The measurement of the combining power of diphtheria toxin and toxoid with anti-toxin in relation to their antigenic efficacy / by A.T. Glenny, C.G. Pope, and Hilda Waddington.

Glenny, A. T.

Date:: [1925?]

Credit: The measurement of the combining power of diphtheria toxin and toxoid with anti-toxin in relation to their antigenic efficacy / by A.T. Glenny, C.G. Pope, and Hilda Waddington. Source: Wellcome Collection.

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$failure of others. All experimental data accumulated during our own ! experience can be explained on Ehrlich’s assumption that the total I amount of toxin and toxoid neutralised in any quantity of the toxin solution is directly proportional to the antitoxin added. Ehrlich : postulated man}^ forms of toxoid and also suggested such modifications ? as toxones and epitoxonoids. The view we wish to bring forward is that all observed phenomena can be explained by the presence of i toxin and toxoid and by the fact that toxin has a much greater affinity y for antitoxin than has toxoid. There may be qualitative differences ^ between different toxoids produced in different ways, but it appears ' unnecessary to assume that there is a definite series of sharply defined . substances. We make no endeavour to criticise in detail Ehrlich’s ; conception of the plurality of constituents of “ toxin ” because we consider that certain observed phenomena, e.g. paralysis, may be ^ explained without reference to a series of modifications of toxin i and toxoid. The object of the present paper is to compare the various animal i tests for diphtheria toxin with one another, to contrast them with I the in vitro test and to establish the best test of antigenic efficiency, j j Methods of measurements. Titration in vivo. \ The determination of the specific toxicity and also of the combining power of diphtheria toxin with antitoxin depends upon the production i of certain toxic symptoms in guinea-pigs. Diphtheria toxin injected | subcutaneously will kill guinea-pigs more or less rapidly; sublethal i doses cause local oedema. Toxin injected intracutaneously even in li high dilution gives rise to an inflammatory reaction. From these i reactions certain units have been fixed. The chief unit of specific I toxicity is called the minimal lethal dose or “ M.L.D. ”; in practice i this is the smallest amount of toxin which will kill a guinea-pig of (j convenient size (250 grm.) in a reasonable time (5 days); it is not <i strictly a minimal dose. The corresponding intracutaneous unit is the i minimal reacting dose, ‘M.E.D.,” which Glenny and Allen (1921) have < defined as the smallest quantity of toxin which will produce a reaction r| when injected into the skin of a guinea-pig. Eor convenience in the j following argument we introduce another unit, the ‘‘minimal oedema | producing dose ” or “ M.OE.D. ” which is the smallest amount of toxin ^ which, injected subcutaneously, will produce detectable oedema in the i guinea-pig. The following ratios appear to hold approximately true for 'j an average toxin: 1 M.L.D. = 20 M.CE.D. = 1000 M.E.D. ! When quantities of antitoxin are successively added to a toxin a. point is soon reached at which the time of death is delayed, and if r more antitoxin is added we reach a point where the mixture is non- { lethal to guinea-pigs. Obviously this affords us a suitable end point$