In other words, the editors at JAMA—and the clinical investigators they represented—were declaring that hormones, as a rule, play little role in the genesis of obesity, even before the relevant hormones could be measured accurately in the human bloodstream. In fact, it’s hard to imagine, as Julius Bauer noted, that hormones wouldn’t play a role. Here again we have that familiar scenario we first discussed with regard to dietary fat and heart disease. Once the “truth” has been declared, even if it’s based on incomplete evidence, the overwhelming tendency is to interpret all future observations in support of that preconception. Those who know what the answer is lack the motivation to continue looking for it. Entire fields of science may then be ignored, on the assumption that they can’t possibly be relevant.

In 1968, Jean Mayer pointed out that obesity researchers may have “eliminated” hormones “from legitimate consideration” as a cause of obesity, or so they believed, but the evidence continued to accumulate just the same. Researchers had demonstrated that insulin seemed to have a dramatic effect on hunger, that insulin was the primary regulator of fat deposition in the adipose tissue, and that obese patients had chronically high levels of insulin. Other hormones, such as adrenaline, had been shown to increase the mobilization of fat from the fat cells. “It is probable that different concentrations of these hormones in blood are characteristic of different body types and fat contents,” Mayer wrote.

At the beginning of this century, when hormones were first discovered, it was commonly believed that obesity would be found to be due to the absolute excess or deficiency of a single hormone. When this was found to be almost never true, the popular medical position swung to the other extreme: “obesity is almost never due to hormonal disturbances; it is almost always due to overeating.” Actually, the reasonable position ought to be: “in order to be obese, you always have to eat more than you expend for a certain period. How often this is due to a slight shift of relative or absolute hormone concentrations, each one of which is in the ‘normal’ range, we don’t know.”

Among the hormones that play a role in regulating fat metabolism and thus potentially play a causative role in obesity, insulin was always an obvious choice. Some failure in what clinicians a century ago called the insular*108 apparatus of the pancreas is the fundamental defect in diabetes, and diabetes is intimately associated with obesity in those who develop the disease as adults, and with emaciation, which was the end stage of the disease in the pre-insulin era. In 1905, Carl von Noorden invoked this intimate association between diabetes and weight to formulate the third of his speculative hypotheses of obesity, what he called diabetogenous obesity. His ideas were remarkably prescient. They received little attention because insulin had not yet been discovered, let alone the technology to measure it.