It seems so unfair. People who devote themselves to exercise and diet programs shed about 10 percent of their weight, and they regain as much as two-thirds of it a year later, according to the National Institutes of Health. Drugs aren't much help, and their side effects make many doctors hesitant to prescribe them. Which makes bariatric surgery—using staples or bands to reduce the stomach from a wine bottle to a couple of grapes—the clear winner for people who are morbidly obese: A 2004 study published in the Journal of the American Medical Association found that patients lost an average of 61 percent of their excess weight. And the majority keep the weight off.

Gastric bypass surgery adds years to people's lives, too. In 2007 The New England Journal of Medicine reported that obese individuals who went under the knife decreased their risk of dying within the following decade by 40 percent.

Still, of the 15 million Americans who qualify for the procedure, only 1 percent will actually get it, mostly because of concerns about safety: "Infection, bleeding, and intestinal obstruction are real risks, and weight loss results aren't always permanent," says Ron Palmon, MD, a clinical instructor in the division of gastroenterology at New York's Mount Sinai School of Medicine. "There's a definite need for a less invasive alternative." That need has not gone unnoticed in the halls of science and venture capitalism, and several groups are vying to be the next big thing in obesity treatment. Some researchers are developing ways to help those who regain the weight after a bypass. Others are ignoring the stomach altogether, looking for brand-new ways to fool the body into shedding pounds.

Mildred Coleman, 58, of Columbus, Ohio, started as a bariatric surgery success story. After a lifelong struggle with obesity, in 1996, weighing 383 pounds, she took the leap and had her stomach stapled. In total she lost 237 pounds. Then, two years ago, everything changed. She had fulfilled a major goal by enrolling in college, but her studies interfered with her efforts to exercise and diet. "My freshman 15 was more like a freshman 40," she says.

When Coleman visited Dean J. Mikami, MD, an assistant professor of surgery at Ohio State University, he wasn't at all surprised: "Stomachs stretch," he says. "Over time, eating just a little too much of even the healthiest foods will add volume and gradually undo the benefits of surgery."

Luckily, Mikami could suggest a different approach for Coleman. He had worked on clinical trials for a device called StomaphyX—it's like a tiny sewing machine that is lowered into the stomach from the mouth. Guided by an endoscope, a doctor can use StomaphyX to gather up folds of stomach tissue and stitch them together, shrinking the stomach. Average weight loss at six months is about 20 percent of a person's excess weight.

From the August 2008 issue of O, The Oprah Magazine

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