Mary-Claire King

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Mary-Claire King

In 1990, after 17 years of painstaking work, geneticist Mary-Claire King (born 1946) announced that she was close to pinpointing the location of a gene that is responsible for some cases of inherited breast and ovarian cancer. Her work cleared the path for future research aimed at predicting who might be at higher risk for developing the disease and possibly devising better treatments.

Mary-Claire King was born on February 27, 1946, in Evanston, Illinois, a suburb of Chicago, to Harvey W. and Clarice King. The family included a brother Paul, who later became a mathematician and business consultant, as well as a stepbrother and stepsister. King's father worked at Standard Oil of Indiana managing the personnel department. King studied mathematics at Carleton College in Northfield, Minnesota, graduating Phi Beta Kappa in 1966. Eager for a challenge, she enrolled in graduate school studying biostatistics at the University of California at Berkeley, where she planned to use her math background in the field of medicine. After a course with geneticist Curt Stern, King found she enjoyed the concrete applications of genetics and changed her major. She was granted a National Science Foundation fellowship from 1968 to 1972 for her graduate studies.

Pursued Political and Social Causes

During the turbulent Vietnam War era, King organized a letter-writing campaign and petition drive at the University of California, protesting the American invasion of Cambodia. After then-governor Ronald Reagan sent the National Guard to the campus to remove students from the buildings, King became dismayed and dropped out. For a while, she worked with consumer watchdog, Ralph Nader, investigating the effects of pesticides on farm workers. He offered her a job in Washington, D.C., and she weighed the option heavily. She told her friend Allan Wilson, a professor of biochemistry and molecular biology at Berkeley, that she was disappointed with her academic research. "'I can never get my experiments to work,' I said," recalled King in Omni. "'I'm a complete disaster in the lab.' And Allan said, 'If everyone whose experiments failed stopped doing science, there wouldn't be any science.' So I went to work in his lab."

At the time, Wilson was looking into the genetic differences between chimpanzees and humans. King worked with him, despite doubts, and finished her dissertation outlining the fact that the DNA of humans and chimps is 99 percent identical. This indicated that the two species possibly had a common ancestor about five million years ago, a time estimate about ten million years sooner than previously thought, based on fossil evidence. The researchers were pictured on the cover of Science magazine in April 1975 for their discovery. Meanwhile, King received her doctorate from the University of California in 1973 and married Robert Colwell, a zoologist. They later had a daughter, Emily, but divorced when she was five. The couple went to the Universidad de Chile to teach. In September, after the assassination of Socialist government leader Salvador Allende, many left-wing supporters were killed, went into hiding, or left Chile. These included some of King's friends and students.

Launched Breakthrough Cancer Research

Returning to the United States, King worked for a year in epidemiology at the University of California in San Francisco, then was hired as an assistant professor in that discipline at the Berkeley campus in 1976. She was promoted to associate professor in 1980 and professor in 1984. King spent her time studying 1,579 women, trying to prove that some breast cancer cases could be traced to a single gene. Aware of the fact that breast cancer sometimes runs in families, she studied chromosomes of related women who had the disease. After tedious work dating from 1974, a new technology breakthrough in the early 1980s made it possible to search for pieces of DNA from blood samples. In 1990, she presented her findings at the American Society of Human Genetics annual meeting in Cincinnati. King had narrowed the possibilities to a gene located on chromosome 17.

Following this remarkable news, a kind of "holy grail" search ensued in the scientific community, with about a dozen teams of researchers fervently trying to isolate the gene, dubbed BRCA1. In September 1994, Mark Skolnick and his colleagues at the University of Utah Medical Center won the race. King and her group, however, did not fail in their mission. Her original research, coupled with ongoing studies of BRCA1 and BRCA2 (another gene that was found a year later), had succeeded in raising awareness of breast cancer and the need for further study. King noted at a 1996 conference in Paris that immense achievements had been made in figuring out how the gene worked. She and some researchers at Vanderbilt University discovered that healthy genes may be able to halt, or even reverse, the effects of the mutant gene. This opened up the possibility of using gene therapy-correcting or replacing the gene-as a future method of treatment. Well into the 1990s, however, scientists still had few clues as to why breast cancer rates were increasing in developed nations such as the United States, Canada, and across Europe.

King's breast cancer research paved the way to determining whether other diseases could be inherited. "Before BRCA1, there was a widespread view that diseases like breast cancer were caused by multiple genes that interact with environmental factors. This didn't provide geneticists with a clear road ahead," noted Maynard Olson, a professor with the University of Washington, in Columns, the university's alumni magazine. "In the midst of that, Mary-Claire's initial report was a jolt. She told a different story: that in carefully selected families she could find a fairly simple genetic link for breast cancer. It provided us with a powerful path forward. We now know that many important diseases can be attacked in the same way."

Crusaded for Argentina's "Disappeared"

King combined her activist zeal and her education in genetics to assist grandmothers in Argentina who had lost their grandchildren during the civil war of the 1970s. After a coup in 1975, the military began kidnapping huge numbers of people in order to instill terror. Many of the "disappeared," as they came to be known, were pregnant women or women with children. Older children were killed, and pregnant women were tortured. Their babies were sold or adopted by military members, after which the mothers were killed. The new parents would claim the children as their own, despite no sign of pregnancy by the military wives. Through subversive contacts, such as midwives and obstetricians who were coerced to deliver the babies, family members tried to keep track of the relatives they had lost. By 1977, families began forming human rights groups to find the missing children.

In 1983, members of Abuelos de Plaza de Mayo asked the American Association for the Advancement of Science to provide a geneticist who could help determine if certain youngsters were their grandchildren. King went to Argentina in June 1984 to identify remains as well as perform HLA (human leukocyte antigens) typing on living children, a test that analyzes blood proteins. Thanks to King's help, dozens of children were reunited with their biological families. She also assisted with performing DNA tests on exhumed remains in order to initiate criminal cases against the murderers. In similar projects, King has helped the U.S. government and the United Nations identify the remains of soldiers who had been missing in action.

In the mid-1990s, King began doing AIDS research, trying to determine whether genetics plays a part in why some people quickly develop full-blown AIDS, while others live for years with the disease. At this time, she accepted a position at the University of Washington, where she teaches in the departments of medicine and genetics. King has worked with the Human Genome Project, a government-sponsored program to map and analyze all 100,000 human genes. In addition, she has served on the Special Commission on Breast Cancer of the President's Cancer Panel; the advisory board of the National Institutes of Health Office of Research on Women's Health; and on committees of the National Academy of Sciences and the National Institute of Medicine.