Dr. Frank Sacks, a professor of nutrition at Harvard, likes to challenge his audience when he gives lectures on obesity.

“If you want to make a great discovery,” he tells them, figure out this: Why do some people lose 50 pounds on a diet while others on the same diet gain a few pounds?

Then he shows them data from a study he did that found exactly that effect.

Dr. Sacks’s challenge is a question at the center of obesity research today. Two people can have the same amount of excess weight, they can be the same age, the same socioeconomic class, the same race, the same gender. And yet a treatment that works for one will do nothing for the other.

The problem, researchers say, is that obesity and its precursor — being overweight — are not one disease but instead, like cancer, they are many. “You can look at two people with the same amount of excess body weight and they put on the weight for very different reasons,” said Dr. Arya Sharma, medical director of the obesity program at the University of Alberta.

Not only can that explain why treatment is so difficult and results so wildly variable, but it can explain why prevention efforts often fail.

If obesity is many diseases, said Dr. Lee Kaplan, director of the obesity, metabolism and nutrition institute at Massachusetts General Hospital, there can be many paths to the same outcome. It makes as much sense to insist there is one way to prevent all types of obesity — get rid of sugary sodas, clear the stores of junk foods, shun carbohydrates, eat breakfast, get more sleep — as it does to say you can avoid lung cancer by staying out of the sun, a strategy specific to skin cancer.

One focus of research is to figure out how many types of obesity there are — Dr. Kaplan counts 59 so far — and how many genes can contribute.

So far, investigators have found more than 25 genes with such powerful effects that if one is mutated, a person is pretty much guaranteed to become obese, said Dr. Stephen O’Rahilly, head of the department of clinical biochemistry and medicine at Cambridge University.

But those genetic disorders are rare. It is more likely that people inherit a collection of genes, each of which predispose them to a small weight gain in the right environment, said Ruth Loos, director of the genetics of obesity and related metabolic traits program at the Icahn School of Medicine at Mount Sinai. Scientists have found more than 300 such altered genes — each may contribute just a few pounds but the effects add up in those who inherit a collection of them, Dr. Loos said.

There are also drugs that, in some people, can cause weight gain. They include medications for psychiatric disorders, some drugs for diabetes, some for seizure disorders, beta blockers to lower blood pressure and slow the heart rate, and steroids to suppress the immune system, for example. People taking them, however, may not realize the drugs are part of their problem. Instead, they blame themselves for a lack of self-control as their weight climbs.

Certain diseases also cause weight gain, Dr. O’Rahilly noted. They include hypothyroidism, Cushing’s syndrome and tumors of the hypothalamus.

To help people find an effective way to lose weight, obesity medicine specialists say they start by asking if there is an obvious cause for a person’s excess weight, like a drug that can be switched for something else. If not, they suggest patients try one thing after another starting with the least invasive option, and hope something works.

“There are 40 therapies I can throw at a patient,” Dr. Kaplan said. “I will try diets and aerobic exercise and sleep enhancement. I have 15 drugs.”

Dr. Caroline Apovian, director of the nutrition and weight management center at Boston Medical Center, said most people can lose weight but keeping it off is the key. For most, she said, finding something that works “is still trial and error.”

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.

“People would say, ‘How can you say all these diets have no effect when I lost 100 pounds on diet X?’ Others would say the same thing about the opposite diet.”

Dr. Sacks believes them. He knows people who have lost weight and kept it off with diets, including a colleague in his department. “He lost 30 or 40 pounds in the 1970s and kept it off all these years,” Dr. Sacks said.

But why him and not someone else following the same regimen?

“Beats me,” Dr. Sacks said.

Every obesity medicine specialist has seen it happen — someone repeatedly tried and failed to lose weight and keep it off. It turned out they were trying the wrong thing. Here are some people who finally found a weight-loss plan that worked.