Charles Brenton Huggins | |
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![]() Huggins in 1966 | |
Born | Halifax, Nova Scotia, Canada | September 22, 1901
Died | January 12, 1997 95) | (aged
Citizenship | Canadian, American |
Alma mater | Acadia University Harvard University |
Known for | prostate cancer hormones |
Awards | Nobel Prize for Physiology or Medicine (1966) Cameron Prize for Therapeutics of the University of Edinburgh (1956) Gairdner Foundation International Award (1966) |
Scientific career | |
Fields | physiology |
Institutions | University of Michigan, University of Chicago |
Charles Brenton Huggins (September 22, 1901 – January 12, 1997) was a Canadian-American surgeon and physiologist known for his work on prostate function, prostate cancer, and breast cancer. Born in Halifax in 1901, Huggins moved to the United States for medical school. He was one of the founding staff members of the University of Chicago Medical School, where he remained for the duration of his professional research career. Huggins's work on how sex hormones influence prostate function ultimately led to his discovery of hormone therapies to treat prostate cancer. For this finding, he was awarded the 1966 Nobel Prize for Physiology or Medicine. In addition to his work on prostate cancer, Huggins explored the relationship between hormones and breast cancer, developed an animal model for breast cancer, and developed chromogenic substrates that are widely used for biochemical analyses. Huggins continued to perform research into his 90s; he died in Chicago in 1997.
Charles Brenton Huggins was born September 22nd, 1901, in Halifax, Nova Scotia, to Charles E. Huggins and Bessie Maria Spencer. [1] [2] At 19, he graduated from Acadia University with a BA degree, supplementing his Acadia coursework with summer courses in physical and organic chemistry at Columbia University. [3] [1] Huggins went on to Harvard Medical School, and received his MD degree in 1924. He served his internship and residency in general surgery with Frederick A. Coller at the University of Michigan. [3] While at Michigan, Huggins met operating room nurse Margaret Wellman; they married in 1927. [1]
In 1927, Huggins was recruited to the new University of Chicago Medical School by chairman of surgery Dallas Phemister. As one of the eight original staff members of the school, Huggins was assigned to the urology department, and had to rapidly teach himself the specialty. [1] In 1931, Phemister offered Huggins a paid research sabbatical in Europe; Huggins spent several months at London's Lister Institute working in Robert Robison's lab to deepen his knowledge in biochemistry. [1] [4] He was promoted to associate professor in 1933, and full professor in 1936. [2]
In 1951, businessman and longtime financial supporter of Huggins's research Ben E. May endowed the Ben May Laboratory for Cancer Research at the University of Chicago. Huggins eventually became the May Laboratory's director, serving in the position until 1969. In 1962, he was granted an endowed professorship, the William B. Ogden Distinguished Service Professor. [1]
Notable students of Professor Huggins included Howard Guy Williams-Ashman, Shutsung Liao, Paul Talalay and A. Hari Reddi. [5] [6]
A plaque in Professor's Huggins office carried his motto: "Discovery is our business." [7] This motto signified his ethos to research and medical discovery.
Huggins's early research work focused on bone physiology. However, he eventually felt this bone work was unlikely to lead to medical progress, and set it aside in favor of studying the male urogenital tract. Through the 1930s, Huggins published work characterizing the constituents of semen and which organ (seminal vesicles or prostate) they derive from. [8] In 1939, Huggins described a method for isolating prostate fluid from dogs, which served as the foundation for much of his subsequent work. [8] He showed that the prostate requires androgens (male sex hormones) in order to function, and that androgen treatment could be counteracted by treatment with estrogens. [8] In the course of this work, he discovered that older dogs tended to have enlarged prostates, and that these enlarged prostates could be shrunk by administering estrogen. [1] [8]
In 1940 and 1941, Huggins – along with students Clarence V. Hodges and William Wallace Scott – published a series of three papers detailing his most famous finding: that counteracting androgen activity by orchiectomy (surgical removal of the testicles) or estrogen treatment shrank tumors in many men with metastatic prostate cancer. [3] [8] These men experienced dramatic pain relief within days of the treatment; four of the original 21 treated went on to survive more than 12 years from the original treatment. [3]
Huggins's work on prostate cancer often necessitated measuring the amount of prostate-derived enzymes in the blood. To this end, Huggins developed colorimetric methods for quantifying the concentration of various phosphatases, glucuronidases, and esterases. These assays relied on chromogenic substrates (substances that change color in response to a given enzyme), a term Huggins coined, and a concept he pioneered. [8]
In the 1950s, Huggins went on to show an analogous relationship between sex hormones and breast cancer – tumor growth was stimulated by estrogens, and slowed by androgens. At the time breast cancer research was hindered by the lack of an animal model. Huggins described the first reliable model: 7,12-dimethylbenz(a)anthracene administered orally to rats, 100% of which rapidly developed breast tumors; the model is now called Huggins's tumor. [1] Around this time, Huggins wound down his surgical practice, turning his attention to full-time scientific research. [3]
Huggins published over 200 peer-reviewed papers describing his research. [1]
Huggins was elected to the United States National Academy of Sciences and the American Academy of Arts and Sciences in 1949. [9] [10] In 1962, he was elected to the American Philosophical Society, [11] and was awarded the Lasker Award the following year. In 1966, following nominations from noted surgeon J. Hartwell Harrison as well as Nobel laureates Otto H. Warburg, William P. Murphy, and Albert Szent-Györgyi, Huggins was awarded the Nobel Prize in Physiology or Medicine "for his discoveries concerning hormonal treatment of prostatic cancer". [12] [2] From 1972 to 1979, Huggins was named the ceremonial chancellor of his alma mater, Acadia University. [3] His prize, shared with fellow cancer researcher Peyton Rous, was just the second Nobel for cancer treatment or research. [13]
Huggins and his wife Margaret had a son and a daughter. His son, Charles E. Huggins, was also a surgeon, and directed the Massachusetts General Hospital blood bank until his death in 1990. Margaret Huggins died in 1983. [1] Huggins devoted much of his time to laboratory work, logging long hours in the lab, and continuing to perform hands-on laboratory work in his 90s. Huggins died on January 12, 1997, in Chicago, Illinois, aged 95. [1]
Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through screening tests, typically blood tests that check for prostate-specific antigen (PSA) levels. Those with high levels of PSA in their blood are at increased risk for developing prostate cancer. Diagnosis requires a biopsy of the prostate. If cancer is present, the pathologist assigns a Gleason score; a higher score represents a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. A higher stage signifies a more advanced, more dangerous disease.
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.
Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency, treatment of prostate cancer and breast cancer, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported adverse reproductive health outcomes linked to DES including infertility, miscarriage, ectopic pregnancy, preeclampsia, preterm birth, stillbirth, infant death, menopause prior to age 45, breast cancer, cervical cancer, and vaginal cancer. While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.
Andrzej Viktor "Andrew" Schally was a Polish-American endocrinologist who was a co-recipient, with Roger Guillemin and Rosalyn Sussman Yalow, of the 1977 Nobel Prize in Physiology or Medicine. This award recognized his research in the discovery that the hypothalamus controls hormone production and release by the pituitary gland, which controls the regulation of other hormones in the body. Later in life, Schally utilized his knowledge of hypothalamic hormones to research possible methods for birth control and cancer treatment.
Elwood Vernon Jensen was the Distinguished University Professor, George and Elizabeth Wile Chair in Cancer Research at the University of Cincinnati College of Medicine's Vontz Center for Molecular Studies. In 2004 he received the Albert Lasker Award for Basic Medical Research for his research on estrogen receptors. He is considered the father of the field of hormone action.
Aminoglutethimide (AG), sold under the brand names Elipten, Cytadren, and Orimeten among others, is a medication which has been used in the treatment of seizures, Cushing's syndrome, breast cancer, and prostate cancer, among other indications. It has also been used by bodybuilders, athletes, and other men for muscle-building and performance- and physique-enhancing purposes. AG is taken by mouth three or four times per day.
Estramustine phosphate (EMP), also known as estradiol normustine phosphate and sold under the brand names Emcyt and Estracyt, is a dual estrogen and chemotherapy medication which is used in the treatment of prostate cancer in men. It is taken multiple times a day by mouth or by injection into a vein.
17β-Hydroxysteroid dehydrogenases, also 17-ketosteroid reductases (17-KSR), are a group of alcohol oxidoreductases which catalyze the reduction of 17-ketosteroids and the dehydrogenation of 17β-hydroxysteroids in steroidogenesis and steroid metabolism. This includes interconversion of DHEA and androstenediol, androstenedione and testosterone, and estrone and estradiol.
Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology, others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.
Selective androgen receptor modulators (SARMs) are a class of drugs that selectively activate the androgen receptor in specific tissues, promoting muscle and bone growth while having less effect on male reproductive tissues like the prostate gland.
Feminizing hormone therapy, also known as transfeminine hormone therapy, is a form of gender-affirming care and a gender-affirming hormone therapy to change the secondary sex characteristics of transgender people from masculine to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people, but also some non-transgender people, take this form of therapy according to their personal needs and preferences.
Male breast cancer (MBC) is a cancer in males that originates in their breasts. Males account for less than 1% of new breast cancers with about 20,000 new cases being diagnosed worldwide every year. Its incidence rates in males vs. females are, respectively, 0.4 and 66.7 per 100,000 person-years. The worldwide incidences of male as well as female breast cancers have been increasing over the last few decades. Currently, one of every 800 men are estimated to develop this cancer during their lifetimes.
Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.
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