Generally, many of the precursors had produced active extracts, i.e., extracts containing insulin. But none of them had been able to purify their extracts sufficiently to eliminate the various possible toxic impurities. These included other proteins; peptides; adenosine derivatives; histamine; serotonin; prostaglandins; lysolecithin and other lipids; bile salts from adjacent tissues; and pyrogens from gram-negative bacterial contaminants.
* Collip’s exact dating of this result in his early accounts suggests that for him it was another thrilling moment of discovery, similar to the exhilarating experience the night he first realized he had purified insulin. One evening in 1981 I received a call from a seventy-nine-year-old lady who thought she should pass on to me her vivid memory of the morning in 1923 when she, a pharmacy student at the University of Alberta, saw Collip emerge from his lab, utterly dishevelled, having not had his clothes off for days, to announce that he had got it. She thought she remembered him discovering insulin, but it was undoubtedly one of the later “discoveries.” Is the pure elation of discovery just as authentic an emotional experience for a scientist when it is later found to be no discovery at all?
* The problem of standardizing insulin had been and continued to be far more complicated and less facetious than this cursory treatment implies. The resolution of the problem in the years 1923 to 1926, culminating in international acceptance through the League of Nations of a specific quantity of powdered insulin as the basic unit, is an important chapter in the history of bioassay. H.H. Dale made his most useful contribution to insulin research in persuading Macleod, Krogh, and others to give up the futile attempt to use rabbit or mouse units, which would inevitably be variable, as standards of measurement. (See Feldberg 1970, Dale 1959.) But that statement, too, is a gross simplification, for the international standard has always been related to animal tests. G.A. Stewart wrote in 1971 that “The rabbit blood sugar and mouse convulsion methods of assay are still the only internationally accepted methods for the determination of insulin potency, and have been used whenever a new International Standard for Insulin has been established.”
* Clowes’ support is particularly evident in the letters he and Banting exchanged that summer. Banting had obviously told Clowes the whole story from his point of view. He expanded on it by arguing to the Lilly man that Macleod could not be trusted not to give the secret of the method away to a competitor. Clowes’ personal feelings toward Macleod are not known, but it was certainly tactically useful to him to have Banting as a kind of personal ally, feeding Clowes with inside information about attitudes and goings-on among the leading members of Toronto’s Insulin Committee.
* For a discussion of this question see chapter four, note 50 (page 262).
* In 1961 Best described the following confrontation between Banting and Graham: “… he came back one day to the Connaught, or the basement of the Medical Building where I was working and said ‘I had a little session with the Professor of Medicine.’ I said ‘Tell me about it.’ And he said, ‘Well, he called me in and told me that I had represented certain things falsely.’ And I remember saying ‘What did you do?’ Banting said, ‘Well, be was sitting down so I went over and lifted him up by the collar and said ‘Professor, are you calling me a liar?’ And if he had said ‘Yes’ I’d have smacked him, but he said, ‘No, just probably a mistake – I’m not calling you a liar.’” (FP, Dictation, Nov. 24)
† Bayliss’ account is very straightforward. He mentions Banting getting the duct-ligating idea, and goes on: “Dr. Banting was then in medical practice at London, Ontario, but gave up his practice and went to Prof. Macleod’s laboratory at Toronto to make the necessary experiments on animals. Here he was joined by Mr. Best, an assistant in the laboratory, by Prof. Macleod himself, and at a later date by Dr. Collip and others. The experiments were successful. In another way it was found possible to prepare active extracts…. But it was clear that these methods could only afford a small supply. Hence attempts were made to discover a means of preparation from the ordinary ox pancreas. Dr. Collip was finally successful by making use of alcohol.” Nature, Feb. 10, 1923, p. 189.
* In 1919, Allen himself said he did not think his work would have succeeded. It appears that he was working with a pancreaticoduodenal serum, apparently on the theory, which seems to have influenced Knowlton and Starling, and Murlin, that secretin, which was necessary to activate the external secretion, was necessary to trigger the activity of the internal secretion.
The Discovery of Insulin Page 46