Mary-Claire King

The Work:

Dr. King’s first breakthrough was in molecular evolution and population genetics. Her research as a PhD student suggested that the differences between humans and chimpanzees are due to a small number of mutations affecting gene regulation and the timing of gene expression, rather than accumulation of differences in protein-coding sequences.

King’s work evolved to focus on proving the existence of inherited susceptibility to breast cancer and identifying BRCA1 as the first gene responsible for it. Her group studied families in which many women developed breast or ovarian cancer. First, based on mathematical modeling, King hypothesized that severe inherited mutations in a single gene could be responsible for breast cancer in some women. At the time, this hypothesis was considered far-fetched and very unlikely.

Then based on this hypothesis, King proved the gene’s existence by mapping the still-hypothetical gene to a specific chromosomal location. She named the gene BRCA1. The idea was no longer far-fetched and an international “race” of four years ensued to clone the gene.

After the gene was cloned, King and her colleagues developed and deployed next-generation sequencing strategies to identify mutations in BRCA1 and its sister genes responsible for multiple forms of inherited cancer. She and many others have applied the same approach to identification of genes with major impact on other complex diseases.

The Impact:

Dr. King’s discovery has transformed the diagnosis, drug development, and treatment of inherited breast and ovarian cancer. The identification of BRCA1 — and subsequently BRCA2 — has made it possible to diagnose whether a woman in an affected family is at extremely high risk of developing breast and ovarian cancer, enabling her to pursue preventative treatment.

King’s passion for gene discovery integrated tools from genetics, statistics, mathematics, epidemiology, molecular biology, genomics and clinical medicine. Her revolutionary approach to gene discovery has had an impact on many other diseases, ranging from prostate cancer to inherited hearing loss to schizophrenia. King is also a pioneer in the development of DNA sequencing for the identification of victims of human rights’ violations.