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, can be heated to 100° C. without decomposition for a short time, 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, with various results. The senior author isolated, in 1876, a crystalline principle as follows:-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. The authors have been unable, through want of material, to deal with the suggestion of F. Norris Wolfenden that the crystals were those of gypsum, their toxic properties being due to adhering impurities.

*

Pedler, 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 PtCl (C17H25N4O7HCl)2.

17

The latest observer of the cobra poison, Edwin Stanton Faust, † claims to have shown that the essential constituent of the cobra poison is a nitrogen-free substance, belonging pharmacologically to the group of the picrotoxins, sapotoxins, and sphacelo-toxins. To this substance he gives the name of "ophiotoxin"; he has obtained it in aqueous solution, but directly the aqueous solution is concentrated in a vacuum, the white residue obtained is in most cases inactive. The solution froths on shaking; if injected subcutaneously it has but little action; on the other hand, if injected intravenously the ordinary effects of cobra poison are produced. Hence Faust appears to believe that the poison of the cobra is some compound of his ophiotoxin and an albuminoid body: the combination being easily dissolved. He thinks that there is some analogy between the cobra poison and the jalapin-elaterin group, in which the free acids and their salts are inactive; while, on the other hand, the anhydrides are active.

*Proc. Roy. Soc., vol. xxvii. p. 17.

+ Die thierischen Gifte, Braunschweig, 1906.

The blood of the cobra is also poisonous. A Calmette * has found that 2 c.c. of fresh cobra blood injected into the peritoneum of a rabbit weighing 15 kilo., causes death in six hours; the same dose of the defibrinated blood injected into the veins is fatal in three minutes.

§ 644. Fatal Dose.-From one of the senior author's 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. Calmette calculated the fatal dose for a man at 10 mgrms., Fraser 317 mgrms., and Elliott about 30 mgrms.

§ 645. Effects on Animals.-There has been much exact physiological work done on the cobra poison since the last edition of this work. One of the most complete researches is that by H. R. Elliott; † he has confirmed the fact that cobra venom raises the blood-pressure; this action can be traced in the vessels of the frog, down to dilutions of 1 in ten million. If the solution is concentrated, it acts directly on the isolated frog's ventricle, killing it in systole; but if the solution is weak, the action of the heart is stimulated; this brings cobra venom into line, pharmacologically, with the glucosides of the Strophantin group. Elliott found that atropine sulphate and cobra venom in the same solution intensify each other.

Cobra venom acts powerfully on the mammalian heart; the action is dual.

(1) A direct action on the muscular fibres or on the nerve endings. (2) An action on the intra-cardial vagal mechanism.

Concentrated solutions cause irregular and extreme cardiac excitation, with early death in systole; with less concentrated solutions, the early stage of excitement yields to a prolonged phase in which the tonic action of the poison in the heart is most pronounced, the beat is regular, steady, and strong.

When given subcutaneously in low lethal doses, death occurs from paralysis of the respiratory centre; there is a gradually increasing venosity of the blood, and if life is prolonged beyond the usual term (five hours) the phrenic and other motor nerves may become paralysed. If a large dose be given intravenously, the respiration may cease almost at once. By applying cobra venom direct to the exposed medulla oblongata of the rabbit, Elliott has shown that the respiratory Compt. rend. Soc. de Biol., 1894. + Phil. Trans., 1905.

centre can be paralysed without the phrenic nerve ends or the heart being appreciably affected.

If very large doses be given, the direct action of the poison on the heart may produce death by cardiac failure. Such large doses cause (a) a sudden fall of blood-pressure; (b) a subsequent rise, if the dose has not been too large; (c) a final fall to zero.

Cobra poison, in common with that of most of the Colubridæ, prevents the coagulation of the blood, in contradistinction to the viper poisons, which strongly coagulate blood; both classes of poison appear to dissolve out the red colouring matter of the blood.

The post-mortem appearances are not very distinctive; at the point of injection, there is often a slight hæmorrhagic oedema. The liver and the spleen show on their surfaces circumscribed hæmorrhagic spots; the peritoneum, the meninges, endocardium, pleura, and mucous membranes show frequently ecchymoses, and the blood is fluid and dark.

§ 646. Effects on Man.-By far the best account hitherto published of the effects of the cobra poison is a paper by Dr. Wall,* 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.

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,

* "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.

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.

§ 647. Cobra Anti-toxin.-All the so-called antidotes, such as gold chloride, potassic permanganate, and others, have proved to be useless; for, although chemical agencies may make the poison clinging to the wound inert, such reagents fail to neutralise the absorbed poison. It had long been known that animals dosed subcutaneously by quantities of cobra or other snake venom, insufficient to kill, acquired a certain degree of immunity against the same poison; this induced Calmette to endeavour to obtain an anti-venom serum on the same principle, as to preparation, as the well-known commercial anti-toxin for diphtheria. In this Calmette, working in the Lille Institute, has been to a great extent successful. Horses and donkeys are the animals selected to produce the immunising and curative serum; these animals are injected with ever-increasing doses of cobra poison, until they bear without reacting two hundred times the otherwise deadly dose-e.g. the fatal dose for a horse is about 10 mgrms. of the dried cobra venom, and a horse after successful treatment will bear the injection of a quantity equal to no less than 2 grms. Many animals during the process die of endocarditis or nephritis, which affections must therefore be considered as true sequelæ to chronic cobra poisoning. The serum obtained from the blood of an animal which is considered highly resistant is tested by mixing a definite quantity of it with an equally definite quantity of cobra venom, and injecting it into some small animal. The serum is

considered sufficiently active if 2 c.c. of serum mixed with 1 mgrm. of cobra venom produces no poisonous symptoms when injected into a rabbit, and if 2 c.c. of the serum injected into a rabbit 2 kilogrammes in weight protects it from the effects of 1 mgrm. of cobra venom injected subcutaneously an hour later.

The serum is preserved with strict antiseptic precautions in 10-c.c. tubes; it is said not to lose its activity for two years or even longer. Another method of preserving the serum is drying it at a low temperature; it then appears in commerce as light dry yellow scales, which for subcutaneous use are dissolved in water at the time. For ten years now the Pasteur Institute at Lille has prepared this form of anti-toxin ; at first it was hoped that in such a substance was to be found a general remedy for, or protection against, snake bite, but this is not so; its action is confined to either the particular species of snake venom, or species nearly allied, against which the horse was immunised. Experiments are, however, being made in order to obtain if possible a general sort of serum, by operating with mixtures of venoms; whether success will be attained time alone can show.

§ 647A. Other Colubrine Snakes.-Bungarus fasciatus, or the Banded Krait, acts similarly to the cobra poison; but since its activity is destroyed by heating from 73°-75°, it is less stable.

Bungarus cæruleus, or the Krait, one of the most dreaded of the Indian snakes, is said to be even more virulent than the cobra.*

Naja Bungarus, or the Hamadryad, possibly the largest poisonous snake in the world, growing to over 13 feet in length; the Naja haje (Cleopatra's asp); Elaps corallinus, the brilliant red coral snake of America; the Elapine of Australia--all possess a venom having a physiological action similar to that of the cobra.

The Viperidae.-The chief poisonous snakes belonging to the Viperidae, besides the true vipers, are the American rattlesnakes, belonging to the genus Crotalus-viz., the Lachesis muta (Crotalus mutus), commonly called the surucucu, or bushmaster of the Dutch colonists of Surinam, one of the largest venomous snakes; the Copperhead, also known under the name of Chunk-head; Deaf Adder and Pilot snake (Trigonocephalus contortus); various species of Bothrops in the Brazils. There is also a species of Trimeresurus in one of the Japanese islands, which appears to be specially aggressive, and kills some 48-70 hours after the bite.

The poisons of these snakes appear to be different from that of the cobra and more analogous to the poison of the true vipers.

* Leonard Rogers, M.D., Phil. Transac., 1904. Major R. H. Elliott and W. C. Sillar, M. B., ibid. Some Observations on the Poison of the Banded Krait (Bungarus fasciatus), by Capt. George Lamb, M.D. Glas., Calcutta, 1904.