NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
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Scientific Memoirs by
Wall's third argument is of much the same quality as the second one, for
until it has been definitely shown that the nervous symptoms are not induced
by blood-change, the absence of other evidence of such change is of no con
-clusive value. As regards the next point, the absence of renal evidence of blood-
change, we find that in cases of CO-poisoning there is no constant renal
evidence of the blood-change which is unequivocally present, and, on the other
hand, that in many cases of poisoning by cobra-venom there is clear evidence of
either abnormal increase or decrease of renal secretion. Finally, in respect to
the microscopical evidence, it has already been pointed out that the blood derived
from the bodies of animals which have just died of intoxication by cobra-venom
may very likely show no appreciable signs of alteration in its formed constituents,
because death occurs at a time when the venom has not yet exerted its full action,
and may be caused by an amount of venom, which, though incapable of producing
conspicuous solvent effects on the corpuscles, is amply sufficient to induce a
fatal depression of the respiratory property of the blood.
None of the above arguments, then, appear to be of any really conclusive
value in demonstrating the absence of any important hæmic change in cases
of intoxication by cobra-venom, and I am not aware of the existence of any of
greater cogency. On the other hand, there are a whole series of phenomena
which appear to be unequivocally adverse to the belief in the primarily neuro
-tic action, of the poison.
Wall himself, in spite of his belief, adduces a very important one when he
points out that a latent period normally intervenes between the entrance of a
lethal dose of venom into the circulation and the appearance of any nervous
symptoms, and quite correctly affirms that this shows " that the mere pre
-sence of the poison in the blood, even in sufficient quantity to kill, is not
capable of producing directly a physiological effect."
* But, if it be incapa
-ble of producing a direct " physiological effect " on the nervous apparatus,
what becomes of its action as a direct nerve-poison ? When a lethal dose
of any direct nerve-poison enters the circulation it manifests its presence at
once and produces its fatal effects with great rapidity. Minimal lethal doses
of the salts of strychnia or of one of the toxins which are present in Daboia
-venom on entering the circulation cause almost immediate death, but this is
not the case with minimal lethal doses of cobra-venom, for their entrance is
followed by a prolonged latent period during which no appreciable symptoms
whatever are present, and those which subsequently appear follow a very slow
and gradually cumulative course ere they terminate in death. The contrast
between the phenomena presenting themselves in such cases is illustrated by the
results of the following experiments in all of which the poisons were directly
* Op. cit., p. 43.
Medical Officers of the Army of India.
I7
injected into the jugular vein, and were, therefore, placed in like circumstances
as regards the production of their specific effects.
Experiment XIII.—Direct introduction of 0.0044 gramme of nitrate of
strychnia into the jugular vein of a fowl.
A fowl received an injection of 0.0044 gramme of nitrate of strychnia in
0.5 c.c. of distilled water directly into the jugular vein. Immediate general
convulsions occurred and were followed by death within a few minutes.
Experiment XIV.—Direct introduction of a minimal lethal dose of Daboia
-venom into the jugular vein of a fowl.
A sample of dried Daboia-venom was carefully tested and the minimal lethal
dose necessary to give rise to fatal general convulsions was ascertained to
amount to between 0.004 and 0.005 gramme. A fowl received an injection of
0.005 gramme in 0.5 c.c. of distilled water directly into the jugular vein.
Furious general convulsions set in before the bird could be set down and
were immediately succeeded by death.
Experiment XV.—Direct introduction of a minimal lethal dose of dried
cobra-venom into the jugular vein of a fowl.
A fowl received an injection of 0.0005 gramme of a stock of dried venom,
of which that amount constituted a minimal lethal dose for fowls of 1 kilo in
weight. The venom was dissolved in 0.5 c.c. of distilled water and the solution
directly injected into the jugular vein at 10-50 A.M. No specific symptoms
whatever manifested themselves until between 2 and 3 P.M., and death did not
occur until between 7 and 8 P.M.
The entire absence of any appreciable latent period in the case of the
entrance of minimal lethal doses of direct nerve-poisons into the circulation, and
the necessary intervention of such a period where nervous symptoms are de
-pendent on certain preliminary effects of the poison on the system could hardly
be more strikingly illustrated than they are by the results of these experiments.
The fact that when relatively excessive quantities of cobra-venom are directly
introduced into the circulation the latent period is very greatly abbreviated or
even practically entirely absent is, of course, no valid argument against the
belief that the primary action is a hæmic one, it only indicates ,that the toxin is
of the nature of a ferment, which, when acting on the blood in large quantities,
is capable of rapidly inducing changes which can only be slowly and gradually
induced by fractional ones. The phenomena in the two cases are precisely
parallel to those which present themselves when large and fractional quantities
of venom act upon blood outside the body. Where the proportion of venom is
relatively excessive an immediate and total loss of respiratory property and co
-agulability, and exceedingly rapid solution of the bodies of the red corpuscles
take place, where it is fractional, equally great changes ultimately occur in so
far, at all events, as respiratory property and solution of the corpuscles are con
-cerned, but their progress is protracted and cumulative.
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Scientific Memoirs by
The phenomena characteristic of the action of minimal lethal doses of
cobra-venom are not those of the action of any material which when present
within the system at once manifests its presence by producing its maximal
effects, but are those of one acting in the manner of a ferment and producing a
gradually cumulative effect. The extreme disproportion between cause and
ultimate effect in cases of fatal intoxication by minimal lethal doses of the venom,
and the fact that fractional doses are capable of ultimately producing the same
results as very much larger doses produce within a very short time, also point to
the presence of a ferment action, which it is hard to conceive of as coming into
direct play upon the nervous apparatus, but which may well ultimately affect
the latter by primarily inducing changes in the blood.
Again, it is apparently universally admitted that the immediate cause of
death in cases of intoxication by cobra-venom is asphyxia. Those who regard the
venom as a direct neurotic poison ascribe this solely to gradual paralytic cessa
-tion of respiratory movements, but there are at least two good grounds for
doubting the correctness of this conclusion. These are supplied by the pheno
-mena following the direct introduction of relatively large masses of venom into
the circulation, and those attending treatment by means of artificial respiration.
The result of the introduction of relatively large quantities, of venom directly
into the circulation is not as is very clearly shown by the data of Experiment XI,
the immediate induction of paralysis, but the immediate induction of respiratory
symptoms and of asphyxial convulsions accompanied by profound changes in the
blood as evinced by permanent abolition of respiratory property and defective
and retarded coagulation. The occurrence of asphyxial convulsions is a normal
terminal phenomenon in all cases of acute fatal intoxication by cobra-venom, and
they are ordinarily credited solely to the gradual, antecedent failure in respiratory
movements, but in cases, like that recorded by Wall in which " violent and irre
-gular contractions of the respiratory muscles " suddenly replaced normal res
-piration thirty seconds after the injection of 1 c.c. of fresh venom into the
saphena vein of a dog,
*
there is no such antecedent failure to account for the
phenomenon and. it can only be interpreted as indicating the effects of sudden
and excessive diminution in the respiratory property of the blood upon the res
-piratory centre. The results of the direct introduction of relatively large quan
-tities of venom into the circulation are precisely those which might logically be
expected to occur on the theory that the material acts as a blood-poison, but
are quite inexplicable by that which regards it as a direct nerve-poison induc
-tive of paralysis.
The phenomena which are present in cases in which treatment by means of
artificial respiration is employed are no less suggestive. There appears to be no
question that the venom produces no appreciable special effect on the circula-
* Op. cit., p.36.
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extent repressive of the normal manifestation of the symptoms connected with
the action of strychnia on the nervous apparatus, as is clearly indicated by the
results of the following experiment.
Experiment XVI—A fowl received an injection of 0.001 gramme of dried
venom, of which 0.0005 gramme constituted a minimal lethal dose for fowls of
1 kilo in weight.
The injection was administered at 10 -55 A.M, and at 1 - 10 P.M. the
characteristic symptoms were already highly developed. An injection of 0.0044
gramme of nitrate of strychnia was now administered. The sumptoms of the
action of the venom continued to progress and a few slight jerking movements
of the tail indicated the action of the strychnia. The symptoms of cobra-
poisoning continued to run their ordinary course and death occurred at 4 P.M.
At 1 -11 P.M. another fowl received an equal dose of strychnia without
any previous treatment. At 1 - 14 P.M. jerking movements set in followed by
violent general convulsions at 1 - 15 P.M. and death at 1-20.P.M.
Here an amount of strychnia sufficing under ordinary circumstances to
give rise to violent general convulsions and death in the course of a few minutes
was quite incapable of doing so in the presence of intoxication by cobra-
venom. It merely served to produce barely appreciable and temporary specific
effects and otherwise in no way affected the normal progress of the intoxi-
cation. The phenomena certainly indicated abnormal depression of func-
tional activity in the nervous centres in connection with the intoxication, but
afforded|no evidence whatever that this was directly dependent on the local ac-
tion of the venom. On the contrary they were precisely of the character which
they might naturally have been expected to present on the theory that the
depression of nervous functional activity is dependent on some general cause
such as defective respiratory property in the blood. Such a condition, as we
know from the phenomena of intoxication by CO does give rise to such
depression, and with the presence of the latter it is easy to see why abnormally
large quantities of any direct nervous stimulant such as strychnia should have to
be introduced into the system in order to occasion specific effects. But there are
no logical grounds for supposing that the introduction of any direct nerve-poison
should in any way necessarily affect the primary specific action of any ferment-
material leading to progressive changes in the quality of the blood. These
changes are an effective agent in giving rise to depression of nervous functional
activity, but no direct stimulation of the latter by means of excessive doses
of strychnia can be expected to touch the primary source of mischief. Death
may be hastened by the employment of very large doses of strychnia, but
no amount of strychnia will prevent the intoxication due to the venom
from steadily progressing towards its normal termination, because no amount
of strychnia is capable of arresting the cumulative ferment-action taking
Medical Officers of the Army of India.
2 1
place in the blood. The effects of the action may be temporarily and partially
masked by those induced by strychnia, but there is no evidence whatever of the
existence of any true physiological antagonism between the two poisons, and, if
this be so, the phenomena certainly afford no support whatever to the view that
the venom acts as a direct nervous depressant, whilst they are readily accounted
for by that which regards it as a primary blood-poison.
The older advocates of the theory that the venom acts as a primary
blood poison laid much weight on the phenomena of variations in suscepti-
bility which are presented by different kinds of animals, and to a certain ex-
tent they were right in doing so. Their data were certainly not always ab-
solutely correct, but the same holds good for those which have been advanced
by their opponents. For example, Boag affirms that " the poison of the ser-
pent has most power over those animals whose blood is the warmest and the
action of whose heart is the most lively ; while, on the contrary, it is not a
poison to the snake itself, nor in general to cold-blooded animals," and
Richards, in commenting on this statement, says : " Mr. Boag observes that a
poisonous snake is protected from the effects of its own poison by its physical
conformation, which enables the animal to live with a very small amount of
oxygen. Unfortunately for this argument, however, venomous and non-
venomous snakes do not differ anatomically, and yet the venom of the former
will kill the latter. " * Now Boag was no doubt in error in supposing that all
snakes are absolutely exempt from the action of venom, but Richards is equally
wrong in implying that nonvenomous snakes as a rule, are as susceptible to the
action of venom as animals with more active circulation and respiration and
consequently demanding a greater supply of oxygen. Had he shown that
non-venomous snakes are normally as susceptible to the action of venom as
animals possessing more active respiration and circulation are, his position
would have been a strong one, but the mere fact that they are liable to
be killed by venom is no argument whatever against Boag's theory, whilst
any evidence showing that they are characterised by minor susceptibility is a
perfectly valid one in its support. The theory assumes that the essential action
of the poison is to diminish the respiratory property of the blood, but it certainly
does not imply that such a change ought not to occur in the case of non-venom-
ous snakes. Boag's error lay in generalising on the phenomena presented in
the case of venomous snakes in which we have to deal with an immunity
which is certainly not dependent solely on minor respiratory requirements, but
also on the presence of a factor interfering with the ferment-action of the poison.
In the case of non-venomous snakes and other harmless reptiles with low
respiratory requirements the theory does not demand the presence of any
absolute immunity but only of a minor degree of susceptibility. It is clear that
* Report of the Indian Commission on snake-venom, page 8.
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a reduction in the respiratory properties of the blood sufficing to cause death
in animals of high respiratory requirements will not be sufficient to kill others
of much lower respiratory requirements, but it does not necessarily follow that
the latter should possess any absolute immunity, for, if the amount of venom
be increased in proportion to the defect in respiratory requirement, there can be
no reason why a fatal effect should not be produced. All then that the theory
requires is that non-venomous snakes and similar animals should be relatively
insusceptible, and there is good ground for believing that they are so and that
degree of susceptibility, so far, runs parallel with that of respiratory require-
ment.
In the first place it can be readily shown that certain unequivocally harm-
less reptiles possess an extraordinarily high power of resistance to the action
of cobra-venom. Those in regard to which this has been most conclusively
demonstrated are Zamenis mucosus, the common." Rat-snake" or Dhamin of
India, and Varanus salvator, the large water-lizard, which abounds in moist
regions in the peninsula. Sir Joseph Fayrer was the first to point out that
Zamenis mucosus possesses at all events a very high relative immunity, and
was perfectly correct in doing so in spite of the imperfection of his data
in regard to the actual quantity and quality of the venom which failed to
produce a fatal result and the weight of the snakes to which it was administer-
ed, and of the fact that, as a rule, the snakes were not kept long enough under
observation to show conclusively that the exemption was a permanent one.
The following experiments, the results of which are entirely confirmatory
of his conclusions, were, however, free from such sources of error.
Experiment XVII .—Marge Zamenis, weighing 888 grammes, received an
injection of 0.01 gramme of dried cobra-venom, of which 0.0005 gramme con-
stituted a minimal lethal dose for fowls of 1 kilo in weight. No symptoms of
any kind followed the operation either at the time or during a succeeding period
of several months' duration during which the snake was kept under observa-
tion.
Experiment XVIII.— A Zamenis, weighing 903 grammes, received an
injection of 0.05 gramme of the dried venom employed in the previous experi-
ment. No symptoms whatever showed themselves during the course of several
succeeding months.
Experiment XIX.—A Zamenis, weighing 663 grammes, received an injec-
tion of 0.05 gramme of the same dried venom as that employed in the previous
experiments with the same result as was present in them.
Experiment XX.—A Zamenis, weighing 788 grammes, received an injec-
tion of 0.05 gramme of the same venom with like results.
Experiment XXI.—A Zamenis, weighing 720 grammes, received an injec-
tion of 0.1 gramme of the same dried venom with like results.
Medical Officers of the Army of India.
In the first of the above experiments the snake received an amount of
venom sufficient to kill 20 fowls, in the next three an amount sufficient to kill
100, and in the fifth enough to kill 200 fowls of I kilo in weight without show-
ing any morbid symptoms either at the time or for several months subsequently.
There can therefore be no doubt whatever of the presence of very high relative
insusceptibility in this species of snake of the absolute harmlessness of which
there can be no doubt. The next question is, how far does this coincide with
low respiratory requirement ? The following experimental data satisfactorily
answer this by showing the results attending the exposure of fowls and speci-
mens of Zamenis to like conditions calculated to affect the respiratory proper-
ties of the blood.
Experiment XXII.—Effects of submersion in water.
A fowl and a large Zamenis were enclosed in separate cages and sub-
merged in a large vessel of water. The fowl was taken out dead after the
lapse of three minutes, but the snake remained apparently unaffected for a
much longer time, did not cease struggling until 23 minutes and a half after
submersion, and, when removed from the water, gradually revived and was pre-
sently none the worse for the treatment.
Experiment XXIII.— Effects of exposure to an atmosphere containing a
large proportion of CO :—
( a ) A f o w l w a s e n c l o s e d i n a c h a m b e r t h r o u g h w h i c h a c u r r e n t o f C O w a s
drawn by means of an aspirator. Shortly after the beginning of the
experiment the bird began to make frequent and conspicuous swal-
lowing movements. These were soon followed by gaping of the
mandibles and staggering gait. Soon after it sat down, with the beak
permanently gaping, and laboured deep respiration, the head inter-
mittently dropping forward and being suddenly elevated again. The
mandibular gaping soon assumed an intermittent type and the head
gradually became permanently depressed and the neck so much
flexed that the vertex rested on the floor of the chamber just as it
does in cases of intoxication by cobra-venom. Slight general con-
vulsions set in 48 minutes after the commencement of the experiment
and death followed almost immediately.
( b ) A large Zamenis was introduced into the same chamber and treated in
the same fashion as the fowl. It never showed any signs whatever
of discomfort, and when removed from the chamber after the lapse
of an hour was quite lively and seemingly unaffected in any way.
( c ) A l a r g e Z a m e n i s w a s p u t i n t o t h e a s p i r a t i n g c h a m b e r a n d t r e a t e d a s
above. It remained in the chamber for two hours without showing
any symptoms of being in any way affected and when removed
from it was quite lively.
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Scientific Memoirs by
The evidence of the coincidence of minor respiratory requirement with
relative insusceptibility to the action of cobra-venom is thus quite unequivocal in
this instance, and that which is afforded by the experimental data regarding
Varanus salvator, which are given below, is quite as clear.
Experiment XXIV.—A Varanus, weighing 2,600 grammes, received an injec-
tion of 0.0125 gramme of dried cobra-venom, of which 0.0005 gramme was a
minimal lethal dose for fowls of one kilo in weight. It never showed any
symptoms whatever of being affected by the poison.
Experiment XXV.—A Varanus, weighing 2,483 grammes, received an injec-
tion of 0.03 gramme of the same dried venom and never showed any appre-
ciable symptoms of its action.
Experiment XXVI.—A Varanus, weighing 2,360 grammes, received an injec-
tion of 0.1 gramme of dried cobra-venom of the same lethal property as that
employed in the previous experiment and died about seven hours later.
Experiment XXVII.—Effects of submersion in water. A Varanus of aver-
age size was submerged in water and died three hours and forty minutes later.
It is quite clear then that in some cases a high degree of insusceptibility to
the action of cobra-venom is present in association with a low degree of respira-
tory requirement, but, at the same time, that even in the case of certain non-
-venomous reptiles the latter cannot be the sole cause of the exemption, for
Dhamins, which, are much more rapidly drowned than Varani, possess a far higher
exemption than the latter do. In the above experiments on submersion twenty-
three and a half minutes was sufficient to reduce a Dhamin to the point of death,
whilst it took more than nine times as long to drown a Varanus, and yet a dose of
0.1 gramme of dried cobra-venom was sufficient to kill a Varanus weighing 2,360
grammes, and one of equal amount was incapable of producing any appreciable
effect on a Dhamin of. 720 grammes weight. The dose which the Varanus
received was equivalent to one of about cos for each kilo of body-weight, an
amount, which, with venom of the lethal property of the stock from which it was
derived, would certainly have killed any fowl of approximately I kilo in weight
within an hour, whilst here it took about 7 hours to cause death. This and the
results of the other experiments on Varanus salvator, show that the species is
endowed with a relative insusceptibility as compared with fowls which may fairly
be credited to the presence of much lower respiratory requirement, but this is
no longer the case with that of Zamenis which with much higher respiratory
requirement than Varanus has an incalculably greater exemption.
It remains to be considered how far there is any evidence to show that the
coincidence of low respiratory requirement with relative insusceptibility is not
an exceptional one, but in regard to this point the data are unfortunately very
defective. A large number of experiments have, no doubt, been tried in regard
to the action of cobra-venom on non-venomous snakes, but they all labour under