THE VENOMS.
=General Nature of Venoms.=--The venoms are more or less toxic products
secreted by certain reptiles, batrachians, and fish; by a large number
of invertebrates; by arachnids, apids, scorpionids, araneids, and a
large number of other insects.
The venoms are toxic principles very closely allied to the microbial
toxins; like the latter, they form two classes, the one alkaloidal,
the other proteid, possessing a true diastatic character. They
closely resemble the microbial toxins, moreover, by the fact that
they are capable of being transformed into vaccins by attenuation of
their virulence, by the action of heat or chemical reagents, and of
leading to habituation of use and the conference of immunity.[142]
Moreover, like the various viruses, the serum of immunized animals is
antivenomous, so that if injected into the veins or beneath the skin of
non-immunized animals, the serum confers upon them an immunity against
venom which lasts for some time.
[142] _Annal. de l'Instit. Pasteur_, VIII, p. 281; _Journ. of
Physiol._, VIII, p. 203; and _Soc. de Biol._, 1894, p. 111.
These venoms, like the microbial toxins, possess but slight toxicity
when absorbed via the stomach. Fraser, utilizing a method previously
advocated, succeeded, by following this method, in vaccinating against
serpent-venom by causing the absorption by animals of constantly
increasing doses of venom.
It was thus possible to make the animals withstand doses a thousand
times greater than the ordinary lethal dose; the blood and serums
of these animals at this point possessed immunizing properties, and
this property passed by heredity to the offspring, to which it is
transmitted by the blood itself, and by the milk during feeding.
Along with these resemblances between the venoms and toxins, attention
must be called to a very important difference. As we have already
seen, the action of the toxins on the organism is always preceded
by a certain period of incubation; the action of the venoms, on the
contrary, is almost instantaneous, and in this respect they behave like
chemical agents and alkaloidal toxins.
If the venoms are preserved in a moist condition, they change because
they undergo putrefaction, which is generally the case with all
diastatic substances, and particularly the toxins.
It is interesting to note that animals which have been bitten by a
venomous serpent, but which, for some reason or other, have not
succumbed to the venom, never recover their former condition; if they
were young, their functions cease to develop, and they droop; if they
are adults, their general condition remains that of stupefaction.
=Venomous Serpents.=--Among the venomous serpents,[143] the most
important as well as the most dangerous are the following: Cobra di
capello (Naja tripudians, the hooded cobra) and its analogues, the
black Naja, Naja hagé, etc.; the elops (coral serpent); the bungurus
of Bengal and Burmah; the Platycercus proteroglyphia, which is found
chiefly in the waters of the Indian Ocean; the crotalian solenoglyphs
of the two Americas, and among which in particular are the rattlesnake,
the fer-de-lance (the yellow viper) of Martinique; the surucucu of
Guiana; and the moccasins and copperheads of Texas and Florida. Lastly,
the entire group of viperian solenoglyphs, among which are the Echidnæ,
the bite of some of which, for instance the daboia or echidna, is
dreadful; the African vipers, among which may be mentioned the horned
viper, the bite of which will kill a camel; the springing viper of
Congo, and the rhinoceros-viper of Gabun; the European vipers, the most
dangerous of which is certainly the asp of France, which is exceedingly
numerous in certain regions.
[143] CALMETTE: _Le Venin des Serpents_, Paris, 1896.
The effects of the bites of venomous serpents on man and animals
are generally well known to the public; it is well to recall them,
nevertheless. From the moment the bite has been inflicted, complete
symptoms of poisoning develop, attended by a condition of extreme and
increasing weakness, with vomiting, hemorrhage, and decomposition of
the blood. There are, besides, particular effects which vary with every
venom.
The following table by Calmette[144] gives the comparative toxicity
of various venoms, taking as the standard of comparison the quantity
sufficient to kill a rabbit in three or four hours:
Naja tripudians 0.00047
Naja hagé 0.0003-0.0007
Acanthophis antarctica 0.001
Ceraste 0.0017-0.0021
Haplocephalus variegatus 0.0025
Trigonocephalus 0.0025
[144] CALMETTE: _Annal. Instit. Pasteur_, VIII, p. 276; IX, p. 229.
=Nature of Serpent-venoms.=--These venoms are homogeneous liquids,
somewhat more dense than water, in which they are soluble, slightly
colored green or yellow, transparent, and insoluble in alcohol; they
contain from 30 to 35 per cent. of solid matter. When fresh, they have
a slightly acid reaction. Towards chemical reagents, and particularly
acids, they behave like albuminoids; almost all the combinations they
afford with the various albuminoid reagents are active, despite their
insolubility. According to Gautier, they are decomposed by caustic
potash.
According to numerous researches, oxidizers like potassium
permanganate, the hypochlorites, hydrogen peroxide, and gold chloride
(in 1% solution) destroy the venoms; in certain cases when immediately
injected hypodermically in the poisoned region, these substances are
excellent antidotes _in vivo_.[145]
[145] WINTER and BLYTH: _The Analyst_, 1877, p. 204; LACERDA: _Compt.
rend. de l'Acad. des Sciences_, XCIII, p. 466; CALMETTE: _Annal.
Instit. Pasteur_, VI, p. 175, and VIII, p. 278.
We shall not here enter upon a detailed study of the toxic albuminoid
principles of serpent-venoms; moreover, our knowledge is rather vague,
as it is, on a number of points. It will suffice us to know that, taken
altogether, the active albuminoids of these venoms are numerous, and
that each venom has its own particular active constituents, differing
according to the species and variety of the snake.
Each one of these substances acts more or less rapidly, and may be
associated with different principles which give rise to the variability
of the action of these toxic agents. Among these toxic albuminoids, the
most virulent appear to be true albumins and globulins, followed by
the nucleo-albumins, as we have already stated; there are also found
in venoms alkaloidal bases, but these principles are present only in
very slight quantity. These bases are but very slightly toxic compared
with the toxins that accompany them.
=Natural Immunity towards Serpent-venoms.=--Certain animals exhibit
a natural immunity toward snake-bites; among them are the snakes
themselves, the hog, the hedgehog, and the mongoos (an Egyptian rat);
the blood of these animals contains apparently an antitoxin.[146]
[146] _Compt. rend. de l'Acad. des Sciences_, CXXI, p. 745; JACODOT:
_Arch. de Médecine Navale_, VII, p. 390.
Fontana[147] had remarked that snakes were quite unaffected by the
bite of the viper, even when inoculated with the venom hypodermically.
Physalix and Bertrand[148] confirmed these statements, and showed
that the snake perfectly resisted quantities of viper-venom capable
of killing at least 20 guinea-pigs. According to these scientists,
this natural immunity is due to the existence in the blood of toxic
principles analogous to those of viper's venom--principles that exist
in the labial glands of the snake, and pass into the blood and the
fluids via the internal secretions. These writers, and also Calmette,
have shown that the blood of venomous serpents becomes antitoxic when
heated.
[147] _Traité sur le Venin de la Vipère_, Florence, 1781.
[148] _Archives de Physiologie_, 1894, p. 423.
It has been known for a long time that the hedgehog and the mongoos
eat certain venomous reptiles, and eagerly hunt for the vipers in
particular. When the hedgehog is bitten, which happens quite often
despite its dexterity, it resists the viper-venom quite well. Physalix
and Bertrand[149] have experimentally demonstrated that the hedgehog
withstands a dose of viper-venom capable of killing at least 40
guinea-pigs. Levin[150] has shown that young individuals are less
resistant, and it is concluded from this, and perhaps incorrectly so,
that the immunity of the hedgehog is naturally acquired, rather than
inherent. Bertrand and Physalix have nevertheless shown that on heating
the blood of the hedgehog to 88° C. it manifests an antitoxic power
toward serpent-venom _in vitro_.
[149] _Bull. Muséum Histoire Naturelle_, I, p. 294; _Compt. rend. Soc.
de Biol._, 1899. p. 77.
[150] _Deutsche med. Woch._, 1898, p. 629.
=Artificial Immunity toward Serpent-venom.=--Immunity may be conferred
upon every individual by utilizing the method of habituation. This
fact was simultaneously elicited by Calmette, Bertrand, and Physalix.
To effect the immunity these scientists prepare an antivenomous serum
and inject it into animals, giving at first very small quantities of
the diluted venom, and gradually increasing the doses, and the periods
intervening between the injections. At the end of about two months of
this treatment, the immunity has reached its maximum. Certain rabbits,
thus slowly inoculated, have been able to withstand 0.04 Gm. of the
venom of the naja at a single injection; such rabbits then yield a
vaccinal serum.[151]
[151] _Annal. de l'Instit. Pasteur_, 1895, p. 229; _Compt. rend. de
l'Acad. des Sciences_, CXXII, p. 203.
At the Institut Pasteur at Lille there is prepared in this manner an
antivenomous serum from the horse; it is capable of acting upon 20 000
times its own weight. This has rendered great service in the treatment
of snake-bites, particularly in hot countries, where the accidents are
of daily occurrence. _In vitro_ it acts quite as well preventively
as therapeutically. It arrests the effects of the naja, the horned
ceraste, the trigonocephalus, the rattlesnake, and of almost every one
of the venomous serpents known.
The relatively considerable immunity possessed by certain
snake-charmers, and which passes for a magical gift, is due to nothing
else but a natural immunity, acquired perhaps by heredity, and it
always appears to follow as a result of a nonfatal snake-bite.
=Venoms of Batrachians and Saurians.=--We observe here a fundamental
difference between these poisons and those of snakes, as we shall see.
These latter, in fact, appear to owe all their toxicity to true toxins
which they contain, while the poisons of batrachians and saurians are
chiefly composed of alkaloidal bases.[152]
[152] CLOEZ: _Compt. rend. de l'Acad. des Sciences_, XXXIV, p. 592.
The poison of toads and frogs (studied by Faust, Bertrand, and
Physalix) is chiefly secreted by the glands of the subcutaneous tissues
of these animals; it has but a very slight action on the unbroken skin,
but it rapidly inflames the nasal and buccal conjunctival mucosa. The
poison is a yellowish liquid, milky and viscid, with a waxy odor and
an insupportably bitter taste. It is strongly acid and caustic. When
dried, the poison yields to ether a fatty matter which, when absorbed
by an animal, plunges the latter into a coma that may end in death.
The residue insoluble in ether contains the non-toxic albuminoids, and
ptomaines, such as methylcarbylamine,[153] and isocyanacetic acid,
resulting from the decomposition of a lecithin that appears to be
soluble in ether.
[153] _Ibid._, XCVIII, p. 538.
To obtain this venom, Physalix and Bertrand[154] skin the toads, first
chloroformed, and dry the skins in a vacuum over sulphuric acid; the
skins are then cleaned by treating with carbon disulphide to remove
fatty matters, and the toxic principles removed by means of 95-per
cent. alcohol; the poison so obtained, however, is impure. A better
procedure is to express the parotid glands which have been placed in
distilled water. Faust found in this venom a principle which he named
_bufonin_. Physalix and Bertrand isolated from it also a resinoid
substance soluble in alcohol and in a large excess of water; this
substance, which they named _bufotaline_, acts upon the heart. These
authors have also obtained another substance which has a paralyzing
action, and which they have named _bufotenin_.
[154] _Ibid._, CXXVIII, pp. 45-48.
The poison of the common toad acts as a paralyzant upon the heart and
on the spinal marrow[155]; that of the common frog possesses similar
properties. The poison of the tritons is quite analogous to that of the
toads; it contains a lecithin hydrolyzable by water with the formation
of alanin, formic acid, and alpha-isocyanopropionic acid.
[155] P. BERT: _Compt. rend. de la Soc. de Biologie_, 1885, p. 524.
Zalnosky[156] isolated from the glands of the skin of the salamander a
white, thick, bitter and alkaline liquid poison, containing a highly
poisonous alkaloid, _salamandrine_, or _samandarine_, which acts on
the brain, the medulla, and the spinal cord, and which has the formula
C{54}H{60}N{2}O{5}; it is a strong base and yields crystallizable
salts.
[156] _Bull. Soc. Chim._ [2], VI, p. 344.
=Fish-poisons.=[157]--Very little accurate knowledge is extant
regarding these. Many fish are poisonous, and among them are the
synanceia, found in the Indian Ocean between the Netherland Isles and
New Caledonia; considerable numbers are found in the neighborhood of
the latter locality. These fish are provided with spiny rays which are
in direct communication with a poisonous system having its seat in the
dorsal fin. The prick of one of the spiny rays of this fish may under
certain circumstances result fatally, and in every case it causes a
rapid and painful gangrene.
[157] BOFFORD: _Thèse de doctorat en Médecine--Les Poissons venimeux_,
Paris, 1889; O. ARCOS: _Thèse de doctorat--Essais sur les accidents
causés par les poissons venimeux_, Paris, 1887.
From the reservoir the poison is conducted to the sharp extremity of
the spines by a deep channel with which each spiny ray is provided; the
animal has 26 poison-sacs, two for each ray, and the sacs burst when
the corresponding sting is in any manner compressed.
The poison is an odorless liquid having a slight styptic or acidulous
taste, and exhibiting a bluish fluorescence; it rapidly becomes turbid.
The weevers, which are numerous on the shores of the Mediterranean Sea,
and which are also met with in the northeastern portion of the Atlantic
Ocean, are likewise very dangerous, which explains their popular names
"viper-weever," "spiderweever," etc. These fish are provided with a
double set of poisonous apparatus, the one opercular, which is the
more dangerous, and the other dorsal. The opercular spine has a double
channel in connection with a conical cavity hollowed out in the base of
the opercular bone. The bottom of this cavity is provided with special
cells which secrete the poison. The dorsal glands have a similar
structure.
The poison of the weever is a liquid, limpid when the fish is alive,
and turbid when dead; it has a slight bluish fluorescence, is neutral
in reaction, and is coagulated by acids and bases. It acts as a
paralyzant, its action being exerted on the medulla and spinal cord; it
retards the heart's action.
These examples will suffice; and we will not dilate further on this
subject, because, as already stated, but little is accurately known
regarding the subject, and what is known may be summed up as follows:
Fish-poisons always give rise to an intense pain, frequently with motor
paralysis, followed by paralysis of sensation; they affect the heart,
arresting it in diastole; and they are more dangerous to fish and
cold-blooded animals than to mammifers.
=Poisons of the Hymenoptera.=[158]--The poison system of the bee, and
of such insects as the wasps, bumblebees, etc., is known to consist of
a hollow sting consisting of two sharp needles communicating with two
poison-bearing glands, and forming a flexible tube. One of these glands
secretes an acid liquid (formic acid); the other secretes an alkaline
fluid.
[158] PHILOUZE: Venin des Abeilles. _Annales de la Société Linn. du
Maine-et-Loire_, IV.
The action of the bee-poison is very often benign, but there have been
cases where death followed the infliction of numerous stings.
Our information regarding the poison of the cantharides and flies is
very vague[159]; the same is true of the poisons of various arachnids,
acarides, and myriapoda. So far as spiders are concerned, it is known
that their poison is an oily liquid having an acid and bitter taste,
and containing a toxalbumin derived from the skin of the insect. The
bite of the ordinary spider occasions simply a slight local pain, with
redness; that of the large poisonous spider, however, may kill the
larger animals, and even man.
[159] JOYEUX-LAFFRIÉE: _Thèse de doctorat en Médecine_, Paris, 1883; P.
BERT: _Compt. rend. de la Soc. de Biol._, II [4], p. 136.
=Poison of Scorpions.=[160]--This poison is a colorless, acid liquid,
having a higher specific gravity than water, in which liquid it is
soluble. The famed legend of the suicide of scorpions is well known to
all. It is stated that when the insect finds itself in a position where
its death is inevitable, it stings itself, and dies from the effects of
its own poison. A simple method has even been described of bringing
this result about experimentally by surrounding the insect with a
circle of fire. Bounne, of Madras,[161] who has studied the procedure,
has demonstrated its entire falsity by showing, first of all, that the
insect dies from the effects of the excessive heat, and further, that
the poison of the scorpion is harmless to individuals of the species
that furnish it.
[160] CALMETTE: _Annales de l'Instit. Pasteur_, X, p. 232.
[161] _Proceedings of the Royal Society_, XLII, p. 17.
Metchinkoff[162] has confirmed these facts, and has moreover
demonstrated that the blood of the scorpion possesses an undoubted
antitoxic power against the poison of the insect.
[162] METCHNIKOFF: _L'Immunité_, p. 344.
The poison of the scorpion serves it to kill the insects which are its
prey. Frogs and birds stung by the scorpion also generally die. A dose
of 0.0005 Gm. kills a guinea-pig in less than one hour; and according
to Calmette[163] less than 0.0005 will kill a white mouse in two hours.
Oxidizers destroy the toxicity of the poison. Guinea-pigs immunized
against the poison of the scorpion resist perfectly very large doses of
the poison.
[163] CALMETTE: _Annal. de l'Instit. Pasteur_, X, p. 232.
=Poisonous Blood and Serums.=--It is an almost general fact that the
blood and blood serum of batrachians, eels, lampreys, snakes (even
non-poisonous ones), and hedgehogs are very poisonous. Mosso has
found in the blood serum of the lamprey a toxin possessing a strong
hemolytic power, and which he has named _ichthyotoxin_. O.5 Cc. of this
serum injected into a dog kills it in a few minutes. He also observed,
in 1888, that the blood of the eel, in like dose, kills a dog almost
immediately, and that the blood contains an ichthyotoxin analogous to
that of the lamprey.
This substance, which appears to be closely allied to the sero-albumin
of the blood, has a phosphorus-like, sharp, and burning taste. By
digestion it loses its toxicity, as well as by heating at 68° to 70° C.
It is easily obtained by precipitating with ammonium sulphate the serum
of eels, and dialyzing the precipitate dissolved in water. The power of
this substance is almost as great as that of the cobra poison, 0.002
Gm. being instantly fatal per kilo of dog.
The blood of snakes is likewise very toxic; the same is true of the
blood of the viper, as 0.02 Cc. will kill a guinea-pig in two hours.
All these bloods lose their toxicity when heated above 70° C. The serum
of the hedgehog is peculiar in this respect; when heated at 38° C.
for fifteen minutes it loses its toxicity, but it then possesses an
immunizing power against the poisons.
The subject possesses great interest, because it was in studying
these immunizing properties that Camus and Gley,[164] and later
on Kossel[165] and Tchistowitch,[166] discovered the first
anticytotoxin,[167] which they obtained by treating the animals with
increasing quantities of the serum of eels. On mixing the antitoxic
serum of these animals _in vitro_ with the red blood-corpuscles of the
species furnishing the serum and of the hemolytic serum of eels, it is
found that the blood-corpuscles kept quite well.
[164] _Archives internat. de Pharmacodynamie_, III and IV.
[165] _Berliner Klin. Wochenschr._, 1895, No. 7.
[166] _Annal. de l'Instit. Pasteur_, XIII, p. 406.
[167] The name "cytases" or "alexins" has been given to hemolyzing
diastatic substances which are found in certain serums. It has been
known for a long time that the serum of the blood of many animals
destroys the red blood-corpuscles of other and different species. The
chemical composition of these cytases or alexins is not yet definitely
known, but the substances rank among the albuminoids; they are
destroyed by a temperature of 55° to 56° C., and act only in saline
solutions (Ehrlich and Morgenroth, _Berlin. Klin. Woch._, pp. 6 and
481). The cytases or alexins, which will be studied in another volume
of this collection, and which will discuss the active principles
of the immunizing serums, constitute one of the numerous soluble
intraleucocytary ferments, and they pass into the serous liquids of the
organism only as the result of a rupture of or injury to the phagocytes.
As to the blood of the hedgehog, we have already seen that Physalix
and Bertrand have shown that it may be a counter-poison towards
serpent-venom under certain conditions. In its normal condition it is
highly toxic.
=Poisonous Meats.=--It is particularly among the fish that we find
these normally present, and it is a singular fact that, for a given
species, the toxicity frequently depends upon the period of the
year. Thus, at the period of spawning, certain fish may be extremely
poisonous, or, on the contrary, may entirely cease to be so. The
anchovy ballassa from the shores of India occasions death even in
very small quantity; the poisonous meltite of the same seas causes
violent vomiting; the fugu of the Japanese seas possesses an extreme
poisonousness at the spawning period, while, on the contrary, it is
perfectly innocuous at all other periods.
Numerous cases of poisoning have been chronicled every year by the
journals, due to the ingestion of mussels; in the flesh of these
crustaceæ is found a dangerous toxin, _methylotoxin_. The flesh of
oysters is also unwholesome at the spawning period.
The toxic symptoms caused by these animals become apparent in not
less than twenty-four hours after ingestion. The poisoning due to
these fresh meats must not, however, be confounded with that caused by
tainted or spoiled meats.
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