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Discovery

tobacco mosaic disease, regular shapes, plaque assay, yellow fever virus, tobacco mosaic virus

By the last half of the 19th century, the microbial world was known to consist of protozoa, fungi, and bacteria, all visible with a light microscope. In the 1840s, the German scientist Jacob Henle suggested that there were infectious agents too small to be seen with a light microscope, but for the lack of direct proof, his hypothesis was not accepted. Although the French scientist Louis Pasteur was working to develop a vaccine for rabies in the 1880s, he did not understand the concept of a virus.

During the last half of the 19th century, several key discoveries were made that set the stage for the discovery of viruses. Pasteur is usually credited for dispelling the notion of spontaneous generation and proving that organisms reproduce new organisms. The German scientist Robert Koch, a student of Jacob Henle, and the British surgeon Joseph Lister developed techniques for growing cultures of single organisms that allowed the assignment of specific bacteria to specific diseases.

The first experimental transmission of a viral infection was accomplished in about 1880 by the German scientist Adolf Mayer, when he demonstrated that extracts from infected tobacco leaves could transfer tobacco mosaic disease to a new plant, causing spots on the leaves. Because Mayer was unable to isolate a bacterium or fungus from the tobacco leaf extracts, he considered the idea that tobacco mosaic disease might be caused by a soluble agent, but he concluded incorrectly that a new type of bacteria was likely to be the cause. The Russian scientist Dimitri Ivanofsky extended Mayer’s observation and reported in 1892 that the tobacco mosaic agent was small enough to pass through a porcelain filter known to block the passage of bacteria. He too failed to isolate bacteria or fungi from the filtered material. But Ivanofsky, like Mayer, was bound by the dogma of his times and concluded in 1903 that the filter might be defective or that the disease agent was a toxin rather than a reproducing organism.

Unaware of Ivanofsky’s results, the Dutch scientist Martinus Beijerinck, who collaborated with Mayer, repeated the filter experiment but extended this finding by demonstrating that the filtered material was not a toxin because it could grow and reproduce in the cells of the plant tissues. In his 1898 publication, Beijerinck referred to this new disease agent as a contagious living liquid—contagium vivum fluid—initiating a 20-year controversy over whether viruses were liquids or particles.

The conclusion that viruses are particles came from several important observations. In 1917 the French-Canadian scientist Félix H. d’Hérelle discovered that viruses of bacteria, which he named bacteriophage, could make holes in a culture of bacteria. Because each hole, or plaque, developed from a single bacteriophage, this experiment provided the first method for counting infectious viruses (the plaque assay). In 1935 the American biochemist Wendell Meredith Stanley crystallized tobacco mosaic virus to demonstrate that viruses had regular shapes, and in 1939 tobacco mosaic virus was first visualized using the electron microscope.

In 1898 the German bacteriologists Friedrich August Johannes Löffler and Paul F. Frosch (both trained by Robert Koch) described foot-and-mouth disease virus as the first filterable agent of animals, and in 1900, the American bacteriologist Walter Reed and colleagues recognized yellow fever virus as the first human filterable agent. For several decades viruses were referred to as filterable agents, and gradually the term virus (Latin for “slimy liquid” or “poison”) was employed strictly for this new class of infectious agents. Through the 1940s and 1950s many critical discoveries were made about viruses through the study of bacteriophages because of the ease with which the bacteria they infect could be grown in the laboratory. Between 1948 and 1955, scientists at the National Institutes of Health (NIH) and at Johns Hopkins Medical Institutions revolutionized the study of animal viruses by developing cell culture systems that permitted the growth and study of many animal viruses in laboratory dishes.



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