Prestigious Lasker Award goes to U. of C. researcher
Elwood Jensen helped revolutionize medicine for breast cancer
By Peter Gorner
Tribune science reporter
Published September 26, 2004
Elwood Jensen, the University of Chicago scientist who discovered how hormones interact with cells and pinpointed the estrogen receptor, leading to a revolution in breast cancer medicine, has been awarded the prestigious Lasker Award for Basic Medical Research.
His discoveries over 20 years led to the development of the drug tamoxifen and other measures that each year save or prolong the lives of more than 100,000 breast cancer patients, according to the Albert and Mary Lasker Foundation, which will announce the award Sunday.
The Lasker Prizes, considered the nation's most distinguished honors for medical discoveries, often are harbingers of the Nobel Prize. Some 68 American scientists who won the Lasker went on to receive the Nobel, including 15 in the last 10 years.
Often called the patriarch of his field, Jensen is an emeritus professor at the U. of C. who teaches at the University of Cincinnati College of Medicine. He shared the basic medical research award with two celebrated colleagues, Pierre Chambon of the Institute of Genetics and Molecular and Cellular Biology in Strasbourg, France, and Ronald Evans of the Salk Institute for Biological Studies in La Jolla, Calif., and the Howard Hughes Medical Institute.
The three scientists were cited for pioneering advances that unlocked the secrets of the giant superfamily of hormone receptors--48 have been found so far--that influence every developmental and metabolic system in animals and humans.
Hormones and their receptors work like keys and locks on the surface of cells, enabling the body to control sugar and salt balance, to respond to essential nutrients, and to regulate hormonal lipids such as fatty acids and cholesterol.
The winning scientists "discovered a family of proteins that allows chemicals as diverse as steroid hormones, vitamin A and thyroid hormone to perform in the body," said Nobel laureate Dr. Joseph L. Goldstein, chairman of the jury that selects recipients of the Lasker Awards.
"Their work provides a blueprint for the development of drugs for many medical problems, including inflammation, diabetes, heart disease and cancer."
In the 1950s, Jensen's mentor, Dr. Charles Huggins, a urologist and future Nobel Prize winner, demonstrated that breast cancer, like prostate cancer, was dependent on specific hormones, and that by removing their sources--the ovaries and the adrenal glands--physicians could cause substantial regression of the disease in 30 to 40 percent of women with advanced breast cancer.
Because there was no way at the time to predict which women might benefit from such surgery, Huggins urged Jensen to develop a method to measure the estrogen-receptor content of breast cancers and use that as a predictor for a response to endocrine therapy.
"The studies were beset by the complication that these hormones are active in such tiny amounts," Jensen has written. He and his colleagues designed radioactive tags that could detect as little as one-trillionth of a gram of hormone in animal tissues.
Next, Jensen showed that only tissues that respond to estrogen, such as the female reproductive tract, were able to concentrate estrogen when it was injected in the blood. To Jensen, that meant that these cells must contain the binding proteins he sought--the "estrogen receptors," he dubbed them.
In 1958, Jensen identified the estrogen receptor on the surface of cells of the female reproductive tract--the first receptor found for any hormone.
Now all breast cancers are classified as estrogen-receptor positive or negative, an important guide to prognosis and therapy. Estrogen-blocking medications such as tamoxifen have become important tools in the prevention and treatment of breast cancer.
Jensen, known for concluding his lectures in verse, summed up his dream of what such discoveries might mean to a woman who learned she had breast cancer in a poem:
A lady with growth neoplastic
Thought surgical ablation too drastic.
She preferred that her ill
Could be cured with a pill,
Which today is no longer fantastic.
Before Jensen's work, the way hormones exert their influence on the human body was "a complete mystery," said Gene DeSombre, professor emeritus at the University of Chicago who worked with Jensen at the Ben May Institute for Cancer Research. In the 1950s, biochemists thought estrogen entered a cell and a series of chemical reactions provided energy for the stimulation of growth and other actions.
Jensen overturned that notion. Working with estrogen, he proved that hormones do not undergo chemical change. Instead they bind to a receptor protein within the cell. This hormone-receptor package then travels to the cell nucleus and regulates the expression of genes.
At the time, the idea was considered heresy. "That really got him into some hot water," DeSombre said. But Jensen's discovery of estrogen receptors "is beyond doubt one of the major achievements in biochemical endocrinology of our time. His work is hallmarked by great technical ingenuity and conceptual novelty," he said.
Another former colleague, Shutsung Liao, who discovered a similar system for testosterone action, remembered that "Jensen struggled quite a lot."
When Jensen presented his early data at a 1958 meeting in Vienna, only five people attended, three of whom were other speakers. Nearby, more than 1,000 scientists attended a simultaneous symposium on the processing of estrogen by enzymes, the prevailing view.
By the early 1970s, Jensen was searching for chemical, rather than surgical, ways to shield estrogen-dependent tumors from circulating hormones. He and a colleague, Dr. Craig Jordan, now at Northwestern University, found that women with breast tumors that contain large amounts of estrogen receptors were likely to benefit from tamoxifen, which competes with estrogen and blocks the hormone's entrance at the receptor site.
Because of such research, patients with few or no receptors could immediately move on to chemotherapy, rather than waiting months to find out the tumors were growing despite tamoxifen treatment.
"We were glad we could do something that helped patients with breast cancer," said Jensen, 84, "to know that our basic research findings could be extended to the clinical management of patients with this terrible disease."
The Lasker Awards will be presented at a luncheon ceremony Friday in the Pierre Hotel in New York City.
On Monday, Jensen will return to the scene of former glories when he gives a brief talk titled "The Discovery of the Estrogen Receptor" at 4 p.m. in the Biological Sciences Learning Center at the University of Chicago, 920 E. 57th St., followed by a reception.
