NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
Medical Officers of the Army of India. 2 5
the defect of yielding no accurate data in regard to relative susceptibility.
They have all been devoted to determining whether it is possible to kill harm-
less snakes with venom—to ascertaining the presence or absence of absolute not
of relative immunity—and, on this account, the data which have been recorded
regarding them afford no accurate information as to the precise relation of
amount of venom and body-weight of the recipient animal, and without informa-
tion on this point• it is of course impossible to determine the degree of relative
immunity or susceptibility with any accuracy.
In the only experiment on harmless snakes other than Dhamins which I
have myself conducted, the subject was a Tropidonotus piscator of moderate size.
It received a dose of 0.05 gramme of dried venom, of which 0.0005 gramme
constituted a certain minimal lethal dose for fowls of about 1 kilo in weight.
No abnormal symptoms of any kind presented themselves during the day on
which the venom was administered or on the two following ones. The snake
continued to be perfectly lively and seemingly quite unaffected until the night
of the third day, but was found dead on the following morning. Taking the
entire absence of any gradual development of symptoms, along with the
fact that the species is a very delicate one in confinement, it appears to be
very questionable whether the fatal result were in any way dependent on the
specific action of the venom ; but, even if it be assumed that it was, the pheno-
mena indicate the presence of relative immunity of high degree, seeing that the
snake certainly could not have weighed above half a kilo and that an amount
of venom sufficient to kill a fowl of one kilo in weight in thirty-four minutes or
So produced no appreciable symptoms whatever for at least sixty hours.
Waddell in a paper which appeared in Part IV of the present periodical*
tabulates the results of a series of experiments which he carried out in regard
to the question of the presence or absence of absolute immunity in various
species of harmless snakes, and although his data do not allow of any definite
conclusions regarding the precise degree of susceptibility present in individual
instances, they appear quite clearly to indicate the presence of relative in-
susceptibility. The table includes the results of sixteen experiments. The
weights of the snakes which were employed are unfortunately not given , but
their lengths are, and an approximate estimate of their weights has been
derived from the latter by taking the average weight of Dhamins of at least
five feet in length and using this as a standard in attempting to calculate the
ratio of weight to length in the other species. The results attainable in such
a fashion are, of course, merely approximate ones, but the error probably
lies in an over, rather than an under estimate of weight to length, as the
Dhamin is by no means a specially slender snake, and some of the speci-
mens from which the average weight was obtained were considerably over
* Are venomous snakes auto-toxic. Surgeon L. A. Waddell.
la
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five feet in length, whilst the length taken as the standard in the cal-
culation was only five feet. Working on this principle it appears that the
total weight of the snakes in Waddell's experiments must have been approxi-
mately 5,188 grammes, and the data regarding the weights of venom show an
expenditure of about 1.049 gramme. The average weight of the snakes
according to this must have been 324 grammes and the average dose of venom
0.065 gramme. But the average duration of life after the administration of
the venom was apparently about six hours, and this clearly shows high relative
resistance to the action of the poison seeing that a dose of 0.05 gramme of dried
venom of good average quality is sufficient to kill a fowl of one kilo in about half
an hour. In other words, an amount of venom more than sufficient to kill
fowls of one kilo within half an hour only sufficed to kill snakes of less than
half that weight in about six hours, or the average dose administered to the
snakes taken in relation to their weight was equivalent to one of at least 0.2
gramme to a fowl of one kilo in weight, and yet death did not follow for about
six hours. These results are only to be taken as roughly approximate ones,
but, such as they are, they afford very conclusive evidence of the existence of
relative insusceptibility in snakes generally.
Whilst snakes as a group appear to be relatively insusceptible to the
action of cobra-venom, this is certainly not the case with Lacertilia in spite of
the fact that certain species, such as Varanus salvator, enjoy a relative immunity.
This comes out very clearly from the results of the following experiments on
the effects following the administration of venom to Calotes versicolor.
Experiment XXVIII.—A Calotes versicolor, weighing 30 grammes, received
an injection of 0.00025 gramme of dried venom of which 0 .0005 gramme con-
stituted a minimal lethal close for fowls of about one kilo in weight.
Death occurred 21 minutes after the introduction of the venom. The
dose of venom was equivalent to one of 0.00825 gramme to a fowl of one kilo
in weight, an amount, which, with venom of the lethal property which this
possessed, would induce death in less than half an hour.
Experiment XXIX, a Calotes versicolor— Weighing 22 grammes, received
an injection of 0.000062 gramme of dried venom and died about two and a half
hours later. Here the dose was equivalent to one of 0.00279 gramme to a
fowl of one kilo in weight and the period of survival corresponded approximately
to that ordinarily present after the administration of such an amount.
According to these data Calotes versicolor is practically as susceptible to
the action of cobra-venom as fowls are. Neither relative immunity nor high
susceptibility, as has been affirmed by certain observers,* is, therefore, a general
Lacertilian peculiarity. Relative immunity is present in very high degree in
* " Étude expérimentale du Venin de Naja tripudians" par Le Dr. A. Calmette. Annales
de L'Institut Pasteur, No. 3, page 160.
Medical Officers of the Army of India.
27
Varanus, whilst great susceptibility replaces it in Calotes. But there are other
very conspicuous coincident differences present in the two cases, for Calotes is
a purely terrestrial and very active animal, whilst Varanus is essentially
aquatic and sluggish, and whilst a submersion of nine minutes' duration serves to
render a Calotes motionless and insensible, one of more than three hours is
required to produce a similar effect on a Varanus salvator. The evidence of the
coincidence of susceptibility or relative immunity with high and low respiratory
requirement is consequently just as clear in this instance as it is where the
phenomena occurring in fowls are compared with those occurring in snakes as
a group.
The data obtained from the following series of experiments indicate the
presence of relative insusceptibility in Batrachia.
Experiment XXX.— A large specimen of Rana tigrina, weighing 200
grammes, received a subcutaneous injection of 0.0005 gramme of dried venom
of which that amount constituted a minimal lethal dose for fowls of about I
kilo in weight. For a long time it appeared to be entirely unaffected, but death
occurred on the evening of the fourth day after the introduction of. the
poison. The dose here was equivalent to one of 0.0025 to a fowl of i kilo in
weight, but death instead of occurring within an hour or two did not take place
for more than four days.
Experiment XXXI.— A small Rana tigrina, weighing only 35 grammes,
received a subcutaneous injection of 0.0005 gramme:of the same dried venom as
was employed in the previous experiment and died in forty-six minutes, or in
about the same time as fowls which have been treated with doses of venom of
only half the equivalent amount die.
Experiment XXXI1.—A large Bufo melanostictus, weighing 72 grammes,
received a subcutaneous injection of 0.0005 gramme of the dried venom employed
in the previous experiments and died during the night of the second day after
that on which the venom was introduced, whilst a proportionate dose in the
case of a fowl would have caused death within an hour.
Experiment XXXIII.— A Bufo melanostictus, weighing 60 grammes, re-
ceived a subcutaneous injection of 0.0005 gramme of the dried venom employ-
ed in the previous experiments and died about two hours later.
Experiment XXXIV.— A Bufo melanostictus, weighing 29 grammes,
received an injection of 0.0005 gramme of the venom employed in the previous
experiment and died between four and five hours later.
Experiment XXXV.—A Bufo melanostictus, weighing 25.5 grammes,
received an injection of 0.0005 grammes of the dried venom employed in the
previous experiments, or a dose equivalent to one of 0.019 gramme to a fowl of
I kilo in weight, and death did not occur until about six hours later.
The above experimental data are all those for which I can personally
D 2
28
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vouch, but both Waddell's and Wall's results afford confirmatory evidence of
the existence of relative insusceptibility in Batrachia generally. Waddell's
table showing the results which he obtained includes eleven experiments on five
distinct species.* The amount of dried venom which was employed was about
0.638 gramme which gives an average of .0.058 gramme per dose. But the
average weight of fair sized toads and frogs only amounts to about 76 grammes
so that the average dose to the average weight of the recipient animals may be
fairly taken as equivalent to one of 0.754 gramme to a fowl of, one kilo in weight,
and yet the average duration of life subsequent to the treatment was about
eight hours even although the venom was directly introduced into the dorsal
lymph-sac, and hence practically directly into the circulation, whilst the intro-
duction of equivalent doses directly into the circulation of fowls or other warm-
blooded animals would inevitably be followed by almost instantaneous death.
Wall's experimental results* in regard to Rana tigrina equally clearly indicate
the presence of high relative insusceptibility in Batrachia, as in one case
death did not occur until, five hours after the injection of a solution of 0.01
gramme of dried venom into the dorsal-sac, and in another, in which no less
than 0.05 gramme was similarly introduced, it did not take place for more than
an hour.
There is little really definite information in regard to the relative suscep-
tibility of invertebrate animals to the action of cobra-venom, but the data which
were obtained from a series of experiments on cockroaches afforded little
evidence of the presence of any specific effects, for although a large mortality
attended the injection of venom, the mortality following the injection of equal
quantities of human saliva was also very considerable. The evidence is not of
any great value but, such as it is, is rather in favour of the view that the specific
action of cobra-venom is one which is exerted upon the blood and which acts
by reducing hæmic respiratory property, seeing that in the case of most
tracheate animals the blood has no special respiratory function and cannot,
consequently, afford the venom a fair field for action. The entire body of
evidence relative to the degree of susceptibility to or exemption from the action
of cobra-venom in various kinds of animals thus affords very considerable sup-
port to the theory that the poison is primarily and essentially a hæmic one, and
is at the same time quite inexplicable on the hypothesis of any primary neurotic
action.
The principal points of evidence in favour of the theory that cobra-venom
acts as a primary blood-poison may be summarised as follows :
—
l. Cobra-venom does produce important changes on the blood outside the
body.
II. There is clear evidence of the occurrence of similar changes in the
*Op. cit.
' Op. cit.
Medical Officers of the Army of India.
29
blood within the body in cases where large doses of venom are introduced
directly into the circulation, or where life is artificially prolonged so as to give
time for the ferment-action of smaller doses to he fully exerted.
III. The nervous phenomena which are present in cases of intoxication
by cobra-venom are closely parallel to those occurring in cases of intoxication
by CO, and the fact that the colour of the blood does undergo alteration on
exposure to air is no proof that it has not sustained a lethal alteration in respira-
tory property.
IV. The fact that, whilst the poison produces no appreciable effect upon
the circulation, artificial respiration, although protracting life, is powerless to
avert an ultimate fatal result, shows that the asphyxia which causes death
cannot be simply dependent on defective exposure of the blood to air.
V. Where minimal lethal doses of cobra-venom are introduced into the
system by direct intravenous injection, a prolonged latent period ensues before
any specific symptoms manifest themselves, and, when the latter do appear,
they follow a gradually progressive, cumulative course, whereas whenever
minimal lethal doses of primarily neurotic poisons have entered the circulation
they give rise to immediate effects.
VI. Were the phenomena of nervous depression attending intoxication
by cobra-venom dependent on a direct action upon the functional activity of the
nervous centres, the administration of salts of strychnia ought to produce some
appreciable effect on their progress, whereas in fact it produces none whatever.
VII. Were the asphyxial termination of ordinary cases of intoxication by
cobra-venom dependent on a gradual, direct depression of the activity of the
nervous centres leading to paralytic cessation of respiratory movements, the
injection of large quantities of venom directly into the circulation ought to be
followed by sudden general paralysis, the quality of the blood remaining un-
altered, whereas it is actually followed by sudden general convulsions and loss
of coagulability in the blood.
VIII. The theory of the direct action of the venom upon the nervous
system is quite incapable of affording any explanation whatever of the conspicu-
ous differences in the degree of susceptibility exhibited by different kinds of
animals, whilst that which regards the action as primarily affecting the blood,
and specially the respiratory property of the blood, is capable of explaining them
so far in a very satisfactory fashion. The neurotic theory might, of course,
explain the phenomena of the coincidence of minor susceptibility with minor
respiratory requirement, were the former indicated merely by minor mortality,
which might be interpreted as owing to the fact that a paralytic decrease in
respiratory movement which must necessarily prove fatal in animals with high
respiratory requirement, will by no means suffice to do so where the latter is
much less. But, as a matter of fact, minor susceptibility is not evinced merely
30
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by minor mortality but by minor tendency to the development of nervous symp-
toms. The Dhamins in Experiments XVII—XXI remained perfectly lively and
vigorous, and showed no nervous symptoms whatever after having been subjec-
ted to the action of doses of venom more than sufficient to have caused the
full development of all the characteristic symptoms preceding death in from 20
to 200 fowls of corresponding weight, and as we have already seen that the
characteristic nervous symptoms are essentially those which attend defective
supply of respiratory O, the whole evidence merely goes to show that in the case
of the snakes no defect in oxggen-supply sufficient to give rise to any appreci-
able symptoms was ever present in spite of the presence of excessive doses of a
material supposed to act directly on respiratory activity through the nervous
system.
II. —The physiological action of the venom of Vipera russenii.
All the older observers would seem to have regarded the physiological
action of the venom of Russell's viper as essentially identical with that of
cobra-venom. Even Fayrer and Brunton, in their communications to the Royal
Society, affirmed the practical identity of the symptoms induced by the action
of the two venoms, and it was left to Wall to be the first clearly to appreciate
that their actions are essentially dissimilar, and that the venom of the Daboia
is practically of a more complicated nature than that of the cobra, seeing that
it contains, or, at all events, may contain two perfectly distinct toxic materials
in lethal amount, each of them possessing independent lethal properties, but
neither of them inducing symptoms identical with those attending fatal intoxi-
cation by cobra-venom.
It is somewhat hard to understand how any doubt could ever have existed in
regard to the different natures of the two venoms, and certainly none could
ever have been entertained had their action in minimal or approximately min-
imal lethal doses been carefully studied. The striking differences in respect
both to lethal property and to the nature of the phenomena attending the action
of the two venoms which any such study reveals are illustrated by the following
data derived from a series of experiments which were conducted simultaneously
with samples of venom of ascertained and high lethal property.
A.—Experiments on the action of the venom of Naia tripudians.
As the result of a series of experiments on the properties of two stocks of
dried venom, which had been accumulated from many distinct snakes and subse
quently thoroughly mixed and reduced to an impalpable powder, it was definitely
ascertained that 0.00025 gramme in the one case, and 0.0005 gramme in the
other constituted minimal lethal doses for fowls of approximately one kilo in
Medical Officers of the Army of India.
31
weight ; that doses of 0.000125 gramme in the former, and 0.00025 in the latter,
although incapable of causing death gave rise to well marked symptoms ; and
that smaller doses were followed by no appreciable results.
The results attending the administration of doses of 0.0005, 0.00025,
0.000125 and 0.0001 gramme of the stronger stock of venom were as follows :—
Experiment XXXVI.—10-23 A.M. A fowl received a subcutaneous injec-
tion of 0.0005 gramme of dried venom in 0.5 c.c. of distilled water.
Apparently somewhat drowsy, and sitting down.
Gaping of the mandibles and gasping, laboured respiration beginning to
appear.
The symptoms of intoxication then rapidly ran their ordinary course.
Inspiration was at first deep and laboured, accompanied by elevation of the
head and conspicuous gaping of the mandibles. The signs of drowsiness con-
tinued and increased in degree, and between each inspiratory movement the head
gradually tended more and more to droop forward until the tip of the beak rested
on the floor of the cage. For a time the eyes were opened and the head suddenly
and violently elevated with each inspiration, but presently this ceased to be
the case and the bird lay flat with the neck so much flexed that the vertex
was in contact with the floor. Futile attempts at raising the head continued
for a time to occur at intervals, but they gradually ceased and the bird then
lay motionless with the neck extended and the head resting on one side, in-
spiring deeply at relatively wide intervals. Still later respiratory movements
became even less frequent and diminished greatly in extent, and, with this,
gradually increasing lividity of the comb and wattles began to appear. Violent
general convulsions presently set in and were repeated at frequent intervals
until death occurred at 3-45 P.M., or five hours and 22 minutes after the injection
of the venom.
Experiment XXXVII.—10-52 A.M. A fowl received a subcutaneous injec-
tion of 0.00025 gramme of dried venom in 0.25 c.c. of distilled water.
Slight gaping of the mandibles with each inspiration beginning to appear.
From this time onwards the ordinary, specific symptoms of the action of
the venom continued slowly and steadily to develope until 1-30 P.M. of the
following day when death occurred. No conspicuous convulsive symptoms
preceded death.
Experiment XXXVIII.—10-45 A.M. A fowl received a subcutaneous
injection of 0.000125 gramme of dried venom in 0.125 c.c. of distilled water.
Slight inspiratory gaping beginning to appear.
The normal symptoms attending the action of the venom slowly and gradu-
ally developed themselves, and during the forenoon of the following day were well
marked, the bird sitting with its eyes closed and the tip of the beak resting on
10-35.
10-40.
1-55 P.M.
1 - 5 5 P . M .
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the floor, save when the head was thrown up with each deep, gaping and gasping
inspiration. During the afternoon, however, the symptoms began gradually to
diminish in intensity, and from this time onwards recovery steadily progressed,
so that, on the morning of the next day, the bird was seemingly almost quite
well. The phenomena in this case were almost ludicrously like those succeeding
a non-fatal exposure to an atmosphere highly charged with CO.
Experiment XXXIX.—10-50 A.M. A fowl received a subcutaneous injec-
tion of 0.0001 gramme of dried venom in 0.1 c.c. of distilled water. No
unequivocal symptoms of the specific action of the venom ever manifested
themselves.
These and similar experiments clearly demonstrate that the symptoms
which are induced by small lethal doses, minimal lethal doses, and sublethal
doses, so long as the latter are capable of giving rise to any appreciable results,
of cobra-venom are practically alike in character, and that the only phenomena
distinguishing the action of larger from smaller doses are that the symptoms
appear sooner and are more rapidly developed, and that convulsions immediately
before death are more common and conspicuous in cases where the former have
been employed. In other words, convulsions immediately before death are more
constant and conspicuous in acute than in chronic cases, which, as has all eady been
pointed out, is a phenomenon which is characteristic of intoxication by CO also.
In all cases in which small doses are employed, even in those in which the
venom is directly introduced into the circulation, a distinct latent period inter-
venes ere the development of any appreciable specific symptoms, and the
duration of the period clearly holds an inverse ratio to the magnitude of the
dose. In experiments, like the above, in which subcutaneous injection is
employed it must, of course, remain more or less uncertain how long some of
the venom does not remain localised at the site of injection, and at what rate
it is removed by absorption into the blood vascular system, and hence in order
to obtain definite information in regard to the relative duration of the latent
period it is necessary to have recourse to direct introduction of various quan-
tities of venom of ascertained lethal properties into the blood. In the following
four experiments this procedure was accordingly adopted, the dried venom
which was employed being derived from the stock of which 0.0005 gramme
constituted a minimal lethal dose for fowls of approximately 1 kilo in weight.
Experiment XL .— 10-50 A.M. A fowl received an injection of 0.0005
gramme of dried venom, in 0.5 c.c. of distilled water, in the left jugular vein.
No symptoms appeared until between 2 and 3 P.M , but they then gradu-
ally developed, ran their normal course and terminated in death between 7
and 8 P.M.