Mary-Claire King

While young Mary-Claire King and her father watched televised baseball games together, he pitched word problems, quizzing her about how that day’s strikeouts changed a rookie’s batting average or standing. Sometimes the Chicago Cubs and White
Sox played at the same time, and the split-screen coverage offered the possibility of simultaneous equations. When her dad wasn’t cheering the local teams, he and King’s mother tuned into the world around them. They often tried to fix injustices, and King learned that she should right wrongs that she encountered.

As a statistics graduate student in the late 1960s, she realized that people get paid to solve thought-provoking genetics puzzles with mathematics. After switching fields to genetics, King and her Ph.D. advisor, Allan Wilson, showed that humans and chimpanzees are much more closely related than traditional evolutionary theory held. The genetic resemblance seemed to contradict anatomical and behavioral distinctions. King and Wilson proposed that the discrepancies arose not from markedly divergent DNA sequences, but because genes in the two hominids turn on and off at different times.

Just as genetic changes send species down new evolutionary avenues, they also push cells closer to a malignant fate. The same tools that revealed DNA disparities between species could uncover peculiarities that predispose people in high-risk families to breast cancer, King reckoned. Genetic anomalies also accrue during an individual’s lifetime, and when one of these “hits” occurs in a vulnerable cell, it can trigger uncontrolled growth. King reasoned that such a scenario might unfold in breast cancer.

She began a quest for the culprit gene, but the undertaking drew criticism. According to prevailing dogma, breast cancer arose from undefined interactions among multiple genetic and environmental mishaps. Furthermore, it usually cropped up sporadically, not in families. Perhaps the occasional clustering arose from shared conditions. No one would ever pin the disease to a single gene.

King persevered.

Aiming to test whether she could find evidence of a flawed gene whose presence correlates with breast cancer, she applied mathematical methods. Her analysis strongly supported the existence of a single gene with this effect in a small proportion of families. King began experimental work to find it. In late 1990—17 years after she began her mission—she identified a stretch of DNA that harbors a gene that predisposes people in some severely affected families to early-onset breast cancer. She named it BRCA1.

This finding instigated an international race to identify the gene, and four years later, scientists crossed the finish line. Glitches in BRCA1 and a second susceptibility gene, BRCA2, increase the lifetime risk of breast cancer from 12 percent in the general population to 80 percent.

King has also deployed her expertise beyond the realm of biomedicine. For example, she helped find the “lost children” of Argentina. Some babies born in prison or captured with their mothers during the military regime of the late 1970s and early 1980s were given to military families. By proving genetic connections, King enabled the reunion of more than 100 children with their relatives. She has since used the techniques she developed in that effort to expose human rights abuses in many countries throughout the world.

Author: Evelyn Strauss, Ph.D.