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[Illustration]
ON
SNAKE-POISON.
ITS ACTION
AND
ITS ANTIDOTE.
BY
A. MUELLER, M.D.
SYDNEY:
L. BRUCK, MEDICAL PUBLISHER,
13 CASTLEREAGH STREET.
1893.
SYDNEY:
WEBDALE, SHOOSMITH & CO., PRINTERS,
117 CLARENCE STREET.
1893.
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 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.
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
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 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 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 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
assume that antidote and recovery stand in the relation of cause and
effect. This sceptical 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 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 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 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 analysis 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 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,
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.
[Illustration]
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 modicum
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 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
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, assuming 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 analysis 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 unobjectionable, 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, 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, for whilst in man a slight excess
in the quantity 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, 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 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
class 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
principal 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 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 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
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 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 quantities 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 principal 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 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 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, 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 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 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 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
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 ueber den Biss der gemeinen Otter."
PRINZ MAXIMILIAN VON WIEDD.--"Beitraege 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 MITCHELL.--"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."
WALL.--"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 structure. 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 is 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
production, loses its acid, and assumes an alkaline reaction, still,
however, though in a modified degree, retaining its toxic properties,
which are completely lost only after an exposure of many months.
Feoktistow found that freezing at 1 deg. R. caused the poison to separate
into a solid mass and a thin, very yellow liquid, which, even at a
temperature of 4 deg. 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 destroys 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. In a 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 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 solution. 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 poison 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
inference leads us on to a second one equally justifiable, namely, that
there is a certain unaccountable attraction 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 of the change in the
nerves, to find out, if possible, whether it is merely functional or an
actual interference 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 microscope, 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 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 confirmed by experiments specially instituted by him for
that purpose. Further proof of its correctness we have in the brilliant
results of the strychnine treatment 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 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, haemorrhages 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 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.--Action on the Anterior Cornua of the Spinal Cord.
The anterior cornua are almost invariably the first of the motor-centres
attacked by the snake-poison, the affection (commencing with paresis and
in serious cases generally culminating in paralysis) beginning in the
lumbar ganglia and taking an upward course. The lower extremities feel
unnaturally heavy and a paretic condition of the muscles supervenes
_simultaneously on both sides_. The walk becomes unsteady and
staggering, very similar to that of persons under the influence of large
doses of alcohol. By a powerful effort of the will, however, persons in
this condition are often able to walk and even run for some distance,
especially if by prompt ligature the absorption of the poison has been
checked. As the affection proceeds, though still able to move the legs
in a sitting posture, they are unable to rise again. Ere long even
sitting up becomes impossible and they collapse helplessly. At this
stage sensation is still intact, and reflex action, by pricking the
skin, &c., still takes place. The upper extremities generally retain the
power of voluntary motion, even after the muscles of the neck have
become paretic and the head is held up with difficulty or sinks to one
side.
With birds, according to Feoktistow, the reverse is the case. The wings
are usually first attacked, or paresis comes on in wings and legs at the
same time.
B.--Action on the Medulla Oblongata.
a.--The Vaso-Motor Centre.
Whilst the voluntary muscles are thus brought under the influence of the
poison, symptoms denoting the invasion of the oblongata are rapidly
developing. The first of these is the deadly pallor and ashy hue of the
cold skin, evidently due to the blood receding from the surface, a
condition not unlike that obtaining in extreme anaemia. As persons in
this state complain of an agonising feeling about the heart and of
deadly faintness, a paretic condition of the heart suggests itself as
the most obvious cause, more especially when taken in conjunction with
the small, frequent, and compressible pulse. But though the heart muscle
is no doubt participating in the general paresis, the condition of the
surface of the body is in reality one of anaemia. The blood, even at this
early stage, begins to accumulate in the large veins of the abdomen,
which expand gradually in consequence of the diminishing motor force
supplied by the splanchnicus, keeping them in the normal state of
contraction when intact and having its centre in the medulla oblongata.
When this large vaso-motor nerve is cut in animals anywhere in its
course, the veins of the abdomen become distended enormously. The animal
is, so to say, bled into its own belly.
By a series of most interesting experiments Feoktistow has shown
conclusively that snake-poison has the same effect on the abdominal
circulation as section of the splanchnicus. Even slight intravenous
injections of the poison produced quickly a high degree of paresis of
the nerve and a corresponding engorgement of the veins of the abdomen,
whilst after lethal doses, the paresis culminated in a few minutes in
complete paralysis, followed by rapid collapse, excessive weakness of
the bloodless heart, and death from paralysis of the latter and anaemia
of the nerve-centres. One experiment deserves special record, as it also
shows the untenability of the blood-poison theory.
The whole vascular system of an animal poisoned by intravenous injection
was thoroughly washed out with the warm defibrinised blood of four
animals of the same species, the blood being infused into an external
jugular vein and allowed to flow out of a crural artery. Although blood
exceeding its normal quantity was left in the animal, when the vessels
named were closed, the nerve affection remained unchanged. The blood
pressure raised during the infusion sank at once again to zero, when it
ceased, and the paralysed veins of the abdomen became engorged once
more with the whole, or nearly the whole, of the blood-mass, leaving the
rest of the body anaemic as before. This interesting experiment also
shows how strong a hold the snake-poison has on the nerve-cells when
they are thoroughly under its influence, and how independent this
paralysing action is of the blood, persisting, as it was in this case,
after all the poison had been washed out of the animal.
The heart in vaso-motor paresis and paralysis is weakened in the first
instance by the direct action of the poison on the medulla oblongata and
the intracardiac ganglia. Its pulsations, at first retarded in
frequency, become accelerated soon after the introduction of the poison,
the pulse rate increasing rapidly and the waves becoming smaller and
more easily compressible in proportion to the frequency of the pulse,
which generally counts from 100 to 120 and more per minute at a
comparatively early stage of the poisoning process. But an equally
potent cause of heart failure is its depletion by the simultaneous
stagnation of the blood mass in the veins of the abdomen. Finally, to
complete the mischief, we have not only anaemia of the semi-paralytic
oblongata, but the scanty blood supply this important centre receives
becomes also surcharged with carbonic acid. Oxyhaemaglobin disappears
almost entirely from the blood under the circumstances detailed, as both
pulmonary and internal respiration are greatly interfered with, the
blood tending more and more towards that thin dark condition which it
presents after death, and which has been taken as _prima facie_ evidence
of the direct blood-poisoning action of snake virus by one and all of
previous investigators.
That under the powerful combination of causes, each of which is in
itself sufficient to endanger life, and greatly intensified as paresis
gradually deepens into paralysis, the heart, even of large animals,
succumbs in a comparatively short time, may be readily understood.
The _blood-pressure_, under the circumstances just detailed, must
necessarily be _nil_. Observations by means of the sphygmograph at the
bedside of a person suffering from snake-poison are scarcely feasible,
except, perhaps, in a hospital, and thus far are not on record. We must,
therefore, once more fall back on Feoktistow's experiments, which show
that even the smallest doses (0.02 to 0.04 mllgr.) of the dried poison
_per kilo_ injected into the vein of a cat caused a fall in the
blood-pressure almost immediately, without influencing either pulse or
respiration, but that two to four mgr. were sufficient to reduce the
blood-pressure to zero and bring on collapse, infusions of blood only
raising it temporarily. Of drugs raising the blood-pressure he found
ammonia the most effective, but only after slight doses of the poison;
after lethal ones it had no effect whatever on the blood pressure but
greatly increased the haemorrhagic process in all internal organs. This
important observation should be kept in mind by those who inject
ammonia in serious snakebite cases, and it probably applies likewise to
_the excessive use of alcohol_.
This leads the writer on to the discussion of this singular haemorrhagic
process principally characteristic of viperine poisoning, and only very
exceptionally produced by the poison of colubrines. It is among the
symptoms of snakebite poisoning one of the most interesting ones, but
also one most difficult of explanation. There can be no doubt that it is
produced by vaso-motor paresis and paralysis. We further know that it is
preceded by dilatation of the capillaries and small veins, and that it
is effected principally through the process known as diapedesis, or the
passage of both red and white corpuscles with plasma through the
unruptured capillary membrane, and even the thin one of small veins,
which is nearly of the same structure, being composed of endothelial
cells united by cement. This membrane possesses a certain degree of
porosity, which is probably increased by dilatation. In the absence of
plain muscular fibres contraction and dilatation of the capillaries can
only be effected by a corresponding contraction and expansion of the
nuclei of the endothelial cells. As fibrils derived from non-medullated
nerves terminate in small end-butts in connection with the capillary
membrane, we may assume that the nuclei of the endothelial cells are
under the sway of vaso-motor nerve currents, that weak ones will expand,
strong ones contract them. We may further assume that the red and white
corpuscles force their way out of the vessels through pores in the
cement substance, since a passage of cell through cell is not thinkable.
Thus far we see our way fairly clear. But the question now arises: what
causes the solid constituents of the blood to force their way through
the capillary membranes all over the mucous surfaces, even the
conjunctiva, and not these alone, but also through serous membranes such
as the pericardium, and strangest of all, through old scars in the skin?
If the most modern ideas as to the cause of diapedesis being blood
pressure are correct, it is quite incomprehensible how it can take place
in the absence of blood pressure, and take place so extensively. The
theory of blood pressure may apply to diapedesis accompanying the
inflammatory process. In snakebite poisoning it is more likely to be due
to passive engorgement of the capillary system and probably also to
blockage of corpuscles in the finest capillary tubes. In vaso-motor
paresis, and still more paralysis, the arterioles supplying the
capillaries are widely dilated, and at the lowest blood pressure
probably send more blood into the latter than in the normal state. This
circumstance in itself is apt to cause capillary engorgement. In the
finest capillaries permitting only a string of corpuscles, one behind
the other but none abreast, to pass through in the normal state,
dilatation may cause blockage by two or three becoming wedged in abreast
and closing the lumen of the vessel by a sort of embolism. On the
arterial side of this obstruction the crowded corpuscles force their way
through the porous cement substance by what little "vis a tergo" there
may be left yet, whilst in the venous side, in the small veins
corresponding with the closed capillaries, engorgement must necessarily
take place through this "vis a tergo" being entirely absent, and
diapedesis, which here also has been observed, follow in due course. The
writer has always been inclined to take this view, the correctness of
which appears to be borne out by an experiment recorded by Feoktistow.
He found on sprinkling a two per cent. solution of snake-poison over the
mesentery of an healthy animal, that wherever a drop of the solution
fell, almost immediately the capillaries and small veins became dilated
and small point-like effusions of blood appeared, gradually enlarging
and ultimately becoming confluent with adjoining ones. Large haemorrhagic
surfaces were thus formed in a comparatively short time. Here paralysis
of the nerve-cells interspersed in the vaso-motor nerve-ends was
evidently the first effect, followed by dilatation of the capillaries
and immediately afterwards by effusion. Without some obstruction within
the capillaries, like that above described, effusion in this purely
local poisoning process appears unexplainable.