The most direct evidence linking overweight or overnutrition to cancer comes from animal experiments. These date back to the eve of World War I, when Peyton Rous, who would later win a Nobel Prize, demonstrated that tumors grow remarkably slowly in semi-starved animals. This line of research lapsed until 1935, when the Cornell University nutritionist Clive McCay reported that feeding rats just barely enough to avoid starvation ultimately extended their lifespan by as much as 50 percent. Seven years later, Albert Tannenbaum, a Chicago pathologist, launched a cottage research industry after demonstrating that underfeeding mice on very low-calorie diets, as McCay had, resulted in a dramatic inhibition of “many types of tumors of divergent tissue origin.” In one experiment, twenty-six of fifty well-fed mice developed mammary tumors by a hundred weeks of age—the typical lifespan of lab mice—compared with none of fifty that were allowed only minimal calories. Tannenbaum’s semi-starved animals not only lived longer, but were more active, he reported, and had fewer “pathologic changes in the heart, kidneys, liver, and other organs.”*63

To explain this inhibitory effect, Tannenbaum considered an idea that had originated in the 1920s with Otto Warburg, a German biochemist and later Nobel Prize winner. Warburg had demonstrated that tumor cells quickly develop the ability to survive without oxygen and to generate energy by a process of fermentation rather than respiration. Fermentation is considerably less efficient, and so tumors will burn perhaps thirty times as much blood sugar as normal cells. Incipient tumors in these calorie-restricted lab animals, it was thought, cannot obtain the huge amounts of blood sugar they need to fuel mitosis—division of the nucleus—and continue proliferating.

Insulin was not considered a primary suspect until just recently, but the evidence has existed for a while. The earliest such link between a dysfuntion in carbohydrate metabolism and cancer dates to 1885, when a German clinician reported that sixty-two of seventy cancer patients were glucose-intolerant. One common observation by clinical investigators over the years was that women with adult-onset (Type 2) diabetes or glucose intolerance had a higher-than-average incidence of breast cancer. By the mid-1960s, researchers were reporting that insulin acts as a promoter of growth and proliferation in both healthy and malignant tissues. Howard Temin, who later won a Nobel Prize for his cancer research, reported that cells turned malignant by a chicken virus would cease to proliferate in the laboratory unless insulin was added to the serum in which they were growing. This growth-factor effect of insulin was also demonstrated in adrenal and liver-cell cancers. Insulin “intensely stimulated cell proliferation in certain tumors,” noted one 1967 report. In 1976, Kent Osborne and his colleagues at the National Cancer Institute reported that one line of particularly aggressive breast-cancer cells were “exquisitely sensitive to insulin.”