On Snake-Poison: its Action and its Antidote Part 1

On Snake-Poison: its Action and its Antidote.

by A. Mueller.

PREFACE.

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 throughout 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 morbid processes engendered by the snake venom and the _modus operandi_ 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 intelligent, 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 prompt.i.tude 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.

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 confreres, 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 _Australasian Medical Gazette_, and to the Hon. J. M. Creed, its able editor, for the ample s.p.a.ce 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 without an elaborate series of experiments on animals, that it is a peaceful conquest not attained by means of doubtful justification, and which have hitherto invariably failed in their object. This object--the discovery of the coveted antidote--instead of being brought nearer, was, in fact, further removed by every succeeding 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 baffled experimenter abandoned his task in despair.

Still, these negative results notwithstanding, the writer is confronted by a certain cla.s.s 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 recovery takes place after proper administration of the antidote in cases which, according to all our previous experience, would have ended fatally, it is not illogical to a.s.sume that antidote and recovery stand in the relation of cause and effect. This sceptical att.i.tude 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 constantly 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 circ.u.mstances, 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 on animal life can be ascribed, were in complete harmony with the writer's views, in fact, a re-statement of his theory. It was a strange coincidence, or whatever it may be called, that, independent of each other, at almost opposite parts of the globe, and by opposite methods, we had arrived at almost identical conclusions.

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 a.n.a.lysis of the symptoms observed at the bedside 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, mistaking the functional a.n.a.logy that exists between the nerve centres of the lower animals and those of man for absolute ident.i.ty, 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, 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 demonstrate the action of snake-poison on a strictly scientific, experimental basis. For this reason, and with so high an authority as Professor Kobert vouching for the correctness of the experiments, they will be frequently quoted hereafter.

[Ill.u.s.tration]

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 snakebite-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 modic.u.m of truth mixed with a large proportion of error, but none but one fulfilling 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 imaginary 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 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 a.s.sume 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 a.s.sert 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 indigenous, and these comparatively harmless snakes. The best scientific talent has, therefore, only exceptionally been brought to bear on the subject. In those countries on the other hand in which venomous snakes abound and opportunities for observing the poison-symptoms on man are more plentiful, the observing element has been comparatively deficient.

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, a.s.suming as a working hypothesis that there is but one law for all snake-poison and not several ones, just as there is one law for the structure 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 observation and careful a.n.a.lysis of the symptoms produced by the poison on man, and as the opportunities for such observation are not of frequent occurrence to the individual, 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 anywhere 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 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 un.o.bjectionable, although, without an elaborate scientific 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 antidote 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 possums_" 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 applied to man. As pointed out before, a.n.a.logy has been confounded with ident.i.ty. 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, for whilst in man a slight excess in the quant.i.ty required to subdue the snake-virus is not only harmless, but actually necessary, 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.

Another cause that has largely contributed to render experiments on animals so barren of results must be sought in the injudicious selection of substances 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, a.r.s.enic, 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 hardy 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 for remedies against the deadly ophidian poison. Hence the great number of vegetable antidotes that have from time to time been recommended and the efficacy of some of which at least has been 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 cla.s.s experimented on. That some of these despised 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 extract made from another variety of the Strychnos family, and largely used by the Chinese, whilst, according to a letter in the _Australasian Medical Gazette_, July, 1892, the princ.i.p.al ingredient of a strange compound used by the native snake doctors of Central America with much success is _Nux 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 to stem the collapse invariably attending snakebite by the administration of stimulants, such as alcohol, ether, ammonia, &c. 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 injurious, 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 anaesthetic and thus add to the existing depression, besides increasing the tendency to internal haemorrhage.

It might, under these circ.u.mstances, 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 designed 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 to the strychnine treatment it would, therefore, be folly to complain, but just cause of complaint is furnished by the unscientific att.i.tude which was a.s.sumed 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 quant.i.ty of it injected must be in proportion to that of snake-venom present in the system, and that the doses in which we dispense it in ordinary 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 quant.i.ties averaging from half a 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 without in one single instance serious strychnine symptoms being evoked, the writer of the paper on "Snakebite and its Cure" based his princ.i.p.al objection to the 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 wilfully shut their eyes against the most conclusive evidence, 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, perchance, 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 dest.i.tute, 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 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 inferences 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? It is true that the mortality among those bitten by snakes is small here as compared with India, though the poison of our snakes, quant.i.ty for quant.i.ty, 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 treatment. Even if n.o.body 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 opposition 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 quant.i.ty 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 disseminating a sound knowledge of the principles of 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 snakebite, recommending, _inter alia_, the free use of alcohol.

The literature on the subject of snake-poison is very voluminous, but those who seek for enlightenment 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 exceptions, they toiled in vain.

FONTANA 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 conclusion 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 unsuccessful in shedding one ray of light on the vexed and obscure problem.

Among the Germans who contributed to the subject may be mentioned:--

WAGNER.--"Erfahrungen uber den Biss der gemeinen Otter."

PRINZ MAXIMILIAN VON WIEDD.--"Beitrage zur Geschichte Brasiliens."

LENZ.--"Schlangenkunde."

HEINZEL.--"Ueber Pelias Berus und Vipera Ammodytes."

Among the French:--

SOUBEIRAN.--"Rapport sur les Viperes de France."

BULLET.--"Etude sur la Mosure de Vipere."

British and American Workers are the most numerous. Commencing with the century we have:--

RUSSELL.--"An Account of Indian Serpents, collected on the Coast of Coromandel." Later on,

S. WEIR MITCh.e.l.l.--"Researches upon the Venom of the Rattlesnake."

HALFORD--"On Australian Snakes, and the Intravenous Injection of Ammonia, in _British Medical Journal_, _Medical Times_, and _Australian Medical Journal_."

JONES.--"On Trigonocephalus Contortrix."

NICHOLSON.--"On Indian Snakes."

SIR JOSEPH FAYRER.--"The Tanatophidia of India." Also, "Researches in conjunction with Richards, Brunton and Eward."