1. _On the Action of Poisons through Sympathy._ In the infancy of

toxicology all poisons were believed to act through sympathy. Since Magendie’s discoveries on venous absorption in 1809, the favourite doctrine has on the other hand been, that most, if not all, act through the medium of the blood. And a recent theory, combining both views, represents that, although many poisons do enter the blood, the operation even of these nevertheless consists of an impression made on the sentient extremities of the nerves of the blood-vessels and conveyed thence along their filaments to the brain or other organs. The nerves certainly possess the power of conveying from one organ to another various impressions besides those of the external senses. This is shown by many familiar phenomena; and in reference to the present subject, is aptly illustrated by the remote or sympathetic effects of mere mechanical injury and natural disease of the stomach. Acute inflammation of the stomach generally proves fatal long before death can arise from digestion being stopped; and it is accompanied with constitutional symptoms, neither attributable to injury of that function, nor developed in so marked a degree during inflammation in other organs. These symptoms and the rapid death which succeeds them are vaguely imputed to the general system sympathizing with the affected part; but it is more probable that one organ only is thus, at least in the first instance, acted on sympathetically, namely, the heart. The effects of mechanical injuries are still more in point. Wounds of the stomach may prove fatal before inflammation can begin; rupture from over-distension may cause instant death; and in either case without material hemorrhage. These observations being held in view, it is impossible to doubt, that some organs sympathize with certain impressions made on others at a distance; nor can we imagine any other mode of conveyance for these impressions except along the nerves. The question, then, comes to be what are the impressions that may be so transmitted? The statements already made will prepare us to expect a sympathetic action in the case of poisons that manifestly injure the structure of the organ to which they are applied. In the instance of the pure corrosives its existence may be presumed from the identity of the phenomena of their remote action with those of natural disease or mechanical injury. It was stated above that the mineral acids when swallowed often prove fatal in a very short space of time; and here, as in mere injury from disease or violence, the symptoms are an imperceptible pulse, fainting, and mortal weakness. Remote organs therefore must be injured; and from the identity of the phenomena with those of idiopathic affections of the stomach, even if there were no other proof, it might be presumed that the primary impression is conveyed along the nerves. We are not restricted, however, to such an argument: The presumptive inference is turned to certainty by the effect of dilution on the activity of these poisons. Dilution materially lessens or even takes away altogether the remote action of the mineral acids. Now dilution facilitates, instead of impeding their absorption: consequently they do not act on remote organs through that channel. There is no other way left by which we can conceive them to act, except by conveyance of the local impression along the nerves.—As to the irritants that are not corrosive, it can hardly be doubted, since they inflame the stomach, that the usual remote effects of inflammation will ensue, namely, a sympathetic injury of distant organs. But it remains to be considered, whether distant organs may sympathize also with the peculiar local impressions called nervous,—which are not accompanied by any visible derangement of structure. This variety of action by sympathy is the one which has chiefly engaged the attention of toxicologists; and it has been freely resorted to for explaining the effects of many poisons. Nevertheless its existence is doubtful. The only important arguments in support of the sympathetic action of poisons are, that unequivocal instances exist of local nervous impressions being conveyed to a limited extent along the nerves,—and that the rapidity of the effects of some poisons is so great as to be incompatible with any other medium of action except the nervous system. In the first place it is maintained, that a limited nervous transmission, that is, the conveyance of a local impression, purely functional in its nature, to parts at a short distance from the texture acted on directly, must occur in some instances,—as, for example, in the action of belladonna in dilating the pupil when applied to the conjunctiva of the eye, and in the effect of opium in allaying deep-seated pain when applied to the integuments over the affected part. It is by no means clear, however, that nervous transmission is in such circumstances the only possible medium of action; and that the phenomena may not as well be owing to the agent being conveyed in substance, by imbibition or absorption, to the parts ultimately acted on. It is not unworthy of remark too, that in the case of hydrocyanic acid,—a poison, which, more perhaps than any other, has been held to act by sympathy, and which produces on the integuments a direct local impression of a peculiar and unequivocal kind,—there is positive evidence of the direct impression not being conveyed along the nerves, even to the most limited distance; for I have not been able to observe the slightest effect beyond the abrupt line on the skin which defines the spot with which the acid had been in contact. Secondly, it is thought that certain poisons, such as hydrocyanic acid, strychnia, alcohol, conia, and some others, produce their remote effects with a velocity, which is incompatible with any conceivable mode of action except the transmission of a primary local impulse along the nerves, and more especially incompatible with the poison having followed the circuitous route of the circulation to the organs which are affected by it remotely. Thus in regard to the hydrocyanic acid, Sir B. Brodie has stated,[8] that a drop of the essential oil of bitter almonds, which owes its power to this acid, caused convulsions instantly when applied to the tongue of a cat; and that happening once to taste it himself, he had scarcely applied it to his tongue, when he felt a sudden momentary feebleness of his limbs, so that he could scarcely stand. Magendie,[9] speaking of the pure hydrocyanic acid, compares it in point of swiftness of action to the cannon ball or thunderbolt. In the course of certain experiments made not long ago with the diluted acid by Dr. Freer, Mr. Macaulay and others,[10] to decide the true rapidity of this poison, several dogs were brought under its influence in ten, eight, five, and even three seconds; during an experimental inquiry I afterwards undertook for the same purpose,[11] I remarked on one occasion that a rabbit was killed outright in four seconds; and Mr. Taylor has more recently stated, that he has seen the effects induced so quickly in cats, that there was no sensible interval of time between the application of the poison to the tongue and the first signs of poisoning.[12] Strychnia, the active principle of nux-vomica, acts sometimes with a speed little inferior to that of hydrocyanic acid; for Pelletier and Caventou have seen its effects begin in fifteen seconds.[13] Alcohol, according to Sir B. Brodie,[14] also acts on animals with equal celerity; for when he introduced it into the stomach of a rabbit, its effects began when the injection was hardly completed. Conia, the active principle of hemlock, is not less prompt in its operation: when it was injected in the form of muriate into the femoral vein of a dog, I was unable, with my watch in my hand, to observe an appreciable interval between the moment it was injected and that in which the animal died;[15] certainly the interval did not exceed three or at most four seconds. Facts such as these have been long held adequate to prove that some poisons must act on remote organs by sympathy or transmission of a local impulse along the nerves; and in the last edition of this work they were acknowledged to warrant such a conclusion. It was thought difficult to account for the phenomena on the supposition that the poison was conveyed in substance with the blood to the organ remotely affected by it; for it appeared impossible that, in so short a space of time as elapsed in some of the instances now referred to, the poison could enter the veins of the texture to which it was applied, pass into the right side of the heart, follow the circle of the pulmonary circulation into the left side of the heart, and thence be transmitted by the arterial system to the capillaries of the organ ultimately affected. But the progress of physiological discovery has lately brought the soundness of these views into question. Some years ago Dr. Hering of Stuttgardt showed that the round of the circulation may be accomplished by the blood much more speedily than had been conceived before; for the ferro-cyanide of potassium, injected into the jugular vein of a horse, was discovered by him throughout the venous system at large in the short space of twenty or thirty seconds, and consequently must have passed in that period throughout the whole double circle of the pulmonary and systemic circulation.[16] This discovery at once shook the validity of many, though not all, of the facts which had been previously referred to the agency of nervous transmission on the ground of the celerity with which the effects of poisons are manifested. More recently an attempt has been made by Mr. Blake to prove, that the circulation is so rapid as to admit even of the swiftest cases of poisoning being referred to the agency of absorption. Mr. Blake, who is altogether opposed to the occurrence of nervous transmission in the instance of any poison, has found that ammonia, injected into the jugular vein of a dog, was indicated in its breath in four seconds; and that chloride of barium or nitrate of baryta, introduced into the same vessel, could be detected in the blood of the carotid artery in about sixteen seconds in the horse, in less than seven seconds in the dog, in six seconds in the fowl, and in four seconds in the rabbit.[17] These interesting discoveries, however, will not absolutely destroy the conclusiveness of all the facts quoted above in support of the existence of a sympathetic action. For example they do not shake the validity of those observations, in which it appeared that an interval inappreciable, or barely appreciable, elapsed between the application and action of hydrocyanic acid and of conia. Mr. Blake indeed denies the accuracy of these observations, insisting that, in those he made himself with the most potent poisons, he never failed to witness, before the poison began to act, an interval considerably longer than what had been observed by others, and longer also than what he had found sufficient for the blood to complete the round of the circulation; that, for example, the wourali poison injected into the femoral or jugular vein did not begin to act for twenty seconds, conia and tobacco for fifteen seconds, and extract of nux vomica for twelve seconds; and that hydrocyanic acid dropped on the tongue did not act for eleven seconds if the animal was allowed to inhale its vapour, and not for sixteen seconds, if direct access to the lungs was prevented by making the animal breathe through a tube in the windpipe. But Mr. Blake cannot rid himself thus summarily of the positive facts which stand in his way. Duly weighed, the balance of testimony is in favour of those whose accuracy he impugns. For in the first place, they had not, like him, a theory to build up with their results, but were observing, most of them at least, the simple fact of the celerity of action. Then, their result is an affirmation or positive statement, and his merely a negative one: They may perfectly well have observed what he was not so fortunate as to witness. And lastly, it is not unreasonable to claim for Sir B. Brodie, Dr. Freer, Mr. Macaulay, and Mr. Taylor, all of them practitioners of experience, the faculty of noting time as accurately as Mr. Blake himself. As for my own observations, I feel confident they could not have been made more carefully, and that I had at the moment no preconceived views which the results upheld, but, if anything, rather the reverse. It is impossible therefore to concede, that Mr. Blake’s inquiries, merely because they are at variance with prior results, apparently not less precise and exact than his own, put an end to the argument which has been drawn, in favour of the existence of a sympathetic action, from the extreme swiftness of the operation of some poisons. At the same time, on a dispassionate view of the whole investigation, it must be granted to be doubtful, whether this argument can be now appealed to in its present shape with the confidence which is desirable. And on the whole, the velocity of the circulation on the one hand, and the celerity of the action of certain poisons on the other, are both of them so very great, and the comparative observation of the time occupied by the two phenomena respectively becomes in consequence so difficult and precarious, that it seems unsafe to found upon such an inquiry a confident deduction on either side of so important a physiological question as the existence or non-existence of an action of poisons by sympathy. In concluding these statements it is necessary to notice certain positive arguments which have been brought against the doctrine of nervous transmission. It is alleged to be contrary to nature’s rule to adopt two ways of attaining the same end; and therefore, that, since many poisons undoubtedly act through absorption, it is unphilosophical to hold that others act by sympathy. There seems no sound reason, however, for thus imposing arbitrary limits on the functional powers conferred by nature on the organs of the animal body. And besides, the presumption thus derived is counterbalanced by the equally plausible supposition, that,—since nature has clearly established an action on remote organs through the medium of the nerves in the case of poisons which cause destruction or inflammation of the tissues to which they are applied,—the same medium of action may also exist in the instance of poisons which produce merely a peculiar nervous impression where they are applied. But it is farther alleged, that poisons of the most energetic action have no effect, when they are applied to a part, the connection of which with the general system is maintained by nerves only. It is true that poisons seem to have no effect whatever when the circulation of the part to which they are applied has been arrested, or when every connecting tissue has been severed except the nerves. Thus Emmert found that the wourali poison does not act on an animal when introduced into a limb connected with the body by nerves alone.[18] And I have ascertained that in the same circumstances no effect is produced on the dog by pure hydrocyanic acid dropped into the cellular tissue of the paw. But it cannot be inferred absolutely from these facts, that the wourali poison and hydrocyanic acid do not act through sympathy; because it has been urged that the integrity of the functions of the sentient extremities of the nerves, more especially their capability of receiving those nervous impressions which are held to be communicated backwards along their course, may be interrupted by arresting the circulation of the part. Still, as the function of sensation is maintained for some time in a severed limb connected with the trunk by nerves only, there is a probability, that all other functions of the nerves must be retained for a time also. And the presumption thus arising is strengthened by an imperfect experiment performed by Mr. Blake, which tends to show, although it does not absolutely prove, that a poison, introduced into the severed limb whose nervous connection with the trunk is entire, will not act, even if the blood be allowed to enter the limb by its artery and to escape from a wound in its vein, so that local circulation is in some measure maintained, without the blood returning to the trunk and general system.[19] On considering impartially all the facts that have been adduced in this inquiry, an impression must be felt that the doctrine of the sympathetic action of those poisons which produce merely a nervous local impression is insecurely founded. But an _experimentum crucis_ is still wanted to decide the question.