_SNAKE-CHARMERS._
In all the countries of the globe where poisonous snakes are formidable
to man, there are certain individuals who profess to be secure from all
ill-effects from the bites of these reptiles, whether because they are
immune to venom, or because they possess secrets which enable them to
cure themselves when they happen to have been bitten. Not unnaturally
these secrets are sometimes turned to profitable account, and the
possessors of them generally enjoy considerable popular influence, and
are very highly venerated. Intimate relations with the divinities are
freely attributed to them.
Among the Romans the jugglers who carried on the profession of
snake-charmers and healers of snake-bites were known as _Psylli_.
Plutarch tells us that Cato, who loved not doctors because they were
Greeks, attached a certain number of them to the army of Libya. They
were accustomed to expose their children to serpents as soon as they
were born, and the mothers, if they had failed in conjugal fidelity,
were infallibly punished by the death of their offspring. If, on the
contrary, the children were lawful, they had nothing to fear from the
bites of the reptiles. “_Recens etiam editos serpentibus offerebant;
si essent partus adulteri, matrum crimina plectabantur interitu
parvulorum; si pudici, probos ortus a morte paterni privilegium
tuebatur_” (Solinus).
The Libyian Psylli of antiquity still have their representatives in
Tunis and in Egypt. Clot Bey writes as follows with reference to the
Egyptian Psylli:--
“The _Ophiogeni_, or Snake-charmers, have been renowned from all
time. Strabo speaks of them, and Prosper Alpinus was a witness of the
singular effects of their art. The majority of modern travellers who
have visited Egypt have been equally struck with the freedom with which
they handle poisonous reptiles and animals.
“The Psylli go from house to house, calling forth and charming the
snakes that they may happen to contain. They claim to attract them by
means of a particular power. Armed with a short wand, they enter the
chamber to be purged from these venomous guests, make a smacking noise
with their tongue, spit upon the ground, and pronounce the following
incantation: ‘_I adjure you, by God, if you are without or within, to
appear_; _I adjure you, by the greatest of names; if you are obedient,
appear! If you disobey, die! die!_’ The snake, submissive to this
command, departs forthwith, issuing from a crack in the wall or
floor.”[86]
India is pre-eminently the country of snake-charmers. There exists an
entire caste of Hindus, called _Mal_, who are professional catchers and
vendors of snakes, but do not perform tricks with them.
The snake-charmers are recruited from among another caste, that of the
_Sangis_ or _Tubriwallahs_ of Bengal.
These men, who are usually clothed in yellow robes and wear large
turbans, manage the Cobra with really marvellous skill. All travellers
who have had the opportunity of crossing India or of touching at a port
on the coast or on that of Ceylon have witnessed scenes similar to that
described by Natalis Rondot (figs. 90 and 91):--
“Towards six o’clock in the evening a Hindu juggler comes on board.
He is poorly clad, and wears a turban decorated with three feathers,
and several necklaces of those amulet-sachets called _gris-gris_ in
Senegal. In a flat basket he carries a spectacled Cobra-di-Capello.
[Illustration: FIG. 90.--INDIAN SNAKE-CHARMER AT COLOMBO
(CEYLON).]
[Illustration: FIG. 91.--INDIAN SNAKE-CHARMER AT COLOMBO
(CEYLON).]
“This man instals himself on deck; we sit down on the seat provided for
the officer of the watch, and the sailors form a circle. The basket is
placed on the deck and uncovered; the Cobra is coiled up at the bottom
of it. The juggler squats a few paces off and commences to play a slow,
plaintive, and monotonous air, with a kind of small clarinet (fig. 92),
the sounds of which recall those of the Breton _biniou_.
[Illustration: FIG. 92.--MUSICAL INSTRUMENT USED BY INDIAN
SNAKE-CHARMERS TO CHARM COBRAS.
(For this figure I am indebted to the kindness of Dr. Pineau.)]
“By degrees the snake moves, extends itself, and then assumes an erect
posture, but without quitting the basket. It begins to appear uneasy
and endeavours to recognise its surroundings; it becomes agitated and
irritated, expands and spreads out its hood, breathes hard rather
than hisses, and frequently and quickly shoots out its slender forked
tongue; several times it makes a violent dart as though to attack the
juggler; it frequently trembles, or rather gives sudden starts. The
juggler keeps his eyes always fastened upon the snake, and gazes at
it with a singular fixed stare. After some time, about ten or twelve
minutes, the Cobra becomes less animated, grows quiet, and then sways
as though influenced by the slow and monotonous rhythm of the musician;
it keeps incessantly darting out its tongue. Little by little it is
brought to a sort of somnolent condition. Its eyes, which at first
watched the juggler as though in order to take him by surprise, are, to
a certain extent, fixed and fascinated by the latter’s gaze. The Hindu
takes advantage of this moment of stupefaction on the part of the snake
by approaching it slowly without ceasing to play, and touches the head
of the Cobra, first with his nose and then with his tongue. Although
this takes but an instant the reptile starts out of its sleep, and the
juggler has barely time to throw himself backwards so as not to be
struck by the snake, which makes a furious dart at him.
“We doubt whether the Cobra still has it fangs, and whether the Hindu
incurs any real danger in approaching it. Accordingly we promise our
man a Spanish piastre if he will make the snake bite a couple of fowls.
A black hen, which struggles violently, is taken and offered to the
Cobra, which half rises, looks at the bird, bites it, and lets it go.
The fowl is released and runs off terrified. Six-minutes later, by the
watch, it vomits, stretches out its legs, and dies. A second fowl is
placed in front of the snake, which bites it twice, and the bird dies
in eight minutes.”[87]
Certain jugglers exhibit snakes from which they have taken care to
extract the fangs; they offer the animal a piece of cloth or soft stuff
into which it drives its poison-teeth, and the fabric is then quickly
snatched away in order by this means to break off the poison-fangs that
have penetrated it. This operation is repeated at certain intervals
with a view to preventing the reserve fangs from coming into use, and
the reptiles can then be handled without any danger.
It is unquestionable, however, and I have personally satisfied
myself of the fact, that many genuine snake-charmers go through
their performances with Cobras whose poison-apparatus is absolutely
intact. That they almost always avoid being bitten is due to a perfect
knowledge of the habits and movements of these reptiles. Nevertheless,
accidents sometimes happen to them, and every year a few of them
succumb in pursuit of their calling (see p. 370). Still, it may be
asserted that some of them really know how to vaccinate themselves
against venom, by making young Cobras bite them from time to time.
It is stated by E. C. Cotes,[88] formerly of the Calcutta Museum, that
the Indian snake-charmers do not extract the poison-fangs from their
snakes. Even though deprived of its fangs, the snake would still be
dangerous on account of its other teeth, the punctures of which would
provide another channel for the penetration of the venom.
Snake-charmers pretend that they owe their immunity to graduated
inoculations. This is not yet conclusively proved; what is better
established is that they take the greatest care to avoid being bitten,
and that in so doing they display the most remarkable skill.
Even in France we are acquainted with professional viper-catchers,
who employ the method of graduated inoculations in order to render
themselves immune to the bites of indigenous reptiles. One of these
men, who lives near Arbois (Jura), takes good care to get himself
bitten, at least once a year, by a young viper; when he forgets this
precaution and happens to be bitten, he always feels the effects much
more severely.
Fraser[89] (of Edinburgh) thinks that the repeated ingestion of small
quantities of venom may suffice to confer immunity, and he mentions
a certain number of experiments performed by him upon white rats and
kittens, from which it would appear that the ingestion of venom,
continued for a long time, finally renders these animals absolutely
refractory to subcutaneous inoculation with doses of the same venom
several times greater than the lethal one. He therefore concludes
that this process of vaccination may probably be in use among
snake-charmers.
I have submitted this hypothesis to the test of experiment. I succeeded
in making _adult_ rabbits, guinea-pigs, and pigeons absorb enormous
doses of _Cobra_-venom by way of the alimentary canal. In this manner
I have administered doses as much as a thousand times greater than the
lethal one, yet I have never been able to prove that the serum of these
animals became antitoxic.
On the other hand, I have succeeded in vaccinating very young
guinea-pigs and young rabbits which were still being suckled, by making
them absorb, every second day, minimal and certainly innocuous doses of
very dilute venom. In the case of young animals, venom is not modified
by the digestive juices, and a portion of it is absorbed by the mucous
membrane of the intestine. When the dose ingested is suitably reduced
they withstand it, and when these ingestions are repeated every second
or third day during the first weeks of life, the animals become
perfectly vaccinated against doses certainly lethal for controls of the
same age and weight. But it is always difficult to push the vaccination
far enough for the serum to acquire antitoxic properties, and I have
never been able to prove the appearance of the latter.
I think, however, that it ought to be possible to arrive at this result
by experimenting upon animals such as lambs, kids, calves, or foals,
the intestine of which remains permeable to toxins for a sufficiently
long period.
It may be that certain snake-charmers, who claim to possess family
secrets which they transmit from father to son, employ an analogous
method in order, in their infancy, to confer immunity to venoms upon
those of their male children who are to inherit their strange and
lucrative profession.
In Mexico, certain Indians called _Curados de Culebras_ know how to
acquire the privilege of being able to be bitten by poisonous snakes
without the least danger to life, by inoculating themselves several
times with the teeth of rattle-snakes.
Dr. Jacolot,[90] a naval surgeon, while staying at Tuxpan, made
enquiries as to these _Curados de Culebras_, and was able to satisfy
himself that their immunity is an actual fact.
The process of vaccination employed by the natives of Tuxpan is as
follows:--A preparatory treatment is necessary. On the very day on
which a man is to inoculate himself or get himself inoculated, he takes
from 5 to 15 tubers of a plant known by the name of _Mano de Sapo_
(_i.e._, Toad’s hand, _Dorstenia contrayerva_, Family _Urticaceæ_).
These tubers must--and this is absolutely necessary--be administered
on a _Friday_, and always in an odd number, 5, 7, 9, &c., up to 15,
according to the tolerance of the subject.
If the plant be gathered on the first Friday in March it possesses
its marvellous properties in the highest degree; in this case, even
if it be dry, it is still excellent for the preparatory stage of the
inoculation.
The physiological effects of _mano de sapo_ are not very marked:
the circulation is slightly diminished and a sensation of cold is
experienced, but there are no nervous troubles. The subject frequently
has attacks of vomiting or nausea. The inclination to vomit must be
fought against, for if the plant should happen to be rejected it would
be dangerous to submit to the inoculation.
The root of the _mano de sapo_ is usually taken fresh. There is another
indispensable precaution: while undergoing this treatment it is
necessary to abstain from all sexual intercourse for three days after
the first inoculation, for two days after the second, and for one day
after the third.
For the inoculation a large snake’s tooth, that is to say, one of the
fangs, is employed, and the fangs of the most poisonous snakes, such as
the rattle-snake (_cuatro narices_), are selected. The snake must be
killed on a _Friday_, and the fangs extracted the same day. The same
fang may serve for several years!
The inoculation is commenced on the dorsal surface of the left foot;
care must be taken to avoid coming into contact with a vein. The skin
is torn with the point of the fang, so that it bleeds a little, and the
incision is in the shape of a square.
From the left foot the operator passes to the right wrist (anterior
surface), then to the right foot (dorsal surface), and left wrist
(anterior surface), always changing from one side of the body to the
other.
Operations are continued on the left thigh, then on the right arm,
right thigh, and left arm; in this way all the limbs are inoculated. On
the body an inoculation is made in the centre of the sternum; another
is made in the nape, and a final one in the centre of the forehead. The
finishing touch is given with the semblance of a square incision in the
tongue.
At least seven series of similar inoculations are necessary to protect
a man from the spells of the serpent, and at the same time to confer
upon him the faculty of curing by suction the bites of the venomous
snakes that are most dreaded.
During the whole of the period in which the Indian thus submits to
successive inoculations, his health shows no noteworthy derangement.
He feels a slight headache and a strange inclination towards alcoholic
drinks. But when the moon is at the full, then indeed, an excitement
which is dangerous in another way takes possession of him. His
cerebral faculties become over-excited, and he feels that his senses
are deserting him; his eyes become bloodshot, and he is pursued and
tormented by an irresistible impulse to bite. He has itching sensations
in his gums, his mouth burns, and salivation is greatly increased. He
feels that he is going to give way to the necessity to bite, and then
he flees to the woods, where he bites the trees viciously, tears their
bark and discharges his venom. His poisonous saliva mingles with the
sap, and, surprising phenomenon, the tree withers and dies!
Woe to the man or animal who happens to be bitten by a _Curado de
Culebra_ in a fit of passion. The victim will die as quickly as if he
had been bitten by a snake!
Almost all the semi-savage people of Guiana, and of the valleys of the
Orinoco and the Amazons, as also the tribes of Central Africa and the
races of India, possess witch-doctors, who pretend to be in possession
of means to preserve themselves from snake-bites, which are just as
ridiculous and infallible as the procedure described above.
The archives of a criminal anthropology contain the story of a Lyonnese
gold-seeker, who had himself immunised against venom by an aboriginal
native of Guiana:[91]--
“The Indian took, from a bottle which contained several of them, a
tooth of the _Grage_ (_Lachesis atrox_), an extremely poisonous snake,
and with it made upon my instep three incisions about 3 centimetres
in breadth. He allowed the wounds to bleed for a minute. I then
experienced a fainting sensation, and large drops of sweat rolled from
my forehead. The wounds were next rubbed with a blackish powder. I
have since learnt that this powder was composed of the liver and gall
of the animal, dried in the sun and pounded up with the poison-glands.
The blood immediately ceased to flow. The Indian chewed some leaves
of a tree mixed with this powder, and, applying his lips to the sore,
injected into it as much saliva as he could, making an effort as though
to inflate a balloon. This completed the operation.
“Since then I have been bitten seven times by different species of
very dangerous snakes, such as the _Grage_, coral-snake, &c., and have
never even had an attack of fever. The Galibi, Boni, and Emerillon
Indians, the Bosse negroes, and all the aboriginal natives of Guiana
employ the same method of procedure. They even pretend that this kind
of vaccination is transmissible to their offspring, and that the
hereditary immunity is maintained through several generations.”
Some years ago Mons. d’Abbadie communicated to the Académie des
Sciences[92] a note from Colonel Serpa Pinto relating to another method
of vaccination employed by the natives of Mozambique, which the Colonel
himself consented to undergo.
“I was vaccinated,” writes Colonel Serpa Pinto, “at Inhambane (on
the East Coast of Africa), among the Vatuas. These people extract
the poison of a snake which is known in Portuguese as the _Alcatifa_
(_i.e._, carpet), and is so called on account of the variegated colour
of its skin, which resembles a carpet. I am not acquainted with the
means employed in order to obtain the poison, which is mixed with
vegetable substances, and forms with the latter a dark brown viscid
paste.
“Two parallel incisions, 5 millimetres in length, are made in the skin,
and into these is introduced the paste containing the poison. These
incisions are made on the arms, near the junction of the radius and
ulna with the carpal bones, on the back of the hand, on the back, on
the shoulder-blades, and on the feet, near the great toes. After the
operation the natives exact an oath that the vaccinated one will never
kill a poisonous snake, because they say that henceforth the snake is
his intimate friend, and they throw upon him an Alcatifa snake, which
does not bite him.
“After undergoing this operation my whole body was swollen up for a
week, and I underwent every possible kind of suffering.
“I have never been bitten by any snake, and cannot vouch for the
infallibility of this remedy. The Vatuas do so, however, and they never
kill a snake.
“A short time after having been vaccinated, I was stung, when in the
Seychelle Islands, by a scorpion, which did me no harm. Ten years
later, at the time of my journey across Africa, I was stung by another
scorpion which hurt me dreadfully, and for a week I thought that I was
going to die or lose my arm.”
Mystification and superstitious ideas play, as we see, a very great
part in this preventive treatment, which is undergone by the natives of
certain countries and snake-catchers or charmers. But it is not very
surprising that, thanks to successive and repeated inoculations, a man
can succeed in acquiring sufficient immunity to preserve himself from
snake-bites.
In ancient times it was even pretended that it was possible for this
immunity to be transmitted in certain cases by heredity, and thus we
can understand how the profession of snake-charmer was hereditary in
certain native families in India or Egypt.
With reference to this subject, Professor Landouzy, in his fine work
on serum therapeutics, quotes a passage from “The Pharsalia” of Lucan
describing, in the year 60 A.D., the customs of the Psylli, a
people encountered by the army of Cato during its sojourn in Africa.
This passage is so interesting that I cannot refrain from reproducing
it:--
“Alone unharmed of all who till the earth
By deadly serpents, dwells the Psyllian race.
Potent as herbs their song; safe is their blood,
Nor gives admission to the poison germ
E’en when the chant has ceased. Their home itself
Placed in such venomous tract and serpent-thronged
Gained them this vantage, and a truce with death,
Else could they not have lived. Such is their trust
In purity of blood, that newly born
Each babe they prove by test of deadly asp
For foreign lineage. So the bird of Jove
Turns his new fledglings to the rising sun,
And such as gaze upon the beams of day
With eyes unwavering, for the use of heaven
He rears; but such as blink at Phœbus’ rays
Casts from the nest. Thus of unmixed descent
The babe who, dreading not the serpent touch,
Plays in his cradle with the deadly snake.”[93]
The only scientific conclusion to be drawn from the facts and
statements that we have just set before the reader is that, under
certain circumstances, man can unquestionably acquire the faculty of
resisting intoxication by snake-venom, by conferring upon himself a
veritable _active immunity_ by means of repeated inoculations of venom.
We shall shortly see that the case is the same with regard to animals.
PART III.
ANTIVENOMOUS SERUM THERAPEUTICS.
CHAPTER XIII.
_VACCINATION AGAINST SNAKE-VENOM--PREPARATION OF ANTIVENOMOUS
SERUM--ITS PREVENTIVE PROPERTIES AS REGARDS INTOXICATION BY
VENOM._
So long ago as the year 1887 it was shown by Sewall, in an important
paper on “Rattlesnake-Venom,”[94] that it is possible to render pigeons
gradually more resistant to the action of this venom by injecting them
with doses at first very small, and certainly incapable of producing
serious effects, and then with stronger and stronger doses. In this
way, although these little animals are very sensitive, he succeeded in
making them withstand doses ten times greater than the minimal lethal
dose.
A little later Kaufmann[95] obtained the same result with the venom of
French vipers. He did not, however, succeed in producing tolerance of
doses more than two or three times greater than the lethal one.
In 1892, at the time of my first experiments with cobra-venom at
Saigon,[96] I arrived at the conclusion that it was possible, by means
of successive inoculations with heated venoms, to confer on animals a
certain degree of resistance to doses invariably lethal to the controls.
From 1894 onwards, the investigations pursued simultaneously at
the Paris Natural History Museum, by Phisalix and Bertrand, upon
viper-venom, and at the Paris Pasteur Institute by myself, upon that of
the cobra, and subsequently upon other venoms of various origins, led
to much more definite results. These investigations show, on the one
hand, that by vaccinating guinea-pigs or rabbits, and taking certain
precautions, it is possible to confer upon these small animals a really
strong immunity to venom; on the other hand, that animals vaccinated
against cobra-venom are perfectly immune to doses of viper-venom
or that of other snakes (_Bungarus_, _Cerastes_, _Naja haje_,
_Pseudechis_) certainly lethal to the controls; and lastly, that _the
serum of the vaccinated animals contains antitoxic substances capable
of transmitting the immunity to other animals_.[97]
According to Phisalix and Bertrand, who, as we have stated,
experimented only with viper-venom, the best method of vaccinating
the guinea-pig consists in inoculating a dose of 0·4 milligramme of
this venom heated for five minutes at 75° C., and, forty-eight hours
afterwards, the same dose of non-heated venom. The latter is always
lethal to the control guinea-pigs in from six to eight hours.
Vaccination against cobra-venom, which is much more toxic, is most
surely effected by the method recommended by me, which consists in
at first injecting small doses of this venom mixed with an equal
quantity of a 1 per cent. solution of hypochlorite of lime. By degrees
the quantity of venom is increased and that of the hypochlorite
progressively diminished, and the injections are repeated every three
or four days, while attentively following the variations in the weight
of the animals. The inoculations are suspended as soon as emaciation
supervenes, and resumed when the weight becomes normal again. After
four injections of chloridated venom the chloride is omitted, and a
direct inoculation made with one-half the minimal lethal dose of pure
venom; then, three or four days afterwards, the injection is increased
to three-fourths of the minimal lethal dose; and finally, after the
lapse of another three or four days, a lethal dose is injected.
If the animals prove resistant, the vaccination can thenceforth be
pushed on rapidly, and the quantity of venom injected each time can be
increased, testing the susceptibility of the organism by the variations
in weight.
As a rule, three months are necessary for the vaccination of a rabbit
against twenty lethal doses. In six months we can succeed in making it
very easily withstand 100 lethal doses.
The serum of rabbits thus treated soon, _i.e._, after they have
received from five to six lethal doses, exhibits antitoxic properties
_in vitro_; these, however, are not very pronounced until after
prolonged treatment. They gradually become just as intense as those
observed in the case of animals vaccinated against diphtheria or
tetanus.
In 1895 Fraser confirmed these results,[98] and on May 15 in that year
exhibited before the Medico-Chirurgical Society of Edinburgh a rabbit
vaccinated against a dose of cobra-venom fifty times lethal.
At once considering the possibility of obtaining serums highly
antitoxic against snake-venoms, and of practical utility in the
therapeutics of snake-bites, I prepared to vaccinate a certain number
of large animals, horses and donkeys, in order to procure great
quantities of active serum. I at first experienced some difficulties
in providing myself with a sufficient store of venom. But thanks on
the one hand to the obliging collaboration of some of my old pupils
or colleagues, and on the other to the valuable co-operation of the
Colonial Governments of Indo-China, the French Settlements in India,
and Martinique, I soon received poisonous snakes and dried venom in
abundance.
[Illustration: FIG. 93.--VACCINATING A HORSE AGAINST VENOM AT THE
PASTEUR INSTITUTE AT LILLE.]
After this I was not long in pushing the vaccination of a few horses
until I made them resist, in a single injection, 2 _grammes_ of dry
cobra-venom, a dose about _eighty times lethal_; for I was able to
satisfy myself that about 0·025 gramme of cobra-venom was sufficient to
kill fresh horses in from twelve to twenty-four hours.
The immunisation of horses to this very high degree of tolerance of
venom is not obtained without difficulties; many animals succumb in
course of treatment from endocarditis or acute nephritis; in the case
of others, each injection of venom leads to the formation of enormous
aseptic abscesses, which have to be opened and drained. It may be said
that on an average an interval of _sixteen months_ is necessary in
order to obtain a serum sufficiently antitoxic.
[Illustration: FIG. 94.--ASEPTICALLY BLEEDING A HORSE VACCINATED
AGAINST VENOM IN ORDER TO OBTAIN ANTIVENOMOUS SERUM AT THE PASTEUR
INSTITUTE AT LILLE.]
When a horse is well vaccinated and tolerates without a reaction 2
_grammes_ of dry cobra-venom in a single subcutaneous injection, it may
be bled on three consecutive occasions in the space of ten days, and in
this way 20 litres of blood may be drawn from it (fig. 94).
The bleeding is arranged in the following manner: _Twelve days_ after
the last injection of venom the horse is bled for the first time to the
extent of 8 litres; five days later it is bled for the second time to
the extent of 6 litres; five days later still the third bleeding takes
place, when 6 litres are again withdrawn.
The animal is then allowed to rest for three months and supplied with
strengthening food, and during this period 2 _grammes_ of venom are
again injected on two occasions at the end of a month, followed, a
month and a half later, by the injection of 2 more _grammes_. The
antitoxic power of the serum is thus maintained approximately at the
same standard.
The serum drawn off at each bleeding must be severely tested, which is
done by gauging its antitoxic power _in vitro_, when mixed with venom,
and also its preventive effect.
An antivenomous serum may be considered to be utilisable when a mixture
of 1 c.c. of serum with 0·001 gramme of cobra-venom produces no
intoxicating effect in the rabbit, and when a preventive subcutaneous
injection of 2 c.c. of serum into a rabbit of about 2 kilogrammes
enables it to resist, two hours later, subcutaneous inoculation with 1
milligramme of venom.
The _preventive power_ may be very quickly tested by injecting a
rabbit, _in the marginal vein of the right ear_ for example, with
2 c.c. of serum, and injecting, _five minutes afterwards_, _in the
marginal vein of the left ear_, 8 milligramme of venom. This dose of
1 milligramme generally kills the control rabbits in less than thirty
minutes when introduced into the veins, and in from two to three hours
when injected beneath the skin.
This rapid proof by _intravenous injection_ is extremely striking and
demonstrative; it can be effected in public during a class or lecture
in less than an hour, and enables an immediate estimate to be formed
of the value of an antivenomous serum. When it is intended to adopt
this method, it is essential to make use of a recent solution of venom,
for solutions from a week to a fortnight old, although sterile, have
already lost a large portion of their toxicity, and, if these be
employed, the dose of venom calculated to kill the control animals in
thirty minutes, for example, takes an hour or more to do so.
I always prepare my test solutions of venom in the following manner:--
Ten milligrammes of dry cobra-venom are weighed in a delicate balance.
The venom is dissolved in 10 c.c. of 0·8 per cent. physiological salt
solution, which takes a few minutes. When the venom is thoroughly
dissolved it is transferred to a test-tube, which is immersed for
three-quarters of an hour in a water-bath heated to + 72° C. In
this way the non-toxic albumins are coagulated without modifying
the neurotoxic substance. The solution is poured on to a filter
of sterilised paper, and the clear liquid which is collected is
immediately put up in glass phials, which are hermetically sealed,
or in small sterilised bottles. Its toxicity is tested upon control
animals, and it may be kept for five or six days if protected from
light, or for several weeks in a refrigerator at about 0° C.
_One-tenth of this solution corresponds exactly to 1 milligramme of dry
venom._
As for the antivenomous serum, as soon as its antitoxic value has been
ascertained by the methods that I have just described, and it has
been separated from clots and red corpuscles by suitable decantation,
it is portioned out, with the usual aseptic precautions, into small
sterilised bottles of 10 c.c. capacity, without the addition of any
antiseptic.
In order to ensure that it will keep for a long time, care is then
taken to heat the hermetically sealed bottles in a water-bath at a
temperature of 58° C. for one hour, and this operation is repeated for
three days in succession.
Serum prepared in this way preserves its antitoxic power unimpaired
for about two years, _in all climates_. I have had occasion at various
times to receive bottles which had been sent eighteen months and two
years previously to India and Indo-China, and I was able to show
that their standard had not perceptibly deteriorated. It was only the
appearance of the contained liquid that was slightly changed; it was
discoloured, and when shaken small white flakes were seen floating
through it. These flakes are not a sign of deterioration; they are
composed of deposits of precipitated albumin. They can be partly
dissolved again by violent shaking, or they may be separated before use
by filtration through sterilised paper.
In a dry state, antivenomous serum may be kept for an almost indefinite
period, in hermetically sealed glass tubes. In this condition it is
usually divided into doses of 1 gramme, and when it is desired to make
use of it, it is sufficient to dissolve a dose in 10 c.c. of water
which has been boiled and allowed to cool, which takes two or three
minutes. This solution is then injected beneath the skin, as though it
were liquid serum.
The Pasteur Institute at Lille prepares in this way large quantities
of antivenomous serum, which are sent all over the world to those
countries in which poisonous snakes are most dangerous.
Recently, special laboratories for the production of this preparation
have been instituted at Bombay and at Kasauli, in the Punjab, by
Drs. G. Lamb and Semple; at Philadelphia, by Professor McFarland;
at São-Paulo, in Brazil, by Dr. Vital Brazil; and at Sydney, by Dr.
Tidswell.
* * * * *
_Specificity and Polyvalence of Antivenomous Serums._--By means of a
large number of experiments I have proved that snake-venoms, whatever
their origin, contain two principal substances: _neurotoxin_, which
exerts its effects upon the elements of the nervous system, and
_hæmorrhagin_ (Flexner and Noguchi), or _proteolytic diastase_, the
effects of which remain exclusively local when the venom is introduced
subcutaneously into the cellular tissue, but which produces coagulation
of the blood when the venom is injected directly into the blood stream.
The venom of COLUBRIDÆ in general is characterised by the
constant predominence of _neurotoxin_, to which it owes its extreme
toxicity, which is especially intense in the case of cobra-venom. It
contains no, or scarcely any _hæmorrhagin_; for this reason the local
symptoms of poisoning by COLUBRINE venom are almost _nil_.
This _neurotoxin_, as we have seen, shows itself very highly resistant
to heat.
The venom of VIPERIDÆ, on the contrary, especially that
of _Lachesis_, is characterised by the almost total absence of
_neurotoxin_, while its richness in _hæmorrhagin_ is considerable.
Consequently, heating for a few minutes at + 75° C. renders it almost
entirely inactive, since _hæmorrhagin_ is very sensitive to heat.
Given venom of some kind or other, the origin of which is unknown, it
is therefore possible to ascertain whether the snake from which it was
extracted belonged to the COLUBRIDÆ or VIPERIDÆ, by
determining its richness in _neurotoxin_ resistant to heating at + 85°
C.
Certain VIPERINE venoms, such as those of the European
_Vipera berus_ and _Vipera aspis_, the African _Cerastes_ and American
_Crotalus_ contain at the same time a small proportion--varying greatly
in amount according to the species--of _neurotoxin_, and a much larger
proportion of _hæmorrhagin_. It is for this reason that these venoms,
although greatly attenuated and deprived of their local action by
heating, still remain toxic when injected in large doses into animals
after having been heated to + 75° C.
On the other hand, some COLUBRINE venoms, such as those of
_Bungarus cæruleus_, which are very rich in _neurotoxin_, contain a
quantity of hæmorrhagin sufficient to differentiate their effects in
appearance from those produced by cobra-venom, when they are injected,
not beneath the skin, but directly into the veins. In this case their
effects upon the blood are added to those of their neurotoxin.
It would seem, too, that the venoms of Australian COLUBRIDÆ
(_Hoplocephalus_, _Pseudechis_) form a special group, which is richer
in _hæmorrhagin_ than are those of the COLUBRIDÆ of the Old
World.[99]
On studying, in the case of these various venoms, the action _in vitro_
and _in vivo_ of a purely _antineurotoxic_ antivenomous serum, such as,
for example, that of an animal vaccinated against cobra-venom heated
to + 75° C., it is found that this serum has a very decided effect
upon cobra-venom, and likewise upon that of snakes belonging to allied
species (_Naja bungarus_, _Naja haje_), and that its action upon the
other venoms is less in proportion as they contain less _neurotoxin_.
It prevents hæmolysis _in vitro_, and suppresses the effects of
intoxication on the nervous system, but does not modify in any way the
phenomena of coagulation or of proteolysis.
If this serum be made to act _in vitro_ on those VIPERINE
venoms that, when heated to + 75° C. and deprived of their hæmorrhagin,
remain neurotoxic, like the venom of the common viper, it is found
that it renders them entirely innocuous. Therefore, in the case
of all species of poisonous snakes, and perhaps also in that of
other poisonous animals (such as scorpions), it appears that the
_neurotoxic_ substance is _one and the same_, and always neutralisable
by an _antineurotoxic_ serum like that of animals vaccinated against
cobra-venom.
_Neurotoxin_ being the essentially active substance in venoms, and that
to which the dangerous properties of poisonous snakes, as regards man
and domestic animals, are especially due, it is the effects of this
that it is most necessary to prevent. Consequently, the first quality
that an antivenomous serum ought to exhibit, in order to be capable
of being used in the therapeutics of poisoning, is the possession of
an _antineurotoxic_ power as high as possible. This antineurotoxic
power is easily obtained by employing cobra-venom for the fundamental
immunisation of the horses destined for the production of the serum.
_Antineurotoxic_ serum thus prepared shows itself perfectly capable
of preventing all effects of intoxication from cobra-bites, which
are much the most frequent in India. In the same way it shows itself
quite sufficiently efficacious with regard to COLUBRINE
and VIPERINE venoms, the neurotoxic activity of which may
cause death. But it does not possess any preventive action upon the
local effects of _hæmorrhagin_, to which the noxiousness of certain
VIPERINE venoms--such as those of _Lachesis_--are almost
exclusively due.
In countries in which VIPERIDÆ are very common, we must
therefore not confine ourselves to vaccinating the animals that produce
serum solely against the _neurotoxin_ of cobra-venom, for instance; we
must prepare these animals, after having immunised them to cobra-venom,
by injecting them with progressively increasing doses of the various
venoms derived from the snakes that are most frequently met with in the
district.
Nothing, moreover, is easier than to train animals vaccinated against
cobra-venom to tolerate strong doses of the venoms of _Lachesis_,
_Vipera russellii_, _Crotalus_, _Hoplocephalus_, or _Pseudechis_. In
a few months we succeed in obtaining serums very active against these
different venoms.
Utilising the horse as producer of antitoxin, I have prepared by this
method _polyvalent_ serums capable of preventing the local action of
VIPERINE venoms, and of suppressing _in vitro_ their coagulant
and proteolytic effects upon the blood.
Unfortunately, great as has been the kindness of the many persons
who have most obligingly given me their assistance in the course of
the fifteen years during which I have studied this question, I have
found it impossible to procure sufficient quantities of venoms of
various origins to furnish each country with the polyvalent serums
corresponding to its particular needs. I have therefore been obliged to
confine myself to preparing for the most part _antineurotoxins_, which
I have been able to do, thanks to the abundant provision of _Cobra_-
and _Bungarus_-venoms, for which I am indebted to the liberality of the
Government of the French Settlements in India, and to that of my pupils
and friends who are at the present time in charge of the Colonial
Laboratories of Indo-China. Moreover, the recent foundation of the
Serum-Therapic Institutes of Bombay and Kasauli, Sydney, São-Paulo, and
Philadelphia, to-day renders it very easy for each country to provide
itself with antivenomous serum, either specific or polyvalent. Other
institutes will doubtless be established for the purpose of extending
the benefits of a method, the efficacy of which is sufficiently evident
for its adoption to be incumbent upon all those who are concerned with
safeguarding human existence.
CHAPTER XIV.
_NEUTRALISATION OF VENOM BY ANTITOXIN._
It is difficult, in the present state of our knowledge on the subject
of toxins and antitoxins, to determine the precise nature of the
reactions that are produced in the living organism as the result of
serum injected for the purpose of preventing the toxic action of venom.
I maintained, some years ago,[100] that the phenomenon in this case
was a purely physiological one, which I considered to be proved by the
fact that, if we mix _in vitro_, in determinate proportions, venom and
antivenomous serum, and if we heat this mixture at 68° C. for half an
hour, the injection of the heated mixture kills animals as if they were
inoculated with venom alone, although with a considerable retardation.
I concluded from this that, in all probability, antitoxic serum does
not modify the toxin with which it is mixed, but that it confines
itself to displaying a parallel and opposite action by preventing the
noxious effects. I therefore supposed that no chemical combination
is produced between these two substances, or, at least, that the
combination effected is very unstable.
My experiments were subsequently repeated by Martin and Cherry,[101]
who showed that the results as stated above were perfectly correct when
the mixture of venom and antitoxin was heated less than ten minutes
after it had been made, but that, if the heating did not take place
until twenty or thirty minutes later, the toxicity of the venom no
longer reappeared.
On the other hand, the admirable researches of Kyes and Sachs, and
subsequently those of Morgenroth, pursued under the direction of
Ehrlich at the Laboratory of Experimental Therapy at Frankfort, have
proved the readiness of venom to enter into chemical combination with
certain elements of normal serums, in particular with _lecithin_,
a combination which results in the formation of _hæmolysing_ and
non-toxic _lecithides_, the _neurotoxin_ being left free.
It therefore seemed impossible to deny the existence of a chemical
reaction between the venom and the serum, which was until quite
recently considered as proved. We shall see presently that this is not
the case. But let us first endeavour to determine the laws that govern
the neutralisation of variable quantities of venom by antivenomous
serum.
If, in a series of test-tubes, we bring the same quantity of
cobra-venom (_e.g._, 0·00005 gramme, a dose which is invariably lethal
to the mouse in two hours) into contact with progressively increasing
quantities of an antivenomous serum (_e.g._, 0·01 c.c., 0·02 c.c.,
&c., up to 0·1 c.c.), and, after thirty minutes of contact, inject
these different mixtures subcutaneously into a series of mice, we find
that all those that have received the mixtures containing less than
0·05 c.c. of serum succumb after variable intervals, while all the
rest survive. It is evident that, under these conditions, the serum
experimented upon has shown itself capable of neutralising _in vitro_,
in a dose of 0·05 c.c., 5 centimilligrammes of venom.
The same serum should therefore neutralise 1 milligramme of venom in a
dose of 1 c.c., that is to say, that this mixture injected into a mouse
ought to be entirely innocuous. Experiments show, however, that in
reality it is necessary to mix 1·2 c.c. of serum with 1 milligramme of
venom in order that the inoculated mouse may not succumb.
This proves that, in the initial mixture of 0·00005 gramme of venom +
0·05 c.c. of serum, there remained an exceedingly small quantity of
non-neutralised venom, and that this quantity of venom in a free state
was insufficient to cause the death of the animal, or even any apparent
malaise. When multiplied by twenty, however, it becomes capable of
producing toxic effects; it is for this reason that, when it is desired
to inoculate a mouse with twenty times the lethal dose of 0·00005
gramme _neutralised_, it is necessary to mix with this twenty times
lethal dose a dose of serum _a little larger_ than twenty times that
which renders 0·00005 gramme of venom innocuous to the mouse, that is
to say, 1·2 c.c.
If, instead of making use of the _mouse_ as test animal, we employ the
_rabbit_, it is found that the same serum, in a dose of 0·75 c.c.,
neutralises 0·001 gramme of venom sufficiently for the mixture to be
innocuous when inoculated. It is clear that, in this mixture, the whole
of the venom was not neutralised by the serum, but the small quantity
left free is incapable of producing harmful effects.
By this method of employing mixtures of the same dose of venom with
variable quantities of antivenomous serum, we are therefore enabled to
determine with the greatest exactness the antitoxic power _in vitro_ of
each specimen of serum. But it must not be forgotten that _the result
obtained applies only to the species of animal into which the mixtures
were injected_.
I have already stated (Chapter VIII.) that a fairly close parallelism
exists between the _neurotoxic_ action of venoms and their _hæmolytic_
action, and I have established that, in order that the sensitive red
blood-corpuscles may be dissolved under the influence of venom, it is
indispensable that the reaction take place in the presence of normal
serum, since venoms have no effect upon red corpuscles freed from serum
by several successive washings and centrifugings.
Preston Kyes has explained this phenomenon very well by showing that
the venom combines with the lecithins in the serum, or with those
contained in the stroma of the corpuscle, so as to constitute a
hæmolysing _lecithide_.
The knowledge of this fact enables us to determine, by means of a very
neat and simple method, and with a sufficient degree of accuracy for
practical purposes, the antitoxic power of an antivenomous serum by
measuring its _antihæmolytic_ power.[102]
To this end it is sufficient to cause variable doses of serum to act
on a given quantity of defibrinated horse- or rat-blood, to which a
constant dose of venom is then added. We employ, for example, a 5 per
cent. dilution of defibrinated horse-blood, which is portioned out in
doses of 1 c.c. into a series of test-tubes. To each of these tubes in
succession is added a progressively increasing quantity of the serum
for titration, starting with 0·01 c.c., and continuing with 0·02 c.c.,
0·03 c.c., &c., up to 0·1 c.c. A control tube receives no serum. There
are then introduced into all the tubes 1 decimilligramme of venom and
0·2 c.c. of normal horse-serum, deprived of alexin by previous heating
for half an hour at 58° C. At a temperature of about 16° C. hæmolysis
commences to manifest itself in the control tube in from fifteen to
twenty minutes. It takes place in the other tubes with a retardation
which varies with the dose of serum added. Tubes are to be noticed in
which it does not occur even after the lapse of a couple of hours.
Experience shows that we may consider as good for therapeutic use
serums which, in a dose of 0·05 c.c., completely prevent hæmolysis by
1 decimilligramme of COLUBRINE venom, such as that of Cobra,
Krait, &c., and those that in a dose of 0·7 c.c., prevent hæmolysis by
1 milligramme of the venom of _Lachesis_ or _Vipera berus_.
By a method calculated upon the foregoing, it is likewise possible
to measure the _antihæmorrhagic_ activity of an antivenomous serum,
for the parallelism existing between the _antineurotoxic_ and
_antihæmolytic_ actions of serums occurs again, as I have been able to
establish in conjunction with Noc, between the _antihæmorrhagic_ and
_antiproteolytic_ action of the same serums.
Now, the _antiproteolytic_ action is easily determined by means of
a series of test-tubes containing the same quantity of 20 per cent.
gelatinised _bouillon_, rendered imputrescible by the addition of
a small quantity of thymol. The gelatine being kept liquid in the
incubating stove, a progressively increasing quantity of serum is
poured into each tube. The same dose of venom, say 1 milligramme, is
then added in each case. The tubes are placed in the stove for six
hours at 36° C. They are then withdrawn and immersed in a bath of cold
water. Those in which the gelatine solidifies are noted, and thus we
establish the dose of antivenomous serum that inhibits the proteolysis
of this substance.
These different methods of control enable us to verify the activity
of antivenomous serums with great exactness, without the necessity of
having recourse to experiments upon animals.
* * * * *
In a very important memoir on the reconstitution of the toxins from a
mixture of _toxin_ + _antitoxin_, J. Morgenroth[103] has shown that
the venom, after being naturalised by the antivenomous serum, can be
dissociated from its combination by means of a method which consists in
adding to the latter a small quantity of hydrochloric acid.
Previous experiments by Kyes had established:--
(1) That antivenomous serum, the antitoxic action of which is so
manifest when it is mixed _in vitro_ with cobra-venom, remains entirely
inert when brought into contact with the combination _lecithin_ +
_venom_, that is to say, with _cobra-lecithide_.
(2) That the addition of lecithin to a neutral combination of _venom_ +
_antivenomous_ serum does not set the venom free again, and that under
these conditions no _lecithide_ is formed.
If, in a neutral mixture of _cobra-hæmolysin_ and _antitoxin_ we could
succeed in dissociating the two constituent elements, and in then
making the _cobra-hæmolysin_ combine with the _lecithin_, we should
have a toxin and antitoxin side by side; for the reasons indicated
above, this toxin (_lecithide_) and antitoxin (_antivenomous_ serum)
would be no longer capable of combining; but the toxin (_lecithide_),
thanks to its hæmolytic properties, could easily be demonstrated.
It is precisely this desideratum that J. Morgenroth has succeeded in
realising, by means of hydrochloric acid, which renders it possible
to dissociate the neutral mixture, _toxin_ + _antitoxin_, into its
constituent elements, and then to obtain a _lecithide_.
Experiments show that the quantity of lecithide thus restored
absolutely corresponds to that of the cobra-hæmolysin originally added
to the antitoxin, and that the antitoxin set free is not injured by
the hydrochloric acid, even after twenty-four hours of contact. It is
sufficient to add the quantity of soda or of ammonia necessary for the
neutralisation of the acid, in order to see the antitoxin reappear in
its original strength.
It is therefore possible, by causing hydrochloric acid (in a solution
not stronger than 3 per cent.) to act on a neutral mixture of
cobra-hæmolysin (toxin) and antitoxin, to set the former at liberty
in the form of _lecithide_, to withdraw the latter from the action of
the antitoxin, and to demonstrate its presence, owing to its hæmolytic
properties.
It has been found by Kyes and Sachs that, under the influence of
hydrochloric acid, cobra-hæmolysin becomes resistant to heat to such an
extent that it is not destroyed even by prolonged heating at 100° C.
If to a neutral mixture of toxin + antitoxin we add a small quantity of
hydrochloric acid, and then heat the mixture at 100° C., the antitoxin
being in this case destroyed, we shall recover the whole of the toxin
originally employed.
Therefore, as was shown by me so long ago as 1894, if the mixture of
toxin + antitoxin produces a chemical combination between the two
substances, this combination is unstable, and can be effectively broken
up into these two constituent elements by various influences.
CHAPTER XV.
_TREATMENT OF POISONOUS SNAKE-BITES IN MAN AND ANIMALS._
_OBJECTS OF THE TREATMENT: TECHNIQUE OF ANTIVENOMOUS SERUM-THERAPY._
In all countries the remedies recommended for the bites of poisonous
snakes are innumerable, and native pharmacopœias abound in so-called
infallible recipes.
Pliny himself wrote on this subject as follows:--
“For poisonous bites, it is customary to employ a liniment made of
fresh sheep-droppings, cooked in wine. Rats cut in two are also
applied; these animals possess important properties, especially at the
epoch of the ascension of the stars, seeing that the number of a rat’s
fibres wax and wane with the moon.
“Of all birds, those that afford most assistance against snakes are
vultures. The black ones are the weaker. The odour of their feathers
when burnt puts snakes to flight. Provided with a vulture’s heart one
need not fear encounters with snakes, and can also defy the wrath of
wild beasts, robbers, and princes.
“Cock’s flesh, applied while still warm, neutralises the venom of
snakes. The brains of the bird, swallowed in wine, produce the same
effect. The Parthians, for this purpose, make use of chicken’s brains.
The fresh flesh of the pigeon and the swallow, and owls’ feet burned,
are good against snake-bites.
“If one has been bitten by a snake or by any venomous animal, another
method of cure is to take salt fish and wine from time to time, so as
to vomit in the evening. This remedy is chiefly efficacious against
the bite of the _Chalcis_, _Cerastes_, _Seps_, _Elaps_ and _Dipsas_.”
* * * * *
In Equatorial America, and especially in India, a multitude of plants
are credited with marvellous properties, which they possess only in
the imagination of the snake-charmers or medicine-men by whom they are
employed. None of them stand the test of experiment, any more than the
more or less compound drugs, numbers of specimens of which from all
sources have passed through my hands.
It cannot, however, be denied that certain chemical substances, of
well-defined composition, are very useful, not as physiological
antidotes to venoms, but as agents for their modification or
destruction in the poisoned wounds, when they have not yet been
absorbed. In this way _permanganate of potash_, _chromic acid_,
_chloride of gold_, and the _alkaline hypochlorites_, especially
_hypochlorite of lime_, may be extremely useful under many
circumstances.
_Permanganate of potash_ was recommended in 1881 by Professor de
Lacerda,[104] of Rio de Janeiro, as the result of experiments made by
him with venoms of Brazilian snakes. When a few cubic centimetres of
a 1 per cent. solution of permanganate of potash are quickly injected
into the actual wound caused by the bite and around the point of
inoculation, there can be no doubt that the venom not yet absorbed is
destroyed. When mixed _in vitro_ with venom, permanganate renders the
latter innocuous.
Here, however, it is a case of actual destruction by direct contact. If
we inject a lethal dose of venom into the right thigh of an animal, for
example, and several cubic centimetres of permanganate solution into
different parts of the body, or beneath the skin of the left thigh,
neither the general intoxication nor the local effects of the venom are
modified.
The same may be said with regard to _chromic acid_ (1 per cent.
solution), recommended by Kaufmann[105] for the bite of the common
viper.
No other effect is produced by a 1 per cent. solution of _chloride of
gold_, or the _alkaline hypochlorites_, which I have shown to possess
a strong oxidising action on the different venoms, even on those that
are most rapidly diffusible, such as cobra-venom (see Chapter V.). They
possess, however, owing to their slight causticity, the advantage of
not producing severe local disorders, and in this respect they are to
be preferred.
The chemical reagent most to be recommended is _hypochlorite of lime_,
in a fresh solution of 2 grammes per cent., and containing about 90
c.c. of chlorine per 100 grammes. It immediately and surely destroys
the venom by simple contact, and the chlorine gas that it gives off,
owing to its great diffusibility, acts at a fairly long distance from
the point of inoculation on the venom which is already beginning to be
absorbed.
Professor Halford, of Melbourne, advises the direct injection into the
patient’s veins of from 10 to 20 drops of ammonia, diluted with an
equal quantity of distilled water. This is a means of reviving nervous
excitability in certain subjects at the commencement of intoxication;
but torpor soon reappears, and, if the dose of venom inoculated is
sufficient to cause death, a fatal ending takes place notwithstanding.
Experimentally the effects of ammonia are _nil_.
No better results are obtained by injections of strychnine, as
recommended by Dr. Mueller, in Australia. Moreover, the statistics
published by Raston Huxtable[106] positively condemn this therapeutic
method. They show that, in 426 cases of snake-bite, out of 113 treated
by strychnine 15 proved fatal, the ratio of mortality being 13·2 per
cent., while the 313 cases not treated by strychnine only resulted in
13 deaths, or a mortality of 4·1 per cent.
In the case of animals intoxicated by venom, injections of strychnine,
morphia, nicotine, or curare in small doses always prove ineffective;
they even considerably assist the progress of the intoxication and
hasten death. The use of these drugs in the case of human beings should
therefore be absolutely forbidden.
It appears, on the other hand, that alcohol and coffee, or tea,
absorbed by ingestion, are very often beneficial. Indeed, it was
long ago observed that the swallowing of alcohol until symptoms of
drunkenness appear retards or diminishes the phenomena of torpor and
paresis that precede the ultimate phase of the intoxication. Its use
may therefore be recommended when it is impossible to have recourse
to the only treatment really specific that modern science places in
our hands--_antivenomous serum-therapy_. It is important, however, to
state that, _when serum is used, alcohol must be forbidden_. The latter
hinders the effects of the former.
In practice, the rational treatment of the bite of a venomous snake
must be directed towards:--
(1) Preventing the absorption of the venom.
(2) Neutralising, by the injection of a sufficient quantity of
antitoxic serum, the effects of the venom already absorbed.
In order to prevent the absorption of the venom introduced into the
wound, the first precaution to be taken is to compress the bitten limb
by means of a ligature of some kind, such as a handkerchief, as close
as possible to the bite, and between it and the base of the limb. The
ligature must be tightly twisted, and, by compressing the tissues
around the bite, an attempt should be made to squeeze out the venom
that may have been introduced into them. The expulsion of the poison
should be hastened, either by making an incision 2 or 3 cm. in length
and 1 cm. in depth in the direction taken by the fangs of the reptile
and also parallel to the axis of the bitten member, or by sucking the
wound hard.
The ligature on the limb should not be applied for more than half an
hour; if it were kept on longer it would interfere with the circulation
to a dangerous degree, and would certainly injure the vitality of the
tissues. The period in question also usually affords sufficient time
for taking the patient to a place where help can be obtained, and for
the preparation of everything necessary for his subsequent treatment.
The wound should then be freely washed with a fresh 2 _per cent._
solution of _hypochlorite of lime_, or with a 1 in 1,000 solution of
_chloride of gold_. In default of hypochlorite of lime or chloride of
gold, either _eau de Javel_, diluted with tepid water to a strength
of 1 in 10, or a 1 per cent. solution of permanganate of potash, may
be employed. These reagents should be made to penetrate as deeply as
possible into the tissues, and a few cubic centimetres of them should
even be injected with a Pravaz syringe into the punctures caused by the
bite and all round them.
The wound being then covered with a damp dressing by means of
compresses saturated with hypochlorite of lime, or at least with
pure alcohol, the next thing to be done is to prepare to apply the
serum-therapic treatment in order to arrest the general intoxication,
if this has already commenced to take effect, or to prevent it from
setting in.
For the employment of serum it is necessary to be in possession of a
sterilisable syringe of the capacity of 10 c.c., similar to those used
in the treatment of diphtheria.
If the life of the patient be not immediately in danger, care should
first be taken to have the syringe boiled, or at least to rinse it out
with boiling water, making sure that the piston fits tightly, and that
the syringe itself is in good working order.
Should a syringe of 10 c.c. not be available, any kind of Pravaz
syringe, previously washed out with boiling water, may be employed, but
in this case the use of so small an instrument renders it necessary to
give several painful injections.
The entire contents of a bottle of serum (10 c.c. of liquid serum, or
1 gramme of dry serum dissolved in 10 c.c. of boiled water) should be
injected into the subcutaneous areolar tissue of the abdomen, on the
right or left side. There is no advantage in making the injection at
the actual spot bitten; the serum is best and most rapidly absorbed
when injected into the loose tissues of the abdominal wall (fig. 95).
[Illustration: FIG. 95.--TECHNIQUE OF THE INJECTION OF ANTIVENOMOUS
SERUM BENEATH THE SKIN OF THE ABDOMEN.]
If it has been impossible to apply the treatment until several hours
after the bite, and if the latter has been inflicted by a poisonous
snake of large size or belonging to a very dangerous species, such as
the Cobra or Indian Krait, it is preferable to inject into the patient
three whole doses of serum at once.
In cases in which the phenomena of serious intoxication have already
appeared, and when asphyxia threatens, one must not hesitate to inject
10 or even 20 c.c. of serum directly _into a vein_. For such an
injection it is most convenient to choose a superficial vein at the
elbow or wrist, or on the back of the hand.
The introduction of serum into the veins is never dangerous if good
care be taken not to allow either bubbles of air or particles of
precipitated albumin to enter.
It is not advisable to repeat the injections beneath the skin or into
the veins unless the general symptoms appear to become more acute.
In most cases the local pain, excitement, and attacks of cramp and
nausea disappear within a few minutes after the first injection.
Improvement progresses very rapidly, and by the following day the
patient has recovered.
The administration of ammonia, alcohol, morphia, or ether by the mouth
is entirely superfluous. These drugs, as I have already stated, may
even be harmful to the patient and hinder the effects of the serum. All
that should be done is to give copious hot drinks, tea or coffee, and
to cover up the patient warmly in order to induce abundant perspiration.
The bitten member should not be cauterised with red hot iron or with
chemical agents of any kind, since such cauterisations only lead to
injuries which are too often prejudicial to the normal action of the
affected organs.
_Treatment of Poisonous Bites in the Case of Domestic Animals._--It
often happens that dogs, horses, or cattle are bitten and succumb to
the poisoning in a few hours or in two or three days. Such accidents
are especially frequent among sporting dogs, even in Europe, in regions
in which _vipers_ are found.
In most cases, dogs, horses, and cattle are bitten on the nose, and
such bites are immediately followed by a very painful swelling,
which arouses the suspicion of the owners of the animals. It is then
necessary, as soon as possible, to inject subcutaneously in the
right or left flank, or at the base of the neck, one or two doses of
antivenomous serum, according to the gravity of the effects observed.
The injection of the serum and the dressing of the wound should be
performed as in the case of poisonous bites in human beings.
_Influence of the Doses of Antivenomous Serum injected, and of the Time
that has elapsed since the Venomous Bite._--I have stated above that
antivenomous serum possesses a preventive and curative power of such
intensity, that it is capable in a few minutes of rendering animals
into which it has been injected absolutely insensible to the most
strongly neurotoxic venoms, such as those of _Naja_ or _Bungarus_. On
the other hand, I have established the fact that, the more sensitive
are the animals to intoxication by venom, the greater is the quantity
of antivenomous serum necessary to immunise them passively or to cure
them.
In experimenting upon mice, guinea-pigs, and rabbits, it is found
that in order to preserve, let us say, a mouse of 25 grammes
against inoculation with half a milligramme of venom, which is ten
times the lethal dose for this little animal, it is necessary to
give a preventive injection of 1 c.c. of serum; while half a cubic
centimetre of the same serum is sufficient to render the dose of half
a milligramme of venom innocuous, when venom and serum are mixed _in
vitro_ before being injected.
In the case of the guinea-pig, it is likewise found that the dose of
serum to be injected preventively, in order to protect the animal from
intoxication by ten times the lethal dose of venom, is about _twice as
much_ as the quantity of the same serum that it is sufficient to mix
_in vitro_ with venom, in order to render ten times the lethal dose of
venom innocuous.
If we inject into animals first venom, in doses calculated to kill
the controls of the same weight in from two to three hours, and the
serum _fifteen minutes afterwards_, it is found that the quantity of
serum that must be injected in order to prevent death is about _thrice
as great_, as that which neutralises _in vitro_ the dose of venom
inoculated.
It is also found that _the amount of curative serum that an animal
intoxicated by venom must receive is inversely proportional to its
weight_.
The experiments upon dogs, performed at the Pasteur Institute at
Lille by my collaborator C. Guérin, are highly demonstrative in this
respect.[107]
A dog of 12 kilogrammes, inoculated with 9 milligrammes of venom (a
dose lethal to controls of the same weight in from five to seven
hours), is completely cured on receiving, _two hours after inoculation
with the poison_, 10 c.c. of serum.
When the treatment does not take place until _three hours after the
injection of the venom_, it is necessary to inject 20 cc. of serum in
order to prevent the animal from dying. With a longer delay than this,
death is inevitable, since the bulbar centres are already affected, and
paralysis of the respiratory muscles commences to appear.
These facts show that:--
(1) _The more sensitive animals are to venom, the greater is the
quantity of serum necessary in order to prevent their intoxication by a
given dose of venom._
(2) _For a given species of animal and a given dose of venom, the
longer the delay in applying the remedy, the greater is the quantity of
serum that must be injected in order to arrest the poisoning._
It will be understood from what has been already stated, that a man
weighing 60 kilogrammes, if bitten by a snake which injects, let us
say, what would amount to 20 milligrammes of venom if collected in the
dry state (the mean quantity that a _Naja_ is able to inoculate in a
single bite), would only require, in order to escape death, to receive
the quantity of antivenomous serum sufficient to neutralise the portion
of venom in excess of the amount that he could tolerate without dying.
Let us suppose, for the sake of example, that the man of 60 kilogrammes
can withstand intoxication by 14 milligrammes of _Naja_-venom. It
follows that, in the case with which we are dealing, we must inject
sufficient serum to neutralise 20-14 (=6) milligrammes of venom;
that is to say, the injection of serum being made immediately after
the bite, 6 _c.c._, if the serum employed neutralises _in vitro_ 1
milligramme of venom per cubic centimetre.
Of course, if the serum is more powerful, less of it will be necessary,
while more will be required if the remedy is applied later, or if the
quantity of venom inoculated by the snake is supposed to have been
greater.
For this reason, in practice, but very little serum is usually
necessary in order to augment the natural resistance of a man of
average weight or of a large animal; it is sufficient in most cases
to give an injection of 10 or 20 c.c. in order to cure human beings
who have been bitten. The clinical proof of this is, moreover, to be
found in the cases, already very numerous, that have been published
in the course of the last few years in the scientific journals of all
countries. I have gathered together a few of these in the concluding
pages of this book, and I would beg the reader to be good enough to
refer to them.
PART IV.
VENOMS IN THE ANIMAL SERIES.
CHAPTER XVI.
1.--_INVERTEBRATES._
Besides reptiles, many other animals possess poison-glands and
inoculatory organs which they employ, either to defend themselves
against their natural enemies, or to capture the living prey upon which
they feed.
The venoms that they produce are still, for the most part, but little
understood. A few of them, however, have excited the curiosity of
physiologists, especially those secreted by certain batrachians, such
as the _Toad_, and certain fishes, such as the _Weever_. Some of them
exhibit close affinity to snake-venom, and are composed, like the
latter, of proteic substances modifiable by heat and precipitable by
alcohol; others possess altogether special characters, and resemble
alkaloids.
The lowest animal group in which these secretions begin to be clearly
differentiated is that of the _Coelenterates_.
A.--COELENTERATES.
It has been shown by Charles Richet[108] that the tentacles of
sea-anemones (_Anemone scultata_) contain a toxic substance which has
the carious property of causing intense itching, pruritus, and even
urticaria. This poison is perfectly soluble in alcohol, and can be
prepared in the following manner:--
The tentacles are cut off close to the body of the animal, and immersed
for a few days in an equal weight of alcohol at 95° C. The red liquid
that results is decanted, and then filtered. The insoluble material is
compressed, and yields large quantities of fluid, which is filtered and
mixed with the previous liquid.
The whole is then evaporated _in vacuo_ until there remains a thick
oily liquid, which forms a red deposit. Filtration through paper
is again employed, in order to separate this colouring matter, and
to the filtered liquid is added an equal amount of alcohol at 95°
C. By this means there is precipitated a blackish, gummy matter,
insoluble in alcohol. The remaining liquid is decanted and once more
evaporated until it is reduced to a smaller volume than before. It
is again treated with twice its volume of absolute alcohol, when
it precipitates, in addition to salts and gummy matter, a white
flocculent substance, which is crude _thalassin_. This can be purified
by redissolving it in alcohol at a temperature of 98° C. On cooling
it separates from the fluid in the form of crystals, which are placed
on a filter and can then be redissolved in a small quantity of water.
Absolute alcohol, added to this solution, precipitates the _thalassin_
in the shape of very pure crystals, which contain 10 per cent. of
azote, and melt at 200° C.
This substance, in aqueous solutions, rapidly deteriorates owing to
ammoniacal fermentation. When injected intravenously into dogs it
produces pruritus, sneezing, and erythema, with intense congestion of
the mucous membranes; 1 decigramme per kilogramme is a dose sufficient
to produce these symptoms. It is not very toxic, since 1 centigramme is
not lethal.
One kilogramme of anemones is capable of furnishing about 3 grammes of
pure crystallised poison.
In addition to _thalassin_, Richet succeeded in isolating from the
tentacles of the same sea-anemones another poison insoluble in alcohol
at 50° C., and richer in azote (14 per cent.), to which he has given
the name _congestin_. This is not destroyed by heating to 107° C. It
is prepared by precipitating, by four times its volume of alcohol, a
solution of anemone-tentacles in 5 per cent. fluoride of sodium. The
solid matter, after being precipitated and dried, is redissolved in
six times its volume of water, and then filtered. On adding to the
filtered and fluorescent liquid its volume of alcohol at 90° C., the
_congestin_ is precipitated. It is purified by redissolving it in
water, and freeing it by dialysis from the fluoride of sodium that
it has retained. In this way there is obtained, after evaporation, a
product sufficiently toxic to kill dogs in twenty-four hours in a dose
of 2 milligrammes per kilogramme.
_Congestin_ exerts a sensitising or anaphylactic effect upon
animals as regards _thalassin_, and is lethal in a dose of about 5
milligrammes per kilogramme of animal, and sometimes even in a dose of
7 decimilligrammes. It is therefore a very active poison.
Dogs, on the other hand, into which is injected first _thalassin_,
and then, some time afterwards, _congestin_, are perfectly resistant
to inoculation by the latter. _Thalassin_ is therefore _antitoxic_ or
antagonistic to _congestin_.
The latter, on the contrary, if injected first of all in non-lethal
doses, renders animals so sensitive to inoculation with _thalassin_,
that from 4 to 5 milligrammes are sufficient to cause death.
The tentacles of these anemones therefore contain two toxic substances
antagonistic to each other, which can easily be separated, since one
(_thalassin_) is soluble in concentrated alcohol, while the other is
completely insoluble in this reagent.
These poisons are not only extremely interesting from a physiological
point of view, but also possess a practical interest, since it is
at the present time almost a matter of certainty that they are the
cause of a malady which specially affects _sponge-divers_ in the
Mediterranean.
A good description of the disease has been given by Dr. Skévos Zervos,
of Athens.[109] It is observed exclusively in men who dive quite naked,
without a diving-dress. Now, beside the bases of the sponges and
sometimes on their surface there live numbers of anemones which secrete
a viscid substance, which is extremely virulent, especially in the
month of August.
The first symptoms that supervene after contact with these Cœlenterates
are an intense itching and burning sensation; a papule of a horny
consistency appears at the outset at the spot at which contact took
place; this is soon surrounded by a red zone, which becomes bluish and
then black, and spreads to a greater or lesser extent, according to
the region attacked and the virulence of the venom. After a few days
the skin sloughs and leaves a deep ulcer, which suppurates in spite of
antiseptic treatment. The onset of the disease is marked by a febrile
attack with shivering, which is soon accompanied by cephalalgia,
thirst, and pains in the back and limbs.
Zervos reproduced these disorders experimentally by rubbing an anemone,
held with forceps, on the shaven abdomen of a dog. In a few minutes the
region affected became quite red and pruriginous; twenty-five minutes
later phlyctenæ full of serum appeared; three days afterwards five
abscesses of different sizes developed, while at the place where it had
been touched by the venom the skin assumed a deep blue colour; on the
fifth day an area 2 cm. in diameter was completely gangrenous.
When ingested, anemones possess toxic properties which are well known
to the sponge-fishers, for they frequently make use of them for the
purpose of poisoning domestic animals. With this object they cut them
up into small fragments, and mix them with bread or meat, which is
given to the animals to eat; the latter die in convulsions in a few
minutes.
In order to preserve the divers from the harmful effects produced
by contact with the anemones, they should be advised to cover their
bodies with a layer of grease, a simple artifice which constitutes an
efficient protection.
B.--ECHINODERMS.
The _Echinoidea_ (Sea-urchins) are provided with soft prehensile
organs, the _pedicellariæ_, of which four kinds are distinguished:
gemmiform, tridactyle, trifoliate, and ophiocephalous.
These pedicellariæ contain a special venom, which causes the paralysis
and death of animals into which it is injected. Uexkull, who was the
first to mention it, considered that the gemmiform pedicellariæ alone
are toxic.
From this point of view various species of sea-urchins,
_Strongylocentrotus lividus_, _Arbacia æquituberculata_, _Sphærechinus
granularis_ and _Spatangus purpureus_, have recently been studied by V.
Henri and Mdlle. Kayalof.[110]
The pedicellariæ were removed and pounded up in sea-water, and the
pulp was injected into crabs, holothurians, star-fish, cuttle-fish,
frogs, lizards, and rabbits; in the case of cuttle-fish and rabbits the
injection was made intravenously; in that of the other animals into the
body-cavity.
For crabs the lethal dose was from 20 to 30 gemmiform pedicellariæ of
_Strongylocentrotus lividus_.
The holothurians, star-fish, and frogs proved immune.
In the case of rabbits weighing 1½ kilogrammes, 40 pedicellariæ of
_Sphærechinus granularis_, pounded up in 1 c.c. of water, produce death
by asphyxia and general paralysis in from two to three minutes. The
heart continues to beat after respiration has ceased.
For lizards and fishes the toxic dose is the same as for the crab. The
cuttle-fish is paralysed and killed in two hours by 50 pedicellariæ.
This venom resists ebullition for fifteen minutes.
V. Henri and Mdlle. Kayalof made experiments in immunisation. Rabbits
that receive every third day increasing doses of gemmiform pedicellariæ
of _Sphærechinus granularis_ tolerate well, after four injections, the
toxin of 40 pedicellariæ, a lethal dose. The serum of these rabbits is
not protective for either rabbit, crab, or fishes.
Frog serum (1 c.c.) injected into the body cavity of a crab, protects
this animal against the pulp of pedicellariæ injected immediately
afterwards.
The pedicellariæ easily become detached from sea-urchins. They remain
fixed to objects which come into contact with them, and the urchin
abandons them like poisoned arrows.
On touching a point on the surface of the body of an urchin, the spines
are seen to incline towards the spot touched, and the pedicellariæ
stretch themselves out and lean with their valves open towards the
seat of the stimulus. In _Sphærechinus granularis_ the heads of the
gemmiform pedicellariæ are covered with sticky mucus forming a tiny
drop, visible under the lens. A specimen of this species possesses more
than 450 pedicellariæ.
C.--ARTHROPODS.
(a) =Araneida= (=Spiders=).
Almost all Arachnids possess poison-glands, which are connected,
in some cases with the buccal apparatus, in others with a special
inoculatory organ situated at the posterior extremity of the body. The
_spiders_ and _scorpions_ belong to this group, and their venom is
particularly active.
On each side of the mouth of spiders is found an appendage ending in a
fang (_chelicera_), at the extremity of which opens the excretory duct
of a more or less developed poison-gland. The venom produced by these
glands is instantly fatal to all small animals upon which spiders
feed. In man and large mammals their bite produces sensations of pain
accompanied by swelling and muscular contractions as though caused by
localised tetanus.
The venom of certain species of spiders sometimes causes very serious
and even fatal results. _Latrodectus malmignattus_ (the _malmignatte_
of the South of France and Italy), and especially _Latrodectus
mactans_, of Chile (fig. 96), are greatly dreaded.[111] The area
of distribution of the latter includes the whole of Tropical and
Sub-tropical America. It is said that it frequently causes the death of
milch cows, and that in man its bite produces tetanic effects, which
last for several days, but are in most cases amenable to treatment.
[Illustration: FIG. 96.--_Lactrodectus mactans_ (_formidabilis
olim_).
1, Female, twice natural size; 1_a_, its eyes, greatly enlarged.]
Another dangerous spider is the _Katipo_ (_Latrodectus scelio_), of New
Zealand. This creature is confined to the sea-shore, and the natives
are often bitten when collecting shell-fish or sea-weed. The Maoris
are so much afraid of the bite of the _Katipo_ that, when one of them
has been bitten in his hut, and the animal cannot be found, they do
not hesitate to burn the dwelling to the ground. Moreover, they are
convinced that the death of the spider is absolutely necessary for the
recovery of the patient.[112]
Kobert[113] has made an experimental study of the venom of species
of _Latrodectus_ and _Epeira_. That of _Latrodectus erebus_ (the
_Karakurte_ of South Russia) is particularly toxic.
If a dry extract of these spiders be prepared and injected into
the veins of dogs or cats, it is found that a few milligrammes per
kilogramme are sufficient to cause death, with phenomena of dyspnœa,
convulsions, and progressive paralysis of respiration and the heart.
Rabbits, rats, birds, frogs, and leeches are also sensitive to this
poison, though the hedgehog is almost refractory. The young spiders,
and even the eggs, are more toxic than the adults.
Spider-venom is destroyed by heating for forty minutes at + 70° C.,
and is precipitated by alcohol. When absorbed by ingestion it has no
effect: it is hæmolytic and coagulates blood.
The study of _arachnolysin_ by Ehrlich’s methods has been undertaken
afresh by Hans Sachs,[114] who has shown that rat’s and rabbit’s blood
are most rapidly dissolved. Twenty-eight milligrammes of extract of
_Epeira_ are capable of completely dissolving 0·05 c.c. of blood.
By immunising guinea-pigs and rabbits, Sachs succeeded in obtaining a
strongly antitoxic serum, which entirely prevents the hæmolysis of the
sensitive red corpuscles.
(b) =Scorpionidea= (=Scorpions=).
The poison-apparatus of the scorpion is constituted by the last
abdominal segment (_telson_), which is swollen and globular, and
terminated by a hard, curved spine, with a very sharp point, near which
can be distinguished, under the lens, two small oval orifices by which
the poison is enabled to escape (fig. 97).
The poison-glands are two in number, symmetrically placed in cavities,
each of which is completely filled by the gland. They are separated
from each other by a muscular septum formed of striated fibres inserted
in the chitinous skeleton; by the contraction of this septum the animal
is enabled to eject its venom.
[Illustration: FIG. 97.--_Scorpio occitanus._ (After
Joyeux-Laffuie.)
1, Scorpion seizing a spider, and piercing it with its sting (natural
size); 2, extremity of the abdomen (telson) enlarged, showing the
poison-apparatus; 3, poison-apparatus detached from the abdomen,
showing an isolated poison-gland.]
The scorpion never stings _backwards_, but always _in front_ of itself.
It delivers stabs with its sting in two distinct ways. For the purpose
of defending itself from attack it elevates its abdomen into a bow, and
then regains its former position by suddenly unbending it. To strike
an animal, such as a spider, which serves it for food, the scorpion
seizes it with its pincers and holds it as in a vice. Then it raises
its abdomen, brings the end of it close to its captive, and, with
a lever-like movement, drives the sting into its body. The victim
immediately becomes paralysed and motionless.[115]
The poison-glands of a _Scorpio occitanus_ from the South of France
contain about 1 to 10 centigrammes of a toxic liquid, capable of
furnishing 10 to 15 per cent. of dry extract. This liquid is decidedly
acid; it reddens litmus paper and is miscible with water.
Its physiological effects are especially intense in the case of the
arthropods upon which the scorpion habitually feeds, and in that of
vertebrates in general. Batrachians, fishes, birds, and mammals are
extremely susceptible to this poison. Half a milligramme of dry extract
injected subcutaneously is sufficient to kill a guinea-pig, and 1
milligramme is lethal to the rabbit.
In poisoned animals there is first observed a period of violent
excitement, accompanied by very acute pains; these are followed by
muscular contractions, and finally by paralysis of the respiratory
muscles, as in the case of intoxication by cobra-venom.
The effects of scorpion-poison, which clearly indicate the presence of
a _neurotoxin_, have been very well described by Valentin,[116] Paul
Bert[117] and Joyeux-Laffuie. Kyes[118] has prepared a _lecithide_ from
scorpion-venom, which hæmolyses red corpuscles as do the lecithides
of cobra-venom, and I myself[119] have established the fact that
the antivenomous serum of a horse vaccinated against cobra-venom
effectively protects mice and guinea-pigs against intoxication by the
venom of _Scorpio occitanus_; this has been verified by Metchnikoff.
There is, therefore, a close affinity between this venom and that of
COLUBRINE snakes.
On the other hand, it has been shown by the investigations of C.
Nicolle and G. Catouillard that the same antivenomous serum has
no effect upon the much weaker venom of the scorpion of Tunis
(_Heterometrus maurus_), which, in the case of man and mammals in
general, scarcely does more than produce a transient œdema at the point
of inoculation.
The venom of _Heterometrus maurus_ is, however, toxic enough to the
sparrow. When one of these little birds is inoculated in the pectoral
muscles with the contents of the poison-glands of a single scorpion
belonging to this species, the following symptoms are observed:
Immediate rigidity, doubtless connected with the pain, then, after
a few seconds, depression and relaxation of the muscles. The bird
remains upright, but its body sinks down more and more until it comes
into contact with the ground; if on a perch, it soon becomes unsteady
and drops off. There is dyspnœa, which any effort increases, and
death supervenes suddenly; all at once the sparrow falls on its side,
stiffens, sometimes has a few convulsions, and then finally becomes
still. The time occupied by these phenomena is always short, although
it varies from two minutes to half an hour.
Scorpion-venom is a strong irritant to the mucous membranes. When
dropped into the eye of a rabbit it produces acute ophthalmia.
It has often been asserted that scorpions kill themselves with their
own venom if enclosed in a circle of fire. This is an absolute myth,
for it is easy to prove by experiment, as was done by Bourne at
Madras,[120] that these animals cannot be intoxicated by their own
poisonous secretion, nor by that of other individuals of the same
species. Moreover, it has been established by Metchnikoff,[121] in very
definite fashion, that the blood of the scorpion is antitoxic. If 0·1
c.c. of this blood be added to a dose of venom lethal to mice in half
an hour, a mouse injected with this mixture resists indefinitely. This
antitoxic power is exhibited both by _Scorpio afer_ and the Algerian
_Androctonus_.
(c) =Myriopods.=
It has been shown by Phisalix and Bertrand that certain species of
Myriopods, including those of the genus _Julus_ (Order _Chilognatha_,
_e.g._, _Julus terrestris_), secrete throughout the entire extent of
their body a volatile venom, which these authors compared to _quinone_.
The species of the genus _Scolopendra_ (Order _Chilopoda_; _Scolopendra
cingulata_, found in the South of France, Spain and Italy; _S.
gigantea_ and other forms, common in Africa, India, Indo-China and
Equatorial America), have the second pair of post maxillary appendages
transformed into formidable poison-claws, with which they can inflict
bites which are very painful to human beings.
[Illustration: FIG. 98.--_Scolopendra morsitans_ (S. Europe).
(After Claus.)]
The tropical species may attain a length of 10 or even 15 cm. Their
bodies are composed of 21 segments, each provided with a pair of
jointed legs. They live in shady places, such as woods, hidden under
stones, dead leaves, or the bark of old trees. They feed upon small
insects, spiders, and larvæ, which they kill with their venom. The
latter is secreted by a racemose gland situated at the base of the
poison-claws; it escapes by a duct which opens at the apex.
This venom, the physiological study of which was commenced by Dubosq,
is an acid, opalescent liquid, hardly miscible with water.
More complete experiments on this subject have been made by A.
Briot,[122] who prepared a solution by sectioning the labium and
poison-claws, and crushing the whole in physiological salt solution.
When injected intravenously into rabbits, it produces immediate
paralysis, with coagulation of the blood; subcutaneously it leads to
the formation of enormous abscesses, with necrosis of the tissues.
Small animals, such as spiders, species of _Scutigera_, beetles, &c.,
are very sensitive to it.
The bite of _Scolopendridæ_ is very painful to human beings. In the
Tropics such bites often cause somewhat serious results: insomnia,
accelerated and intermittent pulse, and local œdema, which usually
disappears after twenty-four hours. Well-authenticated fatal accidents
have never been recorded (Bachelier,[123] Saulie[124]).
(d) =Insects.=
A very large number of insects produce acrid or irritant secretions,
which serve them as a means of defence, but cannot be considered as
true venoms; the species of _Meloë_ (oil-beetles) and _Cantharis_
(blister-beetles), are the most remarkable in this respect.
The Order _Hymenoptera_ is the only one that includes a multitude of
species really provided with poison-glands and an inoculatory apparatus.
[Illustration: FIG. 99.--POISON-APPARATUS OF THE BEE.
_gl.ac_, Acid gland and its two branches; _V_, poison-sac; _gl.al_,
alkaline gland; _gor_, gorget.
(After Carlet: figure borrowed from Hommel.)]
The poison-organs, which have been well studied, especially by
Leuckart,[125] Leydig,[126] Carlet,[127] and more especially by L.
Bordas,[128] Janet,[129] and Seurat,[130] always include two and
sometimes three kinds of glands: the _acid gland_, the _alkaline gland_
or gland of Dufour, and the _accessory poison-gland_ (fig. 99).
The acid gland comprises a glandular portion (which sometimes takes the
shape of a long flexuous tube, always bifid at its extremity, sometimes
that of two tubes, simple or ramified, or again is composed of a bundle
of cylindrical, simple or multifid canals), a poison-sac or reservoir,
ovoid or spherical in shape, and an excretory duct, which is usually
short.
The alkaline gland, or gland of Dufour, exists in all Hymenoptera, and
presents the appearance of an irregular tube, with a striated surface
and a spherical or conical upper extremity. Its excretory duct opens,
beside that of the acid gland, at the enlarged base of the gorget of
the sting (fig. 100).
[Illustration: FIG. 100.--INTERIOR OF THE GORGET OF THE
BEE, SEEN FROM ITS POSTERIOR ASPECT.
_cv_, Poison chamber; _gor_, gorget; _st_, stylet; _ca_, piston.
Between the two stylets is seen the cleft _fa_, by which the air is
able to enter into the air-chamber _cai_.
(After Carlet: figure borrowed from Hommel.)]
The accessory poison-gland, which is lanceolate or ovoid in shape,
consists of a small, granular mass, the extremely narrow excretory duct
of which opens at almost the same point as that of the alkaline gland.
It does not exist in all Hymenoptera.
The stings of hive bees (_Apis mellifica_), wasps (_Vespa vulgaris_),
violet carpenter bees (_Xylocopa violacea_), and humble bees (_Bombus
lapidarius_) cause considerable discomfort. The venom of the carpenter
bee, which is of some strength, has been studied by P. Bert, and I have
myself made experiments with that of the hive bee (_A. mellifica_).
The venom extracted from a couple of bees, by crushing the posterior
extremity of the body in 1 c.c. of water, is sufficient to kill a mouse
or a sparrow.
Death supervenes in a few minutes, from respiratory asphyxia, as in the
case of intoxication by the venom of Colubrine snakes (_Cobra_). In the
blood-vessels and in the heart the blood is black and remains fluid. It
therefore appears that this venom contains a very active _neurotoxin_.
The phenomena of intoxication caused by the venom of these insects are,
as a rule, slight, being limited to an acute pain, accompanied by a
zone of œdema and burning itching. Sometimes however, when the stings
are in the eyelids, lips, or tongue, they produce alarming and even
fatal results, as shown by the following incident:--
On September 26, 1890, a young girl of Ville-d’Avray was eating grapes
in the woods of Fausse-Repose, when she inadvertently swallowed a
wasp. The unfortunate girl was stung in the back of the throat, and
the wound became so rapidly inflamed that, in spite of the attentions
of a doctor, she died in an hour from suffocation, in the arms of her
friends.
Phisalix[131] has studied the physiological action of bee-venom on
sparrows inoculated either by the sting of the insect, or with an
aqueous solution obtained by crushing the glands. In both cases a local
effect, paralysis of the part inoculated, is first produced; this is
followed by convulsions, which may last for several hours; the final
stage is marked by coma and respiratory trouble, which ends in death.
After being heated for fifteen minutes at 100° C. the venom has no
further local action; the general phenomena are merely diminished.
If heated at 100° C. for thirty minutes, the venom ceases to cause
convulsions, but remains stupefactive. Exposure for fifteen minutes to
a temperature of 150° C. renders it completely inert.
This venom therefore comprises: (1) A phlogogenic substance, destroyed
by ebullition, contained in the acid gland of the bee; (2) a poison
causing convulsions, which does not resist a temperature of 100° C.,
if prolonged, and is probably produced by the alkaline gland; (3) a
stupefactive poison, which is secreted by the acid gland, and is not
entirely destroyed until a temperature of 150° C. is reached.
The poison-glands can easily be extracted by gently pulling at the
stings of bees anæsthetised by chloroform.
The eggs of bees, like those of the toad and the viper, contain
the specific venom. The amount, however, is small, since in order
to produce lethal results in the sparrow it was found necessary to
inoculate an emulsion obtained by crushing 926 eggs.
Phisalix[132] makes the approximate calculation that, in the egg the
weight of the toxic substances amounts to the one hundred and fiftieth
part of the whole. Their effects are similar to those produced by the
venom itself, but the convulsions are not so severe. The predominant
poison in the egg appears to be that causing paralysis.
I have easily succeeded in vaccinating mice against doses of bee-venom
certainly lethal, by repeatedly inoculating them with very small doses.
Moreover, we find the same thing in the case of human beings, for we
know that those who are in the habit of handling hives become quite
accustomed to bee-stings, and finally feel not the slightest effect
from them.
It has been shown by J. Morgenroth and U. Carpi,[133] in a paper
recently published, that the venom of bees, like that of the scorpion,
possesses the property of hæmolysing the red corpuscles of several
species of animals (the rabbit, guinea-pig, and goat), and that it is
capable of combining with the lecithin to form a _lecithide_ analogous
to _cobra-lecithide_, the curious properties of which we have studied
in detail.
This lecithide of bee-venom is from 200 to 500 times more hæmolysing
than the venom itself, and resists ebullition like that of the cobra.
In order to isolate it Morgenroth and Carpi employed the method
recommended by P. Kyes: 1½ c.c. of a solution of pure venom is mixed
with 1½ c.c. of a 5 per cent. solution of lecithin in methylic alcohol.
After being kept for twenty-four hours at 37° C., 22 c.c. of absolute
alcohol are added; the liquid is decanted, and the clear filtrate is
mixed with 150 c.c. of ether. There is slowly formed a somewhat copious
flocculent deposit, which is collected on a filter, washed several
times with ether, and finally dried. The lecithide that remains on the
filter dissolves completely in physiological salt solution.
It must be remarked that bee-venom, without the addition of lecithin,
gives a scanty precipitate with ether. This precipitate, dissolved
in physiological salt solution, possesses no hæmolysing power.
The lecithide, on the contrary, dissolves red corpuscles almost
instantaneously.
Normal horse-serum considerably inhibits hæmolysis by bee-venom +
lecithin. This protective action of normal serums has already been
observed by Langer; it is perhaps attributable to the cholesterin that
they contain.
Among other Hymenoptera capable of inflicting very severe stings may be
mentioned the species of _Polistes_ and certain Pompilids, especially a
species of _Pompilus_ found in Natal, the painful stings of which have
sometimes been experienced and described by travellers (P. Fabre, of
Commentry).[134]
In the family _Crabronidæ_ the females are provided with a sting and
venom, which usually has little effect upon man, but is toxic to other
insects. Thus, _Cerceris bupresticida_ is remarkable for the stupefying
effect of its venom upon the _Buprestidæ_ destined for the food of its
larvæ. It stings the beetles between the first and second segments of
the thorax, with the result that the victim is paralysed, though in
other respects its bodily functions appear to continue; in fact, its
intestine is seen to empty itself at long intervals. These effects are
attributed by Mons. J. H. Fabre, of Avignon, to the direct action of
the venom upon the ganglia of the thoracic nervous system.
Instances of Hymenoptera belonging to the tribe _Entomophaga_ actually
depositing their eggs beneath the skin of man are mentioned by Raphaël
Blanchard.[135]
According to P. Fabre, the best treatment for wasp- or bee-stings
would appear to consist in the application of strong saline solution,
or a liniment of ammonia and olive oil. For my own part, I have tried
_hypochlorite of lime_, in a 1 in 60 solution, or _eau de Javel_
diluted to 1 per cent., and have always obtained such excellent results
from these remedies that I do not hesitate to advise their use.
D.--MOLLUSCS.
Certain Gastropodous Molluscs, chiefly _Murex brandaris_ and _M.
trunculus_, possess purple glands from which it is possible to extract
a very active venom (Raphaël Dubois)[136] by crushing them up with
sand and alcohol. The alcoholic liquid, filtered and evaporated in a
water-bath, yields a brown oily fluid. The subcutaneous injection of
a few drops of this into a frog is sufficient to produce very decided
toxic effects. Sluggishness and slowness of movement are seen to
supervene fairly quickly; reflex actions are still exhibited, but the
animal is no longer able to jump.
If the dose be not too strong, this condition of paresis lasts for
several hours, and then disappears. In most cases, however, the
paresis is succeeded by complete paralysis, and the animal appears
as though suffering from curare. Yet the fact is that the venom is
neither curare-like nor cardiac; the heart, muscles, motor endplates,
and motor and sensory nerves are spared; the nervous centres alone
are attacked, especially the encephalon. The animal dies without
convulsions.
Sea and fresh-water fishes (golden carp) are very sensitive to this
venom; warm-blooded animals are refractory. It is therefore probable
that, in the species of _Murex_, the purple gland is a poison-gland
serving for defence, or for the capture of the prey upon which these
molluscs feed.
Among the Cephalopods, the Octopods (_Octopus vulgaris_, common
octopus, _Eledone moschata_, musky octopus, of the Mediterranean)
possess two pairs of salivary glands, a small anterior pair, and a
posterior pair of considerable size.
The Decapods (cuttle-fishes [_Sepia_], &c.), have only posterior
salivary glands, of smaller dimensions in proportion to the size of the
body.
On being crushed and macerated in water, the anterior glands yield a
limpid and slightly acid juice; the posterior glands produce a viscid,
ropy fluid, filterable with difficulty and neutral. The latter has an
immediate paralysing effect upon Crustacea. It contains a substance
of a diastasic nature, precipitable by alcohol, and destructible by
heating for an hour at 58° C.
Owing to the poisonous properties of this juice, Octopods succeed
in overpowering large prey, such as lobsters and crabs. Once they
are seized by the tentacles of the octopus, or cuttle-fish, a bite
inoculates these animals with venom that immediately destroys their
power of movement, and the Cephalopod is able to continue its meal in
perfect security, without having to fear the pincers of its prey.
An experimental study of this venom has been made by A. Briot,[137] who
found that crabs are very sensitive to it, while rats, frogs, rabbits,
and fish do not appear to experience any inconvenience.
CHAPTER XVII.
_VENOMS IN THE ANIMAL SERIES_ (_continued_).
2.--_VENOMOUS FISHES._
The means of defence in fishes are extremely varied. Some species
(torpedoes or electric rays, electric eels) destroy their enemies by
electric discharges; others are provided with true poison-glands and
inoculatory organs, usually represented by opercular spines or by
the fin-rays. The species of the genus _Muræna_, however, possess a
poison-apparatus connected with the buccal teeth, as in the case of
snakes.
It has been clearly established by Bottard[138] that at least three
very distinct types of venomous fishes exist, according as the
venom-apparatus is:--
(1) Entirely closed (_Synanceia_ type); (2) half closed
(_Thalassophryne_ type); (3) in more or less direct communication with
the exterior (_Trachinus_ and _Scorpæna_ type).
The greater part of the following statements has been borrowed from
the excellent work of the author referred to, from the writings of
A. Corre,[139] the fellowship thesis of Henry Coutière,[140] and
the magnificent atlas published at St. Petersburg in 1886 by P.
Savtschenko, of the Russian Imperial Navy.
Except in the case of the species of _Muræna_, the venom of fishes is
generally found in one or more special glands, situate at the base of
the dorsal or caudal fins, or beneath the opercular spines. When the
animal defends itself it inflicts wounds with these rays, and ejects
from its poison-glands a toxic or irritant liquid, which enters the
sores.
The flesh of these fishes is not usually poisonous, whereas a fairly
large number of other species, _which do not inflict wounds_, cause
intoxicating effects when eaten. These latter do not come within the
scope of this work; but the reader who may desire to obtain information
with regard to them will find them well described in J. Pellegrin’s
memoir,[141] in that by Dupont, and especially in the papers of A.
Corre.
_Venomous fishes_ almost all belong to sedentary species, as in the
case of the genera _Trachinus_, _Cottus_, _Scorpæna_, and _Synanceia_.
This fact suggested to Dissard and Noë[142] a very hazardous theory in
order to explain the existence of a poison-apparatus in these animals.
The venomous fishes being sedentary, say these authors, have no need of
a poison-apparatus; their prey offers itself to them without effort on
their part, and, on the other hand, they escape destruction by their
enemies. If, therefore, they possess a poison-apparatus it is because
the conditions under which they live entail the lowest value for the
co-efficient of respiration, diminish the quantity of the ambient
radiations and the oxygenation of the medium, and lead to diminished
hæmatosis. For these reasons the activity of anaerobic life becomes
greater, and the formation of venoms takes place.
This theory, derived from the conceptions of A. Gautier with regard
to the formation of toxic leucomaines, appears scarcely tenable, for
it is evident that the weever, for example, erects its first dorsal
spine as soon as it is seized, and that _Scorpæna_ and _Synanceia_
likewise protrude their venomous spines when conscious of danger. The
poison-apparatus of these fishes is therefore of an eminently defensive
character.
According to Bottard, the spawning season increases the activity of
the poison-glands and at the same time the toxicity of the secreted
product. Several species, such as those of the genus _Cottus_ and the
perch, possess no apparent secreting cells except at this period.
Certain _toxicophorous_ or poisonous fishes, such as the species of
_Tetrodon_, are particularly noxious at the time when their genital
glands are at their maximum activity.
A.--TELEOSTEI.--ACANTHOPTERYGII.
1.--=Triglidæ.=
The fishes of this family are all repulsively ugly. They have an
elongate and but slightly compressed body, covered with ctenoid scales,
and a large head in which the suborbital bones, which are broad, unite
with the præopercular so as to form an osseous plate in the malar
region. The pectoral fins are large, and provided with a few detached
rays, which perform the function of tactile organs; the ventral fins
are situate on the breast. These fishes are extremely voracious.
The most interesting type is the _Synanceia_ termed by the Creoles of
Réunion _Crapaud de mer_, and by those of Mauritius _Laffe_. In Java
it is called _Ikan-Satan_ (Devil-fish), and in Tahiti _Nohu_. It is
distributed throughout almost all the warmer regions of the Indian and
Pacific Oceans, and is found in Cochin-China and New Caledonia.
It is never taken in the open sea, but only among the fringing reefs,
where it lives constantly concealed in holes or buried in the sand. It
does not come out except to make a sudden dart at prey passing within
its reach. When irritated it does not eject venom; for the latter
to be expelled one has either to press hard upon the poison-sacs,
after pushing back with the fingers the membranes covering the dorsal
defensive armature, or the naked foot must be placed on the back of
the fish. The wound is very painful, and is accompanied by a series of
alarming symptoms, which sometimes terminate fatally: fishermen are
consequently much afraid of it.
There are a large number of species of this fish, peculiar to different
regions. _Synanceia brachio_ (fig. 101), the largest specimens of which
attain the length of 45 cm., is the most common form in the Tropical
Pacific.
[Illustration: FIG. 101.--_Synanceia brachio_, var.
_verrucosa_. (After Savtschenko.)]
The spiny rays of the dorsal fin of _Synanceia_ are sharp-pointed,
stout in the middle, and provided on each side with a small canal
hollowed out in the thickness of the spine. Towards the middle of the
latter there is attached a little double sac, or kind of closed pouch,
which, on being compressed, allows the venom to escape in a thin jet
which flows into the grooves of the spine. The expulsion of the venom
is therefore not a voluntary act on the part of the fish; in order that
it shall take place, pressure must be applied to the sacs in which it
is contained.
This venom, when extracted from the glands, is limpid, bluish, and
slightly acid. When introduced into the tissues, it produces very acute
local pain, which extends throughout the affected limb. The pain is
excruciating, and sufferers have been observed to become actually
delirious, striking and biting those around them, throwing themselves
from side to side, and beseeching that the limb should be cut off; some
of them have amputated the injured part themselves.
This condition is accompanied by considerable anxiety, and by attacks
of leipothymia and sometimes of syncope. In some cases syncope has
been followed by death; in others serious phlegmons, complicated by
septicæmia, supervene. The inoculated spot becomes bluish, and then
sphacelates over a larger or smaller area. These gangrenous wounds heal
very slowly, more especially since they are usually produced on the
sole of the foot (Bottard).
A single drop of the venom is sufficient to kill frogs in about three
hours.
[Illustration: FIG. 102.--_Cottus scorpius_ (Sea Scorpion).
(After Savtschenko.)]
The genus _Cottus_, which also belongs to the family TRIGLIDÆ,
includes some forty venomous species found in the seas of the northern
hemisphere, in Europe, Asia, and America.
In France the species of _Cottus_ are generally called _chabots_
(bullheads or miller’s thumbs), _chaboisseaux_ (sea-scorpions), or
_caramassons_. They are abundant on the coast of Normandy, and some of
them (river bullheads) live in fresh water; they do not exceed 25 cm.
in length. They have a liking for holes in rocks, and fishermen are
afraid of being stung by them (fig. 102).
Their poison-apparatus resembles that of the Weevers, but is less
developed. It is situated in the culs-de-sac formed by the opercular
spines. The culs-de-sac are lined with cells which produce a toxic
secretion only during the spawning season, from November to the end of
January. This fact explains how it is that the species of _Cottus_ are
declared by certain fishermen to be very venomous, while others say
that they are absolutely harmless.
The genera _Scorpæna_, _Pterois_ and _Pelor_ also belong to the same
group.
[Illustration: FIG. 103.--_Scorpæna grandicornis_ (Caribbean
Sea). (After Savtschenko.)]
In _Scorpæna_ the body is clothed with scales, and the head is large,
slightly compressed, armed with spines, and has a bare pit behind;
the single dorsal fin is provided with eleven spiny rays, and there
are seven branchiostegal rays. _Scorpæna grandicornis_ (fig. 103),
found in the Caribbean Sea, is from 30 to 50 cm. in length, and has
the back red and the eyes and belly yellow; _Scorpæna diabolus_
(fig. 104), which occurs in the Indian Ocean and Tropical Pacific,
is red and brown, obliquely striped with white and brown; a third
species, _Scorpæna porcus_ (_Scorpène truie_), of smaller size, is met
with in the Mediterranean. The venom of the latter has been studied
by A. Briot,[143] who sectioned the dorsal and opercular spines,
and macerated them either in physiological saline solution, or in
glycerine; he then tested the toxicity of these macerations on certain
animals--frogs, rabbits, and rats.
[Illustration: FIG. 104.--_Scorpæna diabolus_ (Indian and
Pacific Oceans). (After Savtschenko.)]
The frogs alone exhibited, as the result of subcutaneous injection
into a limb, slight transient paralysis. No effect was found to be
produced by the venom when injected intravenously into the rabbit, or
subcutaneously into the rat.
The poison-apparatus of _Scorpæna_ is situated in the spiny rays of
the dorsal and anal fins. These rays are enveloped in the inter-radial
membrane, which forms a sheath for them, and are scored with a double
cannelure. At the bottom of these grooves are the secreting cells,
which are elongate, pressed one against the other, and supported at the
base by a highly vascular substratum of connective tissue. The venom
flows out between the layer of cells and the ensheathing membrane,
which is capable of being pushed slightly back as the result of the
penetration of the spine into the tissues, and then exerts pressure
upon the reservoir. The latter is formed by the distension of the
sheath under the pressure of the secreted liquid.
[Illustration: FIG. 105.--_Pterois artemata_ (East Coast of
Africa, Indian and Tropical Pacific Oceans). (After Savtschenko.)]
There are twelve pairs of dorsal and three pairs of anal glands. The
pairs attached to the second anal spine are, as the direct result of
the size of the latter, more developed than those of the other spines.
In the _Rascasse_, the opercular spines of which are greatly developed,
there is a rudiment of a poison-apparatus at the bottom of the sheath
formed by the skin of the gills.
The species of _Pterois_ (fig. 105) are distinguished from those of
_Scorpæna_ by their dorsal fins, the rays of which are very long and
curved backwards, above the membrane by which they are united. They
are found in the Indian and Equatorial Pacific Oceans, and are very
beautiful in colour, varying from reddish-brown to bright rose.
The poison-apparatus of these fishes is situated in the dorsal fin, and
is precisely similar to that of _Scorpæna_.
[Illustration: FIG. 106.--_Pelor filamentosum_ (Family
_Triglidæ_, Mauritius).]
The species of _Pelor_ (fig. 106) present greater resemblance to those
of _Synanceia_, owing to their heads being crushed in in front. Their
eyes stand up above the head and are very close together, which helps
to give them an extremely ugly appearance. The skin is soft and spongy,
and bristles with jagged fleshy shreds.
Their poison-apparatus is placed in the dorsal fins, as in the case of
_Scorpæna_ and _Pterois_.
2.--Trachinidæ.
Genus _Trachinus_ (Weevers).--Four species of Weevers are found in
European seas: the Greater Weever (_Trachinus draco_), the Lesser
Weever (_T. vipera_), the Striped-headed Weever (_T. radiatus_), and
the Mediterranean Spider Weever (_T. araneus_); other species are met
with on the coast of Chile.
Weevers possess two sets of poison-apparatus, one of which is situated
on the operculum, the other at the base of the spines of the dorsal fin
(fig. 107).
[Illustration: FIG. 107.--_Trachinus vipera_ (Lesser Weever).]
The spine surmounting the operculum exhibits a double cannelure
connected with a conical cavity excavated in the thickness of the base
of the opercular bone. This spine is covered with a sheath, beneath
which lie the secreting cells. The gland is an offshoot from the skin,
and appears as a simple follicle invaginated in the opercular bone
(fig. 108).
The dorsal apparatus is composed of from five to seven spines, to which
the inter-radial membrane forms an adherent sheath which extends almost
to the end of the rays. Each spine exhibits a deep double cannelure.
The venom flows between the layer of cells clothing the cannelures and
the skin, which is distended to allow it to pass.
Towards the base of the spine, the edges of the cannelure are united,
and form a hollow, bony cone, the walls of which are lined with the
cells that secrete the toxic fluid.
[Illustration: FIG. 108.--_A_, Operculum and opercular spine
of the Lesser Weever (_Trachinus vipera_); _ar_, articular surface of
the operculum; _c. op_, body of the opercular spine; _c. an_, canal
of the spine; _z_, space occupied by the poison-gland. _B_, Spine
belonging to the first dorsal fin; _c. an_, efferent poison-canal in
the spine.]
Greater Weevers are usually from 12 to 30 cm. in length, and of a
reddish or yellowish-grey colour, with blue or violet spots. They are
caught in trawls and are fairly common on sandy bottoms. In the month
of June they approach the shore for the purpose of spawning.
The venom of the Weever has formed the subject of interesting studies
by Günther, Gressin,[144] Bottard, Phisalix,[145] and more recently by
Kobert[146] and A. Briot.[147]
In order to procure sufficient quantities of it for experimental
purposes, Briot cuts off the venomous spines and the surrounding tissue
with a pair of scissors; he then pounds the whole in a mortar, and
mixes the pulp with pure glycerine. After filtration through paper, a
toxic solution is obtained, which does not deteriorate by keeping, and
is neutral to litmus.
A few drops of this liquid are sufficient to kill guinea-pigs, which,
immediately after receiving an injection in the thigh, exhibit
paralysis of the leg with tetanic convulsions; twenty-four hours later
an eschar is formed, and death supervenes on the second or third day.
Two or three drops, introduced into the marginal vein of the ear of
a rabbit, cause death from asphyxia in from four to ten minutes. The
heart continues to beat for a fairly long time after respiration has
entirely ceased; the blood is not coagulated.
The toxicity of this venom is completely destroyed by heating it to
100° C., by chloride of lime, and by chloride of gold. Antivenomous
serum prepared from horses vaccinated against cobra-venom has
absolutely no effect upon it _in vitro_. There is therefore no affinity
between this venom and that of snakes.
Weever-venom dissolves the red corpuscles of the horse in the
presence of normal heated horse-serum, but does not dissolve them in
the presence of fresh serum. The non-heated serum, therefore, as I
have shown with reference to the action of cobra-venom on the blood,
contains a natural antihæmolysin.
Briot succeeded in vaccinating rabbits by accustoming them to the
venom, and in obtaining from them a serum capable of neutralising
the latter _in vitro_, and of immunising fresh rabbits against doses
several times lethal, even when injected intravenously.
According to Gressin, the following phenomena are produced in man as
the result of Weever-stings:--
“At first there is felt an excruciating, shooting, paralysing pain,
which, in the case of nervous persons, may cause attacks of leipothymia
ending in syncope. A kind of painful formication next pervades the
injured limb, which becomes swollen and inflamed, and may even, if
treatment be neglected, form the starting point of a gangrenous
phlegmon.
“This condition is frequently accompanied by certain general
phenomena--such as fever, delirium, and bilious vomiting, the duration
of which is variable, since they may only last for two or three hours,
or may continue for several days. Fishermen rightly consider this
variability to depend upon the amount of venom that has penetrated
into the wound, and especially upon the season at which the accident
takes place. The most serious results are recorded during the spawning
season, and fishermen regard the Lesser Weever as being the more
poisonous.”
3.--Gobiidæ.
In the fishes belonging to this family the body is elongated and
depressed, while the spines in the anterior dorsal fin and in the
ventral fins are slender, flexible, and seldom very solid. The ventral
fins are inserted on the breast or on the throat, and are either
separated or united together in the shape of a funnel. The skin is
naked or covered with large scales, and the mouth is furnished with
teeth. The males are distinguished by the presence of a long genital
papilla. These fishes are carnivorous.
[Illustration: FIG. 109.--_Callionymus lyra_ (Dragonet or
Skulpin. Family _Gobiidæ_).]
Several species of venomous =Gobiidæ= are met with on the shores
France and in the tropical zone. The most important of these belong to
the genus _Callionymus_ (_C. belennus_, _C. lacertus_, _C. vulsus_, and
_C. lyra_--fig. 109).
The Dragonet or Skulpin (_Callionymus lyra_), which is common on the
coast of Calvados, may attain the length of 30 cm. In France it is
popularly known as the _Doucet_, _Dragonnet_, _Lavandière_, _Cornaud_,
or _Capouri_. Its colours are very vivid, orange and deep lilac.
In this fish the præopercular bone ends in three strong, conical, and
very sharp points, diverging like the prongs of a trident. The upper
margin of the opercular bone bears another point, which is directed
upwards.
The skin of the gills forms a common sheath for this defensive
armature, and the base of the sheath is prolonged into two culs-de-sac,
the surface of which is clothed, during the spawning season, with
cylindrical cells, the secretion of which is poisonous.
This venom, which is small in amount, does not appear to have any
marked effect upon man (Bottard).
4.--Teuthididæ.
This family of _Acanthopterygii_ includes several species of
brilliantly coloured fishes with elongated and laterally compressed
bodies, provided with a long dorsal fin, and having, on each side of
the tail, a sharp spine placed in front of the anal fin. They are
herbivorous, and are confined to the tropical seas.
The principal genera are: _Teuthis_ (India), _Acanthurus_ (Tropical
Atlantic), _Prionurus_ (Japan), and _Naseus_ (Red Sea and Indian
Ocean). The fishermen of Réunion are much afraid of the wounds
inflicted by _Acanthurus luridus_, which they call _Marguerite Porc_
or _Grande Marguerite_. A sting from this fish causes a very acute
smarting pain, which may last for several hours, but usually has no
serious consequences.
The poison-apparatus of these fishes is situated in the dorsal and anal
fins, as in _Scorpæna_.
5.--Batrachiidæ.
The venomous species belonging to this family are few in number. They
are found in all tropical seas, but have no representatives in Europe.
The best-known species are _Batrachus tau_ (shores of Central America),
and _B. grunniens_, or Grunting Batrachus (fig. 110).
[Illustration: FIG. 110.--_Batrachus grunniens_ (West Indies).]
[Illustration: FIG. 111.--_Thalassophryne reticulata_ (Panama;
Tropical Pacific). (After Savtschenko.)]
The Grunting Batrachus, which does not exceed 30 cm. in length, is
especially common in West Indian waters. When taken from the water
it makes a peculiar grunting sound, whence its name is derived. The
pectoral fins are reddish, the back is brown, and the sides are yellow,
marbled with black. It has three spines in the anterior dorsal fin, and
a fourth spine on the top of the operculum, with a small poison-sac at
the base of each.
Next to this genus come the species of _Thalassophryne_, _T.
reticulata_ (fig. 111), found on the shores of Panama, and _T.
maculosa_, of Bahia (Brazil), which are provided with a precisely
similar poison-apparatus.
The physiological action of the venom of these two species has not yet
been studied, but it is probable that it does not differ from that of
the venom of the Weevers and the species of _Synanceia_.
[Illustration: FIG. 112.--_Lophius setigerus_ (China Sea and
Sea of Japan). (After Savtschenko.)]
6.--Pediculati.
The fishes belonging to this family are of large size and compact
shape, with the anterior part of the body greatly expanded. The head,
which is broad, bears venomous spines, and the mouth is furnished with
large teeth. These fishes are voracious, and lie in wait for their
prey at the bottom of the water in the mud of the shore. In order to
attract it, they make use of cutaneous appendages attached to their
spines, which they are able to elevate, and of filaments situated near
the mouth.
The principal genus is _Lophius_, one species of which, _L. setigerus_
(fig. 112), is found in the seas of China and Japan. Another species,
_L. piscatorius_ (the Sea Devil or Angler), occurs in the temperate
climates of Europe, North America, Asia and Africa.
Certain other _Acanthopterygii_ are _capable of inflicting wounds_,
but, although fishermen often believe them to be venomous, or such
properties are frequently attributed to them in stories, it is doubtful
whether they possess poison-glands. The accidents produced by them are
due rather to the fact that the spines in their fins are extremely
sharp, and that their flesh is toxic. Those belonging to the _Percidæ_
(the Perch family), especially the genus _Serranus_ and _S. ouatabili_
(fig. 113) in particular, are above all remarkable in this respect. The
last-mentioned fish has two or three spines on its operculum.
[Illustration: FIG. 113.--_Serranus ouatabili._ (After
Savtschenko.)]
The same may be said of certain _Squamipinnes_, another family of
_Acanthopterygii_, whose stout bodies are brightly coloured, and have
very sharp, spiny rays in their dorsal and anal fins. The most curious
genus among the fishes belonging to this family is _Holacanthus_, in
which the præoperculum is provided with an enormous spine like that of
the Weever. _Holocanthus imperator_ (fig. 114) is met with fairly often
in the Indian Ocean and Malay Archipelago.
[Illustration: FIG. 114.--_Holacanthus imperator_ (Indian
Ocean and Malay Archipelago). (After Savtschenko.)]
B.--TELEOSTEI.--PLECTOGNATHI.
The Order _Plectognathi_ (Family _Gymnodontes_) includes the genera
_Diodon_, _Tetrodon_ and _Triodon_, globular fishes, in which the jaw
is transformed into a beak and furnished with a sharp dentary plate.
Their œsophagus is dilated into a resonant air-pouch. When removed from
the water they swallow air and dilate the pouch, and the expulsion of
this air is accompanied by a loud noise.
Several species of _Tetrodon_ are armed with spines, which produce
very painful wounds. Their flesh is toxic, but it has not been proved
that poison-glands exist at the base of the spines.
On the shores of the Cape of Good Hope, Brazil, China, and Japan these
fishes are much feared. The principal species are _Tetrodon stellatus_
(Indian and Pacific Oceans; fig. 115) and _T. rubripes_ (Japan; fig.
116).
[Illustration: FIG. 115.--_Tetrodon stellatus_ (Indian and
Pacific Oceans). (After Savtschenko.)]
[Illustration: FIG. 116.--_Tetrodon rubripes_ (Japan). (After
Savtschenko.)]
Closely allied to _Diodon_, and feared like the foregoing on account
of their spines, which are sometimes scattered all over the body, are
the species of the genus _Chilomycterus_, the most important of which
are _C. orbicularis_ (fig. 117), and _C. tigrinus_ (fig. 118), both of
which are found in the Indian Ocean.
[Illustration: FIG. 117.--_Chilomycterus orbicularis_ (Indian
Ocean). (After Savtschenko.)]
[Illustration: FIG. 118.--_Chilomycterus tigrinus_ (Indian
Ocean). (After Savtschenko.)]
C.--TELEOSTEI.--PHYSOSTOMI.
This Order is characterised by the presence of a pneumatic duct to the
air-bladder. It consists of a large, number of families, only two of
which, the _Siluridæ_ and _Murænidæ_, include venomous species.
1.--Siluridæ.
The majority of the very large number of species belonging to this
family live in fresh water, and have the free margin of the lips almost
always furnished with barbules (_Silurus glanis_; fig. 119). A few of
them possess a poison-apparatus, which, however, attains its greatest
development in _Plotosus_, the only genus of Siluridæ found exclusively
in the sea.
The species of _Plotosus_ frequent the shores of the Indian Ocean, and
are met with in the Seychelles, Réunion, and Mauritius. In shape they
resemble eels, and they bury themselves in the sand or mud, a habit
which renders them very dangerous to fishermen.
[Illustration: FIG. 119.--_Silurus glanis_ (Rivers of Central
and Eastern Europe).]
_Plotosus lineatus_, which is of a greenish-brown colour, striped with
from four to six longitudinal whitish bands, is the most common. By
the Creoles of Mauritius and Réunion it is called _Machoiran_, by the
Malays _Sambilang_, and by the Abyssinians _Koomat_.
Its poison-apparatus is situated at the base of the dorsal and pectoral
spines. These spines are strong, sharp, slightly incurved, and
furnished with hooked denticulations, which cause them to remain in
the wound, in which they break off. Near their extremity there opens a
small canal, which communicates with the culs-de-sac situated at the
base of the spiny rays, which produce a venomous secretion. The dorsal
spine has only a single cul-de-sac, while the pectoral spines have two.
The contraction of the local muscles, by compressing these culs-de-sac,
can cause the venom to make its way into the canal of the spine, but
the fluid does not spurt forth in a jet as in the case of _Synanceia_.
The poison-apparatus is therefore passively defensive in character.
_Plotosus_ is capable of wounding only when the hand or foot is placed
on its dorsal or pectoral spines.
Fishermen who are stung immediately feel an excruciating pain, which is
soon accompanied by fever, and lasts for several days. Accidents caused
by this fish are of fairly common occurrence in Réunion.
2.--Murænidæ.
Of the fishes belonging to this family, the species of the genus
_Muræna_ alone concern us. They have an elongated body, without
pectoral fins, and a naked skin, covered with a thick layer of viscid
slime, as in the case of the eels. Their dentition is powerful, formed
of long, recurved fangs, arranged in one or more rows. These fishes
may attain a large size, exceeding 2 metres in length. More than one
hundred species are known, all of which live in tropical or subtropical
seas. _Muræna helena_ is common in the Mediterranean in the vicinity
of Nice and Toulon; _M. moringa_ (fig. 120) is found in the Tropical
Atlantic.
The species of _Muræna_ live in deep water, and feed upon fishes or
crustaceans. In hot countries they frequently venture into fresh water.
Their skins are adorned with brightly coloured markings, which vary
very greatly according to the species.
The poison-apparatus in _Muræna_ consists of a pouch situated above
the membrane of the palate, which may contain ½ c.c. of venom, and
three or four conical, curved teeth, with the convex surface in front,
as in the fangs of snakes. The teeth are not pierced by a central
canal, and the venom flows between them and the mucous membrane of
the palate, which forms a sheath. The latter is withdrawn to the base
of the teeth, while they are penetrating the tissues. The teeth are
mobile; they are articulated with the palatine bone, in which they are
inserted in small depressions, and a resistant fibrous tissue serves as
the means of union. They can be deflexed backwards against the mucous
membrane of the palate; in this position the first, second and fourth
tooth (when the latter exists) disappear completely between the folds
of the membrane. The third tooth normally remains erect, and it is this
by which wounds must in most cases be inflicted. None of these teeth
can be protruded beyond the vertical.
[Illustration: FIG. 120.--_Muræna moringa_ (Tropical
Atlantic). (After Savtschenko.)]
In addition to the palatine teeth there are, among the groups of
maxillary teeth, several mobile teeth, which are connected with the
poison-reservoir.
Besides its toxic action the venom of _Muræna_ has manifest digestive
properties, and, in the case of a fish which has been dead for some
little time the gland is no longer to be found, since its walls have
undergone a rapid autodigestion.
The venoms of all the fishes of which I have just given a brief
description, as regards their physiological action, present a fairly
close resemblance to the venom of the Weever, and show scarcely any
variation except in the intensity of their effects. They have been but
little studied hitherto, and it is desirable that they should be better
understood.
CHAPTER XVIII.
_VENOMS IN THE ANIMAL SERIES_ (_continued_).
3.--_BATRACHIANS. LIZARDS. MAMMALS._
A.--Batrachians.
By the ancients the venom of _salamanders_ and _toads_ was dreaded as
much as the most terrible poisons. These animals, however, are not
very formidable, since they are devoid of inoculatory organs; their
poison-apparatus is localised exclusively in the parotids and the skin.
It is represented simply by more or less confluent glands in the form
of sacs, secreting a viscid mucus, which has a nauseous odour and is
highly toxic, even to animals of large size.
The salamander belongs to the Order _Urodela_, which is characterised
by the persistence of the tail. Its body is heavy and thickset, and the
flanks and the sides of the tail exhibit a series of glandular crypts,
which secrete venom.
“The mucus which flows from the mouth, and resembles milk, eats away
human hair,” wrote Pliny; “the spot moistened by it loses its colour,
which subsequently returns. Of all venomous animals the salamander
is the most terrible; it is capable of annihilating whole nations
by poisoning the vegetation over a vast area. When the salamander
climbs a tree all its fruit is poisoned, and those who eat of it die
as surely as if they had taken aconite. Moreover, if bread be baked
with wood touched by the animal, it is dangerous, and may occasion
serious disorders. If the naked foot be defiled with the saliva of
this creature, the beard and hair soon fall out. Sextius says that a
salamander, preserved in honey, after the removal of the entrails,
head, and limbs, acts as a stimulant if taken internally.”
In ancient Rome, and also in Mediæval France, it was believed that the
most furious fire could be extinguished simply by contact with one of
these animals; charlatans sold the inoffensive salamander, which, if
cast into the most terrible conflagration, was bound, they declared, to
arrest its disastrous progress!
The explanation of this superstition is furnished by Duméril, who
writes: “On being placed in the middle of burning charcoal, these
victims of so cruel a curiosity, when put to the test, instantly
allowed to exude from the many pores with which their skins are riddled
a slimy humour, sufficiently abundant to form a viscid layer over that
part of the glowing charcoal with which the animals were in contact.
Since this surface, being no longer exposed to the air, immediately
became quite black, it was supposed to be extinguished; but the
salamanders sustained such severe burns that they soon succumbed.”[148]
The principal species of salamanders are:--
_Salamandra atra_ (Black Salamander), which is found in the Alps and
the mountains of Central Europe, close to the snow-line, and up to an
altitude of 3,000 metres.
_Salamandra maculosa_ (Spotted Salamander, fig. 121), distributed
throughout almost the whole of Europe, and also found in North Africa.
_Triton cristatus_ (Crested Newt), likewise common all over Europe.
_Triton marmoratus_ (Marbled Newt, fig. 122), which is met with in damp
and dark places, in Portugal, Spain, South and Central France, and as
far north as the Forest of Fontainebleau.
_Cryptobranchus japonicus_ (Great Japanese Salamander, fig. 123), which
often exceeds 1 metre in length, and has a clumsy body covered with
large warts, and an enormous head, broad behind and flattened in front.
This giant salamander is now confined to a few provinces in the centre
of Japan, between long. 34° and 36°, in damp, shady places, from 200 to
800 metres above sea-level. It is eaten by the Japanese, who also use
it as a remedy for, or prophylactic against, contagious disorders. By
nature it is extremely sluggish, but tries to bite when irritated, and
then covers itself copiously with slime.
[Illustration: FIG. 121.--_Salamandra maculosa_ (Europe and
North Africa).]
[Illustration: FIG. 122.--_Triton marmoratus_ (male).
(Europe.)]
The venom secreted by salamanders evidently serves to protect these
creatures against their enemies. So long ago as 1866, Zaleski[149]
isolated from it a substance soluble in alcohol, insoluble in ether,
and with a very strong alkaline reaction, to which he gave the name
_salamandarin_. This substance, which is better known to-day as
_salamandrine_, has been studied afresh by A. Dutartre,[150] Phisalix
and Langlois,[151] and subsequently by Edwin and S. Faust.[152]
[Illustration: FIG. 123.--_Cryptobranchus japonicus_ (Great
Japanese Salamander).]
The action of this poison on the frog is characterised by a period
of violent convulsions, with general tetanic crises, followed by a
period of paralysis, with arrest of respiration and complete muscular
relaxation. According to the quantity of poison absorbed, this
paralytic period may be followed by death, with arrest of the heart in
diastole, or else by return to life, with more or less acute recurrence
of convulsions.
S. Faust prepares salamandrine by pounding up whole salamanders in
a small quantity of physiological saline solution. The thick pulp
obtained in this way is filtered. One cubic centimetre of the filtrate,
taken as a unit, contains about 5 decimilligrammes of active substance,
which can be purified by treating the filtrate with alcohol, which
dissolves the salamandrine and precipitates all the proteic substances
that give biuret reaction. The salamandrine thus freed from proteins
is saturated with sulphuric or phosphoric acid, when there is formed a
crystallisable salt, which is washed and dried. This salt is soluble in
alcohol and in water. Its chemical composition is as follows:--
C^{52}H^{80}Az^4O^2 + H^2SO^4.
The toxicity of this substance is such that from 7 to 9
decimilligrammes per kilogramme represent the lethal dose for dogs,
when injected subcutaneously. The lethal dose for the rabbit is
still smaller. It produces convulsive phenomena, followed by arrest
of respiration. The administration of chloral to the subjects of the
experiment, either preventively or immediately after the poison,
prevents the latter from taking effect. Besides salamandrine, S. Faust
has isolated a second alkaloid, _salamandridine_, which, as a sulphate,
corresponds to the formula (C^{20}H^{31}AzO)^2 + H^2SO^4, crystallises
in rhombic prisms, and is soluble with difficulty in water. The only
difference between the two alkaloids is formed by a methylpyridic
group, and both are derivatives of quinoline. They must therefore be
considered as identical with the exclusively vegetable alkaloids.