Venom

“ Venoms are modified or destroyed by certain normal diastases of the organism. It was shown long ago by Lacerda, Weir Mitchell, Sir Joseph Fayrer, and Lauder Brunton, that it is possible to introduce without danger into the stomachs of adult animals amounts of venom many times greater than the lethal dose. I have repeatedly verified this, but have nevertheless observed that young mammals, while being suckled, readily absorb venom by their alimentary canal, and succumb to the ingestion of doses scarcely larger than those which kill when subcutaneously injected. ”

“ If the venom be introduced in a highly vascular region, or directly into a vein, the result is almost invariably fatal. On the contrary, if the derm be scarcely broken, or if the clothing has acted as a protection, scarcely any absorption will take place. We are here confronted with the same factors of gravity as in the case of bites inflicted upon human beings by animals suffering from rabies. ”

“ Contrary to what is observed with the venoms of Viperidæ in general, all the venoms of Colubridæ and, as exceptions to the rule, the venoms of some North American Crotalinæ (Ancistrodon contortrix and A. piscivorus) suppress the coagulability of the blood in vivo and in vitro. It is, however, important to observe that, in vivo, the blood remains fluid after death only if the dose of venom absorbed has been sufficient. ”

“ B.—Effects of Venom upon the Red Corpuscles. (1) Hæmolysis.—The hæmolytic properties of venoms, that is to say, their faculty of dissolving the red corpuscles, have been the subject of very important researches on the part of a number of investigators during the last few years (W. Stephens,45 Flexner and Noguchi,46 Calmette,47 Phisalix,48 Preston Kyes and Hans Sachs,49 Noc50) . ”

“ When a dose greater than 2 centigrammes of dry extract of the venom of Ornithorhynchus is injected intravenously into the rabbit, it produces phenomena of intoxication analogous to those observed after inoculation with Viperine venoms.166 Death supervenes in from twenty-five to thirty minutes, and at the autopsy hæmorrhagic patches are found beneath the endocardium of the left ventricle. ”

“ Another extremely important fact, which must not be lost sight of, is that differences of toxicity, which are often considerable, are exhibited by the venoms of different specimens of the same species of snake, or by the venom of the same snake collected at different times. ”

“ If the blood of the dog remains non-coagulable when mixed with doses of venom which, on the contrary, are actively coagulant for the blood of the rabbit, the reason would be that the leucocytes of these animals are not equally resistant to venom.
This conception, however, does not conform to the facts that I have myself observed. I have always found that viper-venom, mixed with citrate- or oxalate-plasma of the dog, rabbit, or horse, coagulates these various plasmas when the venom is in weak doses, while with strong doses coagulation is not produced. ”

“ With a longer delay than this, death is inevitable, since the bulbar centres are already affected, and paralysis of the respiratory muscles commences to appear.
These facts show that:—
(1) The more sensitive animals are to venom, the greater is the quantity of serum necessary in order to prevent their intoxication by a given dose of venom.
(2) For a given species of animal and a given dose of venom, the longer the delay in applying the remedy, the greater is the quantity of serum that must be injected in order to arrest the poisoning. ”

“ On making an autopsy of an animal which has succumbed to intoxication by snake-venom, we find that the blood in the heart and large vessels is sometimes coagulated into a mass, sometimes entirely fluid, and that, in certain cases, it is as black as prune-juice, while in others it is of a fine transparent red colour. ”

“ The reptile is placed in a large covered jar, containing a pad of absorbent wool impregnated with chloroform (figs. 86, 87) , and in a few minutes it is stupefied. It is then grasped by the neck with the hands, and the edge of a plate is slipped between its jaws. On compressing the two poison-glands with the fingers, the venom dribbles out on to the plate. ”

“ This venom, when extracted from the glands, is limpid, bluish, and slightly acid. When introduced into the tissues, it produces very acute local pain, which extends throughout the affected limb. The 292 pain is excruciating, and sufferers have been observed to become actually delirious, striking and biting those around them, throwing themselves from side to side, and beseeching that the limb should be cut off; some of them have amputated the injured part themselves. ”

“ Nevertheless, the action of venom is not confined to these physiological phenomena; in diffusing itself through the organism it stays more especially in parts where the circulation has become slower, in the capillaries of the organs where the leucocytes that have disappeared from the general circulation are already to be found agglomerated and altered. ”

“ If we inject a lethal dose of venom into the right thigh of an animal, for example, and several cubic centimetres of permanganate solution into different parts of the body, or beneath the skin of the left thigh, neither the general intoxication nor the local effects of the venom are modified. ”

“ An animal is said to be venomous when it possesses the power of inoculating its venom.
Venomous species are met with in almost all the lower zoological groups, in the Protozoa, Cœlenterates, Arthropods, Molluscs, and in a large number of Vertebrates (fishes, amphibians, and reptiles) .
The reptiles are best endowed in this respect, and it is in this class of creatures that we meet with the species most dangerous 2 to man and to mammals in general. ”

“ The venom flows out between the layer of cells and the ensheathing membrane, which is capable of being pushed slightly back as the result of the penetration of the spine into the tissues, and then exerts pressure upon the reservoir. ”

“ Not exactly; there is another, which I have specimens of, but whose faculties I have never seen put to the test, which is called the spirting snake. It is about three feet long, and its bite, although poisonous, is not fatal. But it has a faculty, from which its name is derived, of spirting its venom into the face of its assailant, and if the venom enters the eye, at which the animal darts it, immediate blindness ensues. There are a great many other varieties, some of which we have obtained possession of during our journey. ”

“ If, instead of making use of the mouse as test animal, we employ the rabbit, it is found that the same serum, in a dose of 0·75 c.c., neutralises 0·001 gramme of venom sufficiently for the mixture to be innocuous when inoculated. ”

“ Those of man, the guinea-pig, and the rat, on the contrary, are more so.
On experimenting with washed corpuscles, it is found that venom alone is incapable of dissolving them. In order that dissolution may take place, we are obliged to add to the mixture either a small quantity of normal horse-serum, preferably heated, and, consequently, deprived of alexin (Calmette) , or 1⁄2 c.c. of a 1 in 10,000 solution of lecithin in physiological saline water (P. Kyes) .
Venom, therefore, is capable of hæmolysing red corpuscles only when it is quickened, either by heated normal serum, or by lecithin. ”

“ Lachesis-venom is especially active in this respect. In Delezenne’s experiments it was generally sufficient to add to 1 c.c. of inactive pancreatic juice, 0·5 to 1 c.c. of a 1 in 1,000 solution, that is 0·5 to 1 milligramme of venom, to obtain the digestion of a cube of albumin weighing 0·5 gramme in the space of from ten to twelve hours. ”

“ The venom and poison apparatus have developed primarily as a means of causing rapid death in small animals that are the usual prey. As a protective device against larger enemies, including man, the venom may have some value; but this was probably unimportant in the evolution of the poison mechanism. A secondary function of the venom is to begin digestion of tissues of the prey. Since food is swallowed whole, injection of digestive enzymes into the body cavity enhances digestion of the prey. ”

“ In cases in which the venom of dead snakes has to be collected, the best method of extraction consists in fixing the head of the animal to a sheet of cork and carefully dissecting out the gland on each side. ”

“ In experiments we are able to eliminate all these factors, and to follow in an animal inoculated with a known quantity of venom the whole series of phenomena of poisoning, the intensity of which can be graduated. ”

“ 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. ”

“ In hot countries they frequently venture into fresh water. Their skins are adorned with brightly coloured markings, which vary very greatly according to the species.
The poison-apparatus in Muræna consists of a pouch situated 310 above the membrane of the palate, which may contain 1⁄2 c.c. of venom, and three or four conical, curved teeth, with the convex surface in front, as in the fangs of snakes. The teeth are not pierced by a central canal, and the venom flows between them and the mucous membrane of the palate, which forms a sheath. ”

“ Venom, ven′um, n. any drink, juice, or liquid injurious or fatal to life: poison: spite: malice.—adj. (Shak.) venomous, poisonous.—v.t. to infect with poison.—n. Ven′om-duct, in a poisonous animal, the duct conveying venom from the sac or gland where it is secreted to the tooth or venom-fang whence it is discharged.—adjs. Ven′om-mouthed, having a venomous mouth: (Shak.) slanderous; Ven′omous, poisonous: spiteful: mischievous.—adv. Ven′omously.—n. Ven′omousness. [Fr. venin (It. veneno) —L. venenum.]
Venose, vē′nōs, adj. (bot.) having well-marked veins, veined.—n. ”

“ When the bite of a poisonous snake is of a character such as I have just described,—and not a few of them have this character,—only a very small quantity of the venom is lodged in the subcutaneous tissues, where the larger blood- and lymph-channels lie, and as a consequence the person bitten escapes serious harm. On the other hand, when the fangs enter the flesh in a less decidedly curving direction, thus permitting a greater quantity of the venom to reach and remain in the deep-lying tissues, serious or even fatal results may be anticipated. ”

“ Fishermen rightly 300 consider this variability to depend upon the amount of venom that has penetrated into the wound, and especially upon the season at which the accident takes place. The most serious results are recorded during the spawning season, and fishermen regard the Lesser Weever as being the more poisonous. ”

“ The white corpuscles themselves do not escape the action of venom. It is possible in vitro to prove this action upon leucocytic exudations obtained, e.g., by injecting sterilised cultures of Bacillus megatherium into the pleura or peritoneum of the rabbit. After a few hours this exudation is removed by means of capillary tubes, and, on mixing these with weak doses of venom, we see, in the course of a microscopic examination, that the large mononuclear cells are the first to be dissolved, then the polynuclears, and lastly the lymphocytes. ”

“ They are caught in trawls and are fairly common on sandy bottoms. In the month of June they approach the shore for the purpose of spawning.
The venom of the Weever has formed the subject of interesting studies by Günther, Gressin,144 Bottard, Phisalix,145 and more recently by Kobert146 and A. Briot.147
In order to procure sufficient quantities of it for experimental purposes, Briot cuts off the venomous spines and the surrounding tissue with a pair of scissors; he then pounds the whole in a mortar, and mixes the pulp with pure glycerine. ”

“ We see, therefore, that partial fixation of the venom upon the nervous elements really takes place, but we cannot conclude from this that these elements exercise an antitoxic function, any more than in the case of tetanus, for animals that receive cerebral emulsions in one thigh and the dose of venom lethal in two hours in the other thigh, succumb at the same time as the controls. ”

“ The liver is more affected than any other organ. In cases in which death has quickly followed the injection of the venom, the protoplasm of the cells is merely cloudy, or granular, and the granulations readily take a stain in their periphery, though the interior remains uncoloured. If, on the contrary, the animal has survived for some hours, the protoplasm becomes condensed in certain parts of the cell, leaving vacuoles, the limits of which are not well defined. ”

“ Later on Weir Mitchell and Reichert, and subsequently Norris Wolfenden, Pedlar, Wall, Kanthack, C. J. Martin, and MacGarvie Smith, showed that venoms, like diastases, exhibit a great complexity in composition; that all their characteristic toxic constituents are precipitable by absolute alcohol, and that the precipitate, when redissolved in water, recovers the properties possessed by the venom before precipitation. ”

“ To each tube 2 drops of defibrinated horse-blood are added, and the tubes are placed in the stove at a temperature of 35° C.
In tubes 1 and 6, which contain fresh rat-serum alone, and fresh serum + antivenomous serum, hæmolysis appears in a few minutes. 210 In tube 4, which received venom alone, hæmolysis is also produced in one hour. It is not produced at all in tubes 2 and 3, which received the neutral mixture of fresh serum and venom, proving that the hæmolytic alexin has been fixed by the venom. The latter, therefore, here plays the part of a true fixator or amboceptor. ”