2025 Elaine Redding Brinster Prize awarded to Mary-Claire King
The Institute for Regenerative Medicine at the University of Pennsylvania has awarded the 2025 Elaine Redding Brinster Prize to Dr. Mary-Claire King for her pioneering work on a genetic basis for breast cancer.
Dr. King proved the existence and precise location of variants of the BRCA1 gene responsible for inherited predisposition to breast and ovarian cancer. Her discovery represented a major advance in our understanding of both these cancers and the genetics of complex human traits. It was particularly remarkable because it was carried out based on genetics, logic, and experimental gene mapping before the human genome project, rather than on known sequence.
Her work has made it possible for women to test for inherited mutations in genes predisposing to breast and ovarian cancer, for mutation carriers to undertake preventive intervention, and for women who have already developed cancer to make use of genotype-specific therapy.
Beginning in 1974, Dr. King developed mathematical models of the genetics of breast cancer, years before the development of genomics tools. In 1990, she proved the existence of a breast cancer gene (that she named BRCA1) by mapping it to chromosome 17q21. When BRCA1 was ultimately cloned, it was at exactly the site she predicted.
After her demonstration that mutations of BRCA1 and its sister gene BRCA2 lead to very high risks of breast and ovarian cancer, Dr. King and her group developed a multi-gene sequencing approach (named BROCA) to simultaneously detect all classes of mutations in all breast and ovarian cancer genes. BROCA was not patented and was immediately put into widespread clinical use.
Dr. King’s approach to gene discovery has been a model for many complex genetic diseases beyond breast and ovarian cancers. Her paradigm is to identify rare families in which a complex phenotype is transmitted by Mendelian inheritance, then find the responsible gene in those families, and then compare to mutations in the same gene in patients without a serious family history.
This paradigm has been applied to millions of women worldwide at risk of breast and ovarian cancer and has provided the basis for gene discovery in diabetes, colon cancer, coronary artery disease, hypertension, Alzheimer disease, Parkinson disease, and other complex traits.
In addition to her pioneering breast cancer work, Dr. King has made major contributions in other fields. In the early 1970s, as a graduate student with Allan Wilson, she demonstrated that humans and chimpanzees are 99% identical in coding sequences of genes, and developed the hypothesis that the major differences between humans and chimpanzees are due to a small number of mutations affecting gene regulation and timing of gene expression during development.
This claim was validated 30 years later by the chimpanzee genome sequence, and the King and Wilson regulatory hypothesis remains a central paradigm of human evolutionary studies.
In the 1980s and 1990s, Dr. King developed genetics tools for the resolution of human rights abuses. In collaboration with the Grandmothers of the Plaza de Mayo of Argentina, she identified grandchildren who were kidnapped as infants after their parents were murdered during the Argentinean military dictatorship of 1975-83.
For this project, Dr. King developed the first application, in any field, of genetic genealogy based on sequencing mitochondrial DNA. Her laboratory has since assisted the United Nations Forensic Anthropology Team to identify remains of victims of extra-judicial execution on six continents and has worked with the U.S. Army to identify remains of US soldiers who had gone missing from Vietnam, Cambodia, Korea, and during WWII.
Dr. King will accept the prize on March 12, 2025, as part of the day-long Ralph L. Brinster Symposium.