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    Pasteur: High Priest ofMicrobiology

    Wherever he turned, Pasteur brought great insightto benefit humanity

    R OBERT I. K R A S N E R '

    This year marks the centennial of Louis Pasteursdeath, occasioning a series of events organized byUNESCO and the Pasteur Institute to celebrate hismany contributions.

    When one thinks of the famous names associatedwith the history of medical science, certainly Pasteurranks among the greatest. Trained as a chemist, Pas-teurs phenomenal success in diverse fields of researchis remarkable. In his 73-year life span, Pasteur distin-guished himself as a teacher, patriot, scientist, andfamily man. His studies on crystallography, fermenta-tion, diseases of wine and beer, spontaneous genera-tion, silkworm disease, cholera, and anthrax were noless significant than was his work on rabies.

    However, the rabies work was Pasteurs crowningglory and established his reputation. Pasteur was 63when he first treated a patient for rabies, and he was inpoor health from overwork and the effects of a strokesuffered at age 46. But Pasteur was already a hero inFrance and beyond.

    Pasteur Heralded in Many Venues

    In 1950, Selman A. Waksman wrote, Pasteur wasnot only the great scientist who was largely responsiblefor the creation of the science of microbiology, he wasits high priest, preaching and fighting for the recogni-tion of its importance in health and in human welfare.

    Numerous books have been written about Pasteur;towns, buildings, avenues, boulevards, streets, andstatues bear his name. Further, many texts in micro-biology and immunology as well as books in generalbiology refer to and contain illustrations about Pas-

    Robert I. Krasner is a professor of biology at Provi-dence College in Providence, R.I.

    VOL.61,NO.11,1995

    teur. Even Hollywood got into the act in 1930 with thefeature film Life of Pasteur, starring Paul Muni. TheSociety of Illinois Bacteriologists established the Pas-teur Award in 1948, which each year recognizes anindividual who has made an outstanding contributionto microbiology.

    Who Was Louis Pasteur?

    Pasteurs early years in school were not particularlyremarkable. He was an average student with a fond-ness and a talent for painting; he did not displaybrilliance. Sent at 16 to Paris to prepare for college, hequickly became homesick and returned home. Eventu-ally, he studied chemistry and graduated but withoutdistinction. However, this mediocrity soon gave way toacademic success at the Sorbonne in 1842-1843. Hewrote in a letter, Once you have got into the way ofworking you cannot live without it. Besides everythingin this world depends on it. This strong work ethicremained with Pasteur throughout his lifetime and,undoubtedly, contributed to his success.

    Over the next 25 years, Pasteurs studies movedfrom chemistry to fermentation, to diseases of wine andbeer, to spontaneous generation, and to silkworm dis-ease, after which in the early 1870s he focused ondiseases of higher animals and humans. His academicpositions during these years were numerous and var-ied and included an appointment at the University ofStrasburg in 1848, during which time he met andmarried Marie-Laurent, daughter of the head of theAcademy. His scientific accomplishments earned himthe Legion of Honor at the age of 31, for his contribu-tions to chemistry, and election to the Academy of .Sciences at the age of 40.

    Pasteurs first scientific paper, on crystallography,

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    was published by the French Academy of Sciences in1848. He next turned to fermentation, demonstratingconclusively that it results from microbial action andthus establishing the germ theory of fermentation. Ina paper published in 1861 he wrote: It is, I believe, thefirst known example of animal ferments, and also ofanimals living without requiring oxygen gas. He hadalso discovered anaerobic bacteria.

    Between 1860 and 1864, Pasteur delivered the finalblow to the concept of spontaneous generation. Biologystudents perhaps associate Pasteur more with disprov-ing spontaneous generation than they do with hisresearch on rabies; illustrations of Pasteurs swan-neckflasks are found in most biology texts. On 7 April 1864at the Sorbonne, Pasteur concluded, Never will thedoctrine of spontaneous generation recover from themortal blow of these simple experiments.

    In 1863, at the command of Emperor Napoleon III,Pasteur undertook studies of diseases of, wine andshowed them to be caused by microbial activity. Hiscure was simple-heat to 50-60C-a process nowcalled pasteurization and applied to many foods, par-ticularly milk.

    In 1865, at the request of the French Government,Pasteur began studying the diseases of silkworms, aproblem that threatened to destroy the European silkindustry. Within five years Pasteur not only solved theproblem but established preventive measures. Despitethese professional successes, these years were difficultpersonally for Pasteur, with the deaths of his fatherand of two of his daughters, Camille at the age of 2 andCecile at 12, due to typhoid fever. His own health wasnot good, and he was worn by the ongoing controversyover spontaneous generation and his compulsion towork under primitive conditions.

    A New Lab and New Ambitions

    During this period, Pasteur wrote to Emperor Na-poleon III requesting financial support for a new labo-ratory: I wish to have a much larger laboratory towhich would be attached a wing where experiments onputrid and infectious diseases could be carried outwithout endangering the public health. Pasteurs re-quest for a larger laboratory for experiments on infec-tious diseases represents a turning point to interest inhuman diseases.

    In 1863, Pasteur advised the emperor of his greatambition to learn the causes of putrid and contagiousdiseases. Early in his career he was impressed withthe relationships between fermentation, putrefaction,spontaneous generation, and infectious diseases. Hereasoned that if microbes could cause such damage inwine, in beer, and in other foods, why not in the humanbody? Some years earlier, Robert Boyle, a distin-guished British scientist, had stated that he who coulddiscover the nature of ferments and fermentation,would be more capable than anyone else of explainingthe nature of certain diseases.

    In 1874, Lord Lister paid tribute to Pasteur. In aletter Lister wrote:

    VOL. 61, NO. 11, 1995

    I do not know whether the records of British surgeryever meet your eye. If so, you will have seen from timeto time notices of the antiseptic system of treatment,which I have been labouring for the last nine years tobring to perfection. Allow me to take this opportunityto tender you my most cordial thanks for having, byyour brilliant researches, demonstrated to me thetruth of the germ theory of putrefaction, and thusfurnished me with the principle upon which alone theantiseptic system can be carried out.

    In the early 1870s Pasteur was well renowned andrespected in France and beyond by the scientific com-munity but was regarded as a mere chemist by themedical establishment, which had difficulty acceptingthe germ theory of disease. Nevertheless, in 8 years,Pasteur developed immunizations against fowl chol-era, anthrax, swine erysipelas, and rabies, all of whichhelped to promote the germ theory of disease.

    The anthrax work began in 1887; anthrax killedfrom 25 to 30% of sheep in France and in some parts ofEurope had been epidemic, attacking humans as well.Koch had isolated the bacillus in pure culture. Pasteurconfirmed Kochs work and in the spring of 1881 at afarm in Pouilly-le-Fort, Pasteur dramatically demon-strated the effectiveness of his anthrax vaccination,when the vaccinated flockunvaccinated animals died.

    remained well while the

    Work on Rabies Lionized Pasteur

    The anthrax studies followed on the heels of Pas-teurs paper on the immunization of fowl against chol-era. Jenner established immunization against smallpox.Almost 90 years after Jenner established immunizationagainst smallpox, the first human immunization againstrabies took place, and this treatment established Pas-teur as a popular hero. Which specific event led Pas-

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    teur to study rabies is not known. One story describeshow, as a young boy, Pasteur had witnessed the ago-nies of a victim bitten by a rabid wolf; the victim wasundergoing cauterization of wounds with a red-hotiron.

    Rabies is considered one of the most dread diseases,and stories of this terrifying disease trace to antiquity.One of Homers warriors called Hector a mad dog.Another ancient, Celsus, described the horror of thisdisease in vivid terms: The patient is tortured at thesame time by thirst and by a revulsion toward water.By Pasteurs time, cauterization was the common andequally terrifying treatment; long, heated needles wereinserted deeply into bite wounds, even those on theface. Another practice was to sprinkle gunpowder overthe wound and set a match to it.

    Pasteur developed a method to cultivate the rabiesvirus in the medulla of rabbits and attenuate it bydrying fragments of medulla in sterilized vials. AfterPasteur showed that such material protected dogs, hewas pressured to use the rabies treatment on humans.

    Early treatments for rabieswere nearly as terrifying as the

    disease: hot needles wereinserted into wounds, or they

    were sprinkled withgunpowder and lit with

    matches.

    Pasteur considered testing it on himself, as indicatedin a letter from March 1885: I havent dared to treathumans after bites, but this moment is not too far off,and I should start with myself.

    Pierre Victor Galtier, a professor at a veterinarianschool in Lyon, preceded Pasteur in vaccinating sheepagainst rabies by using saliva from rabid dogs. Galti-ers studies served a