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Cancer Genetics: Looking Back, Looking Ahead

A Conversation With Mary-Claire King, PhD


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Mary-Claire King, PhD

By offering screening for BRCA1 and BRCA2 to all women at about age 30, it will be possible to prevent breast or ovarian cancer in those with cancer-predisposing mutations because they will know who they are. It is a way to empower women to be able to control their own futures.

—Mary-Claire King, PhD

At the 2014 San Antonio Breast Cancer Symposium, The ASCO Post sat down with geneticist Mary-Claire King, PhD, for some personal musings about her career and how she might guide young researchers who want to follow in her footsteps. Dr. King is known for a variety of accomplishments in genetics, including identification of the “breast cancer gene” BRCA1 (see article).

Empowering Women

You have a long history of advocating for disenfranchised groups, such as the farm workers in the Salinas Valley and the “disappeared” children  of Argentina in the 1970s. Does your proposal that all young women be offered screening for BRCA1 and BRCA2 mutations tap into that place? 

These projects are all related to the same worldview. Most recently, I was delighted when the Supreme Court ruled that genes are natural products. We have a right to own our own genomes. By offering screening for BRCA1 and BRCA2 to all women at about age 30, it will be possible to prevent breast or ovarian cancer in those with cancer-predisposing mutations because they will know who they are. It is a way to empower women to be able to control their own futures.

Medical Scientists

You worked for 40 years on research that eventually led to the discovery of the BRCA1 locus. If you were starting this mission today, you could potentially make this discovery in a matter of months, not decades. How would this have changed your experience as a young researcher?

That’s a very good question! We are the consequence of our historic period in science, as in everything else, and my early work was spent with linkage analysis, physical mapping, positional cloning, and manual sequencing. I learned a tremendous amount by having to do this work base pair by base pair for about 1 million base pairs. It was an incredible education in genetics, molecular and cell biology, and medicine. But I am glad that new investigators don’t have to do the same.

If I were starting out today, I would try to do one thing differently. I would try to go to both medical school and graduate school. As it was, I studied math, then evolutionary biology and genetics, and loved it. But if I had gone to medical school as well as to graduate school, I would have the perspective of both a scientist and a physician, and that is so valuable.

By having dual knowledge, you understand how things work from scientific and clinical perspectives. I look at the young surgeons in our group who come into the laboratory each morning having just cared for their patients. They have insights that I completely miss because of their clinical experience. At the University of Washington, I’m an Associate Director of our Medical Scientist Training Program (MSTP). Our director is Marshall Horwitz, MD, PhD, who studies genetics of hematopoietic malignancies; two other senior faculty members are associate directors as well. All of us find it a terrific privilege to work with MSTP students—they are the very best of their generation.

Family/Work Balance

What other advice would you give young people learning to live in the world of scientific research?

Do work that you enjoy. I think it’s only possible to succeed with work that one lives and breathes. If you love your projects, it’s easy to think about them all the time, and other aspects of life also will fall into place. It’s possible to think about science while playing with children and to think about children while playing with science. The more one does both, the better one becomes at both.

As a young mother, how did you manage to balance family and work?

I can’t claim to have balanced it. I was sleep-deprived for years. I just kept going. It gets easier.

As a young woman in a field previously dominated by men, was your work questioned more than that of your male colleagues? Were you trusted less? 

I don’t really know, because I have only one side of the experience and don’t think it’s worth trying to guess. It’s more important to focus on a current meeting like the 2014 ASCO Annual Meeting, with the attendance and the speakers probably close to half women. Things are changing profoundly in our professions, but the biggest challenge remains how to have enough time in the day to care for children while at the same time having a demanding career.

Being Comfortable With Uncertainty

How does one gain confidence in one’s work, when there is so much competition in the research field?

Perhaps the key is to have—or to pretend to have—enough faith in yourself to get past the disappointments of experiments that fail. It’s easy to think one is a failure, because in science, most experiments do fail. We have to expect that. We have to learn to be comfortable with uncertainty.

A particular challenge for physicians/scientists is to be able to act in the face of uncertainty in their clinical role while painstakingly pursuing conclusive evidence in their scientist role. It’s difficult cognitively and ­philosophically.

Grateful Cancer Survivors

I noticed a group of breast cancer survivors flocking to you after your presentation. Your work means so much to them. What do they say to you?

We recently received flowers at the laboratory with a note that read: “From three sisters who lost our grandmother and our aunt but will not lose our mother and not be lost ourselves.”

But the other side of this coin is that whenever I learn of a woman with ­BRCA-positive breast or ovarian cancer, I ask, “Why? This didn’t need to happen.” And that is at the heart of my proposal for offering BRCA testing on a population scale.

Future Hopes

So, when your career ends (some 50 years from now!), what do you hope has been accomplished from your work?

I hope that genomic testing for inherited cancers will be fully integrated into routine medical care, that we will have seamless referral of women with mutations for medical and surgical follow-up, and that this occurs in a health-care system that serves all of us—so a woman need not be lucky enough to have a job with benefits to receive the care she deserves. ■

Disclosure: Dr. King reported no potential conflicts of interest.

 

Dr. King is American Cancer Society Professor in the Department of Medicine (Medical Genetics) and the Department of Genome Sciences, at the University of Washington School of Public Health, Seattle.

Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO.

 


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It is not enough for Mary-Claire King, PhD, to have identified the germline BRCA1 mutation associated with hereditary breast and ovarian cancers. Her clinically applicable discovery is one of the world’s greatest in genetics and one for which she has been highly lauded.

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