Books: The Harvard Classics Volume 38
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Viewed in this manner, the formation of the proteic substances,
would be independent of the great act of reduction of carbonic
acid gas under the influence of light. These substances would not
be built up from the elements of water, ammonia, and carbonic
acid gas, after the decomposition of this last; they would be
formed where they are found in the cells themselves, by some
process of union between the carbo-hydrates imported by the sap,
and the phosphates of potassium and magnesium and salts of
ammonia. Lastly, in vegetable growth, by means of a carbo-hydrate
and a mineral medium, since the carbo-hydrate is capable of many
variations, and it would be difficult to understand how it could
be split up into its elements before serving to constitute the
proteic substances, and even cellulose substances, as these are
carbo-hydrates. We have commenced certain studies in this
direction.
If solar radiation is indispensable to the decomposition of
carbonic acid and the building up of the primary substances in
the case of higher vegetable life, it is still possible that
certain inferior organisms may do without it and nevertheless
yield the most complex substances, fatty or carbo-hydrate, such
as cellulose, various organic acids, and proteic matter; not,
however, by borrowing their carbon from the carbonic acid which
is saturated with oxygen, but from other matters still capable of
acquiring oxygen, and so of yielding heat in the process, such as
alcohol and acetic acid, for example, to cite merely carbon
compounds most removed from organization. As these last
compounds, and a host of others equally adapted to serve as the
carbonaceous food of mycoderms and the mucedines, may be produced
synthetically by means of carbon and the vapour of water, after
the methods that science owes to Berthelot, it follows that, in
the case of certain inferior beings, life would be possible even
if it should be that the solar light was extinguished. [Footnote:
See on this subject the verbal observations which we addressed to
the Academy of Sciences at its meetings of April 10th and 24th,
1876].
THE GERM THEORY AND ITS APPLICATIONS TO MEDICINE AND SURGERY
[Footnote: Read before the French Academy of Sciences, April
29th, 1878. Published in Comptes Rendus de l' Academie des
Sciences, lxxxvi., pp. 1037-43.]
The Sciences gain by mutual support. When, as the result of my
first communications on the fermentations in 1857-1858, it
appeared that the ferments, properly so-called, are living
beings, that the germs of microscopic organisms abound in the
surface of all objects, in the air and in water; that the theory
of spontaneous generation is chimerical; that wines, beer,
vinegar, the blood, urine and all the fluids of the body undergo
none of their usual changes in pure air, both Medicine and
Surgery received fresh stimulation. A French physician, Dr.
Davaine, was fortunate in making the first application of these
principles to Medicine, in 1863.
Our researches of last year, left the etiology of the putrid
disease, or septicemia, in a much less advanced condition than
that of anthrax. We had demonstrated the probability that
septicemia depends upon the presence and growth of a microscopic
body, but the absolute proof of this important conclusion was not
reached. To demonstrate experimentally that a microscopic
organism actually is the cause of a disease and the agent of
contagion, I know no other way, in the present state of Science,
than to subject the microbe (the new and happy term introduced by
M. Sedillot) to the method of cultivation out of the body. It may
be noted that in twelve successive cultures, each one of only ten
cubic centimeters volume, the original drop will be diluted as if
placed in a volume of fluid equal to the total volume of the
earth. It is just this form of test to which M. Joubert and I
subjected the anthrax bacteridium. [Footnote: In making the
translation, it seems wiser to adhere to Pasteur's nomenclature.
Bacillus anthracis would be the term employed to-day.--
Translator.] Having cultivated it a great number of times in a
sterile fluid, each culture being started with a minute drop from
the preceding, we then demonstrated that the product of the last
culture was capable of further development and of acting in the
animal tissues by producing anthrax with all its symptoms. Such
is--as we believe--the indisputable proof that ANTHRAX IS A
BACTERIAL DISEASE.
Our researches concerning the septic vibrio had not so far been
convincing, and it was to fill up this gap that we resumed our
experiments. To this end, we attempted the cultivation of the
septic vibrio from an animal dead of septicemia. It is worth
noting that all of our first experiments failed, despite the
variety of culture media we employed--urine, beer yeast water,
meat water, etc. Our culture media were not sterile, but we
found--most commonly--a microscopic organism showing no
relationship to the septic vibrio, and presenting the form,
common enough elsewhere, of chains of extremely minute spherical
granules possessed of no virulence whatever. [Footnote: It is
quite possible that Pasteur was here dealing with certain
septicemic streptococci that are now know to lose their virulence
with extreme rapidity under artificial cultivation.--Translator.]
This was an impurity, introduced, unknown to us, at the same time
as the septic vibrio; and the germ undoubtedly passed from the
intestines--always inflamed and distended in septicemic animals--
into the abdominal fluids from which we took our original
cultures of the septic vibrio. If this explanation of the
contamination of our cultures was correct, we ought to find a
pure culture of the septic vibrio in the heart's blood of an
animal recently dead of septicemia. This was what happened, but a
new difficulty presented itself; all our cultures remained
sterile. Furthermore this sterility was accompanied by loss in
the culture media of (the original) virulence.
It occurred to us that the septic vibrio might be an obligatory
anaerobe and that the sterility of our inoculated culture fluids
might be due to the destruction of the septic vibrio by the
atmospheric oxygen dissolved in the fluids. The Academy may
remember that I have previously demonstrated facts of this nature
in regard to the vibrio of butyric fermentation, which not only
lives without air but is killed by the air.
It was necessary therefore to attempt to cultivate the septic
vibrio either in a vacuum or in the presence of inert gases--such
as carbonic acid.
Results justified our attempt; the septic vibrio grew easily in a
complete vacuum, and no less easily in the presence of pure
carbonic acid.
These results have a necessary corollary. If a fluid containing
septic vibrios be exposed to pure air, the vibrios should be
killed and all virulence should disappear. This is actually the
case. If some drops of septic serum be spread horizontally in a
tube and in a very thin layer, the fluid will become absolutely
harmless in less than half a day, even if at first it was so
virulent as to produce death upon the inoculation of the smallest
portion of a drop.
Furthermore all the vibrios, which crowded the liquid as motile
threads, are destroyed and disappear. After the action of the
air, only fine amorphous granules can be found, unfit for culture
as well as for the transmission of any disease whatever. It might
be said that the air burned the vibrios.
If it is a terrifying thought that life is at the mercy of the
multiplication of these minute bodies, it is a consoling hope
that Science will not always remain powerless before such
enemies, since for example at the very beginning of the study we
find that simple exposure to air is sufficient at times to
destroy them.
But, if oxygen destroys the vibrios, how can septicemia exist,
since atmospheric air is present everywhere? How can such facts
be brought in accord with the germ theory? How can blood, exposed
to air, become septic through the dust the air contains?
All things are hidden, obscure and debatable if the cause of the
phenomena be unknown, but everything is clear if this cause be
known. What we have just said is true only of a septic fluid
containing adult vibrios, in active development by fission:
conditions are different when the vibrios are transformed into
their germs, [Footnote: By the terms "germ" and "germ
corpuscles," Pasteur undoubtedly means "spores," but the change
is not made, in accordance with note 3, above.--Translator.] that
is into the glistening corpuscles first described and figured in
my studies on silk-worm disease, in dealing with worms dead of
the disease called "flacherie." Only the adult vibrios disappear,
burn up, and lose their virulence in contact with air: the germ
corpuscles, under these conditions, remain always ready for new
cultures, and for new inoculations.
All this however does not do away with the difficulty of
understanding how septic germs can exist on the surface of
objects, floating in the air and in water.
Where can these corpuscles originate? Nothing is easier than the
production of these germs, in spite of the presence of air in
contact with septic fluids.
If abdominal serous exudate containing septic vibrios actively
growing by fission be exposed to the air, as we suggested above,
but with the precaution of giving a substantial thickness to the
layer, even if only one centimeter be used, this curious
phenomenon will appear in a few hours. The oxygen is absorbed in
the upper layers of the fluid--as is indicated by the change of
color. Here the vibrios are dead and disappear. In the deeper
layers, on the other hand, towards the bottom of this centimeter
of septic fluid we suppose to be under observation, the vibrios
continue to multiply by fission--protected from the action of
oxygen by those that have perished above them: little by little
they pass over to the condition of germ corpuscles with the
gradual disappearance of the thread forms. So that instead of
moving threads of varying length, sometimes greater than the
field of the microscope, there is to be seen only a number of
glittering points, lying free or surrounded by a scarcely
perceptible amorphous mass. [Footnote: In our note of July 16th,
1877, it is stated that the septic vibrio is not destroyed by the
oxygen of the air nor by oxygen at high tension, but that under
these conditions it is transformed into germ-corpuscles. This is,
however, an incorrect interpretation of facts. The vibrio is
destroyed by oxygen, and it is only where it is in a thick layer
that it is transformed to germ-corpuscles in the presence of
oxygen and that its virulence is preserved.] Thus is formed,
containing the latent germ life, no longer in danger from the
destructive action of oxygen, thus, I repeat, is formed the
septic dust, and we are able to understand what has before seemed
so obscure; we can see how putrescible fluids can be inoculated
by the dust of the air, and how it is that putrid diseases are
permanent in the world.
The Academy will permit me, before leaving these interesting
results, to refer to one of their main theoretical consequences.
At the very beginning of these researches, for they reveal an
entirely new field, what must be insistently demanded? The
absolute proof that there actually exist transmissible,
contagious, infectious diseases of which the cause lies
essentially and solely in the presence of microscopic organisms.
The proof that for at least some diseases, the conception of
spontaneous virulence must be forever abandoned--as well as the
idea of contagion and an infectious element suddenly originating
in the bodies of men or animals and able to originate diseases
which propagate themselves under identical forms: and all of
those opinions fatal to medical progress, which have given rise
to the gratuitous hypotheses of spontaneous generation, of
albuminoid ferments, of hemiorganisms, of archebiosis, and many
other conceptions without the least basis in observation. What is
to be sought for in this instance is the proof that along with
our vibrio there does not exist an independent virulence
belonging to the surrounding fluids or solids, in short that the
vibrio is not merely an epiphenomenon of the disease of which it
is the obligatory accompaniment. What then do we see, in the
results that I have just brought out? A septic fluid, taken at
the moment that the vibrios are not yet changed into germs, loses
its virulence completely upon simple exposure to the air, but
preserves this virulence, although exposed to air on the simple
condition of being in a thick layer for some hours. In the first
case, the virulence once lost by exposure to air, the liquid is
incapable of taking it on again upon cultivation: but, in the
second case, it preserves its virulence and can propagate, even
after exposure to air. It is impossible, then, to assert that
there is a separate virulent substance, either fluid or solid,
existing, apart from the adult vibrio or its germ. Nor can it be
supposed that there is a virus which loses its virulence at the
moment that the adult vibrio dies; for such a substance should
also lose its virulence when the vibrios, changed to germs, are
exposed to the air. Since the virulence persists under these
conditions it can only be due to the germ corpuscles--the only
thing present. There is only one possible hypothesis as to the
existence of a virus in solution, and that is that such a
substance, which was present in our experiment in nonfatal
amounts, should be continuously furnished by the vibrio itself,
during its growth in the body of the living animal. But it is of
little importance since the hypothesis supposes the forming and
necessary existence of the vibrio. [Footnote: The regular limits,
oblige me to omit a portion of my speech.]
I hasten to touch upon another series of observations which are
even more deserving the attention of the surgeon than the
preceding: I desire to speak of the effects of our microbe of pus
when associated with the septic vibrio. There is nothing more
easy to superpose--as it were--two distinct diseases and to
produce what might be called a SEPTICEMIC PURULENT INFECTION, or
a PURULENT SEPTICEMIA. Whilst the microbe-producing pus, when
acting alone, gives rise to a thick pus, white, or sometimes with
a yellow or bluish tint, not putrid, diffused or enclosed by the
so-called pyogenic membrane, not dangerous, especially if
localized in cellular tissue, ready, if the expression may be
used for rapid resorption; on the other hand the smallest abscess
produced by this organism when associated with the septic vibrio
takes on a thick gangrenous appearance, putrid, greenish and
infiltrating the softened tissues. In this case the microbe of
pus carried so to speak by the septic vibrio, accompanies it
throughout the body: the highly-inflamed muscular tissues, full
of serous fluid, showing also globules of pus here and there, are
like a kneading of the two organisms.
By a similar procedure the effects of the anthrax bacteridium and
the microbe of pus may be combined and the two diseases may be
superposed, so as to obtain a purulent anthrax or an anthracoid
purulent infection. Care must be taken not to exaggerate the
predominance of the new microbe over the bacteridum. If the
microbe be associated with the latter in sufficient amount it may
crowd it out completely--prevent it from growing in the body at
all. Anthrax does not appear, and the infection, entirely local,
becomes merely an abscess whose cure is easy. The microbe-
producing pus and the septic vibrio (not) [Footnote: There is
undoubtedly a mistake in the original. Pasteur could not have
meant to say that both bacteria are anaerobes. The word "not" is
introduced to correct the error.--Translator.] being both
anaerobes, as we have demonstrated, it is evident that the latter
will not much disturb its neighbor. Nutrient substances, fluid or
solid, can scarcely be deficient in the tissues from such minute
organisms. But the anthrax bacteridium is exclusively aerobic,
and the proportion of oxygen is far from being equally
distributed throughout the tissues: innumerable conditions can
diminish or exhaust the supply here and there, and since the
microbe-producing pus is also aerobic, it can be understood how,
by using a quantity slightly greater than that of the bacteridium
it might easily deprive the latter of the oxygen necessary for
it. But the explanation of the fact is of little importance: it
is certain that under some conditions the microbe we are speaking
of entirely prevents the development of the bacteridium.
Summarizing--it appears from the preceding facts that it is
possible to produce at will, purulent infections with no elements
of putrescence, putrescent purulent infections, anthracoid
purulent infections, and finally combinations of these types of
lesions varying according to the proportions of the mixtures of
the specific organisms made to act on the living tissues.
These are the principal facts I have to communicate to the
Academy in my name and in the names of my collaborators, Messrs.
Joubert and Chamberland. Some weeks ago (Session of the 11th of
March last) a member of the Section of Medicine and Surgery, M.
Sedillot, after long meditation on the lessons of a brilliant
career, did not hesitate to assert that the successes as well as
the failures of Surgery find a rational explanation in the
principles upon which the germ theory is based, and that this
theory would found a new Surgery--already begun by a celebrated
English surgeon, Dr. Lister, [Footnote: See Lord Lister's paper
in the present volume.--Ed.] who was among the first to
understand its fertility. With no professional authority, but
with the conviction of a trained experimenter, I venture here to
repeat the words of an eminent confrere.
ON THE EXTENSION OF THE GERM THEORY
TO THE ETIOLOGY OF CERTAIN COMMON DISEASES
[Footnote: Read before the French Academy of Sciences, May 3,
1880. Published in Comptes rendus, de l'Academie des Sciences,
xc., pp. 1033-44.]
When I began the studies now occupying my attention, [Footnote:
In 1880. Especially engaged in the study of chicken cholera and
the attenuation of virulence--Translator.] I was attempting to
extend the germ theory to certain common diseases. I do not know
when I can return to that work. Therefore in my desire to see it
carried on by others, I take the liberty of presenting it to the
public in its present condition.
I. Furuncles. In May, 1879, one of the workers in my laboratory
had a number of furuncles, appearing at short intervals,
sometimes on one part of the body and sometimes on another.
Constantly impressed with the thought of the immense part played
by microscopic organisms in Nature, I queried whether the pus in
the furuncles might not contain one of these organisms whose
presence, development, and chance transportation here and there
in the tissues after entrance would produce a local inflammation,
and pus formation, and might explain the recurrence of the
illness during a longer or shorter time. It was easy enough to
subject this thought to the test of experiment.
First observation.--On June second, a puncture was made at the
base of the small cone of pus at the apex of a furuncle on the
nape of the neck. The fluid obtained was at once sowed in the
presence of pure air--of course with the precautions necessary to
exclude any foreign germs, either at the moment of puncture, at
the moment of sowing in the culture fluid, or during the stay in
the oven, which was kept at the constant temperature of about 35
degrees C, The next day, the culture fluid had become cloudy and
contained a single organism, consisting of small spherical points
arranged in pairs, sometimes in fours, but often in irregular
masses. Two fluids were preferred in these experiments--chicken
and yeast bouillon. According as one or the other was used,
appearances varied a little. These should be described. With the
yeast water, the pairs of minute granules are distributed
throughout the liquid, which is uniformly clouded. But with the
chicken bouillon, the granules are collected in little masses
which line the walls and bottom of the flasks while the body of
the fluid remains clear, unless it be shaken: in this case it
becomes uniformly clouded by the breaking up of the small masses
from the walls of the flasks.
Second observation.--On the tenth of June a new furuncle made its
appearance on the right thigh of the same person. Pus could not
yet be seen under the skin, but this was already thickened and
red over a surface the size of a franc. The inflamed part was
washed with alcohol, and dried with blotting paper passed through
the flame of an alcohol lamp. A puncture at the thickened portion
enabled us to secure a small amount of lymph mixed with blood,
which was sowed at the same time as some blood taken from the
finger of the hand. The following days, the blood from the finger
remained absolutely sterile: but that obtained from the center of
the forming furuncle gave an abundant growth of the same small
organism as before.
Third observation.--The fourteenth of June, a new furuncle
appeared on the neck of the same person. The same examination,
the same result, that is to say the development of the
microscopic organism previously described and complete sterility
of the blood of the general circulation, taken this time at the
base of the furuncle outside of the inflamed area.
At the time of making these observations I spoke of them to Dr.
Maurice Reynaud, who was good enough to send me a patient who had
had furuncles for more than three months. On June thirteenth I
made cultures of the pus from a furuncle of this man. The next
day there was a general cloudiness of the culture fluids,
consisting entirely of the preceding parasite, and of this alone.
Fourth observation.--June fourteenth, the same individual showed
me a newly forming furuncle in the left axilla: there was wide-
spread thickening and redness of the skin, but no pus was yet
apparent. An incision at the center of the thickening showed a
small quantity of pus mixed with blood. Sowing, rapid growth for
twenty-four hours and the appearance of the same organism. Blood
from the arm at a distance from the furuncle remained completely
sterile.
June 17, the examination of a fresh furuncle on the same
individual gave the same result, the development of a pure
culture of the same organism.
Fifth observation.--July twenty-first, Dr. Maurice Reynaud
informed me that there was a woman at the Lariboisiere hospital
with multiple furuncles. As a matter of fact her back was covered
with them, some in active suppuration, others in the ulcerating
stage. I took pus from all of these furuncles that had not
opened. After a few hours, this pus gave an abundant growth in
cultures. The same organism, without admixture, was found. Blood
from the inflamed base of the furuncle remained sterile.
In brief, it appears certain that every furuncle contains an
aerobic microscopic parasite, to which is due the local
inflammation and the pus formation that follows.
Culture fluids containing the minute organism inoculated under
the skin of rabbits and guinea-pigs produce abscesses generally
small in size and that promptly heal. As long as healing is not
complete the pus of the abscesses contains the microscopic
organism which produced them. It is therefore living and
developing, but its propagation at a distance does not occur.
These cultures of which I speak, when injected in small
quantities in the jugular vein of guinea pigs show that the
minute organism does not grow in the blood. The day after the
injection they cannot be recovered even in cultures. I seem to
have observed as a general principle, that, provided the blood
corpuscles are in good physiological condition it is difficult
for aerobic parasites to develop in the blood. I have always
thought that this is to be explained by a kind of struggle
between the affinity of the blood corpuscles for oxygen and that
belonging to the parasite in cultures. Whilst the blood
corpuscles carry off, that is, take possession of all the oxygen,
the life and development of the parasite become extremely
difficult or impossible. It is therefore easily eliminated,
digested, if one may use the phrase. I have seen these facts many
times in anthrax and chicken-cholera, diseases both of which are
due to the presence of an aerobic parasite.
Blood cultures from the general circulation being always sterile
in these experiments, it would seem that under the conditions of
the furuncular diathesis, the minute parasite does not exist in
the blood. That it cannot be cultivated for the reason given, and
that it is not abundant is evident; but, from the sterility of
the cultures reported (five only) it should not be definitely
concluded that the little parasite may not, at some time, be
taken up by the blood and transplanted from a furuncle when it is
developing to another part of the body, where it may be
accidentally lodged, may develop and produce a new furuncle. I am
convinced that if, in cases of furuncular diathesis, not merely a
few drops but several grams of blood from the general circulation
could be placed under cultivation frequent successful growths
would be obtained. [Footnote: This prediction is fully carried
out in the present day successful use of considerable amounts of
blood in cultures and the resultant frequent demonstrations of
bacteria present in the circulation in many infections.--
Translator.] In the many experiments I have made on the blood in
chicken-cholera, I have frequently demonstrated that repeated
cultures from droplets of blood do not show an even development
even where taken from the same organ, the heart for example, and
at the moment when the parasite begins its existence in the
blood, which can easily be understood. Once even, it happened
that only three out of ten chickens died after inoculation with
infectious blood in which the parasite had just began to appear,
the remaining seven showed no symptoms whatever. In fact, the
microbe, at the moment of beginning its entrance into the blood
may exist singly or in minute numbers in one droplet and not at
all in its immediate neighbor. I believe therefore that it would
be extremely instructive in furunculosis, to find a patient
willing to submit to a number of punctures in different parts of
the body away from formed or forming furuncles, and thus secure
many cultures, simultaneous of otherwise, of the blood of the
general circulation. I am convinced that among them would be
found growths of the micro-organism of furuncles.
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