Noguchi,[51] resuming the study of this extremely curious action of strong doses of venom, observed that the red corpuscles of certain species of animals (such as the horse for example), when previously washed and held in suspension in a physiological solution of sea-salt containing 4 per cent. of Cobra-venom, acquire a considerable augmentation of resisting power with regard to various physical and chemical agents. In consequence of this they are no longer hæmolysed by distilled water, ether, or saponin.
Nevertheless, acids or alkalies, except ammonia, destroy corpuscles treated with venom more easily than those in their normal condition.
If corpuscles, previously treated with a strong dose of venom, are subjected to repeated washings in physiological saline solution, the special resistance acquired by them in the presence of the venom disappears; they even become more sensitive to the action of destructive agents, such as water, ether, or saponin.
The principle contained in venom, to which must be attributed the protective action, is not destroyed by heating to 95° C., although at this temperature Cobra-venom becomes partially coagulated. Moreover, the protective substance is contained in the coagulum, while the hæmolysin remains entirely in the filtrate. The agglutinin of venom, on the other hand, is destroyed at a temperature of 75° C. The protective substance, therefore, can be identified neither with the hæmolysin nor with the agglutinin.
It follows that it is impossible to accept the hypothesis of the “deviation of the complement” suggested by Kyes and Sachs to explain the innocuousness of strong doses of venom. Besides, it would be difficult to reconcile this hypothesis with the fact, observed by Noguchi, that venom in a strong dose protects corpuscles, not only against the action of lecithin (complement), but also against distilled water, ether, &c.
Noguchi, seeking more thoroughly to elucidate the mechanism of this protective action, finds that Cobra-venom forms a precipitate with blood-serum, when the latter is relatively poor in salts or when it is dilated with water. It likewise forms a precipitate with the aqueous extract of red corpuscles, and precipitates the globulins, hæmoglobin, or globin of the corpuscle, when treated separately. The precipitates are insoluble in water, but dissolve with the assistance of a small quantity of acid or alkali, and also in a great excess of saline solution.
Noguchi supposes that red corpuscles, when treated with strong solutions of venom, are protected against destructive agents on account of the formation by the venom and certain constituents of the corpuscle (chiefly hæmoglobin) of a compound insoluble in water. When this compound is removed by repeated washings in physiological solution, the corpuscles can easily be hæmolysed afresh by the ordinary destructive agents. Venom, none the less, exerts a noxious influence upon the corpuscles in all cases; but when strong solutions are employed, this effect is masked by the protective action.
All kinds of red blood corpuscles are not equally sensitive to the protective action of strong doses of venom. In this respect all degrees are observed in the action of venom. Thus the corpuscles of the dog are not protected at all by Cobra-venom. But it is interesting to observe that this venom in no way precipitates either the aqueous extract of dog’s corpuscles, or the hæmoglobin, or the globin of this animal.
The venom of Crotalus and that of Ancistrodon likewise possess protective power, which is, however, less marked than in the case of Cobra-venom.
Noguchi finally points out that corpuscles treated with venom are not hæmolysed by fluorescent substances such as eosin. They are also refractory to the hæmolysing action of tetanolysin.