Louis Pasteur And "Le Rage"—: 100 Years Ago

LOUIS PASTEUR AND "LE RAGE"—100 YEARS AGO HAROLD MALKIN* In the May 27 [1, p. 500] and June 3, 1886 [1, p. 524], issues of the Boston Medical and Surgical Journal, there appears a long letter written by H.O. [2, p. 185],1 in the "Correspondence" section, that describes in detail a visit to Louis Pasteur's laboratory where hundreds of patients from all over the world who had been bitten by rabid animals came to receive the new Pasteur treatment. The development of the rabies vaccine was the culmination of a brilliant career of scientific investigations by Pasteur. It has been speculated that his interest in this disease had its origins in his childhood memories of a rabid wolf charging through his village biting both man and beast, with resulting human fatalities. Although from a purely scientific standpoint the rabies program was probably no more important than his studies on fermentation, silkworm disease, spontaneous generation, chicken cholera, and anthrax, it was the nature of the rabies work that made the name of Pasteur almost a household word in 1886. Rabies did not have the quantitatively devastating character of the black plague, cholera, typhus, or yellow fever, but there were very few diseases that had as much drama associated with almost every case—considering the initial violence and trauma by the rabid animal, the anxiety of waiting during the long incubation period, and finally, perhaps, the terrible signs and symptoms leading to death in all cases. For a period of 5 years, starting in 1880, Louis Pasteur and his two assistants, Emile Roux and Charles Chamberland, carried out a series of experiments that could be considered one of the most brilliant and imaginative in the history of biology. The program had as its goal the attenuation of the rabies virus for use in therapy. The difficulties were enormous. Pasteur, a nonphysician chemist, almost 60 years old, par- *Oslerwelch Laboratories, 488 McCormick Street, San Leandro, California 94577. 1 In most likelihood, H.O. was Hamilton Osgood, a Philadelphia physician who was a lecturer at Jefferson Medical School and was an occasional contributor to the Boston Medical and SurgicalJournal.© 1986 by The University of Chicago. All rights reserved. 003 1 -5982/87/300 1 -05 1 0$0 1 .00 40 Harold Malkin ¦ Louis Pasteur Fig. 1. —Louis Pasteur and his patients circa 1886 tially paralyzed from a stroke, undertook a crusade against a viral disease when most medical people still did not accept the ideas that microorganisms were etiological factors in any infectious disease. In addition, the natural course of rabies was unpredictable, with an incubation period varying from weeks to months, and not all individuals bitten by rabid animals developed rabies. There was no way of knowing whether a vaccine could be produced to give protection against rabies, particularly after the patient had been bitten by a rabid animal. During the first years ofwork, all attempts to isolate a causal organism that could be seen under the microsope or grown in bacteriological media failed. In retrospect this failure was not surprising, because, as more modern research was to show, the rabies virus was too small to be seen with the light microscope, and it was not possible to grow viruses in nonliving media. However, characteristic of Pasteur, his intellectual agility and his mastery of the experimental method always enabled him to devise new techniques when his intuition made him aware that older methods would no longer be fruitful. He eventually developed a method of growing the agent and consistently producing rabies in 6 days by inoculation of nervous tissue from a rabid dog into the brains ofrabbits. This being accomplished , he was then able to solve the problem ofattenuation ofthe virus by serially desiccating the brains of rabid rabbits. By inoculating this material into dogs and then allowing these animals to be bitten by other rabid animals, he was able to produce immunological protection. He presented the data at the International Medical Congress in August 1884, after which great public pressure developed to use the vaccine on humans. In July 1885, against the advice of his chief assistant, Roux, Pasteur released his vaccine to be used on Joseph...