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Decades of antibiotics in farm animals lead to deadly superbugs

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Stuart Levy once kept a flock of chickens on a farm in the rolling countryside west of Boston. No ordinary farmer, Levy is a professor of molecular biology and microbiology and of medicine at Tufts University School of Medicine. This was decades ago, and his chickens were taking part in a never-before-conducted study. Half the birds received feed laced with a low dose of antibiotics, which U.S. farmers routinely administer to healthy livestock -- not to cure illness, but merely to increase the animals' rates of growth. The other half of Levy's flock received drug-free food.

Results started showing up almost instantly. Within two days, the treated animals began excreting feces containing E. coli bacteria that were resistant to tetracycline, the antibiotic in their feed. (E. Coli, most of which are harmless, normally live in the guts of chickens and other warm-blooded animals, including humans.) After three months, the chickens were also excreting bacteria resistant to such potent antibiotics as ampicillin, streptomycin, carbenacillin, and sulfonamides. Even though Levy had added only tetracycline to the feed, his chickens had somehow developed what scientists now call "multi-drug resistance" to a host of antibiotics that play important roles in treating infections in people. More frightening, although none of the members of the farm family tending the flock were taking antibiotics, they, too, soon began excreting drug-resistant strains of E. coli.

When Levy's study was published in The New England Journal of Medicine in 1976, it was met with skepticism. "The other side -- industry -- could not believe that this would have happened. The mood at the time was that what happens in animals does not happen in people," said Levy, who serves as president of the Alliance for the Prudent Use of Antibiotics, in a telephone interview from his office at Tufts. "But we had the data. It was obvious to us even then that using antibiotics this way was an error and should be stopped."

During the intervening 35 years, study after study has confirmed Levy's findings and shown that the problem of antibiotic-resistant "superbugs" is even worse than anyone could have imagined. Each year, 70,000 Americans in U.S. hospitals die from bacterial infections that drugs are unable to kill. And even as the number of infectious diseases is on the rise, more antibiotics are administered to livestock than ever before, from 17.8 million pounds per year in 1999 according to the Animal Health Institute (a trade organization of companies, like Bayer, Novartis, and Pfizer, that manufacture livestock drugs) to 29.8 million pounds in 2009, according to the U.S. Food and Drug Administration (FDA). Fully 80 percent of the antibiotics used in the United States are given to livestock, and the vast majority are administered to promote growth and stave off potential infections, not to treat illness.

From his perspective of more than three decades as a resistant-microbe watcher, Levy sounded almost weary when he said, "Proponents of growth promotion keep asking for more data, and we scientists provide them. But then the findings have never led to removal of the practice."

Getting serious

Last month, the Natural Resources Defense Council, Center for Science in the Public Interest, Food Animal Concerns Trust, Public Citizen, and the Union of Concerned Scientists joined forces to file a lawsuit against the FDA. The groups want the agency to withdraw its approval for most non-therapeutic uses of penicillin and tetracycline in animal feed. They say that it's something regulators should have done decades ago.

The FDA first approved the use of low-dose antibiotics in the 1950s. Concerns about the drugs began appearing within a decade, and by the time Levy's paper was published, the FDA was aware the practice posed a serious risk to human health. The agency proposed to withdraw its approval in 1977, saying that new evidence showed that penicillin- and tetracycline-containing products had not been "shown safe for widespread, sub-therapeutic use."

The proposal drew howls of outrage from two of the most powerful lobbying groups in Washington, agribusinesses and drug manufacturers. Both the House and Senate ordered the FDA to "hold in abeyance any and all implementation of the proposal" until further studies had been conducted. "It was the power of the lobby and the money behind that lobby," Levy recalled.

As requested by Congress, the FDA commissioned three studies during the 1980s, all of which supported initial concerns about the risks of feeding farm animals antibiotics on a daily basis. The FDA received petitions urging it to act from coalitions of scientific and environmental groups in 1999 and 2005. Such respected bodies as the American Academy of Pediatrics, the Centers for Disease Control and Prevention, the National Academy of Sciences, the U.S. Department of Agriculture, and the World Health Organization all identified low-dose antibiotics as the reason antibiotic-resistant bacteria were proliferating in humans and animals. And the FDA -- which is charged with protecting the health of Americans -- failed to act, only going so far as to issue a "Draft Guidance" [PDF] report and a draft "Action Plan" proposing voluntary guidelines. These suggestions have done nothing to stem the deluge of unnecessary antibiotics through the spigot of agribusiness.

"We've been fighting the non-therapeutic use of antibiotics in livestock for more than 30 years," Margaret Mellon, director of the food and environment program at the Union of Concerned Scientists, said in a press release announcing the lawsuit. "And over those decades the problem has steadily worsened. We hope this lawsuit will finally compel the FDA to act with an urgency commensurate with the magnitude of the problem." (Siobhan Delancey, a spokeswoman for the FDA, declined to comment on the suit.)

The trouble with antibiotics

Bacteria are evolutionary dynamos. Untold trillions of them can live in one confined animal feeding operation, or CAFO -- the technical term for a factory farm. They breed rapidly and mutate readily. Exposure to even miniscule levels of drugs equips bacteria with the genetic resilience to fend off higher levels of the same drugs.

From the dawn of modern antibiotics, researchers have been aware that the seeds of the wonder drugs' destruction had already been sown. In his 1945 Nobel acceptance speech for his discoveries related to penicillin, Sir Alexander Fleming said, "There is a danger that the ignorant man may easily under-dose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant." Fleming's prediction was prescient -- except the problem wasn't an "ignorant man" but politicians and business executives whose priorities lay elsewhere.

During the decades that the FDA dithered, a mountain of scientific research accumulated showing that antibiotic-resistant bacteria can not only evolve in the guts of farm animals, but can spread from animals to the humans who tend them, and then be passed on to people who have never been anywhere near a chicken house or hog barn.

In 2004, Dutch doctors discovered a strain of methicillin-resistant Staphylococcus aureus (MRSA) in a 6-month-old baby. Often fatal, MRSA is the original "superbug" because it can survive treatment by the most powerful antibiotics in modern medicine's arsenal. At first, the doctors were puzzled. MRSA was primarily known as a hospital-acquired infection. But the child, who carried the germs but never became sick, as is often the case with the asymptomatic carriers of bacteria, had never been in a hospital. Her parents were pig farmers, and subsequent investigations showed that the MRSA had been passed from the pigs to the parents and on to the baby. (Most bacteria are non-infectious, although they may carry resistance genes. The problem is that they can pass their resistance traits to infectious bacteria.)

Three years later, J. Scott Weese, a professor at the Ontario Veterinary College at the University of Guelph near Toronto, found an identical strain of MRSA in Canadian pigs and their owners. The superbug had somehow leapt over the Atlantic Ocean. Further research by Weese revealed that the swapping of resistant bacteria between animals and humans can be a two-way street. Not only were the farmers affected by MRSA that had originated in pigs, but the pigs carried MRSA that until then had only been found in humans.

For a year or so, American agribusiness continued to claim that MRSA was a problem that couldn't happen here -- a myth they were able to perpetrate because no government agency was routinely testing hogs for MRSA. But during the summer of 2008, Tara Smith, a microbiologist at the University of Iowa and the deputy director of the university's Center for Emerging Infectious Diseases, found that seven out of 10 pigs she and her students tested on farms in Illinois and Iowa carried MRSA.

A graduate student working with Smith recently uncovered a strain of S. aureus associated with hogs and the people who tend them in a day-care worker who had never been near a hog farm. Fortunately, that particular strain was not antibiotic resistant. But the discovery showed that humans do not have to work with infected animals to pick up the bacteria they carry. "Whether the pig bacterium was passed on via another human or via contaminated food products, we can't tell right now," Smith said in an email.


It helps that one of those "science people" is also a representative. Louise Slaughter, a Democrat who represents upstate New York, was a microbiologist before going into politics. In 2009, she introduced a bill called the Preservation of Antibiotics for Medical Treatment Act, which calls for the FDA to withdraw its approval of the practice within two years unless there is reasonable certainty that the low-dose antibiotics cause no harm to human health. "We are witnessing a looming public health crisis that is moving from farms to grocery stores to dinner tables around the country," she said in an email. "As the only microbiologist in Congress, I feel it's my duty to bring public attention to this."

Although Slaughter's bill has yet to pass, it had 127 cosponsors in the last congressional session, more than double its support in the previous Congress. It looks as though even more legislators will sign on this time, and many are hopeful that the combined forces of looming legislation and an active lawsuit will finally lead the FDA to act. "If we don't address it," Slaughter continued, "we risk setting ourselves back to the time before antibiotics, when even common infections could kill a person. That's not any kind of world I want my children and their children to inherit."


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