Genes Take Charge, and Diets Fall by the Wayside

It was 1959. Jules Hirsch, a research physician at Rockefeller University, had gotten curious about weight loss in the obese. He was about to start a simple experiment that would change forever the way scientists think about fat.

Obese people, he knew, had huge fat cells, stuffed with glistening yellow fat. What happened to those cells when people lost weight, he wondered. Did they shrink or did they go away? He decided to find out.

It seemed straightforward. Dr. Hirsch found eight people who had been fat since childhood or adolescence and who agreed to live at the Rockefeller University Hospital for eight months while scientists would control their diets, make them lose weight and then examine their fat cells.

Dr. Hirsch answered his original question — the subjects’ fat cells had shrunk and were now normal in size. And everyone, including Dr. Hirsch, assumed that the subjects would leave the hospital permanently thinner.

That did not happen. Instead, Dr. Hirsch says, “they all regained.” He was horrified. The study subjects certainly wanted to be thin, so what went wrong? Maybe, he thought, they had some deep-seated psychological need to be fat.

So Dr. Hirsch and his colleagues, including Dr. Rudolph L. Leibel, who is now at Columbia University, repeated the experiment and repeated it again. Every time the result was the same. The weight, so painstakingly lost, came right back. But since this was a research study, the investigators were also measuring metabolic changes, psychiatric conditions, body temperature and pulse. And that led them to a surprising conclusion: fat people who lost large amounts of weight might look like someone who was never fat, but they were very different. In fact, by every metabolic measurement, they seemed like people who were starving.

studies that were the inspiration of Dr. Ethan Sims at the University of Vermont, who asked what would happen if thin people who had never had a weight problem deliberately got fat.

His subjects were prisoners at a nearby state prison who volunteered to gain weight. With great difficulty, they succeeded, increasing their weight by 20 percent to 25 percent. But it took them four to six months, eating as much as they could every day.

Once the men were fat, their metabolisms increased by 50 percent. They needed more than 2,700 calories per square meter of their body surface to stay fat but needed just 1,800 calories per square meter to maintain their normal weight.

When the study ended, the prisoners had no trouble losing weight. Within months, they were back to normal and effortlessly stayed there.

The implications were clear. There is a reason that fat people cannot stay thin after they diet and that thin people cannot stay fat when they force themselves to gain weight. The body’s metabolism speeds up or slows down to keep weight within a narrow range. Gain weight and the metabolism can as much as double; lose weight and it can slow to half its original speed.

That, of course, was contrary to what every scientist had thought, and Dr. Sims knew it, as did Dr. Hirsch.

Dr. Stunkard ended up with 540 adults whose average age was 40. They had been adopted when they were very young — 55 percent had been adopted in the first month of life and 90 percent were adopted in the first year of life. His conclusions, published in The New England Journal of Medicine in 1986, were unequivocal. The adoptees were as fat as their biological parents, and how fat they were had no relation to how fat their adoptive parents were.

The researchers concluded that 70 percent of the variation in peoples’ weights may be accounted for by inheritance, a figure that means that weight is more strongly inherited than nearly any other condition, including mental illness, breast cancer or heart disease.

The results did not mean that people are completely helpless to control their weight, Dr. Stunkard said. But, he said, it did mean that those who tend to be fat will have to constantly battle their genetic inheritance if they want to reach and maintain a significantly lower weight.

The findings also provided evidence for a phenomenon that scientists like Dr. Hirsch and Dr. Leibel were certain was true — each person has a comfortable weight range to which the body gravitates. The range might span 10 or 20 pounds: someone might be able to weigh 120 to 140 pounds without too much effort. Going much above or much below the natural weight range is difficult, however; the body resists by increasing or decreasing the appetite and changing the metabolism to push the weight back to the range it seeks.

The message is so at odds with the popular conception of weight loss — the mantra that all a person has to do is eat less and exercise more — that Dr. Jeffrey Friedman, an obesity researcher at the Rockefeller University, tried to come up with an analogy that would convey what science has found about the powerful biological controls over body weight.

He published it in the journal Science in 2000 and still cites it:

“Those who doubt the power of basic drives, however, might note that although one can hold one’s breath, this conscious act is soon overcome by the compulsion to breathe,” Dr. Friedman wrote. “The feeling of hunger is intense and, if not as potent as the drive to breathe, is probably no less powerful than the drive to drink when one is thirsty. This is the feeling the obese must resist after they have lost a significant amount of weight.”