spinal cords, fixed in an unvarying and This is the cardinal point in my fashion. vaccination. I have foreseen for a long time that my method will not be exclusively confined to cholera, but that it permits a crowd of microbes of the feeblist pathogenic power to be increased in intensity, and it is this circumstance which gives it its true value. I have among my notes experiments made in this direction since February of last year, and I have talked with you on the subject during my stay in Calcutta before the memoir of Dr. Klein reached India. I have KLEIN'S CRITIQUE CRITICISED. succeeded in killing animals by the bacillus 1 By M. II. Haffkine. indicus, the proteus vulgaris, without mentioning In a hurried communication we have received the bacillus of Finkler-Prior, but they have refrom M. Haffkine, he refers in the following sisted microbes purely saprophytic, such as the baterms to Klein's commentary on his anti-cho- cillus subtilis, the bacillus megaterium, the torula leraic vaccition (Translation.) alba, taken even in doses 100 to 200 times the I have read the work of Dr. Klein in the fatal doses of my " virus fort." I have concluded B. M. J. and in the Centrcilblat fur Bacterio- from this, accordingly that my method will be logies The basis of the anti-choleraic method is applicable to a number of other illnesses, the beyond attack, because 1st, the comma-bacillus agent of which has not yet been used because of is the microbe of cholera since it is the only its feeble action on animals. These were the one which is found in all epidemics, and is experiments which justified me in affirming to not found elsewhere for cholera nostras with Dr. Manifold and yourself that the vaccine the bacillus of Prior-Finkler (est toujours le against typhoid fever could be prepared by copymeme cholera); 2nd, one dies of cholera be- ing exactly my method of vaccination against one is poisoned by the toxine which is cholera, and probably this hope will be fulfilled cause absorbed from the intestine; 3rd, in order to in the near future. M. Klein suggests to us that the poison which be in a position to combat the microbe, it is in the microbe is not that by which is contained most; the to to be accustomed intense necessary toxine we can produce artificially; 4th,our method the latter kills. How does he know this ? First, of "passage" gives us this means. Permit me the distinction between the two kinds of toxic substances?between that which is in the body to examine somewhat briefly the different pasof of the microbe, and that found around it?is a Dr. work. Klein's sages M. Klein says that the kind of malady that distinction which should be based upon considerations other than those cited by Dr. Klein. my virus produces in the guinea-pig is not similar to that of cholera. One has only to re- The difference between the mortification of the call a propos of this, that the kind of malady tissue through the microbe of tuberculosis, and which the rabic virus produces in the rabbit the effect of tuberculine can it not be much does not resemble that of rabies, and yet this better explained by the difference of the mode of does not influence us. Is this circumstance cited action and the dose of the poison entering the The microbe of tissues at a given moment ? to weaken the reasons for attributing cholera to tetanus does not act as its toxine all at once, Can one cite the form the comma-bacillus? because oue injects the microbe in the state of of rabies in the rabbit as proof that the spinal contain not the does rabic virus? Is the cord spores. AVith the bacillus of diphtheria the of Talaman-Friiukel not the cause trial has never been made, and if one wished pueumococcus to make it should be made under special conof human pneumonia, because in the rabbit and a it in the mouse produces septictemia instead of ditions, because the microbe of cholera does not Or is the bacillus of kill the animals unless it is injected in a partian affection of the lungs? Eberth not the agent of typhoid fever, because cular way. In the case of the proteus, does a one cannot produce this malady in domestic single experiment exist which permits a comanimals? Or the bacillus of Hansen not the parison between the poison within the microbe and its external poison ? Every one knows microbe of leprosy, because we cannot graft it in order to compare the action of two subthat I on animals ? The illness that produce in on the organism, and to arrive at the stances the that aim its for the proof guinea-pigs has not comma-bacillus is the cause of cholera, but the conclusion that they are fundamentally difstrengthening of the natural microbe and its ferent, it is necessary first to have these two maintenance at a fixed intensity like the "pas- substances in a comparable state and in equal sages" of the rabic virus through the rabbit quantities. And second, to administer tliein abwhich have for their aim high virulence solutely in the same manner, to inject them into to rabic
sure
?
giving
?
May
18D3.J
the
same
KLEIN'S
CRITIQUE
CRITICISED BY HAFFKINE.
organs, to allow them to act for the How can au affirmation so imetc. portant and so cardinal be made in science without a single experiment of the kind ? But admitting for a moment that the two toxic substances that which is in the microbe and that which M. Klein finds round the microbe in the gelatine are different. How does M. Klein know that it is the substance which he finds in the gelatine, and not that which is in the microbe which kills us? Among the examples which he has given, he cites tetanus as an example of a microbe in which the specific poison is outside the microbe, and tuberculosis where it seems to him that it is the substance of the microbe itself which is speciHow does he know which is the case with fic. cholera? We have produced here at Agra, by means of the hypodermic injection of our vaccines in natives, and in Europeans who are very susceptible to cholera, nausea, vomiting, a fall of temperature, collapse, muscular reactions, slight diarrhoea. All these symptoms occurred in a very slight degree and without any trace of danger to the health, as it should be in a vaccinal procedure, but at the same time in an indubitable fashion, and that in spite of the destruction of the microbes locally at the point of injection, and by the sole action of the products which they carried with them ready made in the dead bodies of the microbes. What is the value of all these approximative reasonings beside these observations ? Could the gelatine, and one say after this, that it is not the microbe which contains the specific poiIt is true that son which kills us by cholera? the choice may be a little difficult for M. Klein, for so far as I know he is somewhat opposed to the opinion that the comma-bacillus is the cause of cholera; and it would be therefore logical to say that the two substances are indifferent. M. Klein believes that my animals vaccinated against cholera, do not resist the poison of the gelatine. I would be somewhat concerned by this were it not that in nature we are poisoned, not by the products of the microbes in gelatine, but by the microbes themselves, which we introduce into our intestinal canal, and as our animals resist the intro-intestinal infection we may be somewhat tranquillised. In any case the assertion that our animals succumb to poisoning by the gelatine, as this also that the animals treated by the bacillus prodigiosus resist cholera The words must be received with caution. succumb and resist are of no experimental value when they are used in this general way. All animals, even the most resistant, succumb when they are infected with unmeasured doses. There is not a farmer in France who does not know that the "vaccination charbonneuse" of Pasteur protects his flocks against anthrax; same
time,
139
and yefc vaccinated sheep tried by M. Koch with food composed of potatoes and spores of anthrax die. On the other hand, animals most susceptible to a disease resist when tried with too weak doses of a virus. What were the doses of cholera which the animals treated by the prodigiosus resisted? And what were the doses of the gelatine toxine by which the animals M. vaccinated against cholera were killed? Klein ought not to be surprised to find me insisting a little on the question of doses. Everybody knows that there have been memorable misunderstandings with regard to the work just mentioned, especially on the question of dosage. It has been said that the method of vaccinating sheep against charbon was of no value because safe cases have not been found for the rabbit. And when we turn to these notes to find what doses he has worked with, we find in the Centralblatt fur Bacteriologie which follows:? " Es ist mir znr Zei noch nicht moglich, mich in alien Details liber die Dosierung der bei der subkutanen Schutzimipfuug verwendeteii sterilisirten Kultur und iiber die totale Menge, die in jedes Meerschweinchen von den einzelneu species injicirt werdeu muss, ehe ein volkommetier, choleragift-fester "Zustand" erzielt ist, auszusprecheu, aber das Princip, dass eiu solcher Zustand erreichbar ist durch eine vorherige Behandlung mit vibrio Finkler, mit bacillus coli und bacillus prodigiosus, ist sichergestellt." A man who can play That is not sufficient. the fiddle is also to some extent a connoisseur of piano music, but to what degree ? It is necessary to know this degree before we can say that he is a pianist. We may suppose that an animal which has overcome one peritoneal disease, caused by a certain microbe, has become more likely to resist another microbe which is implanted in the same peritoneal cavity; but it is necessary to try that animal with well determined doses before it can be said that that animal is immune against that other disease. This is wanting in the work of Dr. Klein, and when he has corrected this defect and shown in
precise manner that my animals protected against cholera, really resist typhoid fever??no one?and the author of anti-choleraic vaccinaa
tion less than others?will
truly
marvellous result.
complaiu
of such
a
sure
?
giving
?
May
18D3.J
the
same
KLEIN'S
CRITIQUE
CRITICISED BY HAFFKINE.
organs, to allow them to act for the How can au affirmation so imetc. portant and so cardinal be made in science without a single experiment of the kind ? But admitting for a moment that the two toxic substances that which is in the microbe and that which M. Klein finds round the microbe in the gelatine are different. How does M. Klein know that it is the substance which he finds in the gelatine, and not that which is in the microbe which kills us? Among the examples which he has given, he cites tetanus as an example of a microbe in which the specific poison is outside the microbe, and tuberculosis where it seems to him that it is the substance of the microbe itself which is speciHow does he know which is the case with fic. cholera? We have produced here at Agra, by means of the hypodermic injection of our vaccines in natives, and in Europeans who are very susceptible to cholera, nausea, vomiting, a fall of temperature, collapse, muscular reactions, slight diarrhoea. All these symptoms occurred in a very slight degree and without any trace of danger to the health, as it should be in a vaccinal procedure, but at the same time in an indubitable fashion, and that in spite of the destruction of the microbes locally at the point of injection, and by the sole action of the products which they carried with them ready made in the dead bodies of the microbes. What is the value of all these approximative reasonings beside these observations ? Could the gelatine, and one say after this, that it is not the microbe which contains the specific poiIt is true that son which kills us by cholera? the choice may be a little difficult for M. Klein, for so far as I know he is somewhat opposed to the opinion that the comma-bacillus is the cause of cholera; and it would be therefore logical to say that the two substances are indifferent. M. Klein believes that my animals vaccinated against cholera, do not resist the poison of the gelatine. I would be somewhat concerned by this were it not that in nature we are poisoned, not by the products of the microbes in gelatine, but by the microbes themselves, which we introduce into our intestinal canal, and as our animals resist the intro-intestinal infection we may be somewhat tranquillised. In any case the assertion that our animals succumb to poisoning by the gelatine, as this also that the animals treated by the bacillus prodigiosus resist cholera The words must be received with caution. succumb and resist are of no experimental value when they are used in this general way. All animals, even the most resistant, succumb when they are infected with unmeasured doses. There is not a farmer in France who does not know that the "vaccination charbonneuse" of Pasteur protects his flocks against anthrax; same
time,
139
and yefc vaccinated sheep tried by M. Koch with food composed of potatoes and spores of anthrax die. On the other hand, animals most susceptible to a disease resist when tried with too weak doses of a virus. What were the doses of cholera which the animals treated by the prodigiosus resisted? And what were the doses of the gelatine toxine by which the animals M. vaccinated against cholera were killed? Klein ought not to be surprised to find me insisting a little on the question of doses. Everybody knows that there have been memorable misunderstandings with regard to the work just mentioned, especially on the question of dosage. It has been said that the method of vaccinating sheep against charbon was of no value because safe cases have not been found for the rabbit. And when we turn to these notes to find what doses he has worked with, we find in the Centralblatt fur Bacteriologie which follows:? " Es ist mir znr Zei noch nicht moglich, mich in alien Details liber die Dosierung der bei der subkutanen Schutzimipfuug verwendeteii sterilisirten Kultur und iiber die totale Menge, die in jedes Meerschweinchen von den einzelneu species injicirt werdeu muss, ehe ein volkommetier, choleragift-fester "Zustand" erzielt ist, auszusprecheu, aber das Princip, dass eiu solcher Zustand erreichbar ist durch eine vorherige Behandlung mit vibrio Finkler, mit bacillus coli und bacillus prodigiosus, ist sichergestellt." A man who can play That is not sufficient. the fiddle is also to some extent a connoisseur of piano music, but to what degree ? It is necessary to know this degree before we can say that he is a pianist. We may suppose that an animal which has overcome one peritoneal disease, caused by a certain microbe, has become more likely to resist another microbe which is implanted in the same peritoneal cavity; but it is necessary to try that animal with well determined doses before it can be said that that animal is immune against that other disease. This is wanting in the work of Dr. Klein, and when he has corrected this defect and shown in
precise manner that my animals protected against cholera, really resist typhoid fever??no one?and the author of anti-choleraic vaccinaa
tion less than others?will
truly
marvellous result.
complaiu
of such
a
