Astwood believed that obesity and a disposition to fatten are genetic disorders. If genes determine stature and hair color, the size of our feet, and a “growing list of metabolic derangements,” he asked, then “why can’t heredity be credited with determining one’s shape?” Although it’s possible to fatten animals by stuffing them, “and doubtless we could do the same thing to ourselves if we put our minds to it,” Astwood did not consider this a cause of overweight. “Not many people try to get into the circus this way,” he said—“they become candidates spontaneously.” He also considered inactivity to be of dubious importance. “Many of our moderately fat patients sit like bumps on a log,” he said, but that could be an effect, not a cause. “It would be interesting to know whether adiposity and inertia go together for some reason common to both. If fatty acid is needed for energy, a deficit could indeed promote lethargy and indolence.”

Astwood then described what had been learned over the past thirty years about the hormonal regulation of fat metabolism. “To turn what is eaten into fat, to move it and to burn it requires dozens of enzymes and the processes are strongly influenced by a variety of hormones,” he explained. Sex hormones, for instance, determine where fat is stored, as evidenced by the differences in fat distribution between men and women. Thyroid hormones, adrenaline, and growth hormone accelerate the release of fatty acids from fat depots, as does a hormone known as glucagon, secreted by the pancreas. “The reverse process,” Astwood said, “the reincorporation of fat into the depots and the conversion of other food to fat, tends to be reduced by these hormones, but to be strongly promoted by insulin.” All of this demonstrated “what a complex role the endocrine system plays in the regulation of fat.”

Finally, Astwood speculated on what he considered the simplest possible explanation for obesity, and here he echoed Alfred Pennington, although, if he had read Pennington’s work, he neglected to mention it. “Now just suppose that any one of these (or other unlisted) regulatory processes were to go awry,” Astwood said.

Suppose that the release of fat or its combustion was somewhat impeded, or that the deposition or synthesis of fat was promoted; what would happen? Lack of food is the cause of hunger and, to most of the body, [fat] is the food; it is easy to imagine that a minor derangement could be responsible for a voracious appetite. It seems likely to me that hunger in the obese might be so ravaging and ravenous that skinny physicians do not understand it.

There is no reason to suppose that only one of these mechanisms ever goes wrong…. There are so many possibilities here that I am willing to give odds that obesity is caused by a metabolic defect. I would not want to wager about how many enzymes determine the shape of voluminous pulchritude.