Pathogen Discovery 英文参考文献.docVIP

Opinion PathogenDiscovery W.IanLipkin* CenterforInfectionandImmunity,MailmanSchoolofPublicHealthofColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica ‘‘What has become clear to you sincewelastmet?’’ molecular technologies such as MassTag PCR [2–5], microbial microarrays [6–9], andunbiasedhighthroughputsequencing (HTS) [10] have enabled efficient micro- bialsurveillanceanddiscovery.Thedata- bases needed to recognize sequences as hostor microbialhaveimproveddramat- tion is particularly challenging where agents have remote effects or require co- factors for expression. In many acute infectious diseases, the responsible agent is readily implicated because it replicates at high levels in the affected tissue at the timethediseaseismanifest,morphological —BenjaminFranklin Discovery—literally,theactofuncover- ing—implies a new and fundamental ob- servationthatchangesthewayinwhichwe view and respond to the world (Image 1). Eureka (‘‘I have found it’’) moments are rare in science. Given the physiques of manyscientists,thismaybeagoodthing. Legend has it that when Archimedes discovered while bathing that the volume ofanobjectcouldbecalculatedbyfinding thevolumeofwateritdisplaced,heleaped outofthebathtubandrannakedthrough the streets of Syracuse proclaiming his discovery. ically. Sample collection has become changes consistent with infection are sophisticated and comprehensive. Last, butnotleast,ourmodelsforpathogenesis embrace increasingly complex mecha- nisms that consider host–microbe–timing interactionsinacuteandchronicdisease. evident,theagentisreadilyidentifiedwith classical or molecular methods, and there is evidence of an adaptive immune re- sponse. However, implication is more difficult when classical hallmarksofinfec- tion are absent or mechanisms of patho- genesis are indirect or subtle. Here, one mayresorttoastatisticalassessmentofthe strength of epidemiological association based on the presence of the agent or its ProofofCausation Findinganorganismis