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.142Moreover, 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, theserum confers upon them an immunity against venom which lasts for some time.
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,143the 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.
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 Calmette144gives 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 tripudians0.00047Naja hagé0.0003-0.0007Acanthophis antarctica0.001Ceraste0.0017-0.0021Haplocephalus variegatus0.0025Trigonocephalus0.0025
Nature ofSerpent-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, andparticularly 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 antidotesin vivo.145
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 thenucleo-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
Fontana147had remarked that snakes were quite unaffected by the bite of the viper, even when inoculated with the venom hypodermically. Physalix and Bertrand148confirmed 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.
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 Bertrand149have experimentally demonstrated that the hedgehog withstands a dose of viper-venom capable of killing at least 40 guinea-pigs. Levin150has 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-venomin vitro.
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 interveningbetween 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
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 vitroit 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 shallsee. 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
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,153and isocyanacetic acid, resulting from the decomposition of a lecithin that appears to be soluble in ether.
To obtain this venom, Physalix and Bertrand154skin 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 toxicprinciples 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 namedbufonin. Physalix and Bertrand isolated from it also a resinoid substance soluble in alcohol and in a large excess of water; this substance, which they namedbufotaline, acts upon the heart. These authors have also obtained another substance which has a paralyzing action, and which they have namedbufotenin.
The poison of the common toad acts as a paralyzant upon the heart and on the spinal marrow155; 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.
Zalnosky156isolated from the glands of the skin of the salamander a white, thick, bitter and alkaline liquid poison, containing a highly poisonous alkaloid,salamandrine, orsamandarine, which acts on the brain, the medulla, and the spinal cord, and which has the formula C54H60N2O5; it is a strong base and yields crystallizable salts.
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.
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 theHymenoptera.158—The poison system of the bee, and of such insects as the wasps, bumblebees, etc., is known to consist of a hollowsting 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.
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 vague159; 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.
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,161who 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.
Metchinkoff162has confirmed these facts, and has moreover demonstrated that the blood of the scorpion possesses an undoubted antitoxic power against the poison of the insect.
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 Calmette163less 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.
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 namedichthyotoxin. 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 thatCamus and Gley,164and later on Kossel165and Tchistowitch,166discovered the first anticytotoxin,167which they obtained by treating the animals with increasing quantities of the serum of eels. On mixing the antitoxic serum of these animalsin vitrowith 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.
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 isa 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.