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.

The study was rigorous and demanding. It began with an agonizing four weeks of a maintenance diet that assessed the subjects’ metabolism and caloric needs. Then the diet began. The only food permitted was a liquid formula providing 600 calories a day, a regimen that guaranteed they would lose weight. Finally, the subjects spent another four weeks on a diet...