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Thu March 27, 2014

How Being Ignored Helped A Woman Discover The Breast Cancer Gene

Originally published on Sun March 30, 2014 9:17 am

Back in the 1970s, a geneticist named Mary-Claire King decided she needed to figure out why women in some families were much more likely to get breast cancer.

It took 17 years for King and her colleague to identify the single gene that could cause both breast and ovarian cancer. During that time, many people discounted her work, saying that genes couldn't cause complex diseases like cancer. She proved them wrong by mapping the location of the gene she named BRCA1. In 1994, after an international "race" of four years among competing laboratories, the BRCA1 gene was successfully cloned. (King describes her experience in Thursday's issue of the journal Science.)

The discovery revolutionized genetics and cancer treatment. Simple genetic tests now let women know if they have mutations in their BRCA genes that increase cancer risk. They then can act on that knowledge, as actress Angelina Jolie did.

King, now a professor of genome science at the University of Washington, talked with NPR's Audie Cornish on Thursday about how she slowly but surely built evidence to prove that BRCA did indeed cause cancer. The conversation has been edited for length and clarity.

What triggered you to think that there would be this genetic link to cancer?

For breast cancer, there was very good evidence that some families were at high risk of the disease, but without an explanation why that could be true. In the absence of any other explanation I was driven to consider genetics.

How did you come up with the answer?

Our strategy was to use the idea of mapping a gene as an epistemological tool. We felt that we could prove the existence of a gene by showing where it was. And that's what we did. It took 17 years, from 1974 to 1990, but by 1990 we really had incontrovertible proof that there was a gene that lived on chromosome 17 in a particular physical locale.

Now this was all before the Human Genome Project, right? Now we take it for granted that there's this kind of easy mapping technology — if you want to find a gene in a chromosome just go look it up.

You're right — anyone can loop up a gene for free! It costs nothing and it takes 10 seconds on the Genome Browser. You're also absolutely right that the Human Genome Project had not yet begun when we began working on this project. The Human Genome Project and the effort to find BRCA1 were essentially born at the same time.

It seems like we're at a point now where we can do all kinds of mapping, we know about all these genes, but that doesn't necessarily make the decision any easier in terms of what kind of treatment you should do or what kind of risk prevention you should take. The science has outpaced the treatment.

A challenge we face as scientists, and a challenge our physician colleagues face, is how to interpret this very rapidly growing amount of information in a way that can best empower our patients. Our goal is to be able to inform women of genetic information that will lead them to make the best choices for themselves. We need to provide data that is complete and accurate. And we need to be able to do that inexpensively and effectively.

Over time, do you see that there has been too much emphasis on genes and genetic links and that that has that been to the detriment of other factors like environmental factors?

We now are in a position to say genetics only goes this far; beyond this we need to think about environmental causes. Now the understanding of environmental causes and genetic causes are moving hand in hand rather than in conflict.

You've said in the past that as a woman doing this work there was a certain freedom in your research back in the 1970s when you were starting out; freedom in being ignored. In what way?

As a young scientist it can be liberating to not have expectations placed on you; if you can work quietly and if you can obtain funds for your work. And I could obtain modest funds for my work in the 1970s, and I could work in a way that allowed me the time and space to develop evidence until I was convinced of it. That's of course the highest bar — that you convince yourself that your evidence is good. Once you present your evidence then of course you're no longer being ignored. You're being attacked from all sides. Then you need to defend your evidence. But if you've had 17 years to develop your evidence then you're in a much better position to defend it well.

You've said you were a child of affirmative action. At that time did it really feel like not just that people were ignoring you, but they were dismissive of your work?

When one is a child of affirmative action one needs to anticipate that people, particularly those who didn't benefit from affirmative action, won't take you seriously for a while. But there's a wonderful phrase from Simone de Beauvoir: For a woman to be taken as seriously as a man she must be three times as effective. Happily this is not difficult.

Copyright 2014 NPR. To see more, visit http://www.npr.org/.

Transcript

AUDIE CORNISH, HOST:

From NPR News, this is ALL THINGS CONSIDERED. I'm Audie Cornish.

ROBERT SIEGEL, HOST:

I'm Robert Siegel. And in this part of the program a discovery that changed how we understand cancer. Today it's possible for women to take a simple test to determine if they carry a gene that may increase their risk for breast and ovarian cancer. That was not always the case.

CORNISH: Back in the '70s, when geneticist Mary-Claire King led a small research group at the University of California, Berkeley, she sought to answer this question: Is there an inherited form of breast cancer? Well, 20 years ago this year, King's work lead to the cloning and sequencing of BRCA-1. That's the gene that, when working, suppresses tumors, but mutations in this gene can lead to certain breast and ovarian cancers.

King told me earlier today she was able to identify BRCA-1 because she did not accept the prevailing hypothesis that cancer was caused solely by viruses.

MARIE-CLAIRE KING: The way that I thought about the problem was completely different, not in conflict, but simply complimentary to that idea. That is, that there could be some particular families in which predisposition to cancer could be inherited. What my little group and I were trying to do was to determine whether, for a very common cancer, for breast cancer, there was a subset of the illness that could be explained by this inherited predisposition.

CORNISH: So this idea that there are potentially genetic markers that could be identified, where you could track cancer through a family, what triggered your idea that there would be this genetic link?

KING: For breast cancer we had, time and time again, very good demonstration at the level of statistics and at the level of epidemiology that some families were at high risk of the disease, but without an explanation why that could be true. And in the absence of any other explanation, I was driven to turn to genetics.

CORNISH: What was it like when you landed on an answer, when you had started to kind of pinpoint the location on the chromosome where this gene might be?

KING: So our strategy was to use the idea of mapping a gene, which was, of course, an idea current in genetics at the time. And so the epistomological tool - that is, that we felt we could prove the existence of the gene by showing where it was, and that's what we succeeded in doing. It took 17 years. It took from 1974 until 1990, but by 1990 we had really incontrovertible proof that there was a gene that lived on chromosome 17 in a particular physical locale.

CORNISH: Now, this was all before the Human Genome Project, right? I mean, now we sort of take it for granted that there's this kind of easy mapping technology. If you want to find a gene in a chromosome, just go look it up, spend a couple thousand dollars.

KING: Oh, you could look it up for free. Every listener can, at this moment, look up their favorite gene on the UCSC Genome Browser and it costs nothing and it takes 10 seconds. The Human Genome Project, you're absolutely right, the Human Genome Project had not yet begun when we were working on this project. And the Human Genome Project and our effort to identify BRCA-1 were essentially born at the same time.

CORNISH: Now, in the decades since your work led to this mapping of BRCA-1, there have been many other gene mutations that have been mapped, gene mutations linked to breast cancer. But even though the genetic diagnosis is getting better and easier, has all this data kind of out-paced our understanding of it?

KING: Well, my group actually mapped BRCA-1. The race between 1990 and 1994 was to clone the gene - that is, to actually physically pull it out of the chromosome and understand exactly what it does. The gene was cloned in 1994 and the anniversary this year is of the cloning of the gene. And I think it's adorable that the world is celebrating the anniversary of a gene. I think that's great.

CORNISH: It seems like we're at a point now where we can do all kinds of mapping, you can find out about all these different genes, but that doesn't necessarily make the decision any easier in terms of understanding what kind of treatment you should do or what kind of risk prevention you should take. I mean basically, like, the science has outpaced the treatment.

KING: Well, a challenge that we face as scientists, a challenge that our physician colleagues face is how to understand this very rapidly growing amount of information in a way that we can best empower our patients. What our goal is, is to be able to inform women of genetic information that will lead them to be able to make the best choices for them. And we need to be able to give them data that's complete and that's accurate.

And we need to be able to do that inexpensively and effectively.

CORNISH: Over time, though, do you see that there has been too much emphasis on genes and genetic links and has that been to the detriment of research that could focus on other causes of cancer, like environmental factors?

KING: We now are in a position to understand both what genetic factors are that influence disease and what the limitations of those factors are, so that with information we have power. With information we're now in a position to say genetics only goes this far. Beyond this we need to think about environmental causes. And in fact now, the understanding of environmental causes of disease and the understanding of genetic causes of disease are moving hand in hand rather than in conflict.

CORNISH: I wanted to ask you one thing personally. You've said in the past that as a woman doing this work there was a certain freedom in your research when you were starting out in the '70s, freedom in being ignored. In what way?

KING: As a young scientist, it can be liberating to not have expectations placed on you. If you can work quietly, if you can obtain funds for your work - and I could obtain modest funds for my work and I could work in a way that allowed me the time and the space to develop evidence until I was convinced of it, and that's, of course, the highest bar, is to convince yourself that your evidence is good.

Then once you are convinced of your evidence and then you present it, then of course you're no longer being ignored. Then you're being attacked from all sides and you need to be able to defend your evidence. But if you've had 17 years to do it, to build it, you're in a much better position to be able to defend it well.

CORNISH: But it was interesting because I remember you saying that you were a child of affirmative action, and at that time did it really feel like - not just that people were ignoring you, but that they were dismissive of your work?

KING: When one is a child of affirmative action, one needs to anticipate that people, particularly those who have not benefitted from affirmative action, will not take you seriously for a while. But there's a wonderful phrase from Simone de Beauvoir and she says for a woman to be taken as seriously as a man, she must be three times as effective. Happily, this is not difficult.

CORNISH: Marie-Claire King, she's a geneticist and professor of genome sciences and of medicine at the University of Washington in Seattle. Thanks so much for your time.

KING: My pleasure, Thank you.

CORNISH: Marie-Claire King writes about the race to clone BRCA-1 in this month's Science magazine. Transcript provided by NPR, Copyright NPR.

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