t Jo Handelsman, who in 1998 coined the term "metagenomics" to describe methods for studying microbial communities in aggregate. "We've been using petri plates as the prism through which we look at microbes for 150 years," she says. "Now we're looking at vastly more species. That's part of the thrill of it: that we don't know what we're going to find. It really is brand-new life forms that we're seeing."
Intense interest, rapid development
Scientists studying the microbial communities that live in and on the human body -- the human microbiome -- are examining the role of microbes in many different areas of human health: obesity, digestive diseases, esophageal cancer, psoriasis, and sexually transmitted diseases, among others. Marine scientists are exploring how the environment influences microbes' role in carbon cycling. Soil scientists are probing the soil metagenome's ability to produce antimicrobials, which offers the potential for developing new antibiotics and may underlie the spread of antibiotic resistance.
Meanwhile, the technologies that underpin metagenomics are advancing rapidly. "Back in the dark ages of 2007, when we did our first analysis of several hundred microbial communities, we had half a million sequences and that seemed like a lot," says University of Colorado, Boulder, microbiologist Robin Knight. "Now we're routinely dealing with hundreds of millions of sequences, and soon it will be billions. Every year, just about, it's another order of magnitude increase in sequencing capacity for about the same cost."
The scientific community's excitement about metagenomics is reflected in the myriad agencies and private foundations investing in it. "There's a lot of money being poured into this field," says Jacques Ravel, a microbial genomics scientist at the University of Maryland School of Medicine's Institute for Genome Sciences in Baltimore.
Federal agencies making major investments include the National Science Foundation (NSF), the Department of Energy (DOE), the U.S. Department of Agriculture, and the National Institutes of Health, which in 2008 launched the 5-year, $150 million Human Microbiome Project (HMP) from the NIH Common Fund. That project's goals are to catalog the microbes that inhabit the human body, identify their role in health and disease, and create tools -- such as reference data sets, a data resource center, and improved computational technologies -- that can be used to study the human microbiome. HMP is a one-time pot of money, and most of the grants have already been allocated, but NIH hopes the project will spur applications for institute-specific projects, says Maria Giovanni, assistant director for microbial genomics and advanced technologies in the National Institute for Allergy and Infectious Diseases's Division of Microbiology and Infectious Diseases. "If that didn't happen," she says, "it would be like having a party and nobody comes."
Many disciplines, few boundaries
"Metagenomics crosses an exceptional number of disciplinary boundaries -- which after all are not respected or recognized by nature but are human inventions," says University of California, San Diego (UCSD), biochemist and Associate Vice Chancellor of Research John Wooley. Metagenomics training similarly crosses boundaries: Researchers are trained in microbiology, systems biology, ecology, genomics, plant biology, marine biology, soil science, bioinformatics, bioengineering, chemical engineering, biogeochemistry, biochemistry, biophysics, computer science, statistics, and clinical sciences including medical microbiology, gastroenterology, dermatology, and oral science.
The balance of skills needed varies from project to project. Wooley says some current UCSD studies combine bioinformatics, microbiology, ecology, and genomics. Others add structural biology, biophysics, and deep statistical analyses; or marine biology and physical oceanography; or pharmacology and pharmacogenomics. The skills and knowledge needed for doing metagenomics research are so broad, he says, that disciplinary divisions “are not going to be f