Why we eat: the science of obesity.

THE HUNGRY GENE: The Science of Fat and the Future of Thin by Ellen Ruppel Shell Atlantic Monthly Press, $25.00

TWO YEARS AGO, A YOUNG ORGAN transplant doctor told me a harrowing story. Recently he had stood by and watched helplessly as a 15-year-old African-American girl died from an enlarged heart. A transplant might have saved her, but high blood pressure, diabetes, and a body mass of more than 400 pounds made surgery impossible. The memory haunted him as he continued to treat more and more children experiencing the deadly effects of chronic obesity. Mostly poor black kids, they marched through his office suffering from high cholesterol, high blood pressure, enlarged hearts, and adult-onset diabetes that promised to fill their future with kidney failure, amputations, blindness, and early heart attacks and strokes.

Despite the staggering numbers of kids like this who were showing up in District doctors' offices, little was being done about it. The public schools had long since sacrificed physical education to budget cuts; understaffed cafeterias served students Domino's pizza to be washed down with 20ounce bottles of Powerade from school vending machines. The American Diabetes Association, headquartered in nearby Alexandria, Va., did not have a single program in the District for adults, much less children. Even as the casualties mounted, no one was sounding the alarm about all these fat kids. Eventually, though, I discovered that one group of people had taken a keen interest in the local obesity epidemic: drug company researchers. D.C. had so many fat kids, most of whom also had fat parents, that it was a veritable gold mine for gene-hunters looking for new drugs to treat Type 2 diabetes and obesity.

I thought about these kids--and the scientists pursuing them--as I read Ellen Ruppel Shell's new book, The Hungry Gene. As the co-director of the science journalism program at Boston University, Shell's specialty is scientists, and her book is largely a story about them. Her characters run the gamut from geneticists to nutritionists studying indigenous people of Micronesia, where a traditional diet of fish and breadfruit has been replaced by, of all things, Spam. The sum of all their tales isn't particularly heartening for those who may be carrying around a few extra pounds.

As Shell explains, humans are hardwired to get fat. Put us within arm's reach of too much junk food, liberate us from manual labor, and very few will avoid gaining a spare tire. "Obesity represents a triumph of instinct over reason, and as such it embarrasses us," writes Shell. "We prefer to think of ourselves as rational beings, in firm control of our destinies or, at the very least, of our bodies. But the deciphering of the genetic underpinnings to weight regulation has ascertained that it is to some degree biological, and that our drive to eat can sometimes eclipse reason."

The difficulty of overcoming genetic imperatives, though, hasn't prevented the nation from devoting its tremendous scientific resources to finding a pharmaceutical cure for excess poundage. While Shell strives for balance, it's clear that she doesn't think too highly of some of the scientists leading the race to find an obesity drug. Some of those who specialize in the study of gluttony also seem to suffer from another deadly sin: greed. Foremost among them, according to Shell, is Jeffrey Friedman, the head of the Laboratory of Molecular Genetics at Rockefeller University, who eventually helped discover--and patent--the first obesity gene, ob, and the protein it expressed, called leptin. Researchers believe that leptin is the body's tool for regulating appetite, alerting the brain when enough food has been consumed, and have entertained high hopes that someday it could be used as an appetite suppressant in humans.

In getting the gene patent, according to Shell, Friedman screwed over the very people who had helped him make the discovery in the first place, including veterans in the field whose preeminence helped secure the funding for his experiments and lab assistants who had devoted their lives to the cause and labored in horrible conditions for years. Shell says Friedman conveniently took over one assistant's nearly finished experiments while she was out of town, just before the big discovery, thus ensuring that he would be the only one credited with finding the gene. Friedman had also ensconced himself on the scientific advisory board of a drug company, anticipating a windfall from any drugs produced as a result of the discovery of leptin.

Among the many people Friedman denied credit for the achievement was Doug Coleman, who had done the pioneering work on obesity in mice in the '70s, and who had advised Friedman on his work. "Science was once about the free exchange of ideas, about collaboration," Coleman told Shell bitterly. "But today it's about intellectual property and confidentiality. It's all about patents, about ownership."

Another of Shell's targets is George Bray, a professor of medicine at Louisiana State University Medical Center, an esteemed scientist, past president of the International Association for the Study of Obesity, and founding editor of both the International Journal of Obesity and Obesity Research. He's also a guy who thinks that obesity is so dangerous that half the country should be taking diet drugs. As a result, his services have been sought out by various drug companies seeking to promote, or to protect from regulation, highly dubious weight-loss products. According to Shell, Bray has pimped fen-phen, Merida, and Metabolife's dietary supplements containing ephedra, an herb that works much like amphetamine and has been linked to the deaths of more than 100 people.

Not all the scientists in the book are portrayed as scoundrels. Shell finds several who got into the obesity field because they were genuinely interested in helping overweight people. One of them is Stephen O'Rahilly, a professor of metabolic medicine at the University of Cambridge, a doctor who actually likes treating patients and specializes in hard cases. A few years back, he treated a pair of cousins from Pakistan who suffered from what could only be called a pathological case of gluttony. The eight-year-old girl weighed nearly 190 pounds, and, despite liposuction and surgery, could no longer walk. The two-year-old, who weighed 65 pounds, was heading down the same path. The children behaved like "starving explorers," reports Shell, devouring everything in sight. If their parents padlocked the pantry at night, the kids would scavenge "through the trash for soggy French fries and gnawed frozen fish sticks from the freezer. There was no stopping them."

Dozens of doctors had tried to help, but they could find no explanation for such behavior. So the kids went to see O'Rahilly. He was aware of Friedman's work on the effects of leptin deficiency in mice, but scientists had never been able to find a leptin deficiency in humans. (In fact, most fat people have an overabundance of the stuff.) But O'Rahilly located it in the cousins and eventually also found the obesity gene mutation--the first such discovery in humans--which was telling the cousins' brains that they were starving. In an unprecedented experiment, O'Rahilly injected the cousins with leptin, with almost instantaneous results. The cousins stopped their nightly foraging in the kitchen, pushed away from the table, and shed pound after pound. O'Rahilly's work proved conclusively that the drive to overeat had deep genetic roots.

While leptin may have cured the Punjabi cousins of their ruinous cravings, its usefulness in treating other overweight people has so far been limited only to those with the specific, and rare, genetic mutation. More recent studies have shown that leptin does not serve as the body's tool for maintaining slimness, but rather prevents the body from becoming too thin. It's protective--if you're a hunter-gatherer subject to great variations in the availability of food. That's why, as one researcher told Shell, "For one or two months people considered leptin the Great White Hope. But we now know that leptin is not very good at preventing people from eating too much."

Forever Fat

With more than 60 percent of Americans overweight, Shell says scientists and drug companies alike see obesity as the "trillion-dollar disease," which is why, even when their products have failed to deliver, they have resorted to devious and underhanded scheme to deceive people into taking them anyway. Diet drugs have proven notoriously ineffective at helping people lose weight, and also usually rather dangerous. Fen-phen, which caused hundreds of cases of deadly primary pulmonary hypertension and heart-valve damage, is but one example. Shell shows how drug companies manipulated the Food and Drug Administration to get approval for Meridia, a weight loss drug that raises the risk of high blood pressure and stroke--the very things that are supposed to be reduced by losing weight. Meridia now has been linked to at least 19 deaths. And she finds several examples of prominent doctors selling drug companies the use of their names in order to get misleading industry-written articles touting the benefits of drugs like fen-phen into peer-reviewed medical journals.

Not only does Shell hold out these stories as morality tales about the dangers of greed in science, but she also uses the diet drug failures to make a convincing case that the scientific intellect will probably never outsmart the hardwiring of the body to consume excessive calories. Treat one angle of the problem, and another will kick in to compensate for it. That's why something drastic such as gastric bypass surgery--stomach stapling--works, but only for a while. Eventually, people who've undergone the surgery regain their appetites, and find creative ways to circumvent the problem of the smaller stomach, such as drinking melted quarts of ice cream. "Mother Nature wants her children to eat. Knock out a satiety gene like ob and an animal will eat insatiably. But knock out an appetite gene, and animals continue to eat normally," Shell writes. "For this reason, appetite-controlling drugs like fen-phen and Meridia, while they may work for some for a year or two, are not likely to permanently alter the eating habits of millions."

While much of The Hungry Gene is about the science of fat, Shell doesn't overlook environment as a critical factor in the world's obesity epidemic. It's the interplay, she argues, between genetics and environment that has created the current crisis in human waistlines. Our hunter-gatherer genes, designed to conserve energy and food to prepare for times of famine, are clashing with a modern culture of ease and plenty. To that end, she takes on car culture and the fast-food industry, a subject that has been well covered by Eric Schlosser in his bestselling Fast Food Nation.

Like Schlosser, Shell ends with the now-familiar call for a ban on marketing junk food to children. It's absolutely the right prescription, but one that invokes a "Yeah, right" response. This country will never ban Happy Meal ads on TV. Shell might have done better to suggest fighting fire with fire. Let the fast-food industry continue to market to children, but require TV stations to donate air time for anti-junk-food messages, which might, say, show what really goes into those burgers and fries. Or they might offer testimonials on the value of exercise from young people with Type 2 diabetes whose feet have been amputated. A similar requirement in the late 1960s for tobacco ads was so effective that it prompted the industry to voluntarily remove cigarette ads from television all together.

Another possibility would simply be warning labels, stickers on the side of 7-11 Double Gulps that spell out the dangers of consuming a full 64 ounces of Coke. Warning labels may seem trite on cigarettes today, but how many people really could say for sure how many calories are in a Double Gulp? (Answer: 600, almost a quarter of the proper full day's energy budget for an average male.) The food industry lobby has ferociously fought such labeling in the supermarket, a sign that this might be effective, at least for a while.

But why wait for the government to get involved? Instead, the food police at the Center for Science in the Public Interest ought to station themselves outside a busy McDonald's wearing sandwich boards that list the calorie and fat content of a large Extra Value Meal containing a Quarter Pounder with cheese (1,380 calories and 56 grams of fat). With the public duly informed about the restaurant's products, sales might plummet as people would no longer be able to delude themselves that fast food isn't that bad. Again, it might be only a temporary interruption, but it would accomplish what consumer groups can't afford to do now: counteract the onslaught of junk-food marketing. The media would eat up a campaign like this, and give the issue lots of free airtime. No doubt McDonald's would also respond with some ham-fisted legal action that would all but guarantee years of free fast-food bashing to come.

Shell doesn't raise the possibility of such exercises, but I'm sure she would approve. After all, they are far safer than a dose of Xenical. And she concludes that because of our genetic predisposition to amass calories, it's imperative for the U.S. and other countries to create an environment that at least makes us work a little harder for our Krispy Kremes--or shames us into avoiding them all together.

STEPHANIE MENCIMER is an editor of The Washington Monthly.