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Friday, November 23, 2007

But what if fat was just a virus?

In the early 1980s, a bird virus swept through India and killed hundreds of thousands of chickens, and a veterinarian named Sharad Ajinkya noticed that the virus also seemed to make the chickens fat, which was odd -- if the virus was killing them, shouldn't it make them thinner? A few years later, he mentioned the fat chickens to Nikhil Dhurandhar, a young obesity specialist who ran a series of clinics in Bombay. Dhurandhar had seen so many people struggle with weight, fighting epic battles of willpower and poisoning their lives with self-loathing. But what if fat was just a virus?

The first step was obvious. Working with Ajinkya, he got some germ-free chickens and injected them with the bird virus. When he checked them six weeks later, the average weight of the chickens had shot up by 50 percent without getting higher levels of cholesterol or triglycerides, a most intriguing paradox. Then he took samples from ?fty-two of his human patients and checked them for antibodies to the chicken virus and bingo, the fattest patients tested positive for the virus and also for lower cholesterol and triglycerides.

In 1992, Dhurandhar quit his job and took his theory to the United States, giving himself two years to land a research job. The reception he got is reflected in the mockery that still fills the Internet. "I'm not going to work tomorrow, I'm calling in fat. . . . Since when is a fifteen-piece bucket of fried chicken a virus?" It was rooted in religion, Dhurandhar decided, this idea that fat people were gluttons deserving the punishment of every pound. You couldn't just catch fat. So Nikhil was right down to his self-imposed deadline when a job at the University of Wisconsin came through.

The data from his first American tests came back on a cold winter day in Madison, when snow covered the hills around the lab. A similar virus had made American chickens fat, too. "I could see thirty years of research stretching out ahead."

Dhurandhar had stumbled onto one of the hottest new ideas in biochemistry, the idea that our bodies are a kind of rain forest for parasites and bacteria and that we and our parasites have coevolved into a genuine ecology -- the "microbiome," it is called.

Joel Weinstock's eureka moment came on an airplane -- the kind of magic, unscheduled time when a man's mind just naturally drifts to intestinal flora. As he puzzled over a sheaf of statistics that showed a dramatic increase of immunological diseases in developed countries, he remembered some other work he was doing on helminths, parasites that had nearly been eradicated in developed countries -- hookworm and pinworm, for example. Suddenly he made the connection. "Oh my God," he thought. "It could be those helminths."

In those days, nobody had anything good to say about intestinal parasites. Mothers warned their children that going barefoot could result in foot-long worms that would sap your energy and doom you to Third World poverty, if not actually emerging snakelike from your mouth at the smell of a fragrant bowl of soup. But when Weinstock looked at the scientific record, he just didn't see any evidence that helminths were bad. And as soon as his lab started running animal tests, the results showed the opposite. "Lo and behold, we could inhibit immunological diseases with worms."

Like Nikhil Dhurandhar, he had gotten a glimpse into a brand-new scientific revolution, a paradigm shift in the way we think about the human body. In the old way of thinking, the body was a pristine homeland we had to defend from attack by bad germs. Cholera and dysentery were classic bad germs that we defeated with antibiotics and modern sanitation, cleanliness marching next to godliness. But in our fervor we forgot the trillions of resident bacteria that live permanently on our skin and inside our bodies, not to mention the various viruses and fungi and the odd patch of yeast. In fact, an astonishing 90 percent of the cells in the body are microbiotic colonizers. Many have been with us since the beginning of time. Helminths, for example, have been found in petrified stool and petrified humans, in Egyptian mummies and the Iceman who fell into a glacier ?ve thousand years ago. We have coexisted with them for a hundred thousand years. In undeveloped countries, at least 80 percent of the population carries them.

But in the last hundred years we have nearly made them extinct in developed countries. At the same time, developed countries have seen a steady rise in diseases of the immune system, ulcerative colitis and Crohn's disease, hay fever, asthma, and multiple sclerosis. What if that's not just a coincidence? What if a child is like an unprogrammed computer and the worms are like software that boots up our immune defense systems?

In Martin Blaser’s infectious-disease research lab at New York University, Blaser stands in the hallway in a tight tie and short-sleeved shirt, staring fondly at a poster with black squiggles on it. "This microbe has coevolved with humans, so it really understands us well," he says.

He is speaking of Helicobacter pylori, the Elvis Presley of stomach microbes. Associated with Third World dirt and rural lifestyles, Helicobacter was dying out as fast as Weinstock's worms. It was known to cause ulcers and stomach cancer, which were also dying out rapidly in the developed world. Now Blaser was trying to find an association with esophageal cancer. And one day a grad student came into his office with some puzzling data. "There isn't an association. There's a reverse association."

That was his turning point, the moment the light went on. Because esophageal cancer was the fastest rising cancer in the developed world, which meant that the same bug that caused one cancer could be preventing another, which meant that we couldn't just kill the bugs. We had to understand them, had to learn to work with them, to study the models of cooperation that evolution had established between us. Blaser became chairman of the NYU Department of Medicine and president of the Infectious Diseases Society of America, and his work linking the rise in esophageal cancer to the loss of Helicobacter won an award from the American Cancer Society. Now the revolution he and Weinstock and Dhurandhar helped start is exploding across the globe. Scientists are using live "microflora" to reduce infection in childbirth, to treat colitis and vaginosis. Last year, American scientists finished the first survey of the microbes in the colon. And in September, the National Institutes of Health committed $115 million to begin archiving our resident microbes and sequencing their genes.

Visionaries are hoping for cures for some forms of obesity and anorexia along with various forms of cancer, asthma, multiple sclerosis, Alzheimer's, lupus, and most of the major psychiatric diseases. In the future, Blaser says, pediatricians could help prevent these diseases by infecting babies with a starter kit of friendly bacteria. "Bottom line, humans and our fellow animals have been colonized by microbes for a very long time, going back a billion years. The microbes that we carry have been selected because they are helpful to us. They participate in human physiology. They are a compartment of the body, like the liver or the heart."

Like a microbiologist's version of big-game trophies, the hallways of Blaser's lab are lined with conference presentations -- here are the anthrax studies he did for the government after 9/11, here the famous study where he found an average of forty-eight different kinds of bacteria on a single patch of human skin, the first of its kind. Here's a study of how Helicobacter affects human cell mutations, and a study linking the presence of Helicobacter to an almost 40 percent decrease in the risk of having asthma, a huge finding that could save thousands of lives. Then he stops in front of a last poster, a recent study of psoriatic skin. It hasn't been published yet, so he doesn't want to say too much. But he admits to a certain excitement. "There's a difference in the population of microbes," he whispers.

"So you eliminate them and cure psoriasis?"

"Or maybe you have to add some back," he says, smiling at an inner vision. "I'm thinking, maybe you have to add some back."

John H. Richardson

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