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REVIEWS

Microbe Hunting

W. Ian Lipkin
W. Ian Lipkin
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York
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DOI: 10.1128/MMBR.00007-10
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  • FIG. 1.
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    FIG. 1.

    Growth of the viral sequence database mapped to seminal discoveries and improvements in sequencing technology. EM, electron microscopy. (Courtesy of Omar Jabado, reproduced with permission.)

  • FIG. 2.
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    FIG. 2.

    Staged strategy for pathogen discovery and proof of causation. In the molecular era of pathogen discovery, culture and molecular methods are pursued in parallel until an agent is detected, isolated, and characterized. +, positive result; −, negative result. ssRNA, single-stranded RNA; dsRNA, double-stranded RNA.

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  • TABLE 1.

    Criteria for proof of causation

    Criterion reported by:
    Koch (1890)Rivers (1936)Fredericks and Relman (1996)
    A microbe must be present in every case of a diseaseA virus must be associated with a disease with a degree of regularityCandidate sequences should be present in most cases of disease and at sites of disease pathology
    It must not be found in association with any other diseaseThe association cannot be incidentalFew or no sequences should be present in host or tissue without disease
    After isolation and propagation in pure culture, the microbe must be capable of inducing the same diseaseRivers predicted that methods for proving causal relationships would evolve with improvements in technology; at the time of his writing, he invoked seroconversion and experimental inoculations but acknowledged the limitations of bothSequences should diminish in frequency with resolution of disease and increase with relapse
    Sequences should be present prior to the onset of disease
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Microbe Hunting
W. Ian Lipkin
Microbiology and Molecular Biology Reviews Aug 2010, 74 (3) 363-377; DOI: 10.1128/MMBR.00007-10

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Microbe Hunting
W. Ian Lipkin
Microbiology and Molecular Biology Reviews Aug 2010, 74 (3) 363-377; DOI: 10.1128/MMBR.00007-10
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  • Article
    • SUMMARY
    • INTRODUCTION
    • DIVERSITY OF THE MICROBIAL UNIVERSE
    • PROOF OF CAUSATION
    • ISOLATION OR VISUALIZATION OF INFECTIOUS AGENTS
    • COMPLEXITIES OF PATHOGENETIC MECHANISMS MAY CONFOUND DISCOVERY AND IMPLICATION OF MICROBES IN DISEASE
    • MICROBIAL PROSPECTING
    • PATHOGEN DE-DISCOVERY
    • MOLECULAR METHODS FOR PATHOGEN DISCOVERY
    • VIGNETTES IN PATHOGEN DISCOVERY
    • FUTURE PERSPECTIVES
    • ACKNOWLEDGMENTS
    • REFERENCES
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