"Since almost all of our antibiotics and many of our drugs come from cultured bacteria, we might expect there might be an abundance of useful molecules in the uncultured organisms. This [technology] is a way of accessing them," Handelsman said. "With potentially 40,000 species in a gram of soil, it would take a long time to figure out how to culture all of them," she added.

Although culturing has revealed tremendous diversity in soil microorganisms, an estimated 99% of soil microorganisms are still to be cultured. Handelsman and her collaborators have now used metagenomic techniques, extracting the DNA directly from a multitude of organisms rather than trying to culture them, to characterize the diversity of the dirt-dwelling microorganisms on an agricultural research farm in West Madison, Wisconsin.

Analyzing the genes encoding 16S ribosomal RNA in the soil revealed high numbers of the genus Acidobacterium, a group that seems to be one of the most abundant in terrestrial environments. Few species have ever been cultured. Other groups of bacteria found in the farm soil had no cultured members.

To see what kinds of chemicals these soil denizens could produce, the researchers extracted DNA directly from the soil and built clone libraries, one containing 3800 clones of 27-kb DNA inserts, and the other containing 2500 clones of 45-kb inserts. The chemical products of these clones were then screened to work out their functions.

One such screen is that for hemolysis, the ability to lyse red blood cells, a common characteristic of soil microorganisms. From the 38 clones with hemolytic ability, the researchers found 2 new antibiotics, and dubbed them turbomycin A and B. Another screen, that for the violacein, revealed a new pathway for the production of this antibiotic.

Selecting for antibiotic resistance is another way to figure out what new products might be coaxed out of soil organisms. So far, the researchers have found resistance to a variety of antibiotics, including some amino glycosides. They have also found a new group of acetyl transferases, the biochemical pathway that generates resistance to amino glycoside antibiotics.

The work is "cool stuff," said David Myrold, a microbial ecologist at Oregon State University in Corvallis. "The approach itself is a very interesting one for a variety of purposes."

Handelsman's next step is looking at soil from an island in Alaska that has had little human visitation and therefore is not contaminated by human-produced antibiotics. "It's interesting on the antibiotic-resistance front just because it's so far from anyplace antibiotics have been used," she said. "It should give us a background of antibiotic resistance in the soil."