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BACTERIOLOGY

67 animal actively immunized may have one of two properties If this view as to the chemical relationship is correct—and —it may be antitoxic or it may be anti-bacterial. The none of the objections brought forward appear of a cogent term antitoxic signifies that the’ serum has the nature the antitoxin may act on the toxin in one of two serum*lc Power neutralizing the action of the toxin, as ways. It may produce a disintegration of the toxin moleis shown by mixing them together outside the cule, or it may combine with it to produce a body whose body and then injecting them into an animal. The anti- chemical affinities are satisfied. The latter view, strongly toxic serum when injected previously to the toxin also advocated by Ehrlich, is the more probable, as it harmonconfers immunity (passive) against it; when injected after izes with the facts established with regard to toxic action the toxin it has within certain limits a curative action, and the behaviour of antitoxins. His view as to the dual though in this case its dose requires to be large. The composition of the toxin molecule has already been mentioned, antitoxic property is developed in a susceptible animal by and it is evident that if the haptophorous or combining successive and gradually increasing doses of the toxin. In group has its affinity satisfied by union with antitoxin, the the earlier experiments on smaller animals the potency of toxin will no longer combine with living cells, and will the toxin was modified for the first injections, but in thus be rendered harmless. One other important fact in preparing antitoxin for therapeutical purposes the toxin in support of what has been stated is that a toxin may have its unaltered condition is used, the horse being the animal its toxic action diminished, and may still require the same usually employed. The injections are made subcutaneously amount of antitoxin as previously for neutralization. This and afterwards intravenously. To obtain high antitoxic is readily intelligible on the supposition that the toxopower the toxin must, at least ultimately, be a powerful phorous group is more labile than the haptophorous. one j and, while the dose must be gradually increased, care Against the view that antitoxin combines with toxin there must be taken that this is not done too quickly, otherwise has been brought forward the statement, notably by the antitoxic power of the serum may fall and the health Calmette, that in a neutral mixture of the two substances of the animal suffer. The serum of the animal is tested the toxic action reappears when exposed to a temperature from time to time against a known amount of toxin, i.e., sufficient to destroy the antitoxin in its free condition. is standardized. The unit of antitoxin in Ehrlich’s new This result has been questioned on the ground that the .standard is the amount requisite to antagonize the unit of time necessary for complete combination was not taken toxin, i.e., 100 times the minimum lethal dose to a guinea- into account, but even if the result be as stated, it is quite pig of 500 grm. weight, “ antagonizing ” action signifying possible that of two complicated substances in combination that a fatal result does not follow within five days after the more labile may be destroyed by the same temperature the injection. In the case of diphtheria the antitoxic as when free. power of the serum may reach 800 units per cubic centiKega,rding the origin of the antitoxin there has been, metre, or even more. The laws of antitoxin production and still is, much discussion. There are three chief and action are not confined to bacterial toxins, but apply possibilities : (a) that the antitoxin is a modificaalso to other vegetable and animal toxins, resembling them tion of the toxin ; (b) that it is a substance Pormatloa in constitution, viz., the vegetable toxalbumoses and the normally present, but produced in excess under snake-venom group referred to above. stimulation of the toxin ; (c) that it is an entirely °X " The production of antitoxin is one of the most striking new product. The first of these, which would imply a facts of biological science, and two important questions process of a very remarkable nature, is disproved by what re r Action of g& d to it mustnext be considered, viz., how is observed after bleeding an animal whose blood contains antitoxin. ^oes ^ie antitoxin act? and how is it formed antitoxin. In such a case it has been shown that, without within the body ? Theoretically there are two the introduction of fresh toxin, the antitoxin is partly possible modes of action : antitoxin may act by means of restored, and therefore must be produced by the living the cells of the body, i.e., indirectly or physiologically ; tissues. The second theory is the more probable d priori, or it may act directly on the toxin, i.e., chemically. and if established removes the necessity for the third. It The second view is now practically established, and, is strongly supported by Ehrlich who, in his so-called though the question cannot be fully discussed here, the “ side-chain ” (Seitenkette) theory, explains antitoxin prochief grounds in support of a chemical action may be duction as an instance of regeneration after loss. Living given, (a) The action of antitoxin on toxin, as tested by protoplasm, or in other words a biogen molecule, is neutralization effects, takes place more quickly in con- regarded as consisting of a central atom group (Leistungscentrated than in weak solutions, and more quickly at a kem), related to which are numerous secondary atom warm (within certain limits) than at a cold temperature. groups, or side-chains, with unsatisfied chemical affinities. (b) Antitoxin acts more powerfully when injected along The side-chains constitute the means by which other molewith the toxin than when injected at the same time in cules are added to the living molecule, e.g., in the process another part of the body j if its action were on the tissue- of nutrition. It is by means of such side-chains that toxin cells one would expect that the site of injection would be molecules are attached to the protoplasm, so that the living immaterial, (c) Antitoxic action is apparently governed molecules are brought under the action of the toxophorous by the law of simple multiples; that is, the amount of groups of the toxins. In antitoxin production antitoxin necessary to neutralize varies directly with the this combination takes place, though not in “Side-amount of toxin. For example, the amount necessary to amount to produce toxic symptoms. It chain” neutralize five times the lethal dose being determined, sufficient is further supposed that the combination being of * eorytwenty times that amount will neutralize a hundred times the lethal dose. In the case of physiological antagonism somewhat firm character, the side-chains thus combined of drugs this relationship does not hold, (d) It has been are lost for the purposes of the cell and are therefore off. By the introduction of fresh toxin the process shown by Martin and Cherry, and by Kanthack and thrown is repeated, and the regeneration of side-chains is increased. tmbbett, that in certain instances the toxin can be made Ultimately the regeneration becomes an over-regenerao pass through a gelatine membrane, whereas the antioxin cannot, its molecules being of larger size. If, how- tion, and free side-chains produced in excess are set free ever, toxin be mixed with antitoxin for some time, it can and appear in the blood as antitoxin molecules. In other no longer be. passed through, presumably because it has words the substances, which when forming part of the cells fix the toxin to the cells, constitute antitoxin become combined with the antitoxin. molecules when free in the serum. This theory,