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23. Pasteur: The Chemist Who Themist Who Transformed Medicine



THE LIFE WORKS of some men seem to have been specially designed as vehicles by which bits of wisdom of the Infinite may be conveyed to waiting mankind. Among those so selected must have been Louis Pasteur. “By the design of his life,’’ wrote Stephen Paged, “he was always being led straight . . . from each discovery to the next . . . he taught the whole world a new way of thinking of the infective disease, and a new way of dealing with them.’’ Not only had Pasteur the ability to discover new facts: he knew how to adapt his findings to practical applications, and how to teach and inspire others. His discoveries live on in the works of man who came after him. By the middle of the nineteenth century, medical men knew but little more than had their Greek forebears about actual causes of the great scourges of the race-the plagues, the fevers, and the pestilences. At the close of the century, at the end, of Pasteur’s career, the germ theory had been proved and no longer was seriously contested; the patterns of many infective disease were understood; methods had been devised for preventing or for combating some of the most serious infections; conditions under which surgical procedures were carried out had been revolutionized; and the sciences of bacteriology and of preventive medicine had been launched. Indeed, within few life spans have such revolutions taken place in medicine; and he who had brought them about was not a physician, but a chemist. His laboratories were not spacious expanses of glass and steel, but miserable garrets; he had not a background of wealth and means, but was the son of a poor tanner. Louis Pasteur was born December 27, 1822, to Jean-Joseph Pasteur and his life, Jeanne-Etiennette, in a very modest hone adjacent to a tannery, in Dile, Department of Jura, and France. He grew up in nearby Arbois, in which city his father set up a tannery in 1827. Louis’ preliminary education was in schools in Arbois, and his early inclinations were toward art-as in borne out by his youthful paintings of his mother, of his father, and of neighbors. Lousi attended the Royal College of Besancon, from which he received his baccalaureates in science in 1842, ironically with a grade of “mediocre” in chemistry. His eyes set upon the goal of the Ecoloe Normale, Pasteur went to Paris in the fall of 1842, where he tutored to finance his studies until he passed examinations admitting him to the Ecole Normale, Pasteur went to Paris in the fall of 1842, where he tutored to finance is studies until he passed examinations admitting him to the Ecole Normale in October, 1843. Pasteur was appointed assistant to the chemist A.J. Balard at the Ecole Normale, in 1946, and attended courses given by Jean-Baptiste Dumas, then France’s most celebrated chemist, at the Sorbonne. In 1847, Pasteur passed his tests in chemistry and in physics, and developed interest in crystallography.


The year 1848 proved to be fateful for Louis Pasteur; he participated in the revolution of that tear. Peace restored, he returned to his study of crystals, and in his twenty-sixth year, achieved his first claim to scientific fame by presenting to the Academy of Sciences his Report on the Relationship between the Crystalline Form, the Chemical Composition, and the Direction of Rotatory Polarization. Therein he reported having found that tartaric acid crystallizes in two chemically identical but physically different forms, and that these right-faceted and left-faceted crystals in solution consistently rotate rays passing through a polarimeter to the right, or to the left, in accordance with their physical character. Met with skepticism, Pasteur won attention and friendship from leading French scientists, including Jean-Baptiste Biot, when at their insistence he presented them with carefully worked out proof. The joy of this initial triumph was marred for Pasteur by the sudden death of his mother.


In September, 1848, Pasteur was appointed Professor pf Physics at the lyceum (High school) in Dijon, but in December he was offered a collegiate position as Assistant Professor Chemistry at the Faculty of Sciences in Strasbourg. There he could continue his researches on crystals. There, too, he married, may19, 1849, Marie Laruent, daughter of Rector of the college. Marie Pasteur proved to be just the type of wife the scientist needed-she was tolerant of his devotion to research, assisted him with his notes and his records, and looked after his physical well during an active and hectic career.


Pasteur’s teaching career progressed. He was made full Professor off Chemistry at Strasbourg in 1852, and in 1854 he was appointed to the Chair of Chemistry of the Faculty of sciences in Lille, as well as Dean of the University. His work and crystals had launched a new branch of science, stereochemistry; and in Lille, in the heart of the sugar beet country, Pasteur began his studies on fermentation of sugar to form alcohol. Thus did Pasteur, the chemist, begin transformation to Pasteur, the microbiologist? With the help of his microscope Pasteur found the microorganisms were responsible for alcoholic fermentation; and that faulty fermentation resulted from contamination by unwanted types of organisms.


In October, 1857, Pasteur returned to Pairs, having accepted appointments as Administrator of the Ecole Normale abd as Director of Scientific Department of the College. There he sought a place for a LABORATORY. The Only space available was two small rooms in an attic, dark, unsuitable, hot in summer, cold in winter. Nevertheless, Pasteur made the best of them and was able to continue his research. A year later, he moved to a slightly better suite of five narrow rooms. Hid incubator, installed under a stairway, could be approached only on his knees. Finances for laboratory operation came largely from Pasteur’s own pocket. However, as his associate, Emile Ducal, said in later years, “From this wretched garret, which nowadays would hardly be considered fit for a rabbit’s cage, radiated the movement that has revolutionized, all aspects of science.” In these laboratories Pasteur continued his studies on fermentation, culmination in a paper before the Academy of Sciences in 1859. From alcoholic fermentation Pasteur processed to study lactic fermentation; then to butyric microoganisma. Fermentation studies in these laboratories at the Ecole Normale let to Pasteur’s greatest and most revolutionary contributions to science-study and refutation of the theory of spontaneous generation, undisputable proof of their specificity in causing disease. These studies began in 1860.


Pasteur began with study of atmospheric air. His microscope confirmed his belief that germs floated in it. The next question was: Do germs enter putrescible substances due to exposure to air, or are they generated within the substance? Pasteur conducted exhaustive experiments, in the laboratory, on mountain tops, and under every Conceivable condition. When his flasks were heated to boiling and sealed to air, no growths appeared. When his flasks opened, exposed, and resealed in comparative’s pure air of mountain heights remained clear. When reopened at lower levels, growths appeared. But Poached and other supporters of spontaneous generation dogged Pasteur with denunciation, with derision, and with purported contrary evidence.


Pasteur’s most spectacular demonstrations were made with his swan’s neck flasks. Broth was placed in the flask, the neck of which was heated and drawn out to form a lazy, the swan’s neck shape. When the broth in the flask was heated to boiling, air was forced out; on cooling, air pressure outside forced air to re-enter the flask. Due to the lazy shape of the small tubular neck, if entering air were permitted to flow into the flask slowly, air-borne particles would fall by gravity to the surface of the lower curve of the neck, and, as long as the flask was not tipped or agitated, no microbial growth occurred. If, however, the flask were tilted until broth touched the lower curve of the neck, or, if air were drawn in rapidly by violent agitation, growth appeared.


Pasteur summed up his findings in a treatise entitled: Organized Corpuscles Existing in Atmosphere, for which the Academy of Sciences awarded him a prize. But, to clarify his position and to confound his opponents, Pasteur requested that a commission be appointed to settle the debates. Interest in the dispute had reached far beyond the walls of the Academy, however; and on April 7, 1864, Pasteur held a symposium on spontaneous generation, at the Sorborne, before a large audience which included leading scientists of the day. After describing his experiments in detail, Pasteur summed up his findings with these words:


“There is now no circumstance known in which it can be confirmed that microscopic beings have come into the world without germs, without parents similar to themselves. Those who maintain this view are the victims of illusions, of ill-conducted experiments, blighted with errors that they have either been unable to perceive or unable to avoid.” Thus was spontaneous generation laid to rest and the “germ theory’ officially introduced to science. A year later, in 1865, medicine was to receive its first dividend from Pasteur’s work: Joseph Lister, surgeon of Glasgow, Scotland, seeking to apply in practice Pasteur’s findings, used carbolic acid to disinfect the wound of a compound fracture in a patient at the Glasgow Infirmary, and introduced the era of antisepsis in surgery. Detractors were long-lived, however, in Pasteur’s own country and elsewhere. As late as 1886, Morris Longstreth, M.D., of Philadelphia, Pennsylvania, published a serious, 16-page dissertation “Against the Germ Theory of Disease,” in The Therapeutic Gazette.


Important as they were, Pasteur’s experiments concerning spontaneous generation and controversies with Pouchet did not occupy all of his time: he introduced the autoclave to kill hardy germs and spores; he applied his growing knowledge of microbes to problems of fermentation; in 1861, he showed Orleans vinegar manufactures how to improve their yield. From vinegar, he turned to the study of wines. He demonstrated that proper fermentation resulted from action of air-borne wild yeasts deposited on ripening fruit; and that “diseases’ of wines, affecting both their flavor and their keeping qualities, resulted from other parasitic germs either having fallen on the fruit, or having been introduced into the vats or presses. From these studies arose Pasteur’s suggestion that vintners might protect their product, without injury, by heating bottled wine for several minutes at 55 C. (131 F.). Thus was the process, now called pasteurization, introduced. Importance of its subsequent application, in fields of public health and of food preservation, is well known. Pasteur’s wine studies were summed up in his book, Wine and Its Maladies, published in 1866.


Pasteur accepted a professorship at the School of Fine Arts in 1863, in addition to his work at Ecole Normale. The triumphs of this active period of his life were marred by deaths of his father, in 1865, and of three of his daughters: Jeanne, in 1859; Camille, in 1865; and Cecile, in 1866. Only his son, Jean-Baptiste, born in 1851, and his daughter, Marie-Louise, born in 1858, survived. In later years, the son entered government service; and Marie married a young secretary, Rene Vallery- Radot, who became Pasteur’s confidant and biographer.


In 1865, at the insistence of the French Senate, Pasteur undertook studies of two diseases that were responsible for eliminating passage of these parasitic diseases from one generation of worms to the next. Pasteur’s methods saved the silk industry, not only in France, but also in Austria, in Italy, and in Asia Minor. More troubles were in store for Pasteur. In 1867, a series of disturbing incidents at Ecole Normale resulted in Pasteur’s is being relieved of administrative duties. He accepted a chair at the Sorbonne, and a laboratory for physiologic chemistry was built for him at the direction of Napoleon III. In 1868, Pasteur suffered a stroke; which seriously threatened his life and resulted in partial paralysis of his left arm and leg. About the time his work on silk worms was completed, in 1870, the Franco-Prussian War broke out. Not only was Pasteur’s work disrupted; he faced dual concern for the welfare of his country and for that of his only son, then serving in the military. Election of Pasteur (by a margin of one vote) to membership in the Academy of Medicine, in 1873, was a great tribute to the chemist. It brought him into close contact with his friend, Claude Bernard. It also precipitated an almost endless fight with official medicine.

In 1874, too, Pasteur was forced by health to give up his chair at the Sorbonne. He also received from the National Assembly an award in the form of a life pension.

Though Pasteur already had made many important and basic discoveries, the years 1877 t0 1886 were filled with new discoveries of great significance to medicine and to science. Studies a anthrax in livestock proved both that a aerobic spore-forming bacterium is its cause, and that genres cause disease. Further work demonstrated that other germs cause furunculous (boils) and puerperal (childbed) fever in new mothers. These findings demonstrated-despite constant attacks from opponents-the importance of measures to prevent infection and to avoid contagion. However, it was during his work on chicken cholera, in 1879, that a laboratory “accident” led Pasteur to discover methods of attenuating bacterial cultures, of decreasing band of increasing their toxic attributes, at will and of taming dangerous microbes so that they might be changed from killers to benefactors – there by to pave the way for development of vaccines and of antitoxins.


With the collaboration of his former pupil, Emil Roux, Pasteur in 1880 began the study of rabies (hydrophobia), a dreaded infection that always fatal to man and to animals. Terror reigned when rabid dogs or other animals were fiscovere4d, for it was well known that prolonged, agonized illness leading to death frequently followed vicious biters characteristic of these animals’ attacks. Pastier set out to see what could be done to combat rabies.


By 1884, Pasteur had not only developed a method of cachinnating dogs to render them immune to rabies; he had also developed a vaccine against swine erysipelas, and had supervised an expedition to Egypt to study a local outbreak of cholera.
Pasteur did not consider the rabies problem solved by vaccine alone. Inability to discover the causative microbe (later found to be a sub-microscopic virus) handicapped him; however, he did discover the moist virulent source of infective material: the medulla oblongata, or lowermost portion of the brain. Also, Pasteur found that by drying the cord aseptically, the virulence of causative factor that it drying the cord aseptically, the virulence of the causative factor of rabies decreased to the point of virulence in 14 days. Since the incubation decreased to the point of virulence in 14 days. Since the incubation period (from time to bite to onset of disease) for rabies was several weeks, Pasteur found that he could successfully treat an animal, already bitten by a rabid animal, if treatment were began within a few days after the injury. Treatment consisted of injecting daily ban emulsion of cord, beginning to the least virulent material (dried for 14 days) and progressing to the most corpulent (dried for 1 or 2 days). Thus, rabies could be prevented and lives saved. These experiments on animals were repeated and repeated; but Pasteur hesitated to try his method on humans.


Fate precipitated the crucial, experiment: A provincial mother appeared at the laborites with her nine-year-old son, Joseph Meister. The boy had been bitten fourteen times, two days before, by a dog declared rabid. The age of the child, plus the severity of his wounds, made it seem inevitable that he would develop rabies and die. The mother’s imploring, the family doctor’s urging, and the favorable consensus of this scientific colleagues persuaded Pasteur to try his vaccine on the boy. A physician began treatment, July 7, 1885-first, administering a dose of the weakest, then progressively, doses of more virulent emulsions of infected cord. Pasteur anxiously watched for signs of reaction; but the boy stood the test, far better than the scientist. (In later years, Joseph Meister was to join the staff of the Pasteur Institute.) A few weeks later, Pasteur presented to the Academy of Sciences his famous report: Method of Preventing Rabies after a Bite. Publication of this report brought pilgrims to his laboratory for rabies treatment-some patients coming from as far away as New York. On March 1, 1886, Pasteur submitted to the Academy of Sciences his further report. Of 350 persons who had received treatment following bites of rabid animals, there had been but one death-a girl brought to him thirty-seven days after she had been bitten by a rabid animal.


Physicians and scientists from all over the world now flocked to Pasteur’s laboratories to learn firsthand about prophylactic treatment against rabies, and about other Pasteurian doctrines which were rapidly revolutionizing the practice of medicine.
The excitement and labor of this period proved too much for the ageing man: in November, 1886, he developed symptoms of coronary insufficiency. However, with the help of Madame Pasteur and his loyal son-in-law, Rene Vallery-Radot, Pasteur was enabled to supervise the ever-widening scope of work of his associates.


November 14, 1888, the Institute that bears his name was dedicated. The good work went forward: Roux then developed servo-therapy for tetanus; Chalmette, serotherapy for snake bites; and Metchinikoff established existence and action of phagocytes in the blood, and car fried out basic studies on syphilis. Pasteur’s seventieth birthday, December 27, 1892, was occasion for an ovation at the Sorbonne, attended by scientists and political figures from all over the world. Lister paid the tribute: “Pasteur has lifted the veil that for centuries has hidden the infections diseases.’’ At the end of the ceremonies, Pasteur, too moved to speak, asked his son to read his acknowledgment.


The great scientist’s health steadily declined, limiting him to occasional observance of work in the laboratories and to visits from members of his devoted staff. After a series of cerebrovascular accidents, death came to Pasteur, September 28, 1895.
The government of France arranged an imposing state funeral for its great citizen, and Pasteur’s body was interred in a marble crypt in a small chapel within the Institutes On its walls may be seen mosaics and plaques all duding to his work; and most impressive is the imposing list of the areas in which Pasteur’s principal discoveries were made: Molecular Asymmetry; Fermentations; Spontaneous Generation; Studies On Wine; Diseases of Silkworms; Studies on Beer; Virulent Diseases; Virus Vaccines; and Prophylaxis of Rubies.

THE PICTURE

Proof that microbes are reproduced from parent organisms, and do not result from spontaneous generation, came from careful experiments in makeshift laboratories of France’s famed chemist and biologist, Louis Pasteur (1822-1895), at Ecole Normale, Paris. Behind him are portraits of his father and mother, which he painted during his youth. Mme. Pasteur waits patiently for him to complete an observation. From basic work begun in these laboratories came proof of the germ theory of disease, which transformed medical practice; vaccines for virulent diseases, including anthrax and rabies; solution of many industrial biochemical problems; and founding of the famed Pasteur Institute.