How Scientists Stalked a Lethal Superbug—With the Killer’s Own DNA
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A lethal bacterium was running rampant at an NIH hospital. Antibiotics were useless. Then two scientists began a frantic race to track down the killer—with the superbug’s own DNA.
On September 19, 2011, Evan Snitkin sat staring at a computer monitor, its screen cluttered with Perl script and row after row of 0s sprinkled with the occasional 1. To Snitkin, a bioinformatician at the National Institutes of Health, it read like a medical thriller. In this raw genetic-sequencing data, he could see the hidden history of a deadly outbreak that was raging just a few hundred yards from where he sat.
Snitkin was, in a sense, a medical historian: a genetic epidemiologist who traced the paths of disease outbreaks. But now, for the first time in history, he was trying to use his genetic toolkit to reroute an outbreak while it was in progress—and before it turned disastrous. A few weeks earlier, a handful of patients at the NIH Clinical Center, a 243-bed research hospital on the NIH campus in Bethesda, Maryland, had been hit by a vicious strain of bacteria known as KPC. Shorthand for carbapenem-resistant Klebsiella pneumoniae, KPC can hitch a ride on healthy people, setting up residence on their skin. From them it can spread to people with weak defenses—like hospital patients—and bloom into an overwhelming infection that spreads via the bloodstream into the whole body, swiftly shutting down one organ after another. In the past decade, KPC has evolved the ability to withstand every known antibiotic. As a result, roughly half of people who develop an active infection of KPC will die.
This nasty bacterium had arrived in the Clinical Center for the first time in June 2011. A woman was being transferred from a New York hospital, and her admitting nurse noted in her medical history that she was colonized with the bacteria. On her arrival, doctors kept her isolated from other patients to prevent the KPC from spreading, and on July 15 she was discharged. But on August 5 another patient—a man who had been in the hospital for many weeks—tested positive for KPC. And then, roughly every week after that, another new infection cropped up.
As the cases mounted, the Clinical Center gathered as much epidemiological data as it could to figure out the nature of the outbreak. But there wasn’t enough information to create a clear picture. The most befuddling part was the second patient, who became ill long after the first patient had left the hospital—an uncommon onset for this particular bacterium. This second patient died under the ravages of KPC, and there was little that hospital staff could do for the sick.
Such illnesses are becoming more common worldwide. With each passing year, the problem of superbugs—bacteria such as Klebsiella that have evolved resistance to all, or nearly all, antibiotics available—has grown progressively more dire. Gone are the days when pharmaceutical companies could roll out generation after generation of new medications to replace those that bacteria had already surmounted. Such drugs have become much harder to find; and even when they are found, the market for them is far less lucrative than for molecules that combat such high-profile killers as cancer or AIDS. As a result, the flow through the antibiotics pipeline has slowed to a trickle. From 1983 through 1987, the FDA approved 16 new systemic antibiotics; from 2008 through 2011, it approved just two. Rather than administer some new wonder drug, then, the Clinical Center could only quarantine these KPC-positive patients and give them harsh drugs like colistin, an antibiotic so toxic it was all but abandoned in the 1970s. An estimated 90,000 people die every year from infections they acquire in US hospitals—more than the number that die from Alzheimer’s, diabetes, or influenza.
In late August, as word of the outbreak circulated among the NIH staff, Snitkin and his boss, Julie Segre, approached the Clinical Center with an unusual offer. In their jobs at the NIH’s National Human Genome Research Institute, the two scientists had previously sequenced genomes from a bacterial outbreak long after it had died out. But today, sequencing technology had become so fast and so cheap. Why not analyze the bacteria in the middle of an outbreak? By tracking the bug’s transmission route through the hospital, they might be able to isolate it and stop its lethal spread. They put this question to the center’s top brass, who immediately accepted their offer. “It was a no-brainer,” says Tara Palmore, the center’s deputy epidemiologist, who headed up its fight against KPC.
It took nearly a month to retrieve the first results, and now Snitkin was finally navigating through millions of base pairs on his computer screen. The 0s he saw were bases of DNA that were identical in every KPC microbe he was studying. The 1s represented mutations in each microbe not found in the others. By comparing the mutations, Snitkin could see how the bacteria were related to one another. If the history of public health has until now been embodied by the map—as in British physician John Snow’s famous map, which allowed him to curb the London cholera outbreak of 1854 and to found, in doing so, the modern field of epidemiology—Snitkin was embarking on a new kind of epidemiology: one founded on the phylogenetic tree.
And the tree that Snitkin drew was profoundly different from what Palmore had expected. “They showed me the results,” she says, “and I was speechless.”