. 65; MP, Macleod to Dale, May 15, 1923.
101 Robert Noble interview with Harold Ettinger, c. 1967.
102 See MRC 1092/13.
103 Best and Scott 1923C; Best, Smith, and Scott 1924; Best 1924.
104 Academy of Medicine, Toronto, E.C. Noble Papers, Macleod to Noble, undated but clearly summer of 1923.
105 McCormick and Noble 1924; McCormick 1924; IC, University of Toronto Miscellaneous file, A.G. Huntsman to J.G. Fitzgerald, July 14, 1923, reply July 18.
106 IC, clippings file, Royal Gazette (Bermuda), May 18, 1923; Lilly archives, XRDgb, Laboratory notes, vol. 2, p. 24; MRC 1092/11, Dale to Fletcher, Jan. 1, 1924; IC, Great Britain file, Dale to Macleod, Feb. 15, 1924.
107 MRC 1092/23, Macleod to Fletcher, Sept. 28, 1923; Fletcher to Macleod, Sept. 27.
108 MRC 1092/23, Dale to Fletcher, Oct. 11, 1923.
109 Jonathan Meakins Papers, Dale to Meakins, Dec. 6, 1923; pun by D. Hannay.
110 MRC 1092/19, Dale to Fletcher, Oct. 19, 1923.
Chapter Eight: Who Discovered Insulin?
1 See Bliss 1978.
2 New York Times, Oct. 8, 1922.
3 Ledger, Oct. 13, 15, 1922; IC, state and alphabetical files; see also New York American, Oct. 22, 1922, for F.M. Allen’s attempts to correct these misconceptions.
4 Star, and other Toronto newspapers, Nov. 27, 29, 1923. The Star added the qualification.
5 IC, clippings file, syndicated article by “Harley Street Doctor”, May 1923; Toronto Globe, May 17, 1923; see also the confusion stemming from an interview with Geyelin, Toronto Star, Feb. 10, 1923.
6 EH to her mother, Oct. 21, Nov. 21, 1922; for coverage of her see BP, 47, p. 23.
7 BP, 47, p. 73, Corbett clippings, April 1923; Ibid., Vanderlip, April 11; Star, May 21, 1923.
8 Star, June 20, 1923; Star, and other papers, May 19, 1923; see also Slosson 1923, which was commissioned by the Insulin Committee.
9 MRC 1092/23, Macleod to Dale, Feb. 6, 1923; interview with Professor Robert Garry, Oct. 10, 1980; BP, 47, p. 75, clipping March 14, 1923.
10 BP, 47, p. 80, undated clipping, Hadwen letter to the Toronto Globe.
11 Mackenzie King Papers, J2, vol 13, H1000, undated clipping.
12 BP, 47, clippings c. Feb. 1923; Ibid., p. 63, postcards and clippings on vivisection; p. 30, Falconer statement, June 1, 1923.
13 Joslin 1922; Banting 1940, p. 60, seems to condense events between May and July.
14 FP, “Hot” file, Bayliss to Macleod, Sept. 29, 1922.
15 Banting 1922; Noble papers, ms. notes on the discovery of insulin.
16 Star, Sept. 8, 1922.
17 CP, private, Macleod to Collip, Sept. 18, 1922; Macleod 1922; also MP, folder 342, Macleod to A.B. Macallum, Sept. 14, 1922: “Now he claims that I should in the same way give him full credit for all the work which has been done subsequent to this [duct-ligation] experiment. This I will of course not do since he has participated very little in the work, and not at all during the past six months.”
18 Toronto Globe, Sept. 9, 1922; Macleod 1922.
19 CP, private, Macleod to Collip, Sept. 18, 1922; FP, “Hot” file, Macleod to Sir Wm. Bayliss, Sept. 13, 1922; MP, folder 342, Macleod to A.B. Macallum, Sept. 14, 1922.
20 MP, folder 342, Macleod to A.B. Macallum, Sept. 14, 1922.
21 BP, 1, Gooderham to Banting, Sept. 16, 1922; MP, Gooderham to Macleod, Sept. 16.
22 Macleod 1922/78.
23 Banting 1922.
24 Best 1922.
25 See the note Macleod added to his 1922/78 account.
26 BP, 1, Banting to Macleod, Sept. 27, 1922; Banting to J.G. Fitzgerald, Oct. 5, 1922.
27 Banting 1940, pp. 61–64; interview with Stella Clutton, 1980; see also BP, 37, Banting notes on his position, early Oct. 1922; and case 1 for his coldly formal correspondence with Graham.
28 Wilder 1963.
29 FP, “Hot” file, Macleod to Bayliss, Sept. 8, 13, 1922; Bayliss 1923; MP, folder 342, Macleod to Collip, Feb. 28, 1923.
30 Banting 1940, pp. 33–34.
31 Roberts 1922.
32 Macleod 1923.
33 Dale 1922.
34 Pratt 1954ms, p. 31a.
35 Banting 1929.
36 Pratt 1954 and 1954ms. Pratt once remarked that while Banting may have been the quarterback of the team, it was Collip who scored the winning touchdown.
37 Feasby 1958.
38 See Pratt 1954ms. It was Macleod’s erroneous understanding on this point, however, that seems to have inspired Dale’s oft-repeated quip that insulin could only have been discovered in a lab whose director was slightly stupid – a revealing comment in view of Dale’s having publicly scolded Roberts for scornfully belittling Banting and Best.
39 The unpublished version of Joseph H. Pratt’s reappraisal contains a rather different, also meritorious, summary of the steps and those responsible for each, in the discovery of insulin as a therapeutic agent:
There were eight distinct and essential steps or stages leading to the production of an insulin that was sufficiently pure to be used in the treatment of diabetes and which could be produced in adequate quantity to meet the urgent demand. The first of the steps was the use of alcohol in extracting the hormone from the minced pancreas. This was announced by Zuelzer in Berlin in 1907. It was rediscovered by the Toronto investigators in 1921, who did not know of Zuelzer’s work. The second was a method of determining the amount of sugar quickly and accurately in a small quantity of blood. This was devised by Lewis and Benedict in New York in 1913. The third was the discovery of Kleiner and Meltzer in 1915 that an aqueous extract of the normal pancreas injected into the veins of a normal dog reduced hypergly-caemia as well as glycosuria. The fourth step was the discovery that the active principle was insoluble in 95 per cent alcohol. This was made by Banting, Best and Collip in December 1921. The fifth was the preparation by Collip of the first relatively non-toxic insulin to be used in the treatment of diabetes (January 1922) with success. The sixth step was the physiological assay based on Collip’s observation (February 1922 [actually December]) that insulin in adequate amount usually produced convulsions in normal rabbits when the blood sugar fell to 46 mg. per 100 cc. The seventh was the discovery by Doisy, Somogyi and Shaffer of St. Louis, that insulin was precipitated at the isoelectric point… .The eighth and final step was the development of methods of large-scale production by the chemical engineers of the Eli Lilly Co. of Indianapolis in 1922–23.
Chapter Nine: Honouring the Prophets
1 Rochester Democrat-Chronicle, June 4, 1923. See also N.Y. Tribune, July 8, 1923, “Wounded hero gave Insulin to humanity”; and BP, 47, p. 81, undated clipping. Paul De Kruif, perhaps the most famous popularizer of the triumphs of medical research, contributed his share to the myth-making in a long article syndicated by Hearst International in November 1923, and republished in his 1932 anthology, Men Against Death.
2 Toronto Star, August 24, 1923; Ibid., Feb 24; Toronto Evening Telegram, Jan. 18, 1923; New York Tribune, July 8, 1923; BP, 49, p. 22, undated clipping.
3 BP, 47, p. 44, undated clipping. Of Banting’s speech, the reporter wrote that he was “painfully embarrassed, broke brisquely into his exposition without remark and literally fled from the hall after two minutes of nerve-cramped, graceless, almost inaudible explanation of his discovery.” See also Banting 1940, p. 66, for his own recollection of how badly he spoke compared to Voronoff.
4 MP, folder 342, Macleod to Collip, Feb. 28, 1923.
5 BP, 26, desk calendar, May 8, 1923.
6 Mackenzie King Papers, Diary, Feb. 13, 1
923; personal communication.
7 Toronto Evening Telegram, Oct. 13, 1933; New York Tribune, Oct. 14; McGill University Archives, Principal’s files, 641, A.L. Lock wood to Sir Arthur Currie, Jan. 2, 1923 (misdated 1922); reply Jan. 23. I am grateful to Marlene Shore for bringing this exchange to my attention.
8 House of Commons, Debates, Feb. 27, 1923; pp. 729–30; Toronto Star, March 1, 1923.
9 BP, 26, desk calendar, Feb. 27, 1923. Billy Ross later told Lloyd Stevenson he had proposed the research professorship to the provincial government in mid-January. Stevenson 1946, p. 178.
10 BP, 26, desk calendar, March 13, 1923; the correspondence and the testimonials are in case 1, c. March 1923; see especially Banting to Mrs. Hughes, March 14, which may also have been drafted for Banting by Ross. In it Banting writes of Ross’s letter: “I am not completely familiar with its contents, but know it is concerned with certain proposed actions of the Dominion Government with reference to myself.”
11 A politically active medico on the Conservative side who was also helping Banting was Dr. Herbert Bruce. Both Ross and Bruce were simultaneously leading a struggle of old-guard Toronto practitioners against reforms in the university’s faculty of medicine which were giving increased power to full-time faculty members like Duncan Graham. There is some evidence that Bruce and Ross found Banting a useful stick with which to batter further the university’s establishment; he would have been more useful still had not his hero, C.L. Starr, been one of the chief establishment figures that they wanted to batter.
12 Interview with Edward Banting, Alliston, 1981.
13 King Papers, JI, 77025–30, Mulock to King, March 21, 23, 1923.
14 BP, 1, Lillian Hallam to Banting, March 6, 1923; reply March 13.
15 Drury Papers, Banting to Drury, April 4, 1923.
16 CP, UWO, Medicine, signed but undated second page of a letter from Collip to a friend, probably written in the summer or autumn of 1923, discovered in files stored in the biochemistry department. For Collip’s other accounts see chapter 4, note 42.
17 Calgary Herald, May 30, 1923; Edmonton Journal, May 25.
18 King Papers, JI, 74205–09, Hughes to King, March 16, 1923, reply April 6; 77829–30, Ross to King, and reply.
19 King Papers, JI, 72674–6, King to Falconer, June 1, 1923.
20 BP, 47, p. 118, clipping from the Star, Nov. 7, 1923.
21 King Papers, JI, 72677–8, Falconer to King, June 2, 1923. The only other statement of Falconer’s is in a letter to Dr. Lewellys F. Barker, May 11, 1923 (Falconer Papers), in which he says that the discovery “could not have been made unless Macleod and his associates in the Physiological Laboratory had not been ready to help Banting in his work.”
22 King Papers, JI, 78836, Ross to King May 8, 1923; BP, 47, pp. 43, 69, clippings re Academy and CMA; Montreal Gazette, June 14, 1923.
23 House of Commons, Debates, June 27, 1923, pp. 4591–4.
24 BP, 1, Mulock to Ross, undated, in July 1923 file.
25 King Papers, JI, 80795–6, C.A. Stuart to King, June 27, 1923.
26 IC, unsorted, Fitzgerald to King, June 27, 1923.
27 BP, 1, Best to Banting, June 28, 1923.
28 BP, 1, Banting to Hipwell, undated in July 1923 file; Hipwell to Banting, July 28, 1923.
29 Best Papers, private, MMB scrapbooks, Banting to Best, July 15, 1923.
30 IC, unsorted, King to Fitzgerald, July 5, 1923- King Papers, JI, 80797–8, King to C.A. Stuart, July 3.
31 Banting 1940, p. 66; MacFarlane, Florey, p. 77.
32 MP, Macleod to Prof. A.R. Cushny, March 6, 1923.
33 Macleod 1923; BP, 26, desk calendar, July 26, 1923. In 1940, p. 66, Banting wrote of Edinburgh: “There could be no doubt in the minds of the listeners that Macleod was the discoverer of the physiological principles of insulin.”
34 The following account has been compiled almost exclusively from documents in the Nobel archive at the Karolinska Institute in Stockholm. In most cases, the identification of the documents in the text – Nobel Committee minutes, nominations, investigations, etc. – is sufficient identification to locate the original in the archive. The original documents are in Swedish or the native language of their authors. The standard history of the Nobel prizes is Nobel, The Man and His Prizes, by the Nobel Foundation (third revised edition, New York 1972).
35 The other scientists on the short list that year were Gustav Embden, Johannes Fibigers, Solomon Henschens, F.G. Hopkins, Arthur Loos, Thomas Morgan, and Fernand Widal. Fibigers, Hopkins, and Morgan were later awarded Nobel prizes.
36 Banting 1940, p. 72a; personal communication.
37 BP, 1, Banting to Best, Oct. 26, 1923.
38 Star, Nov. 2, 1923.
39 Star, Nov. 7, 1923.
40 Star, Nov. 8, 1923.
41 MP, folder 342, Macleod to B.P. Watson, Jan. 3, 1924.
42 IC, Krogh to Macleod, Oct. 25, 1923 (postscript Oct. 26). Macleod also received an interesting letter from a Western Reserve colleague, T. Win-gate Todd, who had earlier written to British journals claiming that the greatest credit should go to Macleod. Todd was writing without certain knowledge of the award, having heard a rumour that it might go to Banting alone, or to the two of them:
To give Banting the prize at all shows a deplorable lack of scientific judgment on the part of the Committee, but worse than that it shows also a complete lack of scientific common sense. It encourages the all-too-common lay belief in inspiration and indeed sets the stamp of approval of what the layman considers the high court of appeal. Apart altogether from the indignity which it offers to yourself it is a very severe and calamitous setback for medical science….There is no doubt that time will put everything straight but it is heart-breaking to see how even friends and those whom we have hither-to regarded as not lacking in reason, have fallen under the spell of a malicious press-campaign.
MP, folder 342, Todd to Macleod, Oct. 29, 1923.
43 BP, 1, Geyelin to Banting, Nov. 7, 192.3; reply Nov. 10.
44 Nobel archive, Miscellaneous correspondence, Zuelzer to G. Liljestrand, Dec. 22, 1923, 18 Aug. 1924; Paulesco to the president of the Nobel Committee, Nov. 5, 24, 1923.
45 Star, Nov. 27, 1923; also Telegram, Globe, and other clippings.
Chapter Ten: A Continuing Epilogue
1 Anecdote related by Dr. Keith MacDonald, Oct. 23, 1981.
2 Joan Didion, The White Album (New York, 1979), p. 53.
3 Nobel, pp. 224–5.
4 Robert Noble interview with Dr. Harold Ettinger, c. 1967.
5 Collip 1941; interview with Dr. Hugh Lawford, Oct. 16, 1981.
6 Interview with Dr. Rolf Luft, June 1981; Lusk 1928, p. 651.
7 BP, 1, Scott to Banting, Nov. 23, 1923. The fact that a copy of this letter is also in the E.L. Scott Papers, and was seen by his widow, makes A.H. Scott 1972 a nearly dishonest account. Scott also wrote H.H. Dale, at the time of Dale’s attack on Roberts, Jan. 20, 1923, saying “I am sure that it is a matter of indifference to me whether or not Banting and Best are using my method or some modification of it and so long as they and most if not all others who have tried their preparation get the results which they do it can only give me a feeling of elation that perhaps I have played some part in the net result.
“I have never felt that I have not received all the credit that was coming to me in any of the publications from the Toronto Laboratory.”
8 Murlin and Kramer, 1956.
9 IC, Myrtillin file; Allen 1927, 1928.
10 Henderson 1970; Allen papers, manuscript autobiography.
11 IC, unsorted, account of royalties compiled by Albert Fisher.
12 Falconer Papers, case 81, memorandum, Jan. 23, 1923.
13 Modest grants from the Connaught Fund supported the research necessary for this book.
14 BP, 47, pp. 94–9, clippings re Banting Research Foundation.
15 Lusk 1928, p. 655.
16 BP, 1, B.A. Bradley to Banting, Jan. 12, 1926.
17 Leyton 1923.
&
nbsp; Sources
I. Manuscript Collections
Aberdeen University, Physiology Department Records
Frederick M. Allen Papers, in the collection of Alfred R. Henderson, M.D., Washington, D.C.
F.G. Banting Papers
1. Fisher Library, University of Toronto (61 cases)
2. Notebook, Academy of Medicine Toronto
3. National Research Council, Ottawa (4 cases)
C.H. Best and M.M. Best Papers
1. Privately held; to be transferred to Fisher Library
2. Best Institute, University of Toronto; transferred to Fisher Library
Canadian Diabetes Association Archives, Toronto
H.J. Cody Papers, University of Toronto Archives
J.B. Collip Papers
1. University of Western Ontario, Faculty of Medicine Library
2. University of Western Ontario, Library, Special Collections Division
3. Privately held
Connaught Laboratories Archives, Toronto
Sir Henry Dale Papers, Royal Society, London
E.C. Drury Papers, Public Archives of Ontario, Toronto
Eli Lilly and Company Archives, Indianapolis
Sir Robert Falconer Papers, University of Toronto Archives
W.R. Feasby Papers, Canadian Diabetes Association Archives
G. Howard Ferguson Papers, Public Archives of Ontario
Elizabeth Hughes Gossett Correspondence, Fisher Library, University of Toronto
Hannah Institute, Toronto, Oral History Collection
Havens Family Papers, privately held
Insulin Committee (University of Toronto) Records, University of Toronto Archives
W.L. Mackenzie King Papers, Public Archives of Canada, Ottawa
McGill University Archives, Montreal
J.J.R. Macleod Papers, Best Institute, University of Toronto; transferred to Fisher Library
Jonathan Meakins Papers, privately held
Medical Research Council Records, London, England
Nobel Archive, Karolinska Institute, Stockholm
EC. Noble Papers, Fisher Library, University of Toronto
E.L. Scott Papers, U.S. National Library of Medicine, Bethesda, Md.
H. M. Tory Papers, University of Alberta, Edmonton