Health & Medicine / Infectious Diseases

On a bright winter morning high in the Colorado Rockies, a slight young woman in oversize hip boots sidles up to a gap of open water in the icy Cache la Poudre River. Heather Storteboom, a 25-year-old graduate student at nearby Colorado State University, is prospecting for clues to an invisible killer.

Image courtesy of Jessica Snyder Sachs

Storteboom snaps on a pair of latex gloves and stretches over the frozen ledge to fill a sterile plastic jug with water. Then, setting the container aside, she swings her rubber-clad legs into the stream. “Ahh, no leaks,” she says, standing upright. She pulls out a clean trowel and attempts to collect some bottom sediment; in the rapid current, it takes a half dozen tries to fill the small vial she will take back to the DNA laboratory of her adviser, environmental engineer Amy Pruden. As Storteboom packs to leave, a curious hiker approaches. “What were you collecting?” he asks. “Antibiotic resistance genes,” she answers.

Storteboom and Pruden are at the leading edge of an international forensic investigation into a potentially colossal new health threat: DNA pollution. Specifically, the researchers are seeking out snippets of rogue genetic material that transforms annoying bacteria into unstoppable supergerms, immune to many or all modern antibiotics. Over the past 60 years, genes for antibiotic resistance have gone from rare to commonplace in the microbes that routinely infect our bodies. The newly resistant strains have been implicated in some 90,000 potentially fatal infections a year in the United States, higher than the number of automobile and homicide deaths combined.

Among the most frightening of the emerging pathogens is invasive MRSA, or methicillin-resistant Staphylococcus aureus. Outbreaks of MRSA in public schools recently made headlines, but that is just the tip of the iceberg. Researchers estimate that invasive MRSA kills more than 18,000 Americans a year, more than AIDS, and the problem is growing rapidly. MRSA caused just 2 percent of staph infections in 1974; in the last few years, that figure has reached nearly 65 percent. Most reported staph infections stem from MRSA born and bred in our antibiotic-drenched hospitals and nursing homes. But about 15 percent now involve strains that arose in the general community.

It is not just MRSA that is causing concern; antibiotic resistance in general is spreading alarmingly. A 2003 study of the mouths of healthy kindergartners found that 97 percent harbored bacteria with genes for resistance to four out of six tested antibiotics. In all, resistant microbes made up around 15 percent of the children’s oral bacteria, even though none of the children had taken antibiotics in the previous three months. Such resistance genes are rare to nonexistent in specimens of human tissue and body fluid taken 60 years ago, before the use of antibiotics became widespread.

In part, modern medicine is paying the price for its own success. “Antibiotics may be the most powerful evolutionary force seen on this planet in billions of years,” says Tufts University microbiologist Stuart Levy, author of The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers. By their nature, anti­biotics support the rise of any bug that can shrug off their effects, by conveniently eliminating the susceptible competition.

But the rapid rise of bacterial genes for drug resistance stems from more than lucky mutation, Levy adds. The vast majority of these genes show a complexity that could have been achieved only over millions of years. Rather than rising anew in each species, the genes spread via the microbial equivalent of sexual promiscuity. Bacteria swap genes, not only among their own kind but also between widely divergent species, Levy explains. Bacteria can even scavenge the naked DNA that spills from their dead compatriots out into the environment.

The result is a microbial arms-smuggling network with a global reach. Over the past 50 years, virtually every known kind of disease-causing bacterium has acquired genes to survive some or all of the drugs that once proved effective against it. Analysis of a strain of vancomycin-resistant enterococcus, a potentially lethal bug that has invaded many hospitals, reveals that more than one-quarter of its genome—including virtually all its antibiotic-thwarting genes—is made up of foreign DNA. One of the newest banes of U.S. medical centers, a supervirulent and multidrug-resistant strain of Acinetobacter baumannii, likewise appears to have picked up most of its resistance in gene swaps with other species.

So where in Hades did this devilishly clever DNA come from? The ultimate source may lie in the dirt beneath our feet.

For the past decade, Gerry Wright has been trying to understand the rise of drug resistance by combing through the world’s richest natural source of resistance-enabling DNA: a clod of dirt. As the head of McMaster University’s antibiotic research center in Hamilton, Ontario, Wright has the most tricked-out laboratory a drug designer could want, complete with a $15 million high-speed screening facility for simultaneously testing potential drugs against hundreds of bacterial targets. Yet he says his technology pales in comparison with the elegant antibiotic-making abilities he finds encoded in soil bacteria. The vast majority of the antibiotics stocking our pharmacy shelves—from old standards like tetracycline to antibiotics of last resort like vancomycin and, most recently, daptomycin—are derived from soil organisms.

Biologists assume that soil organisms make antibiotics to beat back the microbial competition and to establish their territory, Wright says, although the chemicals may also serve other, less-understood functions. Whatever the case, Wright and his students began combing through the DNA of soil microbes like streptomyces to better understand their impressive antibiotic-making powers. In doing so the researchers stumbled upon three resistance genes embedded in the DNA that Streptomyces toyocaensis uses to produce the antibiotic teicoplanin. While Wright was not surprised that the bug would carry such genes as antidotes to its own weaponry, he was startled to see that the antidote genes were nearly identical to the resistance genes in vancomycin-resistant enterococcus (VRE), the scourge of American and European hospitals.