DIVISION I.—POISONS SECRETED BY LIVING ANIMALS.
I.—Poisonous Amphibia.
§ 623. The glands of the skin of certain amphibia possess a secretion that is poisonous; the animal is unable to empty the poison glands by any voluntary act, but the secretion can readily be obtained by pressure. Zalesky found the juice in the skin glands of the Salamandra maculosa, milky, alkaline in reaction, and bitter in taste. He isolated from it an organic base, which he named Salamandrine (C34H60N2O5), it is soluble in water and in alcohol, and forms salts. Salamandrine is a strong poison; injected subcutaneously into rabbits it causes shivering, epileptiform convulsions, and salivation; then tetanus, followed by oppressed respiration, dilated pupils, and anæsthesia. Death occurs after a kind of paralytic state. When given to dogs, it causes vomiting. In frogs, tetanus occurs first and then paralysis—the result of all the experiments being that salamandrine acts on the brain and spinal cord, leaving the heart and muscular substance unaffected. A similar secretion obtained from the water salamander (Triton cristatus), causes, according to Vulpian, the death of dogs in from three to eighteen hours; the symptoms being progressive weakness, slowing of the respiration, and depression of the heart’s action.
§ 624. The secretion of the skin of the common toad contains methylcarbylaminic acid, carbylamine, and, according to Fornara, an alkaloid which is soluble in alcohol, and to which the name of phrynine has been applied; its action is toxic on all animals experimented upon, save toads. Administered subcutaneously to frogs, it has a digitalis-like action, causing rapid paralysis of the heart, and the breathing soon after ceases; the muscles become early rigid.
II.—The Poison of the Scorpion.
§ 625. There are several species of scorpions. The small European variety (Scorpio europæus) is found in Italy, the south of France, and the Tyrol; the African scorpion (Bothus afer, L.), which attains the length of 16 cm., is found in Africa and the East Indies; Androctonus bicolor in Egypt; and the Androctonus occitanus in Spain, Italy, Greece, and North Africa.
In the last joint of the tail the scorpion is provided with a poisonous apparatus, consisting of two oval glands, the canal of which leads into a round bladder, and this last is connected with a sting. When the sting is inserted, the bladder contracts, and expels the poison through the hollow sting into the wound. The smaller kinds of scorpion sting with as little general effect as a hornet, but the large scorpion of Africa is capable of producing death. There is first irritation about the wound, and an erysipelatous inflammation, which may lead to gangrene. Vomiting and diarrhœa then set in, with general weakness and a fever, which may last from one to one and a half days; in the more serious cases there are fainting, delirium, coma, convulsions, and death. According to G. Sanarelli[632] the blood corpuscles of birds, fishes, frogs, and salamanders are dissolved by the poison; only the nucleus remaining intact; the blood corpuscles of warm-blooded animals are not affected.
[632] G. Sanarelli, Bollet. della Soc. della sez. dei cult. delle Scienze med., v., 1888, 202.
Valentin made some experiments on frogs with the Androctonus occitanus. He found that soon after the sting the animal remains quiet, but on irritation it moves, and is thrown into a transitory convulsion; to this follow twitchings of single muscular bundles. The frog is progressively paralysed, and the reflex irritability is gradually extinguished from behind forwards; at first the muscles may be excited by electrical stimuli to the nerves, but later they are only capable of contraction by direct stimuli.
III.—Poisonous Fish.
§ 626. A large number of fish possess poisonous properties; in some cases the poison is local; in others the poison is in all parts of the body.
Many fish are provided with poison glands in connection with the fins or special weapons, and such are used for purposes of defence; for example, Synanceia brachio is provided with a back fin consisting of 13 spines, each of which has two poison reservoirs; the reservoirs are connected with 10 to 12 tubular glands which secrete the poison, a clear feebly acid bluish fluid, exciting in a concentrated condition, local gangrene; in a diluted one, paralysis of the nervous centres.
Another kind of localisation is the localisation in certain of the internal organs. Remy states, that there are twelve varieties of Tetrodon in Japanese waters, all of which are poisonous. M. Minra and K. Takesaki[633] find that the poison of the Tetrodon is confined to the sexual organs of the female, and at the time of activity of these glands, the poisonous properties are most intense; but, even in winter, when the glands are atrophied, Remy found the glands were so poisonous that he could prepare from them a fluid, which, administered subcutaneously, killed dogs within two hours. The symptoms in the dog are restlessness, salivation, vomiting of slimy masses, dilatation of the pupil, paralysis and great dyspnœa. Death occurs by the lung. After death the appearances are similar to those from asphyxia; in addition to which there are small ecchymoses in the stomach and intestines; the salivary glands and pancreas are also injected. The symptoms observed in man are similar, there is headache, dilated pupils, vomiting, sometimes hæmatamesis, convulsions, paralysis, dyspnœa and death.
[633] Virchow’s Archiv, 1890, Bd. 122.
Some fishes are poisonous on account of the food they live upon; the Meletta venenosa is only poisonous when it feeds upon a certain green monad; Clupea thrissa, C. venenosa and certain species of Scarus, neither possess poison glands nor poisonous ovaries; but also derive their poisonous properties from their food. In the West Indies it is well-known that fish caught off certain coral banks are unwholesome, while the same species caught elsewhere may be eaten with safety.
A good many shell-fish, especially mussels, occasionally cause intense poisonous symptoms; those usually noticed are high fever, nettle rash, dilated pupils, and diarrhœa. It may be that in these cases a ptomaine, the product of bacterial action, has been ingested. To the agency of bacteria has been ascribed illness produced in Russia by a good many fish of the sturgeon species. The symptoms are those of cerebro-spinal paralysis. The “Icthyismus gastricus” of Germany may belong to the same type. Prochorow[634] has described illness from ingestion of Petromyzon fluviatilis in Russia. Whether the fish was eaten raw or cooked, the effect was the same, producing a violent diarrhœa, dysenteric in character. Even the broth in which the fish had been boiled produced symptoms. Fresh blood of the eel is stated to be intensely poisonous; this property is apparently due to a toxalbumin; Pennavaria[635] relates the case of a man who took, in 200 c.c. of wine, 0·64 kilo. of fresh eel blood and suffered from diarrhœa with symptoms of collapse.
[634] Pharmac. Ztg., 1885.
[635] Il Farmacista Italiano, xii., 1888.
In the Linnean Transactions for November, 1860, is recorded a fatal accident, which took place on board the Dutch ship “Postillion” at Simon’s Bay, Cape of Good Hope. The boatswain and purser’s steward partook of the liver of the toad or ball-bladder (Diodon); within twenty minutes the steward died; in ten minutes the boatswain was violently ill; the face flushed, the eyes glistening, and the pupils contracted; there was cyanosis of the face, the pulse was weak and intermittent, and swallowing was difficult, the breathing became embarrassed, and the body generally paralysed. Death took place in seventeen minutes. The liver of one fish only is said to have been eaten. This might weigh 4 drachms. If the account given is literally correct, the intensity of the poison equals that of any known substance.
The poisonous nature of the goby has also led to several accidents, and we possess a few experiments made by Dr. Collas,[636] who fed chickens with different parts of the fish, and proved that all parts were alike poisonous. The effects were slow in developing; they commenced in about an hour or an hour and a half, and were well developed in five hours, mainly consisting of progressive muscular weakness and prostration. Death occurred without convulsions.
[636] Soc. Sci. Rev., July 19, 1862; Brit. and For. Med. Chir. Rev., Oct. 1862, p. 536.
IV.—Poisonous Spiders and Other Insects.
§ 627. It is probable that all spiders are poisonous; the only species, however, of which we have any definite information relative to their poisonous properties, are Lycosa tarantula and the Latrodectus malmignatus, to which may be added the New Zealand katipo. These spiders possess a poisonous gland connected with their masticatory apparatus, which secretes a clear, oily, bitter acid-reacting fluid; the acidity seems due to formic acid.
Zangrilli has observed several cases of tarantula bite; soon after the occurrence the part bitten is anæsthetic, after a few hours there are convulsive shiverings of the legs, cramps of the muscles, inability to stand, spasm of the pharyngeal muscles, quickening of the pulse, and a three days’ fever, with vomiting of yellow, bilious matter; recovery follows after copious perspiration. In one case there was tetanus, and death on the fourth day. The extraordinary effects attributed to the bite of the tarantula, called tarantism in the Middle Ages, are well detailed by Hecker;[637] this excitement was partly hysterical and partly delirious, and has not been observed in modern times.
[637] “The Epidemics of the Middle Ages,” by J. F. C. Hecker, translated by B. G. Babington, M.D., F.R.S. (The Dancing Mania, chap, ii., &c.)
Dax has described the effects of the bite of the L. malmignatus; it occasioned headache, muscular weakness, pain in the back, cramps, and dyspnœa; the symptoms disappeared after several days.
§ 628. The katipo is a small poisonous spider confined to New Zealand. Mr. W. H. Wright has recorded the case of a person who, in 1865, was bitten by this spider on the shoulder. The part rapidly became swollen, and looked like a large nettle-rash wheal; in an hour the patient could hardly walk, the respiration and circulation were both affected, and there was great muscular prostration; but he recovered in a few hours. In other cases, if the accounts given are to be relied upon, the bite of the spider has produced a chronic illness, accompanied by wasting of the body, followed by death after periods varying from six weeks to three months.[638]
[638] Transac. of the New Zealand Inst., vol. ii., 1869; Brit. and For. Med. Chir. Review, July 1871, p. 230.
§ 629. Ants.—The various species of ants possess at the tail special glands which secrete formic acid. Certain exotic species of ants are provided with a sting, but the common ant of this country has no special piercing apparatus. The insect bites, and then squirts the irritating secretion into the wound, causing local symptoms of swelling and inflammation.
§ 630. Wasps, &c.—Wasps, bees, and hornets all possess a poison-bag and sting. The fluid secreted is as clear as water, and of an acid reaction; it certainly contains formic acid, with some other poisonous constituent. An erysipelatous inflammation generally arises round the sting, and in those cases in which persons have been attacked by a swarm of bees, signs of general poisoning, such as vomiting, fainting, delirium, and stupor, have been noticed. Death has occasionally resulted.
§ 631. Cantharides.—Commercial cantharides is either the dried entire, or the dried and powdered blister-beetle, or Spanish fly (Cantharis vesicatoria). The most common appearance is that of a greyish-brown powder, containing shining green particles, from which cantharidin is readily extracted by exhausting with chloroform, driving off the chloroform by distillation or evaporation, and subsequently treating the extract with bisulphide of carbon, which dissolves the fatty matters only. Finally, the cantharidin may be recrystallised from chloroform, the yield being ·380 to ·570 per cent. Ferrer found in the wings and their cases, ·082 per cent.; in the head and antennæ, ·088; in the legs, ·091; in the thorax and abdomen, ·240; in the whole insect, ·278 per cent. Wolff found in the Lytta aspera, ·815 per cent.; Ferrer in Mylabris cichorei, ·1 per cent.; in M. punctum, ·193; and in M. pustulata, ·33 per cent. of cantharidin.
§ 632. Cantharidin (C10H12O4) has two crystalline forms—(1) Right-angled four-sided columns with four surfaces, each surface being beset with needles; and (2) flat tables. It is the anhydride of a ketone acid (cantharidic acid), C8H13O2-CO-COOH. It is soluble in alkaline liquids, and can be recovered from them by acidifying and shaking up with ether, chloroform, or benzene; it is almost completely insoluble in water. 100 parts of alcohol (99 per cent.) dissolve at 18° 0·125 part; 100 of bisulphide of carbon, at the same temperature, 0·06 part; ether, ·11 part; chloroform, 1·2 part; and benzene, ·2 part. Cantharidin can be completely sublimed, if placed in the subliming cell (described at [p. 258]), floating on mercury; a scanty sublimate of crystals may be obtained at so low a temperature as 82·5°; at 85°, and above, the sublimation is rapid. If the cantharidin is suddenly heated, it melts; but this is not the case if the temperature is raised gradually. The tube melting-point is as high as 218°. Potassic chromate with sulphuric acid decomposes cantharidin with the production of the green oxide of chromium. An alkaline solution of permanganate, iodic acid, and sodium amalgam, are all without influence on an alcoholic solution of cantharidin. With bases, cantharidin forms crystallisable salts, and, speaking generally, if the base is soluble in water, the “cantharidate” is also soluble; the lime and magnesic salts dissolve readily. From the soda or potash salt, mineral acid will precipitate crystals of cantharidin; on heating with pentasulphide of phosphorus, o-xylol is produced.
§ 633. Pharmaceutical Preparations of Cantharides.—The P.B. preparations of cantharides are—Acetum cantharides, or vinegar of cantharides, containing about ·04 per cent. of cantharidin.
Tincture of cantharides, containing about ·005 per cent. of cantharidin.
A solution of cantharides for blistering purposes, Liquor epispasticus, a strong solution of the active principle in ether and acetic acid, containing about ·16 per cent. of cantharidin.
There are also—An ointment; a blistering paper, Charta epispastica; a blistering plaster, Emplastrum cantharides; and a warm plaster, Emplastrum calefaciens.
§ 634. Fatal Dose.—It is difficult to state the fatal dose of cantharidin, the unassayed powder or tincture having mostly been taken. A young woman died from 1·62 grm. (25 grains) of the powder, which is perhaps equivalent to 6·4 mgrms. (1 grain) of cantharidin, whilst the smallest dose of the tincture known to have been fatal is (according to Taylor) an ounce. This would be generally equivalent to 15 mgrms. (·24 grain). Hence the fatal dose of cantharidin may be approximately stated as from 6 mgrms. upwards. But, on the other hand, recovery has taken place from very large doses.
§ 635. Effects on Animals.—Certain animals do not appear susceptible to the action of cantharidin. For example, hedgehogs and swallows are said to be able to take it with impunity. Radecki[639] found that cantharidin might even be injected into the blood of fowls without any injury, and frogs also seem to enjoy the same impunity; while dogs, cats, and other animals are sensitive to the poison. Galippe ascertained that after the injection of 5 mgrms. into the veins of a dog, there was exaltation of the sexual desire; the pupils quickly dilated, the dog sought a dark place, and became sleepy. Animals when poisoned die in asphyxia from paralysis of the respiratory centre. Schachowa[640] made some observations on the effect of cantharides on the renal excretion of a dog fed daily with 1 grm. in powder. On the third day, pus corpuscles were noticed; on the fifth, bacteria; on the thirteenth, the urine contained a large quantity of fatty matters, and several casts; and on the seventeenth, red shrivelled blood corpuscles were observed.
[639] Die Cantharidin Vergift., Diss., Dorpat, 1806.
[640] Unters. über die Nieren, Diss., Bern, 1877; Cornil, Gaz. Méd., 1880.
Effects on Man.—Heinrich[641] made the following experiments upon himself:—Thirty living blister-beetles were killed, and digested, without drying, in 35 grms. of alcohol for fourteen days, of this tincture ten drops were taken. There ensued immediately a feeling of warmth in the mouth and stomach, salivation, the pulse was more frequent than in health, there was a pleasant feeling of warmth about the body, and some sexual excitement lasting three hours. In half an hour there was abdominal pain, diarrhœa, and tenesmus, and frequent painful micturition. These symptoms subsided in a few hours, but there was a want of appetite, and pain about the kidneys lasting until the following day. In the second experiment, on taking 1 cgrm. of cantharidin, there were very serious symptoms of poisoning. Blisters formed on the tongue, and there was salivation, with great difficulty in swallowing, and a general feeling of illness. Seven hours after taking the poison, there were frequent micturitions of bloody urine, diarrhœa, and vomiting. Twenty hours after the ingestion the face was red, the skin hot, the pulse twenty beats beyond the normal pulsation, the tongue was denuded to two-thirds of its extent of its epithelium, and the lips and mucous membrane were red and swollen; there was great pain in the stomach, intestines, and in the neighbourhood of the kidneys, continuous desire to micturate, burning of the urethra, and swelling of the glands. There was no sexual excitement whatever; the urine was ammoniacal, and contained blood and pus; the symptoms gradually subsided, but recovery was not complete for fourteen days.
[641] Schroff, Zeitschrift d. Ges. d. Aerzte in Wien, 13, 56.
§ 636. The foregoing is a fair picture of what may be expected in cantharides poisoning. It is remarkable that the popular idea as to the influence of cantharidin in exciting the sexual passion, holds good only as to the entire cantharides, and not with cantharidin. It is very possible that cantharidin is not the only poisonous principle in the insect. The symptoms in other cases, fatal or not, have been as follows:—Immediate burning in the mouth and throat, extending to the stomach and alimentary canal, and increasing in intensity until there is considerable pain. Then follow salivation, difficulty in swallowing, and vomiting, and generally diarrhœa, pain in the kidneys, irritation of the bladder, priapism, and strangury, are all present. The pulse is accelerated, the breathing disturbed, there are pains in the head, and often mydriasis, giddiness, insensibility, delirium, and convulsions; trismus has been noticed. The desire to micturate frequently is urgent, the urine is generally bloody, and contains pus. Pregnant women have been known to abort. In a few of the cases in which a different course has been run, the nervous symptoms have predominated over those of gastro-intestinal irritation, and the patient has sunk in a kind of collapse. In a case of chronic poisoning by cantharides, extending over three months, and recorded by Tarchioni Bonfanti,[642] after the first dose appeared tetanic convulsions, which subsided in twenty-four hours, there was later cystitis, and from time to time the tetanic convulsions returned; gastro-enteritis followed with frequent vomiting, when, cantharides being found in the matters ejected, the otherwise obscure nature of the illness was shown.
[642] Gaz. Med. Ital. Lomb., 1863.
In a case recorded by Sedgwick,[643] following the gastro-enteric symptoms, there were epileptic convulsions; in this instance also was noticed an unpleasant smell, recalling the notion formerly held that cantharides imparted a peculiar odour to the breath and urine. In a case of chronic poisoning related by Tardieu, six students, during several months, used what they thought was pepper with their food, but the substance proved to be really powdered cantharides. The quantity taken each day was probably small, but they suffered from pain about the loins, and also irritation of the bladder. There was no sexual excitement.
[643] Med. Times, 1864.
§ 637. Post-mortem Appearances.—In a French criminal case, in which a man poisoned his step-brother by giving cantharides in soup, the pathological signs of inflammation of the gastro-intestinal tract were specially evident, the mouth was swollen, the tonsils ulcerated, the gullet, stomach, and intestines were inflamed, and the mucous membrane of the intestines covered with purulent matter. In another case there was an actual perforation 3 inches from the pylorus. The inflammatory appearances, however, are not always so severe, being confined to swelling and inflammation without ulceration. In all cases there has been noted inflammation of the kidneys and urinary passages, and this is seen even when cantharidin is administered to animals by subcutaneous injection. In the urine will be found blood and fatty epithelial casts, as well as pus. The contents of the stomach or the intestines will probably contain some remnants of powdered cantharides, if the powder itself has been taken.
§ 638. Tests for Cantharidin, and its Detection in the Tissues, &c.—The tests for cantharidin are—(1.) Its form, (2.) its action in the subliming cell, and (3.) its power of raising a blister.
The most convenient method of testing its vesicating properties, is to allow a chloroformic solution of the substance supposed to be cantharidin to evaporate to dryness, to add to this a drop of olive oil (or almond oil), and to take a drop up on the smallest possible quantity of cotton wool, and apply the wool to the inside of the arm, covering it with good oilskin, and strapping the whole on by the aid of sticking-plaster. In about an hour or more the effect is examined. The thin skin of the lips is far more easily blistered than that of the arm, but the application there is inconvenient.
Dragendorff has ascertained that cantharidin is not present in the contents of a blister raised by a cantharides plaster, although it has been found in the urine of a person treated by one; and Pettenkofer has also discovered cantharidin in the blood of a boy to whose spine a blister had been applied.
The great insolubility of cantharidin in water has led to various hypotheses as to its absorption into the system. It is tolerably easily dissolved by potash, soda, and ammonia solutions, and is also taken up in small proportion by sulphuric, phosphoric, and lactic acids. The resulting compounds quickly diffuse themselves through animal membranes. Even the salts with lime, magnesia, alumina, and the heavy metals, are not quite insoluble. A solution of salt with cantharidin, put in a dialysing apparatus, separates in twenty-four hours enough cantharidin to raise a blister.
Cantharidin has actually been discovered in the heart, brain, muscles, contents of the stomach, intestines, and fæces (as well as in the blood and urine) of animals poisoned by the substance. A urine containing cantharidin is alkaline and albuminous. Cantharidin, although readily decomposed by chemical agents, is so permanent in the body that it has been detected in the corpse of a cat eighty-four days after death.
In any forensic case, the defence will not improbably be set up that some animal (e.g., a fowl poisoned by cantharides) has been eaten and caused the toxic symptoms, for cantharides is an interesting example of a substance which, as before stated, for certain animals (such as rabbits, dogs, cats, and ducks), is a strong poison, whilst in others (e.g., hedgehogs, fowls, turkeys, and frogs), although absorbed and excreted, it appears inert. Experiment has shown that a cat may be readily poisoned by a fowl saturated with cantharides; and in Algeria the military surgeons meet with cystitis among the soldiers, caused by eating frogs in the months of May and June, the frogs living in these months almost exclusively on a species of cantharides.
Dragendorff recommends the following process:—The finely-pulped substance is boiled in a porcelain dish with potash-lye (1 part of potash and 12 to 18 of water) until the fluid is of a uniform consistence. The fluid, after cooling, is (if necessary) diluted with an equal bulk of water, for it must not be too thick; then shaken with chloroform in order to remove impurities; and after separation of the chloroform, strongly acidified with sulphuric acid, and mixed with about four times its volume of alcohol of 90 to 95 per cent. The mixture is kept for some time at a boiling temperature, filtered hot, and the alcohol distilled from the filtrate. The watery fluid is now again treated with chloroform, as above described. The chloroform extract is washed with water, the residue taken up on some hot almond oil, and its blistering properties investigated. The mass, heated with potash in the above way, can also be submitted to dialysis, the diffusate supersaturated with sulphuric acid, and shaken up with chloroform.
In order to test further for cantharidin, it can be dissolved in the least possible potash or soda-lye. The solution, on evaporation in the water-bath, leaves crystals of a salt not easily soluble in alcohol, and the watery solution of which gives with chloride of calcium and baryta a white precipitate; with sulphate of copper and sulphate of protoxide of nickel, a green; with cobaltous sulphate, a red; with sugar of lead, mercury chloride and argentic nitrate, a white crystalline precipitate. With palladium chloride there occurs a yellow, hair-like, crystalline precipitate; later crystals, which are isomorphous with the nickel and copper salts.
If the tincture of cantharides has been used in considerable quantity, the urine may be examined; in such a case there will collect on the surface drops of a green oil, which may be extracted by petroleum ether; this oil is not blister-raising. Cantharides in powder may, of course, be detected by its appearance.
To the question whether the method proposed would extract any other blister-producing substance, the answer is negative, since ethereal oil of mustard would be decomposed, and the active constituents of the Euphorbias do not withstand the treatment with KHO. Oils of anemone and anemonin are dissolved by KHO, and again separated out of their solutions, but their blistering property is destroyed. They are volatile, and found in anemone and some of the Ranunculaceæ. In the Aqua pulsatilla there is an oil of anemone, which may be obtained by shaking with ether; but this oil is not permanent, and if the Aqua pulsatilla stand for a little time, it splits up into anemonic acid and anemonin, and then cannot be reobtained. A blistering substance, obtained from the Anacardia orientalia and the fruit of the Anacardium occidentale and Semecarpus anacardium, is not quite destroyed by a short action with potash, but is by one of long duration; this substance, however, cannot be confused with cantharidin, for it is oily, yellow, easily soluble in alcohol and ether, and differs in other respects.
V.—Snake Poison.
§ 639. The poisonous snakes belong chiefly to two classes, the Proteroglypha and the Solenoglypha.
Weir Mitchell and Ed. T. Reichert[644] have made some important experiments on snake poison, using the venom of some 200 snakes. Most of the snakes were rattlesnakes, a few were cobras and other species. They came to the conclusion that the active constituents are contained in the fluid part alone, the solid particles suspended in the fluid having no action. The poison they considered to consist of two toxalbumins, one a globulin, acting more particularly on the blood, the other, a peptone (albumose?), acting more particularly on the tissues. Differences in snake venom depend on the relative proportions of these two substances. The peptone, which acts more especially locally on the tissues, determines an inflammatory action, with much swelling and multiple extravasation of blood, which may proceed to a moist gangrene. The globulin has a paralysing influence on the heart, the vasomotor centres, the peripheral ends of the splanchnic nerves, as well as on the respiratory centres of both warm and cold-blooded animals. Feoktisow’s[645] researches show that although the heart continues to beat after the respiration has ceased for a few minutes, it has no force. The blood pressure sinks immediately after the injection. Whether the globulin is injected subcutaneously or direct into the veins, there is commonly considerable extravasation of blood in the chest and abdomen; the intestine is often filled with blood as well as the pericardium; and the urine is bloody. The poison of Vipera ammodytes in watery solution may be boiled for six minutes, and yet is as active as before. According to Lewin, snake poison generally can be heated to 125° and yet preserve its poisonous properties. These last observations are not in accordance with the belief of some that the active principle of snake venom is a ferment, or, indeed, in harmony with the idea that it is a globulin or toxalbumin; for such bodies have not, so far as we know, the stability to withstand so high a degree of heat.
[644] Smithsonian Contributions to Knowledge, Washington, 1886.
[645] Exp. Unters. über Schlangengift. Inaug. Diss., Dorpat, 1888.
§ 640. The Poison of the Cobra.—The poison excreted from the salivary glands of the cobra di capello is the most deadly animal fluid known. When first ejected, it is an amber-coloured, rather syrupy, frothy liquid, of specific gravity 1·046, and of feeble acid reaction; it dries rapidly on exposure to air to a yellow film, which readily breaks up into brilliant yellow granules, closely imitating crystals. The yellow powder is very acrid and pungent to the nostrils, and excites a painful (though transitory) inflammation, if applied to the mucous membrane of the eye; the taste is bitter, and it raises little blisters on the tongue. It is perfectly stable, and preserves its activity for an indefinite time. The dried poison as described is perfectly soluble in water, and if the water is added in proper proportions, the original fluid is without doubt reproduced, the solution usually depositing a sediment of epithelial débris, and often containing little white threads.
The poison has been examined by several chemists, but until of late years with a negative result. The writer was the first to isolate, in 1876, a crystalline principle, which appears to be the sole acting ingredient; the yellow granules were dissolved in water, the albumen which the venom so copiously contains coagulated by alcohol, and separated by filtration; the alcohol was then driven off at a gentle heat, the liquid concentrated to a small bulk, and precipitated with basic acetate of lead. The precipitate was separated, washed, and decomposed in the usual way by SH2, and on removing the lead sulphide, crystals having toxic properties were obtained.
Pedler,[646] precipitating the albumen by alcohol, and then to the alcoholic solution adding platinic chloride, obtained a semi-crystalline precipitate, which from an imperfect combustion he thinks may have something like the composition PtCl4(C17H25N4O7HCl)2. I have examined the platinum compound, and made several combustions of different fractions, but was unable to obtain the compound in a sufficient state of purity to deduce a formula. My analysis agreed with those of Pedler for nitrogen—viz., 9·93 per cent. (Pedler, 9·69); hydrogen 4·17 (Pedler, 4·28); but were higher for carbon, 41·8 per cent. (Pedler, 33·42 per cent.); one fraction gave 7·3 per cent. of platinum, another double that amount. Material was insufficient to thoroughly investigate the compound, but it was evident that several double salts were formed. The blood of the cobra is also poisonous. A. Calmette[647] has found that 2 c.c. of fresh cobra blood, injected into the peritoneum of a rabbit weighing 1·5 kilo., causes death in six hours; the same dose of the defibrinated blood injected into the veins is fatal in three minutes.
[646] Proc. Roy. Soc., vol. xxvii. p. 17.
[647] Compt. Rend., Soc. de Biol., 1894.
§ 641. Fatal Dose.—From my experiments on cats, rabbits, and birds, it seems probable that the least fatal dose for cats and rabbits, lies between ·7 and ·9 mgrm. per kilo., and for birds somewhere about ·7 mgrm. per kilo. of the dried poison; the venom contains about 60 per cent. of albuminous matter, and about 10 per cent. of poisonous substance; therefore, the lethal power is represented by something like ·07 to ·09 mgrm. per kilo., if the pure toxic principle free from albumen and diluting impurities be considered.
§ 642. Effects on Animals.—Almost immediately local pain or signs of uneasiness at the seat of injection are observed. There is then a variable interval, seldom exceeding 20 minutes (and generally much less), but in one of my experiments half an hour elapsed after the injection of a fatal dose before any effect was evident. The symptoms once produced, the course is rapid, and consists, first, of acceleration of the respirations, and then a progressive slowing, soon followed by convulsions. The convulsions are probably produced by the interference with the respiration and the deficient oxidation of the blood, and are therefore, the so-called “carbonic acid convulsions.” There is paresis or paralysis of the limbs. Death seems to occur from asphyxia, and the heart beats for one or more minutes after the respirations have ceased. If the dose is so small as not to produce death, no after-effects have been observed; recovery is complete.
Sir J. Fayrer, and Dr. Lauder Brunton consider that the terminations of the motor nerves suffer; on the other hand, Dr. Wall would explain the phenomena by referring the action entirely to the central nervous system, and concludes that the effects of the cobra poison consist in the extinction of function extending from below upwards of the various nerve centres constituting the cerebro-spinal system. In addition to this, there is a special and rapid action on the respiratory and allied nuclei, and this it is that causes death.
§ 643. Effects on Man.—By far the best account hitherto published of the effects of the cobra poison is a paper by Dr. Wall,[648] in which he points out the very close similarity between the symptoms produced and those of glosso-pharyngeal paralysis. This is well shown in the following typical case:—A coolie was bitten on the shoulder about twelve at midnight by a cobra; he immediately felt burning pain at the spot bitten, which increased. In fifteen minutes afterwards he began, he said, to feel intoxicated, but he seemed rational, and answered questions intelligently. The pupils were natural, and the pulse normal; the respirations were also not accelerated. He next began to lose power over his legs, and staggered. In thirty minutes after the bite his lower jaw began to fall, and frothy viscid mucous saliva ran from his mouth; he spoke indistinctly, like a man under the influence of liquor, and the paralysis of the legs increased. Forty minutes after the bite, he began to moan and shake his head from side to side, and the pulse and respirations were somewhat accelerated; but he was still able to answer questions, and seemed conscious. There was no paralysis of the arms. The breathing became slower and slower, and at length ceased one hour and ten minutes after the bite, the heart beating for about one minute after the respiration had stopped.
[648] “On the Difference of the Physiological Effects Produced by the Poison of Indian Venomous Snakes,” by A. T. Wall, M.D., Proc. Roy. Soc., 1881, vol. xxxii. p. 333.
There is often very little sign of external injury, merely a scratch or puncture being apparent, but the areolar tissue lying beneath is of a purple colour, and infiltrated with a large quantity of coagulable, purple, blood-like fluid. In addition, the whole of the neighbouring vessels are intensely injected, the injection gradually diminishing as the site of the poisoned part is receded from, so that a bright scarlet ring surrounds a purple area, and this in its turn fades into the normal colour of the neighbouring tissues. At the margin is also a purple blood-like fluid, replaced by a pinkish serum, which may often be traced up in the tissues surrounding the vessels that convey the poison to the system, and may extend a considerable distance. These appearances are to be accounted for in great part by the irritant properties of the cobra venom. The local hyperæmia and the local pain are the first symptoms. In man there follows an interval (which may be so short as a few minutes, or so long as four hours) before any fresh symptoms appear; the average duration of the interval is, according to Dr. Wall, about an hour. When once the symptoms are developed, then the course is rapid, and, as in the case quoted, a feeling like that of intoxication is first produced, and then loss of power over the legs. This is followed by a loss of power over the speech, over swallowing, and the movement of the lips; the tongue becomes motionless, and hangs out of the mouth; the saliva is secreted in large quantities, and runs down the face, the patient being equally unable to swallow it or to eject it, and the glosso-pharyngeal paralysis is complete.
§ 644. Antidotes and Treatment.—Professor Halford some years ago proposed ammonia, and M. Lacerda in recent times has declared potassic permanganate an antidote to the cobra poison. The ammonia theory has been long disproved, and before Lacerda had made his experiments I had published the chemical aspect of some researches,[649] which showed that mixing the cobra venom with an alkaline solution of potassic permanganate destroyed its poisonous properties. Other experiments were also made in every conceivable way with potassic permanganate, injecting it separately, yet simultaneously, into different parts of the same animal’s body, but so long as it does not come into actual contact with the poison it has no antidotal power whatever over the living subject. Other observers, previous to the researches mentioned and since, all agree that permanganate is no true antidote.[650] It only acts when it comes directly into contact with the venom, but when the venom is once absorbed into the circulation potassic permanganate, whether acid, alkaline, or neutral, is powerless. That it is of great use when applied to a bite is unquestionable, for it neutralises or changes any of the venom hanging about the wound, and which, if allowed to remain, might yet be absorbed; but here it is obvious that the venom is, so to speak, outside the body. A. Galmette (Annales de l’Institut Pasteur, 25th March 1892) has found that gold chloride forms an insoluble compound with the cobra poison, which is not poisonous, and that animal living tissues impregnated with gold chloride will not absorb the poison. He even advances some evidence tending to show that gold chloride may overtake, as it were, the venom in the circulation, and thus act as a true antidote. This is improbable, and, until confirmed, the general treatment most likely to be successful is the immediate sucking of the wound, followed by the application of an alkaline solution of permanganate; and lastly, if the symptoms should nevertheless develop, an attempt should be made to maintain the breathing by galvanism and artificial respiration.[651]
[649] Analyst, Feb. 28, 1877.
[650] See Note on the effect of various substances in destroying the activity of the cobra poison. By T. Lauder Brunton and Sir J. Fayrer, Proc. Roy. Soc., vol. xxvii. p. 17.
[651] Some of my experiments on the cobra poison may be briefly detailed, illustrating the general statement in the text:—
1. A quantity equal to 1 mgrm. of the dried venom was injected subcutaneously into a chicken. The symptoms began in two minutes with loss of power over both legs. In eight minutes the legs were perfectly paralysed. There were convulsive movements of the head and wings, slowing of the respiration, and death in ten minutes. The same quantity of poison was treated with a little tannin, and the clear liquid which separated from the precipitate injected into another chicken. The respiration became affected in ten minutes; in eighteen minutes the bird had become very quiet, and lay insensible; in twenty minutes it was dead, the respiration ceasing before the heart.
2. In seven experiments with cobra poison, first rendered feebly alkaline with an alkaline solution of potassic permanganate, no effect followed. Three of the experiments were on chickens, four on rabbits.
3. A chicken was injected with 1 mgrm. of cobra poison in one leg, and in the other simultaneously with a solution of potassic permanganate. Death followed in sixteen minutes. Another chicken was treated in the same way, but with injections of potassic permanganate solution every few minutes. Death resulted in thirty-seven minutes. Four other similar experiments were made—two with feebly alkaline permanganate, two with permanganate made feebly acid with sulphuric acid—but death occurred with the usual symptoms.
4. Cobra poison was mixed with a weak solution of iodine, and a quantity equal to half a mgrm. was injected into a chicken. The symptoms began directly, were fully developed in ten minutes, and death took place in twenty-one minutes.
5. Equal volumes of cobra venom and aldehyde were mixed, and a quantity equivalent to 1 mgrm. of the cobra poison injected. The symptoms were immediate paralysis and insensibility, and the respiration rapidly fell. Death occurred in four minutes without convulsions.
6. The cobra venom was mixed with a feebly alkaline solution of pyrogallic acid, and injected subcutaneously into a chicken. In six minutes the usual symptoms commenced, followed in thirteen minutes by death.
7. One mgrm. was injected into a chicken. The respirations at the commencement were 120; in twenty-two minutes they sank to 96, in twenty-five minutes to 84, in twenty-seven minutes to 18, and then to occasional gasps, with slight movement of the wings and toes. There was death in thirty-two minutes after the injection.
8. A young rabbit was injected with ·5 mg. (equal to 1 mgrm. per kilo.) of cobra poison. In two hours it was apparently moribund, with occasional short gasps. Artificial respiration was now attempted. There was considerable improvement, but it was intermitted during the night, and the animal was found dead in the morning, having certainly lived six hours.
9. A strong healthy kitten was injected with 1 mgrm. of cobra venom (equal to 5 mgrms. per kilo.). In twenty minutes the symptoms were well developed, and in an hour the animal was gasping—about twelve short respirations per minute. Artificial respiration was kept up for two hours, and the animal recovered, but there was great muscular weakness lasting for more than twenty-four hours.
10. A brown rabbit, weighing about 2 kilos., was injected with 12 mgrms. (6 per kilo.) of the cobra poison. The symptoms developed within ten minutes; ammonia was injected, and also given by the nostril. The heart’s action, which, previous to the administration of the ammonia, had been beating feebly, became accelerated, but death followed within the hour, the heart beating two minutes after the respiration had ceased.
11. A brown rabbit, about 2 kilos. in weight, was injected with 1·5 mgrms. of cobra poison (·75 per kilo.). There were no symptoms for nearly an hour, then sudden convulsions, and death.
12. Another rabbit of the same size was treated similarly, but immediately after the injection made to breathe nitrous oxide; death took place in thirty minutes. A rabbit, a little over 2 kilos. in weight, was injected with 7 mgrms. of cobra venom per kilo., and then 10 mgrms. of monobromated camphor were administered. In fifteen minutes there was general paralysis of the limbs, from which in a few minutes the animal seemed to recover; thirty minutes after the injection there were no very evident symptoms, but within forty minutes there was a sudden accession of convulsions, and death. Experiments were also made with chloroform, morphine, and many other substances, but none seemed to exercise any true antidotal effect.
§ 645. Detection of the Cobra Venom.—In an experiment on a rabbit, the animal was killed by the subcutaneous injection of 8 mgrms. per kilo. of the cobra poison. Immediately after death, 2 c.c. of the blood were injected into a small rabbit; in fifteen minutes there was slow respiration with pains in the limbs; in thirty minutes this had, in a great measure, passed off, and in a little time the animal was well. In any case in which it is necessary to attempt to separate the cobra venom, the most likely method of succeeding would be to make a cold alcoholic extract, evaporate in a vacuum, take up the residue in a little water, and test its effect on small animals.
§ 646. Duboia Russellii.—The Duboia russellii or Russell’s viper is one of the best known and most deadly of the Indian vipers. The effects of the poison of this viper are altogether different from those of the cobra. The action commences by violent general convulsions, which are often at once fatal, or may be followed by rapid paralysis and death; or these symptoms, again, may be recovered from, and death follow at a later period. The convulsions do not depend on asphyxia, and with a small dose may be absent. The paralysis is general, and may precede for some time the extinction of the respiration, the pupils are widely dilated, there are bloody discharges, and the urine is albuminous. Should the victim survive the first effects, then blood-poisoning may follow, and a dangerous illness result, often attended with copious hæmorrhages. A striking example of this course is recorded in the Indian Med. Gaz., June 1, 1872.
A Mahommedan, aged 40, was bitten on the finger by Russell’s viper; the bitten part was soon after excised, and stimulants given. The hand and arm became much swollen, and on the same day he passed blood by the rectum, and also bloody urine. The next day he was sick, and still passing blood from all the channels; in this state he remained eight days, losing blood constantly, and died on the ninth day. Nothing definite is known of the chemical composition of the poison; it is probably qualitatively identical with “viperin.”
§ 647. The Poison of the Common Viper.—The common viper still abounds in certain parts of Great Britain, as, for example, on Dartmoor. The venom was analysed in a partial manner by Valentin. In 1843 Prince Lucien Bonaparte separated a gummy varnish, inodorous, glittering, and transparent, which he called echidnin or viperin; it was a neutral nitrogenous body without taste, it arrested the coagulation of the blood, and, injected into animals, produced all the effects of the bite of the viper. Phisalix and G. Bertrand have studied the symptoms produced in small animals after injection. A guinea-pig, weighing 500 grms., was killed by 0·3 grm. of the dried venom dissolved in 5000 parts of saline water; the symptoms were nausea, quickly passing into stupor. The temperature of the body fell. The autopsy showed the left auricle full of blood, the intestine, lungs, liver, and kidneys injected. The blood of the viper is also poisonous, and produces the same symptoms as the venom.[652] The same observers have shown (Compt. rend., cxviii., Jan. 1894) that the blood of the water-snake (Tropidonotus natrix) and of the Thuringian adder (Tropidonotus viperinus) is poisonous, producing the same symptoms as that of the viper.
[652] Compt. rend. Soc. de Biol., t. v. 997.
The Venom of Naja Haje (Cleopatra’s Asp).—It has been stated that 20,000 persons annually die in Ceylon from the bite of Cleopatra’s asp. Graziani (Rif. Med., October 7, 1893) has undertaken a physiological study of the venom, which has already received attention at the hands of Calmette, Wall and Armstrong, Weir Mitchell, Reichardt, and others. The venom, when dried, appears as transparent scales, easily soluble in water, very slightly so in alcohol, ether, or chloroform; its aqueous solution has an unpleasant odour, and is neutral to test paper. Chemically it gives all the tests described by Weir Mitchell and others as characteristic of the venom of Naja tripudians. The physiological effects of this dried venom were tried on guinea-pigs, rabbits, and frogs, to all of which it proved fatal in extremely minute doses. The guinea-pig, a few seconds after injection, becomes paralysed in its hind limbs, it foams at the mouth, and makes violent attempts at vomiting. The eyes are half closed, but occasionally for short periods there is a partial disappearance of the paralysis, and the animal makes feeble attempts to support itself. Respiratory embarrassment is soon added to the foregoing symptoms, and the animal lies perfectly prone, devoting all its attention to breathing, which is rendered still more difficult by the vomiting and frothy saliva which is secreted in abundance. Finally death ensues from asphyxia. The post-mortem examination reveals the heart still feebly beating, the lungs pallid, and the blood in the organs very dark. The liver and kidneys are hyperæmic, but the brain and cord, with their coverings, are anæmic. In the rabbit the course of the poisoning is practically identical with that described above. Histologically, the following facts are made out in addition to the foregoing. The red blood-corpuscles are in great measure broken down, and there are also effusions into the muscular tissues. The kidneys are very hyperæmic, and there is marked degeneration of the epithelium lining the glomeruli and convoluted tubules. The glomerular capsules are much distended, and numerous leucocytes are discernible throughout the organ. The liver, also, is hyperæmic, and shows numerous broken-down blood-corpuscles, and partial necrosis of many of the liver cells. Examination of the central nervous system reveals no particular changes.