The life of Pasteur

by René Vallery-Radot

Pure cultures of this bacillus, injected on the surface of the excoriated fauces of rabbits, guinea-pigs, and pigeons, produce the diphtheritic membranes: Messrs. Roux and Yersin demonstrated this fact and ascertained the method of its deadly action.

Dr. Roux, in a lecture to the London Royal Society, in 1889, said: “Microbes are chiefly dangerous on account of the toxic matters which they produce.” He recalled that Pasteur had been the first to investigate the action of the toxic products elaborated by the microbe of chicken-cholera. By filtering the culture, Pasteur had obtained a liquid which contained no microbes. Hens inoculated with this liquid presented all the symptoms of cholera. “This experiment shows us,” continued M. Roux, “that the chemical products contained in the culture are capable by themselves of provoking the symptoms of the disease; it is therefore very probable that the same products are prepared within the body itself of a hen attacked with cholera. It has been shown since then that many pathogenic microbes manufactured these toxic products. The microbes of typhoid fever, of cholera, of blue pus, of acute experimental septicæmia, of diphtheria, are great poison-producers. The cultures of the diphtheria bacillus particularly are, after a certain time, so full of the toxin that, without microbes, and in infinitesimal doses, they cause the death of the animals with all the signs observed after inoculation with the microbe itself. The picture of the disease is complete, even presenting the ensuing paralysis if the injected dose is too weak to bring about a rapid death. Death in infectious diseases is therefore caused by intoxication.”

This bacillus, like that of tetanus, secretes a poison which reaches the kidneys, attacks the nervous system, and acts on the heart, the beats of which are accelerated or suddenly arrested. Sheltered in the membrane like a foe in an ambush, the microbe manufactures its deadly poison. Diphtheria, as defined by M. Roux, is an intoxication caused by a very active poison formed by the microbe within the restricted area wherein it develops.

It was sufficient to examine a portion of diphtheritic membrane to distinguish the diphtheritic bacilli, tiny rods resembling short needles laid across each other. Other microbes were frequently associated with these bacilli, and it became necessary to study microbian associations in diphtheria. The Klebs-Loeffler bacillus, disseminated in broth, gave within a month or three weeks a richly toxic culture; the bottom of the vessel was covered with a thick deposit of microbes, and a film of younger bacilli floated on the surface. By filtering this broth and freeing it from microbes, Messrs. Roux and Yersin made a great discovery: they obtained pure toxin, capable of killing, in forty-eight hours, a guinea-pig inoculated with one-tenth of a cubic centimetre of it.

Now that the toxin was found, the remedy, the antitoxin, could be discovered. This was done by Behring, a German scientist, and by Kitasato, a Japanese physician. Drs. Richet and Héricourt had already opened the way in 1888, while studying another disease.

M. Roux inoculated a horse with diphtheritic toxin mitigated by the addition of iodine, in doses, very weak at first, but gradually stronger; the horse grew by degrees capable of resisting strong doses of pure toxin. It was then bled by means of a large trocar introduced into the jugular vein, the blood received in a bowl was allowed to coagulate, and the liquid part of it, the serum, was then collected; this serum was antitoxic, antidiphtheritic—in one word, the long-desired cure.

At the beginning of 1894, M. Roux had several horses rendered immune by the above process. He desired to prove the efficiency of the serum in the treatment of diphtheria, with the collaboration of MM. Martin and Chaillou, who had, both clinically and bacteriologically, studied more than 400 cases of diphtheria.

There are in Paris two hospitals where diphtheritic children are taken in. It was decided that the new treatment should be applied at the hospital of the Enfants Malades, whilst the old system should be continued at the Hôpital Trousseau.

From February 1, MM. Roux, Martin, and Chaillou paid a daily visit to the Enfants Malades; they treated all the little diphtheria patients by injection, in the side, of a dose of twenty cubic centimetres of serum, followed, twenty-four hours later, by another dose of twenty, or only of ten cubic centimetres. Almost invariably, not only did the membranes cease to increase during the twenty-four hours following the first injection, but they began to come away within thirty-six or forty-eight hours, the third day at the latest; the livid, leaden paleness of the face disappeared; the child was saved.

From 1890 to 1893 there had been 3,971 cases of diphtheria, fatal in 2,029 cases, the average mortality being therefore 51 per 100. The serum treatment, applied to hundreds of children, brought it down to less than 24 per 100 in four months. At the Trousseau Hospital, where the serum was not employed, the mortality during the same period was 60 per 100.