tory cultivation methods in the middle 1800s taught us how a few microbes make their livings as individuals, and the molecular biology and genomics revolutions of the last half of the 20th century united this physiological knowledge with a thorough understanding of its underlying genetic basis. Thus, almost all knowledge about microbes is largely “laboratory knowledge,” attained in the unusual and unnatural circumstances of growing them optimally in artificial media in pure culture without ecological context. The science of metagenomics, only a few years old, will make it possible to investigate microbes in their natural environments, the complex communities in which they normally live. It will bring about a transformation in biology, medicine, ecology, and biotechnology that may be as profound as that initiated by the invention of the microscope.
Like genomics itself, metagenomics is both a set of research techniques, comprising many related approaches and methods, and a research field. In Greek, meta means “transcendent.” In its approaches and methods, metagenomics circumvents the unculturability and genomic diversity of most microbes, the biggest roadblocks to advances in clinical and environmental microbiology. Meta in the first context recognizes the need to develop computational methods that maximize understanding of the genetic composition and activities of communities so complex that they can only be sampled, never completely characterized. In the second sense, that of a research field, meta means that this new science seeks to understand biology at the aggregate level, transcending the individual organism to focus on the genes in the community and how genes might influence each other’s activities in serving collective functions. Individual organisms remain the units of community activities, of course, and we anticipate that metagenomics will complement and stimulate research on individuals and their genomes. In the next decades, we expect that the top-down approach of metagenomics, the bottom-up approach of classical microbiology, and organism-level genomics will merge. We will understand communities, and the collection of communities that forms the biosphere, as a nested system of systems of which humans are a part and on which human survival depends. In some situations, it will be possible to apply the new understanding to problems of urgency and importance.
Metagenomics in either sense will probably never be circumscribed tightly by a definition, and it would be undesirable to attempt to so limit it now, but the term includes cultivation-independent genome-level characterization of communities or their members, high-throughput gene-level studies of communities with methods borrowed from genomics, and other “omics” studies (see Box 1-1), which are aimed at understanding transorganismal