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2004 Gruber Genetics The Science

Mary-Claire King is responsible for three major findings in modern genetics that span the fields of molecular evolutionary biology, genetic epidemiology and cancer biology, and forensic biology. They are so significant that even non-scientists know about them:

1. The close similarity of the human and chimpanzee genomes;

2. The discovery of a gene (BRCA1) that predisposes to breast cancer;

3. A robust means for identifying people (or their remains) by comparing their DNA to that of relatives.

The first of King's remarkable achievements was the quantification of the degree of identity between the genes of humans and those of chimpanzees. Her doctoral thesis (done under the supervision of the late Allan Wilson at Berkeley) showed that the protein-encoding sequences in the genomes of these species are more than 99% identical.

The second, and most significant, of Mary-Claire King's scientific achievements was the detection by linkage mapping using DNA polymorphisms, of a gene on human chromosome 17 that predisposes to breast cancer. She and her group spent many years collecting and analyzing families in which there were many cases of breast cancer. Her success depended on an insight that families displaying early-onset disease might represent a more homogeneous etiology; ultimately she was able to use this insight to separate signal from noise in the linkage data in a statistically rigorous and robust way. The group’s work was published in 1990, and was the first in which a gene predisposing to a common disease with many different and potentially complex causes had been mapped.

Although the BRCA1 gene itself ultimately was isolated by others, King’s group continued their family studies. In 1994 they reported nine different BRCA1 germline mutations in ten extended families, confirming the identity of BRCA1 as the gene on chromosome 17q21 that predisposes to breast and ovarian cancer. By 1998, her group, among others, had found that BRCA1 actually accounts for only a few percent of all breast cancer, forcefully illustrating that the original success had depended upon King’s decision to focus on only those families displaying early-onset disease.

The third, and by far the most far-reaching contribution to society from King's work, was the introduction (with Christian Orrego) of DNA technology in the 1980s to the problem of identifying the families of children orphaned and kidnapped during the Argentinean dictatorship. She introduced direct sequencing of PCR-amplified segments of mitochondrial DNA to the world as a robust and reliable means of identification from very tiny samples. This work required not only intellectual insight and technical acumen, but also uncommon caring for people, courage and conviction. King’s work not only demonstrated the technical power and accuracy of DNA forensics, but also became the basis for routine identification of human remains of soldiers (including the previously "unknown soldier" entombed at Arlington, and more recently in every kind of instance of mass genocide or disaster. In this most direct of ways, Mary-Claire King's career has demonstrated how genetic technology can directly benefit humanity.

Mary-Claire King's scientific achievements stand out because they matter to the larger community as well as to scientific and medical specialists. She has had a direct impact on the progress not only of medicine, but also justice.

By David Botstein