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Superbugs Predate Wonder Drugs

In the war between germs and modern medicine, the bugs came well prepared. A new study concludes that bacteria have been resistant to modern antibiotics for far longer than humans have actually used these drugs. Indeed, the researchers isolated resistance genes from bacterial DNA preserved in ice for more than 30,000 years.

A miracle of medicine, synthetic antibiotics were first developed at the beginning of the 20th century and have been widely used only since the end of the Second World War. The first signs of resistance emerged a few years later. Since then, the development of every new antibiotic has been followed swiftly by the appearance of microbes resistant to it. With few new wonder drugs in the pipeline, some doctors are warning of a postantibiotic age, in which simple infections will become untreatable again.

Most antibiotics are based on chemicals used by bacteria or fungi to fight other bacteria, and researchers have speculated that antibiotic resistance must have coevolved with these compounds millions of years ago. Some scientists even claimed to have cultured ancient resistant bacteria from frozen Siberian soil in the lab, but those experiments lacked important controls and were never replicated, says biochemist Gerard Wright of McMaster University in Hamilton, Canada: "No one ever proved this conclusively." Wright, who conducted the new study with McMaster biologist Hendrik Poinar and other colleagues, says it took his team 5 minutes to sketch the idea of the project but 3 years to carry it out.

The researchers acquired samples of soil that had been frozen for 30,000 years by drilling into sediments close to Dawson City, in Canada's Yukon Territory. To rule out any modern DNA contaminating the samples, the outside of the drilling equipment and the cores were sprayed with fluorescent Escherichia coli cells. This way, if any material leaked into the core, it would show up immediately under ultraviolet light.

When the researchers analyzed DNA from the drill cores back in the lab, they found fragments of genes conferring resistance against various antibiotics, such as penicillin, tetracycline, and vancomycin. (As further proof that they were indeed looking at ancient DNA, the scientists identified sequences in the samples from animals and plants common in the area 30,000 years ago, such as mammoths, bison, and certain grasses; they did not find any DNA from modern animal or plant life.)

The researchers used some of the ancient DNA fragments to recreate a vancomycin resistance gene and its protein product. It showed the same activity and had almost the same structure as its modern counterpart, they report online today in Nature. "We see antibiotic resistances in the clinic, but that is just the tip of the iceberg," Wright says. "Resistance predates our use of antibiotics; it is part of the natural world."

George Drusano, an expert on antibiotic resistances at the University of Florida, Gainesville, calls the paper one of the best documented studies he has ever read. It's a "carefully done study," adds George Church, a geneticist at the Massachusetts Institute of Technology in Cambridge. "Non-scientists (and even scientists) forget how important it is to confirm ideas that are widely accepted," he writes in an e-mail. Church's only gripe is that the samples were 30,000 years old, even though antibiotic resistance genes have likely been around for a billion years. It's "analogous to a super-elegant proof that humans have been using weapons for at least the past 30 years," he writes.

Wright himself wants to go back further in time. But even the current study holds an important lesson about ecology, he says: With so many resistance genes present in nature, no antibiotic can last forever. "We should not think of them as wonder drugs but as really special resources, and there are natural responses to them we should take into account."