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result. Why should this be? Other and nonvenomous snakes die readily of venom poisoning. The many noxious compounds man carries in his liver, gastric glands, or thyroid gland are fatal if they enter the blood in large amount. There is, indeed, scarcely an organ of his body which is not a possible source of poison to him, the sole question being as to his constant competency to rid himself of the fractional doses ever passing into and out of his blood and to secure himself against certain products which are not meant at any time to pass out of the issues of certain organs of the body into the hurrying currents of the circulation.
But to all creatures save itself the venomous serpent is noxious in varying degrees. Certainly the cobra surpasses as a poisoner all of our American snakes. In India other serpents
creatures die slowly from snake bite, and the hog escapes only because he does not get seriously bitten. His bristles, tough skin, and clever mode of attack save him. Little pigs are often bitten and die like other creatures. We have never been able to poison plants with snake venom.
Practically speaking, there is something more to be said as to the question of relative toxicity. The size of the serpent, the time which has elapsed since it has bitten, determine also the extent of the damage it can do. A snake which has lately bitten two or three times is ill provided with poison, but captive snakes long undisturbed are apt to inflict fatal wounds.
The serpents used in our recent research were brought chiefly from Florida by the potent aid of the Smithsonian Institution, and the
dried venom of the cobra was procured from India through the assistance of her Majesty's Indian Government, and more largely by the private aid of Vincent Richards, Esq. The living snakes reached us in coffee-bags secured by strings, the sacks having been placed in a perforated box. When they came we opened the case, undid the strings and tumbled the poisoners into a box some five feet deep. There they lived very well if provided with water; and coiled in corners, or piled in numbers one on another, they lay sluggish and inert until danger threatened. There were half a dozen of these snake cages in our laboratory and at times they contained a hundred snakes, each genus or species having its own box. If disturbed, the rattlers were apt to start a chorus which was somewhat appalling to strangers.
When we desire to collect venom, we use the snake loop. With it a serpent is caught by the neck and lifted up to the top of the box. The lip of a saucer is then slipped into the snake's mouth. Angry at this liberty, it lifts its fangs, which catch on the inner edge of the saucer, against which the serpent bites furiously again and again. As it does so a thin yellow fluid squirts out of the perforation near to the needle-like end of the fangs. We slacken the loop, let the snake fall into a box cage, and seize a second, and a third, until we have all the venom we desire. It is innocent-looking enough. In water a drop of it sinks, whitening as it falls. It has no smell and no taste. A boiling heat clots it as it does white of egg, for, like that body, it is albuminous in its nature. If we dry it with care there is the same resemblance to egg albumen in its shining, yellow scales. Once desiccated it keeps well, as it does also in glycerine or in alcohol.
When I first studied this strange poison I thought of it as a single albuminous body. As such it had always been regarded since it had been proved by Prince Bonaparte to belong to the albumens. When once I chanced to think that venom might be a complex fluid, holding in solution more than one poison, reasons for such a belief multiplied, and so excited my interest that, in 1882, with Professor Reichert's aid, I began to put my theory to the sharp test of experiment.
To prove in the outside laboratory what the inside mental laboratory has comfortably settled is not always easy, and many months of careful research were required before the answer came to us. I will try to make clear our methods and results. When a little of the venom is placed in sufficient water it dissolves readily. If now we heat the solution a coagulation takes place, just such as happens when white of egg hardens on boiling. If by means of a filter we separate this substance clotted by
heat, it is found to be innocuous. The clear fluid which passes through the filter is, however, poisonous, but does not cause much local effect. As a whole the poison has been damaged by heat, presumably because one or more of its ingredients had been injured by heat. The next step is to learn if the substance made solid and inert by boiling cannot be separated in some other way and in such a form as will leave it also poisonous.
All soluble substances are divisible into two classes, one of which will pass through an animal membrane into a current of pure water and one of which will not. Those which can so pass are said to be dialysable, and the filter is known as a dialyser, and the process is called dialysis. We dissolve some of the poison in water and put it in an inverted funnel, the wide mouth of which, being covered with a thin animal membrane, is placed in distilled water. Under these circumstances the water goes through the membrane and dilutes the fluid above it and certain substances pass out to the water.
The matter which thus finds its way out to the water is said to be dialysable. When examined it proves to be poisonous - to be uncoagulable by heat, and to be the same as the matter left unaltered when we boil the diluted poison for a few moments. This substance resembles the albuminous matter which is formed when gastric juice digests white of egg; and as the material so obtained is called peptone, we named our product which passed through the dialyser to water venom peptone.
As the thinner water enters the dialyser and the peptone goes out, within the vessel there falls down a white substance, which is easily redissolved if we add a little common salt. It falls out of solution because the salts belonging to venom and which keep the white matter dissolved are, like all saline substances, dialysable and pass out along with the peptone. This white precipitate has certain likenesses to the albuminous bodies known as globulin, and of which there are several kinds in our bodies. That which thus falls out of the solution of venom we named venom globulin. It was to be had also in a simpler way. When we add plenty of pure water to clear fresh venom the water added makes the whole fluid relatively less salt and a white matter falls down. When this is separated and examined it proves to be the same as that left within the dialyser. Other matters of like nature but less important are found in some snake venoms, but essentially all examined by us contained at least two albuminous matters.
Mix these two in pure water with a little common salt and you practically reconstruct
a venom-the other ingredients are of less
If we put venom peptone under the skin of a living animal it behaves much as boiled venom does. The local injury it causes is at first slight. Little or no blood oozes forth, but, if the animal survive, in an hour or two a watery swelling is seen, the tissues soften as if they were melted or dissolved, a horribly swift putrefaction occurs, and the tissues near and far swarm with the little rod-like bodies known as bacteria, which are the essential accompaniment and cause of putrefaction. Meanwhile the breath-sustaining centers become weak, and cease to respond by rhythmical effluxes of energy to the various excitations which stimulate the muscles so as to cause them to move the chest. The animal dies from failure to breathe. Internal bleeding is rare and slight, nor are the changes in the blood at all remark
Venom peptone is present in cobra poison, and
in that of the rattlesnake. In the Indian serpent it constitutes, however, nearly the whole of the toxic albumen present, there being but two per cent. of the other element in question. The venom peptone of the cobra is also a far more active agent than the substance which corresponds to it in the venom of our crotalus, although chemically we can see but little difference between the two; since venom peptone passes with ease through membranes, and hence is rapidly absorbed, cobra poison may not always be swallowed with impunity, whereas it is possible to feed a pigeon on crotalus venom day after day and see it live unhurt.
While rattlesnake venom owes a part of its activity to venom peptone, its peculiar virulence and destructiveness belong chiefly to venom globulin, of which it has relatively nearly twenty-five per cent.-fifteen times as much as in cobra. Venom globulin, like the peptone poison, at first and briefly enfeebles the heart, but next attacks the respiratory centers, and finally
paralyzes the spinal ganglia. When separated and redissolved in a weak and saline solution with water it is a most potent poison; and besides its influence on the centers which sustain life, it has, soon or late, distinctive effects on almost all the tissues which somewhat resemble the changes seen in certain maladies, such as yellow fever; yet that which in them exacts days is brought about from globulin poisoning within an hour or less. At the spot where we inject globulin the vessels give way and pour out blood which cannot clot, and this change by and by occurs here and there throughout any or every organ of the body, so that at last the blood becomes what physicians call diffluent, and may remain until it decays, free from the clots usually seen in the healthy fluids when drawn and allowed ⚫ to stand.
Thus it is that, because the cobra has little venom globulin and the rattlesnake much, the local appearances of the bite in either are readily recognizable. Then, also, as the Indian snake has much venom peptone and our serpent little, the former kills more surely and sooner, and does not cause the blood to stay fluid, so that in most cases the general phenomena would also enable us to say which snake had bitten. Certain other Indian snakes give us symptoms like those caused by the bite of our crotalidæ, and probably will be found to resemble them in the composition of their venoms. While we can thus separate and analyze the influence of the two poisons found so far in all venoms examined by us, neither alone occasions the tremendous and perfect effects seen when both are combined by mischievous nature in a suitable solution. Nor, indeed, is the poison ever quite so effective after it has been once dried and redissolved for experimental use.
There are vegetable poisons which possess power to destroy life by enfeebling the respiratory nerve centers; but we know of no poison save snake venom which has the ability to ruin in a few minutes the capacity of the lesser vessels to keep the moving blood within their guarding walls. Our every function-nay, life itself depends on the blood being so restrained. If by accident a drop or two of normal blood escape from a small vessel, instantly the blood clots and tends to cork up the tiny tear through which it came. Venom not only seems to rot the vessels, but it also makes the blood fluid, and so facilitates the hemorrhages of which it is the primary cause. To study this singular process of destruction closely a small animal was so completely etherized as to cease to feel pain, and a loop of its intestinal cover called the peritoneum was examined with the microscope. The spectacle of the blood globules driven swiftly through transparent capillaries, VOL. XXXVIII.-67.
the smallest of vessels, is a constant source of wonder to him who sees it. Venom peptone in solution disturbs this local flood stream but little. Venom globulin exhibits its effects with difficulty, and solutions of dry venom cause but slight and tardy results. If, however, we touch the thin membrane with fresh rattlesnake poison, in a few minutes the delicate little cells, which are like a thatch on the inside of the capillary vessels, seem to be roughened, and become less transparent. Then, abruptly, here and there a drop of blood oozes out. Presently the fanlike expansion of the minute vessels we are watching begins to look like a bunch of red grapes, as these tiny blood points increase in size and number, until at last the whole field of view is covered with escaped blood. It is then a question of time as to how long it will be before the same disintegration of vessels, and the same loss of power in the blood to clot, occur in hundreds of places remote from the spot first poisoned.
If after poisoning an animal we examine the blood cells at intervals, we find that they very early lose their usual flat, disklike aspect, and become smaller and round. They also acquire for a time a singular stickiness and elasticity, so that they adhere in masses, and when compressed spindle out, and then run together anew when we cease to subject them to press
The power of venoms to hasten and favor putrescence must have something to do with the symptoms which occur when death takes place after a long interval, as a day or two, or when slow recovery occurs. This tendency is an indirect effect. If we sterilize venom,—that is, subject it to dry heat until all germs are destroyed,-- and leave it then in contact with sterilized soup guarded from the germs afloat in the air, no putrefaction ensues; but if to this sterilized broth we add venom not so deprived of bacterial germs, putrefaction is hastened at a rate never seen under other circumstances.
Now, as bacteria are always present in fresh venom, enough enter a wound to account for the fact that animals envenomed swarm within an hour or two with the organisms which cause putrefaction. Their rate of increase is inconceivably great, and seems to be favored by the poison, which provides them with some mysterious conditions of growth. Thus it is that the blood, the nervous centers, the vessels, are all in turn attacked by these fearfully destructive poisons, and that at last putrescent changes may be added to the causes of a multiform group of perplexing phenomena.
The general reader will ask what good has come out of these clearer views as to the mechanism of this poisoning. Our own labors and the brilliant work of Fayrer, Lauder-Brun
ton, Wall, and Vincent Richards have certainly brought us somewhat more plainly to understand that which happens. What gain is there for man? As yet there is little, except that, while a few years ago we were merely groping for remedies, to-day we are in a position to know with some definiteness what we want and what we do not want.
Let us see what the actual present gain is. If we mix any venom with a strong enough solution of potassa or soda we destroy its power to kill. A solution of iodine or perchloride of iron has a like, but a lesser capacity, and so also has bromohydric acid; but by far the best of all, as was first shown by Lacerda, is permanganate of potash. If this agent be injected at once or soon through a hollow needle into the fang wound, wherever it touches the venom it destroys it. It also acts in like destructive fashion on the tissues; but, relatively speaking, this is a small matter. If at once we can cut off the circulation by a ligature and thus delay absorption and then use permanganate freely, we certainly lessen the chances of death; yet, as the bites occur usually when men are far from such help, it is but too often a futile aid, although it has certainly saved many lives. The first effect of venom is to lessen suddenly the pressure under which the blood is kept while in the vessels. Death from this cause must be rare, as it is active for so short a time. Any alcoholic stimulus would at this period be useful; but, despite the popular creed, it is now pretty sure that many men have been killed by the alcohol given to relieve them from the effects of snake bite, and it is a matter of record that men dead drunk with whisky and then bitten have died of the bite. For the consequences to the blood and to the nerve centers which follow an injection of venom there is, so far as I am aware, no antidote; but as to this I do not at all despair, and see clearly that our way to find relief is not by stupid trials of this sort and that, but by competently learning what we have to do. Moreover, we are in a position at present to say what not to do, and there is a large measure of gain in being able to dismiss to the limbo of the useless a host of so-called antidotes.
and although in its effects so unlike the albumens which make our tissues and circulate in the blood, it is yet so like these in composition that whatever alters it destructively is pretty sure to affect them in like fashion. Hence the agents which do good locally at some cost to the tissues are worse than valueless when sent after the venom into the circulating blood. Yet, possibly, we may hope to find remedies which will stimulate and excite the vital organs which venom enfeebles. In this direction lie our hopes of further help. Anything which delays the fatal effect of the poison is also a vast advantage in treatment, because there are agencies at work which seem to be active in renewing the blood and repairing the damage done to the tissues, so that recoveries are sometimes remarkably abrupt. It is possible that free bleeding followed by transfusion of healthy blood may prove efficient.
I am often asked what I would do if bitten while far from help. If the wound be at the tip of a finger, I should like to get rid of the part by some such prompt auto-surgical means as a knife or a possible hot iron affords. Failing these, or while seeking help, it is wise to quarantine the poison by two ligatures drawn tight enough to stop all circulation. The heart weakness is made worse by emotion, and at this time a man may need stimulus to enable him to walk home. As soon as possible some one should thoroughly infiltrate the seat of the bite with permanganate or other of the agents above mentioned. By working and kneading the tissues the venom and the antidote may be made to come into contact, and the former be so far destroyed. At this time it becomes needful to relax the ligatures to escape gangrene. This relaxation of course lets some venom into the blood-round, but in a few moments it is possible again to tighten the ligatures, and again to inject the local antidote. If the dose of venom be large and the distance from help great, except the knife or cautery little is to be done that is of value. But it is well to bear in mind that in this country a bite in the extremities rarely causes death. I have known of nine dogs having been bitten by as many snakes and of these dogs but two died. In India there would have been probably nine