When venom is brought into contact with certain kinds of highly sensitive red corpuscles, those of the rat for example, these corpuscles, although washed and freed from serum, may undergo hæmolysis. This result is due to the fact that these corpuscles contain sufficient quantities of lecithin, which becomes liberated from their protoplasm and, uniting with the venom, constitutes the active lecithide.
It was already known that lecithin is capable of combining with various albuminoid matters and with sugars to form lecithides. We must not, therefore, be surprised to find that such a combination may take place with the proteic substances in venom. The combination in this case is a truly chemical one. Lecithin in its natural state, or that which is normally found in serums which quicken venom, such as horse-serum, even when heated to 65° C., therefore plays the part of complement according to Ehrlich’s theory, or that of alexin according to the theory of Bordet, while venom itself would be an amboceptor or sensitiser.
This is not, however, the way in which the phenomenon should be understood, for it is impossible to admit the identification of heated serum or lecithin with the complementary substances or alexins, seeing that the essential characteristic of the latter is that they are intolerant of heat and become entirely inactive on being raised to a temperature of 58° C., or even by simply being kept for a few days exposed to the air and light. We must therefore suppose, with P. Kyes and H. Sachs, that the red corpuscles themselves contain substances capable of playing the part of complements (endo-complements), and that it is with these that the venom combines when quickened by the presence of lecithin or heated serum, the latter only acting because it contains free lecithin.
All substances that contain lecithin, such as bile, hot milk, or cephalin, are capable of exerting the same quickening action, but do not themselves possess any inherent hæmolytic power.
Cholesterin, on the contrary, represents a kind of antidote to lecithin, as also to normal serums. It prevents hæmolysis of the red corpuscles in a mixture of washed corpuscles and venom, yet it does not in any way modify the properties of true alexins or complements.
Moreover, no correlation exists between lecithides and the neurotoxin in venoms. The combination lecithin + venom possesses hæmolytic action, but is in no way neurotoxic. Conversely, venom can be freed from its groups of molecules combinable with lecithin, and remain neurotoxic.
Lecithide is insoluble in ether and acetone, but soluble in chloroform, alcohol, toluene, and water. Its properties are therefore entirely distinct from those of its two components. It precipitates slowly from its aqueous solutions, without losing its hæmolytic power; it does not show biuret-reaction; it dissolves with equal readiness the red corpuscles of all species of animals, and its effects, like those of venom, are impeded by cholesterin.
Kyes has succeeded in obtaining lecithides with all the hæmolytic venoms that he was able to study: thus he has prepared lecithides from Lachesis lanceolatus, Naja haje, Bungarus, Lachesis flavoviridis, and Crotalus. It is therefore probable that the lecithinophile group exists in all venoms, even when these differ as regards their other properties.
A wide range of difference is exhibited by the various venoms, as regards their hæmolysing power in the presence of normal heated serum or lecithin. The venom of Naja and that of Bungarus are the most active. The action of the venoms of Viperidæ, and especially of those of Crotalus, is very weak. For example, while 1 milligramme of Cobra-venom dissolves in from five to ten minutes 1 c.c. of a 5 per cent. dilution of red corpuscles in the presence of lecithin or normal heated serum, the same dose of the venom of Vipera russellii takes thirty minutes to effect the dissolution, and the venom of Lachesis lanceolatus takes three hours.
P. Kyes and H. Sachs have discovered the apparently paradoxical fact that, if to the red corpuscles of certain species of animals Cobra-venom be added in increasing doses, hæmolysis augments up to a certain point, beyond which the destruction of the corpuscles shows progressive diminution. In a large dose Cobra-venom no longer produces any effect upon the corpuscles of the horse, for example, even when the venom is added in presence of a great excess of lecithin or heated serum. It would seem, then, that, according to the theory of Ehrlich, under the influence of an exaggerated amount of venom-amboceptor there is produced a deviation on the part of the complement (serum or lecithin), and that the latter, instead of fixing itself upon the corpuscles, becomes united with the surplus fraction of the amboceptors, which has remained free in the liquid.