Elwood Jensen, PhD, 1920-2012, pioneer in cancer biology research
December 20, 2012
Elwood V. Jensen, PhD, known worldwide for his pioneering research on how steroid hormones exert their influence through specific receptors in target cells, died from pneumonia on Sunday, Dec. 16, at a nursing and rehabilitation facility in suburban Cincinnati. He was 92.
Jensen was the Charles B. Huggins Distinguished Service Professor Emeritus in the Ben May Department for Cancer Research and the Department of Biochemistry and Molecular Biology at the University of Chicago.
His discoveries led to the development of drugs that can enhance or inhibit the effects of hormones, earning him many honors, including membership in the National Academy of Sciences in 1974 and the Lasker Award in 2004 for outstanding contributions to basic and clinical medical research. They transformed the treatment of breast cancer patients in a way that, according to the Lasker Foundation, "saves or prolongs more than a 100,000 lives annually."
"Jensen's revolutionary discovery of estrogen receptors is beyond doubt one of the major achievements in biochemical endocrinology of our time," said Gene DeSombre, PhD, professor emeritus at the University of Chicago, who worked with Jensen as a post-doctoral fellow and then as a colleague.
"His work is hallmarked by great technical ingenuity and conceptual novelty," DeSombre said. "His promulgation of simple yet profound ideas concerning the role of receptors in estrogen action has been of greatest importance for research on the basic and clinical physiology of not only estrogens, but also of all other categories of steroid hormones."
Before Jensen, DeSombre said, how hormones caused their effects was "a complete mystery."
In the 1950s, biochemists thought a hormone entered a cell, where it triggered a series of oxidation and reduction reactions. These provided energy for growth stimulation and other estrogen-specific actions.
Working with estradiol, Jensen proved that hormones do not undergo chemical change to elicit a response -- an accepted explanation at the time. Instead, he found that they bind to a receptor protein within the cell. This hormone-receptor complex then travels to the cell nucleus, where it regulates gene expression.
"That really got him into some hot water," DeSombre recalled.
But his initial exposure was limited. When he first presented preliminary data at a 1958 meeting in Vienna, only five people attended. Three of them were the other speakers.
From the late 1950s to the 1970s, Jensen published a series of major and highly original discoveries in four related areas that transformed hormone research:
- In 1958, he showed that only the tissues that respond to estrogens, such as those of the female reproductive tract, were able to concentrate injected estradiol from the blood. This uptake pattern suggested that these cells must contain specific binding proteins, which he called "estrogen receptors." He subsequently identified the estrogen receptor in cells of the uterus -- the first receptor found for any steroid hormone.
- In 1967, Jensen and Jack Gorski of the University of Illinois showed that these putative receptors were macromolecules that could be extracted from these tissues. When estrogens bound to this receptor in the nucleus, the receptor complex activated specific genes, stimulating new RNA synthesis.
- By 1968, Jensen had devised a reliable test for the presence of estrogen receptors in breast cancer cells. It had been known for decades that about one-third of premenopausal women who had advanced breast cancer would respond to estrogen blockade brought about by removing their ovaries, the source of estrogens, but there was no way to predict which women would respond. In 1971, Jensen showed that women with receptor-rich breast cancers often have remissions following removal of the sources of estrogens, but cancers that contain few or no estrogen receptors do not respond to estrogen-blocking therapy.
- In 1980, Jensen and Geoffrey Greene, PhD, also in the University of Chicago's Ben May Institute, had developed monoclonal antibodies directed against the human estrogen receptor, which enabled them to quickly and accurately detect and count estrogen receptors in breast and other tumors. By the mid-1980s, this test had become a standard part of care for breast cancer patients.
Following Jensen's lead, researchers soon discovered that the receptors for the other major steroid hormones -- such as progesterone, testosterone and cortisone -- worked essentially the same way.
By the early 1970s, Jensen was searching for medications, rather than surgical procedures, to shield estrogen-dependent tumors from circulating hormones. He and colleague V. Craig Jordan (then at the Worcester Foundation for Experimental Biology in Massachusetts) found that most women with cancers that contain large amounts of estrogen receptor could benefit from treatment with tamoxifen, a compound that blocks some of the effects of estrogens. The Food and Drug Administration approved tamoxifen for breast cancer treatment in 1977 and for breast cancer prevention in 1990.
"We were glad," Jensen would later recall, "we could do something that helped patients with breast cancer, to know that our basic research findings could be extended to the clinical management of patients with this terrible disease."
Born Jan. 13, 1920, in Fargo, N.D., Elwood Vernon Jensen grew up in Springfield, Ohio. His mother, a schoolteacher, taught him to read at a young age, so when he entered school at the age of 4 he immediately jumped ahead two grade levels.
"I was kind of tall, skinny, and socially immature," he said in an interview in 2009. "This was a handicap."
But he took up boxing as a student at Wittenberg College and found that being tall and thin was an advantage. He decisively won his first two matches, at a local golden gloves tournament with 3,000 people watching, including his future wife.
"All the applause," he recalled in an interview many years later with an Ohio newspaper. "That was the turning point in my life."
He graduated from Wittenberg in 1940 with a degree in chemistry, began a graduate chemistry program at the University of Chicago in the fall, and married Mary Collette in June 1941. Six months later, the Japanese attack on Pearl Harbor and the ensuing war altered their plans. Poor eyesight kept him from becoming a pilot, so he joined a research project on chemical warfare at the University.
Two hospitals stays, after his experiments "proceeded more vigorously than anticipated," helped him focus his nascent career on combining chemistry with medicine.
Despite the delay, he completed his PhD in 1944, spent a year working with his doctoral adviser on a synthetic rubber project, then obtained a Guggenheim Fellowship to study steroid chemistry at the Federal Institute of Technology in Zurich.
Jensen often declared that his most important lesson from a year in Europe was learned not in the lab but in the Alps. Despite having no experience, he accepted a friend's invitation to climb the Matterhorn, the last major peak in Europe to be conquered.
"It was the hardest physical challenge I would ever encounter," he would later write, but the history of this fabled peak taught him "the lesson of the alternative approach." The first team to reach the summit, in 1865, took a route up the northeast face that others had dismissed as impossible.
In 1947, Jensen joined the University of Chicago as an assistant professor of surgery where he worked closely with Charles Huggins, who would win the Nobel Prize in 1966 for his work on hormones and prostate cancer. Huggins "taught me medicine," Jensen wrote in a commentary for Nature Medicine in 2004, "and I taught him some chemistry."
In 1951, Jensen became one of the original members of the Ben May Laboratory for Cancer Research, founded that year by Huggins. In 1957, working with colleagues at Fermilab in Batavia, Ill., Jensen built an apparatus for labeling estradiol with tritium, a radioactive marker that let him track the hormone as it traveled through the blood stream to the tissues, such as the uterus, that contained its receptor. This was his alternative approach: to "determine not what the hormone does to the tissue, but what the tissue does with the hormone."
"I really admired him," said former colleague Shutsung Liao, PhD, Professor in the Ben May Department for Cancer Research and an authority on male hormones and cancer. "He was very careful, very serious in how he applied his knowledge of chemistry to biological problems. He opened a whole new field."
He was promoted to professor in 1960. He became director of the Ben May Laboratory in 1969 when Huggins stepped down. He served in that role until 1982. After his wife died in 1982, Jensen took an extended leave from the University to serve as medical director for the Ludwig Institute for Cancer Research in Zurich from 1983 to 1987.
In Zurich, he met Hiltrud Herborg, known as Peggy, a popular cabaret singer. They married in December 1983. She later was diagnosed with breast cancer. After testing positive for the estrogen receptor, she was successfully treated with a medication that prevents estrogen synthesis.
Jensen returned to Chicago with his wife in 1988. In 1990, he turned 70, which was the mandatory retirement age at the time. Jensen continued to do research and spent time at the National Institutes of Health, Cornell Medical College, the University of Hamburg and the Karolinska Institute in Stockholm. In 2002, he joined the University of Cincinnati where he was the George J. and Elizabeth Wile Chair in Cancer Research. He was able to continue his research there until late last year.
Jensen retained a strong relationship with the University of Chicago. He was honored at a symposium held in 2001 marking the 50th anniversary of the Ben May Institute for Cancer Research and again in 2004 on the day his Lasker Award was announced.
"We all miss Elwood already," said Geoffrey Greene, PhD, the Virginia and D. K. Ludwig Professor and Vice Chair of the Ben May Department for Cancer Research, who came to the Jensen lab as a post-doctoral student in 1974. "He was my mentor and had an enormous influence on my career and the careers of many investigators from around the world who spent time in his lab. He knew everything that was going on in the lab and the field of hormone action, but encouraged us to question existing dogma and follow our data. Despite his international reputation and stature in the field, he was very easy going, approachable and friendly."
Jensen is survived by his second wife and two children from his first marriage: Thomas Jensen, MBA, who lives in Ecuador; and Karen Jensen, MD, a radiologist who graduated from the University of Chicago's Pritzker School of Medicine in 1977 and lives in New Hampshire.
"He loved his work and was very devoted to the laboratory and to his scientific colleagues, but he was also a good father," said Thomas Jensen, "He learned to ski in Switzerland and he taught my sister and me at a very early age. We skied together in the winters and spent many of our summers at a place we called Jensen Island, in the middle of Lake Meddybemps in Maine. When I think of my father, I imagine him at the lake cottage, hammering, fixing something."
The University of Cincinnati is arranging a memorial service in his honor in January 2013, and the University of Chicago is planning symposium in his honor for the spring.
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