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Most of the bacteria studied by Pasteur and his early followers were big enough to be trapped in fine porcelain filters, devised by Pasteur's assistant Charles Chamberland, and to be seen under the 19th century light microscope. It was a temperamental Dutch botanist, Martinus Beijerinck (1851-1931), who found that whatever caused mosaic disease in tobacco plants could slip through the minute pores of these filters. In 1897 he concluded that this infectious, filter-passing fluid was a "filterable virus." The word virus had been loosely used for centuries to denote any "poison" that caused infectious disease.
For 40 years, the one clear mark of the virus was this ability to slip invisibly through porcelain filters. In those four decades, without waiting to see what a virus looked like, brilliant men did brilliant things about viruses and viral diseases. At Manhattan's Rockefeller Institute, Dr. Peyton Rous in 1910 proved that a filterable virus is the cause of sarcoma (a kind of cancer) in chickens. At Harvard and then at the Rockefeller Foundation, South Africa-born Max Theiler performed the delicate and dangerous feat of getting yellow-fever virus to grow in the brains of mice. With infinite patience, Theiler in 1936 grew 176 generations of virus in tissue cultures of chick embryo cells,* weakening the virus with each "pass" and seeking a generation that would be too feeble to induce the disease, yet strong enough in a vaccine to spur the system to create antibodies. The vaccine that he achieved won Max Theiler a Nobel Prize.
A Ton of Tobacco. But the study of viruses in the 1930s was still a toddler among the sciences; no U.S. university even had a chair in virology. Medical texts of the period were studded with such notations as: "The cause of this disease is believed to be a filterable virus, but has not been isolated," Virology needed new foundations to build on.
One appeared in 1938: the electron microscope, in which beams of electrons are focused sharply enough to take photographs of objects less than a millionth of an inch across. This made many virus particles visualizable—and another Rockefeller fellow had something to visualize. Indiana-born Wendell Stanley went back to Beijerinck's favorite, the tobacco mosaic virus, or TMV, and spent years in a Princeton laboratory cooking down a ton of sickly tobacco leaves, filtering and re-filtering, dissolving and redissolving, until he had isolated the cause of this economically costly disease. What he had to show for years of imaginative perseverance was about a teaspoonful of white crystals that looked no more impressive than powdered sugar. It was pure TMV, and the feat won Stanley a Nobel Prize in chemistry.
Stanley thus gave a crystal-clear answer to the question: What is TMV? Electron micrographs showed thin rod-shaped crystals, little more than a hundred-thousandth of an inch long. This answer raised an intriguing new question. Is a virus animate or inanimate, living or dead, animal or mineral? Dr. Stanley's way out of the dilemma is to broaden the definition of "living'' to include any particles that are capable of reproducing or replicating themselves. That covers viruses.