NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
11-35 A.M.
11-37 A.M.
11-40 A.M.
11-45 A.M.
12-5 Noon.
10-53 A.M.
1 0 - 5 6 A . M .
10-57 A.M.
10-59 A.M.
1 1 - 3 7 .
11-38.
Medical Officers of the Army of India.
33
Experiment XLI.—11-25 A.M. A fowl received an intrajugular injection
of 0.01 gramme of dried venom in 1.5 c.c. of distilled water.
Beginning to gape, gasp, and throw up its head with each inspiration.
Lying motionless with the neck extended and the head on one side.
Shifting about staggeringly at intervals.
General convulsions, repeated at intervals.
Dead.
Experiment XLII.—10-51 A.M. A fowl received an intrajugular injection
of 0.1 gramme of dried venom in 1.5 c.c. of distilled water.
Mandibular gaping, and gasping inspiration beginning to appear.
The tip of the beak resting on the floor of the cage ; the head elevated
in characteristic fashion with each inspiration and then dropping
forward again ; comb and wattles gradually becoming livid.
Head falling over on one side.
Violent general convulsions ; repeated at intervals until 11-1 A.M. when
death occurred.
Experiment XLIII—11-35 A.M. A fowl, weighing 1,550 grammes, received
an intrajugular injection of about 0.34 gramme of dried venom in 1.5c.c. of dis-
tilled water in the jugular vein.
Respiratory symptoms in the form of mandibular gaping, and laboured,
gasning inspiration set in at once.
Violent general convulsions.
Dead.
This entire group of experiments very clearly indicates that the essential
action of the venom remains unaltered whatever doses of it may be employed,
and that practically the only phenomena distinguishing the action of excessive
from that of minimal lethal ones is that the former gives rise to maximal effects
at once, whilst the latter only does so gradually and progressively. In the case
of excessive doses there is no appreciable latent period and death occurs almost
instantaneously ; in that of doses of somewhat less amount a brief latent period
makes its appearance, and the indications of the maximal action of the venom
are correspondingly delayed ; and in the case of fractional -doses the latent
period is greatly protracted, and the development of the specific symptoms is
very gradual and progressive. So long, however, as a dose remains capable of
producing any appreciable symptoms whatever, these are of the same nature as
the initial symptoms of excessive doses, and in the case of minimal lethal doses
the ultimate state of the victim is precisely alike that almost instantaneously
induced by excessive doses, save that convulsive phenomena are not so con-
spicuous. The differences in the phenomena present in the individual experiments
E
34
Scientific Memoirs by
of this group come out very clearly when they are stated, as below, in tabular
form :—
Table showing the course of intoxication following intravenous injections of various
amounts of venom.
No. of
experiment.
Dose or venom.
Period after administration at
which respiratory symtoms
appeared.
Period after administration when
convulsions occurred.
Period after administra
ion when death
occurred.
XL 0.0005 gramme. Over three hours .
......
Over eight hours.
XLI
0 . 0 1 „ . Ten minutes .
Twenty minutes . . Forty minutes.
XLII
0.1 ,, . 'Iwo minutes. .
Eight minutes . . Ten minutes.
XLIII
0.34 „ . At once . . . . Two minutes. . Three minutes.
The dose of 0.0005 gramme in Experiment XL was just as certainly fatal
as that of 0.34 gramme in Experiment XLIII, and the only difference in the two
cases was that whilst in the former one a latent period of several hours inter-
vened between the entrance of the venom into the circulation and the manifesta-
tion of any specific symptoms of its action, in the latter there was no appreci-
able latent period whatever and symptoms manifested themselves at once. The
initial symptoms were in both cases alike, and alike indicative of defective
respiratory supply, but those dependent on the action of the large dose of venom
ran a rapid course and terminated in well-marked convulsions and death within
a few minutes, whilst those caused by the minimal lethal dose followed a slowly
cumulative course in which general convulsions were absent or, at all events,
were not conspicuous.
It appears, thus, that cobra.venom is a material the action of which is in
no way essentially affected by the amount of it which enters the system. Large
quantities give rise to more rapid effects than small ones, and in the case of the
latter, a latent period intervenes between the period of access of the venom and
the manifestation of any appreciable symptoms of its action, whereas maximal
doses give rise to maximal affects.at once. The introduction of large quantities
of venom into the circulation gives rise to almost instantaneous death, preceded
by violent general convulsions ; moderate doses are followed by the development
of a series of symptoms, which begin to appear after a brief latent period, and
culminate in general convulsions and death ; fractional doses are incapable of
causing any appreciable symptoms until a prolonged latent period has intervened,
but the symptoms which then appear are identical in character with those induced
by moderate doses, save that general convulsions are neither so constant nor so
well marked. But these phenomena surely warrant the conclusion that the
essential principle of the venom is of the nature of a ferment and, consequently,
not only capable of producing certain effects instantaneously when it enters the
system in great excess, but of inducing them gradually and cumulatively when
it enters in fractional quantities only.
12-5 Noon.
3-35 P.M.
12-30 Noon.
4 P.M
1 P . M .
7 P.M
Medical Officers of the Army of India.
35
Two other distinctive properties of cobra-venom are, first, that the power of
even minimal lethal doses is in no way appreciably affected by dilution ; and
second, that the same results ultimately follow the repeated, cumulative introduc-
tion of quantities of venom, quite incapable individually of producing any appre-
ciable effects, as those which attend the administration of quantities of lethal
amount at one time. That this is the case is illustrated by the results of the
following experiments.
Experiment XLIV.—(a) 10-25 A.M. A fowl received a subcutaneous injec-
tion of 0.001 gramme of dried venom, of which 0.00025 constituted a minimal
lethal dose, in 1c.c. of distilled water.
Respiratory symptoms beginning to appear.
Death occurred.
(b) 10-55 A.M. A fowl received a subcutaneous injection of 0.001 gramme
of the same dried venom in 5c.c. of distilled water.
Respiratory symptoms beginning to appear.
Death occurred.
Experiment XLV.—(a) 10-51 A.M. A fowl received a subcutaneous injec-
tion of 0.0005 gramme of dried venom, of which that amount constituted a
minimal lethal dose, in 0.5c.c. of distilled water.
Respiratory symptoms beginning to appear.
Death occurred.
(b) 10.30 A.M. A fowl received a subcutaneous injection of 0.0005 gramme
of the same dried venom, in 1.5c.c. of distilled water.
Respiratory symptoms beginning to appear.
Death occurred.
Experiment XLVI.— 10.44 A.M. A fowl received a subcutaneous injection
of 0.000058 gramme of dried venom, of which 0.00025 constituted a minimal
lethal dose, and, subsequently, four other similar injections at intervals of twenty
minutes.
Respiratory symptoms beginning to appear.
They slowly and gradually followed their ordinary course, and death
occurred at 4 A.M. of the following morning.
The final outcome of the entire series of experiments goes to show that
the essential toxic principle of cobra-venom is a powerful ferment-substance, the
action or which is neither affected by dilution previous to introduction into the
system, or by cumulative introduction in quantities which are individually in-
capable of giving rise to any appreciable effects, and which is not subject to
rapid decomposition or excretion subsequent to absorption. It now remains to
consider how far any such conclusions are warranted in regard to Daboia-
venom.
B.—Experiments on the action of the venom of Vipera russellii.
Daboia-venom would appear never to be so lethal weight for weight as cobra-
E2
11-50 A.M.
8 P.M.
2 P.M.
10-40 A.M.
11-40 A.m.
Scientific Memoirs by
36
venom, for the normal lethal doses of all the samples of dried venom of the best
quality which have yet been tested have ranged from 0.003 to 0.006 gramme,
whilst those of potent cobra-venom are only 0.00025 to 0.0005 gramme, or twelve
times smaller. But, whilst this is the case, minimal lethal doses of Daboia-
venom of the best quality are far more rapidly fatal than minimal lethal doses
of the best cobra-venom. The results of the following experiments illustrate the
effects following the administration of various amounts of dried venom of potent
quality.
Experiment XLVII.—10-45 A.M. A fowl received a subcutaneous injec
tion of 0.001 gramme of dried venom in 1 c.c. of distilled water. Strong
muscular twitching occurred at the site of injection. The bird remained during
the rest of the day sitting, or standing motionless and apparently somewhat
drowsy, but on the following morning showed no appreciable symptoms of any
kind, nor did any appear subsequently.
Experiment XLVIII.—10-24 A.M. A fowl received a subcutaneous injec.
tion of 0.001 gramme of dried venom in 1 c.c. of distilled water. Well-marked
muscular twitching occurred at the site of injection.
Sitting down ; motionless ; very dull
Sitting motionless with the head permanently dropped forwards ; but
no tendency to mandibular gaping, laboured inspiration or closure of
the eyes.
The bird remained in this condition until about 4-30 P.M. and then gra-
dually recovered.
Experiment XLIX.— 11 A.M. A fowl received a subcutaneous injection of
0.002 gramme of dried venom in 1 c.c. of distilled water. Well-marked mus-
cular twitching occurred at the site of injection. The bird sat down at once
and remained perfectly motionless. There were no signs whatever of drowsi-
ness or of respiratory symptoms, but merely extreme, watchful immobility. It
remained in this condition until the evening and then gradually recovered.
Experiment L.—10-20 A.M. A fowl received a subcutaneous injection of
0.002 gramme of dried venom in 1 c.c. of distilled water.
There was marked local muscular action at the site of injection. The
bird presently sat down and remained perfectly still and very dull almost con-
tinuously until 4 P.M. when it began to become livelier, and, by the following
morning, it was seemingly quite well.
Experiment LI.—(a) 10.32 A.M. A fowl received a subcutaneous injection
of 0.003 gramme, of the same sample of dried venom as was employed in the
previous experiments, in 1 c.c. of distilled water.
Strong local muscular action occurred at the site of injection. Violent
general convulsions set in after a few minutes and lasted until 10-38 A.M. when
death occurred.
10-39 A.M.
10-41 A.M.
11-20 A.M.
1 1 - 2 2 A . M
1 1 - 2 2 A . M .
11-22 A.M.
11-42 A.M.
12-2 Noon.
12-22 Noon.
12-45 Noon.
38 Scientific Memoirs by
0.0056 gramme of dried venom in 1c.c. of distilled water. Excessive local
muscular action attended the injection.
For a short time the bird remained standing, and seemingly somewhat
excited, judging from the jerky character of the movements which it made.
It sat down, making slight mandibular movements.
Furious general opisthotonic convulsions set in, the body revolving back-
wards on its transverse axis, the wings being at the same time widely
expanded. Loud screaming occurred coincidently, and death took
place a minute later.
Experiment LIV.—11-18 A.M. A fowl received a. subcutaneous injection of
0.0056 gramme of dried venom in 1 c.c. of distilled water. Well-marked local
muscular action attended the injection.
The bird sat down.
Violent general convulsions set in
Death occurred.
The record of results of this nature might be indefinitely extended, but
even the data furnished by the above experiments are sufficient to indicate con-
clusively that in Daboia-venom we are dealing with a poison the lethal action
of which is entirely distinct from that of cobra-venom, Before, however, enter-
ing into this question in detail, it may be well to consider the nature of the
phenomena attending the cumulative action of fractional doses of Daboia-venom
of ascertained lethal property, and that of those following the immediate intro-
duction of excessive ones.
Ex p e r i me n t LV. —On t h e e f f e c t s o f r e p e a t e d i n j e c t i o n o f 0 . 0 0 1 g r a mme o f
dried venom, of which 0.003 gramme in 1c.c. of water when introduced into the
system at once sufficed to cause violent general convulsions and death within the
course of ten minutes.
A f o w l r e c e i v e d a s u b c u t a n e o u s i n j e c t i o n o f w o o l g r a m m e o f d r i e d
venom in 0.5 c. c. of distilled water. Violent local muscular action
occurred at the site of injection.
No special symptoms present. A second injection of 0.001 gramme of
dried venom was introduced into the same site as the former one and
was attended by renewed local muscular action.
The bird was standing perfectly motionless and watchful. A third in-
jection of wool gramme of dried venom was introduced into the same
site and local muscular action again manifested itself.
Sitting motionless. A renewed injection administered in the same site.
Local muscular action barely perceptible.
A subcutaneous injection was introduoed into the opposite thigh and
was followed by vigorous local muscular action.
Three more injections were administered in the same site as the previous
one. The first of them was attended by well-marked local muscular action, but
in the two latter the phenomenon was almost absent.
1 0 - 5 8 .
11-1.
12-35 Noon.
Medical Officers of the Army of India.
37
(b ) 10-56 A.M. A fowl received a subcutaneous injection of 0.003 gramme
of the same dried venom in 3 c.c. of water.
Strong muscular action occurred at the site of injection. The bird sat
down motionless and for a time seemed to be very drowsy.
At noon the drowsiness had entirely passed off and it now sat " still as
a stone" and watchful, like the birds in the earlier experiments. As in these
experiments these symptoms persisted until about 4 P.M. when recovery gradu-
ally set in.
Experiment LI.— (a) 1 0 - 4 8 ½ A . M . A f o w l r e c e i v e d a s u b c u t a n e o u s i n j e c t i o n
of 0.003 gramme of the same stock of dried venom in 1 c.c. of distilled water.
Strongly marked local muscular action occurred at the site of injection,
and for a time the bird seemed to be somewhat excited and restless. It then
began occasionally to close its eyes and to make frequent swallowing movements.
It sat down.
Violent general convulsions set in and death occurred almost immediately.
(b) 11-5 A.M. A fowl received an injection of 0.003 gramme of dried venom
in 3 c.c. of distilled water. The solution of venom was the same as that em-
ployed in a after dilution to the required extent. Well-marked local muscular
action attended the injection.
The bird presently sat down and presented the same symptoms as those
which occurred in the first four experiments. It did not, however, recover as
the birds in the latter did, but continued sitting motionless and died quite quietly
during the night.
All the preceding experiments were tried with venom of the most powerful
lethal quality ; in those which follow the potency of the venom was not so great
owing apparently to the fact that at the time the latter was collected the snakes
were feeding freely, whereas the more powerful material was procured during
the course of the winter and when they were continuously fasting.
Experiment LII.— (a) 12-30 noon. A fowl received a subcutaneous injection
of 0.006 gramme of dried venom in 1 c.c. of distilled water. Strongly-marked
local muscular action occurred at the site of injection.
For a few minutes the bird sat quietly. It then became restless, stood up
and made conspicuous swallowing movements.
Violent general convulsions and screaming set in and were immediately
succeeded by death.
(b) 12-52 noon. A fowl received a subcutaneous injection of 0.006 gramme
of dried venom in 3c.c, of distilled water. The solution of venom was the same
as that employed in ( a) after dilution to the required extent.
The bird showed just the same symptoms as those in the first four experi-
ments and then gradually recovered.
Experiment LIII.—10-35 A.M. A fowl received a subcutaneous injection of
Medical Officers of the Army of India.
39
The bird remained sitting perfectly motionless, and after a time the respira-
tion was somewhat hurried and the beak kept permanently gaping. There
were throughout no signs of the peculiar laboured gasping respiration so
characteristic of cases of intoxication from cobra-venom, and the head never
tended to droop forward. The symptoms continued unchanged until 3 A.M. of
the following morning when death occurred.
In this case 0.008 gramme of dried venom, when cumulatively introduced
entirely failed to give rise to any symptoms of centric nervous irritation, although
a dose of 0.003 gramme would certainly have induced fatal general convulsions
within the course of a few minutes had it been introduced at once in 1 c. c. of
distilled water.
Experiment LVI.—On the effects of repeated subcutaneous injections of
0.001 of dried Daboia-venom, of which woo6 gramme certainly caused violent
general convulsions and death within the course of aim minutes when intro-
duced at once in c.c. of distilled water.
11-40 A.M. A fowl received a subcutaneous injection in the right thigh of
0.001 gramme of dried venom in 1 c.c. of distilled water. Well-marked local ,
muscular action occurred.
Four more similar injections were introduced into the right thigh and four
into the left one at intervals of twenty minutes. Muscular action failed to ap-
pear in either thigh after the first two injections. Soon after the beginning of the
experiment the bird sat down in one corner of the cage and remained absolutely
motionless, with the neck somewhat retracted and the back elevated. On the
following day it remained in the same state, sitting perfectly motionless, with
the eyes permanently closed, but the head showing no tendency whatever to
droop forward. Blood-stained evacuations were occasionally passed. On the
third day it showed signs of recovery, for, although still sitting as before, the
eyes were now open and it chirped at intervals. On the next day recovery
continued to progress, and the head was occasionally moved, and from this time
onwards no relapse took place and in a short time health appeared to be com-
pletely restored.
Experiment LVII.—10-50. A.M. A fowl received a subcutaneous injection
of 0.001 gramme of dried venom, of the same lethal quality as that employed in
t he previ ous experi ment , i n 1 c. c. of wat er i n t he ri ght t hi gh, and, subsquent l y, at
intervals of twenty minutes, two more similar injections in the same site, Strong
local muscular action attended the first injection, but were absent after the latter
ones. After another interval of twenty minutes a similar injection was introduced
into the opposite thigh and was followed by well-marked local muscular action.
Four more similar injections were subsequently introduced into the right thigh
at intervals of twenty minutes. Local muscular action attended the first of
them but was entirely absent in the subsequent ones. After the first few
40
Scientific Memoirs by
injections had been administered the bird became absolutely motionless.
It remained standing for a short time and then sat down, still and watchful.
After sometime a tendency to permanent mandibular gaping manifested itself.
On the following day it remained sitting absolutely motionless, with the neck
retracted, the eyes open, and the back somewhat elevated. There were no
symptoms whatever resembling the specific symptoms of chronic intoxication
by cobra-venom. It remained in the same condition for the three next days,
and on the morning of the following one was found dead and rigid, still retain-
ing the same position.
The results of these and similar experiments clearly demonstrated the
impossibility of inducing general convulsions and rapid death by means of
cumulative administration of the venom, and that in order to the occurrence
of such phenomena the latter must enter the system at once in certain
quantity and with a certain degree of concentration. With the most potent
samples of dried venom the introduction of 0.003 gramme sufficed certainly
to induce violent general convulsions and death when introduced simulta-
neousl y and i n sol ut i on i n 1 c. c. of wat er, but a l i ke amount was powerl ess
to do so when in solution in 3 c. c. of water, and the same held good of
the cumulative introduction of much larger quantities by means of repeated
injections of fractional doses. The latter are capable of inducing phenomena
of local nervous irritation followed by symtoms of local nervous exhaustion, but
they fail either individually or cumulatively to give rise to any appreciable signs
of centric irritation. The condition of local nervous exhaustion following the
primary irritation in certain cases seems to be of a transitory nature, as in some
instances in which local muscular action entirely fails to make its appearance
in connection with injections of venom repeated at intervals of twenty minutes,
it will again begin to manifest itself if the period of the intervals be doubled.
The general phenomena attending the cumulative administration of normal
Daboia-venom in doses too small or too dilute to induce violent general convul-
sions and death within the course of a few minutes, are of precisely the same
nature as those attending the action of relatively large quantities of venom in
which the nerve-irritant toxin is deficient in amount or entirely absent, as
it frequently is in samples which have been kept for any length of time, and as
it certainly is, as Wall first pointed out,* in specimens which have been heated
to boiling. All evidences of direct centric nervous stimulation are absent and
are replaced by an excessive immobility and by indications of the occurrence
of blood-change, but of blood-change of a nature absolutely distinct from that
attending the action of cobra-venom, and manifesting itself in a great tendency
to the occurrence of sanguinolent effusions, and in a peculiar brick-red colour
and absence of coagulability in the blood when removed from the vessels.
* Op. cit.