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 F lix H. d H relle 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 L ffler 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.
Evolution
Three theories have been put forth to explain the origin of viruses. One theory suggests that viruses are derived from more complex intracellular parasites that have eliminated all but the essential features required for replication and transmission. A more widely accepted theory is that viruses are derived from normal cellular components that gained the ability to replicate autonomously. A third possibility is that viruses originated from self-replicating RNA molecules. This hypothesis is supported by the observation that RNA can code for proteins as well as carry out enzymatic functions. Thus, viroids may resemble prehistoric viruses.
Importance of Viruses
Because viral processes so closely resemble normal cellular processes, abundant information about cell biology and genetics has come from studying viruses. Basic scientists and medical researchers at university and hospital laboratories are working to understand viral mechanisms of action and are searching for new and better ways to treat viral illnesses. Many pharmaceutical and biotechnology companies are actively pursuing effective antiviral therapies. Viruses can also serve as tools. Because they are efficient factories for the production of viral proteins, viruses have been harnessed to produce a wide variety of proteins for industrial and research purposes. A new area of endeavor is the use of viruses for gene therapy. Because viruses are programmed to carry genetic information into cells, they have been used to replace defective cellular genes. Viruses are also being altered by genetic engineering to kill selected cell populations, such as tumor cells. The use of genetically engineered viruses for medical intervention is a relatively new field, and none of these therapies is widely available. However, this is a fast-growing area of research, and many clinical trials are now in progress. The use of genetically engineered viruses extends beyond the medical field. Recombinant insect viruses have agricultural applications and are currently being tested in field trials for their effectiveness as pesticides.