NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
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Scientific Memoirs by
bite are quite sufficient to affect masses of blood of sufficient magnitude to
account for the death of even very large animals in consequence of the bites of
cobras.
Experiment I.— On the action of relatively large quantities of cobra-venom
on blood outside the body : —
Two sterilised test tubes, a and b, were taken, and 1 c.c. of distilled water
introduced into each of them.
The water in a was unmixed with anything, but that in b contained 0.01
gramme of dried venom, of which 0.0005 gramme constituted a minimal lethal
dose for fowls weighing about 1 kilo.
A little blood from a fowl which had just been killed was then introduced
into each tube.
The blood in a exhibited the normal phenomenon of very rapid coagulation
and subsequent brightening of the surface of the coagulum to a vivid scarlet ;
that in b, immediately assumed an intensely dark, almost black colour, and
remained permanently perfectly fluid.
Experiment II.— Action of 0.05 gramme of dried venom on 11.5 grammes
of blood :
—
A solution of 0.05 gramme of dried venom in 0.5 c.c. of distilled water was
introduced into a test tube and grammes of blood added to it direct from
the throat of a fowl and thoroughly mixed by shaking.
The blood assumed a black colour at once and never shewed any tendency
to coagulate.
Half an hour later the peripheral portions of the red blood-corpuscles were
practically entirely dissolved, leaving the nuclei free in a dark red fluid.
Experiment III.—Action of 0.01 gramme of dried venom on 16.7 grammes
of blood : —
This experiment was conducted in precisely the same fashion as the previous
one.
The blood coagulated rapidly. At first it was of a deep plum-colour, but
rapidly began to darken, and half an hour after the beginning of the experiment
was black throughout. No serum ever separated from the soft, gelatinous clot.
One hour after the beginning of the experiment the peripheral portions
of the red corpuscles had undergone almost as complete solution as in
experiment II.
Experiment IV.—Action of 0.01 gramme of dried venom on 26.2 grammes
of blood outside the body : —
Two covered, sterilised glass capsules, a and b, were taken ; into the former
1 c.c. of distilled water containing 0.01 gramme of dried venom in solution, and
into the latter 1 c.c. of pure distilled water were introduced.
At 10-32 A.M., 26.2 grammes of blood were received into a, and 24.1
grammes into b, direct from the throat of a fowl.
Medical Officers of the Army of India.
7
a. The blood coagulated at once.
11 A.m.—Surface of the coagulum dull, dark red.
11-35 A.m.—Surface considerably darker than before.
12 Noon.—Surface of the coagulum almost black.
12-30 P.M.—No contraction of the coagulum from the sides of the capsule. Only
a very little free serum present, and that opaque and dark red.
On the following day, at 9-55 A.M., the coagulum was black throughout.
There was no separation of it from the sides of vessel to which it adhered firmly.
Only about 1 c.c. of free serum was present ; opaque, intense brownish red and
yielding an abundant whitish precipitate on dilution with distilled water.
b. The blood coagulated at once.
11 A.M.—Surface of the coagulum bright scarlet.
12-30 P.M.—Surface vivid scarlet; coagulum already well contracted from the sides
of the vessel ; serum limpid, straw coloured.
On the following morning the substance of the coagulum was plum-coloured,
and the surface dull scarlet ; coagulum floating free in 8.75 c.c. of deep red
serum.
Experiment V.—Action of 0.002 gramme of venom on 27.1 grammes of
blood outside the body : —
Two capsules, prepared as in the previous experiment a, containing 0.002
gramme of dried venom in 1 c.c. of distilled water, and b, 1 c.c. of distilled water
alone.
At 10-40 A.M. 27.1 grammes of blood were introduced into a, and 18.26
grammes into b, from the throat of a fowl.
a. The blood coagulated at once.
11-5 A.M.—Exudation of serum beginning to occur ; surface of clot scarlet, but not so
vivid in colour as in b.
1-30 P.M.—Surface of clot very deep, dull red.
On the following morning the coagulum throughout was almost black ;
there was about 6.5 c.c. of free serum of very deep, blackish-red colour, quite
opaque, and throwing down an abundant whitish precipitate on dilution with
distilled water.
b. Coagulation occurred at once.
11-5 A.m.—Exudation of serum beginning to occur ; surface vivid scarlet.
1-30 P.M.—Surface of coagulum vivid scarlet.
On the following morning the surface of the coagulum was bright scarlet,
and the substance plum-colour, and about 4 c.c. of bright red serum were
present.
Experiment VI.—Action of 0.002 gramme of dried venom on 29.9 grammes
of blood :—
Two capsules, a and b, prepared as in the previous experiments, the former
containing 1 c.c. of distilled water with 0.002 gramme of dried venom in solution,
the latter 1 c.c. of distilled water alone.
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Scientific Memoirs by
At 10-46 A.M., 29.9 grammes of blood from the throat of a fowl were intro
-duced into a, and 29.1 grammes into b, and in both cases the vessel was shaken
so as to mix the blood and water thoroughly.
a. The blood coagulated rapidly. At first the surface of the coagulum
was of a deep red, but in place of brightening on exposure to air, it speedily
darkened.
10-55 A.M.—Coagulum almost black throughout.
2 P.M.—The coagulam everywhere in contact with the sides of the vessel, and not a
trace of free serum visible.
On the following morning the surface of the clot was almost black and
its substance black throughout it was densely adherent to the sides of the
vessel, and, when turned out of it, its lateral surfaces underwent no change
in colour on exposure to air. There was not a trace of any free serum present.
The peripheral portions of the red corpuscles were entirely dissolved and the
nuclei free.
b. The blood coagulated rapidly. The surface of the clot was at first
dark red, but speedily became bright scarlet.
2 P.M.—Surface bright scarlet and substance plum-coloured ; clear straw coloured
serum exuding.
On the following morning the surface was dull scarlet and the substance
plum-coloured. The coagulum was readily detached from the sides of the
vessel and its lateral surfaces brightened to dull scarlet on exposure to air,
6.5 c.c. of red serum were present, and the red corpuscles were well preserved.
Experiment VII.—Action of 0.002 gramme of dried venom on 26.4 grammes
of blood:—
This experiment was conducted in precisely the same fashion as the
preceding one, a receiving 26.4, and b, 22.6 grammes of blood from the neck of
a fowl at 10-32 A.M.
a. The blood remained fluid for about eight minutes, and then slowly
coagulated. It was at first dark coloured and for a short time the surface
brightened considerably on exposure to air. Renewed darkening, however, soon
set in, and progressed rapidly.
10-52 A.m.—Surface dark red ; substance of the clot plum-coloured.
1 P.M.—Practically black throughout ; not a trace of free serum.
On the following morning the coagulum was black throughout. It was very
firmly adherent to the sides of the vessel, and, when turned out of it, its lateral
surfaces underwent no change of colour on exposure to air. There was
not a trace of any free serum, and the nuclei alone of the red corpuscles
were recognisable.
b. The blood was at first dark coloured, but the surface of it rapidly
became vivid scarlet.
11-10 A.M.—Surface bright scarlet ; serum beginning to exude.
1 P.M.—Surface vivid scarlet ; substance plum-coloured ; exudation of serum advancing.
1Medical Officers of the Army of India. 9
On the following morning the surface of the coagulum was dull scarlet
and the substance plum-coloured. When turned out of the vessel the edges of
the clot became dull scarlet. The bodies of the red corpuscles were well pre
-served and 3.5 c.c. of limpid bright red serum were present.
Experiment VIII.—Action of 0.0005 gramme of dried venom on 26.3
grammes of blood:—
This experiment was conducted in precisely the same fashion as the
preceding two, save that a contained only 0.0005 gramme of dried venom.
The blood was introduced into the capsules at 10-58 A.M., 26.3 grammes
being introduced into a, and 30.46 grammes into b.
a. Coagulation occurred within four minutes. The surface of the clot
was at first dark red. It gradually brightened to scarlet, and then presently
began to darken anew.
11.30 A.M.—Surface dark red ; substance plum-coloured.
12 Noon.—Surface almost black ; substance plum-coloured ; no sign of any exudation
of serum.
1 P.M.—Surface and substance nearly black ; no visible contraction of the clot, but a
little dark-red serum present.
On the following morning the coagulum was practically black throughout.
There was no appreciable retraction of the clot from the sides of the vessel, but
about 0.25 c.c. of very dark opaque serum, depositing an abundant whitish
precipitate on dilution with distilled water, was present. The sides and
artificially exposed surfaces of the clot showed no change of colour on exposure
to air. The peripheral portions of most of the red corpuscles were absent, lea
v-ing the nuclei free. The texture of the coagulum was soft and gelatinous.
b. The blood coagulated rapidly, and the surface of the clot soon became
vivid scarlet.
11-30 A.M. —Surface vivid scarlet ; substance dark red ; exudation of serum just be
-ginning.
12 Noon. —Surface bright scarlet ; substance dull red ; exudation of serum advanc
-ing.
1 P. M.—Surface vivid scarlet ; substance plum-coloured ; clot well contracted from
the sides of the vessel, and a large quantity of clear, straw-coloured serum
present.
On the following morning the surface of the clot was dull scarlet and the
substance of it plum-coloured. The coagulum was widely shrunk from the sides
of the vessel and lying free in 9 c.c. of clear, straw-coloured serum. When the
coagulum was removed from the serum it rapidly became bright scarlet on the
surface and dull red on the sides, and surfaces artificially exposed by section
also became scarlet on exposure to air. The texture of the clot was firm and
the red corpuscles were well preserved.
In the above experiments the mixture of the venom and the blood was B
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Scientific Memoirs by
effected outside the body, but in the following ones it took place within the
body as in cases of snake-bite.
Experiment IX.—Effects produced on the blood of a fowl by the hypodermic
injection of 0.01 gramme of dried venom : —
a. A fowl received an injection of 0.01 gramme, i.e., twenty times a minimal
lethal dose, of dried venom in 1 c.c. of distilled water at 10-38 A.M. At 11-20
A.M., asphyxial convulsions had set in, and 55.5 c.c. of blood were received from
the throat in a sterilised and covered glass capsule.
b. At 11-22 A.M., 39.5 c.c. of blood from the throat of a healthy fowl were
received in a similar capsule.
a. The blood was of a dull, plum-red colour and coaguluted at once.
11-45A.M.—Dull plum-coloured, the surface somewhat brighter than the substance of
the coagulum. (The capsule was now placed in an incubator at 37°C.,
and the cover replaced by a bell-glass.)
12-3 P. M.—Exudation of serum beginning to occur.
12-32 P.M.—Surface very dark plum-coloured throughout.
2-5 P.M. —Serum deep, brownish-red; coagulum very dark plum-coloured throughout.
On the following morning the surface of the coagulum was of a very dark
brown and the substance deep brownish plum-coloured. The coagulum was not
in the least retracted from the sides of the vessel, but adhered firmly to them.
The free serum, which amounted to 5.5 c.c., was of an intensely dark brown
colour.
b. The blood coagulated at once and the surface rapidly became of a
bright scarlet colour.
11-45 A.M.—Surface bright scarlet and substance dull red. (The capsule was now
placed in the incubator like that of a.)
12-3 P.M.—Exudation of serum beginning to occur.
12-32 P.M.—Surface of the coagulum bright scarlet ; substance dull red.
2-5 P.M.—Surface bright scarlet ; substance plum-coloured ; serum straw-coloured.
On the following morning the surface of the coagulum, where covered by
serum, was plum-coloured, and, where exposed to the air, dull scarlet ; the clot
was well retracted from the sides of the capsule and non-adherent. There were
4.5 c.c. of dull reddish serum present.
Experiment X.—Effects produced on the blood of a fowl by the hypodermic
injection of 0.005 gramme, i. e., ten times a minimal lethal dose of dried venom :
—
a. A fowl received an injection of 0.005 gramme of dried venom in 1 c.c. of
distilled water at 8-15 A.M. Two hours later it was dying and 19 c.c. of blood
from its throat were received in a sterilised glass capsule.
b. At 10-35 A.M., 26.5 c.c. of blood from the throat of a healthy fowl were
received into a similar capsule.
a. The blood was of a very dark colour and coagulated at once. The
surface of the coagulum gradually brightened to scarlet.
10-30 A.M.—Exudation of serum beginning to occur.
Medical Officers of the Army of India
.
1111-20 A.M.—One or two pools of serum on the surface.
11-45 A.M.—Slight retraction of the clot from one point of the sides of the capsule.
1-20 P.M.—Hardly any retraction of the clot from the sides of the vessel. Surface
very dark red, save in the centre.
On the following morning the coagulum was of a very deep brownish red
throughout. No farther retraction from the sides of the capsule had occurred.
The serum was of a deep brownish red and opaque and amounted to 3 c. c.
b. The blood was originally of a very dark red. It coagulated at once, and
the surface of the clot rapidly assumed a vivid scarlet colour.
11-20 A.M.—An abundance of free serum present ; surface of clot bright scarlet
.
11-45 A.M.—Coagulum well retracted from the sides of the capsule.
1-20 P.M.—Coagulum widely retracted from the sides of the capsule ; surface bright
scarlet throughout; serum limpid, straw-coloured.
On the following morning the surface of the coagulum, where covered by
serum, was deep plum-coloured, and, where exposed to the air, dull scarlet. The
serum was limpid, bright red and amounted to 11.0 c.c.
Experiment XI.—Effects produced on the blood of a fowl by the introduc
-tion of 0.34 gramme of dried venom directly into the circulation :
—
A fowl, weighing 1550 grammes, received an injection of 0.34 gramme of
dried venom, of which 0.0005 gramme constituted a minimal lethal dose,
dissolved in 1.31 c.c. of distilled water, in the jugular vein at 11-35 A.M.
Respiratory symptoms, in the shape of gaping and gasping inspirations, set in at
once, and it presently fell down. Two minutes after the injection general con
-vulsions set in, and a minute later death occurred. Blood from the throat was
immediately received into a sterilised glass capsule. It was of intensely dark,
almost black colour, and for a long time remained perfectly fluid. At 12-15 P.M.
the surface had hardly undergone any perceptible brightening in colour, and,
although coagulation had now occurred, the clot was semi-fluid, and no separa
-tion of serum had occurred. An hour later it was in the same state, and on the
following morning, it was perfectly black throughout and formed a very soft
loose coagulum from which no serum whatever had separated.
The results of this series of experiments appears clearly to show that
cobra-venom does produce certain definite, specific effects on any mass of
blood with which it may come into contact, either without or within the
body. When the proportion of venom to blood is relatively very high, it gives
rise to an immediate and total loss of coagulability and of respiratory pro
-perty accompanied by destruction of all save the nuclear portions of the red
corpuscles ; where it is lower, it gives rise to similar results only neither so
completely nor so rapidly. The action, however, remains alike in nature
whatever the ratio of venom to blood may be, and whether it occurs without
or within the body, and the amount of venom which is ultimately cap
-able of affecting very considerable changes in relatively very large masses of
B 2
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Scientific Memoirs by
stage of intoxication, and hence there is not merely a chance of a larger,
absorption of venom into the vascular system before the occurrence of death,
but more time is given for that which has been absorbed to produce its effects
on the blood. It is very unfortunate that there should be no satisfactory record
of the condition of the blood in the case of lower animals in which life has been
prolonged by means of artificial respiration, but in the only case in which I can
find any note regarding the subject it is stated that partial incoagulability was
present.*
There are thus no satisfactory a priori grounds for denying that cobra-
venom acts by producing changes in the blood, and there is positive experi
-mental evidence that it has the power of causing important changes, and
specially respiratory changes in it, and that, owing, apparently, to the action
being of a ferment character, such minute amounts of venom are capable
of profoundly affecting such relatively large masses of blood that there is no
difficulty in accounting for the death of even very large animals from cobra-
bite as essentially dependent on blood-change. On the other hand we have
seen that the evidence on which the belief in the primary neurotic action of the
poison is founded is not of a conclusive character, as the phenomena which are
regarded as indicative of such action are not in any way in conflict with
the theory that the primary action is a hæmic one. Experiment unequivocally
demonstrates the presence of a powerful hæmic action, and the nervous
phenomena which present themselves in the course of the intoxication are
of a nature parallel to that of those which we find arising in cases of poisoning
in which there can be no question that a loss in respiratory property of the
blood is the primary factor, in the production of disease, why, then, should it be
affirmed that the venom acts essentially as a primary and direct nerve-poison?
Wall goes carefully into this question, and it may be well to consider the
value of the arguments which he adduces in order to justify his conclusion that,
"though cobra-venom is a nerve-poison of surpassing deadliness, as a blood
poison it is not an agent of much power."† His arguments are the following :
—
I.—Death from anything save nervous symptoms is unknown.
II.—In cases of recovery the subject at once regains normal health after
the nervous symptoms have passed off.
III.—In most cases there is no symptom of serious blood-poisoning even
whilst the nervous symptoms are present.
IV.—The kidneys give no evidence of altered relation to the blood.
V.—The microscope affords no evidence of structural changes in the blood
of animals which have died from the effects of the venom.
With regard to the first of these arguments it is sufficient to point out that,
* Report of the Indian Commission, Appendix No. I, p. VI .
† Indian Snake Poisons, Their Nature and Effects, by A. J. Wall, M. D., 1883, page 47.
Medical Officers of the Army of India.
15
if it is to be regarded as an evidence of the absence of blood-change in cases of
cobra-poisoning, it must hold the same place in regard to cases of CO-poisoning
in which, as a matter of fact, we know that important blood-change is present.
The second one has no weight whatever in the absence of proof that the nerv
-ous symptoms are dependent on a direct action of the poison on the nervous
apparatus. It is only an argument if it be assumed that such an action is
present, for, if the nervous symptoms be dependent, as they probably, in greater
part at all events, are on defective respiratory property in the blood, their dis
-appearance implies the disappearance of the abnormal hæmic condition caus
-ing them. If the damage to respiratory property caused by a dose of venom
falls short of causing death, the blood must naturally gradually regain its normal
properties, possibly in part as the result of the recovery of respiratory property
by red corpuscles which have only, partially suffered, and, in any case, certainly
owing to the constant addition of new red corpuscles, and when it has regained
its normal respiratory properties the symptoms must naturally disappear.
Exactly the same thing occurs in many cases of intoxication by CO in which
the blood has not been so far affected as to cause death. After removal from
the atmosphere containing the gas, nervous symptoms continue to be present
for some time, but they gradually wear off and then no symptoms of blood-
change present themselves because no blood-change is present. The results of
the following experiment very clearly illustrate this.
Experiment XII.—A fowl was introduced into an aspirating chamber into
which a stream of CO was passed for some time. It very soon became pro
-foundly affected, making conspicuous swallowing movements, gaping and in
-spiring laboriously. It shortly became unable to stand and sat down with its
head drooping more and more forward. It was removed from the chamber
in this state and gradually recovered so far as to be able to stand up in a totter
-ing fashion and to raise its head. It still, however, was very drowsy and con
-tinued to make conspicuous swallowing movements.
On the following day recovery had very greatly progressed and it was feeding
freely. Conspicuous swallowing movements were still, however, frequent, and
occasionally it appeared as though it were imitating the initial stages of intoxica
-tion by cobra-venom, as it became very drowsy, the eyes closing, and the head
gradually drooping forward until the lip of the beak rested on the floor and then
being suddenly and abruptly elevated.
On the following day recovery was almost complete and soon all abnormal
symptoms disappeared entirely.
In this case it is clear that nervous symptoms continued to be present so
long as the blood was defective in respiratory property and disappeared when it
had regained its normal condition, the phenomena being precisely parallel with
those presenting themselves in cases of intoxication by subminimal lethal doses
of cobra-venom.