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January 13, 1997
January 13, 1997
Nobel Prize winner Charles Brenton Huggins, MD, the William B. Ogden Distinguished Service Professor Emeritus of Surgery at the University of Chicago Medical Center, died at his Hyde Park home on January 12, 1997. The last survivor of the original eight faculty members of the medical school, Dr. Huggins was 95 years old.
A plaque in his office, posted above his desk, carried his motto: "Discovery is our business."
The death was reported by his daughter Emily Huggins Fine.
Dr. Huggins' research on prostate cancer changed forever the way scientists regarded the behavior of all cancer cells and for the first time brought hope to the prospect of treating advanced cancers. 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 with widespread metastases, Dr. Huggins provided an immense stimulus to research on cancer chemotherapy.
He also founded the renowned Ben May Laboratory for Cancer Research at the University of Chicago. He trained and inspired the lives of numerous medical scientists. And he became the leading urologist of his day, bringing a new level of scientific curiosity and inquiry to a neglected surgical specialty. Dr. Huggins was a pioneer in understanding the physiology and biochemistry of the male urogenital tract and was able to extend his findings from this field into many other areas.
In 1966, Dr. 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 an active and useful life to patients with advanced cancer over the entire civilized world--patients who would have been lost to other forms of therapy."
Peyton Rous, who shared the prize with Dr. Huggins, was one of the first to recognize the true importance of Dr. Huggins' research. Although Dr. Huggins had demonstrated for the first time that cancers that had spread throughout the body could actually be cured, "the importance of this discovery far transcends its practical applications," Rous emphasized. For it meant that previous "thought and endeavor in cancer research have been misdirected in consequence of the belief that tumor cells are anarchic."
Dr. Huggins, in collaboration with his students Clarence V. Hodges and William Wallace Scott, published three papers in 1941 that demonstrated the relationship between the endocrine system and the normal functioning of the prostate gland. They also showed that by blocking the male hormones that were involved in prostate function--through removal of the testicles or administration of estrogens which would neutralize the male hormones--they could cause regression of prostate tumors. The regression and the consequent relief of pain was often spectacular and occurred within days or sometimes even hours after treatment. Four of Dr. Huggins' original 21 hormone-therapy patients lived for more than 12 years after treatment, and since then many bedridden, moribund men have been returned to active and useful lives.
"Humanity owes Charles Huggins deep gratitude," wrote Paul Talalay, MD, director of pharmacology and experimental therapeutics at Johns Hopkins University, (and a former student of Dr. 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 Dr. 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 the internal environment of the host."
In 1950, Dr. Huggins shifted his attention to breast cancer, then the most common cancer in women. He demonstrated in 1951 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 Dr. Huggins demonstrated in 1945 were a source of both male and female hormones--he could cause substantial regression 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, Dr. Huggins convinced his colleague Elwood Jensen, PhD, the Charles Huggins Distinguished Professor Emeritus in the University's 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, Dr. Huggins developed an experimental model of human breast cancer, the lack of which had been a major obstacle to research. By giving a single small dose of certain chemicals (aromatic polycyclic hydrocarbons) to selected strains of female rats he found he could produce, within a few weeks, malignant mammary tumors--many of which were hormone dependent--in 100 percent of the treated animals. The hormone-dependent tumors grew or shrank in response to modification of the hormonal balance of the host. The method, now universally known as the "Huggins tumor," quickly became the most intensely investigated laboratory animal model of human breast cancer.
Although they are often overshadowed by his pioneering contributions to the hormonal treatment of cancer of the prostate and breast, Dr. 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, which are now widely used in biochemistry and molecular biology. These colorless substances give rise to brightly colored products after being split by certain enzymes, allowing scientists to measure the activity of those enzymes. In work that he began in the late 1920s, abandoned for several decades and returned to the in early 1970s, Dr. 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.
Dr. Huggins also founded the Ben May Laboratory for Cancer Research at the University of Chicago, which opened on June 1, 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. In a five-minute meeting in late winter of 1950, Huggins convinced Ben May, an Alabama businessman, to serve as patron--"our Lorenzo de Medici," Dr. Huggins often called him. This brief meeting ended with a hand-shake agreement that has lasted for decades.
Born on September 22, 1901, in Halifax, Nova Scotia, Huggins earned his bachelor of arts degree in three years from Acadia University in 1920. In 1924, at the age of 22, he was graduated from Harvard Medical School. He served his internship and residency in general surgery with Frederick A. Coller at the University of Michigan.
In 1927, when Dr. Huggins first came to the University of Chicago, few would have predicted his remarkable success. He was invited to become a research fellow, where Dr. Dallas Phemister, founding chairman of surgery at the University, encouraged him to take over urological surgery. Having never done any medical research and with no special training in urology, he nevertheless accepted the position, bought the standard textbook of urology and memorized it in three weeks. Before long he was referring to urology as the "queen of the sciences" and describing science as "the art of our century."
Dr. Huggins became an assistant professor in 1929, associate professor and United States citizen in 1933, and professor in 1936. In the 1950s, he gradually gave up his surgical practice to devote all of his time to research. In 1962, he was named the William B. Ogden Distinguished Service Professor at the University of Chicago.
He has won more than 100 awards and honorary degrees. Besides the 1966 Nobel, the honors of which he was most proud include membership in the National Academy of Sciences (1949), the American Philosophical Society (1962), the Order "Pour le Murite" from the German Federal Republic (1958), and the Chancellorship of his alma mater, Acadia University (1972-79).
Despite his scientific renown, Dr. Huggins successfully avoided major administrative responsibilities, deciding early in his career to remain at the research bench--where he spent 60 to 70 hours a week--and to limit the size of his laboratory. "Discovery is for the single mind, perhaps in company with a few students," he insisted, exhorting his colleagues: "Don't write books. Don't teach hundreds of students. Discovery is our business. Make damn good discoveries."
"Research," he said, "has always been my pleasure as well as my job. There is nothing that matches the thrill of discovery." For example, 20 years after the event, Dr. Huggins remembered the day he realized that "we knew for sure that we had learned how to treat advanced prostate cancer."
"I was excited, nervous, happy," he recalled. "That night I walked home--one mile--and I had to sit down two or three times, my heart was pounding so. I thought, 'This will benefit man forever . . . A thousand years from now people will be taking this treatment of mine.'"
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.
"Exposure to Charles Huggins is a mutational event," said one. "Few have come under the stamp of his influence without discovering in themselves unrecognized abilities and intellectual powers, without gaining a deeper awareness of their scholarly responsibilities and capabilities."
Dr. Huggins married Margaret Wellman, a nurse at the University of Michigan, in 1927. After their marriage, she became a collaborator in his research and an editor for his scientific papers. They have lived in Hyde Park, the Chicago neighborhood that surrounds the University, since 1927. She died in 1983.
They had two children: Charles Edward Huggins, who died in 1989, and Emily Huggins Fine, who lives in San Francisco. Dr. Huggins had seven grandchildren and eight great-grandchildren.
A memorial service is planned at the University.