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.”

By the late 1970s, researchers had also reported that malignant breast tumors had more receptors for insulin than did healthy tissue. The more insulin receptors on the surface of a cell, the more sensitive it will be to the insulin in its environment. Having a greater number of insulin receptors than healthy cells, as one report noted, might confer “a selective growth advantage to tumor cells.”

“Selective growth advantage” speaks directly to the process of Darwinian evolution that is considered the controlling force in tumor development. We can think of human cells as existing in a microscopic ecosystem, living in harmony with their environment, and balanced, as are all species, between the opportunities for growth and proliferation and the processes that lead to aging and death. In such an environment, the billions of cells that eventually constitute a tumor will be the descendants of a single cell that has accumulated a series of genetic mutations, each adding to its proclivity to proliferate unfettered by any of the normal inhibitions to growth. The process in which a healthy cell eventually results in malignancy is a gradual evolution driven by a series of mutations in the DNA of the genes, each bestowing on the cell either the inclination to multiply or a breakdown in the control and repair mechanisms that have evolved to counter precisely such potentially deleterious mutations. The descendants of such a mutant cell would inherit this fitness advantage over other cells in the tissue, and so, within a few years, a single such mutant cell will leave millions of descendants. As one of those descendants in turn gains, purely by chance, yet another advantageous error or mutation, its descendants will now come to dominate.