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New York Times Sunday Review
March 8, 2014
By PAGAN KENNEDY
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
come.
It 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.
Pagan Kennedy is a frequent contributor to The New York Times Magazine who is working on a
book about the science of invention.