Little did the learned Dutchman Leeuwenhoek dream when, more than two
hundred years ago, he recorded, in his Arcana Naturæ, that he had
found "viva animalcula" in his saliva, that this, the first beginning
of bacteriology, would lead, a couple of centuries later, to the
inauguration of a new era in the treatment of disease, in which these
so-called animalcula, from being considered as curiosities, would come
to be regarded as powers for good and evil of the first importance.
Protective inoculation or serum therapy, of which the public have
lately heard so much in connection with diphtheria, is the direct
outcome of bacterial investigations which during the last two decades
have been pursued with such zeal in every part of the globe.
The vast domain of immunity, which until recently was an undiscovered
country, is now being bit by bit annexed, and in all directions
workers are engaged upon opening up new tracts, in overcoming
difficulties, in changing chaos into order.
The problems which surround immunity are of so complex and subtle a
character that their mastery is by no means either easy or rapid, and
many recondite researches appear at frequent intervals on this subject
in foreign and other scientific journals, rendering it a difficult
matter to keep pace with the new discoveries and the latest theories.
The interest in this country in toxins and anti-toxins not unnaturally
centres round that branch of the subject which deals with diphtheria,
this disease having of late years figured so prominently in our
mortality tables, whilst the production of diphtheria and other
anti-toxic serums has been so finely elaborated abroad that it already
constitutes an article of commerce, and doubtless helps to swell the
exports of our great continental commercial rival.
In this connection the following statistics, published by Dr. Jalzer,
of the Mülhaus Hospital, are of interest regarding the mortality from
diphtheria before and after the introduction and application of
diphtheria anti-toxin. The death-rate from this disease, writes Dr.
Jalzer, which in 1892 and 1893 was fully 50 per cent., fell in 1895 to
38·5 per cent., in 1896 to 28·8 per cent., in 1897 to 16 per cent., to
20 per cent. in 1898, 15·15 per cent. in 1899, and 18·75 per cent. in
1900.
So far the efforts which have been made to mitigate human suffering
have attracted most attention; but it will be remembered that Pasteur,
before he commenced the study of hydrophobia, had already won his
laurels in combating disease in the victory he gained over anthrax,
the ravages of which so frequently decimated the herds of the French
farmer and robbed him of his well-earned return on his capital and
labour.
In summoning the brilliant Director of the German Imperial Board of
Health to South Africa to investigate the nature of rinderpest, and,
if possible, discover a means of protecting cattle from its onslaught,
the Cape Government afforded another opportunity for the scientific
study of a disease associated with animals, upon the successful
mastery and limitation of which the agricultural prosperity of South
Africa is so largely dependent, being as it is one of the most fatal
and contagious maladies to which cattle are subject. Apart from the
great commercial importance attending Dr. Koch's discovery of a device
whereby cattle can be immunised or protected from contracting
rinderpest when exposed to its contagion, this discovery is of great
scientific interest, inasmuch as it has inaugurated a new departure in
methods of immunisation.
The previous methods in vogue for inducing immunity in animals from a
particular disease consisted in converting the virus itself into a
vaccine, as was done by Pasteur in his classical investigations on
anthrax and its prevention; and secondly, the employment of anti-toxic
serums, in which the virus is not directly inoculated into the animal
to be protected, but in which an intermediary is employed between the
virus and its victim. This intermediary, or living machine for the
generation of the anti-toxin, is usually a horse, which is
artificially trained by being given gradually increasing doses of the
virus or toxin, until it ultimately withstands doses which in the
first instance would infallibly have killed it. When the animal has
arrived at this satisfactory stage or condition of complete immunity,
some of its blood is from time to time drawn off, and the serum thus
obtained constitutes the anti-toxin which now figures so prominently
in modern therapeutics. Besides diphtheria-anti-toxic serum there are
also those of tetanus, or lock-jaw, plague, the famous anti-venene
serum, about the discovery and preparation of which greater detail is
given later on, and many others which are still the subject of
experimental inquiry.
Now Koch's method for the compassing of rinderpest differed from both
the systems above mentioned, inasmuch as he neither employed
artificially weakened cultures of the virus, or an anti-toxic
rinderpest-serum; instead he took one of the natural secretions of an
animal infected with rinderpest, and by injecting this into a healthy
animal it was discovered that the latter, as is the case with a
vaccine, suffered only local and temporary discomfort, and acquired
pronounced immunity from the active virus. The secretion selected by
Dr. Koch and his assistant, Dr. Kolle, for this purpose was the gall,
and it might be supposed, from the fact that its inoculation into
healthy animals did not communicate the disease, that the rinderpest
bacteria were absent from the gall. But this is not so, for Dr. Kolle
has succeeded in isolating the latter from the gall of infected
animals, and, moreover, has proved them on isolation to possess their
full complement of virulence. Further investigations made by Koch and
Kolle have shown that the explanation of this seeming anomaly is to be
found in the fact that the gall of an animal suffering from rinderpest
contains a substance which prevents the migration of the rinderpest
bacteria, with which it is associated, from the point of inoculation.
Hampered in their movements by the controlling influence of this
special substance which has been generated in the gall, the bacteria
remain rooted to the spot where they are first situate, and only a
passing and exceedingly slight local affection results, which on its
departure leaves the animal with an immunity from rinderpest lasting
some four months. A number of interesting investigations have not
unnaturally been stimulated by this remarkable discovery, and
researches on the properties inherent in the gall of healthy animals
of various kinds have been recently carried out by Dr. Neufeld, of the
Institute for Infectious Diseases in Berlin, which are, however, of a
too technical nature to deal with here.
As an illustration of the practical use to which Koch's gall
immunisation method may be put in dealing with outbreaks of
rinderpest, reference to a recent report furnished by the Health
Officer of Shanghai may be of interest. Dr. Arthur Stanley describes
the outbreak as follows:—
"A large herd of cattle infected with cattle-plague was brought to
Shanghai from the Tanyang district, around the Grand Canal, for export
to the allied troops in the north of China. The disease spread to an
adjacent dairy, most of the cattle dying. On this dairy becoming
infected a police cordon was established round it to prevent ingress and
egress of cattle and ingress of persons unconnected with the dairy,
while the outside infected herd was removed to an isolated part of the
settlement. Having been previously convinced of the futility of police
cordons in the prevention of cattle-plague, I was not surprised to find,
within a short time, that the disease had spread, by the meeting
together of cattle-coolies at a common tea-house, to three other dairies
at a distance of a quarter, a half, and two miles from the original
source of infection.
"As the animals are not, as a rule, taken away from the immediate
vicinity of the dairy, there being no grazing fields, and as
neither fodder nor dung is taken from one dairy to another, it is
practically certain the infection was carried by the
dairy-coolies.
"Immediately on this second series of dairies becoming infected it
was resolved to apply the gall immunisation method of Koch as
being the means at hand. About 1,500 cubic centimetres were
collected from the gall-bladder of a rinderpest animal, and 10
cubic centimetres were injected into the dewlap of each of the
twenty remaining cattle in the dairy.
"The injection caused slight local swelling and tenderness, but no
constitutional symptoms and no alteration in the milk-supply, an
important matter in a dairy. In all sixty-eight cattle were
injected with cattle-plague gall. Of these, seventeen were among
isolated uninfected herds; the remaining fifty-one belonged to
infected herds, and among the latter eleven died of cattle-plague
subsequent to the injection."
Dr. Stanley points out that ten of these animals, judging by the time
which elapsed after the injection, when they showed the first
symptoms of the disease, must have been already infected when the
injections were made; the eleventh animal, however, undoubtedly
contracted the disease after and in spite of the injection.
"Considering," continues Dr. Stanley, "the usual excessive
mortality during an outbreak of this disease, the result may
almost be compared to the success of vaccination against
small-pox. Three young bullocks, each having received 20 cubic
centimetres of cattle-plague gall, were purposely exposed to
severe infection. They remained well, while unprotected animals
around them died of the disease."
In the domain of immunity there is, however, no more fascinating or
interesting story than that which deals with the discovery and
elaboration of a cure for snake-bites, a discovery which, while
attracting but comparatively little attention in this country, should
prove of paramount importance to our fellow-subjects in the great
Indian Empire. The significance to India of Professor Calmette's
discovery of a specific cure for snake-poison may be gathered, indeed,
from the statistics which have been compiled of the number of deaths
attributed by Indian officials to this cause alone, amounting, it is
said, to some 22,000 annually.
The Pasteur Institute in Paris has despatched many pioneers of science
to various quarters of the globe, but perhaps no scientific missionary
has produced more fruitful results than has Dr. Calmette. It was while
acting in the double official capacity of Médecin de 1st Classe du
Corps de Santé des Colonies and Director of the Bacteriological
Institute of Saïgon, in Cochin China, in the autumn of 1891, that
Calmette first commenced his experiments on the neutralisation of
serpent venom in the animal system.
He had, indeed, exceptional opportunities in the matter of serpent
venom wherewith to carry out his investigations, for during the rainy
season a village in the neighbourhood of Bac-Lieu (Cochin China) had
been attacked by a band of most venomous serpents.
These creatures, driven by the floods into the very huts of the
natives for shelter, created a terrible panic, and no fewer than forty
individuals were bitten by them. The panic was certainly not without
justification, for these serpents belonged to the species known as
naja tripudians, or cobra de capello, renowned for the deadly
nature of their venom, and widely distributed over India, Burmah,
Sumatra, Java, Malacca, and Cochin China; but until Calmette set to
work to systematically study the nature of this reptile's venom but
little precise or reliable information had been obtained as to its
character.
The governor of the district gave orders that as many as possible of
the reptiles were to be captured alive and forwarded to the Director
of the Bacteriological Institute, and a plucky Annanite actually
succeeded in securing ninety specimens, which were forwarded in a
barrel to Dr. Calmette.
This formidable gift was received with enthusiasm by the director, who
realised the importance and scope of the inquiry, which he at once set
himself to systematically work out.
Forty of these reptiles arrived alive, and several were at once
sacrificed to secure their venom glands. Each gland, resembling both
in size and shape a shelled almond, contains about thirty drops of
venom, and in this transparent limpid liquid is embodied a toxin of
extraordinary strength. It was, of course, necessary in the first
instance to ascertain, within as narrow a limit as possible, the exact
degree of toxic power inherent in the venom, and to determine, if
possible, the precise lethal dose in respect of each variety of animal
experimented upon.
A correct calculation of the quantity of venom required in every case
was, however, found to be quite impossible, for so virulent is the
poison that a single drop of an emulsion produced by pounding up eight
glands in 300 grammes of distilled water is sufficient, when
introduced into the vein of a rabbit's ear, to kill it in five
minutes. All the mammals to which Calmette administered this cobra
venom, such as monkeys, dogs, rabbits, guinea-pigs, rats, succumbed
more or less quickly, according to the size of the dose.
Small birds and pigeons die very rapidly, but the domestic fowl is
more fortunate, being somewhat less susceptible. Frogs also fall a
prey to the venom, but they are far more refractory than rabbits, for
it takes thirty hours to kill a frog with a dose of venom which would
infallibly destroy a rabbit in ten minutes. Toads, curiously, do not
enjoy to the same extent this power of resisting its toxic action, for
they die more quickly than frogs, whilst it makes short work of
lizards and chameleons. Fish form no exception to the rule, and even
invertebrates, such as leeches, are killed by minute traces of venom.
Whilst Calmette has found that the venom of different kinds of
reptiles exhibits marked differences in its toxic character, he has
also discovered that the venom secreted by one and the same serpent
varies considerably, according to the length of time the animal has
fasted. He describes how he kept a naja haje (Cleopatra's asp) in
his laboratory, which during the whole eight months that it lived
never took any food whatever, although it was offered the most diverse
dainties. On its arrival it was made to bite on a watch-glass, this
being one method adopted for collecting the venom; the liquid was at
once dried, and 0·7 milligramme was found to kill a rabbit weighing
nearly four pounds in four hours. Two months later on, when the venom
was again collected, 0·25 milligramme proved a fatal dose. On the
death of the animal, at the end of eight months, the venom extracted
from the glands was so toxic that it only required 0·1 milligramme to
kill a rabbit of about the same weight as the previous one. The same
curious fact was noted in the case of a cobra's venom. Another
circumstance which appears to control the degree of toxicity inherent
in serpent venom is the interval of time which elapses between two
successive bites. The longer the interval the more virulent is the
venom; and Calmette points out that these observations are in
accordance with what has for a long time been known in France with
respect to indigenous vipers—that their bites are far more dangerous
and far more fatal in the spring, after the winter period of torpor is
over, than in the autumn.
Until quite recently it was thought that the only creatures which
could resist the fatal action of this poison were serpents, both
poisonous and non-poisonous. Calmette was led to this conclusion
because, although he inoculated large doses, as much as ten drops,
into cobras, they suffered absolutely no inconvenience, and the same
results were obtained with harmless snakes. On repeating these
experiments, however, and using much larger quantities of venom,
Calmette has found that they do ultimately succumb. That their
susceptibility in comparison with other animals is very slight, may be
gathered from the fact that a lethal dose of venom for reptiles is
roughly estimated to amount to as much as three times the quantity of
venom normally present in their respective poison glands. These
animals, therefore, although very refractory, are not absolutely
immune from the action of venom-toxin.
There are, however, other animals which enjoy a relative although not
absolute immunity to snake poison, and amongst these may be mentioned
swine, hedgehogs, and the mongoose. Swine, it is well known, will
greedily devour reptiles, and in some countries they are specially
trained up and employed for this purpose. Of particular interest,
however, are some experiments which were carried out to test the
traditional immunity towards this toxin ascribed to the mongoose.
These animals are very useful in sugar plantations, and are largely
employed to keep down the serpents and rats with which they abound,
for the carnivorous little mongoose is extremely partial to such prey.
Attempts have been made by sugar planters to introduce them into
Martinique, where they are not found in the wild state, as in the
island of Guadeloupe.
Six specimens of the mongoose were forwarded to Calmette from
Martinique, and these particular animals, it was stated, had never
been set at liberty since they were imported, so that they had had no
previous experience of snakes or venom. On arriving at the laboratory,
one of these little creatures was placed in a glass cage along with a
large cobra. The cobra, at once rising up and dilating its neck,
darted with fury upon the mongoose; but the latter, thanks to its
extraordinary agility, escaped being caught, and took refuge,
stupefied and terrified for the moment, in a corner of the cage. This
stunned condition, however, did not last long, for just as the
incensed cobra was preparing to make a fresh attack upon its
insignificant little victim, the latter, with wide-open mouth, rushed
and jumped upon the head of its enemy, viciously bit through its upper
jaw, and broke its skull in a few seconds. Thus, although in size but
a little larger than a squirrel, this tiny creature was more than a
match for a cobra two yards long.
Artificial inoculations of cobra venom into the mongoose fully
substantiated all the observed facts as to its remarkable immunity
from this poison. A dose sufficient to kill a large rabbit in three
hours was absolutely without effect; only when the venom was
introduced in quantities amounting to as much as eight milligrammes
was it followed by fatal results. Thanks, therefore, to their
extraordinary agility and remarkable power of resisting the effects of
this lethal toxin, these little animals are able to battle
successfully with the most dangerous reptiles.
The rapidity with which serpent venom becomes absorbed by the system
is almost incredible, and is well illustrated by the following
experiment. A rat was inoculated with venom near the tip of its tail.
One minute later the latter was cut off a short distance above the
point of inoculation; but this operation was quite unable to save
the animal's life, for even in that brief interval the poison had
accomplished its fatal work, and a few hours later claimed its victim.
This rapid diffusion of the venom helps to explain the difficulty
which is experienced in arresting the course of the poison by local
treatment, for its passage is too rapid to permit of its being
overtaken by superficial measures of even the most stringent
character. But Calmette points out that local precautions are not to
be neglected, for although they cannot nullify the action of the
venom, they undoubtedly do delay its progress, and thus create a
longer interval or respite, during which an opportunity is afforded
for administering the anti-toxin. Before, however, passing on to the
investigations which have culminated in the production of a specific
antidote for this terrible toxin, there are a few more details which
Calmette has furnished as to its character which are of interest.
Serpent venom is characterised not only by its intensely virulent
properties, but also by the tenacity with which it retains them under
diverse circumstances. Thus it may be stored up for a whole year, and
yet at the end of that time be as active as ever; and even after
several years, although its toxic powers are somewhat reduced, it
still retains them to a very appreciable extent.
Unlike the bacterial toxins, this venom toxin can stand exposure to
considerable temperatures without injury to its activity, and that of
the cobra only suffers after it has been submitted to 98° Centigrade
for twenty minutes. Sensitiveness to temperature varies, however,
with the snake from which the venom is derived. Thus the venom of
the so-called "tiger-snake" of Australia will stand being exposed
for ten minutes to from 100° to 102° degrees Centigrade, and its
virulence only disappears when this temperature has been applied
for twenty minutes. The venom of the "black snake," another
Australian variety, loses its toxicity at a temperature of between
99° and 100° Centigrade; whilst an exposure to only 80° Centigrade
for ten minutes is sufficient in the case of viper venom, according
to Messrs. Phisalix and Bertrand, to profoundly modify its lethal
action. A continuous exposure for a fortnight to a temperature of
38° Centigrade does not affect cobra venom in the least; but if during
that same time it has been placed in the sunshine, it entirely loses
all its lethal properties. Thus, a pigeon was inoculated with about
thirty drops of venom which had been exposed to the sun's rays for
fourteen days, and it survived; whilst another pigeon was inoculated
with a little over six drops of similar venom which had been kept
during this time in the dark, and it died in a quarter of an hour.
All these elaborate researches as to the character of serpent venom
were essential to enable the next step to be taken in the elaboration
of the antidote. Before this great achievement could be accomplished
it was necessary to first succeed in artificially immunising animals
against the effects of this powerful toxin, so that the serum of such
animals could be applied for the protection and cure of other animals
from the effects of snakebites.
It may be readily conceived that the task of artificially rendering
animals immune from snake poison was not an easy one, for the process
depends upon training the animal to gradually withstand larger and
larger doses of the venom; and considering the intensely toxic
character of the substance which had to be handled, the danger was
ever present of the animal succumbing to venom poison before its serum
had acquired the requisite pitch of protective power to render it of
service as an anti-toxin. Dr. Calmette tells us that he carried out a
very large number of experiments before he met with success. But it is
not necessary here to discuss his various efforts; suffice it to say
that at length his labours were rewarded, and the following extract
from one of his memoirs describes the methods which he adopted for
this purpose:—
"The best method of procedure for the purpose of vaccinating large
animals destined to produce anti-venomous serum consists in injecting
them from the outset with gradually increasing quantities of the venom
of the cobra mixed with diminishing quantities of a one-in-sixty
solution of hypochlorite of lime.[8] The condition and the variations in
the weights of the animals are carefully followed, in order that the
injections may be made less frequently if the animals do not thrive
well. Quantities of stronger and stronger venom are in turn injected,
first considerably diluted, and then more concentrated; and when the
animals have already acquired a sufficiently perfect immunity, the
venoms derived from as large a number of different species of snakes as
possible are injected. The duration of the treatment is of considerable
length—at least fifteen months—before the serum is
sufficiently active to be used for the purposes of treatment."
An immense number of animals have been vaccinated by this method at
the Pasteur Institute at Lille, where Dr. Calmette is now director;
and in one of his memoirs we are told that they have horses there
which have yielded during a period of eighteen months serum extremely
active against venom. These horses receive in a single inoculation,
without suffering the least inconvenience, doses of venom sufficient
to kill fifty horses fresh to the treatment.
Large quantities of this serum have been forwarded from the Lille
Institute to various parts of the world where venomous serpents are
most frequently met with, and already important evidence has been
collected as to its efficacy in cases of human beings bitten by
dangerous reptiles. So impressed with its importance are Indian
medical authorities, that its preparation has been included in the
work which the new great bacteriological institute at Agra is carrying
on.
The importance of the production in situ of this anti-venomous serum
has been recently demonstrated by the experiments which have been
conducted in the Plague Research Laboratory, Bombay, by Mr. Lamb and
his colleagues, on the keeping properties of such serums in India.
From the careful investigations which have been made on this subject,
these gentlemen state that anti-venomous serum undergoes a progressive
and fairly rapid deterioration when stored in hot climates, and that
this deterioration is greater and more rapid the higher the mean
temperature to which it is subjected.
The protective potency of this horse-serum may be gathered from the
fact that it suffices to inject a rabbit, for example, with a quantity
amounting to about one two-hundred-thousandth of its weight to ensure
the latter acquiring complete immunity from a dose of venom capable of
otherwise killing it in twelve hours.
The rapidity with which it acts is also extremely remarkable. Thus, if
a rabbit receive two cubic centimetres (about fifty drops) of
anti-venomous serum in the marginal vein of one of its ears, it will
suffer with absolute impunity an injection of venom into the marginal
vein of the other ear capable of killing it under ordinary
circumstances in a quarter of an hour. Its curative powers are not
less remarkable, for it is possible to inject venom sufficient to kill
an animal in two hours, and to let one hour and three-quarters elapse
before administering the antidote, and yet at this late stage to save
the victim's life, although it is necessary where such a long interval
has occurred between the respective venom and serum injections to
employ the latter in larger quantities than is usually required. Dr.
Calmette believes that the anti-toxin may be applied at an even more
advanced stage of the disease if it is employed in yet larger doses.
Another novel and important feature about this anti-venomous serum is
the fact that it not only protects animals from one species of very
active venom, such as that of the cobra and other poisonous snakes,
but it also affords protection from the dreaded venom of scorpions.
This is a very remarkable and significant discovery, for hitherto the
opinion has been stubbornly held that each toxin requires its specific
anti-toxin for its correction. Dr. Calmette has, however, frequently
indicated by his researches that this view cannot be considered so
completely proven as is claimed by its supporters, and his latest
investigations support the theory that particular toxins may be
counteracted by several anti-toxins of different origin. Thus it has
been shown by Calmette and Roux that rabbits hyper-vaccinated against
rabies acquire the power of resisting venom-poison, and that the serum
of horses vaccinated against tetanus or lock-jaw also nullifies the
action of serpent venom.
The practical bearing of this discovery is obvious, and the hope is
justified that the at present cumbrous appliances required for the
elaboration of anti-toxins of such varied origin will ultimately give
way to simpler and less costly methods, which will admit of these new
antidotes being more widely circulated and applied.
We have seen that although most animals fall an easy prey to serpent
venom, yet there are a few notable exceptions, amongst which may be
mentioned hedgehogs, swine, and the mongoose. Now the very natural
question arises why, if these animals are already in such a high
degree immune from this poison, should not they be employed to furnish
forth protective serum, instead of laboriously training up susceptible
animals to become artificially immune and supply this venom
anti-toxin?
This brings us face to face with one of the many problems connected
with the subject of immunity which so far have successfully eluded all
attempts made to solve them. Experience has shown repeatedly that
although artificially acquired immunity from a particular poison can
be handed on by means of an animal's serum, yet the natural immunity
from a given poison enjoyed by one species of animal cannot be
similarly transferred to less-favoured varieties.
This fact has long been recognised in the case of poisons of bacterial
origin. Thus, white rats are absolutely immune from diphtheria, but
Wassermann showed some years ago that the serum of these animals has
no power whatever to counteract the action of diphtheria-toxin in
other animals. Guinea-pigs were inoculated with fatal doses of
diphtheria toxin along with white-rat serum; but although other
guinea-pigs treated with the same toxin mixed with the ordinary
artificially elaborated anti-diphtheritic serum survived, those which
received the rat serum died in every case.
Now very similar results have been obtained by Calmette in respect to
the serum of animals naturally immune from serpent venom. The serum of
the refractory little mongoose, as well as that of the hedgehog, is
wholly unable to save other animals from the lethal effect of venom
poison, and similar results have been noted in respect to swine serum.
But a very curious fact has also been discovered by Calmette—i.e.
that these so-called naturally immune animals very frequently are
quite incapable of being artificially trained to elaborate a serum
possessing protective powers which can be transferred to another
animal.
How splendid a domain for beneficent research lies before the
scientific investigator is apparent to all, and the important work
already accomplished is but an augury of yet greater discoveries
awaiting the labours of such leaders as Calmette. It is not
surprising, therefore, that the scientific interest in toxins and
anti-toxins shows no signs of abatement. On the contrary, the
competition for obtaining and working the new "claims" which pioneer
research enthusiasts are constantly engaged in "pegging out" remains
as keen as ever.
Despite, however, the extraordinary interest which this subject has
aroused in scientific circles all over the world, nearly ten years
elapsed before any notice was taken of the curious discovery made by
two brothers that the blood of eels contained a highly poisonous
principle, and the memoir containing this remarkable announcement
remained until comparatively recently buried in the Italian journals
where it was first published.
Calmette was, we believe, the first to call attention to this
discovery of the brothers Mosso and give it the prominence it
deserves, and both he and other investigators have not only fully
confirmed it, but have greatly added to our knowledge concerning the
character of the poison contained in eel serum.
Now the venerable Izaak Walton, in one of his quaint and most
fascinating discourses, which although written more than two centuries
ago have a freshness as if penned but yesterday, waxes enthusiastic
over the eel, and supplies an elaborate recipe for its preparation for
the table, telling us "it is agreed by most men that the eel is a most
dainty fish; the Romans have esteemed her the Helena of their feasts,
and some the queen of palate-pleasure." The announcement that the
blood of eels is poisonous will hardly, despite its scientific
interest, form a comfortable subject for reflection to the modern
votaries of this novel Helena. Indeed, in the present timid temper of
the public, this article of diet would not improbably share the
ill-odour which befell the unfortunate oyster and be practically
banished from our tables; but although the oyster is perhaps
justifiably at present ostracised from our menus, taking the
majority of its breeding-grounds into consideration, it would be the
height of injustice to measure out similar drastic treatment to the
eel.
That the oyster bred in sewage-contaminated beds may revenge itself
upon its consumer by infecting him with the germs of typhoid has been
repeatedly contended, but that the eel, although its unsavoury
surroundings are proverbial, can be held responsible for poisoning
those who eat it has never, we believe, been seriously maintained,
although there is an old Italian saying which bids us "give eels and
no wine to our enemies."
Public confidence, however, in the eel as an article of food need not
be shaken, for it is satisfactory to learn that researches which, on
the one hand, condemn eels as living generators of a highly poisonous
substance, on the other hand allay any alarm which they may have
reasonably raised by showing that this toxic principle is entirely
destroyed in the processes of digestion, and that, therefore, taken
through the mouth it is rendered harmless, and only when introduced
into the system by inoculation beneath the skin or injected into the
peritoneum can it assert its dangerous properties. That the blood of
eels is, however, justifiably to be in future classed amongst the
toxins, the number of which has of late been so increased, is at once
apparent when we learn that about a dozen drops inoculated into a dog
weighing about fourteen pounds will destroy the latter in less than
ten minutes, whilst pigeons, rabbits, and guinea-pigs similarly
treated, only with smaller quantities, also invariably succumb to its
lethal action.
Quite recently an endeavour has been made to determine precisely the
degree of toxicity possessed by eel's blood, or, in other words, to
standardise the poisonous principle contained in it, so as to afford a
guide to those experimenting on the subject; and it has been asserted
that one cubic centimetre, or about twenty drops, injected into the
veins of a rabbit weighing four pounds, may be regarded as a fatal
dose for such an animal. But many difficulties surround such an
attempt to exactly define the degree of toxic action possessed by such
a substance, for, in the first place, the blood varies in respect to
this property in different eels, whilst it also differs widely in
character at different stages of the life of the fish. This seasonable
variation in toxic character has been noticed in the case of viper
venom, which it will be remembered was shown to be far more lethal in
action when collected from snakes in the spring of the year than in
the winter months.
The toxic substance contained in eel serum was originally called by
its discoverers, the Mosso brothers, ittio-tossina; and they record
the fact that the blood of rabbits and frogs, which animals had
succumbed to its action, did not coagulate after death, whilst,
curiously, in the case of dogs this abnormal phenomenon was not
observed.
There are various means which may be resorted to for destroying the
poisonous principle contained in eel blood, and from a dietetic point
of view it is satisfactory to know that heat-exposure for a quarter of
an hour to a temperature of from 57·7° to 77·7° Cent. entirely removes
it, whilst its virulence is greatly modified by submitting it for a
longer period, twenty-four hours, to a much lower temperature, i.e.
37° Cent. It also gradually loses its toxic properties eight days
after it has been collected, even when carefully shielded from light,
a feature which contrasts favourably with viper venom, which can be
kept for more than a year and remains as active as when first derived
from the snake. We have seen also that its toxic properties invariably
succumb to the processes of digestion, so that even if fashion or fad
or advertising speculators, backed by scientific names, were to decree
that a wealth of nourishment and support was contained in raw eel
"juice," and the edict went out that it was a desirable and highly
important article of invalid diet, the general public may, according
to its wont, innocently accept the edict and in this case suffer no
evil consequences.
But another and very remarkable method of mitigating the virulence of
eel blood, and one which so far has received no explanation, is
mentioned by Dr. Wehrmann, of Moscow, who has been lately studying the
character of this fish's blood in Dr. Calmette's laboratory at the
Pasteur Institute at Lille. Dr. Wehrmann found that if blood serum be
taken from animals previously rendered artificially immune to the
action of serpent venom, and if some of this so-called anti-venomous
serum be injected under the skin of eels some hours before they are
killed, the lethal properties of their blood after death are
considerably reduced. Thus, an eel weighing about six ounces received
subcutaneous injections of five cubic centimetres of anti-venomous
serum; after the lapse of four-and-twenty hours it was killed and
bled, and its serum inoculated into animals in the usual way. But
whereas two cubic centimetres of normal eel blood sufficed to kill a
guinea-pig, this eel's blood had to be administered in twice that
quantity to produce a fatal result, so that its toxic character had
been reduced to a very appreciable extent. The readiness with which
eel serum parts with its lethal properties, and the restricted
conditions under which they can operate, sufficiently assure us that
in the present state of our knowledge there is no danger to be
apprehended from this fish, and in the absence of any experiments to
show what is the effect on human beings of subcutaneous inoculations
of such blood, there is no call for this substance to be scheduled
under the Poisons Act. We have, however, by no means exhausted the
extremely curious properties which characterise this material, and
these properties are brought to light in a remarkable manner in
connection with the investigations which have been carried out to
artificially protect animals from its lethal influence, and also in
some interesting experiments which have been made to compare the
toxicity of eel blood with that of vipers.
It is far from an easy matter to secure for experimental purposes an
adequate supply of eel serum, for even a big fish weighing nearly five
pounds is not capable of yielding more than about twenty-five cubic
centimetres of blood, and from this only from ten to twelve cubic
centimetres of serum are obtainable. Calmette has shown that not only
the venom glands of reptiles contain toxic substances, but that the
blood of such snakes also possesses lethal properties, only in a far
less degree. Curiously, the serum of eels is no less than three times
as toxic as the serum of the most vicious viper, and, moreover,
produces far more discomfort and pain to the animals into which it is
introduced than accompanies the injection of viper blood. In the case
of viper blood its introduction is followed by no symptoms of
discomfort, the animal remains quite quiet, growing more and more
somnolent, a condition which is followed by an abnormal fall of
temperature, ultimately ending in complete collapse, symptoms which in
a much more modified degree characterise the injection of heated eel
serum into animals. This heated eel serum, which we have seen is
deprived of the objectionable characteristics of ordinary eel serum,
produces but very transitory symptoms in animals, occasioning some
degree of somnolence, and now and again a reduction in temperature, a
condition from which, however, the animals rapidly recover in from two
to three hours. Animals, however, treated with this heated eel serum
acquire a power of resisting the lethal action of unheated or ordinary
eel serum, and this artificially induced condition of immunity
continues for about three days after the completion of the treatment.
The protective properties of this heated serum are not restricted to
animals subsequently inoculated with eel serum, but are extended also
to animals which afterwards receive injections of viper serum; but of
much greater interest and importance is the remarkable fact that
heated eel serum, as well as weak doses of the latter not heated but
diluted with water, are capable of protecting animals from the fatal
consequences of the far more potent viper venom.
It is interesting to note that, although diluted eel serum can protect
an animal from so deadly a poison as viper venom, the serum of vipers
is quite unable to afford any such service in the case of animals
inoculated with ordinary eel serum. The full complement of protective
power obtainable from this treated eel serum is only able to slowly
assert itself, for it is necessary for a period of as long as
twenty-four hours to elapse after its introduction to ensure the
animal's system being thoroughly impregnated with it and enable it to
withstand a lethal dose of viper venom.
In this respect, what may be designated treated or protective eel
serum differs very markedly from anti-venomous serum, which we have
seen is serum derived from animals trained up to withstand fatal does
of serpent venom, for anti-venomous serum acts immediately, and at
once confers immunity on an animal from the lethal effects of such
venom.
The rapidity with which it acts is indeed one of the most astonishing
properties of this particular anti-toxin. Thus if two cubic
centimetres of anti-venomous serum be inoculated into the marginal
vein of a rabbit's ear, it at once confers upon the latter complete
immunity from snake poison. Immediately after the injection of the
serum, venom sufficient to destroy an ordinary rabbit in a quarter of
an hour may be injected with impunity into the vein of the other ear.
But not only are the protective powers of this serum so remarkable
in their degree, but its curative powers, a much more difficult
property to establish in a substance, are extraordinarily intense, as
may be gathered from the following example. Four rabbits were
inoculated with a quantity of venom calculated to destroy them in the
space of two hours; one of these four animals was abandoned to its
fate, but the other three received, practically at the eleventh hour,
viz. just fifteen minutes before the expiration of the calculated two
hours' respite, an intravenous injection of a small quantity of
anti-venomous serum, only amounting to one four-hundredth part of the
weight of each animal respectively. The rabbit which received only the
venom died at the end of two hours, whilst the other three remained in
perfect health.
But although eel serum can be persuaded to part with its poisonous
character and even exercise protective powers over otherwise doomed
victims, it is not able to stretch forth a healing hand to the
afflicted, for, when once the poison has been introduced, whether it
be eel or viper blood, or the venom of snakes, it is absolutely
powerless to mitigate or stop in any way the deadly progress of the
toxin. Thus whilst eel blood may acquire protective properties it
cannot acquire curative properties, and, therefore, treated eel
serum cannot be legitimately enrolled with the anti-toxins which have
been elaborated, as, for example, anti-venomous serum, for, to be
worthy of such rank, a substance must be capable of wielding both
protective and curative powers.
But, although eel serum may under certain conditions protect from the
lethal action of serpent venom, eels are not themselves under ordinary
circumstances endowed with any power to withstand the influence of
this poison, for a good-sized eel will succumb to a dose of venom
which is sufficient to kill a guinea-pig.
Considerable interest is attached to the fact that anti-venomous serum
not only acts as an anti-toxin towards serpent venom, but also towards
a poison of quite a different character, such as that present in the
normal blood of eels, for this fact tends to confirm the view upheld
by some authorities, that specific toxins do not necessarily only
yield to specific anti-toxins, and that a particular anti-toxin may
act as such towards divers toxins of varied origin and character.
Calmette has brought this point out very clearly in his later
investigations on the vegetable poison abrine, a very powerful toxin,
furnished by the active principle of the seeds or beans of a
leguminous plant common in India and South America, and frequently
used, as already mentioned, by the natives in India to revenge
themselves on their enemies in poisoning their cattle. Immunising
serums of various kinds were selected for testing their protective
action on animals poisoned with abrine, and it was found that
anti-tetanic, anti-diphtheritic, anti-anthrax, and anti-cholera serums
all individually exerted a decided immunising action with regard to
this powerful vegetable poison. The hope is, therefore, perhaps not
beyond the realm of possibility, that at some future time the
complexity of drugs which now figure in the chemists' pharmacopœia
may be replaced by a few substances the application of which will come
within the means and understanding of all. So far we have not dealt
with the artificial immunisation of an animal from the action of eel
poison, but this apparently offers very little difficulty, and is
accomplished by introducing very small and gradually increasing doses
of eel serum into the system, care being taken to proportion the
quantity given according to the weight and general condition of the
animal to be immunised. A rabbit, for example, treated in the above
manner, subsequently yielded a serum which was proved to possess both
preventive and curative powers in respect to both eel poison, and
viper venom and blood, entitling this so called anti-eel serum to take
its place amongst the anti-toxins, and furnishing yet another instance
of a substance exercising its immunising influence over various
toxins.
This process of gradually acclimatising, as it were, animals to a
particular poison by repeated doses of the same poison, recalls the
old proverb, "Seek your salve where you got your sore," and brings us
to a consideration of some of the primitive antecedents of a practice
which, at the present time, promises to bring about so profound a
revolution in the art of medicine. The modern system of inoculation
has, however, arisen quite without reference to such antecedents,
which latter were not based upon any scientific laws or
considerations, but owed their evolution to local customs and
experience handed down from age to age by tradition, and in many cases
preserved through a simple faith in the superstitions which surrounded
them.
To such a category must be added the curious superstitions indulged in
by the native population of Tunis regarding methods of preventing
hydrophobia in persons bitten by rabid animals. Dr. Loir refers to
these primitive ideas on the art of healing in a report of the work
carried out at the Anti-rabic Institute at Tunis, one of the many
centres for the prevention of rabies by Pasteur's method which have
been established in every quarter of the globe except Great Britain,
the inhabitants of this "great conservative island-Empire," as a
renowned foreign scientist describes it, still preferring a trip to
Paris to countenancing the establishment of an anti-rabic institute in
their own country. The Arab physicians in Tunis have from time
immemorial sought to specially identify themselves with cures for this
disease, which is so prevalent as to be a veritable scourge to the
country. A much-vaunted remedy advocated by the profession consists in
pounding up the charred head of a rabid dog with vinegar, and
administering an emulsion of the same to the patient. The dung of
camels is also highly prized as a remedy, as also the water of certain
wells which the simple faith of the natives has endowed with
supernatural curative properties. But the strangest prescription of
all consists in broth made from lambs a year old, to which is added a
peculiar kind of beetle, but in such a small quantity that the latter
ingredient only equals the weight of a grain of corn. This concoction
is given to the unfortunate patient twenty-three days after he has
been bitten. In the urine, according to the Arabian doctors, seven
small worms should be found which represent the embryos of dogs
engendered by the virus in the human body, and which when once got rid
of the patient recovers!
In the face of such crude traditions upheld with so much tenacity by
the native population, it is surprising that the Tunisian Anti-rabic
Institute has met with such a large measure of support in the shape of
applicants for admission, which, on an average, number over one
hundred annually. The mortality amongst those treated closely
approaches the satisfactory results obtained at the Paris Institute,
where the death-rate amounts to about 0·38 per cent. of the persons
treated.
There is perhaps no more interesting chapter in the history and
literature of medicine than might be compiled by searching out the
early uses of drugs and the primitive application of methods in the
art of healing, and tracing their connection, if possible, with the
practices which are in vogue at the present day. In the matter of
toxins and anti-toxins, or in respect to the modern theories of
preventive medicine, there would appear to be a curious link between
the methods based upon elaborate scientific inquiries and those which
arose through simple experience and expediency.
The idea of a poison, as the old proverb above tells us, being a
corrective for itself is no new idea, for we read how in ancient
times, for example, the Ophiogenes of the Hellespont were renowned for
their immunity to snake poison, and one account of them states
particularly that they fed upon serpents, and that to this diet they
probably owed their reputed magical art in withstanding the action of
serpent venom. Again, a traveller in Egypt, Hasselquist, tells us how
the serpent-charmers there eat serpents, making them into a kind of
broth, and that invariably before starting off to catch these reptiles
they partake of some of it.
In a paper by Mr. T. R. Rao on the Yánádés tribe of the Nellore
district, Madras Presidency, the author mentions that these strange
people have, amongst other characteristics, absolutely no fear in
catching cobras, which they draw out of their holes without any alarm
as to their fangs, and that they appear to protect themselves against
the effects of snake-bites by swallowing the poison-sacs of snakes.
Bruce describes how he saw a serpent-charmer in Cairo who allowed
himself to be bitten by a viper between the forefinger and the thumb,
and made no endeavour whatever to apply remedies, neither did he
exhibit the slightest anxiety as to the consequences. That this was no
trick, and that the viper was really possessed of all its deadly
faculties at the time it bit the man, was proved by the fact that a
pelican subsequently bitten by the same animal died in thirteen
minutes. Bruce also tells of a man who "with his naked hand took a
viper from a number of others lying at the bottom of a tub. He put it
on his head, then in his breast, and tied it about his neck like a
necklace. Next it was made to bite a hen, which died in a few minutes;
and, to complete the experiment, the man took it by the neck, and,
beginning at the tail, ate it as one does a carrot or a stick of
celery, without any seeming repugnance."
A most interesting account of snake-charmers is given by Drummond Hay,
in his book on Western Barbary, in which he relates his experiences
with some of these wonderful individuals belonging to the sect called
Eisowy. Members of this sect, he mentions, frequently handled
scorpions and poisonous reptiles without fear or hesitation, and they
were never attacked by them. He was present at one of their
exhibitions of feats with snakes in which they both allowed themselves
to be bitten and provoked the snake to bite them. The charmer thus
bitten then in his turn ate or chewed the reptile, which, he remarks,
writhing with pain, bit him in the neck and hands till it was actually
destroyed by the Eisowy's teeth.
In South Africa snake poison is actually taken as a protection against
snake-bites, and if we turn to the Lancet of the year 1886, we shall
find a letter from Mr. Alfred Bolton stating that his curiosity had
been aroused by the fact that while in South Africa cattle and horses
frequently died from the effect of snake-bites, the natives themselves
seldom or never appeared to suffer any inconvenience from such
injuries other than would follow any accident which would set up local
inflammation. On inquiry he found that they were in the habit of
extracting the poison gland from the snake immediately it is killed,
squeezing it into their mouths and drinking the secretion, thereby
apparently acquiring absolute immunity from snake-bites. So impressed
was Mr. Bolton by what he observed that he adds: "I can no longer
refuse to believe in the efficacy of the snake virus itself as a
remedy against snake poison."
Savage tribes have learnt from bitter experience how to protect
themselves from snake-bites, and it is well known that they have a
method of inoculation which they employ with success. The Creoles of
Surinam use an ointment as a protection against snake-bites, which is
regarded as highly efficacious. It is reputed to consist principally
of the pounded head of a rattlesnake, which concoction would therefore
include the contents of the venom glands. This is then mixed with the
juices of a certain plant, which addition probably mitigates the
intensity of the venom by acting as a diluent. This substance is
generally applied by making an incision in the wrist or forearm and
rubbing it in, after which individuals thus treated appear to enjoy
security from the venom of snake-bites.
What applies to serpent venom would also appear to hold good in regard
to other poisons, such as that contained in the sting of a bee. This
poison is extraordinarily tenacious of its irritant properties, and,
unlike eel poison, retains its virulence even when exposed to high
temperatures.
An interesting memoir on the immunity of the bee-keeper from the
effects of bee poison was published a short time ago by Dr. Langer in
a German scientific journal. He issued a number of circulars with
questions to be answered, and sent these to more than a hundred
bee-keepers in different parts of the country, with the result that a
hundred and forty-four stated that they were now immune to bee poison,
nine having been fortunately endowed with a natural immunity to this
irritant, whilst only twenty-six out of the whole number applied to
stated that they were still susceptible.
This condition of immunity to bee poison is obtained after a varying
number of stings have been inflicted; in some cases thirty, at the
rate of from three to four a day, are sufficient to ensure freedom
from further discomfort, but the inoculations may have to be prolonged
up to one hundred stings to secure complete immunity.
In experiments carried out on animals this immunity to bee poison has
been also induced by repeated application of the irritant. It was
formerly generally supposed that the irritant nature of a bee's sting
was due to the presence of formic acid; but inasmuch as bee poison can
retain its poisonous character in spite of being submitted to heat,
which would effectually volatilise the formic acid present, this
assumption must be abandoned, and opinion is more inclined now to
regard this irritant substance as partaking of the nature of an
alkaloid.
Before closing this brief review of some of the most recent
discoveries which have been made in the domain of immunity, we must
mention some extremely suggestive and important researches on the
poison of tetanus, or lock-jaw, which have emanated from Dr. Roux's
laboratory at the Institut Pasteur in Paris.
It will perhaps be remembered that Pasteur, when working at
hydrophobia, experienced the greatest difficulty in exciting rabies in
animals with certainty, and that it was only when the fact of its
being a disease which essentially affects the nervous system of the
animal was taken into account that it occurred to him to cultivate the
virus in the medium for which it had seemingly the greatest affinity,
viz. the nervous tissue of an animal; it was only on taking this step
that he succeeded in invariably provoking rabies in the animals under
experiment.
In the case of tetanus we have another disease affecting the
nerve-centres of the body, and although many authentic cases have been
cited in which the treatment with anti-tetanic serum has been entirely
successful, a great many instances have occurred in which it has been
of no avail at all, more especially when the disease has obtained a
firm hold on its victim. Now Dr. Roux has not only been carrying out
experiments to ascertain what is the result of directly attacking, as
Pasteur did in the case of rabies, the nerve-centres of an animal with
the tetanus toxin, but he has also taken another and very important
step further, and has investigated, not only the action of the toxin,
but also that of the anti-toxin on the nerve-centres of an animal
suffering from tetanus.
In describing the cerebral inoculations which he has conducted on
animals, Dr. Roux points out that the operation, in itself, is
attended with no pain or even inconvenience to the animal in question,
that subsequently it eats with its usual appetite, and shows no signs
of discomfort.
First, as regards the infection of an animal with the tetanus virus
introduced directly into the brain, it has been found that very much
smaller quantities produce a fatal result than when subcutaneously
inoculated. Thus, a rabbit which received two cubic centimetres of the
poison under the skin took four days to succumb to tetanus, whilst
one-twentieth of the quantity inoculated into the brain sufficed to
kill another rabbit of the same size in less than twenty hours.
Another very instructive example of this susceptibility of the
nerve-centres for certain poisons is afforded in the case of rats
and the toxin of diphtheria. Rats possess a natural immunity from
this substance, and can successfully withstand a dose of diphtheria
poison introduced under the skin which would infallibly kill several
rabbits. This state of immunity, however, entirely disappears when
the toxin is brought directly in contact with nervous tissue, for
a very small quantity of diphtheria poison—insufficient to cause
under ordinary circumstances even a passing swelling at the seat of
inoculation—will, when introduced into the brain of a rat, kill the
animal.
Again, rabbits are generally credited with possessing high powers of
resisting the action of morphia, a large dose of this substance
introduced subcutaneously producing no result whatever. A cerebral
inoculation, however, of a minute quantity of morphia causes an
immediate reaction, and the animal, after remaining in a more or less
dazed condition for several hours, finally succumbs to this drug. Dr.
Roux is inclined to regard this difference in the susceptibility
exhibited by animals to one and the same poison as being due to a good
deal of the toxin, when subcutaneously introduced, failing to reach
the nerve-centres, it having been destroyed or arrested in the system
before it could attack them.
What is the nature of the subtle forces which may so beneficially
intervene between the toxin and its victim has long been a problem
which has excited the interest and ingenuity of some of the most
brilliant scientific authorities of the day, and it is one which, even
in the hands of men like Metchnikoff, is still awaiting a satisfactory
solution!
The important point was next approached by Dr. Roux as to whether an
animal, successfully trained to withstand large doses of the poison,
as ordinarily introduced, could also resist it when directly
inoculated into the brain. Is, in fact, the undoubted immunity to
tetanus poison which may be possessed by an animal due to the
nerve-centres having become insensible to this substance? The answer
to this question would appear to be in the negative, for animals
artificially protected from tetanus poison introduced under the skin
succumbed to a small dose inoculated direct into the brain, which
would otherwise have not produced even a slight passing tetanic
affection of the limb where the inoculation was made. Immense numbers
of experiments were made under varying conditions, but the result was
fully confirmed, showing that the nerve-centres had not acquired any
immunity to the poison, although the blood serum of the victims to
such cerebral inoculations was proven over and over again to be
endowed with strong protective properties against tetanus poison.
The endeavour was then made to, in Dr. Roux's words, "place the
anti-toxin where the toxin is working," and preserve the vital force
of the nervous tissue. To arrest tetanus by substituting cerebral for
subcutaneous inoculations of the anti-tetanic serum was the next feat
attempted. Several guinea-pigs and rabbits were inoculated
subcutaneously with virulent doses of tetanus poison sufficient to
kill them in about seventy hours; some were subsequently treated with
anti-toxic serum introduced in the ordinary way under the skin, whilst
others were inoculated with from six to seven drops of this protective
serum direct into the brain. The results were extraordinarily
successful. Although but a few drops of the anti-toxin were used for
the cerebral inoculations, the animals survived the otherwise fatal
doses they had received of the toxin; whilst out of seventeen
guinea-pigs which received subcutaneous inoculations of the
anti-toxin only two recovered, and the quantity of the anti-toxin
employed reached as much as from ten to twenty cubic centimetres in
some of the experiments, contrasting in a remarkable manner with the
few drops which sufficed in the case of the cerebral inoculations.
Dr. Roux sums up this splendid result in the following modest words:
"Il ne suffit pas de donner de l'anti-toxine, il faut la mettre au bon
endroit."
The significance and far-reaching application of this most important
discovery cannot easily be overestimated. Hitherto the preparation of
an anti-toxin has been the chief point considered, but Dr. Roux and
his able coadjutor, M. A. Borrel, have shown how great may be the
results which attend its method of administration, and have opened up
an entirely new direction for investigation.
Although the subject of immunity is not, as we have seen, by any means
wholly a latter-day creation, yet its approach and consideration from
a modern point of view, assisted by the resources and equipment
provided by modern scientific methods, justifiably entitles the
nineteenth century to claim it as its own discovery.
However brilliant and successful the labours may be of those who will
follow in the future, subsequent generations will know how to venerate
those great leaders of scientific thought, amongst whom we must rank
Pasteur, to whose genius the world owes so great a debt of gratitude,
and the vast extent of whose labours cannot be adequately measured at
the present day by reason of the restricted scientific horizon which
encircles public opinion in this country.
THE END
PLYMOUTH
WILLIAM BRENDON AND SON
PRINTERS