Sunday, January 24, 2010

LOUIS PASTEUR

microbiologist, pioneer of germ research

LOUIS PASTEUR
Born: 27 December 1822
Birthplace: Dole, Jura, France
Died: 28 September 1895 (complications from a series of strokes)
Best Known As: Renowned inventor of pasteurization

Stereochemistry Investigations
Pasteur, under special dispensation from the minister of education, received a leave of absence from his duties as professor of physics at the lycée of Tournon to pursue research on the optical properties of crystals of the salts of tartrates and paratartrates, which had the capacity to rotate the plane of polarized light. He prepared 19 different salts, examined these under a microscope, and determined that they possessed hemihedral facets. However, the crystal faces were oriented differently; they were left-handed or right-handed, thus having the asymmetrical relationship of mirror images. Furthermore, each geometric variety of crystal rotated the light in accordance with its structure, while equal mixtures of the left-and right-handed crystals had no optical activityinasmuch as the physical effects canceled each other. Thus he demonstrated the phenomenon of optical isomers.

Pasteur was elated; he repeated his experiment under the exacting eyes of Jacques Biot, the French Academy's authority on polarized light who had brought Eilhardt Mitscherlich's work to Pasteur's attention. The confirmation was complete to the last exacting detail, and Pasteur, then 26, became famous. The French government made him a member of the Legion of Honor, and Britain's Royal Society presented him with the Copley Medal.

In 1852 Pasteur accepted the chair of chemistry at the University of Strasbourg. Here he found not only a wife but an opportunity to pursue another dimension of crystallography. It had long been known that molds grew readily in solutions of calcium paratartrate. It occurred to him toinquire whether organisms would show a preference for one isomer or another. He soon discovered that his microorganism could completely remove only one of the crystal forms from the solution, the levorotary, or left-handed, molecule.

Studies on Fermentation
In 1854, though only 31 years old, Pasteur became professor of chemistry and dean of sciences at the new University of Lille. The course of his activities is displayed in the publications which he gave to the world in the next decades: Studies on Wine (1866), Studies on Vinegar (1868), Studies on the Diseases of Silkworms (1870), and Studies on Beer (1876).

Soon after his arrival at Lille, Pasteur was asked to devote some time to the problems of the local industries. A producer of vinegar from beet juice requested Pasteur's help in determining why the product sometimes spoiled. Pasteur collected samples of the fermenting juices and examined them microscopically. He noticed that the juices contained yeast. He also noted that the contaminant, amyl alcohol, was an optically active compound, and hence to Pasteur evidence that it was produced by a living organism ("living contagion").

Pasteur was quick to generalize his findings and thus to advance a biological interpretation of the processes of fermentation. In a series of dramatic but exquisitely planned experiments, he demonstrated that physical screening or thermal methods destroyed all microorganisms and that when no contamination by living contagion took place, the processes of fermentation or putrefaction did not take place either. "Pasteurization" was thus a technique which could not only preserve wine, beer, and milk but could also prevent or drastically reduce infection in the surgeon's operating room.

Another by-product of Pasteur's work on fermentation was his elucidation of the fact that certain families of microbes require oxygen whereas others do not. Yeast, he showed, was a facultative anaerobe; when oxygen was not present, as in the vats of beer or wine manufacturers, it would derive its energy from the sugar, converting it to alcohol; under more favorable conditions (for the yeast) where oxygen was available, alcohol did not accumulate, and the process continued to the complete conversion of sugar to carbon dioxide and water. This insight divided the scientific community, and it was only in 1897, 2 years after the death of Pasteur, that the dispute was resolved, when a cell-free extract of yeast proved capable of fermenting a sugar solution. Thus it turned out that the living organism synthesized an enzyme which carried out the conversion.

Silkworms and Microbial Disease Theory
In 1865 Pasteur was called upon to assist another ailing industry of France - silk manufacture - which was being ruined by an epidemic among silkworms. He took his microscope to the south of France and in an improvised laboratory set to work. Four months later he had isolated the pathogens causing the disease, and after 3 years of intensive work he suggested the methods of bringing it under control.

Pasteur's scientific triumphs coincided with personal and national tragedy. In 1865 his father died; his two daughters were lost to typhoid fever in 1866. Over-worked and grief-stricken, Pasteur suffered a cerebral hemorrhage in 1868 which left part of his left arm and leg permanently paralyzed. Nonetheless, he pressed on, hardly with interruptions, on his study ofsilkworm diseases, already sensing that these investigations were but his apprenticeship for the control of the diseases of higher animals, including humans.

The Franco-Prussian War, with its trains of wounded, stimulated Pasteur to press his microbialtheory of disease and infection on the military medical corps, winning grudging agreement to thesterilization of instruments and the steaming of bandages. The results were spectacular, and in 1873 Pasteur was made a member of the French Academy of Medicine - a remarkable accomplishment for a man without a formal medical degree.

Pasteur was now prepared to move from the most primitive manifestations of life, crystals and the simpler forms of life in the microbial world, to the diseases of the higher animals. The opportunity arose through a particularly devastating outbreak of anthrax, a killer plague of cattle and sheep in 1876/1877. The anthrax bacillus had already been identified by Robert Koch, and Pasteur now set about proving that the agent of disease was precisely the living organism and not a related toxin. He diluted a solution originally containing a source of infection of anthrax by a factor of 1 part in 100100. Even at this enormous dilution, the residual fluid carried death, thus proving that it was the constantly multiplying organism that was the source of the disease.

In 1881 Pasteur had convincing evidence that gentle heating of anthrax bacilli could so attenuatethe virulence of the organism that it could be used to inoculate animals and thus immunize them. In a dramatic demonstration of this procedure, carried out with the whole of France as witness, Pasteur inoculated one group of sheep with the vaccine and left another untreated. Upon injection of both groups with the bacillus, the untreated died; the others lived, and thus ascourge that had crippling economic effects was brought under control.

Pasteur's ultimate triumph came with the conquest of rabies, the disease of animals, particularly dogs, which gives rise to the dreaded hydrophobia of humans. The problem here was that the causative agent was a virus, hence an entity not capable of growth in the scientists' broth which nurtured bacteria. Pasteur worked for 5 years in an effort to isolate and culture the pathogen. Finally, in 1884, in collaboration with other investigators, he perfected a method of cultivating the virus in the tissues of rabbits. The virus could then be attenuated by exposing the incubationmaterial to sterile air over a drying agent at room temperature. A vaccine could then be prepared for injection. The success of this method was greeted with jubilation all over the world. Animals could now be saved, but the question arose as to the effect of the treatment on human beings. In 1885 a 9-year-old boy, Joseph Meister, was brought to Pasteur. He was suffering from 14 bites from a rabid dog. With the agreement of the child's physician, Pasteur began his treatment with the vaccine. The injections continued over a 12-day period, and the child recovered.

Honors from the World:
In 1888 a grateful France founded the Pasteur Institute, which was destined to become one of the most productive centers of biological study in the world. In the closing paragraphs of his inaugural oration, Pasteur said: "Two opposing laws seem to me now to be in contest. The one, a law of blood and death opening out each day new modes of destruction, forces nations always to be ready for the battle. The other, a law of peace, work and health, whose only aim is to deliver man from the calamities which beset him. The one seeks violent conquests, the other, the relief of mankind. The one places a single life above all victories, the other sacrifices hundreds of thousands of lives to the ambition of a single individual. The law of which we are the instruments strives even through the carnage to cure the wounds due to the law of war. Treatment by ourantiseptic methods may preserve the lives of thousands of soldiers. Which of these two laws willprevail, God only knows. But of this we may be sure, science, in obeying the law of humanity, will always labor to enlarge the frontiers of life."

Pasteur's seventieth birthday was the occasion of a national holiday. At the celebration held at the Sorbonne, Pasteur was too weak to speak to the delegates who had gathered from all over the world. His address, read by his son, concluded: "Gentlemen, you bring me the greatest happiness that can be experienced by a man whose invincible belief is that science and peace will triumph over ignorance and war.… Have faith that in the long run … the future will belong not to the conquerors but to the saviors of mankind."

On Sept. 28, 1895, honored by the world but unspoiled and overflowing with affection, Pasteur died near Saint-Cloud. His last words were: "One must work; one must work. I have done what I could." He was buried in a crypt in the Pasteur Institute. There is a strange postscript to this story. In 1940 the conquering Germans came again to Paris. A German officer demanded to see the tomb of Pasteur, but the old French guard refused to open the gate. When the German insisted, the Frenchman killed himself. His name was Joseph Meister, the boy Pasteur had saved from hydrophobia so long ago.

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