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Edinburgh Conference, had been made at the National Institute for Medical Research, London ; i milligramme of this preparation to be regarded as containing 8 units of insulin as provisionally denned by the Insulin Committee of the University of Toronto, so that 0.125 milligramme of the standard preparation would contain exactly one unit of insulin. Professor Macleod further gave details concerning the method of physiological comparison with this standard, which, on behalf of the Toronto Committee, he recommended for adoption.
The President mentioned some details concerning the preparation of the standard material now recommended for adoption, and quoted four independent determinations of different laboratories of its value, on the basis of the units previously current in Canada, the United States and Great Britain. The four determinations gave respectively 8.6, 8.4-8.6, 8.5 and 8.8 as the number of units present in i milligramme of the standard. He strongly supported Professor Macleod's proposal that, for the sake of simplicity, the standard should be so defined that i milligramme would contain 8 units of insulin. He further mentioned a modification of the Toronto method of biological comparison, which had been for some time in successful use in his own department.
Professor Krogh described his later experience with the method of biologically standardising this product, by determination of the proportion of convulsions produced by a dose, in a series of mice kept in a thermostat.
Professor Meyer mentioned a new method, devised by Professor Loewi, of the University of Graz, according to whom insulin altered the distribution of dextrose between the plasma and corpuscles of shed blood. It was agreed that the method was one which deserved careful further investigation, but that experience with it was as yet insufficient to warrant any recommendation as to its adoption.
Professor Macleod and Professor Krogh were asked to act as a Sub-Committee to put into the form of definite resolutions the points on which agreement had been reached. These, as presented to and unanimously adopted at a later meeting of the Conference, were as follows : "It is recommended :
"i. That the dry preparation of insulin hydrochloride, prepared by the Medical Research Council of Great Britain, at the request of the Edinburgh Conference, should be accepted as the International Standard preparation of insulin. That i milligrame of this standard contains 8 units of insulin (or i unit = 0.125 milligramme), as provisionally defined by the Insulin Committee of the University of Toronto. 4«-Ittture -t^e-teHft—^^tait-'-in- c^njaeettnri-with-ift^aJm should be used m-this Dense emly.. „
"2. That this standard preparation be kepj^J^J^lie^J^^ who will undertake to test the permanence of its potency fi^olrTtlrne to time.W ^
"3. That samples of this preparation, weighing o.ioo gramme each, be sent to some / responsible organisation in each country (such as an Insulin Committee or a Government C/rfG institution) who will undertake further distribution to testing laboratories. In those n K^ countries in which no suitable organisation for this purpose exists, samples of the standard j, *^ will be distributed by the Medical Research Council after consultation with the Insulin ^\ j( Committee of the University of Toronto, or, in case this Committee be discontinued, / with one appointed by the Health Committee of the League of Nations.
"4. That each testing laboratory should prepare a standard of its own, and should compare the potency of this with the sample of the international standard placed in its hands for this purpose. When the latter is exhausted, further comparisons with the international standard should, where possible, be undertaken by the responsible authority for the particular country.
"5. That either of the following methods be considered as suitable for^the bio-assay of insulin :
"[«) Methods depending on the effect on blood- sugar.
J^v^fVj <;£>*• fyr}T Varying quantities of insulin that are less than the convulsive dose are injected subcutaneously into rabbits of about two kilograms body-weigh^r£ncT) from which food has been withheld for 18-24 hours and the average of the blood- sugar percentages over-a period of five hours after the injection is subtracted from the blood- sugar percentage|*V-^r. immediately preceding the injection. The number of units of insulin present in each cubic centimetre of trie preparation is then calculated by use of a formula (see report). Each rabbit used in the assays is tested at suitable intervals with a standard preparation whiclys periodically compared with the international standard.
^WxKA M-ct£fr^#) Alternatively, one-half of a series of rabbits receives, in each case, an injection of Y2 unit of the standard preparation per kilogram, and the other half receives, on the same day, the dose supposed to be equivalent of the sample under test. The percentage fall of the blood-sugar content over a period of five hours is determined as above. A few days later the determinations are repeated on the same series of rabbits in this way, that the rabbits previously receiving the standard preparation now receive that under test and vice versa.
"From the relation between the falls of blood-sugar content produced, on the one hand, by the standard preparation, and on the other hand by the sample under test, , \ the true activity of the latter in units per c.c. can be calculated. ( S^i. c*JLfois\. tJtL yuL-AfrVf-' )
"(b) Method depending on the incidence of symptoms in white mice.
"The assay is carried out by comparison with a standard preparation injected simultaneously with the unknown sample on an equal number of mice from a common stock.