_TOXICITY OF THE BLOOD OF VENOMOUS SNAKES._
Several physiologists, among whom it is right to mention Fontana,[69]
Leydig,[70] Reichel,[71] Raphael Blanchard,[72] Phisalix and
Bertrand,[73] and S. Jourdain,[74] have pointed out the presence of
poison-glands in _Tropidonotus natrix_ or other non-venomous snakes,
and have explained the immunity enjoyed by these animals with regard to
venom as being due to the existence of an internal secretion of this
poison.
We also know, from the writings of Phisalix and Bertrand, that the
blood of the viper, and that of the salamander and toad are toxic.
For my part I have found[75] that the blood of _Naja_, _Bungarus_,
_Lachesis_, and _Cerastes_ possesses the same properties, and a
comparative study has been made by Wehrmann,[76] in my laboratory, of
the toxicity of the blood of the viper and of that of the blood of the
eel, already established by Mosso (of Turin).[77]
It is remarkable to find that the blood of the various venomous or
non-venomous snakes, like that of certain fishes, such as eels,
produces, when injected beneath the skin or into the peritoneum, local
and general effects very similar to those of venoms. Injections of
0·5 c.c. to 1 c.c. of the blood of the viper or of the common snake,
beneath the skin of the guinea-pig, provoke an intense local reaction,
which always results in the formation of an eschar. The injection of
slightly stronger doses, 1 c.c. to 2 c.c., into the peritoneum, almost
always kills these animals, like venom, with symptoms of respiratory
asphyxia.
The blood of _Naja tripudians_, injected subcutaneously, is lethal to
the mouse in a dose of 0·25 c.c.
When this blood is heated, after having been suitably diluted with
three or four parts of distilled water, in order to prevent it from
coagulating, it is found that a temperature of 70° C. maintained for
fifteen minutes is sufficient to cause it to lose all toxic effect.
The same applies to the blood of the other poisonous or non-poisonous
snakes, and to that of the _Murænidæ_.
Now, since the majority of venoms resist even prolonged heating at
this temperature, it cannot be supposed that the toxicity of the blood
is due to its containing venom derived from the internal secretion of
the poison-glands, as was thought by Phisalix and Bertrand. On the
contrary, it is probable that the toxicity results from the fact that
the blood contains diastasic substances of cellular origin, which
themselves represent certain of the constituent elements of venoms.
These substances, moreover, possess some of the properties of venoms,
as, for instance, the faculty of producing hæmorrhages and of being
influenced by antivenomous serum, which causes them to lose a large
portion of their toxic qualities.
I have found that they can even be utilised to vaccinate animals
against venom; by injecting weak, non-lethal, and repeated doses of
dilute _Cobra_-blood into guinea-pigs and rabbits, I have succeeded in
rendering them immune to doses of _Cobra_-venom several times greater
than the lethal dose.
There is no doubt that it is to these substances that the poisonous
and non-poisonous snakes owe the partial immunity that they
themselves enjoy with respect to venoms. We know, in fact, that
common snakes suffer without danger many bites from vipers (Phisalix
and Bertrand[78]), and that the _Cobra_ is relatively little
affected by inoculation with its own venom or with that of other
COLUBRIDÆ, such as _Bungarus_, or even of VIPERIDÆ,
such as _Vipera russellii_.
This immunity, however, is far from being absolute; I have killed
common snakes (_Tropidonotus natrix_) with doses of _viper_-venom
ten times greater than the lethal one for the rabbit, and _Lachesis
lanceolatus_ (from Martinique) with 0·02 gramme of the venom of _Naja
tripudians_.
Phisalix,[79] on his part, has shown that, while it was necessary to
inject from 100 to 200 milligrammes of _viper_-venom into other vipers
or common snakes, beneath the skin or into the peritoneum, in order to
cause death, the introduction of only 2 to 4 milligrammes of this venom
into the brains of these reptiles was sufficient to kill them with the
same symptoms of intoxication. This dose, however, is only twenty-five
to thirty times greater than the lethal one for the guinea-pig.
The practical lesson to be learnt from the establishment of the
foregoing facts is that poisonous snakes of different species must
never be placed in the same cage, for these animals sometimes bite each
other, and may thus kill one another.
Simon Flexner and Noguchi[80] have studied the action of the serums of
_Crotalus_, _Ancistrodon_, and a non-poisonous species, the pine snake
(_Pituophis catenifer_), on the venoms of _Naja_, _Ancistrodon_, and
_Crotalus_. They found that the serum of _Crotalus_ rapidly dissolves
the red corpuscles of man, the dog, rabbit, guinea-pig, sheep, rat,
pigeon, and horse.
The serum of the pine snake affects the same red corpuscles, but in
a lesser degree. Heating to 58° C. suppresses the hæmolytic power of
these serums, but they can be restored to activity by the addition of a
very small quantity of the same serum in a fresh condition, of fresh
serum derived from other snakes, or of fresh serum from the guinea-pig.
Antivenomous serum also, when added in a suitable dose, entirely
suppresses the hæmolytic action of snake-serums; it has, however,
greater effect upon the hæmolysin of _Cobra_-blood than upon that of
the blood of other snakes. This observation had previously been made by
W. Stephens,[81] and it has been verified by Noc in my laboratory.
_Crotalus_-serum dissolves the red corpuscles of the mongoose
(_Herpestes ichneumon_) of Jamaica, whose extraordinary resistance to
venom is well known. But if variable doses of _Ancistrodon_-venom and
_Crotalus_-serum be made to act simultaneously upon these corpuscles,
the latter are no longer dissolved. Again, if, instead of red
corpuscles which are but little sensitive, like those of the mongoose,
we employ the highly sensitive corpuscles of the guinea-pig, the result
is the same. These experiments are regarded by Flexner and Noguchi
as proving that the amboceptors of the toxic serum become fixed, in
conformity with Ehrlich’s theory of the lateral chains, upon the
receptors of the sensitive erythrocytes, and leave no more receptors
free for the fixation of the venom.
The same investigators have endeavoured to determine the respective
toxicity of the tissues of the different organs of _Crotalus_. They
found that the most toxic organs are the spleen and the liver; the
toxicity of the spinal cord, kidney and muscles is much less. It
appears that this toxicity is intimately connected with the quantity of
blood that the tissues retain, for the physiological effects observed
are identical with those that follow the injection of blood or serum
alone.
They also ascertained that the contents of the eggs of _Crotalus_ are
especially rich in poison, and this poison appears to consist for
the most part of _neurotoxin_, since it does not cause hæmorrhages.
Phisalix has observed that the ovules of the viper exhibit analogous
toxicity.[82]
Summing up what has been stated above, we find that the blood of
both poisonous and non-poisonous snakes contains toxic substances,
destructible by heating to 68° C., and physiologically distinct from
venoms, but like the latter possessing the property of dissolving
the red corpuscles of the majority of vertebrates and of producing
hæmorrhages.