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We will try just about anything--short of giving up our overeating, couch-potato habits. Just three weeks ago, a U.S. Department of Agriculture researcher presented a fat substitute made from the hulls of oats, corn and soybeans. If it is remotely palatable, it is sure to sell. History suggests, however, that it won't make much difference. Despite the arrival of Olestra last winter, despite NutraSweet and 1% milk, despite an estimated $33 billion spent every year on diet books, over-the-counter medications, health-club memberships and low-calorie foods, the flab still remains, entrenched solidly on waists, hips and thighs. News of a truly effective weight-loss drug will have people beating down doctors' doors, despite the worrisome side effects.
This marks a striking change in attitude. The idea of using drugs to treat excess weight was anathema 20 years ago, when M.I.T. neurologist Dr. Richard Wurtman first learned about the compound fenfluramine. At the time, the term diet pill was synonymous with amphetamines, and conjured up an image of sleazy feel-good doctors getting patients hooked on speed. Pharmaceutical companies wanted nothing to do with the weight-loss business.
But Wurtman was convinced that obesity must to some degree have a physiological basis. He had been doing research on the relationship between serotonin and appetite. Carbohydrates in the blood can help produce elevated levels of serotonin in the brain; Wurtman and his wife Judy, a nutritionist, theorized that eating high-carbohydrate food might be an unconscious attempt to elevate mood by giving the brain extra jolts of serotonin. "We reasoned," says Wurtman, "that people were using these foods as drugs." And because the best-tasting high-carbohydrate foods--ice cream, French fries, potato chips--are high in fat, the calories and pounds pile up.
If the Wurtmans were right, then a chemical that could generate a similar serotonin jolt might be highly effective for weight control. Wurtman began combing the medical literature for such a substance and discovered that the French pharmaceutical company Servier had discovered one called fenfluramine. "We tested it," he says, "and we found that it worked in selectively suppressing carbohydrate overeating."
Unfortunately, there was a rather dramatic and unpleasant side effect. Like many organic molecules, fenfluramine comes in both a left-handed and a right-handed version. The molecules are like a pair of gloves, with identical composition and structure except that they are mirror images of each other. That gives them different chemical properties. In this case, the right-handed molecule, dexfenfluramine, was an appetite suppressant. But the left-handed version, levofenfluramine, made people uncontrollably drowsy. And Servier didn't have a commercially viable way to separate the two.