Editor's Note: This story was originally published in the December 2004 issue of Scientific American.
In an episode of the classic 1950s television comedy The Honeymooners, Brooklyn bus driver Ralph Kramden loudly explains to his wife, Alice, “You know that I know how easy you get the virus.” Half a century ago even regular folks like the Kramdens had some knowledge of viruses—as microscopic bringers of disease. Yet it is almost certain that they did not know exactly what a virus was. They were, and are, not alone.
For about 100 years, the scientifi c community has repeatedly changed its collective mind over what viruses are. First seen as poisons, then as life-forms, then biological chemicals, viruses today are thought of as being in a gray area between living and nonliving: they cannot replicate on their own but can do so in truly living cells and can also affect the behavior of their hosts profoundly. The categorization of viruses as nonliving during much of the modern era of biological science has had an unintended consequence: it has led most researchers to ignore viruses in the study of evolution. Finally, however, scientists are beginning to appreciate viruses as fundamental players in the history of life.
Coming to Terms
It is easy to see why viruses have been diffi cult to pigeonhole. They seem to vary with each lens applied to examine them. The initial interest in viruses stemmed from their association with diseases—the word “virus” has its roots in the Latin term for “poison.” In the late 19th century researchers realized that certain diseases, including rabies and foot-and-mouth, were caused by particles that seemed to behave like bacteria but were much smaller. Because they were clearly biological themselves and could be spread from one victim to another with obvious biological effects, viruses were then thought to be the simplest of all living, gene-bearing life-forms.
Their demotion to inert chemicals came after 1935, when Wendell M. Stanley and his colleagues, at what is now the Rockefeller University in New York City, crystallized a virus— tobacco mosaic virus—for the fi rst time. They saw that it consisted of a package of complex biochemicals. But it lacked essential systems necessary for metabolic functions, the biochemical activity of life. Stanley shared the 1946 Nobel Prize— in chemistry, not in physiology or medicine—for this work.
Further research by Stanley and others established that a virus consists of nucleic acids (DNA or RNA) enclosed in a protein coat that may also shelter viral proteins involved in infection. By that description, a virus seems more like a chemistry set than an organism. But when a virus enters a cell (called a host after infection), it is far from inactive. It sheds its coat, bares its genes and induces the cell’s own replication machinery to reproduce the intruder’s DNA or RNA and manufacture more viral protein based on the instructions in the viral nucleic acid. The newly created viral bits assemble and, voilà, more virus arises, which also may infect other cells.
These behaviors are what led many to think of viruses as existing at the border between chemistry and life. More poetically, virologists Marc H. V. van Regenmortel of the University of Strasbourg in France and Brian W. J. Mahy of the Centers for Disease Control and Prevention have recently said that with their dependence on host cells, viruses lead “a kind of borrowed life.” Interestingly, even though biologists long favored the view that viruses were mere boxes of chemicals, they took advantage of viral activity in host cells to determine how nucleic acids code for proteins: indeed, modern molecular biology rests on a foundation of information gained through viruses.