With regard to the nerve-cells, spermatozoids and ova of cold-blooded animals (frogs, fish, arthropods, worms, and echinoderms) Cobra-venom proved to be the most active; then that of Ancistrodon, and lastly that of Crotalus.
These cytolysins are not destroyed by heating for thirty minutes at 85° C. in a damp medium, nor by dry heating for fifty minutes at 100° C.
C.—Bacteriolytic Action.
If we bring into contact with a 1 per cent. solution of Cobra-venom, rendered aseptic by filtration through porcelain, sensitive micro-organisms, such as the cholera vibrio, or the bacterium of anthrax in a very young non-sporulated culture, or in its non-spore-producing variety, we find that these microbes are dissolved by the solution of venom in varying periods of time.
On making a direct microscopical examination we see that Koch’s vibrios become immovable, then break up into granulations and disappear in the liquid. The bacteriolysis is even more distinct in the case of the bacterium. The enveloping membrane seems to dissolve, and the microbe appears as though composed of a series of granulations placed end to end, which finally disperse and disappear.
By my instructions this bacteriolytic property of venom with respect to different species of micro-organisms was studied by Noc. It was especially clearly seen with the non-spore-producing bacterium of anthrax, the cholera vibrio, Staphylococcus aureus, the bacillus of diphtheria, and B. subtilis in a young culture; it is less distinct with B. pestis, B. coli, and B. typhi, is almost nil with the pyocyanic bacillus and B. prodigiosus, and nil with B. tuberculosis.
Investigations have likewise been made by Noc, and subsequently by Goebel,[58] in order to determine whether cobra-venom dissolves Trypanosomes. These hæmatozoa are more resistant than bacteria, but they nevertheless end by being dissolved after twenty to thirty minutes’ contact in the 1 per cent. solution.
The bacteriolytic substance in venom is distinct from that which produces proteolysis, for the latter is destroyed at 80° C., while the former only disappears with a temperature of and beyond 85° C. maintained for half an hour. It is likewise distinct from the hæmolysin, for this resists temperatures considerably higher than 85° C. Moreover, venom which has dissolved microbes until the saturation point has been reached, is found to have preserved in its entirety its hæmolytic power upon the red corpuscles of the horse. Neither does it act upon the microbes owing to the presence of a cytase or alexin. The well-known characteristics of alexins are not met with here—destruction at 55° to 56° C., sensitivity to light, rapid alteration at ordinary temperatures, &c.
We cannot, again, compare the bacteriolytic action of venom to that of rat-serum, which dissolves B. anthracis by aid of a substance distinct from vibrionicide alexin. According to the researches of Malvoz and Y. Pirenne, the lysin of rat-serum appears to be a basic substance, the neutralisation of which destroys its activity. Now Cobra-venom in a very active solution is perfectly neutral to sensitive litmus papers, while these are turned blue by rat-serum. Moreover, venom acts not only upon microbes of the same kind, but also on very different species which are not affected by rat-serum, especially upon B. pestis, for which, on the contrary, this serum, when fresh, proves a favourable culture medium. The bacteriolytic power of Cobra-venom therefore constitutes a special property of venom.
“In their work on the cytolysins of venom, S. Flexner and Noguchi have shown that animal cells, when heated to 55° C. and rendered inactive, do not undergo complete dissolution under the influence of venoms which destroy the fresh cells. The authors in question infer the existence of cellular receptors (endo-complements, according to the theory of Ehrlich), which fix the amboceptors of venom. Pursuing the same order of ideas, I have observed that bacteria killed by heating for one hour at 60° C. do not undergo total disintegration as do living bacteria. But, while Flexner and Noguchi infer the plurality of the cytolysins in venom for different animal cells, I have not been able to prove the same thing with regard to the bacteriolysin; venom saturated with cholera vibrios to such an extent that vibrios added at repeated intervals are no longer dissolved, is incapable of dissolving another highly sensitive species of microbe, such as the asporogenous bacterium, and vice versâ. Besides, it would be difficult to understand the existence in venom of cytolysins specific for a whole series of species of micro-organisms” (Noc).[59]