Despite 300 years of peering through microscopes, growing bacteria in culture, and screening soil, air, and water for new microbial species, scientists have clearly overlooked much of life on earth. Thanks to powerful new research tools, bacteriologists are discovering that the living world is suddenly far bigger and more complex than they imagined even a decade ago. The finding is similar in magnitude, perhaps, to Dutch microscopist Antonie van Leeuwenhoek's first glimpse of microbes-he called them "animalcules"-cavorting beneath his crude glass lenses.

Because bacteria were essentially undetectable unless they could be grown in culture, most species-which exist in hard-to-replicate environments-have been, in a sense, off limits. "Imagine if our entire understanding of biology were based on visits to zoos," says Norman R. Pace, a biologist at University of California, Berkeley. "That is analogous to our situation with respect to understanding the microbial world."

Melvin Simon, chair of the department of biology at the California Institute of Technology, estimates that "about 99 percent of the bacteria out there can't yet be grown" in laboratory culture dishes. That's because scientists often can't determine the precise combination of conditions-including oxygen, temperature, and light-that microbes need and because it's difficult to simulate these requirements all at once to make them happy. About 6,000 species of microorganisms have been formally described. And until now, he says, the rest have remained "invisible" to us.

The key to gaining a first glimpse at this new world was in learning how to isolate, amplify, and study an organism's genetic material directly from the environment without culturing the organism itself. By using molecular instruments that selectively pick out a bacterium's highly specific genes from a broth of DNA, scientists can now quickly identify new organisms, explore their properties, and determine their kinship to organisms that are already known.