Microbe hunting

Abstract

Platforms for pathogen discovery have improved since the days of Koch and Pasteur; nonetheless, the challenges of proving causation are at least as daunting as they were in the late 1800 s. Although we will almost certainly continue to accumulate low-hanging fruit, where simple relationships will be found between the presence of a cultivatable agent and a disease, these successes will be increasingly infrequent. The future of the field rests instead in our ability to follow footprints of infectious agents that cannot be characterized using classical microbiological techniques and to develop the laboratory and computational infrastructure required to dissect complex host-microbe interactions. I have tried to refine the criteria used by Koch and successors to prove linkage to disease. These refinements are working constructs that will continue to evolve in light of new technologies, new models, and new insights. What will endure is the excitement of the chase. Happy hunting!

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.

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.