Translation
by Evelyn T. Cohn and David V. Cohn (rev. 30 March 2001)
The Anthrax Vaccination
Reply of M. Pasteur to a paper of M. Koch
Extract from the Scientific Review Paris
20 January 1883
Forward
Shortly after the London International Medical Congress where I
made known the attenuation of viruses, there appeared in Berlin the first volume of the
collected work of the Imperial German Health Office. Not only this discovery of
attenuation, but all my previous research on the microbes of disease, were attacked with
an odd brusqueness by Dr. Koch and two of his pupils. I wanted to reply when a
favorable opportunity should present itself. It was offered to me in September 1882. At
that time I returned to Geneva to an international congress of hygiene with the hope of
meeting Doctor Koch at the sessions. My wait was not in vain. In his presence and as a
matter of course, I refuted his criticisms; but he declined all discussion, alleging that
he would reply in the press. He took three months to publish a little brochure entitled:
On the anthrax vaccination; reply to the speech given in Geneva by Pasteur, by Doctor
Robert Koch, confidential adviser of the government. Berlin, 1882. I have it in my hands
and I am going to say what I think of it.
To Monsieur Koch
Confidential Adviser of the Government at Berlin,
Paris December 25, 1882
Monsieur:
In 1881 you hastily and thoughtlessly attacked my work in
the first volume of the collected work of the Imperial German Health Office. In
Geneva, 5 September 1882, I refuted your errors as a matter of course. It is deplorable
that you refused to have a public discussion. Although different than the conditions of a
face-to-face debate in the presence of competent judges, in which one is no longer able to
engage, I nevertheless accept them.
You say I didn’t bring any scientific innovations to the
Geneva Congress. Truly Monsieur! A general method of viral attenuation by a simple
exposure to the oxygen of air, knowledge of new microbes, research on the conditions of
their attenuation, variable according to their respective properties, in all of that
nothing appears new to you?. It is true that in the collected German work which I cited
just now, you suggested that the attenuation of the virus was a myth, the probable effect
of some adulteration of my cultures or of the deposit of a strange germ on the needle
employed in the vaccination.
Somewhat accustomed as I am to all sorts of contradictions, I
confess that I have been disconcerted while reading in your brochure that:
In the study of an illness, I don’t study the microbes,
that I don’t bother to learn where the microbes are and that I lack in each
particular case the demonstration of the parasitic character.
It is truly necessary to have these lines in view to persuade
oneself that they have been written.
It is thus, you continue with certainty, that
Pasteur doesn’t say if he has, in the illness designated by him as a new illness of
rabies, explored the organs of the child who succumbed to rabies and who served him as a
point of departure for the inoculation experiments, and if he searched microscopically for
the presence of the specific microbe in the sublingual glands.
I find here, Monsieur, a new example of the manner of discourse
that served you previously in 1881; you attribute to me some errors which I hadn’t
committed; you refute them and then exult noisily. So where have you read a work of mine
relating to a new illness of rabies? Without doubt in some second hand account.
No, Monsieur, I have never claimed to have found a new rabies
disease. I have said, and I repeat, that I have found a new illness which has been
obtained for the first time from the saliva of a child who died from rabies; that this
saliva , or rather the mucus of the mouth inoculated in rabbits, made them perish rapidly
through the presence of a microbe that nobody had reported previously, this I wrote in my
name and in the name of my three collaborators, Chamberland, Roux and Thuillier. I have
described this microscopic organism. I have indicated the lesions which it causes; I have
shown that this microbe, although pathogenic for dogs and rabbits and although it is
present in the saliva from the mouths of people who die from rabies, has nevertheless no
relation whatsoever with the etiology of this last malady; which in short one usually
encounters in the mouths of dead children of common illnesses and equally in the saliva of
adults in good health. That is what I said, and that should be easy for you to recall. You
continue imperturbably:
Pasteur, when he tried to transmit rabies of the cadaver of
this child to animals, likewise did not use tissue of the sublingual gland but the saliva;
but one knows that this contains an incalculable number of diverse bacteria, notably as
Vulpian and Sternberg have shown that some pathogenic bacteria are present even in quite
healthy people. (Vulpian, Bulletin de l’Académie de médecine, 29 March 1881, and
Sternberg, National Board of Health Bulletin, 30 April 1881.)"
You ignore therefore, Monsieur, that the rabid saliva was the
only substance in which one had determined with certainty the presence of the rabid virus
and that even today one denies the presence of this virus in the glands. This isn’t
the only thing I wish to raise. I simply want to point out that you possess the art of
mixing up things and confusing dates, that MM. Vulpian and Sternberg came, not to
forestall, but to confirm the statement of the existence of a pathogenic microbe in the
saliva of people in good health. It suffices to refer to the sessions of the 22 and 29
March 1881 of the Académie de médecine. Here, moreover, is how M. Vulpian expressed
himself, the 29th of March 1881: "I regret not having been present at the
Academy, when M. Parrot read M. Pasteur’s letter inserted in the last bulletin
(Letter in which I announced to the Academy the presence in the saliva of children dead of
common illnesses, and in that of an adult in good health, of a new microbe which I had
discovered in the saliva of children with rabies and in which I concluded that the illness
produced by this microbe had no relation to rabies.). I should have informed the Academy
that I had induced the very rapid death of a rabbit by subjecting it to a subcutaneous
injection of normal saliva derived from healthy adults… The blood of the first rabbit
and of the second, examined some hours after death contained numerous microbes; many among
them, in each preparation presenting the characteristics of those which had been found by
M. Pasteur in the blood of dead rabbits following the inoculation of the saliva derived
from children who died of hydrophobia or children who died of broncho-pneumonia. M.
Pasteur had the kindness to show me these microbes and I was able thus to recognize them
easily". Monsieur, do I need to add that Sternberg subsequent to your critique was
the third to authenticate the existence of this microbe?
Concerned as you obviously are to detract a part of the novelty
from the discovery of the new microbe in saliva and of the illness which it causes, you go
on gratuitously to assert that this illness is identical to septicemia in the rabbits of
Davaine, which is absolutely incorrect. As you are prudent enough to give no proof for
your assertion, I won’t dwell on this.
Your general method of argument is to be found in the manner in
which you present what I have said of another equally new microbe, the one that we have
encountered in the foamy matter from the nostrils of a horse who died of the infection
known as horse typhoid fever.
Why do you say that at Geneva I spoke of the discovery of the
microbe of horse typhoid fever? Quite the contrary, I had expressly observed that I left
aside the question of knowing if our microbe, in spite of its origin, had any part in the
cause of this infection. You know very well that the purpose of my communication at Geneva
was to give some examples of the attenuation of viruses by the influence of oxygen in the
air, and that for one of these examples I took the microbe, the origin of which I just
indicated. You state, in addition, without the least proof, that this fourth microbe is
again identical with the pathogenic microbe of the saliva. This is a new error on your
part. These two microbes differ physiologically as much as possible. The day when you
would wish to be enlightened on this point and all the preceding points, I will be at your
disposal before a congress or a commission of which you will be able to designate the
members. If you accept my proposition, perhaps you will not maintain the tone of certainty
that is reflected in the wording I extract from your brochure itself:
…All this was disregarded (it is a question of the fourth
microbe, above) and a malignant accident, required that here again, one found the fatal
microbe in the shape of a figure 8 that killed the rabbits in about 24 hours. Here again
it is a question of the same septicemia of the rabbit which Davaine has already described
and which is identical to the new illness (rabies) of Pasteur, certainly without a shadow
of doubt to whoever is knowledgeable about the inoculation of animals…. Even if one
accepts that the inoculation of horse mucus induces in the rabbit a variety of
experimental infection not observed previously, I would consider this discovery of
secondary importance to such a degree that I would not judge it to be communicated to an
international congress as something important.
This lofty disdain, Monsieur, for these poor Figure 8 microbes is
without doubt typical of your method for the examination of illnesses which compared with
mine, according to you, makes a radical difference. It is regrettable that it induces you
to leave aside that which others esteem worthy of the most serious studies, and permits me
to think that, with more attention to little things, you would have perhaps better
followed the details of my first note of February 28, 1881, on the subject of the
attenuation of the anthrax vaccination. In addition you would have spared yourself the
error of believing that at 43º the anthrax bacillus yields some spores, and that in
consequence, even the principal of the method of attenuation of the bacillus is false.
You return, Monsieur, to the experiment of the anthrax
inoculation of chickens by simply cooling the subjects. This experiment merits in effect
all of your attention because it has been judged up to present as one of the remarkable
experiments in physiology. In 1881 in the collected works of the German Health Office you
doubted its accuracy. More reserved today, you accept it as true. I am pleased with your
change of opinion.. Nevertheless you don’t accept the interpretation that I have
given of these results. The method of maintaining the wings of the chickens by fastening
them to a board does not meet with your approval; you infer, this with little logic, that
that which happens to certain birds is due to the fowls themselves; and finally you allege
still that under normal conditions 33 out of 100 hens succumb to anthrax.
German chickens are perhaps more accommodating than French
chickens. For my part, I have never been able to induce anthrax in non-chilled chickens
whether or not fastened to a board..
As the chilled fowl receive the anthrax inoculation and at the
moment that they are overrun by the bacillus, it merely suffices to rewarm them for the
bacillus to disappear and simultaneously for the hens to regain their health, I take this
as sufficient proof to infer a simple effect of temperature.
It would be desirable were all physiological facts established on
proofs as substantial. It would be desirable, above all, that you have experimental
support as solid for your interpretation. But you content yourself with a completely
fantastic interpretation in declaring that you have deemed it unnecessary to verify the
data.
The history of older and recent studies relative to the anthrax
infection, to its etiology, to the application of the new vaccination of animals, all
questions which appear to be of much interest to you, further places in evidence the
weakness of your polemic.
Your first work bears on anthrax or Milzbrand. It was
published, as you yourself recall, in 1876. Here is how I spoke of it on 30 April 1877
before the Académie des sciences:
"In a remarkable report, Dr. Koch stated the small
threadlike bodies discovered by M. Davaine are able to pass to the state of bright
corpuscles after being reproduced by scission, then being resorbed …." And I
added later on: "One must think that these corpuscles can survive from one year to
another without perishing, ready to propagate the disease; this is the opinion of Doctor
Koch".
You see, Monsieur, that I was one of the first who recognized the
merit of your work on the spores of the anthrax bacillus and the value of understanding
the role of these spores in the etiology of anthrax. Yet, if you would be kind enough to
refer to the first volume of my studies on the malady of silk worms, you will see there on
pages168, 228 and 256, that the priority of the discovery of the formation of spores in a
pathogenic bacillus belong to me, that I described and pictured this bacillus, that I
pointed out the formation of the spores as well as the resolution of the surrounding
material of the filaments, finally I have proved that these spores or cysts could
regenerate many years after their formation.
Why, Sir, have you hidden all that from the readers of your first
report? Will you say that you ignored the existence of my work on the malady of silk
worms, which appeared in 1869-1870? Your assertion would be without weight, because in
science nobody is supposed to ignore a discovery; but since 1877,on occasions haven’t
you had to consider these facts! You were deliberate in not speaking of this so that your
study of the anthrax bacillus wouldn’t have to be recognized, despite its merit, as a
new application of earlier principles that I established.
In summary, it isn’t you, Monsieur, who discovered the
method of propagation of the bacilli and vibrios from spores; it isn’t you who
indicated their curious mode of formation; it isn’t you who recognized their
preservation as particles and their long life span. The precision with which I have
described and pictured the formation of these cysts, corpuscles-microorganisms, spores, is
such that you would have been able to limit yourself to a copy of the plate which
represents it on page 228 of my book, in order to introduce it in your report of 1876, and
allow it to serve what you said about bacillus anthracis.
Would the opinion that the spores of the anthrax bacillus can
propagate the anthrax disease from one year to another, in the same manner that the spores
of the silkworm bacillus can produce the malady in the following years suffice to give us
the complete and true etiology of anthrax? This would be unsustainable. The understanding
of this etiology dates only from the discovery of the role of earthworms.
Yes, it is necessary to remind you of this, Monsieur. It is true
that in your eyes the discovery of the role of earthworms does not merit your attention,
and, in the compilation of the German Health Bureau, you are amused at the thought that it
had been able to attract the attention of your compatriots. You are wrong, Monsieur! You
again set yourself up for the disappointment of changing your opinion. Thus today, after
having rejected the great fact of viral attenuation, you were forced to accept it and to
praise it. You will come back to the role of the earthworm.
The retrospective review that you have required me to conduct is
not over yet. I ask the reader to pardon me for taking up so much space for my work; but
you seem, Monsieur, to ignore or disregard the chain of facts. There is in your brochure a
great number of passages where "the impertinence of the error", as expressed by
Pascal, is truly, too much!
Since ancient times, all men, and most particularly those who
devote themselves to the practice of medicine, have compared two natural phenomena of
capital importance: the disease or fever and fermentation. The dough and the unfermented
wine mash which, spontaneously rise and heat up, bring to mind the accelerated activity of
the chickens accompanied by a rise in temperature which changes the state of all the body
fluids.
At diverse epochs in the history of science and in the darkness
that had hidden the understanding of these great phenomena, one had been led to believe
that the mystery which envelopes them is of similar nature. It is that which the
celebrated Professor Tyndall in one of his brilliant lectures at the Royal Institute of
London, expressed recently in citing these profound words of the physicist Boyle: "He
who can plumb to the depths the nature of the fermentative enzymes and fermentation will
be without doubt very much more capable than any one else of giving a correct explanation
of the various morbid phenomena (as well as of the fevers of other infections), phenomena
which perhaps will never be well understood without a thorough knowledge of the theory of
fermentation."
Also one sees, in all the epochs, the medical theories, and most
particularly those that concern the etiology of contagious diseases, suffering in some
manner the result of imagined explanations to clarify the phenomenon of fermentation. When
in 1856 I attempted my first studies, the doctrine of Liebig was in full favor. The
enzymes, said Liebig, are all those nitrogenous substances, albumin, fibrin, casein…
or the organic liquids which contain them, milk, blood, urine…, in an altered state
which they undergo upon contact with air. They are able to share this altered state with
fermentable materials that then resolve themselves into new products.
Under the pressure of ideas on the nature of fermentations that
were zealously and skillfully supported by the learned chemist, viruses and the course of
diseases were similarly considered to be the resultant of intestinal movements of
substances in the course of alteration being able to communicate with the diverse matter
of the living being.
This spontaneous movement, as in those of fermentation, was
invoked in the origin and course of diseases. During 20 years all the work that I
communicated to the Académie des sciences contributed, directly or indirectly, to
demonstrate the inaccuracy of Liebig’s opinions. In the first place, I showed that in
so-called fermentations, one finds necessarily, some specific microbes, and that in this
process in which one thought to be dealing with dead matter, in the course of chemical
change, life appeared correlative to the fermentation. Furthermore, I constituted a
fermentable medium in which there existed but three sorts of substances: the fermentable
matter, some mineral salts, and third, the germs of the microbe-ferment. Correlative to
the multiplication of the latter was the establishment of the fermentation and its
reaching completion. All albuminoid material being thus removed at the start of
fermentation, the doctrine of Liebig collapsed and the phenomenon of fermentation
presented itself as a simple chemical action of decomposition in relation to the nutrition
and the growth of microbes that borrowed from the surrounding substances (mineral and
fermentable) the elements of their own tissues.
Permit me, Monsieur, a short digression. When I refer, as I do at
this moment, to the studies which concerned me from 1856 to 1876, a long period of life
during which you weren’t involved in science, since your first work dates from 1876,
and where my unique preoccupation was to isolate and to make some microbes live in a state
of purity, in appropriate milieus, isn’t it ludicrous, in truth, that you have the
flippancy to accuse me of not being able to make pure cultures!
Accordingly, have you read, Monsieur, among other things, in Comptes
rendus de l’Académie des sciences, in 1871, this manner in which I challenged
your eminent compatriot Liebig, on the subject of the great inaccuracy in his theory of
fermentation? Have you read, therefore, that, if he had agreed to submit the debate to a
commission, I would have allowed him the choice of members, I was in a position to present
to it some complete fermentations involving large weights of pure sugar conducted by a
yeast uniquely formed and nourished in a sugar mineral medium, a circumstance which
demonstrates in most a most absolute way that the yeast was grown in a state of
irreproachable purity, in contact with pure air?
But why do I dwell on your childish assertions on the above
point? I move on and take up my account.
The knowledge from the results of my work will soon be
assimilated by human medicine and veterinary medicine to their benefit. One is notably
eager to discover if viruses and contagions wouldn’t be microscopic living beings.
Doctor Davaine (1863) endeavored to place in evidence the real
functions of the bacteria of anthrax; Doctor Chauveau (1868) established that the
virulence was due to solid particles previously seen in the virus; Doctor Obermeier (1868)
described the spirillum of recurrent fever; Doctor Klebs (1872) attributed the traumatic
viruses to some microscopic organisms.
The most striking proof of the influence of my work on
fermentation was in the birth and development of the movement related to the etiology of
diseases granted to us by a particular circumstance concerning the history of anthrax
infection.
In the month of August 1850, Monsieur Doctor Rayer rendering an
account of some research which he had done, in collaboration with Doctor Davaine, on the
contagion of the illness called anthrax or spleen fever expresses himself thus:
"There was, in addition, in the blood, little threadlike
bodies having about twice the length of the blood corpuscle. These small bodies exhibited
no spontaneous movement." (Bulletin de la Société de biologie of Paris for
1850.)
Such is the true date of the first observation on the presence of
bacterial bodies in anthrax infection.
For 13 years, Rayer and Davaine, paid no attention to these
little filaments of the blood of cadavers dead of anthrax. But Davaine informed us that he
returned in 1863 to the possible role of these elements of blood following some thoughts
suggested to him by the reading of my communication of 1861, at the Académie des
sciences, on butyric fermentation. I had announced at the Academy that the ferment of this
fermentation, far from being an albuminoid substance in the course of spontaneous
decomposition, as it was understood in the theory of Liebig, was formed by some mobile
anaerobic vibrions. Davine, struck by the great resemblance of this new microbial ferment
with the threadlike bodies of anthrax blood, questioned if these last weren’t in some
way the ferment of the malady that he had studied previously with Doctor Rayer. It is
necessary to say, in addition, that in this same year of 1863, I just proved decisively
that, in a healthy state, the body of animals is closed to the introduction of all
exterior germs, that the blood and urine are liquids similarly exempt from microbial germs
of all sorts so that one is able to expose them to contact with air, when such is deprived
of the germs that it carries naturally in suspension, without ever provoking, at all
temperatures of the atmosphere, the putrefaction of these natural liquids and their
invasion by microscopic beings.
A little while after Davaine’s research the first work of
MM. Coze and Feltz appeared. These able and courageous experimenters place the point of
departure of their studies in the reading of my report on putrefaction.
In Germany, one no longer fails to realize the need to profoundly
modify the prevailing ideas on the etiology of many diseases by placing them in harmony,
as Davaine attempted for anthrax, with views that would suggest the results of these
researches were due to microbial ferments. I will cite only one example: at the beginning
of Year 1864, a new journal, the Berliner Klinische Wochenschrift was published in
Berlin. One finds in its second issue a clinical lesson by the learned Professor Traube in
which he sets forth a new doctrine on the ammoniacal fermentation of urine. After giving
the report on his patient, he reflects as follows:
"For a long time, he said, one regarded the vesical mucus as
the agent for the alkaline decomposition of urine. One believed that, owing to the
distension resulting in the retention of liquid, the irritated bladder produced a larger
quantity of mucus, and this mucus was assumed to be the ferment which brought about the
decomposition of urea through application of the appropriate chemical force. This opinion
(that of Liebig’s) is not tenable in light of the research of M. Pasteur. This
observer demonstrated in a most peremptory fashion that alkaline fermentation, as
alcoholic, as acetic fermentation, is produced by living things, in which their
pre-existence in the fermentable liquid is the condition sine qua non of the
process. The preceding fact offers a remarkable demonstration of Pasteur’s doctrine.
Despite the long duration of the retention of urine, the alkaline fermentation of the
urine was not produced by an exaggerated secretion of vesical mucus or of pus; it only
developed beginning with the time when the germs of vibrions arrived in the bladder from
the outside..."
One clearly sees here in contrast the two doctrines,
Liebig’s and mine, on fermentation and their inverse and comparative actions on the
etiology of one of the most serious diseases of the bladder. And since 1864, the
significance of my research on the microbe-ferments, in Germany as in France, was doubted
by no one.
In England starting from 1865, Doctor Lister began the brilliant
series of successes in surgery by the application of his antiseptic method, universally
adopted today. The letter which he wrote to me in the month of February 1874 and which
does such honor to his sincerity and modesty is the living witness of the opinion which I
sustain at this moment. I take the liberty of reproducing some lines:
I like to believe that you will read with some interest what I
wrote of an organism which you first studied in your report on lactic fermentation (1857).
I am unaware if the annals of Britannic Surgery have ever passed
before your eyes. In case you would have read them, you would have found there from time
to time, some news of the antiseptic system that, in these recent last years, I have
endeavored to perfect.
Permit me to seize this occasion to convey to you my most cordial
thanks for having by your brilliant research, demonstrated to me the truth of the germ
theory of putrefaction and thereby given me the sole principle by which I was able to
bring the antiseptic system to a satisfactory conclusion….
In 1864 and 1865 I demonstrated that all the diseases of wine and
of fermented drinks in general were produced by microbes that can be easily destroyed at
temperatures well below 100º, thus permitting the subsequent conservation of these
drinks. Finally, I began my research on the diseases of the silk worm, maladies that
likewise I proved to be the consequence of the action of various microscopic beings.
All of the preceding accounts, Monsieur, perhaps will permit you
to understand that if I am neither physician or veterinarian, as you love to recall, there
is agreement nevertheless in England and Germany as in France, to recognize the large part
I have played in the actual etiological doctrines.
You, Monsieur, who came into science only in 1876, following all
the great names that I just cited, can admit without demeaning yourself that you are a
debtor of French science.
Although I might never deliver studies comparable to the
customary work of the Académie de médecine, I had the honor to be
named in 1874, to a vacant place in the category of honorary members of the Academy. I
immediately had to enter into lively discussions. These make evident the opposition to new
ideas, and that the doctrine of pathological spontaneity always includes numerous
partisans. That’s what I recalled in the note presented to this Academy and the Académie
des sciences, 30 April 1877, in collaboration with M. Joubert, on the subject of anthrax
fever: "A prudent critic, I said, reviewing at the beginning of 1877 a new edition of
a treatise on microscopy, expresses himself thus:
"One has modified one’s thinking about parasitic
maladies principally in the role of infusoria, vibrions and bacteria. The authors of this
treatise estimate that one has singularly misunderstood the existence and the role of
these living beings and that never will they be considered as giving rise to infectious
diseases. At best they may be able to imprint on the evolution of a disease of this type a
special character, and if one is right, to consider them as the agents of certain
complications of these diseases. These ideas have conformed to those recently expressed by
M. Paul Bert."
In effect, M. Paul Bert had just announced at the Société de
biologie in the session of 13 January 1877, "that it was possible to destroy the
anthrax bacillus in a drop of blood by compressed oxygen, to inoculate that which remains
and to reproduce the disease and death without the bacteria appearing. He added: the
bacilli are not therefore either the cause nor the necessary effect of anthrax disease.
This is due to a virus" (Note: The term virus used here by M. Bert refers to a
toxic agent or venom, not a virus in modern usage. ed.) "
These data and conclusions were produced, Monsieur, subsequent to
your first study of 1876 which you see contained nothing to deny or refute. It would have
been impossible for you to refute the experimental data of M. Paul Bert.
This is the time that I resolved to enter fully into the study of
this anthrax malady, which by the many studies it had occasioned, served as a reference
point in all the discussions. Struck by hemiplegia at the end of 1868, deprived of the use
of the left hand since then, I needed a devoted collaborator whom I found in the person of
a former student of the École normale superieure, M. Joubert, a most distinguished
physics professor of Rollin College.
What had M. Joubert and I to do to resolve the question of
whether anthrax disease should be attributed to a solid substance or liquid associated
with the filaments discovered by Davaine or if it depends exclusively on the presence and
life of these filaments? It sufficed to apply the methods that for 20 years served me in
the study of microbial ferments. In order to demonstrate, for example, that the
microbe-ferment of the butyric fermentation and of the decomposition is the same agent, I
prepared an artificial medium mixed with the fermentable material, in which I grew the
microbe in a state of purity. This microbe inoculated in another artificial liquid,
similar to the first, multiplied there and provoked anew, an identical fermentation, and
so on indefinitely. It was necessary therefore to isolate the microbe of the anthrax
blood, to cultivate it to a state of perfect purity in some inert liquid and to return
then to investigate its action on animals. It is this method that we applied with
variation necessitated by goal of the study. It is this method that everyone endeavored to
follow and which had been already practiced by some investigators. In the paper I
read at the Académie des sciences 30 April 1877, it was demonstrated, this time
without reply, that the bacillus discovered by Davaine in 1850 was in fact the unique
agent of the disease. After some control experiments, M. Paul Bert hastened to concur with
this opinion before the Société de biologie de Paris, in a manner totally French.
– Today, when I rethink all the proofs which have been produced to show that a
bacterium is indeed the unique cause of anthrax, perhaps only one of these proofs, leaves
no room for doubt. It is the proof that derives from an experiment we performed in the
cellars of the Observatory. It consisted of placing a dense culture of the anthrax
parasite in a slightly tapered test tube suspended vertically in the constant temperature
of the caves for several days. Under these conditions, the filaments and the spores of
this parasite fall little by little to the bottom of the liquid that was chosen for its
absolute clarity. Then upon simultaneous inoculation of the liquid of the upper layers in
comparison with that of the lower layer, it was observed that the former was harmless, and
that the latter caused death by anthrax. Filtration itself of the anthrax blood or of a
culture liquid through plaster or on a porcelain filter plate, fails as proof because one
can object that the filtration matter can retain a dissolved substance in which one would
suppose resides the harmfulness of the blood or of the culture. M. Vulpian recently
informed me that he had made this very interesting observation that the filtration of a
solution of strychnine, sufficiently loaded with the poison to kill some animals, can give
up the strychnine to the plaster of the filter thus rendering the filtered liquid
harmless.
I now hasten to take up discussion of the attenuation of the
anthrax virus and the immunity which it itself confers.
Monsieur, I know you wish to establish that you and your students
have entirely changed conviction since the publication of the Imperial Health Collection
of 1881. Today, far from denying the existence of viral attenuation and in particular that
of the anthrax virus, you extol it as a scientific conquest of foremost importance. We are
completely in agreement on this point. It is entirely in vain that you try to attribute
the honor of this discovery to a person who was only inspired by my first work.
Why then in 1881 did you pretend that the very principle of the
attenuation of Bacillus anthracis rested upon an error? Instead of admitting
that you were mistaken in affirming that at 42º-43º the bacillus forms spores, which is,
in effect, totally contrary to the principle of the method that I had demonstrated, you
excuse yourself by insisting that my note of 28 February 1881 gave an incomplete procedure
for attenuation of the anthrax virus. That which is true, is that when you restricted
yourself to follow step by step the instructions of this note, without changing anything,
you succeeded as did the learned Doctor Feltz and many others, in attenuating the anthrax
virus at 41º-43º and obtaining cultures deprived of spores.
But if today you praise the value of the discovery of the
attenuation of virus in your scientific report, you hasten to condemn it from a practical
point of view.
I hesitate, Monsieur, to undermine your criticism by citing
literally the principal passage of your brochure on this point:
In France, you say, the number of vaccinated sheep rose, at
the beginning of the month of September to 400,000 and that of horned beasts to 40,000.
The losses occasioned by the prophylactic inoculations, following the estimations of
Pasteur, were from 3 per 1000 for the sheep, and from 0.5 per 1000 for the horned animals.
It follows that I do not by any means put in doubt the exactitude of these numbers, but it
is necessary to add a commentary. These numbers, in effect, teach us absolutely nothing,
if this means only that a considerable number of animals were subjected to prophylactic
inoculation without loss. Now that which is important to us, and of which M. Pasteur does
not inform, is to know if the goal of the prophylactic inoculation was attained and if
these animals in truth acquired immunity. Surely, nothing would more rapidly provide
confidence in the prophylactic inoculation than to ascertain how many thousands of animals
were saved from this disease. It is this that M. Pasteur has thus far not done. On the
contrary, recently complaints related to the failure of the prophylactic inoculation have
accumulated, and the weakness of this practice has become more and more evident.
You are strongly mistaken, Monsieur. I reproduced some days ago
before the Académie des sciences results which respond fully to your concerns and
which are sufficiently well done to reassure you. It isn’t I who compiled them, and I
hope that they will interest you on two accounts. I reproduce textually my communication
of 18 December 1882:
"The department of Eure-et-Loir is the one where the
anthrax infection or spleen fever exercises the most havoc. Therefore this
department was the one most eager to take account of the effects of the prophylactic
vaccination against anthrax. Scarcely had the success of the experiments of
Pouilly-le-Fort in Seine-et-Marne been ascertained, that some proofs of the same order
were carried out, with the cooperation of M. Roux, at the entrance to Chartres, at the
Lambert farm. The administrator, members of the general council, doctors, veterinarians
and farmers followed the diverse phases with the most lively interest. The success was no
less than at Pouilly-le-Fort. Since then the new prophylaxis has spread to a great number
of farms in the Beauce. Nearly 80,000 sheep, 4000 to 5000 bulls or cows and 500 horses
have been vaccinated in Eure-et- Loir, in 1882, under the supervision of veterinarians of
the department.
"The Société vétérinaire et agricole de
Chartres was zealous in compiling the results of this first year as it related to the
application of the new vaccination. It just published them in an interesting report, read
at the meeting of 29 October, by one of its members, M. Ernest Boutet, veterinarian at
Chartres.
"I request permission of the Academy to place before
you the conclusions of this report:
"The resume of the vaccinations used in the
department of Eure-et-Loir, says Mr. Boutet, since the experiments of Pouillly-le-Fort and
of Lambert, is very instructive.
"In the last year the number of vaccinated sheep has
risen to 79,392; of those herds the average annual loss had been 7237, or 9.01 percent.
Since the vaccination, only 518 animals died of anthrax or 0.65 percent. It is necessary
to observe that this year, probably because of great humidity, the mortality in
Eure-et-Loir rose only to 3 percent. The losses would have been 2,382, instead of 518
after the vaccinations.
"In the herds which have been
partially vaccinated, we have 2308 vaccinated and 1659 not vaccinated; the loss in the
first has been 8, or 0.4 percent; of the second, the mortality rose to 60, or 3.9 percent.
We note that in these herds taken in different cantons of the department, the vaccinated
and the non-vaccinated sheep were subjected to the same conditions of soil, lodging,
nutrition and temperature, and that consequently, they experienced totally identical
influences.
"The veterinarians of Eure-et-Loir vaccinated 4562
bovines. Of this number one lost annually 324 animals. Since vaccination, only 11 cows
died. The annual mortality, which was 7.03 percent becomes 0.24 percent..
"Some congestion generally not serious occurred
after vaccinating horses, and the anthrax mortality of this species, being slightly
elevated, the veterinarians did not believe it prudent to conduct this vaccination on a
large scale. Only 524 horses were vaccinated of which 3 died between the two vaccinations.
"These results seem convincing to
us: in the presence of such numbers it is no longer permissible to doubt the effectiveness
of the anthrax vaccination.
"If our farmers of the Beauce want to protect their
interests, the anthrax infections will no longer be more than a memory, because anthrax,
spleen fever and malignant pustule are never spontaneous, and that in preventing death of
their livestock by vaccination, they will destroy all causes of anthrax propagation, and
consequently will cause this dreadful infection to disappear from the Beauce in a few
years. E. Boutet,
Reporter
(Extract from l’Union agricole d'Eure-et-Loir, number of 2
November 1882.)
As one sees it, this statistic on the subject of vaccination in
one of our most tested departments, on more than 85,000 animals, is very satisfying. Note
well, moreover, that this statistic was made at the end of last October, that is to say
after those months in which the most spontaneous anthrax raged, thus allowing us to judge
at the same time the question of the duration of immunity following vaccination.
One of the passages of M. Boutet’s report merits particular
attention. The year which ends hasn’t been favorable to the development of the
anthrax fever. It is a fact of observation that the humid years are less deadly than the
warm and dry years. One might be able to think therefore that the lesser mortality of the
vaccinated herds is due to this circumstance. Not only does the resume of the report of
the Société vétérinaire de Chartres anticipate this objection, but also it is
necessary to observe that some intelligent owners, in order to better judge the effects of
the vaccination, had the precaution, as we learn from this report of M. Boutet, to
partially vaccinate their animals. Thus in these partly vaccinated herds, in which one
counts 2,308 vaccinated sheep and 1,659 non-vaccinated, all these sheep subsisted under
the same conditions of feeding and environment, all mixed together at the sheepfold as at
the pens. Well, of 2308 vaccinated only 8 died whereas of 1,659 non-vaccinated, 60
died, a number which would have been calculated to be 83 if there had been 2,308
non-vaccinated instead of 1,659; 83 non-vaccinated deaths against 8 vaccinated: this is a
mortality more than 10 times greater in the non-vaccinated than in the vaccinated.
I must add, in conclusion, that everything predicts that
preventative vaccination will be even more effective in the future. Let us not forget that
we are at the end of a first year of application, that the vaccines are already better
known to us, that one strives to improve them every day, and that the veterinarians
acquire greater certainty in their use.
To this point in the last six weeks 13,000 sheep, 3500 cows, 20
horses, have been vaccinated and of this total of 16,520 animals there not been any
incident.
As to the effectiveness of these last vaccines it has been
verified in the run of November on 12 sheep conducted with M. Chamberland with virulent
virus, that there was not a single death after vaccination. To the contrary none of the
control sheep resisted.
For the other numerous departments where vaccination has been
practiced, there has not been as yet a general statistical work as that for Eure-et Loir.
But a great many letters from veterinarians inform me that the results haven’t been
less satisfying. In this number, there are striking examples of proofs that testify to the
great efficacy of the new vaccination, in being able to compare deaths in the herds in
which the vaccinated and the non-vaccinated animals were reunited and subjected to the
same influences.
You will acknowledge, Monsieur, that the summary of the Société
veterinaire de Chartres on vaccinations employed in the department of Eure-et-Loir,
comprising some 85,000 animals, answers all of your insinuations. I consider therefore
that it would be hardly inappropriate to follow up the manner in which you judged the
experiments of Kapuvar in Hungary; of Packisch in Germany; of the Veterinary School of
Turin in Italy;and some farms of Beauchery and Montpottier in Seine-et Marne in France.
What bias, Monsieur, and what errors in your account! If, in the
experiments of Packisch,a great majority of vaccinated sheep (22 of 22 in the first
series, and 24 of 25 in the second) resists the virulent virus, you state that the trial
virus sent by me must have been already attenuated. Not only did this virus used kill all
the control sheep, which is the guarantee in the two series of tests of its virulence; but
it is expressly stated at the outset in the report of the Berlin Commission, that this
same one used, contrary to your assertion, blood taken from the cadavers of sheep dead of
anthrax. On the other hand, you declare that the results on the fields of Packisch, where
one brought the vaccinated animals, in order to compare them with others non-vaccinated,
very unfavorable to the vaccination, whereas it is established notably in the last report
of M. Doctor Müller, mdd esi suc éoembre 1882, that
up to the present twice the number of non-vaccinated sheep died (8) as compared to
vaccinated (4); what you are silent on is that whatever the number of dead vaccinated
sheep, this represents about a fifth of the number of non-vaccinated animals. Let us wait
for the number of dead to go up in order to be better enlightened. As to the cows, you
remark that a vaccinated one died as did a non-vaccinated one. But you fail to say that
there were twenty times more vaccinated than non-vaccinated. The report doesn’t give
the number of non-vaccinated cows: I am obliged to M. Thuiller to learn that there were 4
unvaccinated while there were 83 vaccinated.
I don’t have the results at hand of the comparison of losses
of vaccinated and non-vaccinated sheep at Kapuvar in the domain of M. le Baron de Berg;
but what I know is that M. de Berg, in a recent letter asks for vaccine to vaccinate 5000
sheep, sufficient proof of the value of the results that he expects to obtain.
At the Veterinary School of Turin, a first experiment failed
totally; but it was established that the anthrax blood that had been injected on 23 March
1882, in the vaccinated and non-vaccinated sheep came from a sheep dead from anthrax more
than 24 hours. Now from the facts established in the experiments which we did in 1877, and
which were communicated to the Académie des sciences the 16th and 17th
of July of the same year, that the blood of this sheep should have been both anthracoid
and septic. I recognize that quite recently the Veterinary School of Turin published and
sent to many scholars in Europe, a protest against the interpretation which I give here,
an interpretation reported in the meeting of the Société centrale vetérinaire de
Paris 8 June 1882. I keenly regret to find myself in disagreement on this point, with the
Veterinary School of Turin. Although six of its members had signed the protest of which I
speak, the respect for the truth obliges me to maintain my assertion. The School of Turin,
I am convinced, will later recognize its oversight.
The second experiment which the School of Turin very much wanted
to do at my request has had a relative success which I very greatly value, although of the
virulent inoculation, there were 2 dead sheep of 6, but neither cow nor horse, while in
the non-vaccinated there were 4 dead sheep out of 4, 1 cow of 2 and 2 horses of 2. Again
it was necessary for M. Bassi who directed this second series of experiments, to inform us
as to what quantity of anthrax blood he had used to inoculate the two dead vaccinated
sheep. At the Lambert farm, near Chartres, in1881, one likewise had killed some vaccinated
sheep by deliberately forcing the dose of the inoculation material. These experiments have
been repeated with the same results by M. Guillebeau at Berne.
It appears, Monsieur, that you are compelled to give in a most
erroneous manner the results of the vaccination of Beauchery and of Montpottier, in
Seine-et-Marne, the account of which is entered in the Bulletin of the session of 14 July
1882 of the Société centrale de médecine vetérinaire de Paris, an
account made by one of its members, M. Mathieu. You present these results as quite opposed
to the utility of the vaccination process, while in reality they are all to its credit.
You cite 296 vaccinated sheep at Beauchery, in April and May 1882, who, after a month lost
4 of their number, and you compare this to 80 non-vaccinated sheep which in the same
interval had no losses. However, what you don’t mention, and which is found on one
side of this preceding passage in the account of M. Mathieu, is that the herd of 80
non-vaccinated sheep had been removed from another herd which contained 140 sheep and
which previously had lost 15 subjects. What you likewise don’t mention is that it
isn’t 296 but rather 672 vaccinated which were compared with 80 non-vaccinated. Above
all you fail to state that the herd in question belongs to a farm where anthrax rages.
Indeed, here is the first part of the observation related by M. Mathieu:
In the course of July 1881, M.T.J.,
breeder at Beauchery (Seine-et-Marne), lost 60 animals from his herd.
In August, Professor Nocard vaccinated at his place, 380
sheep; 140 were left unvaccinated as controls. On 15 January 1882, the vaccinated lot
(380) had lost 4. Of the non-vaccinated lot (140) 15 had been lost. Thus, more than 10
percent were lost among the non-vaccinated, and only 1 percent among the vaccinated.
What is more convincing in favor of vaccination! Besides, what is
more astonishing, that on a farm as deadly as this one, only 4 vaccinated sheep out of a
total of 672 died of anthrax in the month of June? Will so much bias in your assessments
not surprise your readers?
For the farm of Montpottier, you are still more inexact. I limit
myself to point out just one of your omissions in the account which you borrow from M.
Mathieu; that it deals with a farm that was so decimated by anthrax, that in 1878 it lost
250 of 250 sheep from anthrax and that it was struck with anthrax at the moment of
vaccination.
Another passage of your brochure singularly surprised me. Here
are your own words:
The immunity can not be induced in all species of
animals. Until now the method of M. Pasteur appears to be applicable for only horned
animals and sheep….
Loeffler found that guinea pigs, rats, rabbits and mice
can not acquire immunity, and this fact has been confirmed by all the experimenters who
paid attention to this point. Gotti of Bologna inoculated 6 rabbits, without speaking of
other animals; subsequently he inoculated them with anthrax blood. All of these rabbits
succumbed to anthrax. The rabbits inoculated by M. Guillebeau at Berne, with M.
Pasteur’s vaccine likewise died of anthrax after having been subsequently inoculated
with anthrax blood. In the experiments instituted on the guinea pigs and the mice with
vaccinal virus sent from Paris, all the animals succumbed to anthrax. At the Office
sanitaire, numerous experiments have been carried out on rabbits, guinea pigs and mice
with virus having undergone different degrees of attenuation and finally with some of the
viral vaccine furnished by M. Pasteur. In spite of all efforts, one has never succeeded in
conferring immunity in any of these animals against non-attenuated anthrax virus.
In another passage of your pamphlet, you rely on some experiments
of the same order done in England by Doctor Klein and put in the British Medical
Journal of last September.
It is truly inconceivable that the practice of preventive
vaccination is attacked based on all the experiments in your account that I just cited
above, experiments as defective in their principle as in their conclusions. Has it ever
happened, Monsieur, that one would recommend the vaccination of rabbits or guinea pigs
with vaccines prepared for sheep and cows?
You are strongly mistaken, however, when you affirm that these
breeds of small animals can not be vaccinated against virulent anthrax. The matter is not
difficult and again recently Doctor Feltz easily attained it, as one is able to see in an
account of the Académie des sciences. You have not succeeded in your experiments
and that is all there is to it. I would be tempted, if you had taken a different tone in
all this discussion, to send you in Berlin some guinea pigs and vaccinated rabbits which
you would not have been able to kill with anthrax, in order to have you realize that what
you have always considered as unattainable, in as much as you have not been able to
reproduce it, is due to an insufficiency of experimentation.
Doctor Klein has committed the same fault. With the vaccine of
the sheep, he inoculated rabbits and guinea pigs. I am saddened to note that Doctor Klein,
who enjoyed correctly in England, a reputation of worthy experimenter, had chosen for
testing the immunity of two vaccinated sheep, an anthrax-infected blood which he had kept
for 21 days at 42°, without seeming to be concerned about what was happening to this
blood, if its purity was preserved, if it hadn’t given refuge to some foreign
microbes.
You attach, Monsieur, a great importance to experiments in which
you have given to vaccinated or non-vaccinated sheep meals made infectious by spores of
bacteria mixed in with their food.
You try to conclude from these results that:
Natural anthrax infection is more dangerous to the sheep
than is anthrax developed by the technique of inoculation.
How can you hold such an exceptional heresy?
To begin with, you should remember, Monsieur, that the
experiments you relate copy the ones that I did in 1878, with the collaboration of M.
Chamberland, in the farm fields of Saint Germain, near Chartres; it is with such a meal
contaminated by the anthrax spores that we produced the disease and death; but the
proportion of mortality had been only 33 percent, whereas by direct inoculation it was 100
percent. Likewise, you should have recalled that we augmented the number of deaths when
barbs such as the rough edges of cut barley, were associated with the spores in the food.
I readily concede that the spores alone, even without the barbs, could produce anthrax and
impart it via the intestinal mucous membrane as well as the mucous of the mouth and of the
pharynx; but how are you reasonably able to deduce from your experiments that in the
fields the conditions of contagion are more dangerous than those of the anthrax directly
inoculated? How is it that you do not see that it is impossible to compare the number of
spores in contaminated meals, with the spores that the animals are able to ingest by
foraging in the fields or in the stables? How can you not see that the question of knowing
if one is able to kill vaccinated sheep by infected meals is entirely separate from the
opinion one holds on the practice of vaccination? Finally, how is it that you do not see
that it is useless to ask the vaccination to turn handsprings? Is it not already great
enough to prove that immunity is conferred by vaccination, by showing that the great
majority and often the sum total of the vaccinated animals resist the virulent
inoculation! Would you dare to try the same proof with Jenner’s vaccine? Would you
dare, after having vaccinated 100 children, inoculate them with the smallpox virus? A
great number would die perhaps of smallpox, and meanwhile would you reject Jenner’s
vaccine as some would foolishly propose? Ah well! The impressive proof is the new
vaccination we did at Pouilly-le-Fort, at Packisch, at Kapuvar and many other places.
To sum up, Monsieur, leaving aside the obvious errors of your
citations and judgments, I would estimate that there is but one thing to retain in your
brochure: it is that you were forced, after disregarding it, to celebrate the discovery of
the attenuation of viruses (see
Notes and
Definitions for use of the term virus., ed.)
At this time our only concern is a judgement on the benefits that
it can render to agriculture of all nations. Up to the present time, the results obtained
in the first year of application are considerable enough, so that the criticisms and the
contradictions have not been able to stop the progress in its development.
Entirely violent as are your attacks, Monsieur, they will not
impede its success. I likewise await with confidence the consequences that this method of
viral attenuation yet holds in aiding humanity in its struggle against the diseases that
besiege it.
Paris. – Typ. A. QUANTIN, rue Saint-Benoit, 7. (174)
Translation copyright 12 March 2001. May be reproduced in
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