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SOME OBSERVATIONS ON THE POISON OF THE BANDED KRAIT
(BUNGARUS FASCIATUS).
IN recent papers 1 on the problems surrounding the physiological actions of the
venoms of the different species of snakes and the antitoxic sera prepared
with these venoms, I have brought forward facts, which show that no con-
clusions can be drawn regarding the action of the poison of one species of
poisonous snake from the observations made on the action of the venom of
another species, no matter how closely allied to each other the two spe-
cies may be ; facts, which show that the venom of each species must be
studied separately. Let us take, for example, the case of the poisons of
Naia tripudians (cobra) and of the snake known as Bungarus fasciatus. The
former of these snakes is a species of the genus Naia and the latter of the genus
Bungarus. Both these genera belong to the same sub-family, viz., Elapinæ,
of Colubridæ, and are very closely allied. Now, I have shown that an immune
serum prepared with the venom of Naia tripudians causes a well-marked precipi-
tum with this poison but has no such action when tested with the venom of
Bungarus fasciatus. We can, therefore, conclude that the proteids of cobra
venom are of a different nature, or at any rate do not possess the same
' h a p t o p h o r i c g r o u p s ' a s t h e p r o t e i d s o f t h e v e n o m o f B u n g a r u s f a s c i a t u s .
Further, I have shown that a serum antitoxic to cobra venom, e.g., Calmette's
serum, has no power to neutralise the venom of Bungarus fasciatus. Similar
phenomena can be demonstrated in the case of the venoms of the cobra and
of the Australian tiger-snake (Hoplocephalus curtus), which also belongs
to the same sub-family, viz., Elapinæ, of Colubridæ, as the cobra. Thus, a
serum prepared with cobra poison, which causes a precipitum with this venom,
has no precipitating action for the venom of Hoplocephalus curtus, and a
serum which is highly antitoxic for the venom of Hoplocephalus curtus has no
neutralising power for cobra poison. It is, therefore, evident that snake
venoms, even the poisons of allied species, will probably differ markedly, if not
entirely, from one another in physiological action, and that it is necessary to
study more thoroughly than has hitherto been done the action of each venom
separately. With this end in view I have taken up the study of the poisons of
the various species of the poisonous Indian snakes. Regarding the venoms of the
cobra and of the daboia some observations have already been published.2 This
work had special reference to the action of these poisons on the nervous system,
on the red blood corpuscles and on the blood, plasma. I have shown that those
two venoms differ from one another in every detail of their physiological action.
B
2
In the present communication we shall consider some observations which were
made with the venom of Bungarus fasciatus, and compare, as far as can be
compared, the action of this poison with the actions of the two venoms mentioned
above. When opportunity and material permit, I propose to do the same with
the venoms of Bungarus caeruleus, Naia bungarus and Echis carinata.
Up to the present time very few observations have been made with the
poison of any species of the genus Bungarus. As a result of a few experiments
with the venom of Bungarus fasciatus, Wall 3 h a s c o m e t o t h e c o n c l u s i o n t h a t
this poison differs markedly in physiological action from the venom of the
cobra. He has pointed out that experimental cases of intoxication with the
venom of Bungarus fasciatus may be divided into two classes; (1) a class of
acute cases, and (2) a class of chronic cases. In the acute cases death takes
place within 48 or 72 hours after the injection of the poison. There is some-
times slight swelling at the site of inoculation: profuse salivation, accompanied
sometimes by vomiting, is a common symptom: ultimately paralysis with twitch-
ing of the muscles developes: death rapidly follows from paralysis of respiration.
Wall states that these cases present symptoms which are indistinguishable from
the symptoms seen in the case of cobra venom intoxication; there is, however,
one difference, namely, that the local reaction is not nearly so severe as is the
case in cobra venom poisoning. At the post-mortem examination he found a slight
effusion of a pale pinkish serum in the areolar tissue round the site of inocula-
tion: there was no extravasation of blood and apparently little or no breaking up
of the red cells. The blood was found to clot solidly on withdrawal from the
vessels.
Wall has stated that in his experience in cases of cobra venom intoxication,
if the animal survives 49 hours, ultimate recovery takes place. While not limit-
ing myself to this exact interval of time, I can say from observations on
a very great number of these cases, that if an experimental case of cobra venom
poisoning is going to end fatally it does so within the first two or three days.
Wall's second class of cases of intoxication with the venom of Bungarus
fasciatus shows that the same statement cannot be made as regards this poison.
For, in the class of chronic cases described by him death is long delayed, per-
haps for ten or twelve days. After the injection of the poison there is an interval
varying from two to six days, during which period no symptoms are observed,
the animal being apparently in perfect health. After this interval of time a more
or less chronic disease begins, which, Wall states, invariably ends fatally. The
symptoms observed during this late period of intoxication are not in the least
like the symptoms seen in the acute form of poisoning either with cobra venom
or with the venom of Bungarus fasciatus itself. There are loss of appetite
and great depression: there is a marked diminution in the urinary secretion.
3
Then follow a slight failure of the respiratory function and irregular elevations of
temperature, accompanied by great muscular weakness. Purulent discharges
from the eyes, nose and rectum are also seen. There is no tendency to
hæmorrhages. Death closes this scene after a few days' illness.
As a result of the observation of the symptoms in these two groups of cases,
Wall arrived at the conclusion that the venom of Bungarus fasciatus acts mainly
on the central nervous system, causing paralysis in the acute cases and great
weakness and depression in the chronic cases. On the coagulability of the blood
he considered it had little or no action, although in the chronic cases he noticed
that the coagulum was of a loose and imperfect character. Further, he thought
that it had a slight destructive action on the red blood corpuscles, as shown by
the pale pinkish exudate at the site of inoculation. This short description
completes the summary of Wall's researches.
The observations which I shall bring forward in this communication, while
confirming Wall's statements in almost every detail, further extend his results and
also demonstrate some new facts as regards the action of this particular venom.
The material which was used in all my experiments was pure, dry, fresh
venom of Bungarus fasciatus. This was collected, under my personal super-
vision, during a period of a month or two from two full-sized living snakes.
The poison was obtained by allowing the snakes to bite through a sheet of
American cloth tightly stretched over the mouth of a strong wine-glass. When
the poison had been thoroughly dried over lime, it was added to the general
stock, which was preserved in an air-tight tube kept from the light.
Before the venom was weighed, it was reduced to an impalpable powder and
again dried over lime. In this way it was found possible to obtain a poison of
uniform strength for all experiments at different intervals of time, thereby ensur-
ing observations comparable amongst themselves.
Amount of coagulable proteid in the venom of Bungarus fasciatus.
The temperature at which the coagulable proteids were thrown down was
found to be between 7o° and 75° C. An experiment was made with the view of
estimating the amount of proteid which was coagulated at this latter temper-
ature. A reference to the protocols (series No. 1) will show that this amount
was about 20 per cent, of the total venom.
I have al ready 4 det ai l ed some si mi l are x p e r i m e n t s w h i c h w e r e m a d e w i t h
cobra and daboia venoms. As the samples of the venoms which were used
for these estimations had been procured by squeezing the glands of the
snakes, it was suggested to me by Professor Martin of Melbourne, that this
rather rough treatment of the glands might cause a certain amount of serous
exudation into them, and that in this way the coagulable proteids of the venom
B2
4
might be augmented. To get rid of this possible fallacy I made another experi-
ment with cobra venom, using the same technique as before, with the exception
that the sample of venom was obtained from three snakes by allowing them to
bite through a sheet of rubber stretched over a strong wine-glass, no pressure
being made over the glands. The amount of coagulable proteid obtained in
this experiment was found to be 24.6 per cent., practically the same quantity
as in the first observation, the details of which have already been published.
We may, therefore, take it that squeezing the glands causes no increase in the
amount of coagulable proteid contained in the venom.
For the sake of comparison the results of the estimation of the coagulable
proteids in the three poisons with which I have worked are tabulated as
follows:—
Cobra venom.
Daboia venom.
Venom of Bungarus fasciatus.
Amount of proteid
coagulable by heat.
24 per cent.
25 per cent.
20 per cent.
Rapid death, the result of the intravenous injection of the venom
of Bungarus fasciatus.
I have mentioned above that Wall has divided cases of intoxication with
this venom into two groups, and that he has accurately described the symptoms
which are observed in those two classes of cases. There is, however, still
another class of case, which would probably only be met with in experimental
work.
When a comparatively large quantity of this poison is injected directly into
the blood stream of an animal, death takes place within a few minutes after the
injection. On post-mortem examination a more or less extensive intravascular
thrombosis is found. The following two experiments will serve as illustrations
of this class of case.
RABBIT 3.—Weight 1,700 grammes. Received intravenously 17
milli-grammes of venom, viz., 10 milligrammes per kilo. Death, preceded by general
convulsions, opisthotonus and dyspnœa took place 2¾ minutes after the
injection. At the post-mortem examination, made immediately after death, the
blood in the portal vein and inferior vena cava was found to be liquid. The
pulmonary arteries were full of solid clot. Thrombi were also found in the right
auricle. There were no clots in either ventricle. The blood collected in a test-
tube from the inferior vena cava clotted solidly soon after withdrawal. The
serum which exuded from this clot was perfectly clear and free from staining
with hæmoglobin.
5
RABBIT 18.— Weight 1,570 grammes. Received intravenously 6.28 milli-
grammes of venom, viz., 4 milligrammes per kilo., along with 2 c.c. of
Calmette's serum. General convulsions soon set in and ended in death, which
took place 2½ minutes after the injection of the poison. At the post-mortem
examination, made immediately after death, the blood in the portal vein and in
the inferior vena cava was found to be liquid. Clots were found in the right
heart and in the pulmonary arteries. Blood collected in a test tube from the
inferior vena cava clotted solidly. Three hours after withdrawal no serum
had exuded from this clot.
It would appear from these observations that, when death rapidly follows
an injection of the venom of Bungarus fasciatus directly into the blood stream,
a more or less extensive intravascular clotting is found on careful post-mortem
examination performed immediately after death. Further, there can be no
doubt that this thrombosis is the direct cause of the symptoms observed and of
death in these cases.
I have already shown in another communication 5 that a similar result follows
the injection of daboia venom, either intravenously or subcutaneously, if
the quantity of venom be sufficient. But, while in the case of daboia venom
a comparatively small amount, namely, about 0.1 milligramme per kilo.,
injected intravenously into a rabbit is sufficient to bring about this remark
-able phenomenon, it requires a much larger quantity of the venom of
Bungarus fasciatus to produce a like effect. For, while thrombosis and death
may possibly result from the intravenous injection of 4 or 5 milligrammes
per kilo. of this latter venom, it is necessary to inject as much as 10 milli-
grammes per kilo. to be certain of killing a rabbit in this .way. In the same
paper I showed that, when cobra venom, even in very large quantity, is
injected directly into the blood stream of an animal, and when death results
almost immediately afterwards, the most careful post-mortem examination does
not reveal the least trace of intravascular clotting. The heart is still beating
and the blood throughout is quite liquid. In these cases the fatal result is
probably due to a direct action of the poison on the central nervous system.
This question, however, is still under investigation and will form the subject of
another communication.
Acute cases of intoxication with the venom of Bungarus fasciatus.
As a result of many experiments on different species of animals I have been
able to confirm and extend the observations made by Wall, a summary of which
has been given above. Let us first consider the cases he classifies as acute
cases.
The symptoms which Wall has described in this group of cases are well.
6
exemplified in the following experiments, which are typical of the results I have
obtained
:—
RABBIT 4.—Weight 1,640 grammes.
12-53 P.m.—Received intravenously 8.2 milligrammes of venom, i.e.,
5 milligrammes per kilo.
1-1 P.M.—Appears ill: the respiration much quickened: paresis of the legs.
1-4 P. M.—Paralysis of legs well marked.
1-6 P. M.—Completely paralysed in all legs.
1-8 P. M.—Dyspnœa with inspiratory effort.
1-9 P. M.—Slight convulsions: breathing slow and laboured.
1-10 P.M.—General convulsions.
1-11 P. M.—Died, viz., 18 minutes after the injection of the poison.
Post-mortem examination, made immediately after death. The heart was
beating vigorously. No clots were found in the portal vein, inferior vena cava,
pulmonary arteries or right heart. Blood collected from the inferior vena cava
in a test-tube clotted almost immediately.
RABBIT 22.—Weight 1,490 grammes.
1-35 P. M.—Received intravenously 5.96 milligrammes of venom, i.e., 4
milligrammes per kilo.
1-55 P. M.—Appears ill: slight paresis.
2 P. M. —Completely paralysed: dyspnœa with inspiratory effort: general
convulsions at intervals.
2-5 P. M. —Died, viz., half an hour after the injection of the venom.
Post-mortem examination, made immediately after death. The heart was
beating vigorously. No clots were found anywhere. Blood collected from the
heart clotted solidly almost immediately.
RABBIT 5.—Weight 1,560 grammes.
1-30 P. M.—Received intravenously 5.5 milligrammes of venom, i.e., 3.5
milligrammes per kilo.
2-30 P. M.—Slight paralysis: breathing rapid.
3-30 P. M.—Paralysis almost complete: dyspnœa.
4-35 P. M. —Paralysis complete: respiration slow, with inspiratory effort.
4-44 P. M.—General convulsions and tremors.
4-45 P. M. —Died, viz., 3¼ hours after the injection of the venom.
Post-mortem examination, made immediately after death. Heart still
beating, although feebly. No intravascular thrombosis was found. Blood.
collected from the inferior vena cava and the heart clotted immediately. No
lesion of any organ was discovered.
RABBIT 6.—Weight 1,600 grammes.
3 P. M. —Received intravenously 4.8 milligrammes of venom, i.e., 3 milli-
grammes per kilo.
7
3-4o P. M.—Legs appear to be paralysed.
3-45 P. M. —Paralysis of legs complete.
3-52 P. M.—Marked dyspnœa.
3-55 P. M. —Slight convulsive movements, repeated at short intervals : respira
-tion slow, with , inspiratory effort.
3-59 P. M.—Died, viz., 59 minutes after the injection of the venom.
Post-mortem examination, made immediately after death. Heart still
beating, although feebly. No clots were found in any of the vessels. Blood
collected from the heart and the inferior vena cava clotted solidly immediately
on withdrawal. The serum which exuded from the clots was quite clear and
free from hæmoglobin staining.
RABBIT 10.—Weight 1,280 grammes.
20th January, I P. M.—Received intravenously 0.96 milligramme of venom,
i.e., 0.75 milligramme per kilo.
21st January. — Is ill and refuses food : slight paralysis of legs.
22nd January. — Paralysis almost complete.
I P. M.—Died, from paralysis of respiration.
Post-mortem examination.—Rigor mortis well marked. The upper and
lower lobes of the right lung as well as the upper lobe of the left lung were
infiltrated with blood, which was quite liquid. No clots were found anywhere.
Blood collected in test tubes from the heart and the inferior vena cava clotted
slowly, namely, in about 11 minutes : the clots were loose and not at all firm.
RABBIT 14.—Weight 1,530 grammes.
20th January, 1 P. M.—Received subcutaneously 3.8 milligrammes of venom,
i.e., 2.5 milligrammes per kilo.
21st January, 1 P. M. —Is very ill : paralysis nearly complete : considerable
swelling around the site of inoculation.
3 P. M.— Died.
Post-mortem examination.—Slight serous exudation at the site of inocula
-tion but no ecchymosis. All the organs appear healthy. Blood collected in
test tubes from the heart and the inferior vena cava clotted only after some time
the clots were very loose and soft.
These six cases, examples of many I have observed, confirm in a striking
manner the accurate observations made by Wall, the results of which have been
summarised above. It is, therefore, unnecessary to again detail the symptoms
which one meets with in these cases. It is sufficient to draw attention to the
fact that no difference can be seen between the symptoms observed in these
cases and the symptoms seen in cases of cobra venom intoxication. It is probable
that death is due in both instances to the action of the poison on the central
nervous system, paralysis of respiration being the primary cause of death. I shall
return later on to the consideration of the action which the venom of Bungarus
fasciatus has on the blood plasma and on the red blood corpuscles.
Chronic cases of intoxication with the venom of Bungarus fasciatus.
The observations which I have made in this class of cases confirm Wall's
statement, namely, that there is a chronic form of intoxication following the
injection of this venom, a condition which is never met with in cases of cobra
venom poisoning.
The following experiments will serve as examples of this disease, which has
been studied both in monkeys and in rabbits:
—
MONKEY 5.—Weight 1,950 grammes.
4th February 1902.—Received subcutaneously in the front of the chest
4.87 milligrammes of venom, i.e., 2.5 milligrammes per kilo.
5th February.—No swelling or extravasation of blood at the site of injection.
Is not eating well, but appears to be otherwise in good health.
6th February.— Is eating well and seems to be quite well.
7th February.— Weight 1,845 grammes. Is very ill to-day: is not eating
and is much depressed. There is great muscular weakness, and apparently
slight paralysis.
8th February.— Weight 1,771 grammes. There is much emaciation and
muscular weakness: paralysis is almost complete. Died at 2 P.M. to-day.
MONKEY 2.—Weight 1,640 grammes.
27th February 1902.—Received subcutaneously in the front of the chest
6.2 milligrammes of venom, i.e., 3.7 milligrammes per kilo.
28th February.—Very slight swelling at the site of injection. Œdematous
swelling of the abdominal wall between the pubes and umbilicus. The animal
otherwise is in good health.
1st March.—W eight 1,500 grammes. Appears ill and is not eating. There
is no paralysis.
2nd March.— Is apparently in good health.
3rd March.—Weight 1,330 grammes. Is very ill and dèpressed, and has
become very emaciated. It is unable to walk, and when laid down on its side is
unable to rise up. In addition to this great muscular weakness there appears
to be slight paralysis, affecting principally the hind legs. There is considerable
muscular atrophy.
4th March.— Died this morning.
Post-mortem examination.—The animal was much emaciated. No lesion
of any kind was found at the site of inoculation. All the internal organs
appeared normal. The medulla, cord and motor area of the cortex were removed
for special microscopical examination, the results of which will be detailed later.
9
MONKEY 6.—Weight 1,260 grammes.
29th April 1902.—Received subcutaneously in the front of the chest 3.15
milligrammes of venom, i.e., 2.5 milligrammes per kilo.
30th April.—Weight 1,200 grammes. Is eating and appears quite well.
There is no swelling at the site of inoculation.
1st May.—Weight 1,170 grammes. Is ill and appears depressed. There
is no paralysis.
2nd May.—Weight 1,190 grammes. Is better than it was yesterday, but
is still depressed.
3rd May—7th May.—Continued dull and ill, but without any marked
symptoms.
8th May. —Weight 940 grammes. Is eating nothing: has become much
emaciated: there is great muscular atrophy and weakness: appears to be com-
pletely paralysed.
9th May.— Died this morning.
Post-mortem examination.—The body was much emaciated. No lesion
of any kind could be found. Pieces of the central nervous system were removed
for special histological examination, the results of which will be detailed later.
RABBIT 9 .—Weight 1,590 grammes.
20th January 1902.—Received intravenously 1.27 milligrammes of venom,
i.e., 0.8 milligramme per kilo.
21st J anuary.—Is eating: on being stimulated there is slight general twitch-
ing of the muscles: there is no paralysis.
22nd J anuary.— Weight 1,380 grammes. Is eating and appears quite well.
23rd January.— Weight 1,360 grammes. Is very ill and depressed, and
is not eating well. Has become considerably emaciated.
24th J anuary.—Weight 1,180 grammes. Is very ill, greatly depressed
and emaciated: muscular atrophy marked: there does not appear to be any
paralysis.
25th January.—Moribund: was killed.
Post-mortem examination.—No lesion of any kind was found in the internal
organs.
RABBIT 12.—Weight 1,380 grammes.
20th J anuary 1902.—Received intravenously 0.82 milligramme of venom,
i.e., 0.6 milligramme per kilo.
21st January—27th J anuary.— During this time the animal appeared to
be in good health, although there was a progressive loss of weight. The weight
on 27th January was 1,130 grammes.
28th J anuary.—Weight 1,151 grammes. Is very ill and depressed: mus-
cular atrophy and weakness marked: there is no paralysis: a thick purulent
discharge from the eyes is present.
C