THE ATTENUATED VIRUS, OR VACCINATION OF VIRULENT DISEASES.
THE VACCINE OF FOWL CHOLERA.

Among the scourges which afflict humanity there are none greater than virulent diseases. Measles, scarlatina, diphtheria, small-pox, syphilis, splenic fever, yellow fever, camp typhus, the plague of the East—what a terrible enumeration! I pass over some, such as glanders, leprosy, and hydrophobia. The history of these diseases presents extraordinary circumstances. The most strange, assuredly, is that which has been from all time established with a great number of these diseases, that they are non-recurrent. As a general rule, notwithstanding some rare exceptions, man can only have measles, scarlet fever, plague, yellow fever once. What explanation, even hypothetically, can be given of such a fact? Still more difficult is it to explain how vaccination, which is itself a virulent though benign disease, preserves from a more serious malady, the small-pox? Has there ever been a discovery more mysterious in its causes and origin, standing, as it does, alone in the history of medicine, and for more than a century defying all comparison?

After dwelling long on Jenner's discovery this question arose in Pasteur's mind: If contagious maladies do not repeat themselves, why should there not be found for each of them a disease different from them, but having some likeness to them, which, acting upon them as cow-pox does upon small-pox, would have the virtue of a prophylactic? A chance occurrence, one of those chances which not unfrequently occur to those who are steadfastly looking out for them, opened out to Pasteur the way to a discovery which may well be called one of the greatest discoveries of the age.

In causing the microbe of fowl cholera to pass from culture to culture, in an artificial medium, a sufficient number of times to render it impossible that the least trace of the virulent matter from which it originally started should still exist in the last cultivation, Pasteur gave in an absolute manner the proof that infectious microbes are the sole authors of the diseases which correspond to them. This culture may be repeated ten, twenty, a hundred, even a thousand times: in the latest culture the virulence is not extinguished, or even sensibly weakened. But it is a fact worthy of attention that the preservation of the virulence in successive cultures is assured only when no great interval has been allowed to elapse between the cultures. For example, the second culture must be sown twenty-four hours after the first, the third twenty-four hours after the second, the hundredth twenty-four hours after the ninety-ninth, and so on. If a culture is not passed on to the following one until after an interval of several days or several weeks, and particularly if several months have elapsed, a great change may then be observed in the virulence. This change, which generally varies with the duration of the interval, shows itself by the weakening of the power of the contagium.

If the successive cultures of fowl cholera, made at short intervals, have such virulence that ten or twenty inoculated birds perish in the space of twenty-four or forty-eight hours, a culture which has remained, say, for three months in its flask, the mouth of which has been protected from the introduction of all foreign germs by a stopper of cotton wool, which allows nothing but pure air to pass through it—this culture, if used to inoculate twenty fowls, though it may render them more or less ill, does not cause death in any of them. After some days of fever they recover both their appetite and spirits. But if this phenomenon is extraordinary, here is one which is surely in a different sense singular. If after the cure of these twenty birds they are reinoculated with a very virulent virus—that, for instance, which was just now mentioned as capable of killing its hundred per cent. of those inoculated with it, in twenty-four or forty-eight hours—these fowls would perhaps become rather ill, but they would not die. The conclusion is simple; the disease can protect from itself. It has evidently that characteristic of all virulent diseases, that it cannot attack a second time.

However curious it may be, this characteristic is not a thing unknown in pathology. Formerly it was the custom to inoculate with small-pox to preserve from small-pox. Sheep are still inoculated to preserve them from the rot; to protect horned cattle from peripneumonia they are inoculated with the virus of the disease. Fowl cholera offers the same immunity; it is an additional scientific acquisition, but not a novelty in principle.

The great novelty which is the outcome of the preceding facts, and which gives them a distinct place in our knowledge of virulent diseases, is that we have here to do with a disease of which the virulent agent is a microscopic parasite, a living organism cultivated outside of the animal body, and that the attenuation of the virulence is in the power of the experimenter. He creates it, he diminishes it, he does what he wishes with it; and all these variable virulences he obtains from the maximum virulence by manipulation in the laboratory. Looked at in juxtaposition with the great fact of vaccination for small-pox, this weakened microbe, which does not cause death, behaves like a real vaccine relatively to the microbe which kills, producing a malady which may be called benign, since it does not cause death, but is a protection from the same malady in its more deadly form.

But for this enfeebled microbe to be a real vaccine, comparable to that of cow-pox, must it not be fixed, so to speak, in its own variety, so that there should be no necessity for having recourse again to the preparation from which it was originally derived? Jenner, when he had demonstrated that cow-pox vaccination preserved from small-pox, feared for some time that it would be always necessary to have recourse to the cow to procure fresh vaccinating matter. His true discovery consisted in establishing that the cow-pox from the cow could be dispensed with, and that inoculation could be performed from arm to arm. Pasteur made his enfeebled microbe pass from one cultivation to another. What would it become? Would it resume its very active virulence, or would it preserve its moderate virulence?