CHAPTER I.

ON THE PHYSIOLOGICAL ACTION OF POISONS.

I shall discuss this subject by considering first the mode in which poisons act, and secondly, the causes by which their action is liable to be modified.

SECTION I.—_On the Mode of Action of Poisons._

On attending to the effects which follow the application of a poison to the body, we perceive that they are sometimes confined to the part where it is applied, and at other times extend to distant organs. Hence the action of poisons may be naturally considered as _local_ and _remote_.

The local effects of poisons are of three kinds. Some decompose chemically or corrode the part to which they are applied. Others, without immediately injuring its organization, inflame or irritate it. Others neither corrode nor irritate, but make a peculiar impression on the sentient extremities of the nerves, unaccompanied by any visible change of structure.

We have examples of local _corrosion_ or chemical decomposition in the effects of the concentrated mineral acids or alkalis on the skin, and in the effects of strong oxalic acid, lunar caustic, or corrosive sublimate on the stomach. In all of these instances the part to which the poison is applied undergoes chemical changes, and the poison itself sometimes undergoes chemical changes also. Thus oxalic acid dissolves the gelatin of the animal textures; and in the instance of corrosive sublimate, the elements of the poison unite with the albumen, fibrin, and other principles of the tissues.

Of local _irritation_ and its various consequences we have many examples, from redness, its slightest, to ulceration and gangrene, its most severe effect. Thus externally, alcohol reddens the skin; cantharides irritates the surface of the true skin and causes vesication; tartar-emetic causes deep-seated inflammation of the true skin and a pustular eruption; the juice of manchineel[1] spreading inflammation of the subcutaneous cellular tissue; arsenic inflammation of all these textures, and also death of the part and subsequent sloughing. Internally, alcohol reddens the stomach, as it does the skin,—but more permanently; while other substances, such as the diluted mineral acids, arsenic, cantharides, euphorbium, and the like, may cause all the phenomena of inflammation in the stomach and intestines, namely, extravasation of blood, effusion of lymph, ulcers, gangrene. Many of these irritants, such as arsenic, are in common speech called corrosives; but they have not any power of causing chemical decomposition: if they produce a breach in the texture of an organ, it is merely through the medium of inflammation and its effects.

Of _nervous impressions_, without any visible organic change, few well authenticated and unequivocal instances are known. A good example has been mentioned by Sir B. Brodie in the effect of monkshood on the lips when chewed,[2] an effect which I have also often experienced: it causes a sense of numbness and tingling in the lips and tongue, lasting for some hours, and quite unconnected with any affection of the general nervous system. Another instance, first mentioned to me by M. Robiquet, and which I have verified, occurs in the effects of the strong hydrocyanic acid: when this acid is confined in a glass tube with a finger on its open end, the point of the finger becomes benumbed, exactly as from the local action of great cold. These are undoubted instances of a purely nervous local impression on the external surface of the body. The most unequivocal instance I know of a similar impression on internal parts is a fact related by Dr. W. Philip with regard to opium.[3] When this poison was applied to the inner coat of the intestines of a rabbit during life, the muscular contractions of the gut were immediately paralyzed, without the general system being for some time affected. The same effect has been observed by Messrs. Morgan and Addison to follow the application of ticunas to the intestine:[4] an instant and complete suspension of the peristaltic movement took place as soon as it touched the gut. A parallel fact has also been described by Dr. Monro, _secundus_:[5] when an infusion of opium was injected between the skin and muscles of the leg of a frog, that leg soon became palsied, while the animal was able to leap briskly on the other three. Analogous results have farther been obtained with the prussic acid by M. Coullon.[6] He remarked, that when one hind-leg of a frog was plunged in the acid, it became palsied in thirty-five minutes, while the other hind-leg continued perfectly sensible and irritable. Acetate of lead probably possesses the same property.

These facts are important, because some physiologists have doubted whether any local impressions of a purely nervous nature, unconnected with appreciable organic change, may arise from the action of poisons. Yet the existence of impressions of the kind is essential to the stability of the doctrine of the sympathetic operation of poisons,—that is, of the transmission of their influence from organ to organ along the nerves. Nay, in the instance of many poisons supposed to act in that manner, we must still farther believe in the existence of primary nervous impressions, which are not only unconnected with organic change, but likewise undistinguishable by any local sign whatsoever.

Of the three varieties in the local effects of poisons—corrosion, irritation, and nervous impressions,—the first two may take place in any tissue or organ; for example, they have been observed on the skin, on the mucous membrane of the stomach, intestines, windpipe, air tubes, bladder, and vagina, in the cellular tissue, in the serous membranes of the chest and abdomen, in the muscular fibre. We are not so well acquainted with the nature of local nervous impressions on different tissues; but it is probable that in some textures of the body they are very indistinct.

So much for the local effects of poisons.

On tracing the phenomena which follow more remotely, we observe that the affected part sometimes recovers without any visible change, sometimes undergoes the usual processes consequent on inflammation, sometimes perishes at once and is thrown off; and if the organ is one whose function is necessary to life, death may gradually ensue, in consequence of that function being irrecoverably injured. The purest example of the last train of phenomena is to be seen in the occasional effects of the mineral acids or alkalis: death may take place simply from starvation, because the inner surface of the stomach and intestines is so much injured that a sufficient quantity of nutriment cannot be assimilated.

But death and its antecedents can seldom be accounted for in this way. For symptoms are often witnessed, which bear no direct relation to the local injury: death is generally too rapid to have arisen from the function of the part having been annihilated: and the rapidity of the poisoning is not proportional in different cases to the local injury produced. Even the mineral acids and alkalis seldom kill by impeding or annihilating digestion, because they often prove fatal in a few hours; and among other poisons there are few which ever cause death simply by disturbing the function of the part primarily acted on. Death and the symptoms preceding it arise from an injury of some other organ, to which they are not and cannot be directly applied. We are thus led to consider their remote action.

The term _remote_ is here used in preference to the common phrase _general_ action, because the latter implies an action on the general system or whole body; whereas it appears that an action of such a kind is rare, and that most poisons which have an indirect action exert it on one or more of the important organs only, and not on the general system.

There is not a better instance of the remote action of poisons than oxalic acid. It has been already mentioned that concentrated oxalic acid is a corrosive: yet it never kills by destroying the function of the stomach. Man, as well as the lower animals, will live several days or weeks without nutriment. Now this poison has been known to kill a man in ten minutes, and a dog in three minutes only. Neither does it always induce, when swallowed, symptoms of an injury of the stomach; for death is often preceded by tetanus, or apoplexy, or mortal faintness. Nor is the violence of the poisoning proportional to the extent of the local injury: in fact, death is most rapid under circumstances in which the stomach is least injured, namely, when the acid is considerably diluted.[7]

Let us now proceed to enquire, then, in what way the influence of a poison is conveyed from one organ to another.

Here it will at once be perceived that the conveyance can be accomplished in one of two ways only. Either the local impression passes along the nerves to the organ secondarily affected; or the poison enters the bibulous vessels, mingles with the blood, and passes through the medium of the circulation. In the former way poisons are said to act through _sympathy_, in the latter, through _absorption_.

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.

2. _Of the Action of Poisons through Absorption._—If doubts may be entertained whether poisons ever act by the transmission of local impulses, from the part to which they are applied, along the nerves to the organ upon which they act, no reasonable doubt can be entertained that many poisons act through the medium of absorption into the blood.

Poisons are believed to act through the blood for the following reasons. First, they disappear during life from the shut cavities or other situations into which they have been introduced; that is, they are absorbed. Several clear examples to this effect have been related by Dr. Coindet and myself in our paper on oxalic acid. In one experiment four ounces of a solution of oxalic acid were injected into the peritoneal sac of a cat, and killed it in fourteen minutes; yet, on opening the animal, although none of the fluid had escaped by the wound, we found scarcely a drachm remaining.[20] In recent times Professor Orfila has proved that various poisons, such as arsenic, tartar-emetic, and acetate of lead, disappear in part or wholly from wounds into which they had been introduced.[21] Next, many poisons act with unimpaired rapidity, when the nerves supplying the part to which they are applied have been previously divided, or even when the part is attached to the body by arteries and veins only. Dr. Monro, _secundus_, proved this in regard to opium;[22] and the same fact has been since extended by Sir B. Brodie and Professor Emmert to wourali,[23] by Magendie to nux vomica,[24] by Coullon to hydrocyanic acid,[25] by Charret to opium,[26] and by Dr. Coindet and myself to diluted oxalic acid.[27] Magendie’s experiment was the most precise of all: for, besides the communication with the poisoned part being kept up by a vein and an artery only, these vessels were also severed and reconnected by two quills. Farther, many poisons will not act when they are applied to a part of which the circulation has been arrested, even although all its other connections with the body have been left entire. This has been shown distinctly by Emmert in regard to the hydrocyanic acid; which, when introduced into the hind-leg of an animal after the abdominal aorta has been tied, produces no effect till the ligature be removed, but then acts with rapidity.[28] An experiment of a similar nature performed by Mr. Blake with the wourali poison yielded the same result.[29] Again, many poisons act with a force proportional to the absorbing power of the texture with which they are placed in contact. This is the criterion which has been commonly resorted to for discovering whether a poison acts through the medium of the blood. It is applicable, however, only when the poison acts sensibly in small doses; for those which act but in large doses cannot be applied in the same space of time over equal surfaces of different textures. The difference in the absorbing power of the different tissues has been well ascertained in respect to a few of them only. The most rapid channel of absorption is by a wound, or by immediate injection into a vein; the surface of the serous membranes is a less rapid medium, and the mucous membrane of the alimentary canal is still less rapid. Now it is proved of many poisons that, when applied in similar circumstances to these several parts or tissues, their activity is proportional to the order now laid down. Lastly, it has been proved of nux-vomica, that if the extract be thrust into the paw of an animal after a ligature has been tightened round the leg so as to stop the venous, but not the arterial circulation of the limb, blood drawn from an orifice in a vein between the wound and the ligature, and transfused into the vein of another animal, will excite in the latter the usual effects of the poison, so as even to cause death; while, on the contrary, the animal from which the blood has been taken will not be affected at all, if a sufficient quantity be withdrawn before the removal of the ligature. These interesting facts, which are capable of important practical applications, were ascertained by M. Vernière.[30]

On weighing attentively the arguments here brought forward, it seems impossible to doubt, that some poisons are absorbed into the blood before they act, and that their entrance into the blood is not a mere fortuitous antecedent, but a condition essential to their action.

But it is farther held that poisons which act through absorption, do so by being conveyed in substance along with the blood to the part where their action is developed,—that their action eventually depends on the organ, whose functions are thrown into disorder, becoming impregnated with poisoned blood. Now, the arguments detailed above do not absolutely prove this conveyance and impregnation. They show that poisons enter the blood, and act somehow in consequence of entering it; but they do not prove in what manner the action subsequently takes place.

It was at one time indeed supposed that the same facts, which prove their admission into the blood, proved also their transmission in substance to the organs acted on by them. But Dr. Addison and Mr. Morgan have shown that this is not a legitimate conclusion, and that a different theoretical view may be taken of the facts,—namely, that the action may really take place by the poison producing on the sentient extremities of the nerves of the inner membrane of the blood-vessels a peculiar impression which is conveyed through the nerves to the part ultimately affected.[31] They have endeavoured to found this theory upon evidence, that the poison is not carried beyond the venous system; or that, if conveyed farther, it is carried incidentally, and not for the purpose of impregnating the textures of the organ which suffers. The evidence they have brought forward on this head is chiefly the following. 1. Poisons which act on a particular organ at a distance do not act more quickly when introduced into the artery which supplies it, than when introduced into its vein, or even into the principal artery of a distant part of the body.[32] 2. If a poison be introduced into a great vein with a provision for preventing its passage towards the heart, it will act with as great rapidity, as if no obstacle of the kind existed. Thus, if the jugular vein, secured by two temporary ligatures, be divided between them and reconnected by a tube containing wourali, the animal will not be affected more quickly on the removal of both ligatures, than on removing only the ligature farthest from the heart.[33] 3. The arterial blood of a poisoned animal is incapable of affecting another animal. Thus, if the carotid artery and jugular vein of one dog be divided, and both ends of each reciprocally connected by tubes with the divided ends of the corresponding vessels of another dog, and extract of nux-vomica be introduced into a wound in the face of one of them,—the animal directly poisoned alone perishes, and the other remains unharmed to the last.[34]

These are at first view strong arguments against the transmission of poisons with the blood to the organs remotely acted on; and the facts on which they are founded are on the other hand easily explained under the new theory advanced by the authors, that the medium of action is the nerves which supply the inner membrane of the blood-vessels. But their inquiries, however ingenious and plausible, have not stood the test of physiological scrutiny. Their first experimental fact has been contradicted by Mr. Blake; who has found that the wourali poison, which does not begin to act for twenty seconds when injected into a vein, will produce obvious effects in seven seconds only if injected into the aorta through the axillary artery.[35] The second experiment, showing that poison confined in a vein will act although prevented by a ligature from reaching the heart, is held by the opponents of Dr. Addison and Mr. Morgan to be fallacious, in as much as the blood behind the ligature may be carried backwards till it meets with an anastomosing vein and is so carried by a collateral vessel to the heart. To the third experiment it may be objected, that there was, in the mode in which they conducted it, no satisfactory evidence that the reciprocal circulation was kept up by the carotid artery and jugular vein. And this will appear an important objection to every one practically acquainted with experiments of transfusion. For on the one hand it is exceedingly difficult, in such complicated experiments, to prevent coagulation of the blood in one vessel or another, before the connection of all the arteries and veins is established; and on the other, it may be urged, as Mr. Blake has done, that the pressure of the blood in the distal end of the carotid artery in the animal not directly poisoned may be equal, or even superior, to the pressure in the proximal end of the same vessel in the other animal,—so that the blood may not pass from the latter into the former, although it should continue fluid.

In opposition to the theory of Dr. Addison and Mr. Morgan, and in support of the doctrine, that poisons act by being carried in substance with the blood into the tissues of the remote organs on which they act, a variety of important experimental evidence has been brought forward since the publications of the Essay of these gentlemen. In the first place, the concurrent testimony of a great number of recent chemical inquirers establishes undeniably, that poisons absorbed into the veins of the part to which they are applied are to be detected throughout many of the tissues of distant organs. This fact will be enlarged on and illustrated presently. Secondly, on the authority of Mr. Blake, and in contradiction of the experiments of Dr. Addison and Mr. Morgan, it appears that, as already stated, poisons act more quickly when injected into the aorta than into the venous system; a fact which is easily understood, on considering that when injected into the aorta they reach their destination directly, whereas, if injected into a vein they must first arrive at the right side of the heart, and then be transmitted through the circle of the pulmonary circulation before reaching even the aorta. Thirdly, the relative rapidity with which poisons act on different animals follows the ratio of the velocity of the circulation in each. Thus, Mr. Blake found, that in the horse nitrate of baryta is conveyed by the circulation from the jugular vein to the carotid artery in sixteen seconds, and that strychnia injected into the jugular vein begins to act on the nervous system after exactly the same interval: That in the dog chloride of barium passes from the vein to the artery in seven seconds, and extract of nux-vomica begins to act as a poison in twelve seconds: That in the fowl the passage of the blood seems to take place in six seconds, and the nitrate of strychnia to act in six seconds and a half: And that in the rabbit the passage of the blood is effected in four seconds only, and the first signs of the action of strychnia occur in four seconds and a half.[36]

On the whole, then, it may be considered as well established, that probably all, but certainly some, poisons,—of the kind whose topical action does not consist in causing destruction or inflammation of the textures to which they are applied,—produce their remote effects solely by entering the blood, and through its means impregnating the organs which are acted on at a distance. And farther, if this doctrine be admitted as established, it may also be allowed, that many poisons which do cause topically destruction or inflammation, and remotely the usual sympathetic effects of these changes of structure, also possess the power of affecting distant organs through the medium of the blood.

_Of the discovery of Poisons in the Blood._—Such being the case, it becomes an object of paramount interest, with reference both to the practice of medical jurisprudence, to inquire whether poisons can be detected in the circulating fluids, or generally in parts of the body remote from the place where they are introduced.

A variety of circumstances long rendered it impossible to determine satisfactorily the question, whether poisons could be detected in the blood, the secretions, and the soft textures of the body. In the first place, we now know that the quantity of the more active poisons, which is required to occasion death, is so small, that, considering the crude methods of analysis formerly trusted to, and the obstacles opposed to the successful application of them by the presence of organic matter, there can be no wonder that chemists, even but a few years ago, could not satisfy themselves whether the objects they were in search of had been detected or not. Then, it was partly known before, and is now fully established, that various poisons are removed beyond the reach of analysis before death, in consequence of passing off with the secretions, particularly the urine. Farther, it seems probable that, of the poisons which act through absorption, several do not remain or at least do not accumulate, in the blood; and that they are not distributed with it throughout the textures indifferently, but are deposited, as absorption goes on, in particular organs, such as the liver,—which it was not much the practice to examine in former investigations. And lastly, some poisons are speedily decomposed on entering the blood: They either cause obvious changes in the constitution of the blood, and themselves undergo alteration likewise; or without the blood becoming appreciably different in its properties from the healthy state, the poison undergoes a rapid change in the molecular affinities of its elements, and so disappears. Of the former course of things distinct illustrations are furnished by nitric oxide gas and sulphuretted-hydrogen gas when injected into a vein in a living animal: of the latter an equally unequivocal example occurs in oxalic acid, which Dr. Coindet and I found to be undiscoverable in the blood of the vena cava of a dog killed in thirty seconds by the injection of eight grains and a half of it into the femoral vein.

But the improvements that have been lately made in the methods of analysis for the detection of poisons in a state of complex mixture with organic substances have done away with a great part of the obstacles which prevented a thorough inquiry as to the existence of poisons in the blood and textures of the body. Some important researches of this kind were referred to in the last edition of the present work; and since then many additional facts, of equal variety and precision, have been communicated by different observers, but especially by Professor Orfila. Under the head of each poison an account will be given hereafter of the evidence in support of the discovery of it by chemical analysis in the blood, textures, and excretions. In the present place it is sufficient to state in general terms that the evidence is quite satisfactory in the instances of iodine, sal-ammoniac, oxalic acid, nitre, sulphuret of potassium, arsenic, mercury, copper, antimony, tin, silver, zinc, bismuth, lead, hydrocyanic acid, cyanide of potassium, carbazotic acid, sulphuretted-hydrogen, camphor, and alcohol.

_Of the Organs affected by the remote action of Poisons._—Having now taken a general view of the mode in which poisons act on distant parts, I shall next consider what organs are thus brought under their operation. Poisons have been often, but erroneously, said to affect remotely the general system. A few of them, such as arsenic and mercury, do indeed appear to affect very many organs of the body. But by much the larger proportion seem on the contrary to act on one or more organs only, not on the general system.

Of the poisons which act remotely through a sympathy of distant parts with an organic injury of the textures directly acted on, many appear to act sympathetically on the heart alone. Taking the mineral acids as the purest examples of poisons that act independently of absorption into the blood-vessels, it will be seen on inquiry that all the symptoms they produce, in addition to the direct effects of the local injury, are those of depressed action of the heart,—great feebleness, fainting, imperceptible pulse, cold extremities. Even the less prominent of the secondary symptoms are almost all referrible to a depressed state of the circulation. In particular, they are not necessarily, and indeed are seldom actually, blended with any material symptom of disorder in the brain; which certainly could not be the case if the general or whole system suffered.

With respect to that more numerous class, which act remotely either through the medium of the blood or by the transmission along the nerves of an undiscernible impression made on their sentient extremities, some certainly possess a very extended influence over the great organs of the body; but the greater number are much more limited in their sphere of action. Some act chiefly by enfeebling or paralyzing the heart, others principally by obstructing the pulmonary capillaries, others by obstructing the capillaries of the general system, others by stimulating or depressing the functions of the brain or of the spinal cord, others by irritating the alimentary canal, others by stimulating one or another of the glandular organs, such as the salivary glands, the liver, the kidneys, or the lymphatic glands.

Some poisons of this kind act chiefly, if not solely, on the _heart_. The best examples are infusion of tobacco, and upas antiar. Sir B. Brodie observed, that when the infusion of tobacco was injected into any part of the body, it speedily caused great faintness and sinking of the pulse; and on examining the body instantly after death, he found the heart distended and paralyzed, not excitable even by galvanism, and its aortal cavities filled not with black, but with florid blood, while the voluntary muscles were as irritable as after other kinds of death.[37] The upas antiar he found to be similarly circumstanced.[38] Arsenic and oxalic acid are also of this kind. In an animal killed by arsenic, and in which the gullet and voluntary muscles continued long contractile, Dr. Campbell found the heart immediately after death containing arterial blood in its aortal cavities, and insensible to galvanism.[39] Dr. Coindet and I frequently witnessed the same facts in animals killed with oxalic acid: When the heart at the moment of death was completely palsied and deprived of irritability, we saw the intestines moving, and the voluntary muscles contracting long and vigorously from the mere contact of the air.[40]

An interesting series of investigations has been lately made by Mr. Blake, relative to the influence of poisons on the heart, when they are directly introduced into the great veins. It does not absolutely follow that an action on the heart manifested in this way proves the occurrence of a similar action when the substance is admitted into the body through more ordinary channels, such as the stomach, intestines or cellular tissue. For on the one hand, some of the substances used by this physiologist cannot be admitted into the blood through ordinary channels in the quantity necessary for developing that action on the heart, which is excited when they are injected at once into the blood-vessels. And on the other hand, the results at which he thus arrives are not always in conformity with what have been obtained by prior observers, who resorted to the ordinary channels for introducing poisons into the body. It is possible, therefore, that Mr. Blake’s researches may not have the extensive bearings, which might at first sight appear, on the physiology of poisons and remedies. Nevertheless they are in themselves full of interest. They show that the salts of magnesia, zinc, copper, lime, strontia, baryta, lead, silver, ammonia, and potash, also oxalic acid, and digitalis, if injected into the jugular vein, produce a powerful and permanent depression of the heart’s action; which is evinced by the hæmadynamometer,[41] indicating diminution of pressure in the great arteries, by the heart becoming motionless or nearly so before the breathing ceases, by its muscular structure presenting little or no irritability when stimulated immediately after death, and by the left cavities being found full of florid arterial blood.[41]

Other poisons act on the _lungs_; but probably few, perhaps none, act on them alone. Magendie found that in poisoning with tartar-emetic the lungs are commonly inflamed and sometimes even hepatized.[42] Mr. Smith and M. Orfila both remarked similar signs of pulmonary inflammation in animals poisoned with corrosive sublimate.[43] But these poisons produce important effects on other organs likewise.

A set of novel and important facts setting forth the frequent operation of poisons on the lungs when they are admitted directly into the blood, has been recently brought to light by the researches of Mr. Blake. Many of the poisons mentioned above as acting powerfully on the heart were found by him not to exert any influence upon the lungs, such as oxalic acid and the salts of magnesia, lime, zinc, copper, ammonia, potash, and strychnia. Others, however, such as the salts of strontia, baryta, lead, and silver, as well as digitalis, all of which powerfully affect the heart, and, in addition to these, the salts of soda, which have no action at all on the heart, and hydrocyanic acid, tobacco, and euphorbium, which influence it feebly, or even dubiously,—produce, when injected into the jugular vein, obstruction of the capillaries of the pulmonary circulation, and consequently asphyxia. This is proved by the hæmadynamometer introduced into a vein indicating great increase of pressure in the venous circulation a few seconds after the introduction of the poison; by this instrument introduced into the femoral artery indicating great diminution of arterial pressure, although the heart continues to beat vigorously; by the breathing becoming at the same time laborious, without the heart suffering; by these symptoms preceding any signs of action on the nervous system; by the heart pulsating for some time after death; and in many instances by frothy mucus having accumulated in the air-passages, and congestion and extravasation having taken place in the lungs themselves.[44]

A great number of the poisons whose action is remote, operate on the _brain_. The most decided proof of such an action is the nature of the symptoms; which are, giddiness, delirium, insensibility, convulsions, palsy, coma. Some physiologists have also sought for evidence in the body after death, and have imagined they found it in congestion of the vessels in the brain, and even extravasation of blood there; but it will be seen under the head of Narcotic Poisons that such appearances are far from being essential, and indeed are seldom witnessed. All narcotic poisons act on the brain, and most narcotico-acrids too; but very frequently other organs are affected at the same time, and in particular the spine and heart.

The influence of poisons on the brain seems to be sometimes induced, not immediately, but indirectly through the intervention of a more direct influence on the pulmonary circulation. Thus Mr. Blake appears to have succeeded in proving that the insensibility and tetanic convulsions which immediately precede death, when certain substances, such as the salts of soda, are injected into the veins, depend simply on the obstruction directly produced in the pulmonary circulation causing increased pressure in the systemic veins, and consequently upon the brain and nervous centre generally. For when the jugular vein was opened after the development of tetanic convulsions, and blood was allowed to flow out, the nervous symptoms ceased, and the animal continued for two hours sensible and without any return of convulsions, dying eventually of hemorrhage.[45] But more generally the effect produced on the brain is direct and specific. Thus opium and its active principle morphia suspend the functions of external relation, which are peculiarly dependent on the brain; while for a long time the respiration and circulation are little affected. Even when the poison is admitted directly into the veins, the pulmonary capillaries are not obstructed, and the heart is only somewhat enfeebled in its contractions;[46] and in ordinary cases of poisoning with these substances the heart continues to pulsate, and the lungs also discharge their office, long after sensibility is extinguished and voluntary motion arrested,—until at length the circulation and respiration become affected consecutively by the depressed state of the nervous system.

Some poisons act specifically on the _spinal cord_. Those which are best known to possess such an action are nux-vomica, the other species of plants which, like it, contain strychnia, and also conia and the wourali poison. The tribe of poisons of which nux-vomica may be taken as the type excite violent fits of tetanus, during the intervals of which the mind and external senses are quite entire; and death takes place during a paroxysm, apparently from suffocation caused by spasmodic fixing of the chest. Their action on the spine is quite independent of any action on the brain; if indeed such action exist at all. For when the spinal cord is separated from the brain by dividing the medulla oblongata, the effects on the muscles supplied by the spinal cord are produced as usual.[47] Conia, the active principle of hemlock, according to my own researches, produces in the lower animals, howsoever introduced, gradually increasing paralysis, without insensibility or delirium, and without the circulation or respiration being for some time affected, till at length death takes place from stoppage of the breathing by palsy of the respiratory muscles; and after death the heart continues beating vigorously, the muscles contract when irritated, and arterialization of the blood in the lungs may be kept up long by maintaining artificial respiration. In this instance it would appear, that the first effect is arrestment of the functions of the spinal cord; that the paralysis does not depend upon a direct action on the muscles; and that neither the brain, heart, nor lungs can be influenced, except secondarily through the consequences of general muscular paralysis.[48] Many poisons which act on the brain also act on the spinal cord.

Other poisons apparently possess the singular property of impeding or arresting the _general capillary circulation_, and produce their tangible effects more or less through the medium of this operation. Such at least are the inferences which seem to flow from the researches of Mr. Blake; who found that many substances, soon after they are injected backwards by the axillary artery into the aorta, produce increased pressure in the arterial system indicated by the hæmadynamometer during life, and frequently congestion of the membranous textures as observed after death. Some substances have no effect of this kind. Others act on the general capillaries in concurrence with a similar action on the capillaries of the pulmonary circulation, such as the salts of strontia, baryta, lead, silver, and soda, euphorbium, tobacco and digitalis. But a few, such as potash and ammonia, with their salts, seem to influence the capillaries of the general circulation only.[49] These are important conclusions, if legitimate; but it cannot be denied, that the facts on which they are based must be very difficult to isolate and observe with accuracy and without bias.

The organs not immediately necessary to life may be likewise all acted on by poisons indirectly. On this subject details are not called for at present. It may be sufficient to remark that there is hardly a considerable organ in the body, except perhaps the spleen and pancreas, which is not acted on by one poison or another. Arsenic inflames the alimentary mucous membrane, mercury the salivary organs and mouth, cantharides the urinary organs, chromate of potass the conjunctiva of the eyes, manganese the liver; iodine acts on the lymphatic glands; lead on the muscles; and spurred rye causes gangrene of the limbs.

Some poisons, as was already mentioned, may act on one important organ only, every other being left undisturbed: thus nux-vomica in general acts only on the spine. But much more commonly they act on several organs at once; and the action of some of them is complicated in an extreme degree. I may instance oxalic acid and arsenic. Oxalic acid when swallowed irritates and inflames the stomach directly, and acts indirectly on the brain, the spine, and the heart. A large dose causes sudden death by paralyzing the heart; if the dose is somewhat less, the leading symptom is violent tetanic spasm, indicating an action on the spine, and death takes place during a paroxysm, the heart continuing to contract for some time after; if the dose is still less, the spasms, at first distinct, become by degrees fainter and fainter, while the sensibility in the intervals, at first unimpaired, becomes gradually clouded, till at length pure coma is formed without convulsions,—thus indicating an action on the brain. As for arsenic, coupling together the symptoms during life and the appearances in the dead body, it will be seen afterwards to have the power of acting on the brain, heart, and lungs,—the throat, gullet, stomach, and intestines,—the lining membrane of the nostrils and eyelids,—the kidneys, bladder, and vagina; and, what is remarkable, proofs of an action on all these parts may be witnessed in the course of a single case. The effects of mercury are hardly less multifarious.

SECTION II.—_On the Causes which modify the Actions of Poisons._

By a variety of causes the action of poisons may be modified both in degree and in kind. The most important of them are—quantity; state of aggregation; state of chemical combination; mixture; difference in tissue; difference in organ; habit; idiosyncrasy; and lastly, certain states of disease.

1. _Quantity_ affects their action materially. Not only do they produce their effects more rapidly in large doses; it is sometimes even quite altered in kind. A striking example has just been related in the case of oxalic acid; which, according to the dose, may corrode the stomach, or act on the heart, or on the spine, or on the brain. In like manner arsenic in a small dose may cause gastritis of several days’ duration; while a large dose may prove fatal in two or three hours by affecting the action of the heart. White hellebore in small doses excites inflammation in the stomach and bowels, in larger doses giddiness, convulsions, coma; and in either way it may prove fatal.

2. _As to state of aggregation_,—poisons act the more energetically the more minutely they are divided, and hence most energetically when in solution. Some which are very energetic in the fluid state, hardly act at all when undissolved. Morphia, the alkaloid of opium, may be given in powder to a dog without injury in a dose, which, if dissolved in oil or alcohol, would soon kill several. Previously dissolving poisons favours their action in two ways,—by diffusing them quickly over a large surface, and by fitting them for entering the bibulous vessels. Poisons, before being absorbed, must be dissolved; and hence, those which act though solid and insoluble in water, must, as a preliminary step, be dissolved by the animal fluids at the mouths of the vessels. In this way the poisonous effects of carbonate of baryta and arsenite of copper are explained; for though insoluble in water, they are soluble in the juices of the stomach.

Differences in aggregation, like differences in quantity, may affect the kind as well as the degree of action. Camphor in fragments commonly causes inflammation of the stomach; dissolved in spirit or olive oil, it causes delirium or tetanus and coma.

The reduction of certain poisons to the state of vapour serves the same end as dissolving them. When poisons are to be introduced by the skin, no previous operation is more effectual than that of converting them into vapour.

3. The next modifying cause is _chemical combination_. This is sometimes nothing more than a variety of the last. If a poison, in combining with another substance, acquire greater solubility, it also generally acquires greater activity, and _vice versa_: Morphia, itself almost inert, because insoluble, becomes active by uniting with acids, for they render it very soluble: Baryta as a very active poison, becomes quite inert by uniting with sulphuric acid, for the sulphate of baryta is altogether insoluble.

In regard to the influence of chemical combination two general laws may be laid down. One is, that _poisons which only act locally, have their action much impaired or even neutralized, in their chemical combinations_. Sulphuric acid and muriatic acid on the one hand, and the two fixed alkalis on the other, possess a violent local action; but if they are united so as to form sulphates or muriates, although still very soluble, they become merely gentle laxatives. But the case is altered if either of the combining poisons also act by entering the blood. For the second general law is, that _the action of poisons which operate by entering the blood, although it may be somewhat lessened, cannot be destroyed or altered in their chemical combinations_. Morphia acts like opium if dissolved in alcohol or fixed oil; if an acid be substituted as the solvent, a salt is formed which is endowed with the same properties: The sulphate, muriate, nitrate, acetate of morphia all act like opium. Strychnia, arsenic, hydrocyanic acid, oxalic acid, and many more come under the same denomination: Each produces its peculiar effects, with whatever substance it is combined, provided it do not become insoluble.

Mr. Blake has recently laid down what may be considered a branch or corollary of the second of these general propositions, and has confirmed it by many appropriate experimental facts,—namely, that _the salts of the same base produce the same actions, independently of the acids with which they are combined_.[50] The law, however, is a more general one, as given above, and was stated in former editions of the present work. It applies not only to bases, but likewise to acids, such as the hydrocyanic, oxalic, arsenious, and arsenic acids, and also to neutral organic principles which act through the blood, such as picrotoxin, colocynthin, elaterin, and narcotin.

The same author considers it to be also a probable conclusion from a variety of experiments on the salts of various bases, that _those salts which are isomorphous, or possess the same crystalline form, are closely allied in action_.[51]

4. The effect of _mixture_ depends partly on the poisons being diluted. Dilution, by prolonging the time necessary for their being absorbed, commonly lessens their activity; yet not always; for if a poison which acts through the blood is also a powerful irritant, moderate dilution will enable it to enter the vessels more easily: a small dose of concentrated oxalic acid acts feebly as an irritant or corrosive; moderately diluted, it quickly enters the blood and causes speedy death.[52] The effect of mixture may depend also in part on the mere mechanical impediment interposed between the poison and the animal membranes. This is particularly obvious when the mass containing the poison is solid or pulpy; for then the first portions of the poison that touch the membrane may cause an effort of the organ to discharge the rest beyond the sphere of action,—if, for example, it is the stomach,—by vomiting. The effect of mixture in interposing a mechanical impediment is also well illustrated where the substance mixed with the poison is a fine, insoluble powder, capable of enveloping its several particles. Thus it is that small, yet poisonous doses of arsenic may be swallowed and retained with impunity, if mixed with finely powdered charcoal, magnesia, and probably cinchona-bark, or the like. Besides diluting and mechanically obstructing their application, the admixture of other substances may alter the chemical nature of poisons, and so change their action.

It is important to keep in view, that the influence of mixture may be exerted in consequence of the cavity into which a poison is introduced being at the time filled with contents. Some of the most powerful and unerring poisons may in such circumstances altogether fail to produce their usual effect, if speedily vomited. Thus Wibmer notices the case of a man, who swallowed an ounce and a half of arsenic after a very hearty meal, had merely a severe attack of vomiting with subsequent colic, and got quite well in four days.[53] And a still more pointed instance has been briefly mentioned by Dr. Booth of Birmingham, where an ounce of corrosive sublimate was swallowed after a full meal without any material ill consequence, vomiting having been speedily induced.[54]

5. _Difference of tissue_ is an interesting modifying power in a physiological point of view, but does not bear so directly on medico-legal practice as the rest, and may therefore be passed over cursorily.

On the corrosives and irritants a difference of tissue acts but indirectly: their effects vary not so much with the tissue as with the organ of which it forms part. But as to poisons which act through the blood, their energy must evidently depend on the activity of absorption in each texture.

The cutaneous absorption is slow, on account of the obstacle presented by the cuticle, and by the intricate capillaries of the true skin. Accordingly many active poisons are quite inert when applied to the unbroken skin, or even to the skin deprived of the cuticle. Hydrocyanic acid, perhaps the most subtle of all poisons, was found by Coullon to have no effect when dropped on the skin of a dog.[55] Some authors have even gone so far as to deny that poisons can be absorbed at all through the skin, unless they are pressed by friction through the cuticle. But this is an error; most gaseous poisons, such as carbonic acid and sulphuretted hydrogen, and some solid poisons when volatilized, such as the vapours of cinnabar, will act though simply placed in contact with the skin; and there is distinct evidence that corrosive sublimate will bring on mercurial action in the form of a warm bath, or when used as a liniment.

On the mucous membrane of the stomach and intestines, poisons act much more energetically than on the skin; which clearly depends in a great measure on the superior rapidity of absorption there,—or, according to some, on the facility with which poisons come in contact with the sentient extremities of nerves.

The serous membranes possess an activity of absorption which hardly any other unbroken texture can equal. Accordingly many poisons act much more rapidly through the peritonæum than through the stomach. When oxalic acid is introduced under the same collateral circumstances into the stomach of one dog and the peritonæum of another, the dose may be so apportioned, that the same quantity, which does not prove fatal to the former, kills the latter in fourteen minutes.[56]

While the preceding modes in which poisons enter the blood are indirect, they may be introduced directly by a wound in the vein. There is no way in which poisons, that act through the blood, prove more rapidly fatal. Some which act very slowly through the stomach cause instant death when injected into a vein. A peculiar variety of this mode of introducing poisons deserves to be distinguished, namely, the application of them to a wound. If the surface bleeds freely, they may not act at all, because they are washed away. But if they adhere, they soon enter the divided veins. Hence, if they act in small doses, this mode of applying them is hardly less direct than if they were at once injected into a vein.

So far the effect of difference in tissue has been determined. Poisons that act through the blood act least energetically on the skin, more actively on the alimentary mucous membrane, still more so on serous membranes, and most powerfully of all when introduced directly into a vessel. There are other textures, however, which merit notice, although their place in the scale of activity has not been exactly settled.

On the mucous membrane of the pulmonary air-cells and tubes, poisons act with a rapidity which is scarcely surpassed by their direct introduction into a vein. This is plainly owing to the exceeding delicacy and wide surface of the membrane. Hence three or four inspirations of carbonic oxide gas will cause instant coma. A single inspiration of the noxious gas of privies has caused instant extinction of sense and motion. Nay, liquid poisons have been known to act through the same channel with almost equal swiftness. For M. Ségalas found that a solution of extract of nux-vomica caused death in a few seconds when injected in sufficient quantity into the windpipe; and that half a grain will thus kill a dog in two minutes, while two grains will rarely prove fatal when injected into the stomach, peritonæum, or chest.[57]

As to the nervous tissue, it is a fact worthy of mention, that the poisons which appear to act on the sentient extremities of the nerves, do not act at all on the cut surface of the brain and nerves, or upon any part of the course of the latter. This has been proved with respect to most active narcotics.

The power of the cellular tissue as a medium of absorption, has not been, and cannot easily be, ascertained. On the one hand it is difficult to apply poisons to it, without also applying them to the mouths of divided vessels; and, on the other hand, it is difficult to make a set of experiments for comparison with others on the stomach, pleura, or peritonæum, as the cellular tissue does not form an expanded cavity, and consequently, the extent of surface to which a poison is applied cannot be made the same in each experiment of a series. It is a ready medium, however, for admitting poisons into the blood, especially if an artificial cavity be made where the tissue is loose, as, for example, by separating the skin from the muscles of the back with the finger introduced through a small incision in the integuments.

The variations caused by difference of tissue in the activity of poisons have been viewed in the previous remarks as depending chiefly on the relative quickness with which absorption goes on. But in this way it is impossible to explain the whole amount of the differences sometimes observed. Some poisons cause death when applied to a wound in the minutest quantity, but are quite harmless when swallowed in large doses: Others are diminished a little in activity, but still remain powerful and fatal poisons. There is not much difference in the power of arsenic when it is applied to different textures, the skin excepted. But oxalic acid injected into the peritonæum will act eight or ten times more rapidly than when swallowed and the poison of the viper may prove fatal to a man through a wound in almost invisible doses, while the whole poison of six vipers may be swallowed by so small a creature as a blackbird, with complete impunity.[58] Differences in the absorbing power of the tissues cannot explain these facts.

The only rational way of accounting for them is by supposing that a part of the poison is decomposed,—the change being greatest where absorption is slowest and the power of assimilation strongest, namely, in the stomach,—and least where absorption is quickest and assimilation almost wanting, namely, in a wound. This explanation derives support from the different effects of change of tissue on poisons of the different kingdoms. Mineral poisons are least, and animal poisons are most, affected in their action by differences of tissue, while vegetable poisons hold the middle place:—an arrangement which coincides with the respective difficulty of decomposition among mineral, vegetable, and animal substances generally, whether under physical or under vital processes.[59]

6. With respect to differences arising from _difference of organ_, these will, of course, be partly attributable to differences in tissue, but not altogether. For example, in the case of the pure corrosives or irritants, the injury caused will depend for its danger on the importance of the organ to the general economy of the body: Inflammation caused by a local poison in the stomach will be more quickly fatal than that excited in the intestines only; and such a poison may act violently on the external parts without materially impairing the general health.

7. _Habit and Idiosyncrasy._—The remarks to be made under the present head are important in a medico-legal point of view: for they show how one man may be poisoned by a substance generally harmless, and another not harmed by a substance usually poisonous.

The tendency of _idiosyncrasy_ is generally to increase the activity of poisons, or even to render some substances deleterious which are commonly harmless.

The effect of opium in medicinal doses is commonly pleasant and salutary; but in some individuals it produces disagreeable and even dangerous effects. Calomel, which in moderate doses is for the most part a mild laxative or sialagogue, will cause in some people, even in the dose of a few grains, violent salivation, ulceration of the mouth, nay, fatal gangrene. On the other hand, a few substances, which to most people are actively poisonous, have on some individuals comparatively little effect. There are extremely few poisons, however, in regard to which this kind of idiosyncrasy is well established and prominent. Mercury and alcohol are examples. The compounds of mercury, which in moderate quantity are mildly laxative or sialagogue to most people, but to some persons dangerously poisonous in very small doses, would, on the contrary, appear in other constitutions to be extremely inactive; for it has occasionally been found impossible to bring on the peculiar constitutional action of mercury by continuing the use of its preparations for months together. In general children are not easily affected by calomel as a sialagogue, but easily by its laxative action. As to alcohol, it is a familiar fact, that independently of the effects of habit, there are some constitutions which cannot be brought under the influence of intoxicating liquors without an extraordinary quantity of them and a long-continued debauch, while others are overpowered in a short space of time, and by very moderate excess; and there is no reason to doubt that very great constitutional differences also prevail in regard to the operation of a single large dose. A rarer idiosyncrasy is unusual insensibility to the action of opium. I am acquainted with a gentleman unaccustomed to the use of opium who has taken without injury nearly an ounce of good laudanum,—a dose which would certainly prove fatal to most people.

But not only does idiosyncrasy modify the action of poisons: Through its means, too, some substances are actually poisonous to certain individuals, which to mankind in general are unhurtful, nay, even nutritive.

With some people all kinds of red fish, trout, salmon, and even the richer white fish, herring, mackerel, turbot, or holibut, disagree as it is called—that is, act after the manner of poisons: They produce fainting, sickness, pain of the stomach; and if they were not speedily evacuated by vomiting, dangerous consequences might ensue. The same is often the case with mushrooms. The esculent mushrooms act on some people nearly in the same way as the poisonous varieties. Bitter almonds and other vegetable substances that contain hydrocyanic acid, sometimes produce stupor or nettle-rash in the small quantities used for seasoning food. In like manner many flowers, which to most persons are agreeable and not injurious, cannot be kept in the same room with some people on account of the severe nervous affections that are developed.

This idiosyncrasy may even be acquired. One of my relations, who was for many years violently affected by very small quantities of the richer kinds of fish, used at a previous period to eat them, and can now again do so, with impunity. Many people have acquired a similar idiosyncrasy with respect to eggs; instances of the same kind will be afterwards mentioned in respect to shell-fish, particularly muscles; indeed there are probably few articles of food in regard to which such idiosyncrasies may not in a few rare instances be met with, if we except the grains and common kinds of butcher-meat. I may add, that from facts which have come under my notice, I have sometimes suspected that a similar idiosyncrasy may be acquired in a slight degree, and for a short time only, in regard even to some kinds of butcher-meat, especially the flesh of young animals and pork. On this subject some illustrations will be found at the close of the chapter on diseased and decayed animal matter.

It does not appear well ascertained, that the effect of idiosyncrasy is ever to impair materially the energy of poisons, except in the instances of mercury, alcohol, and opium.

On the contrary, the tendency of _habit_ when it does affect their energy, is, with a few exceptions, to lessen it. By the force of habit a person may take without immediate harm such enormous quantities of some poisons as would infallibly kill an unpractised person or himself when he began. There have been opium-eaters in this country who took for days together ten or even seventeen ounces of laudanum daily.

The influence of habit has been ascertained precisely in the case of a few common poisons only. On the whole, it would appear that more change is effected by habit in the action of the organic than in that of the inorganic poisons; and that of the former, those which act on the brain and nervous system, and produce _narcotism_, are altered in the most eminent degree. The best examples of the influence of habit are opium and vinous spirits. The action of such poisons is not always, however, entirely thrown away; they still produce some immediate effect; and farther, by being frequently taken, they may slowly bring on certain disease, or engender a predisposition to disease. A very singular exception to this rule prevails in the instance of tobacco; which, under the influence of habit, may be smoked daily to a considerable amount, and, so far as yet appears, without any cumulative effect on the constitution, like that of opium-eating or drinking spirits.

The inorganic poisons are most of them little impaired in activity by the force of habit. The pure irritants, indeed, do lose a little of their energy: for it seems that persons have acquired the power of swallowing with impunity considerable doses of the mineral acids. But as to inorganic poisons that enter the blood, habit certainly does not diminish, probably rather increases, their power. There is no satisfactory evidence, that a person by taking gradually-increasing doses of arsenic may acquire the power of enduring a considerably larger dose than when he began: On the contrary, the stomach rather becomes more tender to the subsequent dose by each repetition. I have little hesitation in avowing my disbelief of the alleged cases of arsenic-eaters and corrosive-sublimate-eaters, who could swallow whole drachms at once with impunity. Some have expressed surprise at this statement having been made in former editions of the present work, when there is such authority as Byron, Pouqueville, &c., for the hackneyed story of Soleyman, the sublimate-eater of Constantinople, who lived to the age of a hundred, eating a drachm of corrosive sublimate daily. I must avow, however, that such reporters of a feat so very extraordinary, and where deception was so highly probable, are to me no authority at all.

In the relative influence of habit on poisons of the three kingdoms of nature, a new argument will be discovered for the opinion given above respecting the partial decomposition of organic poisons in some of the tissues. In fact this partial decomposition accounts very well for the effect of habit: The effect of habit is probably nothing more than an increased power acquired by the stomach of decomposing the poison,—just as it gradually acquires an increased facility in digesting some alimentary substances which are at first very indigestible.

8. The last modifying cause to be mentioned comprehends certain _diseased states of the body_. The effect of disease, like that of habit, is in general to impair the activity of poisons. But it is only in the instance of a few diseases that this diminution is so strongly marked as to be important in relation to medical jurisprudence.—In the continued fever of this country there is a diminished susceptibility of the constitutional action of mercury; and this peculiarity is very strongly marked in the yellow fever, as well as in the bilious fevers generally of tropical climates. In some varieties of typhoid fever there is obviously a diminished sensibility to the action of wine and other spirituous liquors; but this diminution in a great majority of cases is much inferior to what some physicians have represented.—In severe dysentery the susceptibility of the narcotic action of opium is so much impaired, that a person unaccustomed to the use of that drug, may continue to take daily, for several days together, a quantity which might prove fatal to him in a state of health. In the severe form which dysentery occasionally puts on in this country I have known a patient take from twenty-four to thirty grains of opium daily, and retain it all, without experiencing more than a mild narcotic action.—In epidemic cholera the same insensibility has been remarked to the operation of opium.—It also occurs in the instance of excessive hemorrhagy.—According to the doctrines and practice of the present dominant school in Italy, there is an unusual insensibility during inflammatory dropsy to the irritant action of gamboge, so that sixty or eighty grains may be taken without harm.—There is no disease, however, in which the power of mitigating the action of poisons is more remarkably exhibited, than in tetanus: It is often scarcely possible to bring on the narcotic action of opium by any doses which can be administered; calomel, too, acts with much less energy than usual; and even common purgatives must be administered in doses considerably larger than those required in most other disorders.—Mania is similarly circumstanced: almost all remedies must be given in increased doses, narcotic remedies in particular. But there is good reason for believing that the impaired susceptibility of the action of poisons remarked in this disorder is far from being always so great as some have alleged.—Another disease allied to the last, where the diminution of susceptibility is often great, is delirium tremens. It has in particular been often found, that to produce sleep in this disease opium must be given in frequent large doses,—so large indeed, that they would undoubtedly prove fatal to a person in health. At the same time it is worthy of remark, that in some cases of delirium tremens, even violent in degree, the peculiarity now specified, as I have myself several times witnessed, is far from being strongly marked.—Hydrophobia always, and hysteria sometimes, impair the activity of poisons. I have seen cases of hysteria, more particularly those assuming the form of tetanus, where very large doses of opium were required to produce a calmative effect and sleep; and in hydrophobia it is well shown that the narcotic action of opium is not produced even by large doses often repeated.—The same state occurs in excessive hemorrhage.

In the operation of this class of modifying agents it is a general law, to which there are probably few exceptions, that they chiefly affect poisons of the organic kingdoms, and the narcotics above all. At least in the instance of most mineral poisons their influence is very inferior. Their operation may be accounted for in various ways. Sometimes, as in dysentery and cholera, the poison is carried with unusual rapidity through the alimentary canal. Sometimes again it remains comparatively inert, because on account of the impaired activity of absorption, it is not taken up with the usual quickness by the absorbent vessels. And sometimes, as in the instance of tetanus, mania, and rabies, the nervous system is in a state of peculiar excitement, by which the customary action of the poison is in a great measure, if not entirely, counteracted.

In a few diseased states of the system there is an increased susceptibility of the action of poisons: and it is important that the medical jurist should attend to this circumstance. When a poison has a tendency to bring on a peculiar pathological state of the system, or of a particular organ, which state is also produced by a disease existing at the time or impending, violent and even fatal consequences may ensue from doses of poisons which in ordinary circumstances are innocuous or beneficial. Thus in persons affected with apoplexy an ordinary dose of opium may accelerate death; and in people even with a mere tendency to apoplexy, if it is strongly marked, or appears from what are called warning symptoms to be on the point of developing itself, a common dose of such narcotics as occasion determination to the brain may excite the apoplectic attack. Thus, too, in cases of inflammatory disorders of the alimentary canal, irritating substances, in doses not otherwise injurious, may produce dangerous impressions on the tender membrane with which they come in contact. But in respect to this last example, it must be remarked, that the improvements or the caprice of medical practice have gone directly in face of the rule, by suggesting that some internal inflammations of the alimentary canal may be successfully treated with irritating remedies.

I might here perhaps have added among the causes which modify the action of poisons, sleep, and the administration of other poisons. The latter subject, however, will be better considered at the end of the Individual Poisons, under the title of Compound Poisoning. The former agent is of doubtful effect. Some observations on its influence will be found in the chapter on the Evidence of General Poisoning, p. 41.

_Application of the preceding remarks to the Treatment of Poisoning._ As an appendix to what has been said respecting the physiological action of poisons, and the causes by which it is liable to be modified, I shall here state shortly certain applications to the treatment of poisoning.

In the instance of internal poisoning, the great object of the physician is to administer an antidote or counter-poison. Antidotes are of two kinds. One kind takes away the deleterious qualities of the poison before it comes within its sphere of action, by altering its chemical nature. The other controls the poisonous action after it has begun, by exciting a contrary action in the system. In the early ages of medicine almost all antidotes were believed to be of the latter description, but in fact very few antidotes of the kind are known.

Chemical antidotes operate in several ways, according to the mode of action of the poison for which they are given. If the poison is a pure corrosive, such as a mineral acid, it will be sufficient that the antidote destroy its corrosive quality: Thus the addition of an alkali or earth will neutralize sulphuric acid, and destroy or at least prodigiously lessen its poisonous properties. In applying this rule care must be taken to choose an antidote which is either inert in itself, or, if poisonous, is, like the poison for which it is given, a pure corrosive or local irritant, and one whose properties are reciprocally neutralized.

If the poison, on the other hand, besides possessing a local action, likewise acts remotely through absorption, or by an impression on the inner coat of the vessels, mere neutralization of its chemical properties is not sufficient; for we have seen above that such poisons act throughout all their chemical combinations which are soluble. Here, therefore, it is necessary that the chemical antidote render the poison insoluble or nearly so; and insoluble not only in water, but likewise in the animal fluids, more particularly the juices of the stomach. The same quality is desirable even in the antidotes for the pure corrosives; for it often happens that in their soluble combinations these substances retain some irritating, though not any corrosive power. When we try by the foregoing criterions many of the antidotes which have been proposed for various poisons, they will be found defective; and precise experiments have in recent times actually proved them to be so.

The other kind of antidote operates not by altering the form of the poison, but by exciting in the system an action contrary to that established by the poison. On considering attentively, however, the phenomena of the action of individual poisons, it will be found exceedingly difficult to say what is the essence of a contrary action, and still more how that counter-action is to be brought about. Accordingly, few antidotes of the kind are known. Physiology or experience has not yet brought to light any mode of inducing an action counter to that caused by arsenic and most of the irritant class of poisons. It appears probable that the remote operation of lead may be sometimes corrected by mercury given to salivation, and that the violent salivation caused by mercury may be occasionally corrected by nauseating doses of antimony. But these are the only instances which occur to me at present of antidotes for irritant poisoning which operate by counter-action, unless we choose to designate by the name of antidote the conjunction of remedial means which constitute the antiphlogistic method of cure. In the class of narcotics we are acquainted with equally few constitutional antidotes, although the nature of the action of these poisons seems better to admit of them. Ammonia is to a certain extent an antidote for hydrocyanic acid, but by no means so powerful as some persons believe; and I am not sure that in this class of poisons we can with any propriety mention another antidote of the constitutional kind.

On the whole, then, it is chiefly among the changes induced by chemical affinities that the practitioner must look for counter-poisons; and the ingenuity of the toxicologists has thence supplied the materia medica with many of singular efficacy. When given in time, magnesia or chalk is an antidote for the mineral acids and oxalic acid, albumen for corrosive sublimate and verdigris, bark for tartar-emetic, common salt for lunar caustic, sulphate of soda or magnesia for sugar of lead and muriate of baryta, chloride of lime or soda for liver of sulphur, vinegar or oil for the fixed alkalis; and these substances act either by neutralizing the corrosive power of the poison, or by forming with it an insoluble compound.

In recent times a new object in the treatment of poisoning has been pointed out by the discoveries made in its physiology. As it has been proved that many of the most deadly poisons enter the blood, and in all probability act by circulating with that fluid, so it has been inferred that an important object in the treatment is to promote their discharge by the natural secretions. In support of this reasonable inference it has been lately rendered probable by Orfila, as will be seen under the head of the treatment of the effects of arsenic, that it is of great advantage in some forms of poisoning to increase the discharge of urine.

In the instance of external poisoning the main object of the treatment is to prevent the poison from entering the blood, or to remove it from the local vessels which it has entered.

One mode, which has been known to the profession from early times, and after being long in disuse was lately revived by Sir D. Barry, and applied with success to man, is the application of cupping-glasses to the part where the poison has been introduced.[60] This method may act in various ways. It certainly prevents the farther absorption of the poison by suspending for a time the absorbing power of the vessels of the part covered by the cup. It also sucks the blood out of the wound, and may consequently wash the poison away with it. Possibly it likewise compresses the nerves around, and prevents the impression made by the poison on their sentient extremities from being transmitted along their filaments.

Another mode is by the application of a ligature between the injured part and the trunk, so as to check the circulation. This is a very ancient practice in the case of poisoned wounds, and is known even to savages. But as usually practised it is only a temporary cure: As soon as the ligature is removed the effects of the poison begin. It may be employed, however, for many kinds of poisoning through wounds, so as to effect a radical cure. We have seen that most poisons of the organic kingdom are in no long time either thrown off by the system or decomposed in the blood. Hence if the quantity given has not been too large, recovery will take place. Now, by means of a ligature, which is removed for a short time at moderately distant intervals, a poison, which has been introduced into a wound beyond the reach of extraction, may be gradually admitted into the system in successive quantities, each too small to cause death or serious mischief, and be thus in the end entirely removed and destroyed. Such is a practical application which may be made of some ingenious experiments performed not long ago by M. Bouillaud with strychnia, the poisonous principle of nux-vomica.[61]

The last mode to be mentioned is by a combination of the ligature with venesection, deduced by M. Vernière from his experimental researches formerly noticed (p. 19). Suppose a fatal dose of extract of nux-vomica has been thrust into the paw of a dog; M. Vernière applies a tight ligature round the limb, next injects slowly as much warm water into the jugular vein as the animal can safely bear, and then slackens the ligature. The state of venous _plethora_ thus induced completely suspends absorption. The ligature is next tied so as to compress the veins without compressing the arteries of the limb, and a vein is opened between the wound and the ligature in such a situation, that the blood which flows out must previously pass through, or at least near the poisoned wound. When a moderate quantity has been withdrawn, the ligature may be removed with safety; and the extraction of the poison may be farther proved by the blood that has been drawn being injected into the veins of another animal; for rapid death by tetanus will be the result.[62] It is not improbable that in this plan the preliminary production of venous plethora may be dispensed with; and then the treatment may be easily and safely applied to the human subject.