The first successful attempt in extending the system of inoculation to other diseases was made only after the discovery of the fact that ‘infection’ is caused by living animal or vegetable parasites, capable in the majority of cases of being cultivated and bred in artificial media outside the animal body. Pasteur found that he was able to effect protection against disease similar to vaccination against smallpox by the use of such artificially bred micro-organisms.
It may be interesting to relate that this important discovery was made unintentionally, and represents one of those happy ‘accidents’ which occur to those who diligently search. Pasteur had been working with cultures of chicken-cholera microbes, an extremely fatal form of virus when it is introduced into fowls and small birds. It so happened that one of his cultures was left forgotten in the incubator when work was stopped for the vacation. On the return of Pasteur and his assistants the experiments were continued. When the bottle was discovered, thinking that the microbes might have been exhausted or dead from long starvation, Pasteur tried to make what is called a fresh culture of them, by inseminating a sample from the old bottle into a freshly prepared nutritious broth. The microbes were not dead, and multiplied and grew luxuriantly; but when they were injected into a fowl they caused only a transient and non-fatal disease. To make a fresh start, Pasteur took some old blood, which he had drawn a long time previously from a chicken-cholera fowl and preserved in a cupboard in the laboratory in a sealed-up tube, and made a culture with the material that was in that tube. The culture thus obtained killed fresh fowls as usual, but when it was injected into the bird that had resisted the first culture it resisted this injection also. Pasteur, who excelled all men I ever knew in his ability of quickly analyzing and discerning true connections between facts, required no further hints. Others might perhaps have dwelt on the peculiarity of the fowl that happened to resist the injections, or on some other circumstances. Pasteur relinquished this and other suggestions at once, and thought of the microbe. The fact that old specimens of microbes may become impotent when injected into animals was known to him, and was readily explained by the vitality of such microbes being lowered or exhausted by starvation. But, then, such a microbe when transferred into a fresh medium, if not dead, generally regains its vigor, and after that, when inoculated into an animal, it produces its usual effect. The remarkable circumstance about the culture left in the incubator was that even when it was transferred into a fresh medium and its vitality renewed, it remained still impotent. Pasteur concluded from this that an infectious microbe possesses two distinct properties: one, which it shares with any other living being—viz., vitality—which may be weakened or strengthened according to the conditions of life and food; and another, which he considered as its ‘virulence,’ its power of causing diseases, which may be also weakened or strengthened by special means, but which is quite independent of ‘vitality.’
The lucidity of thought of which Pasteur made proof on this occasion was magnificent. Later researches confirmed and explained these facts with a singular completeness, and now the idea, as is always the case, looks simple and self-evident. One must remember that at that time Pasteur had every reason to believe that disease is caused by the mere fact of a foreign micro-organism of a given species penetrating and settling down to live in the system of a man or animal. Its capability of living there, i. e., its vital properties, seemed all that was necessary for causing disease. It was only later that it was found that pathogenic microbes cause diseases by producing so-called toxines or poisonous substances distinct from their own bodies and separable from them. The process may be illustrated by a comparison, for instance, with a cobra or any other animal producing a special venom. By starvation or some other treatment the vitality of the cobra may be temporarily weakened. When it obtains fresh food again and gets generally in good condition, it recovers, without its ability of producing venom having been in any way impaired. On the other hand, a snake may be by an operation deprived of its fangs and power of secreting poison without its health and strength being in the least affected. Pasteur at once asserted that in a similar way it was possible by starvation to weaken a breed of microbes without their virulence being diminished, and, on the other hand, to deprive them of their power of producing disease without impairing their vitality, though what the above power consisted in he did not know. He called the latter result attenuation of a virus. An attenuated virus in his meaning is therefore a special breed of pathogenic microbes which can be maintained, by suitable breeding, in best conditions of health, but which has lost either partially or entirely its power of producing poison and disease.
Pasteur extracted from the few experiments related above a further most-important conclusion—viz., that such an attenuation was due to and could be produced artificially by the effect of oxidation. This he deduced from the fact that the microbes in the sealed-up tube had not lost their virulence, while those forgotten in the open bottle in the incubator and exposed to the access of air had done so. Oxidation proved indeed to be one of the most general methods of artificially producing attenuated virus, to which method later on were added others—the effect of light, of chemicals, of passage through certain animals, etc.
And, of course, the last and crowning conclusion was that an ordinary, susceptible fowl that has undergone the injection with an attenuated culture becomes immune against a culture which kills other fowls; and that conclusion, in the particular circumstances under which Pasteur was working, proved to be true.
Pursuing the new line of research, Pasteur demonstrated that a protection similar to that obtained against smallpox and chicken cholera could be secured also against anthrax, a disease which, by the destruction it caused among sheep and cattle, was entailing heavy loss on the farmers of France. After a long series of experiments he prepared two specimens of virus, different in strength, but both weaker than the natural contagion, and worked out the proportions in which sheep, horses and cows could be safely injected first with the weakest virus and then with the virus of the somewhat greater strength, after which they became capable of withstanding the strongest anthrax infection.
In honor of Jenner, who was the first to discover the way of preparing a virus of a fixed strength safe to be used for the preventive treatment of men, Pasteur proposed that all such artificially bred, so to say, domesticated forms of microbes be called vaccines, while the word virus be reserved for a contagion growing in nature in a natural condition, or taken direct from an infected individual. The French distinguish between ‘vaccin,’ which is used as a generic term in Pasteur’s sense, and ‘vaccine,’ which name they reserve for smallpox vaccinia lymph. The word ‘vaccination’ has been also extended to designate inoculation with artificially vaccinized virus, while the word ‘inoculation’ is used for the injection of a natural, not vaccinated virus, taken direct from a patient. The latter distinction is, however, not yet strictly maintained in English literature, nor in the subsequent pages of this paper.
Pasteur gave a memorable demonstration of the efficiency of his method of anthrax vaccination. At Pouilly-le-Fort, in the midst of an assemblage of scientists, delegates of agricultural societies, government officials, landlords, farmers and representatives of the press, he performed the following experiment: Sixty sheep were taken; ten of these were put aside, twenty-five were vaccinated with the two attenuated anthrax vaccines at an interval of twelve days, and twenty-five were left untouched. Twelve days afterward the two groups of twenty-five sheep were inoculated with virulent anthrax; and the result was that at the next visit the twenty-five unvaccinated and one vaccinated pregnant female were found dead, while twenty-four out of the twenty-five that had been vaccinated were perfectly well, and exhibited during the whole time they were kept under observation the same degree of health as the ten sheep that had been put aside for comparison.
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An impetus was given by these discoveries to researches having for their object the protection of men against infectious diseases. The most important of these researches was Pasteur’s own into the nature of hydrophobia and rabies, and the way of inoculating against that disease. This was followed a few years later by the preparation of a prophylactic against cholera.