[Chronicle]

Jan. 23, 1997
Vol. 16, No. 9

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    Obituary: Nobel Prize winner Huggins: 'Discovery is our business'

    Nobelist Charles B. Huggins, the William B. Ogden Distinguished Service Professor Emeritus in Surgery and the last survivor of the eight original faculty members of the medical school, died at his Hyde Park home on Jan. 12. He was 95.

    Huggins' research on prostate cancer changed forever the way scientists regard the behavior of all cancer cells, and for the first time brought hope to the prospect of treating advanced cancers. His motto, on a banner behind his research bench, said simply, "Discovery is our business."

    Huggins provided an immense stimulus to research on cancer chemotherapy by showing that cancer cells were not autonomous and self perpetuating, as previously believed, but were dependent on chemical signals such as hormones to grow and survive, and that depriving cancer cells of those signals could restore the health of patients who have widespread metastases.

    In 1966, Huggins received the Nobel Prize (shared with virologist Peyton Rous) for his research on the relationship between hormones and prostate cancer. The Nobel Committee cited his "fundamental discoveries concerning the hormone dependence of normal and neoplastic cells in experimental animals and their immediate practical application to the treatment of human prostatic and breast cancer." The committee went on to note that his work had already given many years of active and useful life to patients worldwide who had advanced cancer -- patients who would have been lost without these developments in the treatment of the disease.

    "Humanity owes Charles Huggins deep gratitude," wrote Paul Talalay, director of pharmacology and experimental therapeutics at Johns Hopkins University (and a former student of Huggins) in 1965. "Since cancer of the prostate constitutes one of the most common cancers of man, the untold benefits and relief of suffering which this treatment has brought to many older men can hardly be overemphasized."

    The implications of this discovery, however, reached far beyond prostate cancer. "It heralded an era of rational chemotherapy of cancer," added Talalay. Estrogens "were the first agents . . . which, when taken by mouth, influenced cancer beneficially. . . For the first time a strong ray of hope appeared in the treatment of carcinomatosis, for it was demonstrated that patients with widespread metastases could be restored to health by regulation of their internal environment."

    In the 1950s, Huggins gradually gave up his surgical practice to devote all of his time to research, founding the Ben May Laboratory for Cancer Research in 1951. The laboratory was designed to cut across established disciplines to combine scientists from many different fields in the advanced study of experimental medicine and cancer.

    Huggins by that time had shifted his attention from prostate cancer to breast cancer, then the most common cancer in women. In 1951 he demonstrated that, like prostate cancer, many breast cancers were dependent on specific hormones, and that by removing the sources of those hormones -- the ovaries and the adrenal glands, which Huggins demonstrated in 1945 were a source of both male and female hormones -- he could cause substantial regression of the cancer in 30 to 40 percent of women with advanced breast cancer.

    Since there was no way to predict which women would benefit from such endocrine surgery, Huggins convinced his colleague Elwood Jensen, the Charles Huggins Distinguished Professor Emeritus in the Ben May Laboratory, to develop a method to identify the estrogen-receptor content of breast cancers and to use that as a predictor of a response to endocrine therapy. Now, all breast cancers are classified as estrogen-receptor positive or negative, an important guide to prognosis and therapy, and medications, such as tamoxifen, that can block the effects of estrogen have become important tools in the treatment and possible prevention of breast cancer.

    In 1961, Huggins developed an experimental model of human breast cancer, the lack of which had been a major obstacle to research.

    Although they are often overshadowed by his pioneering contributions to the hormonal treatment of cancer of the prostate and breast, Huggins made a series of other discoveries of major significance. He was the first to measure the concentration of many of the components of seminal fluid. He was the first to demonstrate the competitive antagonism between male and female hormones. He developed the concept of chromogenic substrates, now widely used in biochemistry and molecular biology. In work that he began in the late 1920s, abandoned for several decades and returned to the in early 1970s, Huggins helped discover a family of substances that induce bone formation. These bone-growth factors are just beginning to be explored for possible uses in orthopedic, reconstructive and periodontal surgery.

    "Research," he said, "has always been my pleasure as well as my job. There is nothing that matches the thrill of discovery."

    He was able to pass on that thrill to his students, many of whom went into positions of academic leadership in surgery, urology, biochemistry, pharmacology, endocrinology, cancer research and pathology at institutions around the country.

    A native of Halifax, Nova Scotia, Huggins received his B.A. from Acadia University in 1920. In 1924, at the age of 22, he received his M.D. from Harvard. Huggins became Assistant Professor at Chicago in 1929, Associate Professor and a U.S. citizen in 1933, and Professor in 1936. In 1962, he was named the William B. Ogden Distinguished Service Professor.

    Huggins is survived by a daughter, Emily Fine, of San Francisco, seven grandchildren and eight great-grandchildren. His wife, Margaret, who was a collaborator in his research and an editor of his scientific papers, died in 1983. A son, Charles Edward Huggins, died in 1989.

    A memorial service at the University will be announced at a later date.