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How Congress Ignored Science and Fueled Antibiotic Resistance

How Congress Ignored Science and Fueled Antibiotic Resistance
From Wired - September 12, 2017

The gray clapboard house on the two-lane road in a western suburb of Boston looked, in the fall of 1974, the way you would expect a comfortable old Massachusetts house full of children to look. It was rambling and tall, made out of a house and a barn butted together. There were other barns out back, down a long gravel drive that stretched to a grove of trees: small sheds and one big building, 200 feet on the long side, painted an iconic barnyard red. There was a milk cow, a few horses, a couple of pigs, and chickens: white laying hens, some in a chalet-shaped coop and some skittering underfoot between the trees.

Inside the house, kids were everywhere, seemingly as much underfoot as the chickens were: Richard, Mary, and the twins (Peter and Paul); Steve, Ronnie, and Mike; Christopher, Christine, and Lisa. Their parents, Richard and Joan Downing, were Catholic and had wanted a big family. Richard had done well in business, establishing credit-reporting firms around Boston. When the twins turned out to be their last biological children, he and Joan had committed to using their money to improve other kids lives, so there were always extra children in the house, up to a dozen at a time.

Some stayed a few months or years as fosters; others joined the family permanently through adoption. The Downings were sturdy people, no-nonsense but warm. Their house was mostly happy chaos, with kids racing around corners clutching sports equipment and homework, and dashing outside to feed the pigs and milk the cow.

There was just one note of stern discipline, in a notice stuck on the front of the refrigerator. It had been written by Mary, the oldest daughter, in the careful printing she was learning in college biology. It said, in block letters, No Juice Until I Get Your Poop.

Inside the refrigerator, along with celery and cold cuts and the much desired juice, were a couple of brown paper lunch bags. All of the bags held the same thing: a cluster of long, clear tubes, tightly capped, each one holding swabs that looked like long Q-tips. Each of the swabs was stained at one end. The swabs in one bag came from the Downing kids. The swabs in another came from the neighbors, who dropped them off once a week. (They didnt wait for juice.) The swabs in the third had been swirled over the butts of chickens in the big barn at the back.

It looked like arrangements for a kids jokey science fair exhibit, but this endeavor was deadly serious. The Downings had agreed to host an experiment, one that centered on the animals out back and involved their sprawling family and their neighborhood. The experiment was the first attempt to explore, in an organized, documented way, that antibiotics given routinely to animals represented a threat to human health.

Actually, at first, it intended to disprove it. The sponsors of the study were industry: the Animal Health Institute, the trade group representing the companies that made and sold antibiotics used on farms. At this point, antibiotics to promote animal growth were a routine component of agriculture: 40 percent of the ones made in the United States were going into livestock, not to human patients. But it was also 10 years since scientists had begun claiming a connection between farm antibiotic use and human illness, and growth promoters and preventive dosing were coming under increased public scrutiny. The animal drug industry was under pressure to prove its products were safe, and it had agreed to fund a study to demonstrate that.

The study would not go the way the industry hoped, and it would change the debate about agricultural antibiotic use for good.

Meet the Downings

The study was being conducted by Dr. Stuart B. Levy, a researcher in Boston. Levy was 36 in 1974. He was the son of a family doctor from Delaware and had grown up accompanying his father on house calls and discussing cases afterward. He was a faculty member at Tufts University School of Medicine, in a part of Boston that is gentrified now but was cheap and seedy then, and he had taken a circuitous route to get there, studying first literature, then medicine, and then microbiology in Italy and France.

Researchers had confirmed an earlier discovery that genes conferring antibiotic resistance could stack up and be carried from one bacterium to another. That would allow an organism to acquire resistance in advance of ever being exposed to a drug, while also allowing multiple types of resistance to spread. It threatened to make resistance much harder to track and combat.

The Animal Health Institute found Levy and offered to fund a study on behalf of farm antibiotics. That was why there were tubes of poop-stained sample swabs in the Downings refrigerator. They were tools that would help Levy establish, or disprove, whether resistance could migrate through the environment, from animals that had received antibiotics, to animals and people who had not. Growth promoters proponents hoped the answer would be no.

Levy did not know the Downings, but he knew what he needed to make the proposed study possible: a place that looked like a farm but had not been functioning as one. He needed new animals that had never received antibiotics, a place to raise them where antibiotics had not been used in the recent past, and a group of animal handlers numerous enough to conduct the experiment and healthy enough to not be taking antibiotics themselves. For bonus points, the location needed to be close enough to his office that he and his staff could travel back and forth affordably. In the affluent suburbs of Boston, that was a complex order to fill. He was not sure even where to look, but he began to ask around. Bostons rural exurbs are very unlike the city, but so many people commute in and out that they are more tightly tied than they look. The news of Levys search for a place to conduct his study percolated through the medical community, and after a while, someone got in touch: a veterinarian responsible for the mice and other animals that Massachusetts General Hospital kept to do research. He lived in the tiny town of Sherborn, 20 miles southwest of Boston. His across-the-street neighbors were a relaxed, irreverent family; they had lots of kids; and they lived on a big parcel with a couple of barns that had once been an egg-sorting business. He offered to make an introduction.

Levy drove out to meet the Downings. He described what he envisioned: a temporary farm housing 300 chickens, to be maintained for at least a year. Richard Downing liked the impish, focused physician, and he liked the idea of contributing to knowledge and letting his kids watch an experiment up close. But he had grown up on a poultry farm, in the coastal town of Weymouth, and he knew Levy did not know how to accomplish what he wanted to do.

I told him he was crazyhe had no idea what this would take, Downing recalls. Hed have to build the pens, buy the feed, set up the watering system, put in heat, find someone to look after them, get someone to clean up. And he said I was right, and he hoped we could help.

The Downings accepted the challengefor fun and out of curiosity, and because being unconventional had never worried them before. To manage the experiment, they nominated their oldest daughter, Mary. A sophomore at a local college, she was living at home to save money. She wanted to go to France after graduation, but with so many other kids in the household, spare funds were in short supply. She and her parents and Levy struck a deal. She would supervise the chickens, water and feed them, and collect all the data Levy would need, which, she learned, meant collecting poop, and not just from the birds. He offered to pay her $50 every week, about $250 now. She signed on.

In the big barn at the back of the property, Levy and 10 medical students, along with the Downings and their kids, built six wire pens, each equipped with gas heaters and independent food trays and water systems. Four were inside the barn, 50 feet apart; two more stood outside its thick timber walls. Then Levy went in search of chicks. To ensure there would be no contamination, nothing in the chickens systems that would slant the study results, he bought them from a company that supplied pathogen-free eggs to laboratories.

In July 1974, the day-old Leghorn chicks arrived in Sherborn and were stashed in one of the pens with a heat lamp and water and antibiotic-free food. When they were two months old, the experiment began. Levy divided the chicks into six batches, 50 per pen. At the local feed store, he bought two types of feed, one antibiotic free and another that was sold premixed with antibiotics. It contained oxytetracycline in a ratio of 100 grams per ton. Half of the birds, in three of the six pens, got the drug-free feed. The other half got the tetracycline-laced mix. Levy had several questions to answer. First, did the antibiotics in feed cause resistant bacteria to emerge or multiply in the chickens receiving it? Second, did that resistance cross from those chickens to the rest of the flock? And third and most crucial, could it make the leap from chickens to humans?For the experiment to establish everything that Levy planned, he needed to recruit people beyond the Downings to participate. At their invitation, he drove out to meet the neighbors. Joan and Richard threw a barbecue and invited the five families10 parents, 14 kidswho lived up and down the road. After the hamburgers and hot dogs and corn were handed around, the Downing boys rolled a washtub over to make a podium. Levy had discussed with the parents what he planned to say, and they had reassured him that it was best to be straightforward. Still, he felt a little nervous as he climbed up on the tub.

Were asking you all to be part of an experiment, he told the guests. The parents made murmurs of interest and shushed their kids. He described the puzzle of antibiotic resistance, how the chickens might help solve it, and that the Downings had agreed to assist. Then he got to the hard part.

Wed like you to donate something that you have to science, he said. The small crowd perked up with curiosity. He heard one woman say, This is exciting!

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