The Fat Drug
IF you walk into a farm-supply store today, you’re likely to find a bag of antibiotic powder that claims to boost the growth of poultry and livestock. That’s because decades of agricultural research has shown that antibiotics seem to flip a switch in young animals’ bodies, helping them pack on pounds. Manufacturers brag about the miraculous effects of feeding antibiotics to chicks and nursing calves. Dusty agricultural journals attest to the ways in which the drugs can act like a kind of superfood to produce cheap meat.
But what if that meat is us? Recently, a group of medical investigators have begun to wonder whether antibiotics might cause the same growth promotion in humans. New evidence shows that America’s obesity epidemic may be connected to our high consumption of these drugs. But before we get to those findings, it’s helpful to start at the beginning, in 1948, when the wonder drugs were new — and big was beautiful.
That year, a biochemist named Thomas H. Jukes marveled at a pinch of golden powder in a vial. It was a new antibiotic named Aureomycin, and Mr. Jukes and his colleagues at Lederle Laboratories suspected that it would become a blockbuster, lifesaving drug. But they hoped to find other ways to profit from the powder as well. At the time, Lederle scientists had been searching for a food additive for farm animals, and Mr. Jukes believed that Aureomycin could be it. After raising chicks on Aureomycin-laced food and on ordinary mash, he found that the antibiotics did boost the chicks’ growth; some of them grew to weigh twice as much as the ones in the control group.
Mr. Jukes wanted more Aureomycin, but his bosses cut him off because the drug was in such high demand to treat human illnesses. So he hit on a novel solution. He picked through the laboratory’s dump to recover the slurry left over after the manufacture of the drug. He and his colleagues used those leftovers to carry on their experiments, now on pigs, sheep and cows. All of the animals gained weight. Trash, it turned out, could be transformed into meat.
You may be wondering whether it occurred to anyone back then that the powders would have the same effect on the human body. In fact, a number of scientists believed that antibiotics could stimulate growth in children. From our contemporary perspective, here’s where the story gets really strange: All this growth was regarded as a good thing. It was an era that celebrated monster-size animals, fat babies and big men. In 1955, a crowd gathered in a hotel ballroom to watch as feed salesmen climbed onto a scale; the men were competing to see who could gain the most weight in four months, in imitation of the cattle and hogs that ate their antibiotic-laced food. Pfizer sponsored the competition.
In 1954, Alexander Fleming — the Scottish biologist who discovered penicillin — visited the University of Minnesota. His American hosts proudly informed him that by feeding antibiotics to hogs, farmers had already saved millions of dollars in slop. But Fleming seemed disturbed by the thought of applying that logic to humans. “I can’t predict that feeding penicillin to babies will do society much good,” he said. “Making people larger might do more harm than good.”
Nonetheless, experiments were then being conducted on humans. In the 1950s, a team of scientists fed a steady diet of antibiotics to schoolchildren in Guatemala for more than a year,while Charles H. Carter, a doctor in Florida, tried a similar regimen on mentally disabled kids. Could the children, like the farm animals, grow larger? Yes, they could.
Mr. Jukes summarized Dr. Carter’s research in a monograph on nutrition and antibiotics: “Carter carried out a prolonged investigation of a study of the effects of administering 75 mg of chlortetracycline” — the chemical name for Aureomycin — “twice daily to mentally defective children for periods of up to three years at the Florida Farm Colony. The children were mentally deficient spastic cases and were almost entirely helpless,” he wrote. “The average yearly gain in weight for the supplemented group was 6.5 lb while the control group averaged 1.9 lb in yearly weight gain.”
Researchers also tried this out in a study of Navy recruits. “Nutritional effects of antibiotics have been noted for some time” in farm animals, the authors of the 1954 study wrote. But “to date there have been few studies of the nutritional effects in humans, and what little evidence is available is largely concerned with young children. The present report seems of interest, therefore, because of the results obtained in a controlled observation of several hundred young American males.” The Navy men who took a dose of antibiotics every morning for seven weeks gained more weight, on average, than the control group.
MEANWHILE, in agricultural circles, word of the miracle spread fast. Jay C. Hormel described imaginative experiments in livestock production to his company’s stockholders in 1951; soon the company began its own research. Hormel scientists cut baby piglets out of their mothers’ bellies and raised them in isolation, pumping them with food and antibiotics. And yes, this did make the pigs fatter.
Farms clamored for antibiotic slurry from drug companies, which was trucked directly to them in tanks. By 1954, Eli Lilly & Company had created an antibiotic feed additive for farm animals, as “an aid to digestion.” It was so much more than that. The drug-laced feeds allowed farmers to keep their animals indoors — because in addition to becoming meatier, the animals now could subsist in filthy conditions. The stage was set for the factory farm.
And yet, scientists still could not explain the mystery of antibiotics and weight gain. Nor did they try, really. According to Luis Caetano M. Antunes, a public health researcher at the Oswaldo Cruz Foundation in Brazil, the attitude was, “Who cares how it’s working?” Over the next few decades, while farms kept buying up antibiotics, the medical world largely lost interest in their fattening effects, and moved on.
In the last decade, however, scrutiny of antibiotics has increased. Overuse of the drugs has led to the rise of antibiotic-resistant strains of bacteria — salmonella in factory farms and staph infections in hospitals. Researchers have also begun to suspect that it may shed light on the obesity epidemic.
In 2002 Americans were about an inch taller and 24 pounds heavier than they were in the 1960s, and more than a third are now classified as obese. Of course, diet and lifestyle are prime culprits. But some scientists wonder whether there could be other reasons for this staggering transformation of the American body. Antibiotics might be the X factor — or one of them.
Martin J. Blaser, the director of the Human Microbiome Program and a professor of medicine and microbiology at New York University, is exploring that mystery. In 1980, he was the salmonella surveillance officer for the Centers for Disease Control and Prevention, going to farms to investigate outbreaks. He remembers marveling at the amount of antibiotic powder that farmers poured into feed. “I began to think, what is the meaning of this?” he told me.
Of course, while farm animals often eat a significant dose of antibiotics in food, the situation is different for human beings. By the time most meat reaches our table, it contains little or no antibiotics. So we receive our greatest exposure in the pills we take, rather than the food we eat. American kids are prescribed on average about one course of antibiotics every year, often for ear and chest infections. Could these intermittent high doses affect our metabolism?
To find out, Dr. Blaser and his colleagues have spent years studying the effects of antibiotics on the growth of baby mice. In one experiment, his lab raised mice on both high-calorie food and antibiotics. “As we all know, our children’s diets have gotten a lot richer in recent decades,” he writes in a book, “Missing Microbes,” due out in April. At the same time, American children often are prescribed antibiotics. What happens when chocolate doughnuts mix with penicillin?
The results of the study were dramatic, particularly in female mice: They gained about twice as much body fat as the control-group mice who ate the same food. “For the female mice, the antibiotic exposure was the switch that converted more of those extra calories in the diet to fat, while the males grew more in terms of both muscle and fat,” Dr. Blaser writes. “The observations are consistent with the idea that the modern high-calorie diet alone is insufficient to explain the obesity epidemic and that antibiotics could be contributing.”
The Blaser lab also investigates whether antibiotics may be changing the animals’ microbiome — the trillions of bacteria that live inside their guts. These bacteria seem to play a role in all sorts of immune responses, and, crucially, in digesting food, making nutrients and maintaining a healthy weight. And antibiotics can kill them off: One recent study found that taking the antibiotic ciprofloxacin decimated entire populations of certain bugs in some patients’ digestive tracts — bacteria they might have been born with.
Until recently, scientists simply had no way to identify and sort these trillions of bacteria. But thanks to a new technique called high-throughput sequencing, we can now examine bacterial populations inside people. According to Ilseung Cho, a gastroenterologist who works with the Blaser lab, researchers are learning so much about the gut bugs that it is sometimes difficult to make sense of the blizzard of revelations. “Interpreting the volume of data being generated is as much a challenge as the scientific questions we are interested in asking,” he said.
Investigators are beginning to piece together a story about how gut bacteria shapes each life, beginning at birth, when infants are anointed with populations from their mothers’ microbiomes. Babies who are born by cesarean and never make that trip through the birth canal apparently never receive some key bugs from their mothers — possibly including those that help to maintain a healthy body weight. Children born by C-section are more likely to be obese in later life.
By the time we reach adulthood, we have developed our own distinct menagerie of bacteria. In fact, it doesn’t always make sense to speak of us and them. You are the condo that your bugs helped to build and design. The bugs redecorate you every day. They turn the thermostat up and down, and bang on your pipes.
In the Blaser lab and elsewhere, scientists are racing to take a census of the bugs in the human gut and — even more difficult — to figure out what effects they have on us. What if we could identify which species minimize the risk of diabetes, or confer protection against obesity? And what if we could figure out how to protect these crucial bacteria from antibiotics, or replace them after they’re killed off?
The results could represent an entirely new pharmacopoeia, drugs beyond our wildest dreams: Think of them as “anti-antibiotics.” Instead of destroying bugs, these new medicines would implant creatures inside us, like more sophisticated probiotics.
Dr. Cho looks forward to this new era of medicine. “I could say, ‘All right, I know that you’re at risk for developing colon cancer, and I can decrease that risk by giving you this bacteria and altering your microbiome.’ That would be amazing. We could prevent certain diseases before they happened.”
Until then, it’s hard for him to know what to tell his patients. We know that antibiotics change us, but we still don’t know what to do about it. “It’s still too early to draw definitive conclusions,” Dr. Cho said. “And antibiotics remain a valuable resource that physicians use to fight infections.
When I spoke to Mr. Antunes, the public health researcher in Brazil, he told me that his young daughter had just suffered through several bouts of ear infections. “It’s a no-brainer. You have to give her antibiotics.” And yet, he worried about how these drugs might affect her in years to comeIt has become common to chide doctors and patients for overusing antibiotics, but when the baby is wailing or you’re burning with fever, it’s hard to know what to do. While researchers work to unravel the connections between antibiotics and weight gain, they should also put their minds toward reducing the unnecessary use of antibiotics. One way to do that would be to provide patients with affordable tests that give immediate feedback about what kind of infection has taken hold in their body. Such tools, like a new kind of blood test, are now in development and could help to eliminate the “just in case” prescribing of antibiotics.
In the meantime, we are faced with the legacy of these drugs — the possibility that they have affected our size and shape, and made us different people.