Translation: H.C. Ernst,
Extension Of The Germ Theory To The Etiology Of Certain Common Disease [1]
[Footnote 1: 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,2 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.
[Footnote 2: In 1880. Especially engaged in the study of chicken cholera and the
attenuation of virulence. - Translator.]
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 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, consistang 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 widespread 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.3 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 begun 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 or otherwise, of the
blood of the general circulation. I am convinced that among them would be found growths of
the micro-organism of furuncles.
[Footnote 3: 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.]
II. On Osteomyelitis. Single observation. I have but one observation relating to this
severe disease, and in this Dr. Lannelongue took the initiative. The monograph on
osteomyelitis published by this learned practitioner is well known, with his suggestion of
the possibility of a cure by trephining the bone and the use of antiseptic washes and
dressings. On the fourteenth of February, at the request of Dr. Lannelongue I went to the
Sainte-Eugenie hospital, where this skillful surgeon was to operate on a little girl of
about twelve years of age. The right knee was much swollen, as well as the whole leg below
the calf and a part of the thigh above the knee. There was no external opening. Under
chloroform, Dr. Lannelongue made a long incision below the knee which let out a large
amount of pus; the tibia was found denuded for a long distance. Three places in the bone
were trephined. From each of these, quantities of pus flowed. Pus from inside and outside
the bone was collected with all possible precautions and was carefully examined and
cultivated later. The direct microscopic study of the pus, both internal and external, was
of extreme interest. It was seen that both contained large numbers of the organism similar
to that of furuncles, arranged in pairs, in fours and in packets, some with sharp clear
contour, others only faintly visible and with very pale outlines. The external pus
contained many pus corpuscles, the internal had none at all. It was like a fatty paste of
the furuncular organism. Also, it may be noted, that growth of the small organism had
begun in less than six hours after the cultures were started. Thus I saw, that it
corresponded exactly with the organism of furuncles. The diameter of the individuals was
found to be one one-thousandth of a millimeter. If I ventured to express myself so I might
say that in this case at least the osteomyelitis was really a furuncle of the bone marrow.4 It is undoubtedly easy to induce osteomyelitis artificially in living animals.
[Footnote 4: This has been demonstrated, as is well known. - Translator.]
III. On puerperal fever. - First observation. On the twelfth of March, 1878, Dr.
Hervieux was good enough to admit me to his service in the Maternity to visit a woman
delivered some days before and seriously ill with puerperal fever. The lochia were
extremely fetid. I found them full of micro-organisms of many kinds. A small amount of
blood was obtained from a puncture on the index finger of the left hand, (the finger being
first properly washed and dried with a sterile towel,) and then sowed in chicken bouillon.
The culture remained sterile during the following days.
The thirteenth, more blood was taken from a puncture in the finger and this time growth
occurred. As death took place on the sixteenth of March at six in the morning, it seems
that the blood contained a microscopic parasite at least three days before.
The fifteenth of March, eighteen hours before death, blood from a needle-prick in the
left foot was used. This culture also was fertile.
The first culture, of March thirteenth, contained only the organism of furuncles; the
next one, that of the fifteenth, contained an organism resembling that of furunculosis,
but which always differed enough to make it easy usually to distinguish it. In this way;
whilst the parasite of furuncles is arranged in pairs, very rarely in chains of three or
four elements, the new one, that of the culture of the fifteenth, occurs in long chains,
the number of cells in each being indefinite. The chains are flexible and often appear as
little tangled packets like tangled strings of pearls.
The autopsy was performed on the seventeenth at two o'clock. There was a large amount
of pus in the peritoneum. It was sowed with all possible precautions. Blood from the
basilic and femoral veins was also sowed. So also was pus from the mucous surface of the
uterus, from the tubes, and finally that from a lymphatic in the uterine wall. These are
the results of these cultures: in all there were the long chains of cells just spoken of
above, and nowhere any mixture of other organisms, except in the culture from the
peritoneal pus, which, in addition to the long chains, also contained the small pyogenic
vibrio which I describe under the name organism of pus in the Note I published with
Messrs. Joubert and Chamberland on the thirtieth of April, 1878.5
[Footnote 5: See preceding paper.]
Interpretation of the disease and of the death. - After confinement, the pus that
always naturally forms in the injured parts of the uterus instead of remaining pure
becomes contaminated with microscopic organisms from outside, notably the organism in long
chains and the pyogenic vibrio. These organisms pass into the peritoneal cavity through
the tubes or by other channels, and some of them into the blood, probably by the
lymphatics. The resorption of the pus, always extremely easy and prompt when it is pure,
becomes impossible through the presence of the parasites, whose entrance must be prevented
by all possible means from the moment of confinement.
Second observation. - The fourteenth of March, a woman died of puerperal fever at the
Lariboisiere hospital; the abdomen was distended before death.
Pus was found in abundance by a peritoneal puncture and was sowed; so also was blood
from a vein in the arm. The culture of pus yielded the long chains noted in the preceding
observation and also the small pyogenic vibrio. The culture from the blood contained only
the long chains.
Third observation. - The seventeenth of May, 1879, a woman, three days past
confinement, was ill, as well as the child she was nursing, The lochia were full of the
pyogenic vibrio and of the organism of furuncles, although there was but a small
proportion of the latter. The milk and the lochia were sowed. The milk gave the organism
in long chains of granules, and the lochia only the pus organism. The mother died, and
there was no autopsy.
On May twenty-eighth, a rabbit was inoculated under the skin of the abdomen with five
drops of the preceding culture of the pyogenic vibrio. The days following an enormous
abscess formed which opened spontaneously on the fourth of June. An abundantly cheesy pus
came from it. About the abscess there was extensive induration. On the eighth of June, the
opening of the abscess was larger, the suppuration active. Near its border was another
abscess, evidently joined with the first, for upon pressing it with the finger, pus flowed
freely from the opening in the first abscess. During the whole of the month of June, the
rabbit was sick and the abscesses suppurated, but less and less. In July they closed; the
animal was well. There could only be felt some nodules under the skin of the abdomen.
What disturbances might not such an organism carry into the body of a parturient woman,
after passing into the peritoneum, the lymphatics or the blood through the maternal
placenta! Its presence is much more dangerous than that of the parasite arranged in
chains. Furthermore, its development is always threatening, because, as said in the work
already quoted (April, 1878) this organism can be easily recovered from many ordinary
waters.
I may add that the organism in long chains, and that arranged in pairs are also
extremely widespread, and that one of their habitats is the mucous surfaces of the genital
tract.6
[Footnote 6: When, by the procedure I elsewhere described, urine is removed in a pure
condition by the urethra from the bladder, if any chance growth occurs through some error
of technic, it is the two organisms of which I have been speaking that are almost
exclusively present.]
Apparently there is no puerperal parasite, properly speaking. I have not encountered
true septicemia in my experiments: but it ought to be among the puerperal affections.
Fourth observation. - On June fourteenth, at the Lariboisiere, a woman was very ill
following a recent confinement: she was at the point of death: in fact she did die on the
fourteenth at midnight. Some hours before death pus was taken from an abscess on the arm,
and blood from a puncture in a finger. Both were sowed. On the next day (the fifteenth)
the flask containing the pus from the abscess was filled with long chains of granules. The
flask containing the blood was sterile. The autopsy was at ten o'clock on the morning of
the sixteenth. Blood from a vein of the arm, pus from the uterine walls and that from a
collection in the synovial sac of the knee were all placed in culture media. All showed
growth, even the blood, and they all contained the long strings of granules. The
peritoneum contained no pus.
Interpretation of the disease and of the death. - The injury of the uterus during
confinement as usual furnished pus, which gave a lodging place for the germs of the long
chains of granules. These, probably through the lymphatics, passed to the joints and to
some other places, thus being the origin of the metastatic abscesses which produced death.
Fifth observation. - On June seventeenth, M. Doleris, a well-known hospital interne,
brought to me some blood, removed with the necessary precautions, from a child dead
immediately after birth, whose mother, before confinement had had febrile symptoms with
chills. This blood, upon cultivation, gave an abundance of the pyogenic vibrio. On the
other hand, blood taken from the mother on the morning of the eighteenth (she had died at
one o'clock that morning) showed no development whatever, on the nineteenth nor on
following days. The autopsy on the mother took place on the nineteenth. It is certainly
worthy of note that the uterus, peritoneum and intestines showed nothing special, but the
liver was full of metastatic abscesses. At the exit of the hepatic vein from the liver
there was pus, and its walls were ulcerated at this place. The pus from the liver
abscesses was filled with the pyogenic vibrio. Even the liver tissues, at a distance from
the visible abscesses, gave abundant cultures of the same organism.
Interpretation of the disease and of the death. - The pyogenic vibrio, found in the
uterus, or which was perhaps already in the body of the mother, since she suffered from
chills before confinement, produced metastatic abscesses in the liver and, carried to the
blood of the child, there induced one of the forms of infection called purulent, which
caused its death.
Sixth observation. - The eighteenth of June, 1879, M. Doleris informed me that a woman
confined some days before at the Cochin Hospital, was very ill. On the twentieth of June,
blood from a needle-prick in the finger was sowed; the culture was sterile. On July
fifteenth, that is to say twenty-five days later, the blood was tried again. Still no
growth. There was no organism distinctly recognizable in the lochia: the woman was
nevertheless, they told me, dangerously ill and at the point of death. As a matter of
fact, she did die on the eighteenth of July at nine in the morning: as may be seen, after
a very long illness, for the first observations were made over a month before: the illness
was also very painful, for the patient could make no movement without intense suffering.
An autopsy was made on the nineteenth at ten in the morning, and was of great interest.
There was purulent pleurisy with a considerable pocket of pus, and purulent false
membranes on the walls of the pleura. The liver was bleached, fatty, but of firm
consistency, and with no apparent metastatic abscesses. The uterus, of small size,
appeared healthy; but on the external surface whitish nodules filled with pus were found.
There was nothing in the peritoneum, which was not inflamed; but there was much pus in the
shoulder joints and the symphysis pubis.
The pus from the abscesses, upon cultivation, gave the long chains of granules - not
only that of the pleura, but that from the shoulders and a lymphatic of the uterus as
well. An interesting thing, but easily understood, was that the blood from a vein in the
arm and taken three-quarters of an hour after death was entirely sterile. Nothing grew
from the Fallopian tubes nor the broad ligaments.
Interpretation of the disease and of the death. - The pus found in the uterus after
confinement became infected with germs of microscopic organisms which grew there, then
passed into the uterine lymphatics, and from there went on to produce pus in the pleura
and in the articulations.
Seventh observation. - On June eighteenth, M. Doleris informed me that a woman had been
confined at the Cochin Hospital five days before and that fears were entertained as to the
results of an operation that had been performed, it having been necessary to do an
embryotomy. The lochia were sowed on the 18th; there was not the slightest trace of growth
the next day nor the day after. Without the least knowledge of this woman since the
eighteenth, on the twentieth I ventured to assert that she would get well. I sent to
inquire about her. This is the text of the report: "The woman is doing extremely
well; she goes out tomorrow."
Interpretation of the facts. - The pus naturally formed on the surface of the injured
parts did not become contaminated with organisms brought from without. Natura medicatrix
carried it off, that is to say the vitality of the mucous surfaces prevented the
development of foreign germs. The pus was easily resorbed, and recovery took place.
I beg the Academy to permit me, in closing, to submit certain definite views, which I
am strongly inclined to consider as legitimate conclusions from the facts I have had the
honor to communicate to it.
Under the expression puerperal fever are grouped very different diseases,7 but all appearing to be the result of the growth of common organisms which by their
presence infect the pus naturally formed on injured surfaces, which spread by one means or
another, by the blood or the lymphatics, to one or another part of the body, and there
induce morbid changes varying with the condition of the parts, the nature of the parasite,
and the general constitution of the subject.
[Footnote 7: Interesting as the starting point of the conception of diseases according
to the etiological factor, not by groups of symptoms. - Translator.]
Whatever this constitution, does it not seem that by taking measures opposing the
production of these common parasitic organisms recovery would usually occur, except
perhaps when the body contains, before confinement, microscopic organisms, in contaminated
internal or external abscesses, as was seen in one striking example (fifth observation).
The antiseptic method I believe likely to be sovereign in the vast majority of cases. It
seems to me that immediately after confinement the application of antiseptics should be
begun. Carbolic acid can render great service, but there is another antiseptic, the use of
which I am strongly inclined to advise, this is boric acid in concentrated solution, that
is, four per cent. at the ordinary temperature. This acid, whose singular influence on
cell life has been shown by M. Dumas, is so slightly acid that it is alkaline to certain
test papers, as was long ago shown by M. Chevreul, besides this it has no odor like
carbolic acid, which odor often disturbs the sick. Lastly, its lack of hurtful effects on
mucous membranes, notably of the bladder, has been and is daily demonstrated in the
hospitals of Paris. The following is the occasion upon which it was first used. The
Academy may remember that I stated before it, and the fact has never been denied, that
ammoniacal urine is always produced by a microscopic organism, entirely similar in many
respects to the organism of furuncles. Later, in a joint investigation with M. Joubert, we
found that a solution of boric acid was easily fatal to these organisms. After that, in
1877, I induced Dr. Guyon, in charge of the genito-urinary clinic at the Necker hospital,
to try injections of a solution of boric acid in affections of the bladder. I am informed
by this skillful practitioner that he has done so, and daily observes good results from
it. He also tells me that he performs no operation of lithotrity without the use of
similar injections. I recall these facts to show that a solution of boric acid is entirely
harmless to an extremely delicate mucous membrane, that of the bladder, and that it is
possible to fill the bladder with a warm solution of boric acid without even
inconvenience.
To return to the confinement cases. Would it not be of great service to place a warm
concentrated solution of boric acid, and compresses, at the bedside of each patient; which
she could renew frequently after saturating with the solution, and this also after
confinement. It would also be acting the part of prudence to place the compresses, before
using, in a hot air oven at 150 C., more than enough to kill the germs of the common
organisms.8
[Footnote 8: The adoption of precautions, similar to those here suggested, has resulted
in the practically complete disappearance of puerperal fever. Translator.]
Was I justified in calling this communication "On the extension of the germ theory
to the etiology of certain common diseases?" I have detailed the facts as they have
appeared to me and I have mentioned interpretations of them: but I do not conceal from
myself that, in medical territory, it is difficult to support one's self wholly on
subjective foundations. I do not forget that Medicine and Veterinary practice are foreign
to me. I desire judgment and criticism upon all my contributions. Little tolerant of
frivolous or prejudiced contradiction, contemptuous of that ignorant criticism which
doubts on principle, I welcome with open arms the militant attack which has a method in
doubting and whose rule of conduct has the motto "More light."
It is a pleasure once more to acknowledge the helpfulness of the aid given me by
Messrs. Chamberland and Roux during the studies I have just recorded. I wish also to
acknowledge the great assistance of M. Doleris.
Source:
Scientific papers; physiology, medicine, surgery, geology, with introductions,
notes and illustrations. New York, P. F. Collier & son [c1910] The Harvard
classics v. 38.
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