|
But Pasteur was not content with simply destroying the ferments
of
these diseases, he wished above all to prevent their introduction.
At
the moment when the wort is raised to the boiling-point, when the
germs
of disease are destroyed by the heat, if the cooling of the wort
is
effected in contact with both air and yeast free from exterior
germs,
the beer may be made under conditions of exceptional purity.
Some
brewers, taking for their basis Pasteur's principles, constructed
an
apparatus which enabled them to protect the wort while it was
cooling
from the organisms of the air, and to ferment this wort with a
leaven
as pure as possible. At the Exhibition of Amsterdam there might
be
seen bottles half full, containing a perfectly clear beer, which
had
been tapped from the time of opening of the Exhibition. This was
French
beer, manufactured according to Pasteur's principles, by a
great
brewer of Marseilles, M. Velten. The happy effect of these
studies
is universally recognised. At Copenhagen, M. Jacobsen has had a
bust
of Pasteur, by Paul Dubois, placed in the _salle d'honneur_ of
his
celebrated laboratory.
* * *
* *
In terminating his _Studies on Beer_, Pasteur recalled to mind
the
principles which for twenty years had directed his labours,
the
resources and applications of which appeared to him unlimited.
'The
etiology of contagious diseases,' he wrote with a scientific
certainty
of conviction, 'is on the eve of having unexpected light shed upon
it.'
_VIRULENT
DISEASES._
SPLENIC FEVER
(CHARBON)--SEPTICÆMIA.
'He that thoroughly understands the nature of
ferments and
fermentations,' said the physicist Robert Boyle, 'shall probably
be
much better able than he that ignores them, to give a fair account
of
divers phenomena of certain diseases (as well fevers as others),
which
will perhaps be never properly understood without an insight into
the
doctrine of fermentations.'
At all times, medical theories, more
particularly those which concern
the etiology of virulent diseases, have had
to encounter the opposition
of explanations invented to account for the
phenomena of fermentation.
When Pasteur in 1856 began his labours on these
subjects, the ideas
of Liebig were everywhere revived. Like the ferments, so
the viruses
and processes of disease were considered as the results of
atomic
motions proper to substances in course of molecular change, and able
to
communicate themselves to the diverse constituents of the living
body.
The researches of Pasteur on the part played by microscopic
organisms
in fermentation, changed the course of these ideas. The
ancient
medical theory of parasites and living contagia was revived. A
German
Professor, Dr. Traube, in 1864, put forward, in one of his
clinical
lectures, a new doctrine of the ammoniacal fermentation of
urine.
'For a long period,' he said, 'the mucus of the bladder was
regarded
as the agent of the alkaline decomposition of urine. It was
supposed
that, in consequence of the distension produced by the
retention
of the liquid, the irritated bladder produced a larger quantity
of
mucus, and this mucus was regarded as the ferment which brought
about
the decomposition of urea, by an innate chemical force. This
opinion
(which was that of Liebig) cannot hold its ground in presence of
the
researches of Pasteur. This investigator has demonstrated, in the
most
decisive manner, that alkaline fermentation, like alcoholic and
acetic
fermentation, is produced by living organisms, the pre-existence
of
which in the liquid is the _sine qua non_ of the process.' And
Dr.
Traube, citing some facts which confirmed the doctrine of
Pasteur,
concluded thus: 'Notwithstanding the long retention of the urine,
its
alkaline fermentation is not produced by an increased secretion
of
mucus or of pus; it only begins to develop from the moment when
the
germs of vibrios find access to the bladder from without.
The
opposite doctrines of Liebig and Pasteur are here brought into
clear
juxtaposition; and thus was their mutual and reciprocal influence
established
in dealing with the etiology of one of the most serious
diseases of the
bladder. So far back as 1862, Pasteur, in his memoir
on spontaneous
generation, had announced, contrary to all the notions
then held, that
whenever urine becomes ammoniacal, a little microscopic
fungus is the cause
of this alteration. Later on he established that
in affections of the bladder
ammoniacal urine was never found without
the presence of this fungus; and in
order to show how in these studies
therapeutic application often runs hand in
hand with scientific
discovery, Pasteur, having proved, with his assistant,
M. Joubert,
that boracic acid is antagonistic to the development of the
ammoniacal
ferment, advised Dr. Guyon, Clinical Professor of Urinary Diseases
in
the Faculty of Paris, to combat the dangerous ammoniacal
fermentation
by injection of boracic acid into the bladder. The celebrated
surgeon
hastened to follow this advice, and with the most happy results.
While
attributing to Pasteur the honour of this discovery, M. Guyon, in
one
of his lectures, said:--
'Boracic acid has this immense advantage,
that it can be applied in
large doses--3 to 4 per cent.--without causing the
slightest pain.
It has therefore become, in our practice, the agent
continually and
successfully used for injections. I also have recourse to a
solution
of boracic acid to produce large evacuations after the operation
of
breaking up stones in the bladder (lithotrity). I never omit to
use
this antiseptic agent in operations where breaking up is required,
and
I never wash the bladders of lithotritised patients with any
other substance.
I have also had good results from copiously washing
the bladders and the
wounds of patients on whom lithotomy has been
performed with boracic acid. I
always finish the operation by prolonged
irrigations with a solution of from
3 to 4 per cent.'
It was not only into France and Germany that Pasteur's
ideas
penetrated; in England, surgery borrowed from Pasteur's
researches
important therapeutic applications. In 1865 Dr. Lister began
in
Edinburgh the brilliant series of his triumphs in surgery by
the
application of his antiseptic method, now universally adopted. In
the
month of February 1874 in a letter which does honour to the
sincerity
and modesty of the great English surgeon, he wrote to Pasteur
as
follows:--
'It gives me pleasure to think that you will read with
some interest
what I have written about an organism which you were the first
to
study in your memoir on lactic fermentation. I do not know whether
you
read the 'British Medical Journal;' if so, you will from time to
time
have seen accounts of the antiseptic system which for the last
nine
years I have been trying to bring to perfection. Allow me to take
this
opportunity of sending you my most cordial thanks, for having, by
your
brilliant researches, demonstrated to me the truth of the germ
theory
of putrefaction, thus giving me the only principle which could lead
to
a happy end the antiseptic system.'
Pasteur followed with lively
interest the movement of thought and the
successful applications to which his
labours had given rise. It was
a realisation of the hopes he had ventured to
entertain. Already,
in 1860, he expressed the wish that he might be able to
carry his
researches far enough to prepare the way for a profound study of
the
origin of diseases. And, as he gradually advanced in the discovery
of
living ferments, he hoped more and more to arrive at the knowledge
of
the causes of contagious diseases.
Nevertheless, he hesitated long
before definitely engaging himself in
this direction. 'I am neither doctor
nor surgeon,' he used to repeat
with modest self-distrust. But the moment
came when, notwithstanding
all his scruples, he could no longer be content
himself to play the
part of a simple spectator of the labours started by his
studies on
fermentation, on spontaneous generation, and on the diseases of
wines
and beer. The hopes to which his methods gave rise, the eulogies
of
which they were the object, obliged him to go forward. In February
1876
Tyndall wrote to him thus:--
'In taking up your researches relating to
infusorial organisms, I have
had occasion to refresh my memory of your
labours; they have revived
in me all the admiration which I felt on first
reading them. It is my
intention to follow up these researches until I shall
have dissipated
every doubt that has been raised as to the unassailable
exactitude of
your conclusions.
'For the first time in the history of
science we are able to entertain
the sure and certain hope that, in relation
to epidemic diseases,
medicine will soon be delivered from empiricism, and
placed upon a
real scientific basis. When this great day shall come, humanity
will
recognise that it is to you the greatest part of its gratitude is
due.'
Pasteur approached the study of viruses by seeking to penetrate
into
all the causes of the terrible malady called splenic fever
(_charbon_,
Germ. _Milzbrand_). Each year this disease decimates the flocks
not
only in France but in Spain, in Italy, in Russia, where it is
called
the Siberian plague, and in Egypt, where it is supposed to date
back
to the ten plagues of Moses. Hungary and Brazil pay it a
formidable
yearly tribute; and to come back to France, the losses have
amounted
in certain years to from fifteen to twenty millions of francs.
For
centuries the cause of this pest has eluded all research; and
further,
as the malady did not always exhibit the same symptoms, but
varied
according to the kind of animal that was smitten by it, the disease
was
supposed to vary with the species that was attacked by it. The
splenic
fever of the horse was distinct from that of the cow; the
splenic
fever of horse and cow were again different from that of the sheep.
In
the latter, splenic fever was called _sang-de-rate_; in the cow, it
was
_maladie du sang_; in the horse, splenic fever; in man,
malignant
pustule.
It was not until 1850 that trustworthy data were
first collected
regarding the nature of the malady, its identity with and
difference
from other maladies. From 1849 to 1852 a commission of the
Medical
Association of Eure-et-Loir made a great number of
inoculations,
applied other tests, and proved that the splenic fever of the
sheep
is communicable to other sheep, to the horse, to the cow, and to
the
rabbit; that the splenic fever of the horse is communicable to
the horse and
to the sheep; that the splenic fever of the cow is
communicable to the sheep,
to the horse, and to the rabbit. As for the
malignant pustule in man, no
doubt remained that it must arise from the
same cause as splenic fever in
animals. What class of men is it that
the malignant pustule most frequently
attacks? Shepherds, cowherds,
cattle breeders, farm servants, dealers in
hides, tanners, wool
cleaners, knackers, butchers--all who derive their
living from domestic
animals. In handling contaminated subjects the slightest
excoriation
or scratch of the skin is sufficient to allow the virus to enter.
When
others besides the class that we have named become infected, it
is
because they live in the neighbourhood of herds smitten with
splenic
fever. There are also certain flies which transport the virus.
Suppose
one of these flies to have sucked the blood of an animal which has
died
of splenic fever, a person stung by that fly is forthwith
inoculated
with the virus.
At the very time (1850) when these first
experiments were being made
by the Medical Association of the Eure-et-Loir,
Dr. Rayer, giving
an account in the 'Bulletin de la Societe de Biologie de
Paris' of
the researches he had made, with his colleague, Dr. Davaine, on
the
contagion of splenic fever, wrote:--'In the blood are found
little
thread-like bodies about twice the length of a blood corpuscle.
These
little bodies exhibit no spontaneous motion.'
This is the date
of the first observation on the presence of little
parasitic bodies in
splenic fever, but, strange to say, no attention
was paid to these minute
filaments. Rayer and Davaine also paid no
attention to them. This
indifference lasted for thirteen years; it
would have lasted longer still, if
the parasitic origin of communicable
diseases had not been brought before the
mind by each new publication
of Pasteur's. From 1857 to 1860 it will be
remembered that he had
demonstrated lactic fermentation, like alcoholic
fermentation, to
be the work of a living ferment; in 1861 he had discovered
that the
agent of butyric fermentation consisted of little moving
thread-like
bodies, of dimensions similar to those of the filaments
discovered by
Davaine and Rayer in the blood of splenic fever patients; in
1861 he
had announced that no ammoniacal urine existed without the
presence
of a microscopic organism; in 1863 he had established that the
bodies
of animals in full health are sealed against the introduction of
the
germs of microscopic organisms; that blood drawn with
sufficient
precaution from the veins and the arteries, and urine taken
direct
from the bladder, could be exposed to the contact of pure air
without
putrefaction, and without the appearance of living
thread-like
organisms of any kind whatever, mobile or immobile. It was all
these
facts which in 1863 brought back the attention of Davaine, as
he
himself has acknowledged, to the observation which he had made in
1850.
'M. Pasteur,' said M. Davaine in a communication made to the
Academy
of Sciences, 'published some time ago a remarkable memoir on
butyric
fermentation, which consists of little cylindrical rods,
possessing
all the characteristics of vibrios or of bacteria. The
thread-like
corpuscles which in 1850 I saw in the blood of sheep attacked
with
_sang-de-rate_, having a great analogy with these vibrios, I was
led
to examine whether filiform corpuscles, analogous to or of the
same
kind as those which determined the butyric fermentation, would
not,
if introduced into the blood of an animal, equally act the part of
a
ferment. Thus would be easily explained the alteration, and the
rapid
infection of the mass of the blood, in an animal which had
received
accidentally or experimentally into its veins a certain number of
these
bacteria--that is to say, of this ferment.'
But two summers
passed before M. Davaine was able to procure a sheep
affected with the
_sang-de-rate_. It was only in 1863 that he first
recognised the constant
presence of a parasite, in the blood of sheep
and rabbits which had died from
successive inoculations with blood
taken after death or in the last hours of
life. He further proved that
the inoculated animal, in the blood of which no
parasites were as yet
visible with the microscope, had every appearance of
health, and that
in these conditions the blood could not communicate splenic
fever.
'In the present state of science,' Davaine concluded, 'no one
would
think of going beyond these corpuscles to seek for the agent of
the
contagion. This agent is visible, palpable; it is an organised
being,
endowed with life, which is developed and propagated in the same
manner
as other living beings. By its presence, and its rapid
multiplication
in the blood, it without doubt produces in the constitution of
this
liquid, after the manner of ferments, modifications which
speedily
destroy the infected animal.' 'For a long time,' he
repeated,
'physicians and naturalists have admitted theoretically that
contagious
diseases, serious epidemic fevers, the plague, &c., are caused
by
invisible animalculæ, or by ferments, but I do not know that
these
views have ever been confirmed by any positive observations.'
A
few months after the publication of the results obtained by Davaine,
two
professors of Val-de-Grace, MM. Jaillard and Leplat, sought to
refute the
preceding conclusions. After having inoculated rabbits and
dogs with various
putrefying liquids filled with vibrios, they could
not cause the death of
these animals. To bring about this result it was
necessary to introduce into
the blood of these dogs and rabbits several
cubic centimeters of very putrid
liquid. Again in this case, which only
added another example to the
experiments of Gaspard and Magendie upon
the action of putrid liquids, they
failed to generate any virulence in
the blood. Davaine had no difficulty in
showing that MM. Jaillard and
Leplat's experiments were made under conditions
totally different from
his; that he, Davaine, had not made use of the vibrios
or bacteria of
unselected infusions, but of bacteria which had been found in
the blood
of sheep which had died from _sang-de-rate_.
Jaillard and
Leplat returned to the charge, and this time with entirely
new and unexpected
experiments. They inoculated some rabbits, as
Davaine desired, with the blood
of a cow which had died of splenic
fever. The rabbits died rapidly, but
without showing before or after
their death the least trace of bacteria.
Other rabbits, inoculated with
the blood of the first, perished in the same
manner, but it was still
impossible to discover any parasite in their blood.
MM. Jaillard and
Leplat offered Davaine some drops of this blood. Davaine,
taking up the
experiments of his opponents, confirmed the exactitude of the
facts
they had announced, but concluded by saying that these two
professors
had not employed true splenic fever blood, but the blood of a
new
disease, unknown up to that time, which Davaine proposed to call
the
cow disease.
'The blood which we used,' replied MM. Jaillard and
Leplat, 'was
furnished to us by the director of the knacker's establishment
of
Sours, near Chartres, and this director is undeniably competent as
to
the knowledge of splenic fever.'
Full of sincerity and conviction,
MM. Jaillard and Leplat recommenced
their experiments, using this time the
blood of a sheep which had
died of splenic fever, and which M. Boutet, the
most experienced
veterinary surgeon of the town of Chartres, had procured for
them.
Their results were the same as those obtained with the blood of
the
cow. Notwithstanding the replies of Davaine, which, however,
added
nothing to the facts already adduced on one side or the other, it
was
difficult to pronounce decidedly in such a debate. Unprejudiced
minds
received from these important discussions the impression that
Jaillard
and Leplat, in producing facts the exactitude of which were admitted
by
Dr. Davaine himself, had given a blow to the assertions of the
latter,
and that the subject required, in every case, new experimental
studies.
In 1876, a German physician, Dr. Koch, took up the question.
He
confirmed the opinion of Davaine, but without in the least
producing
conviction, since he threw no light upon the facts adduced by
MM.
Jaillard and Leplat, of which, indeed, he did not even deign to
speak.
At the very same moment when the memoir of Koch appeared in
Germany,
the eminent physician Paul Bert came forward to corroborate the
opinion
of Jaillard and Leplat.
'I can,' said M. Paul Bert, 'destroy
the bacteria in a drop of blood
by compressed oxygen, inoculate with what
remains, and reproduce the
disease and death without any appearance of
bacteria. Therefore, the
bacteria are neither the cause nor the necessary
effect of the disease
of splenic fever. It is due to a virus.'
This
was indeed the opinion of Jaillard and Leplat. Pasteur, in
obedience to the
necessity he felt to get at the fundamental truth of
things, and also in his
eager desire to discover some decisive proofs
as to the etiology of this
terrible disease, resolved in his turn to
attack the subject.
Dr. Koch
had stated in his memoir that the little filiform bodies,
seen for the first
time by Davaine in 1850, had two modes of
reproduction--one by fission, which
Davaine had observed, and another
by bright corpuscles or spores. The
existence of this latter mode of
reproduction Pasteur had already discovered
in 1865, reasserted and
illustrated in 1870, as being common to the filaments
of the butyric
ferment, and to all the ferments of putrefaction. Was Dr. Koch
ignorant
of this important fact, or did he prefer by keeping silence to
reserve
to himself the advantage of apparent priority?
In order to
solve the first difficulty which presented itself to
his mind--that is to
say, the question as to whether splenic fever
was to be attributed to a
substance, solid or liquid, associated or
not associated with the filaments
discovered by Davaine, or whether
it depended exclusively upon the presence
and the life of these
filaments--Pasteur had recourse to the methods which
for twenty
years had served him as guides in his studies on the organisms
of
fermentation. These methods, delicate as they are, are very
simple.
When he wished, for example, to demonstrate that the
microbe-ferment
of the butyric fermentation was the very agent of
decomposition, he
prepared an artificial liquid formed of phosphates of
potash, of
magnesia, and of sulphate of ammonia, added to the solution of
the
fermentable matter, and in this medium he caused the
microbe-ferments
to be sown in a pure state. The microbe multiplied, and
provoked
fermentation. From this liquid he could pass to a second or
third
fermentable liquid composed in the same manner, and so on
in
succession. The butyric fermentation appeared successively in
each.
Since the year 1857 this method was supreme. In this
particular
research on the disease of splenic fever Pasteur proposed to
isolate
the microbe of the infected blood, to cultivate it in a state of
purity
in artificial liquids, and then to come back to the examination
of
its action on animals. But as, since his attack of paralysis in
1868,
Pasteur had not recovered the use of his left hand, and
consequently
found it impossible to carry on a long series of experiments
alone, he
was obliged to seek for a courageous and devoted assistant. He
found
one in a former pupil of his at the Ecole Normale, M. Joubert,
now
Professor of Physics at the College Rollin. If M. Joubert incurred
the
danger of these experiments on splenic fever, he also shared with
Pasteur, in
the Comptes-rendus of the Academy of Sciences, the honour
of the researches
and the triumph of the discoveries.
On April 30, 1877, Pasteur read to
the Academy of Sciences, in his own
name and in that of his fellow-worker, a
note in which he demonstrated,
this time in a completely unanswerable manner,
that the bacilli called
bacteria, bacterides, filaments, rods, in a word the
bacilli discovered
by Davaine and Rayer in 1850, constituted the only agent
of the malady.
A little drop of splenic fever blood, sown in urine or in
the water of
yeast, previously sterilised--that is to say, rendered
_un_putrescible
by contact with air free from all suspended germs--produces
in a few
hours myriads of bacilli or of bacteria. A little drop of this
first
cultivation sown in a second flask containing the same liquid as
the
first and prepared with the same precautions as to sterility
and
purity, shows itself no less fertile. Finally, after ten or
twenty
similar cultures the parasite is evidently freed from the
substances
which the initial drop of blood might carry with it; yet, if a
very
small quantity of the last culture is injected under the skin of
a
rabbit or a sheep, it kills them in two or three days at most, with
all
the clinical symptoms of natural splenic fever.
It might be
objected that the parasite was associated in the
cultivating liquid with some
dissolved substance that it had
produced during its life and which acted as a
poison. Pasteur
accordingly transported some cultivating tubes into the
cellars of
the Observatory, where a temperature absolutely constant
reigned,
a circumstance which permits of the deposit of all the
parasitic
filaments at the bottom of the tubes. Inoculating afterwards both
with
the clear upper liquid and with the deposit at the bottom, he
found
that the latter alone produced disease and death. It is, then,
the
bacteria which cause splenic fever. The proof was given and no
further
doubt
remained.
I.
Yes, splenic
fever is no doubt produced by bacteria just as itch is
produced by acaries
and trichinosis by trichinæ. The only difference
is that the parasite of
splenic fever can only be seen by means of a
rather powerful microscope.
Here, then, is a disease in the highest
degree virulent, due in its first
cause to the _infinitely little_.
Pasteur laid hold of and isolated this
terrible virus. It was in a
microscopic parasite, and in it alone, that the
virulence of splenic
fever resided. A great scientific fact had been gained.
A virus might
consist not of amorphous matter, but of microscopic beings.
The
virulence was due to their life.
Liebig, and all the chemists and
doctors who had accepted and
maintained his doctrine, totally repudiated all
vital action in
fermentation as well as in contagious and infectious
diseases.
Dominated by their hypotheses, they allowed themselves to be
deceived
by false assimilations to facts of a purely chemical kind,
which
appeared to them to be connected with the phenomena of fermentation
and
virulence.
Liebig wrote, 'By the contact of the virus of small-pox
the blood
undergoes an alteration, in consequence of which its elements
reproduce
the virus, and this metamorphosis is not arrested until after
the
complete transformation of all the globules capable of
decomposition.'
This vague theory of viruses was forced to give way
before the
multiplied experiments of Pasteur. But before occupying himself
with
further discoveries, although it had been irrefutably proved that
the
microscopic parasite was the true contagium, it was necessary to
throw
light upon the facts, mainly accurate, which had been announced
by
Jaillard and Leplat, and to bring them into harmony with the facts,
not
less certain, which had been advanced by Davaine. The rabbits
which
Jaillard and Leplat had inoculated with a drop of the blood of a cow
or
sheep stricken with splenic fever, died rapidly, and the blood of
these
rabbits was shown to be also virulent. It was sufficient to
inoculate
other rabbits with a very minute quantity to cause their death.
But
Jaillard and Leplat affirmed that the examination of that blood did
not
reveal the existence of any microscopic organisms. Paul Bert, on
his
part, had succeeded in destroying the bacteria by compressed
oxygen,
and yet the virulence had continued.
Were there, then, two
kinds of virus? What escape was there from this
darkness? A new light
suddenly began to dawn. Pasteur had already some
years previously
demonstrated that the animal body is sealed against
the introduction of lower
organisms--that in the blood, the urine, the
muscles, the liver, the spleen,
the kidneys, the brain, the marrow,
and the nerves, in a normal state, no
germ is found, or particle of
any kind, known or unknown, which could be
transformed into bacteria,
vibrios, monads, or microbes. The intestinal canal
alone is filled
with matters associated with a host of germs and living
products in
process of development, and in divers states of physiological
action.
Not only is its temperature favourable to the life of
infusoria,
but it receives incessantly matters charged with the germs of
these
microscopic organisms. To the upper portions of the canal the
air
still has access, so that even in the stomach aerobic microbes may
be
found, but in the lower parts of the intestinal canal oxygen is
absent,
and only anaerobic microbes can be developed there. Although the
life
exerted in the mucous surface of the intestines opposes itself to
the
passage of those little organisms into the interior of the body,
this
ceases to be the case after death. There is no longer any obstacle
to
arrest or prevent them from acting according to the respective laws
of
their evolution and of the decomposing influence which belongs to
them.
It is by anaerobic organisms, in fact, that the putrefaction of
dead
bodies is begun. They penetrate into the organs and into the blood
as
soon as this liquid is deprived of oxygen; and it is not long
before
this happens, the oxygen fixed in the globules being soon consumed.
In
the body of an animal which has died of splenic fever, putrefaction
is
still more rapid, because, through the action of the disease, the
blood
is already in a great degree deprived of oxygen at the time of
death.
Nothing is more striking than the rapid inflation and almost
immediate
putrefaction of animals which have succumbed to splenic fever. Of
all
the vibrios ready to pass from the intestinal canal into the
network
of mesenteric veins which surround the canal those which seem to
take
the foremost place are the septic vibrios. These specially merit
the
name of vibrios of putrefaction, from the very putrid gases
which
result from their action upon nitrogenous and sulphurous
substances.
The others diffuse themselves more or less slowly in the blood,
but
the septic vibrio takes almost immediate possession of the dead
body.
Already after twelve or fifteen hours, the blood of the
diseased
animal, which at the time of its death and during the first
following
hours contained exclusively the parasite of splenic fever,
harbours
at one and the same time both the bacillus of splenic fever and
the
septic vibrio. Then occur the very curious effects arising from
the
anaerobic nature of these vibrios, and their opposition to the
bacillus
of splenic fever, which is exclusively aerobic. Diffused in
blood
deprived of oxygen gas, the splenic bacillus soon perishes. In
its
place are to be found amorphous granulations deprived of all
virulence.
The septic anaerobic vibrio, on the contrary, finds itself after
death
in the most favourable conditions for its life and development.
Not
only does it penetrate into the blood by the deep mesenteric veins,
but
also into the liquids which ooze out of the abdomen and
muscles.
From the antagonism existing between the physiological
peculiarities of
the splenic bacilli and the septic vibrio, it results that
if, in order
to inoculate an animal capable of contracting the fever, a drop
of
blood be taken from one that has just died of it, and if the
operation
is performed during the first few hours after death, it is certain
to
communicate to that animal splenic fever, and splenic fever only.
If,
on the other hand, the operation is performed after a greater
number
of hours--say, between twelve and twenty, according to the season
of
the year--then the inoculation of the blood will communicate, at
one
and the same time, splenic fever and septicæmia--acute septicæmia,
as
it may be called, because of the rapid inflammatory disorders that
the
septic vibrio causes in the inoculated animal. The two diseases may
be
developed simultaneously in the inoculated animal, but generally
one
precedes the other. The septic contagium is the quickest in its
action;
it generally causes death before the splenic fever has had time
to
develop itself and to produce appreciable effects.
We are now in a
position to explain all the contradictory results
obtained by MM. Jaillard
and Leplat on one side, and by Davaine on
the other. In a country which
splenic fever had made famous, the
Departement d'Eure-et-Loir, they had asked
for a little splenic fever
blood. Now, what takes place in a farm where an
animal has died of
this disease? The dead body is thrown upon a dungheap, or
into some
shed or stall, until the knacker's cart happens to pass. The
knacker
takes his own time, and the body often remains there twenty-four
or
forty-eight hours. The blood taken from this animal is more or
less
invaded by putrefaction, and vibrios are mingled with the bacteria
of
splenic fever, the development of which is arrested the moment
the
animal dies. In short, it may be easily conceived that an
experimenter
writing to Chartres to procure some splenic fever blood might,
without
his knowledge, or the knowledge of his correspondent, receive blood
at
the same time both splenic and septic. And this septicæmia is
sometimes
manifold, for a special septicæmia may be said to correspond to
every
sort of vibrio of putrefaction.
Such were the circumstances
which, without their being aware of
it, accompanied Jaillard and Leplat's
researches upon splenic fever
infection. This impression will be derived from
reading the successive
notes laid by them before the Academy of Sciences. The
blood of the cow
which had died of splenic fever, sent from the knacker's
establishment
of Sours, and the blood of the sheep sent by M. Boutet, must
both have
been taken from the bodies of animals which had been dead a
sufficient
number of hours to render their blood both splenic and septic; and
it
was septicæmia, so prompt in its action, that had killed the rabbits
of
Jaillard and Leplat. As the examination of the blood of these
animals showed
no signs of bacteria, they had concluded, with great
apparent truth, that the
inoculation of splenic blood could cause death
without any appearance of
these organisms, even while the blood used
for inoculation was full of them.
The presence of _septic_ vibrios in
the blood of the inoculated rabbits
escaped their notice. When Davaine
replied that Jaillard and Leplat had not
worked with pure splenic blood
he had hit upon the truth, but he could not
give plausible reasons for
it. The contest was carried on by experiments in
which, on both sides,
truth and error were closely blended.
The work
of M. Paul Bert, at the close of 1876, was surrounded with
circumstances no
less complex. To thoroughly understand them we must
call to mind Pasteur's
discovery as to the mode of reproducing the
anaerobic germs of putrefaction.
These vibrios reproduce themselves
by spores. In the vibrio of acute
septicæmia this is the mode of
generation. Short or long jointed filaments
show themselves studded
with brilliant points, which are precisely the spores
of which we
speak. Experience proves that these spores resist perfectly
the
poisonous action of compressed oxygen. Inoculating an animal with
blood
which is at the same time septic and splenic, after the blood has
been
compressed, the septic germs, remaining alive, produce death,
although
neither bacteria nor filaments may be perceptible in its blood
at
the moment of death. It was likewise from Chartres that M. Paul
Bert
obtained his supply of splenic fever blood. The blood he had
received
was without doubt not only splenic but also septic. The filaments
of
bacteria and the filaments of septic vibrios had perished under
the
influence of the compressed oxygen; but the spores were there, and
the
great pressure of oxygen gas had not affected them. The new
contagium
which had appeared, and which had killed the inoculated animals,
was
due to these spores.
As regards the proof that this virulence in
the blood of the body of
an animal which has died of splenic fever is really
the effect of
the septic vibrio, Pasteur, assisted by Joubert and a new
assistant,
M. Chamberland, has given that proof, as he did in the case of
the
bacterium of splenic fever, by resorting to the method of
successive
cultivations in an artificial medium. These cultivations, however,
of
the septic vibrio require very special precautions and conditions.
They
should be carried on in as perfect a vacuum as it is possible
to obtain, or
in contact with carbonic acid gas without the presence
of air. In contact
with air the cultivations of septic vibrios would
prove sterile, because the
vibrio is exclusively anaerobic and air
kills it. If a spore of this organism
could germinate in contact with
the air, the product of the germination would
be at once arrested and
would perish by the action of the oxygen. It is
exactly the contrary
with the bacilli of splenic fever, which prove sterile
in a vacuum or
in presence of carbonic acid gas. If one of the spores of the
splenic
fever bacillus (for it also produces spores) could germinate,
the
product of the germination, deprived of free oxygen, would at
once
perish. And, to mention in passing a very ingenious experiment
of
Pasteur's, we thus obtain a means of separating by culture the
bacillus
of splenic fever from the septic vibrio when they are
temporarily
associated together. If this mixture of pathogenic organisms
is
cultivated in contact with the air, the bacilli of splenic fever
alone
will be developed. If this same mixture is cultivated without
air,
either in a vacuum or in carbonic acid gas, the septic vibrio
alone
will be developed. This device of culture is one of the best which
can
be employed to demonstrate that the blood of a body dead from
splenic
fever possesses immediately after death a single contagium, that
of
splenic fever, and that twenty-four hours after death, on the
contrary,
there are two contagia, that of splenic fever and that of
septicæmia.
* * * *
*
Some months ago a very hot discussion arose between Pasteur and
a
commission formed principally of professors of the veterinary school
in
Turin, regarding the facts above mentioned. One experiment, in
the success of
which Pasteur was extremely interested, had been made
at this school. Instead
of employing pure splenic fever blood, free
from all contagium, the Italian
professors, whether from ignorance
of the preceding facts or from
inadvertence, employed the blood of
a diseased sheep, which, from their own
showing, had been dead more
than twenty-four hours. Pasteur immediately
wrote, pointing out that
the commission had done wrong in using blood which
must have been at
the same time splenic and septic. The Turin professors grew
angry,
and affirmed that this assertion of Pasteur's was incorrect;
that
this sheep's blood had been studied with care, and that no
filaments
had been found in it except those of splenic fever; and it
would,
moreover, be marvellous, they added ironically, that Pasteur
from
the depths of his laboratory in Paris should be able to assert
that
this blood was mixed with septic poison, whilst they, good
observers,
armed with a microscope, had had this sheep's blood under their
eyes.
Pasteur contented himself with replying that his assertion
rested
upon a principle, and that he was perfectly able, without having
seen
the blood of the sheep, to affirm that under the conditions in
which
it had been collected that blood was septic. A public
correspondence
ensued, but no understanding could be come to. Pasteur then
offered to
go himself to Turin, in order to demonstrate upon as many bodies
of
sheep dead of splenic fever as they would like to give him, that
the
blood of these dead bodies--at the end of twenty-four hours if in
the
month of March, and in twelve or fifteen hours if in the month of
June,
would be found to be both splenic and septic. Pasteur also
proposed,
by appropriate cultures, to withdraw at pleasure the splenic
fever
poison or the septic poison, or the two together, at the choice of
the
Italians. The Italians, however, shrank from Pasteur's proposal to
pay
them a visit in order to convince them of their error.
The
clearness and certainty of Pasteur's assertions are celebrated, but
what
gives such authority to all that he advances is, as M. Paul Bert
once said,
that Pasteur's boldness of assertion is only equalled by his
diffidence when
he has not experiment to back him up. He never fights
except on ground with
which he has made himself familiar, but then he
fights with such resolution,
and sometimes with such impetuosity, that
one might say to his adversary,
whoever he be, 'Je vous plains de
tomber dans ses mains
redoutables.'
'Take care!' said a member of the Academy of Sciences to a
member of
the Academy of Medicine, who a short time after the incident
just
related was proposing scientifically to 'strangle' Pasteur, 'take
care!
Pasteur is never mistaken.'
One day, in 1879, a professor
attached to a faculty of medicine in
one of the provinces announced to the
Academy of Sciences that he had
found, in the blood of a woman who had died
in a hospital after two
weeks' illness from severe puerperal fever, a
considerable number of
motionless filaments, simple or jointed, transparent,
straight, or
bent, which belonged to the genus Leptothrix. Engaged in studies
on
puerperal fever, and having never met with a fact of this kind in
his
researches, Pasteur wrote at once to this professor to ask him for
a
specimen of the infected blood. The blood arrived at the laboratory,
and
some days after Pasteur wrote to the doctor, 'Your leptothrix is
nothing else
than the bacterium of splenic fever.'
This answer perplexed the doctor
very much. He wrote to Pasteur that he
did not dispute the affirmation, but
that he proposed to control it;
that if he found he had been in error he
would publish it.
Pasteur offered to send him guinea-pigs which had been
inoculated with
splenic fever. 'You will receive them still living; they will
die under
your eyes. You will make the autopsy and you will yourself
recognise
your leptothrix.' The doctor accepted the test. Pasteur
inoculated
three guinea-pigs, had them placed in a cage and sent by rail to
the
professor. They arrived the following morning and died
twenty-four
hours afterwards under the doctor's own eyes. The first had
been
inoculated with the infectious blood of the dead woman, the second
with
the bacterium of splenic fever blood from Chartres, the third with
the
blood of a cow which had died of splenic fever in the Jura. At
the
autopsy it was impossible to discover the slightest difference in
the
blood of the three animals. Not only the blood but the internal
organs,
and especially the spleen, were in exactly the same
condition.
Then, in the most honourable manner, the doctor hastened to
state, in a
communication to the Academy of Sciences, that he regretted
doubly not
having known about splenic fever the year before, as he might have
been
able, on the one hand, to diagnose the formidable complication
which
had manifested itself in the woman who died on April 4, 1878, and,
on
the other hand, to have traced out the mode of contamination which
now
eluded him. He had, however, succeeded in learning a few details
regarding
the unhappy woman. She was a charwoman, and lived in a little
room adjoining
the stables of a horse-dealer. Through these stables a
large number of horses
passed continually.
But to return to our septic vibrios. If air destroys
them, if their
culture is impossible in contact with air, how can septicæmia
exist,
since air is everywhere present? How can blood exposed to the
air
become septic from particles of dust on the surface of objects or
which
the air holds in suspension? Where can the septic germs be formed?
The
objection seems a serious one, but it disappears before a very
simple
experiment. Take some serum from the abdomen of a guinea-pig which
has
died of acute septicæmia. It will be found full of septic vibrios
in
process of generation by fission. Let this liquid be then exposed
to
the contact of air, with the precaution of giving a certain depth
to
the liquid--say, a centimeter of depth. In some hours, if examined
with
the microscope, the following curious spectacle will be witnessed:
In
the upper layers the oxygen of the air is absorbed, which is
manifested
by the already changed colour of the liquid. There the
filamentous
vibrio dies, and disappears under the form of fine
amorphous
granulations deprived of virulence. At the bottom of this layer of
one
centimeter in thickness, on the contrary, the vibrios, protected
from
the approach of oxygen by those of their own kind which have
perished
above them, continue to multiply by fission until by degrees they
pass
into the state of spores; so that instead of moving threads of
all
dimensions, the length of which sometimes even extends beyond
the
field of the microscope, nothing is now seen but a dust of
brilliant
isolated specks, upon which the oxygen of the air has no action.
It
is thus that a dust of septic germs can be formed even in contact
with
air. And thus it becomes possible to understand how anaerobic
organisms may
be sown in putrescible liquids by the dust suspended in
the atmosphere. Thus
also may be explained the permanence of putrid
diseases, even of those which
are caused by anaerobic microbes, that
cannot live in the atmosphere and
which escape destruction by becoming
spores.
By means of these
experiments, as unexpected as they were conclusive,
Pasteur had demonstrated
that Jaillard and Leplat had not really
inoculated their rabbits with an
amorphous virus, liquid or solid, but
with a virus constituted of a living
microscopic organism--in other
words, with a true ferment. By the side of the
parasite of splenic
fever we have thus a fresh example of a living animated
virus, with
germs forming dust. And the extraordinary thing is that among
the
microbes of special maladies--which they produce by penetrating
and
multiplying in the bodies of animals--are to be found aerobies
like
the bacilli of splenic fever, and anaerobies like the vibrios of
acute
septicæmia.
II.
In
these two virulent maladies, then, splenic fever and septicæmia,
the
researches of Pasteur had clearly established the parasitic theory.
A
grand and novel opening was made for future studies on the origin
of
diseases. Yet, judging from the surprising differences which
separate
septicæmia and splenic fever, we can foresee that should the
future,
copying the past, in regard to this and still more recent
discoveries,
have in store, as it no doubt has, the knowledge of new microbes
of
disease, the specific properties of these microscopic organisms
will
demand, for each new exploration, ceaselessly repeated efforts,
not
only to make the existence of these organisms evident, but also
to
furnish decisive proofs of their morbific power. But the question
which
may be considered as already solved is the non-spontaneity of
these
infectious microbes. By what is called spontaneous disease
is meant parasitic
disease. But in the present state of science
spontaneous disease has no more
existence than spontaneous generation.
Such aphorisms, however, are not
allowed to pass without occasional
contradictions, all the more vehement from
their rarity. At the
International Medical Congress held in London, August
1881, Dr.
Bastian, who practises in one of the principal hospitals of
London,
declared that though he was unable to deny the existence of
parasitic
diseases, yet, in his opinion, the microbes were the effect and not
the
cause of these diseases.
'Is it possible,' cried Pasteur, who was
present at the meeting, 'that
at this day such a scientific heresy should be
held? My answer to Dr.
Bastian will be short. Take the limb of an animal and
crush it in a
mortar; let there be diffused in this limb, around these
crushed bones,
as much blood, or any other normal or abnormal liquid as you
please.
Take care only that the skin of the limb is neither torn nor laid
open,
and I defy you to exhibit on the following day, or during all the
time
the malady lasts, the least microscopic organism in the humours of
this
limb.'
After the example of Liebig in 1870, Dr. Bastian did not
accept the
challenge.
But if a disease like splenic fever is carried
by a microbe, this
microbe is under the influence of the medium in which it
finds itself.
It does not develop everywhere. Easily inoculable and fatal to
the
ox, the sheep, the rabbit, and the guinea pig, splenic fever is
very
rare in the dog and in the pig. These must be inoculated several
times
before they contract the disease, and even then it is not
always
possible to produce it. Again, there are some creatures which are
never
assailable by it. It can never be taken by fowls. In vain they
are
inoculated with a considerable quantity of splenic blood; it has
no
effect upon them. This invulnerability had very much struck Pasteur
and
his two assistants, Joubert and Chamberland. What was it in the
body of a
fowl that enabled it to thus resist inoculations of which
the most
infinitesimal quantity sufficed to kill an ox? They proved
by a series of
experiments that the microbe of splenic fever does not
develop when subjected
to a temperature of 44° Centigrade. Now, the
temperature of birds being
between 41 and 42 degrees, may it not be,
said Pasteur, that the fowls are
protected from the disease because
their blood is too warm--not far removed
from the temperature at which
the splenic fever organism can no longer be
cultivated? Might not the
vital resistance encountered in the living fowl
suffice to bridge over
the small gap between 41-42, and 44-45 degrees? For we
must always
allow for a certain resistance in all living creatures to disease
and
death. No doubt, life to a parasite in the body of an animal would
not
be as easy as in a cultivating liquid contained in a glass vessel.
If
the inoculating microbe is aerobic, it can only be cultivated in
blood
by taking away the oxygen from the globules, which retain it with
a
certain force for their own life. Nothing was more legitimate than
to
suppose that the globules of the blood of the fowl had such an
avidity
for oxygen that the filaments of the splenic parasite were deprived
of
it, and that their multiplication was thus rendered impossible.
This
idea conducted Pasteur and his assistants to new researches. 'If
the
blood of a fowl was cooled,' they asked, 'could not the splenic
fever
parasite live in this blood?'
The experiment was made. A hen was
taken, and, after inoculating it
with splenic fever blood, it was placed with
its feet in water at 25
degrees. The temperature of the blood of the hen went
down to 37 or 38
degrees. At the end of twenty-four hours the hen was dead,
and all its
blood was filled with splenic fever bacteria.
But if it
was possible to render a fowl assailable by splenic fever
simply by lowering
its temperature, is it not also possible to restore
to health a fowl so
inoculated by warming it up again? A hen was
inoculated, subjected, like the
first, to the cold-water treatment, and
when it became evident that the fever
was at its height it was taken
out of the water, wrapped carefully in cotton
wool, and placed in an
oven at a temperature of 35 degrees. Little by little
its strength
returned; it shook itself, settled itself again, and in a few
hours
was fully restored to health. The microbe had disappeared. Hens
killed
after having been thus saved, no longer showed the slightest trace
of
splenic organisms.
How great is the light which these facts throw
upon the phenomenon
of life in its relation to external physical conditions,
and what
important inferences do they warrant as to the influence of
external
media and conditions upon the life and development of living
contagia!
There have been great discussions in Germany and France upon a
mode
of treatment in typhoid fever, which consists in cooling the body
of
the patient by frequently repeated baths. The possible good effects
of
this treatment may be understood when viewed in conjunction with
the
foregoing experiment on fowls. In typhoid fever the cold arrests the
fermentation, which may be regarded as at once the expression and the cause of
the disease, just as, by an inverse process, the heat of the body arrests the
development of the splenic fever microbe in the
hen. |
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