Medicine: AIDS Research Spurs New Interest in Some Ancient Enemies

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Contaminated liquids that had been passed through porcelain filters designed to purify laboratory solutions and capable of blocking the passage of the smallest known bacteria were still able to infect both plants and test animals. However, careful microscopic scrutiny of the filtered liquids failed to reveal the "filterable agents" that caused the diseases. Also, unlike bacteria, these agents could apparently not be grown in culture dishes, where scientists hoped they might form colonies large enough to be seen with the naked eye. The source of such diseases as mumps, smallpox, yellow fever, rabies and dengue remained a mystery. And yet, wrote frustrated Bacteriologist William Henry Welch in 1894, "these are the most typically contagious diseases, which it might have been supposed would be the first to unlock their secrets."

One clue to the activity of viruses emerged during World War I, when a British and a French scientist independently noticed the appearance of clear circular spots in laboratory cultures grown over with bacteria. When material from a clear spot was applied to a different location in the bacteria culture, another circular area devoid of bacteria soon appeared. Felix d'Herelle, the French bacteriologist, thought he knew why. "What caused my clear spots," he wrote, "was in fact an invisible microbe, a filterable virus, but a virus parasitic on bacteria." D'Herelle named the unseen bug a bacteriophage (from the Greek phage, to devour).

While some of the properties of viruses were becoming evident in the 1920s, no one had yet seen one; on the average, scientists now know, viruses are ten to 100 times as small as the typical bacterium, and in fact far smaller than the wavelength of visible light. That makes them too diminutive to be seen with the most powerful optical microscopes. But in 1931 the invention of the electron microscope -- for which German Physicist Ernst Ruska finally won the Nobel Prize this year -- broke the light barrier. The new instrument -- along with a technique called X-ray crystallography (in which X rays are diffracted through crystallized virus particles to reveal their molecular structure) -- at last provided a view of the bizarre and startling world of the tiny creatures.

Some viruses, like the ones that cause the common cold, look vaguely like soccer balls: round with a surface of bumpy triangular facets. Others, particularly the larger bacteriophages, resemble lunar landing modules. The flu virus looks like the head of a Roman mace, with spikes protruding in all directions; herpes viruses are spherical, as is the AIDS variety. Whatever their shape, all viruses have something in common. They are models of biological minimalism, consisting simply of a core of genetic material -- either a DNA or RNA molecule -- and a protective envelope made of proteins (most varieties have a double coat, the outer one consisting either of another protein shell, or of proteins and lipids, fatty substances similar to those in a cell membrane). "There's no waste in a virus," says Dr. Stephen Straus of the National Institutes of Health (NIH). "Every piece is there for a reason. It's a magnificent little structure."