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By Shannon Brownlee
Sunday, May 21, 2000; Page B03

Lester Crawford was not actually there for the revolution in animal agriculture, but he knows the story so well he might as well have been. The year was 1949, the place was an American Cyanamid plant on the Pearl River, just north of New York City. People had been noticing that the fish swimming downstream from the pharmaceutical plant were larger than average, and chemist Thomas Jukes set out to discover why.

As Crawford tells it, the plant was manufacturing the antibiotic tetracycline, but the process wasn't very efficient. Chemists grew tetracycline-producing mold on a "mash" of grain in giant vats. After extracting only about 5 percent of the drug, they dumped the leftovers into the river.

When Jukes fed the mash to laboratory animals, the results were astonishing: Chicks grew 10 to 20 percent faster than those on plain rations. Piglets did even better. "Mice, chickens, whatever, they grew like crazy," says Crawford. Cyanamid marketed the mash as a feed booster, until Jukes determined that the active ingredient in this magical concoction was the tetracycline itself.

Jukes's discovery--that animals fed low doses of antibiotics grow bigger faster and on less food--enabled millions of farmers to get pigs, poultry and cattle to market weight at less expense, and helped America become the agricultural powerhouse it is today. But there is no free hamburger, it seems, and Jukes's discovery has turned out to have a potentially deadly downside: The more we use antibiotics, the more bacteria evolve into forms that resist them. Which means that farmers are inadvertently helping to create new and potentially deadly strains of food-borne illnesses that can't be cured by many of our best drugs.

Now we are running out of medicines that work. It's time to stop squandering drugs as precious as antibiotics to reduce the price of meat by a few cents a pound.

It's troubling to realize how long these concerns have been around. Crawford, who worked alongside Jukes in the 1960s, was among the scientists who recognized the dangers inherent in adding antibiotics to livestock feed a quarter-century ago. In the mid-'70s he found himself opposing Jukes, spearheading the Food and Drug Administration's first fight to end the use of antibiotics to promote growth in animals. The FDA lost that battle in 1980. Twenty years later, the agency is--ever so tentatively--poised to try again.

This time it has a new weapon: Scientists have finally been able to establish a chain of evidence linking antibiotics in animal feed to a particular human in a hospital bed. Until now, the powerful farm and drug lobbies have been able to exploit the lack of proof to block efforts to restrict the use of antibiotics. That may no longer work. This month, Cathy Woteki--an undersecretary in the U.S. Department of Agriculture, which historically has sided more with the farmers than the FDA--conceded that "antibiotic use in animals contributes to the [antibiotic resistance] problem . . . the agricultural community must accept part of the responsibility."

Scientists have known almost from the moment penicillin was discovered in 1928 that the more an antibiotic is used, the more quickly it becomes useless. Humans and bacteria are locked in a biological arms race: We find a drug; the germs develop resistance; we come up with a newer, more deadly weapon. Sometimes all that's needed is a minor variation on an existing drug. "All antibiotics have a limited window of utility before the bugs catch on," says J. Glenn Morris, an infectious disease specialist at the University of Maryland. "With enough time, bacteria will develop resistance to everything."

That's why doctors are always looking for new drugs--and so are farmers and veterinarians. In 1986, the FDA approved the first of a powerful new class of antibiotics for humans with the tongue-twisting name of fluoroquinolones, capable of replacing old-line antibiotics that could no longer beat the bugs. Only nine years later, in 1995, the FDA gave the go-ahead for veterinarians to begin dosing sick chickens with fluoroquinolones for the same reason: The old drugs no longer worked.

More than a third of the antibiotics sold in the United States--about 18 million pounds a year--wind up on the farm. They are used for three reasons: to treat sick animals; to prevent others housed in confined barns or coops from getting sick, too; and to make the animals grow faster. In terms of volume, most antibiotics are used for the first two reasons. Only 6.1 percent of the drugs goes toward growth promotion.

But in terms of the number of animals affected, the role of growth promotion is huge. That is because growers give antibiotics, in low but daily doses, to entire herds or flocks. Crawford, who is now director of the Georgetown University Center for Food and Nutrition Policy, estimates that 75 percent of the 92 million pigs in this country routinely chow down on feed laced with antibiotics. So do about 6 percent of cattle, 25 percent of chickens and half the turkeys.

With every dose, animals are turned into walking petri dishes, breeding strains of antibiotic-resistant bacteria. As Crawford puts it, "Low doses don't kill off bacteria--they just make them mad."

How could the resistant bacteria get from animals to people? The most obvious route would be through raw or undercooked meat. But the idea that a person's infection is resistant because he or she ate an animal that had been fed antibiotics is a lot harder to prove than you might think.

That's why studies like one published last year in the New England Journal of Medicine have shifted the balance of the debate. Public health researchers from the state of Minnesota and the U.S. Centers for Disease Control reported on bacterial cultures taken over several years from Minnesota residents infected with the bacterium Campylobacter jejuni. Campylobacter lives happily in the guts of animals without a peep. But it wreaks havoc in human beings, causing an estimated 2 million to 8 million cases of gastroenteritis in the United States each year.

Ordinarily, a bout of food poisoning causes little more than diarrhea or vomiting, and maybe a day or two away from work. Antibiotics are needed only if the infection persists or becomes "invasive"--meaning it has moved into the bloodstream. That's when the effectiveness of an antibiotic can mean the difference between life and death.

In 1992, the Journal article said, only 1.3 percent of the Minnesota cases were caused by strains of Campylobacter that were resistant to fluoroquinolones. By 1998, the number had risen to 10.2 percent. That's a pretty steep rise, and the researchers determined it was almost certainly because of antibiotic use on farms. Only a small fraction of the patients had ever taken fluoroquinolones themselves; and the genetic strain of resistant bacteria found in a significant number of the samples matched the genetic strain found on a variety of chicken products purchased at local grocery stores. Out of 91 chicken products, 80 were contaminated with Campylobacter. Twenty percent of those bacteria were resistant to ciprofloxacin, a fluoroquinolone that is needed to treat invasive gastroenteritis in humans.

Lately when I open the freezer at dinnertime to stare at those slabs of meat and yellow lumps of chicken, I think about cooking veggie-burgers for my 4-year-old instead.

Then there's DT104, a particularly nasty strain of salmonella that is rampant in Europe and has begun to show up in the United States. DT104 can blow off several antibiotics, and it is twice as likely to land you in the hospital as less virulent strains.

The National Chicken Council does not appear to think any of this is a problem. After the Minnesota paper came out, the council issued a press release noting that "properly handled and cooked chicken product would be free of Campylobacter." Fair enough. But by now, most Americans have heard that they are supposed to cook meat until it's charred. But many of us like our meat rare, and we never know whether the sous chef in our favorite restaurant has handled the steak with the proper care. Whatever the reasons, there are 78 million cases of food-borne illness in this country every year, 5,000 of which are fatal.

Besides, undercooked meat is not the only route bacteria can take from farm to human. Last month, the New England Journal of Medicine reported the case of a 12-year-old boy who came down with a nasty case of salmonella that was resistant to no fewer than 13 antimicrobial agents. The child almost certainly got sick from working around the cattle on his family's Nebraska ranch.

I try not to think about all the resistant bacteria in the animal waste that is washing off farms into rivers and streams, or the fact that bacteria can pass resistance genes from one species to another. "We are all in one great big gene pool," says the University of Maryland's Morris. "From the point of view of bacteria, you can't say the hospital, the farm and the community are separate places."

None of this would be a problem if we had an infinite supply of new antibiotics. Indeed, there were thousands of drugs available in the mid-1960s, and if one didn't work, doctors simply went on to the next. By the 1970s, pharmaceutical companies had shifted their research efforts from antibiotics to new drugs for cancer and heart disease. After all, who needed another tetracycline?

We do, it turns out. There are bacteria that can resist practically every antibiotic, and the drug companies have very few new ones ready for market. There are only so many ways you can attack bacteria, since they are simple organisms with few moving parts. In the past five years, the FDA has approved exactly two really new antibiotics (a handful of others were approved, but they were variations on existing drugs). One of them, Synercid, at first seemed to be something of a wonder drug--it can treat strains of bacteria that are resistant to vancomycin, one of the most powerful antibiotics now in use. But Synercid's days may already be numbered because a closely related drug has been used on animals since 1974. Bugs that are resistant to that antibiotic, it turns out, are also resistant to Synercid.

To be fair, the lion's share of blame for antibiotic resistance lies not with farmers but with doctors, who prescribe new drugs when old ones will do, and offer antibiotics for ailments as minor as the sniffles. The highest rates of resistant bacteria are found in middle-class suburbanites--precisely the people who demand antibiotics from their doctors whether they need them or not. But while patients and doctors can learn not to abuse antibiotics, consumers don't have much choice about how their meat is raised.

Where has the FDA been in all this? The answer is, the farm and pharmaceutical lobbies wield a lot of power in Washington, and the agency has been, well, chicken. When it lost the fight against antibiotics in feed in 1980, Congress wrote language into an appropriations bill threatening to suspend the agency's funding if it persisted in its attempts to limit the agricultural use of antibiotics.

Now, the FDA is ready to try again, and this time there's reason to hope it might just pull it off. The agency has the backing of the CDC and the World Health Organization; last month the General Accounting Office released a study of antibiotic use in agriculture recommending that the FDA and other federal agencies work together to come up with a sensible plan.

The FDA has already done that. What it proposes is a ranking of new and existing antibiotics according to their importance to human health. Drugs like the fluoroquinolones and Synercid would be in the most protected class, restricted to human use. Other drugs could be given to sick animals or to prevent disease among animals, but not put into feed for growth promotion. The third class of drugs, which have little value to human medicine, such as the topical ointment Bacitracin, could be widely available to farmers.

The agency is moving very slowly, trying to forge a consensus between public health officials on the one hand and industry on the other. Already drug companies are getting the message. "We're not seeing many companies coming in with applications for [low-dose antibiotics] use any more," says Stephen F. Sundlof, director of the FDA Center for Veterinary Medicine. "I think they realize the regulatory hurdles are going to be higher because they are exposing a lot more animals to the drug."

Others who have gone through the antibiotic wars are not so sure. "The industry is very powerful," says Abigail Salyers, a microbiologist at the University of Illinois at Urbana-Champaign. "Unless they go along to some extent, the fight could be ugly." But not nearly as ugly as the possibility that researchers like Crawford fear most--the possibility that in the fight between bacteria and antibiotics, the bugs will one day get the upper hand.

Shannon Brownlee is a freelance writer specializing in health and science.

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