Good Calories, Bad Calories

accomplished in ways that are “reciprocal, redundant and ubiquitous.”

The idea that obesity in humans is caused, as it is in animals, by a defect in the homeostatic maintenance of energy distribution and fat metabolism—that we overeat because we’re getting fat, and not vice versa—barely survived into the second half of the twentieth century, although the evidence has always supported it.

This homeostatic hypothesis effectively vanished from the mainstream thinking on human (as opposed to animal) obesity with the coming of World War II. The war destroyed the German and Austrian community of clinical investigators, who had done the most perceptive thinking about the causes of obesity and had a tradition of rigorous scientific research dating back two hundred years. In the United States, it resulted in a suspension of obesity research that lasted for most of a decade. Meanwhile, Stephen Ranson had died, Hugo Rony and Julius Bauer retired. The generation of physiologists who had founded the field of nutrition in the United States and actually studied human metabolism disappeared with them. Francis Benedict’s Nutrition Laboratory at the Carnegie Institution did contract work for the armed services during the war and then was shut down in 1946. The Russell Sage Institute of Pathology, where Graham Lusk and Eugene Du Bois did their research, was also gone by the 1950s. Lusk himself died in 1932, Francis Benedict retired in 1937. Du Bois retired four years later.

Among the few investigators whose careers spanned the war years, Louis Newburgh was the most influential and conspicuous. As late as 1948, Newburgh was still promoting his perverted-appetite hypothesis of obesity. The first obesity textbook published after the war, Obesity… (1949), by Edward Rynearson and Clifford Gastineau, would be considered the standard text on obesity for twenty years. It faithfully communicated Newburgh’s belief that obesity is caused by overeating. Any suggestion to the contrary, wrote Rynearson and Gastineau, constituted little more than “an excuse for avoidance of the necessary corrective measures.”

An entire generation of young researchers and clinicians effectively started the study of obesity from scratch after the war. They did so with little concern for whatever understanding had been achieved before they arrived, and so they embraced a hypothesis of causation that flew in the face of much of the evidence. The institutionalized skepticism and meticulous attention to experimental detail that are necessary to do good science—“being ruthless in self-criticism and…taking pains in verifying facts,” as the Nobel laureate chemist Hans Krebs said—had also been left behind.

Chapter Twenty-two

THE CARBOHYDRATE HYPOTHESIS, II: INSULIN

Every woman knows that carbohydrate is fattening.

REGINALD PASSMORE AND YOLA SWINDELLS, British Journal of Nutrition, 1963

The fact that insulin increases the formation of fat has been obvious ever since the first emaciated dog or diabetic patient demonstrated a fine pad of adipose tissue, made as a result of treatment with the hormone.

REGINALD HAIST AND CHARLES BEST, The Physiological Basis of Medical Practice, 1966

IN 1929, WHEN LOUIS NEWBURGH FIRST rejected the possibility of an “endocrine abnormality” as the cause of obesity, and insisted instead that all fat people had a perverted appetite, hormones were still widely known as “internal secretions” and endocrine glands as “ductless glands.” The first purification of growth hormone had been only nine years earlier, the purification of insulin only eight years before. In 1955, when The Journal of the American Medical Association declared unconditionally that those “theories that attributed obesity to an endocrine disturbance have been shown to be erroneous,” it was five years before Rosalyn Yalow and Solomon Berson would publish the details of the first method for measuring the insulin level in the blood, and a few more years after that before the ensuing revelations that obesity was associated with the endocrine disturbances and abnormalities of hyperinsulinemia and insulin resistance.

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.

Von Noorden suggested that obesity and diabetes are different consequences of the same underlying defects in the mechanisms that regulate carbohydrate and fat metabolism. In severe diabetes (Type 1), he noted, the patients are unable either to utilize blood sugar as a source of energy or to convert it into fat and store it. This is why the body allows the blood sugar to overflow into the urine, which is a last resort since it wastes potentially valuable fuel. The result is glycosuria, the primary symptom of diabetes. These diabetics must be incapable of storing or maintaining fat, von Noorden noted, because they eventually become emaciated and waste away. In obese patients, on the other hand, the ability to utilize blood sugar is impaired, but not the ability of the body to convert blood sugar into fat and store it. “Obese individuals of this type have already an altered metabolism for sugar,” von