Pathogen Discovery

Discovery—literally, the act of uncovering—implies a new and fundamental observation that changes the way in which we view and respond to the world (Image 1). Eureka (‘‘I have found it’’) moments are rare in science. Given the physiques of many scientists, this may be a good thing. Legend has it that when Archimedes discovered while bathing that the volume of an object could be calculated by finding the volume of water it displaced, he leaped out of the bathtub and ran naked through the streets of Syracuse proclaiming his discovery. The rate of discovery of new microbes, and of new associations of microbes with health and disease, has accelerated over the past two decades. Many factors are implicated. New pathogens have truly emerged with the globalization of travel and trade, changes in demographics and land use, susceptibility to opportunistic organisms associated with immunosuppression, and climate change [1]. New molecular technologies such as MassTag PCR [2–5], microbial microarrays [6–9], and unbiased high throughput sequencing (HTS) [10] have enabled efficient microbial surveillance and discovery. The databases needed to recognize sequences as host or microbial have improved dramatically. Sample collection has become sophisticated and comprehensive. Last, but not least, our models for pathogenesis embrace increasingly complex mechanisms that consider host–microbe–timing interactions in acute and chronic disease.