Louis Pasteur (182295). Scientific Papers. The Harvard Classics. 190914.
On the Extension of the Germ Theory to the Etiology of Certain Common Diseases
1 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.
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 airof 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 experimentschicken 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 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.
Fifth observation.July twenty-first, Dr. Maurice Reynaud informed me that there was a woman at the Lariboisière 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.
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 aërobic 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 aërobic 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.
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-Eugènie 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.
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 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 oclock. 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
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.
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.
Fourth observation.On June fourteenth, at the Lariboisière, 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 oclock 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. Doléris, a wellknown 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 oclock 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. Doléris 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 granulesnot 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. Doléris 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.
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 not air oven at 150° C., more than enough to kill the germs of the common organisms. 8
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 ones 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. Doléris.
Note 1. Read before the French Academy of Sciences, May 3, 1880. Published in Comptes rendus de lAcadémie des Sciences, xc., pp. 103344. [back]
Note 2. In 1880. Especially engaged in the study of chicken cholera and the attenuation of virulence.Translator. [back]
Note 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. [back]
Note 4. This has been demonstrated, as is well known.Translator. [back]
Note 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. [back]
Note 7. Interesting as the starting point of the conception of diseases according to the etiological factor, not by groups of symptoms.Translator. [back]
Note 8. The adoption of precautions, similar to those here suggested, has resulted in the practically complete disappearance of puerperal fever.Translator. [back]