Andrea Gardner, a registered nurse who lives in Weymouth, Mass., is in the midst of that process. She has tried one diet after another, losing weight and gaining it back. She is 5 feet 5 inches tall, and her body, she says, seems to want to settle at a weight of about 185 pounds, which is not acceptable to her.

She continues to work with Dr. Apovian, ever hopeful that this time a diet and, she said, willpower, will do the trick.

But about 15 to 20 percent of patients respond to measures short of surgery, with response defined as a change in their body weight that is maintained without constant hunger or cravings. While people seldom end up thin, their permanent weight loss is a proof of principle, showing that treatments can lower the weight the brain forces a person to maintain.

The last resort, for those whose obesity is extreme, is bariatric surgery, which elicits a permanent and substantial weight loss in almost everyone.

In the meantime, there is Dr. Sacks’s challenge.

His study involved 811 overweight and obese adults, randomly assigned to follow one of four diets and undergo behavioral counseling to help them stick to their diets. The diets ranged over the span of what has become popular. Two diets were low in fat but one low-fat diet was high in protein and the other had average amounts of protein. Two others were high in fat and one of those high-fat diets had an average amount of protein while the other was high in protein.

The research was designed to answer the question of whether one diet was any better than another and it provided an answer: None of the diets elicited much weight loss on average, and no diet stood out from the others.

But buried in those averages were the outliers: In every one of the four diet groups were a few superresponders who dropped huge amounts of weight and a few nonresponders who did not lose any. And as soon as his paper on the diets was published, with the conclusion that no diet stood out and none elicited much of a weight loss, he started hearing from people who challenged him.