The search for unrecognized pathogens

The distribution and diversity of microorganisms in the world are far greater than have been previously appreciated. Molecular, cultivation-independent methods have played a key role in this insight. To what extent do humans remain ignorant of microbial diversity within the human body and the settings in which microorganisms cause human disease? In addition to implicating microbial agents in nontraditional infectious dis-eases, the use of methods such as broad-range polymerase chain reaction, representational difference analysis, expression library screening, and host gene expression proÞling may force a reassessment of the concepts of microbial disease causation. Within the world of cultivated bacteria, vi-ruses, and unicellular eukaryotes that inhabit the human body, the number and variety of relations between microbe and host are breathtaking. Yet, surveys of many terrestria