Correll University Library Sthaca, New York BOUGHT WITH THE INCOME OF THE FISKE ENDOWMENT FUND THE BEQUEST OF WILLARD FISKE LIBRARIAN OF THE UNIVERSITY 1868-1883 1905 RETURN TO ALBERT R. MANN LIBRARY ITHACA, N. Y. snake-poison; its action and its anti SNAKB-POISON ITS ACTION NT ITS ANTIDOTE. SYDNEY: -BONAGe. SYDNEY: WesspaLe, SuoosmirH & Co., PRINTERS, 117 CLARENCE STREET. 1893. OOYRBO PREFACE. So >—__—_—_ Since the method of treating snakebite-poisoning by hypodermic injections of strychnine, discovered by the writer and published but a few years ago, has already been adopted by the medical profession through- out the Australian colonies, and practised even by ‘laymen in cases of urgency with much success, it has been repeatedly suggested to him that the subject calls for further elucidation at his hands; that the mor- bid processes engendered by the snake venom and the modus operand? of the antidote should be explained by him in a manner satisfying the demands of science, and at the same time within the grasp of the intelli- gent, moderately educated layman. When the latter, in a case of pressing emergency and in the absence of medical aid, is called upon to administer a potent drug in heroic doses, the. aggregate of which would be attended by serious consequences in the absence of the deadly ophidian virus, an intelligent insight alone into the process he is about to initiate will give him that decision and promptitude of action, on the full exercise of which on his part it may depend whether, within a few hours, a valuable and to him probably dear life will be saved or lost, li. PREFACE. The foregoing applies, not to Australia only, but to all other countries infested by venomous snakes. The introduction of the writer’s method in every one of these countries is merely a question of time, for snake-poison acts everywhere according to one uniform principle, however different the symptoms it produces may appear to the superficial observer. The antidote, therefore, that cures snakebite in Australia will as surely cure it elsewhere if properly and efficiently applied. To his Australian confréres, more especially to those who adopted his method but had to practise it more or less empirically, the writer also owes a more elaborate explanation of his theory of the action of snake-poison in all its bearings on the various nerve centres than is to be found in the scattered writings he has from time to time published in our periodical literature. His warmest thanks are due to them for the records of cases they have furnished to the Austra- lasian Medical G'azette, and to the Hon. J. M. Creed, its able editor, for the ample space he has invariably allotted to the subject, and the valuable support he has given him throughout. By our united efforts we have reared in a dark and hitherto barren field of research a column of solid knowledge, and on this column Australia now occupies the highest and will ever occupy the most prominent place. Not the least pleasing feature in the history of this discovery is the fact that it has been made with- out an elaborate series of experiments on animals, that PREFACE. ill. it is a peaceful conquest not attained by means of doubtful justification, and which have hitherto invari- ably failed in their object. This object—the discovery of the coveted antidote—instead of being brought nearer, was, in fact, further removed by every succeed- ing series of experiments. However fruitful in results this mode of research has been in other domains, in this particular one it has not only been a failure but an actual bar to progress. Nature invariably refused to yield her secret when thus interrogated. The tortured animals, like the victims of Torquemada, either did not answer at all or they answered with a lie, and the bafiled experimenter abandoned his task in despair. Still, these negative results notwithstanding, the writer is confronted by a certain class of would-be rigorous scientists, who tell him that his theory of the action of snake-poison, though it explains all the phenomena, cannot be accepted as correct until it has been proven so by strict test experiments on animals, and that the successful administration of the antidote is proof only of the fact of neither antidote nor snake- poison having killed the patients, who, probably, might have recovered if left to themselves. This may be strict logic, but common sense replies to it that if recoverytakes place after proper administra- tion of the antidote in cases which, according to all our previous experience, would have ended fatally, it is not illogical to assume that antidote and recovery stand in the relation of cause and effect, This sceptical 1 lv, PREFACE, attitude of the scientific mind can justly be maintained _ only with regard to cases limited in number and in which the symptoms left room for doubt as to their final result, but in view of the formidable and con- stantly increasing records of cures from snakebite during the last three years, it is, to say the least of it, unreasonable. The demand for experiments on animals, in proof of the correctness of his theory, the writer does not feel called upon to satisfy, for, apart from the theory proving itself by explaining all the symptoms the snake-poison produces, it has also stood the test of practical application. It is proven to be correct by the success of the antidote to which it led, and which is the logical outcome of it. After finally attaining a goal one has striven for, it is quite unnecessary to retrace one’s steps with a view of ascertaining whether the road that has led up to it is the right and proper one. By a fortuitous concurrence of circumstances, however, even this demand for experiments shall be satisfied in these pages. The writer published his theory of the action of snake-poison in May, 1888, after having practised the strychnine treatment for some years and thoroughly satisfied himself of its efficacy. In the latter part of 1888 accounts of Feoktistow’s researches reached this country. His final conclusions to the effect that snake-poison is solely a nerve poison, that it does not destroy protoplasm, and has no effect whatever on the blood to which its destructive potency PREFACE. Vv. on animal life can be ascribed, were in complete har- mony with the writer’s views, in fact, a re-statement of his theory. It was a strange coincidence, or what- ever it may be called, that, independent ot each other, at almost opposite parts of the globe, and by opposite methods, we had arrived at almost identical con- clusions. Those of Feoktistow were drawn from 400 elaborate experiments on animals, both vertebrates and invertebrates, made in the laboratory of Professor Kobert at the University of Dorpat and in that of Professor Owsjannikow at the Imperial Academy of Sciences of St. Petersburg. The writer’s conclusions, on the other hand, resulted entirely from a careful and happy analysis of the symptoms observed at the bed- side of his patients suffering from snakebite. On one point only, but the most important one, he differs from Feoktistow. The latter shared the fate of all previous experimenters on animals. Though his experiments with snake-poison led him to the correct theory of its action, and even to the correct antidote, his experiments with strychnine and snake-poison were a failure. The animals experimented on died, and, falling into the error of his predecessors, mnistaking the functional analogy that exists between the nerve centres of the lower animals and those of man for absolute identity, which does not exist, especially not when they are under the influence of the two poisons, he concluded his researches with the confession that a physiological antidote for snake-poison cannot even be thought of at the present state of science. Although, PREFACE. vi. therefore, Feoktistow’s labors would have led to no practical result, they are, nevertheless, a most valuable -contribution to science as being the first to demon- strate the action ot snake-poison on a strictly scientific, experimental basis. For this reason, and with so high -an authority as Professor Kobert vouching for the cor- rectness of the experiments, they will be frequently quoted hereafter. HISTORICAL REVIEW. Snakebite and its cure have always been the despair of medical science. On no other subject has our knowledge remained for centuries so unsatisfactory, fragmentary and empirical. The history of the subject, in fact, may be summed up briefly as a series of vain and spasmodic attempts to solve the problem of snake- bite-poisoning and wring from nature the coveted’ antidote. Various and contradictory theories of the action of snake-poison have been propounded, some absolutely erroneous, others containing a modicum of truth mixed with a large proportion of error, but none but one ful- filling the indispensable condition of accounting for all the phenomena observable during the poisoning process and of reducing the formidable array of conflicting symptoms to order by finding the law that governs them all. We have the advocates of the blood-poison theory ascribing the palpable nerve-symptoms to imag- inary blood changes produced by the subtle poison, and alleged to have been discovered by the willing, but frequently deceiving microscope. Even bacteriology has been laid under service and innocent leucocytes have been converted under the microscope into deadly germs, introduced by the reptile, multiplying with marvellous rapidity in the blood of its victims, appropriating to 2 HISTORICAL REVIEW, themselves «all the available oxygen and producing carbonic acid, as the saccharomyces does in alcoholic fermentation. Others again, and among them those supposed to be the highest authorities on the subject now living, divide the honors between nerve and blood. Some snakes they allege are nerve-poisoners others as surely poison the blood, but with one solitary exception they assume the terminations of the motor-nerves and. not the centres to be affected. Thus then with regard to theories we have hitherto had “confusion worse confounded,” and as with theories so it has been with antidotes. They were proposed in numbers, but only to be given up again, some intended to decompose and destroy the subtle poison in the system, others to counteract its action on the system with that action unknown. It is scarcely too much to assert that there are but few chemicals and drugs in the materia medica that have not been tried as antidotes in experiments on animals and dozens upon dozens that have been tried in vain on man. The reasons for this somewhat chaotic state of our science on a subject of so much interest to mankind are various. The countries of Europe, in which scientific research is most keenly pursued, have but few indi- genous, and these comparatively harmless snakes. The best scientific talent has, therefore, only exceptionally been brought to bear on the subject. In those coun- tries on the other hand in which venomous snakes abound and opportunities for observing the poison- HISTORICAL REVIEW. 3 symptoms on man are more plentiful, the observing element has been comparatively deticient. A still more potent source of failure must be sought in the faulty methods of research pursued by most investigators. Experiments on animals were far too much resorted to, and their frequently misleading results accepted as final, whilst observations on man did not receive the attention their importance demanded. In the investigation of this subject the first desideratum was no doubt to find the correct theory of the action of snake poison and to define the law governing that action, assuming as a working hypothe- sis that there is but one law for all snake-poison and not several ones, just as there is one law for the struc- ture of these reptiles, admitting of variations, but not of absolute divergence from the general plan. The shortest and surest way to find this law is close obser- vation and careful analysis of the symptoms produced by ‘the poison on man, and as the opportunities for such observation are not of frequent occurrence to the indi- vidual, co-operation and careful comparison of notes on the part of many observers. This method of investigation, which, during the last few years, has been pursued in Australia with most satisfactory results, was never practised any- where else, not even in America, but instead of it each observer, with few exceptions, kept his own notes to himself, and if there happened to be one here and there hungry for more knowledge than his scanty 4 HISTORICAL REVIEW. opportunities for observation on man would supply, his resort was usually experiments on animals. A few snakes were caught, a few luckless dogs or other animals procured, and the slaughter of the innocents began. As test experiments to confirm observations on man, or made with a view of finding a correct theory of the action of snake-poison, these attempts were unobjectionable, although, without an elaborate scien- tific apparatus and in other than skilled hands, they were not likely to produce results of any value. But most of the experimenters were not content with purely theoretical aims. They were seeking to find the anti- dote by a purely empirical method, and had nothing to guide them in the choice of drugs. A dose of snake- poison was administered to an animal, and then a dose of some drug or chemical, chosen ad libitum, sent after it. Next day another presumed antidote was tried, another animal slaughtered, and so on ad nauseam, until finally the baffled antidote-searcher, not one whit the wiser for all his trouble and the useless tortures inflicted, confessed himself beaten and joined in the “non possumus ” of his predecessors. One important point has been completely left out of sight and ignored in all this experimenting on animals. It is the fact that the action of snake-poison on the human system and on that of animals, more especially dogs, though very similar, is not absolutely identical, and that for this reason alone results of experiments on the latter cannot be indiscriminately HISTORICAL REVIEW. 5 applied to man. - As pointed out before, analogy has been confounded with identity. When a dog, for instance, has been bitten by a snake he does not. usually collapse as quickly as a human being, but is able to drag himself about much longer before his hind legs refuse their service and he is unable to walk. This longer duration of the first stage of the poisoning process is no doubt owing to a higher organisation and greater functional power of the motor nerve centres of dogs. The amount of motor force at their disposal is greater, and hence they offer greater resistance to the invader seeking to turn off this force. When finally the latter gains the ascendency, irregular discharges of motor nerve force still take place and find their expression in convulsions, which in man only exceptionally occur. But the difference between man and dog becomes more marked yet when strychnine is administered to a dog suffering from snake-poison. It counteracts the latter quite as effectually in a dog as in man, but has to be injected with extreme caution, tor whilst in man a slight excess in the quantity required to subdue the snake-virus is not only harmless, but actually neces- sary, any excess of it in a dog will at once produce violent tetanic convulsions and cause the animal to die even quicker than the snake-poison would have killed it, if allowed to run its course. In the face of these facts the judiciousness of the proposal lately made both here and in India to subject the strychnine treatment of snakebite once more to a series of test experiments on animals appears more than questionable. 6 HISTORICAL REVIEW. Another cause that has largely contributed to render experiments on animals so barren of results must be sought in the injudicious selection of sub- stances intended to serve as antidotes. It is simply impossible to act on an organic compound like snake- poison, coursing through a living system, by chemicals that will either combine with it or decompose it in a manner likely to deprive it of its deadly qualities and render it innocuous. Yet what do we find? Acids and alkalis, arsenic, bromides and iodides, chlorine, mercurial preparations, &c., &c., have been poured into the luckless animals as if they were so many test tubes. A chemical antidote, a substance possessing special affinity to snake-poison and by means of this affinity combining with it in some mysterious and incomprehensible manner, one can hardly imagine to exist. Physiological antidotes, on the other hand, substances acting on the. system in a manner the exact reverse of, and in direct antagonism to the snake-poison, though apparently the only feasible ones, have been strangely neglected and almost despised by experimenters. In the vast storehouse of Nature the department most likely to furnish such antidotes is the vegetable kingdom. The untutored human mind has for centuries past intuitively clung to this idea, and sought among plants tor remedies against the deadly ophidian poison. Hence the great number of vegetable anti- dotes that have from time to time been recommended and the efficacy of some of which at least has been HISTORICAL REVIEW. 7 confirmed by reliable observations. But the hint thus given to science was not taken. Instead of research being pushed on diligently in the only direction that promised any chance of success, it was cut short by the baneful method of experimenting on animals. When it had been demonstrated that a dog, a cat, or other animal, after having been saturated with snake- poison, did not recover after the administration of an alleged antidote, the illogical conclusion was drawn at once that it could not possibly be of any use to man, whilst, in reality, the only proof rendered by the experiment, if made properly, was that the respective antidote could not be relied on in treating animals of the class experimented on. That some of these des- pised antidotes are worth a little further investigation may, in the light of present experience as to the value of strychnine in snakebite, be inferred from the fact, that among them is the wood of Strychnos Colubrina, and also the well-known Huang Noo, a vegetable ex- tract made from another variety of the Strychnos family, and largely used by the Chinese, whilst, accord- ing to a letter in the Australasian Medical Gazette, July, 1892, the principal ingredient of a strange com- pound used by the native snake doctors of Central America with much success is Nuxw Vomica. It is superfluous to enter into a criticism of the treatment of snakebite until recently in vogue, for, with the exception of the local one by ligature and excision, it stands self-condemned by its complete inefficiency. It may be summed up as a vain attempt 8 HISTORICAL REVIEW. to stem the collapse invariably attending snakebite by: the administration of stimulants, such as alcohol, ether, ammonia, &. The attempt is vain, for a person in collapse from snakebite cannot be stimulated by any of these remedies, since neither the heart nor the nerve centres respond to them in the slightest degree, as they do in the absence of snake-poison, the only one that has any effect at all in slight cases being ammonia. But the attempt is not only in vain, it is highly in- jurious, especially if made with the usual large doses of alcohol, for, in addition to the latter not having the slightest influence on the snake-poison and its baneful effects, they act as an anesthetic and thus add to the existing depression, besides increasing the tendency to internal hemorrhage. It might, under these circumstances, have been expected that any new method of treating snakebite, based on scientific grounds and holding out a sure prospect of success, would be hailed with pleasure, and that conservatism, opposing the new simply on account of its newness, would refrain from its usual tactics in a case where there was really nothing to conserve. But this was not to be, and strange, indeed, it would have been if the writer had escaped the opposition which is almost invariably offered to the discoverer. It appears to be one of the laws of human evolution, wisely de- signed to prevent precipitate advance, that every new discovery must run the gauntlet of men whose mission it is to act as brakes on the wheels of progress, Of the opposition which has been offered HISTORICAL REVIEW. 9 to the strychnine treatment it would, therefore, be folly to complain, but just cause of complaint is furnished by the unscientific attitude which was assumed from the very first and has been maintained throughout by its opponents. Not a single attempt has been made to disprove the correctness of the theory on which it is founded, yet to leave this theory unquestioned but object to the conclusion to which it leads, must strike even the lay mind as a most illogical proceeding. It is self-evident that, when strychnine is administered as an antidote to snake-poison, the quantity of it injected must be in proportion to that of snake-venom present in the sys- tem, and that the doses in which we dispense it in ordin- ary practice must be entirely left out of sight. Still, in the face of these obvious conclusions, we have had veterans, grave and grey, arguing pompously that the heroic doses advocated by the writer could not be countenanced, and that even medical men could not be entrusted with the serious task of administering them. Even as late as the last medical congress at Sydney this absurd objection to large doses of the antidote was again brought forward. After quantities averag- ing from halfa grain to a grain have been injected many times in Australia with continuous success, after Banerjee has even gone as high as three and four grains in India without a single failure, and with- out in one single instance serious strychnine symptoms being evoked, the writer of the paper on “Snakebite and its Cure” based his principal objection to the 10 HISTORICAL REVIEW. treatment on the alleged ground of there not being © sufficient evidence before us to justify heroic doses and show them to be safe in practice. When people wil- fully shut their eyes against the most conclusive evi- dence, it is improbable that any amount of it would satisfy them. Apart, however, from the fully proven antagonism between the two poisons rendering the large doses of the antidote, which in all serious cases are indispensable, perfectly safe, the fear of strychnine is, in itself, a very strange aberration of judgment on the part of my opponents, considering how easy it is to counteract any noteworthy excess in its action, if, per- chance, it should occur through unnecessary overdosing, by appropriate remedies. All other objections to the treatment require but to be glanced at to show their absurdity. Certain crude experiments on dogs made many years ago in India, and put forward as irrefutable at first, have been abandoned of late, and my learned opponents have now taken up a position in their stronghold of statistics, supposed to be impregnable, but in reality only the last refuge of the destitute, a position from which, by dexterous handling of alleged facts, anything and everything can be proven, in short, to use a strong expression, not my own, a convenient and respectable form of lying. By means of these statistics they try to prove, in the first place, that Australian snake- poison is not at all the insidious death-dealing agent it is supposed to be, since, according to statistics, only 126 persons died from it in three colonies within the HISTORICAL REVIEW. Il last ten years. Further study of these statistics leads them to the inference that a strong healthy adult will recover from snakebite without any treatment, and thus they finally arrive at the conclusion aimed at, that persons cured by strychnine injections would probably have recovered without them. These are the infer- ences drawn by men, who, practising in towns, have probably never seen a case of snakebite. How do they tally with the facts of the case? Itis true that the mortality among those bitten by snakes is small here as compared with India, though the poison of our snakes, quantity for quantity, has been proven to be quite as deadly as that of the Indian ones. Our greater immunity is due to our snakes giving off less poison at a bite, and with their short and (excepting ‘those of the death adder) merely grooved poison fangs injecting it very superficially, thus making the process of elimination of the poison by ligature and incision or excision of the punctures much more easy and successful. It is to this treatment, which, as a rule, is immediately adopted in the bush, that our small mortality is due. Our children are taught it in school, and the most illiterate bushman knows how to carry it out. Where it is omitted by persons not knowing that they are bitten until the poison has been absorbed recovery is as rare as it is with the ox and the horse left to themselves without any treatment. But it requires a prodigious stretch of the logical faculty to understand what our small mortality from snakebite has to do with the intrinsic merits of the strychnine 12 HISTORICAL REVIEW. treatment. Even if nobody died at all its effects in doing away with the misery and suffering, which, before its introduction, invariably followed snakebite, and often was never got rid of completely, would still be sufficiently beneficial to render the senseless opposi- tion to it on the part of a small section of medical men little short of criminal ; for these effects are a matter of constant observation, and cannot, like the rescues from death, be called into. question. The statistics brought forward to prove that the treatment has not reduced the death-rate are also most faulty. Until it is thoroughly understood and in every instance properly applied it is manifestly foolish as well as unfair to lay non-success and failures at its door. When a medical man is called upon to treat a serious case, and instead of boldly addressing himself to the task of combating the symptoms by injecting the antidote irrespective of the quantity he may require until it has conquered the snake-poison, becomes nervous and ceases to inject, when, after what in ordinary practice would be a dangerous dose, he sees but little effect, or if from the first he injects small doses at long intervals, the cause of failure surely lies with him and not with the antidote, which rarely fails where it is properly applied. The duty of dissemin- ating a sound knowledge ofthe principles ot the strychnine treatment unquestionably devolves on our health authorities, who ought, by this time, to have taken some notice of it. But officialdom remains obtuse and issues circulars on the treatment of snake- HISTORICAL REVIEW. 13 bite, recommending, inter alia, the free use of alcohol. The literature on the subject of snake-poison is very voluminous, but those who seek for enlighten- ment in it will be as disappointed as the writer was after wading through it. The toilers in this barren field of research were numerous, but with few excep- tions, they toiled in vain. Fonrana may be looked upon as the founder of that hideous experimentalism by which, in his hands alone, four thousand animals were tortured to death without a single tangible result except that in his great work, ‘ Reserche Fisiche sopra il Veneno della Vipera,” which he wrote at the con- clusion of his cruel labours, he left us a grotesque monument of patient, but ill-guided research. Other Italians, following his method, Redi, Mangili, Metaxa, &c., were equally unsuccesstul in shedding one ray of light on the vexed and obscure problem. Among the Germans who contributed to the subk- ject may be mentioned :— Waener.—“Erfahrungen iiber den Biss der ge- meinen Otter.” Prinz Maximitian von Wizpp.—“ Beitriige zur Geschichte Brasiliens.” Lenz.—“ Schlangenkunde.” Hertnzex.— Ueber Pelias Berus und Vipera Am- modytes.” Among the French :— Sovuperran. — ‘Rapport sur les Vipéres de France.” . 14 HISTORICAL REVIEW. Butier.— Etude sur la Mosure de Vipére.” British and American Workers are the most numerous. Commencing with the century we have :— Russett.—“ An Account tof Indian Serpents, collected on the Coast of Coromandel.” Later on, S. Were Mrrcuztt.— Researches upon the Venom of the Rattlesnake.” Hatrorp —“On Australian Snakes, and the Intra- venous Injection of Ammonia, in British Medical Journal, Medical Times, and Australian Medical Journal.” Jones.—‘‘ On Trigonocephalus Contortrix.” Nicuotsoy.—‘ On Indian Snakes.” Sir Joseph Fayrer.— ‘The Tanatophidia of India.” Also, “ Researches in conjunction with Richards, Brunton and Eward.” Watt —“ On the Difference in the Physiological Effects produced by the Poison of Indian Venomous Snakes.” Proc. Royal Soc., 1881, vol. xxxii., p. 333. Among those enumerated above Wall is the only one who formulated a correct and thoroughly scientific theory of the action of snake-poison, which has since been confirmed by Australian research and by Feoktistow’s elaborate experiments. It is strange that, after finding the theory that explained all the phenomena, he did not follow it up by applying the antidote to which his theory should have led him. SNAKE-POISON AND ITS ACTION. The poison gland of snakes is the analogue of the parotid gland of mammals, both in position and_ struc- ture. Its acini or alveoli are lined with a layer of secretory, columnar, finely granular cells and arranged with great regularity along the excretory duct, which is straight and cylindrical and opens with vipers into the hollow poison fang, with our colubrines into the groove on the anterior surface of it. Snake-poison, as it leaves this gland, is a thin, albuminoid, yellow liquid of neutral reaction. On exposure to the air it becomes viscid and slightly acid. Of its chemical composition we know as yet but little, and it 1s very questionable whether the most perfect chemical analysis of its constituents would ever have given us a clue to its action or will enrich our present knowledge of it. Like all albuminoid secreta it becomes putrid after prolonged exposure and then, through ammonia pro- duction, loses its acid, and assumes an alkaline re- action, still, however, though in a modified degree, retaining its toxic properties, which are completely lost only after an exposure of many months. Feok- tistow found that freezing at 1° R. caused the poison to separate into a solid mass and a thin, very yellow 16 SNAKE-POISON AND ITS ACTION. liquid, which, even at a temperature of 4° R., remained liquid, and the poisonous properties of which greatly exceeded those of the solid mass. Boiling diminishes and, continued for any length of time, completely des- troys the potency of the poison. The microscope has done good service in the investigation of snake-poison, It has, in the first place, informed us with absolute certainty that there are no micro-organisms or germs of any kind in the fresh poison immediately after it leaves the gland. But a still more important revelation we owe to it is the fact that these organisms, when we introduce them into a 2 % solution of the poison, do not die, but live, multiply, and enjoy their existence most lustily, as they do in any other non-poisonous albuminoid liquid, whilst animals of a higher type—say a snail or a frog —soon perish in it. In watching the movements of the latter we find that they get slower and slower, and finally cease. We now follow up the interesting research, and take two frogs. Under the skin of one of them we inject a few drops of the poison solution, the other one for comparison we leave intact, and place both into a glass globe partly filled with water. Ina very short time we have no difficulty to identify the poisoned frog. Its hind legs begin to drop and their movements become sluggish. This difficulty increases from minute to minute, until at last all motion ceases, and the legs hang down completely paralysed. At the same time we observe that the animal shows increasing difficulty of breathing, that, even when taken SNAKE-POISON AND iTS ACTION. 17 out of the water, and placed on the table before us it gasps for breath and is unable to move. At last respiration ceases altogether and the frog dies. Two problems now present themselves for solu- tion. In the first place we have to account for the fact of the snake-poison leaving the lower forms of animal life intact and being fatal to the higher ones. The symptoms we have observed in the frog point unmistakably to an affection of the nervous system as their cause. Now we know that the lower forms which the pvison does not affect have no such system, and we are justified to infer that to the absence of this system they owe their immunity. This infer- ence leads us on to a second one equally justifiable, namely, that there is a certain unaccountable attrac- tion between the delicate nerve tissue and the subtle ophidian poison, which renders the latter a specific nerve poison. Our second problem is to ascertain the nature ot the change in the nerves, to find out, if possible, whether it is merely functional or an actual interfer- ence with the structure of either cells or fibres. With this end in view we once more consult the microscope. We make two preparations, one of nerve fibres and of nerve cells of the poisoned frog, and, under the micro- scope, compare them carefully with an analogous one from the killed healthy frog. The result is purely negative as regards structural change. Both present identical and perfectly normal pictures of apparently 18 SNAKE-POISON AND ITS ACTION. healthy cells and fibres. There being no visible structural change we are driven to the conclusion that only a functional one has been effected by the poison, and with the symptoms observed all pointing in that direction, that it is of central origin. The writer’s theory as to the action of snake- poison, formed, in the first instance from observations made at the bedside of his patients only, is thus con- firmed by experiments specially instituted by him for that purpose. Further proof of its correctness we have in the brilliant results of the strychnine treat- ment of snakebite in Australia, which is the outcome and practical application of this theory. In those desperate cases more especially, reported from all parts of the colonies, in which death was imminent, and pulse at wrists as well as respiration had already ceased, the strychnine injections could not possibly have effected complete recovery within a few hours if the structure of the nerve centres had been impaired or blood changes brought about incompatible with life. Feoktistow’s experiments, made with viper poison, fully bear out the correctness of the writer’s theory, besides proving that there is no essential difference between the action of the viperine and_ colubrine poisons. He proved conclusively that snake-poison does not destroy protoplasm or interfere with infusorial life, that injected into the heart of a mollusc it causes an almost immediate cessation of its action, that SNAKE-POISON AND ITS ACTION. 19 hypodermic injections of it in fish produce contraction of the pigment cells and bleaching of the integuments, followed by asphyxial respiration, general paralysis and death. Similar results were observed on frogs. In mammals the symptoms were : dyspnoea, asphyxia, paresis and paralysis of the lower extremities with succeeding general paralysis, sometimes tonic and clonic convulsions, hemorrhages from bowels, lungs, nose and bladder, and finally complete paralysis of respiration and of heart. Action of Snake-Poison on Special Nerve Centres. It must be borne in mind that the symptoms as about to be detailed are successive only to some extent in the order presented. They commence generally at the lower part of the spinal cord, but immediately afterwards, if not simultaneously, are ushered in with great rapidity from other centres, masking each other and rendering it extremely difficult to observe and analyse them separately. They are also very variable through the poison concentrating its action on special centres, leaving others comparatively intact, and this not only when from different varieties of snakes, but also from snakes of the same variety. Another element increasing the difficulties of correct analysis are the depressing effects of fear, inseparable in all but the strongest minds from the consciousness of having been 20 SNAKE-POISON AND ITS ACTION. bitten, and so similar in appearance to those of snake- poison, that sometimes it is by no means easy to decide which of the two is in operation, and that only those cases are of real value to the observer from which this element of fear is completely excluded. A.—