Over four thousand people infected, nine hundred of them suffering hemolytic-uremic syndrome, a disorder whose first symptoms are vomiting and diarrhea. For fifty individuals, it ended in death. Such is the grim toll that the 2011 E. coli epidemic wrought upon Europe, and in particular France and Germany.

When Yonatan Grad, an infectious disease physician at Brigham and Women’s Hospital and research fellow at the Harvard School of Public Health (HSPH), first read of the outbreak in the New York Times, he thought he and his colleague, Bill Hanage, could contribute to the understanding of the outbreak.

Grad was right. For Hanage had taken the Francis Crick’s ‘gossip test and combined his knowledge of infection disease with his interest in evolution to pursue a career in infectious disease epidemiology. As a result, Hanage’s career crossed paths with the world of genomic sequencing.

Speaking of the E. coli O104:H4 strain responsible for the outbreak, Hanage says, “It’s often not clear exactly how virulent an emerging infection is. But that said, it was pretty plain that this was a fairly vicious strain. My first reaction was that this would be a really interesting project for sequencing.”

Hanage, also an associate professor at HSPH, knew that conventional molecular epidemiology methods wouldn’t do for the scale of the project he had in mind. He also knew that the Sanger Institute in the United Kingdom had been using next-generation technologies to sequence large pathogen samples consisting of hundreds of strains for several years.

“This sort of work represents a basic shift in the way we think about sequencing, from thinking about one representative isolate, to thinking about many. In an outbreak like the one we are talking about here, if you sequence just one isolate you can find out useful things like how the outbreak relates to the rest of the species. However if you sequence more than one isolate from an outbreak you can define things like the diversity of the outbreak, and any individual lineages within it. Using this information, you can say things about transmission, or how things relate to one another.”

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