Sometimes the most stunning advances in science are based on a hunch that a dedicated investigator just can’t shake.
That was the case with Mary-Claire King, professor of genome sciences and of medicine at University of Washington. King discovered the region on the genome that eventually became known as BRCA1, the first gene linked to a higher than average chance of developing breast cancer and ovarian cancer. While it seems obvious now that genes can be tied to cancer, at the time King conducted her studies, the idea was too radical to have many supporters.
But King was used to being unusual. As a graduate student at the University of California Berkeley, where she first studied mathematics and then switched to genetics, she petitioned the university protesting the U.S.’s invasion of Cambodia during the Vietnam War. When the National Guard removed demonstrating students, King dropped out and helped consumer rights advocate Ralph Nader to study how pesticides affected farm workers.
She returned to Berkeley and contributed to groundbreaking genetic work that showed humans and chimps shared 99% of the same DNA.
Today, BRCA1 and the related BRCA2 are responsible for about 5% of breast cancer cases in the U.S., or up to 25% of inherited breast cancer, and screening for changes in the genes can help steer women toward potentially lifesaving treatments. The Supreme Court recently ruled that BRCA1 and BRCA2 are not patentable, since they are products of nature, a decision that King supports so that more companies can now devise tests for the cancer-causing mutation.
We spoke with King when she was in New York for the World Science Festival. Here's what we learned:
On how she discovered BRCA1, and the importance of believing in your gut instincts:
"If we cast our minds back to the 1970s, when my work [on BRCA] began, the mainstream theory was that breast cancer was viral. And some cancers are, so it wasn’t a crazy theory.
My thinking—and, believe me, this was not a theory in the field but just a notion I had—was that there was good evidence that there were some families in which breast cancer was especially common. There was no evidence of a smoking gun. That opened the possibility that there was something else. That went side by side in my mind with the logical way of thinking about cancer, that all cancer is genetic in the sense that it’s a consequence of changes in DNA. That also was not mainstream thinking at the time. But that was the basis of my own thinking, and I’m a stubborn person, so it allowed me to keep pushing my little idea in a very quiet way."
On seeing her little idea become a big one:
"I was absolutely convinced that cancer had to be genetic. I did not see any other way the relationship between a tumor and host could possibly persist. But I honestly didn’t appreciate at all how important and directly useful the inherited component would be. The idea that oncologists and medical geneticists would take that information and systematically be able to put into place screening programs that enable women to learn that they had mutations, and do something about it to save their lives, wasn’t the way I thought. If somebody had said that this was possible, I would have said, ‘Golly, maybe it was.’ But nobody said that to me."
On whether every woman 30-plus should have a BRCA1 and BRCA2 screening:
"I am increasingly convinced that it is both feasible and a good idea to offer a blood test, a sequencing test for BRCA1 and BRCA2 and some of their sister genes for every woman after about age 30. Once a young woman reaches 30 or so, if she has a mutation in one of the genes, she should know about it. ... These mutations are inherited from fathers half the time, and from mothers half the time. Because families in America are so small, we did a study that showed that in exactly half of women who had BRCA1 or BRCA2 mutations, there was no family history that would have led them or anyone in their family to think they carried the mutation. All of these women inherited the mutation from their father, and their fathers either didn’t have sisters or had sister who didn’t inherit the mutation.
Sequencing is now cheap, prices are coming down and the quality is going up. So there’s no reason not to do this. The point is to have a process that is benign enough to the individual—a blood draw—and inexpensive enough to identify people who are really at high genetic risk and then move them into very good screening programs to enable them to make a plan about preventive surgery or other options."
On how being a woman in science has changed, and remained the same:
"I always assumed I would be an assistant to someone else, because there have always been women in those roles. I always assumed I would work for someone else. And I assumed implicitly that 'someone else' would be a man. There are obviously many more women in the field now. Acceptance in principle of women in the field is completely different and that’s absolutely fabulous; it’s just splendid.
The thing that hasn’t changed is the number of hours in a day. The coincidence of one’s child-bearing years with exactly the time one needs to build a career—that's challenging. Science is also a very demanding child—you can’t just walk away from either. That hasn’t changed. It’s not realistic to say one can drop out of science and drop back in.
Really good child care is incredibly important. Creating a context in which young women scientists have child care they can rely on, and can afford, and that’s close enough to where they work, is enormously difficult, and institutions are working on it. One thing I try to do is run a family-friendly lab. I think it’s the responsibility of those of us whose children are now grown to remember what it was like, and to run family-friendly labs. When women in my lab get pregnant, we know they simply will not be there for a while. But you need the infrastructure in place so their experiments won’t rot when they’re not there, and so they can come back when they are ready."
On being a mother and being a scientist:
"You never get over the guilt. My daughter would come into the lab when she was six or seven, and she had an area in my office with books, picture books and toys. She made posters that went on the door to my office. One was the First Mommy to Walk on Land. Another was the Sister of the First Mommy to Walk on Land. And there was the Brother of the First Mommy to Walk on Land. When I asked her why she was making the posters, she said, 'They are to keep people happy while they have to wait for you.’
You have to have an environment in which it’s clear that having children is a part of life, and welcomed. You have to recognize that a scientific career can be very long, and you need to go into the business of being there for your child when you have a child. It’s possible. It’s not possible to do and get enough sleep, but it’s possible to do."