Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (12 page)

There were only a handful in the room to listen, but the congressman had captured the essence of why we need to do something. His committee reported favorably about the legislation, which eventually became part of a federal act to create incentives for companies to develop new antibiotics. However, the paradox remains that we use far too many antibiotics, but we don’t have enough of the right ones to treat an emerging burden of these antibiotic-resistant infections. Actually, the problems are related; the first drives the likelihood of the second.

But antibiotic resistance is not just a problem of people overusing antibiotics. The problem also stems from how we treat animals down on the farm.

7.

THE MODERN FARMER

Imagine cattle grazing peacefully in a pasture, chewing their cud, moving from place to place to eat fresh green grass. You might envision a Norman Rockwell scene of our agrarian past: carefully tended barns, beautiful picket fences, contented cows, and, breaking the silence, the buzzing of an occasional fly and flapping of tails.

Here’s another picture: cows lined up in small metal pens, row after row of them, with their heads braced into corn-filled troughs. A dense, pungent odor of cow manure wafts from miles away. Cows are released into vast feedlots where they mill around on bare ground, eating all the time, surrounded by their poop.

Most antibiotics produced in the United States go not to humans but to these massive feedlots and their equivalents for swine, chickens, and turkeys. They are modern, integrated, industrial operations for fattening up millions of animals for slaughter, billions in the case of chickens. Agricultural science operates to maximize meat production, with a particular focus on optimizing feed efficiency—the conversion of calories in animal feed into meat. Feeding antibiotics to farm animals plays a central role in that process, fattening them up. But it has also led to antibiotic resistance in the microbes inhabiting livestock and to antibiotic residues in our food and water. And it provides an important, albeit distasteful, analogy about what we might be doing to our children.

We now know that antibiotic resistance develops in humans when a drug kills susceptible microbes while sparing the occasional microbes that through genetic variation have acquired resistance. The resistant species proliferate, making further antibiotic treatments less effective. The same thing happens on the farm, but here I will elaborate on the process in more detail.

Bacteria, fungi, and algae have been fighting one another for hundreds of millions of years to gain the upper hand in an endless game of chemical warfare. In their struggle to survive, they produced natural antibiotics for self-defense. At the same time, they evolved genes that would counteract their own antibiotics and those of their enemies. Thus, two classes of sophisticated genes emerged in microorganisms: those involved in making antibiotics and those that provide resistance to antibiotics.

In 2011 scientists analyzing thirty-thousand-year-old bacteria from the Yukon permafrost found that these bacteria were able to resist antibiotics, both those occurring naturally as in bread mold and the semisynthetics, which have similar core structures. The finding provides direct evidence that ancient genes for antibiotic resistance were widespread and long preceded our human use of antibiotics for treating illness. One implication of the ancient arms race is that we didn’t cause resistance. To say that it is not our fault is only partly true; although resistance is ancient, we have made it a lot worse. We don’t even know how many orders of magnitude we have multiplied it, within our human space, but it is surely considerable. Even ocean life, offshore but living in our wastes, shows evidence of the spread of resistance from our activities. It is a fingerprint that we are leaving everywhere.

Another implication of the ancient nature of resistance is that there will be no easy solution to the problem. We will never make resistance go away, because Darwin was correct in his theories. There always will be strong selection for resistance when populations encounter stress, in this case, microbes under antibiotic pressure. A corollary is that we will never invent a superantibiotic that cures everything. Microbes are too diverse, and Nature will always come up with new ammunition.

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Our bucolic barnyards have been replaced by those feedlots and henhouses containing tens of thousands of animals. A single barn from a large hog operation can hold two thousand or more pigs. A single henhouse can hold twenty thousand or more chickens. By packing the animals into small, unsanitary spaces, farmers set up the perfect conditions for bacteria to proliferate and spread.

But the main reason farmers give their animals antibiotics isn’t so they can crowd them together with fewer diseases. In fact, they don’t give their animals full therapeutic doses, the levels that would be used to treat infections. On most factory farms, animals are given food or water treated with a low, subtherapeutic dose of an antibiotic. Farmers do this to enhance feed efficiency. This effect of subtherapeutic antibiotics is called growth promotion.

The practice dates back to the mid-1940s when pharmaceutical manufacturers discovered that animals fed antibiotics gain more weight in terms of muscle mass more quickly than do animals fed a drug-free diet. In reviewing the older literature, I found a particularly interesting study from 1963. Amazingly (at least to me), the nature of the interplay between gut microbes and antibiotics was described way back then. These scientists asked themselves whether the observed growth promotion effects in animals were due to antibiotics themselves (acting on tissues) or to their effects on the microbiome (which they called the normal flora). So they raised two groups of chickens: one in the usual circumstances, what we call conventionally, and the other under germ-free conditions. Germ-free animals have been raised so that there are no microbes at all living in or on their bodies. In each group, half the animals received antibiotics in their feed while the other half, serving as controls, did not.

As expected, conventionally raised chickens exposed to low-dose antibiotics grew bigger than the untreated controls. But the two groups of germ-free chickens turned up a surprise: those given antibiotics were no bigger than the ones who weren’t. This suggested that a chicken’s microbes are essential for the growth-promoting effect to occur; antibiotics alone were ineffective. These findings have been available for more than fifty years, but they were ignored and then forgotten.

The upshot is that farmers quickly realized that their animals could gain an extra 5, 10, or 15 percent of their normal body weight at a relatively low cost. And the corollary to this was that they gained more weight per unit of food that they consumed. This was called improved feed efficiency. The pharmaceutical companies found that they could make big profits by selling antibiotics to farmers by the ton rather than by the milligram to physicians.

Today, an estimated 70–80 percent of all antibiotics sold in the United States are used for the single purpose of fattening up farm animals: hundreds of millions of cattle, chickens, turkeys, pigs, sheep, geese, ducks, and goats. In 2011, animal producers bought nearly 30 million pounds of antibiotics, the largest amount yet recorded, for their livestock. We don’t know the exact number because these amounts are closely guarded secrets. Both the agricultural and pharmaceutical industries are defensive about their practices. According to the former chairman of the Food and Drug Administration David Kessler, until 2008 Congress didn’t require drug companies to tell the agency the quantities of antibiotics they sold for use in agriculture. Nor do the firms provide information on how drugs are administered or to which animals and why. Industry lobbyists have successfully blocked most attempts to curtail antibiotics in animal feed. And because of this ongoing battle, there has been little research on the pros and cons of growth promotion. With the exception of a few industry-oriented scientists, few people have been paying much attention.

Meanwhile, ecologists and medical doctors bemoan the practice of growth promotion, noting that farmers give animals the same drugs that people get from their doctors and surgeons. In 2013, Consumers Union tested hog carcasses and found that 13 of 14
Staphylococcus
samples isolated from pork were resistant to at least one antibiotic. So were 6 of 8
Salmonella
samples and 121 of 132
Yersinia
samples. One sample was found to have MRSA, the fearsome drug-resistant and sometimes fatal form of staph that we discussed. Why would we squander our precious antibiotics, including the ones that save lives when nothing else helps, to make meat a few cents a pound less expensive?

In 2011 more than half of samples of ground turkey, pork chops, and ground beef collected from supermarkets for testing by the federal government contained bacteria resistant to antibiotics, what we sometimes call superbugs. Actually there is no such thing as a superbug (a term invented by reporters), but if one of these highly resistant organisms were to attack and infect your knee or heart valve and there were no effective antibiotics, you would readily think it had superpowers.

Resistance is not the only problem. The National Antimicrobial Resistance Monitoring System (a joint program of the Food and Drug Administration, the Department of Agriculture, and the Centers for Disease Control and Prevention) found that some 87 percent of the meat collected from supermarkets contained either normal or antibiotic-resistant forms of enterococcus bacteria, which are an indication of fecal contamination. Two such species of the bacteria,
Enterococcus faecalis
and
Enterococcus faecium
, are leading causes of infections in the intensive care units in U.S. hospitals. One possibility is that some of those patients acquired resistant versions of them from their food.

Sweden banned the use of antibiotics for growth promotion in 1986. The European Union forbade the practice in 1999. Since then, the use of all antibiotics in animal feed for growth promotion has been banned in all of Europe.

American food producers and pharmaceutical companies argue that there is no solid proof that antibiotic-resistant microbes from animals are infecting humans. But in fact we have evidence going back more than thirty years showing the same organism—with the same patterns of antibiotic resistance—turning up in sick people and in animals fed growth-promoting antibiotics. For example, more than two thousand different strains of
Salmonella
have been typed and have names, so we know who they are. A long series of
Salmonella
outbreaks in people have been traced back to factory farms. The microbes isolated from the animals, the food, and the infected people were shown to have identical molecular profiles as well as patterns of antibiotic resistance.

The stonewalling defies reason and represents the kind of hands-off libertarianism that is eroding our public health. Bacteria don’t respect political dogma any more than they recognize political boundaries and jurisdictions. In March 2013, a Danish study provided yet another smoking gun. Using whole-genome sequencing of bacteria, researchers demonstrated that the MRSA infections of two Danish farmers were caused by the same organism that infected their animals, which could not happen by chance, providing evidence that they became infected by the strain from contact with their animals.

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The problem is not limited to the resistant bacteria that come to us in the food we buy from industrial farms. The antibiotics themselves arrive in our food, particularly in meats, milk, cheeses, and eggs. The Food and Drug Administration requires farmers to establish a washout period between giving the last dose of an antibiotic and when the animal is slaughtered. But inspections are infrequent and enforcement is minimal.

Foods on our supermarket shelves are allowed maximum residue limits for antibiotics, establishing upper boundaries of what is permitted. For example, milk can legally have up to 100 micrograms of tetracycline per kilogram. This means that a child who drinks two cups of milk a day will ingest about 50 micrograms of tetracycline every day. That is not a lot, but consider the fact that many children drink milk every day, year after year. And that level is just for tetracycline. All other antibiotics have their own allowable limits. A 1990 report indicated that 30–80 percent of milk samples had detectable antibiotics, especially sulfa drugs and tetracycline.

Surveys in the 1980s and 1990s showed that legal limits were exceeded 9 percent of the time in meats, milk, and eggs. Thus, you are likely to be ingesting antibiotics whenever you eat nonorganic meats, milk, or eggs. Most people who say they have not had an antibiotic in years are mistaken. Millions of us are exposed every day and not only from foods. Antibiotics are found in our water, especially around farm runoff and treated human sewage. Current water purification treatments are excellent for reducing harmful bacteria and viruses but they do not fully remove antibiotics. A 2009 study of several cities in Michigan and Ohio found antibiotic-resistant bacteria and genes in all source waters, drinking water from treatment plants, and tap water. The amounts were small, with the greatest levels in tap water. The point is that it all adds up.

Densely farmed commercial fish, such as salmon, tilapia, and catfish as well as shellfish like shrimp and lobster, are given relatively high doses of antibiotics, not so much to promote growth as to combat diseases associated with the crowded conditions in which they are raised. As with livestock, the FDA requires a washout period, but fish raised domestically are rarely inspected. Fish and shellfish raised in Asia are more tainted. Violations abound.

The antibiotic oxytetracycline—closely related to a form of tetracycline widely used in people—and streptomycin are even used on organic apples and pears to combat fire blight, a bacterial disease of fruit trees. The use of such drugs does not have to be divulged. You probably never imagined that produce labeled organic could contain antibiotics. Drug-resistant bacteria also end up in fertilizer and soil, further contributing to the reservoir of resistance in our ecosystem.