Summary Report of the Experiments Conducted at Pouilly-Le-Fort, Near Melun, on the Anthrax Vaccinationa

CLASSICS OF BIOLOGY AND MEDICINE

Summary Report of the Experiments Conducted at Pouilly-le-Fort, Near Melun, on the Anthrax Vaccinationa

Louis Pasteur (with the Collaboration of Mr. Chamberland and Mr. Roux)

[Editorial note: The famous French microbi- attenuation, but with vaccine prepared by the ologist and chemist, Louis Pasteur, pioneered bichromate inactivation methods of his com- the use of bacterial vaccines for prevention of petitor Jean-Joseph Henri Toussaint.] infectious diseases in animals and humans. One of his early successes was in the development of a vaccine for the agriculturally important disease anthrax, a vaccine that is In a lecture which I presented to the still in use today for animals worldwide and Academy last February 28, the purpose of humans in some countries. He demonstrated which was to discover a method for prepa- the effectiveness of his vaccines often with ration of attenuated anthrax, I spoke on dramatic public trials, one of the most famous behalf of myself and my young collabora- of which was the spectacle at the small French village of Pouilly-le-Fort in May tors: 1881. This paper, translated from the original Each one of our attenuated anthrax microbes report in French, describes the set-up and out- is a vaccine for the virulent microbe, that is to come of this public test of anthrax vaccina- say, an adapted virus which produces a more tion. Pasteur uses the term virus in its nine- benign variety of disease. After all, what teenth century context meaning any agent that could be easier than to find, among the off- transmits disease rather than in its more spring of the anthrax microbe, some adapted restricted modern sense. It is interesting to ones which can give the anthrax fever to note that neither here nor elsewhere does sheep, cows and horses without having them Pasteur provide a description of the methods perish? We have practiced this procedure with of preparation of his vaccine or other experi- great success in sheep. As soon as the time mental details. He kept these confidential. comes for rounding up the herds in Beauce, Indeed, recent scholarship (G.L. Geison, The we will try to apply this method on a large Private Science of Louis Pasteur, 1995) scale. shows that his public pronouncements allud- ing to the success of his method for vaccine preparation are at odds with his laboratory Anthrax is responsible for the loss of notebooks, which show that he conducted many millions of animals every year in these famous tests at Pouilly-le-Fort not with France. Consequently, it would be desir- vaccine prepared by his method of oxygen able to be able to save the ovine, bovine, aOriginally published in Comptes Rendus de l’Academie des Science92:1378-1383, June 13, 1881. Translated by Tina Dasgupta, Yale School of Medicine, Original Contributions Editor, Yale Journal of Biology and Medicine.

59 60 Pasteur: Anthrax vaccination

and equine species if the above method of prove that the new sheep can be infected spontaneously by the vaccination can be offered to us almost anthrax microbes brought back to immediately, and without having to wait the surface of the ground by earth- for the sheep round-up. worms. Last April, the president of the 8.Another twenty-five other new Agriculture Society of Melun, Baron de la sheep will be herded a few meters Rochette, proposed that I conduct a deci- away from the enclosure described sive experiment to obtain the results of above. No animals infected with which I recently presented to the anthrax have ever been interred in Academy. I was pleased to accept, and on this new area, and thus this experi- April 28 we met and agreed upon to the ment will show that none of these following: new sheep will contract anthrax. 1.The Agriculture Society of Melun Addendum to the preceding agreement: will put sixty sheep at the disposal of Mr. Pasteur. When the president of the Agriculture 2.Ten of these sheep will not undergo Society of Melun asked that these experi- any treatment. ments be extended to cows as well, I 3.At an interval of twelve to fifteen responded that we were ready to do so. days, twenty-five of these sheep will However, I would like to inform the receive two vaccinations of unequal- Society that, at the moment, the vaccina- ly attenuated anthrax. tion experiments in cows are not at as 4.These twenty-five sheep will be advanced a level as in sheep, so that the inoculated by very virulent anthrax results obtained may not be as obviously at the same time as the remaining twenty-five (uninoculated sheep), convincing as with the sheep. In any case, after a new interval of twelve or fif- I would like to acknowledge the Society of teen days. All twenty-five sheep that Melun for having put ten cows at our dis- were not vaccinated will perish; all posal. Six of these cows were vaccinated twenty-five that were vaccinated and four were not. After receiving the vac- will resist infection, and we will ulti- cination, the ten cows were inoculated mately compare them with the ten with a highly virulent strain of the microbe untreated sheep above. This is to (at the same time as the fifty sheep). I show that vaccination does not pre- hypothesized that the six vaccinated cows vent the sheep from returning to a would not become very ill, while the four normal state. unvaccinated cows would perish or at least 5.After the general inoculation of very virulent microbe to the two batches become very ill. of vaccinated and unvaccinated I agree that my predictions sounded sheep, the fifty sheep will remain boldly prophetic, and it is true that my together in the same cattle shed; one brashness can be excused only by clear will distinguish one from the other successes with these experiments. Several by punching a hole in the ear of the people had the kindness to reproach the twenty-five vaccinated sheep. scientific imprudence of this approach. 6.All the sheep which will die of the However, the Academy must understand anthrax will be buried in distinct pits that we devised such a scheme without neighboring each other in a pallisad- solid, supporting results from previous ed enclosure. experiments, despite the fact that none of 7.In May 1882, we will put twenty- five new sheep — which have never these previous experiments were as large been subjected to these treatments as the one we are proposing. Fortune, how- — in the enclosure in question to ever, favors those who are prepared, and it Pasteur: Anthrax vaccination 61

is in this spirit, I believe, that I might quote When the visitors arrived on June 2, the words of the inspired poet: Audentes they were astounded. The twenty-four fortuna juvat. sheep, the goat, and the six cows which The experiments started on May 5, in had received the vaccinations of attenuated the commune of Pouilly-le-Fort, near anthrax, all appeared healthy. In contrast, Melun, in a farm belonging to Mr. twenty-one sheep and the goat which had Rossignol. not been vaccinated had already died of Upon a request by the Agriculture anthrax; two other unvaccinated sheep Society, which had undertaken these tests, died in front of the viewers, and the one we agreed to replace two sheep with two remaining sheep died at the end of the day. goats, and since we had not specified con- The unvaccinated cows had not died ditions of age or of breed, the fifty-eight [upon exposure to the virulent anthrax]. sheep were of different ages, breeds and We have already shown before that cows sexes. Of the ten animals from bovine were less prone than sheep to die of species, there were eight cows, one ox and anthrax. However, [within 48 hours], the one bull. unvaccinated cows all showed significant On May 5, 1881, we used a Pravaz edema at the place right behind the shoul- syringe to inoculate twenty-four sheep, der where they were inoculated. In some one goat and six cows each with five drops cases, this edema increased in severity in attenuated anthrax. On May 17, we revac- the following days, to the extent that they cinated these twenty-four sheep, the goat contained several liters of fluid: one of and the six cows by more anthrax. While these swellings even touched the ground. this microbe was also attenuated, it was The temperature of these cows increased more virulent than the anthrax used in the 3º C. The vaccinated cows did not show an previous vaccination. elevation in temperature, swelling, or even On May 31, we proceeded to inocu- the slightest loss of appetite. This confirms late these animals with the very virulent the predicted outcome to be quite as com- anthrax which would determine the effica- plete for the cows as for the sheep. cy of the preventative inoculations given On Friday June 3, one of the vaccinat- between May 5 and 17. To this end, we ed ewes died. An autopsy was performed inoculated the thirty-one vaccinated ani- that same day by Mr. Rossignol and Mr. mals above [with the very virulent strain], Garrouste, a military veterinarian. The ewe and also twenty-four other sheep, one goat was pregnant, carrying a full-term lamb and four other cows, none of which had which had died in her womb twelve to fif- been exposed to this treatment previously. teen days ago. The opinion of the veteri- The very virulent anthrax used on narians performing the autopsy was that May 31 was regenerated from spores of the death of this ewe was due to the death the anthrax parasite stored in my laborato- of her fetus. ry since March 21, 1877. The experiments which I have come To make the experiments more defin- to report have elicited sharp curiosity in itive, we inoculated both a vaccinated and Seine-et-Marne and in its neighboring an unvaccinated animal [with the very vir- departments. They were witnessed by sev- ulent anthrax]. With the inoculations com- eral hundred people, of which I will men- pleted, all the people present decided to tion the President of the Agriculture meet again on Thursday June 2, 48 hours Society of Melun, Mr. de la Rochette; Mr. after the inoculations with the very viru- Tisserand, director of Agriculture; the pre- lent anthrax. fect of the Seine-et-Marne, Mr. Patinot; one of the senators of the department, Mr. 62 Pasteur: Anthrax vaccination

Foucher de Careil, president of the cholera and anthrax. Today, these individ- General Council; Mr. Bonley, member of uals are the most enthusiastic disciples of this Academy; the mayor of Melun, Mr. our new doctrines. One of them — who Marc de Haut, president, and Mr. was much more skeptical at the beginning Decauville, vice-president of the Fair of — trusts our method to the extent that he Seine-et-Marne; several general advisers; wants to start a vaccination program him- all major farmers of the district; Mr. self [Biot]. This is a good omen. They will Gassend, director of the Agricultural become proponents of the anthrax vacci- research station of Seine-et-Marne; Dr. nation; we have converted them at last. It Remilly, president and Mr. Pigeon, vice- is particularly important that, at least for president of the Agriculture Society of the time being, the vaccine cultures are Seine-et-Oise; Mr. de Blowitz, correspon- prepared and controlled in my laboratory. dent of the Times; the military surgeons A faulty application of the method could and veterinarians stationed in Melun; compromise the future of a method that finally, a great number of civil veterinari- promises to be of great service to the field ans, among which I will name, in addition of agriculture. to Mr. Rossignol of Melun, Garnier and In summary, we now possess a vac- Percheron, of Paris; Nocart, from Alfort; cine of anthrax which is capable of saving Verrier, from Provins; Biot and Grand, animals from this fatal disease; a virus- from the Medical Society of Yonne; vaccine that is itself never lethal; a live Thierry, from Tonnerre; Butel, from vaccine, one that can be cultivated at will Meaux; Borgnon, from Couilly; Caffin, and transported without alteration. Finally, from Pontoise; Bouchet, from Milly; Pion, this vaccine is prepared by a procedure that from Grignon; Mollereau, from we believe can be generalized since, the Charenton; Cagnat, from Saint-Denis, etc. first time around, this was the method we I cannot conceal my satisfaction in used to develop a fowl cholera vaccine. naming these veterinarians who were Based on all the conditions that I list here, brought to Pouilly-le-Fort, to the farm of and by looking at everything only from a their colleague Mr. Rossignol, by a desire scientific point of view, the development of to know the truth. A large number of them a vaccination against anthrax constitutes — if not all — had been incredulous at the significant progress beyond the first vac- results of our [previous] treatments. In cine developed by Jenner, since the latter their conversations and journals, they had never been obtained experimentally. resisted accepting as true the artificial preparation of our vaccines against fowl