Bigger than the World Series

October is always a reminder that it’s time for Major League Baseball’s World Series. Today, October is also celebrated as Breast Cancer Awareness Month, in no small measure because of Geneticist Mary-Claire King.

It was October 1990 in Cincinnati, Ohio at the American Society of Human Genetics’ Annual Meeting that King, after a painstaking 17-year research journey, announced her proof for a specific breast cancer gene, later called BRCA1.

King revealed to her fellow geneticists that there was a region on Chromosome 17 that was responsible for inherited predisposition to breast cancer. Until then, mainstreamed research believed that the cause of all breast cancer, similar to other cancers, was viral.  King’s linkage to genes was radical.

Since the mid-20th century, doctors and women patients noticed that some families had more women with breast cancer than other families.  “I was interested in breast cancer because it’s an extremely important problem.  It clearly clustered in some families and there was no obvious explanation for why that was true.  The only remaining explanation appeared to be genetics.”

King always used genes to find answers to important questions.  She co-authored research demonstrating that humans and chimpanzees are 99% genetically identical, and she used her genetic acumen to identify human rights abuses from Argentina’s Dirty War.  This time, King set out to prove that genetics played a role in this form of breast cancer.

King and colleague Beth Newman began the tedious genetic analysis with 23 families having 146 cases of breast cancer.  The idea to map the human genome was still ten years in the future, and advanced computing power was also non-existent.  King and Newman used the tools at hand.  Imagine scrolls of paper lining the halls at Berkeley to track and trace these family histories.

King’s background as a graduate student at the University of California, Berkeley in the 60’s gives a window into her persistent nature.  She also received a BA in math from Carleton College, an interest piqued from her childhood. If you are curious about the baseball analogies, King as a child spent hours alongside her father and brother reviewing stats for their beloved Chicago Cubs!

Mary-Claire King would need such fortitude when a commercial venture with more robust financial and computing resources cloned the BRCA1 gene on Chromosome 17.  Ultimately the 2013 Supreme Court ruled that “A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.”

“I had the honor of naming it and I named it BRCA1 for breast cancer one,” stated King.

Inherited breast cancer is rare and affects about 5-10% of all breast cancer patients–both women and men; those who test positive for the BRCA1 and 2 mutations have a 45-65% chance of getting breast cancer.

“Despite all the work that’s been done by many groups on BRCA1, BRCA2 and their sister genes, it’s still that case that probably half of severely affected families with breast cancer are not solved,” explained King.

The technique that King discovered has jettisoned research in the hereditary nature of many complex human diseases.  Today the King lab at the University of Washington, Seattle continues this genetic journey into inherited breast cancer and on mutations that lead to schizophrenia and occur newly [de novo] in that person.

We salute Mary-Claire King for transforming our understanding of inherited breast cancer and saving lives.