Number of words: 758

To choose a medical specialty is also to choose its cardinal bodily liquid. Hematologists have blood. Hepatologists have bile. Huggins had prostatic fluid: a runny, straw-colored mixture of salt and sugar meant to lubricate and nourish sperm. Its source, the prostate, is a small gland buried deep

in the perineum, wrapped around the outlet of the urinary tract in men. (Vesalius was the first to identify it and draw it into human anatomy.) Walnut-shaped and only walnut-sized, it is yet ferociously the site of cancer. Prostate cancer represents a full third of all cancer incidence in men— sixfold that of leukemia and lymphoma. In autopsies of men over sixty years old, nearly one in every three specimens will bear some evidence of prostatic malignancy.

But although an astoundingly common form of cancer, prostate cancer is also highly variable in its clinical course. Most cases are indolent—elderly men usually die with prostate cancer than die of prostate cancer—but in other patients the disease can be aggressive and invasive, capable of exploding into painful lesions in the bones and lymph nodes in its advanced, metastatic form.

Huggins, though, was far less interested in cancer than in the physiology of prostatic fluid. Female hormones, such as estrogen, were known to control the growth of breast tissue. Did male hormones, by analogy, control the growth of the normal prostate—and thus regulate the secretion of its principal product, prostatic fluid? By the late 1920s, Huggins had devised an apparatus to collect precious drops of prostatic fluid from dogs. (He diverted urine away by inserting a catheter into the bladder and stitched a collection tube to the exit of the prostate gland.) It was the only surgical innovation that he would devise in his lifetime.

Huggins now had a tool to measure prostatic function; he could quantify the amount of fluid produced by the gland. He found that if he surgically removed the testicles of his dogs—and thereby depleted the dogs of the hormone testosterone—the prostate gland involuted and shriveled and the fluid secretion dried up precipitously. If he injected the castrated dogs with purified testosterone, the exogenous hormone saved the prostate from shriveling. Prostate cells were thus acutely dependent on the hormone testosterone for their growth and function. Female sexual hormones kept breast cells alive; male hormones had a similar effect on prostate cells.

Huggins wanted to delve further into the metabolism of testosterone and the prostate cell, but his experiments were hampered by a peculiar problem. Dogs, humans, and lions are the only animals known to develop prostate cancer, and dogs with sizable prostate tumors kept appearing in his lab during his studies. “It was vexatious to encounter a dog with a prostatic tumor during a metabolic study,” he wrote. His first impulse was to cull the cancer-afflicted dogs from his study and continue single-mindedly with his fluid collection, but then a question formed in his mind. If testosterone deprivation could shrink normal prostate cells, what might testosterone deprivation do to cancer cells?

The answer, as any self-respecting cancer biologist might have informed him, was almost certain: very little. Cancer cells, after all, were deranged, uninhibited, and altered—responsive only to the most poisonous combinations of drugs. The signals and hormones that regulated normal cells had long been flung aside; what remained was a cell driven to divide with such pathological and autonomous fecundity that it had erased all memory of normalcy.

But Huggins knew that certain forms of cancer did not obey this principle. Variants of thyroid cancer, for instance, continued to make thyroid hormone, the growth-stimulating molecule secreted by the normal thyroid gland; even though cancerous, these cells remembered their former selves. Huggins found that prostate cancer cells also retained a physiological “memory” of their origin. When he removed the testicles of prostate cancer–bearing dogs, thus acutely depriving the cancer cells of testosterone, the tumors also involuted within days. In fact, if normal prostate cells were dependent on testosterone for survival, then malignant prostate cells were nearly addicted to the hormone—so much so that the acute withdrawal acted like the most powerful therapeutic drug conceivable. “Cancer is not necessarily autonomous and intrinsically self-perpetuating,” Huggins wrote. “Its growth can be sustained and propagated by hormonal function in the host.” The link between the growth-sustenance of normal cells and of cancer cells was much closer than previously imagined: cancer could be fed and nurtured by our own bodies.

Excerpted from pages 211-213 of ‘The Emperor of All Maladies: A biography of Cancer’ by Siddharth Mukherjee