Chapter 1: What is the main topic discussed in this episode?
Hey, I'm Flora Lichtman, and you're listening to Science Friday. Today, it's common knowledge that many diseases and conditions have some kind of genetic link. But that wasn't always the case.
Chapter 2: What is the significance of the BRCA1 gene discovery?
Long before the Human Genome Project tied so many health issues to differences in genetics, way back in 1990, researchers identified a gene called BRCA1. This was the first gene linked to a hereditary form of any common cancer. People with a mutation of BRCA1 stood a higher risk of developing breast and ovarian cancer than those without the mutation.
Dr. Mary Claire King is a geneticist at the University of Washington. She and her lab were the first to identify that gene back in 1990. That discovery changed the way we thought about the inheritance of certain cancers. But that's not her only claim to fame. She used genetics to reunite children who were born in captivity or kidnapped by the Argentinian military dictatorship with their families.
Her Ph.D. work upended conventional wisdom about our evolutionary origins. Her research has changed the game again and again. Last September, I got the chance to sit down with Mary Claire King to find out about how she thinks about her work, what propels her, and what we can learn from her remarkable life in the lab. She joined us from KUOW in Seattle.
Mary Claire, thank you for being here and welcome back to Science Friday.
Thank you very much, Flora.
Thank you. Let's go back to your salad days. I read your interest in problem solving began with Cubs games.
When I was about six, my dad was already disabled. He was retired early with what was a very serious form of Parkinson's and was home. And already, even in the early 50s, one could have on black and white TV... You know, baseball games every day. So we would watch together the Cubs games. And my favorite player was, of course, Ernie Banks.
And my dad would make up story problems about Ernie Banks. So my favorite one that I have, of course, remembered all these years goes like this. Ernie Banks is coming up to bat. He's been batting .277. He'll probably have three at-bats this game. What's it going to take for his average to go up to .280?
And I was six. You're six, yeah. Most kids at six are like working on counting.
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Chapter 3: How did Mary-Claire King's early experiences shape her career?
You'll be always working for someone else.
If you don't get a PhD.
Well, in my particular case, if you don't get a PhD. But I think it's generally true that it's very important to stick with it through the discouragements in order to get to the point in whatever field, whether it's medicine or law or science, that you get to decide what the projects will be.
It can be hard to stick it out, though.
It's terribly hard to stick it out. And I think that one thing that I'm seeing now in students post-pandemic is that the discouragement from the period of the pandemic, the upheaval from that time, the need to be able to turn on a dime more. during that time in order to cope with an ever-changing larger environment have made sticking it out even more difficult.
So I think for people, for those of us of my era, it's very important just to continually encourage people that this has always been true. Obviously, the particulars are different, but the need to stick it out is really, really important. And if you look at all the people that any of us admire historically in whatever field, they're people who stuck it out.
You stuck it out. And during your PhD, you made this discovery that humans and chimps share 99% of our protein-coding DNA. Okay, when I read this, I was like, that's a pretty big discovery for a PhD student. Mm-hmm.
Of course, I had the world's best mentor in Alan. And the main thing that struck me about the project was that I had indeed mastered the electrophoretic techniques that Alan recommended because they were relatively straightforward compared to honest biochemistry that was otherwise going on in his lab.
And I had got pretty good at them based mostly on the work of Ilo Giblet, the late Ilo Giblet, who was up here in Seattle at the time, elegant, elegant protocols for doing all of these experiments. So I just followed them as one, in the same way that when I went home, I followed Julia Child. I had Julia Child on one side and I had Ido Gibbett on the other.
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Chapter 4: What challenges did Mary-Claire King face during her PhD?
She was called a statistician at the time, Jane Lane Coypon, who worked in the first part of the 20th century for the British Home Office. And she was a public health person. And she was very interested in what we would now call familial clustering.
So she asked the question, are daughters of women who die of breast cancer more likely to die of breast cancer than daughters of women who've died of something else? And the answer was emphatically, yes. But almost uniquely in her work, Dr. Wayne Claypond did not posit any environmental exposure that might be responsible. Bear in mind her
her brief is to sort out public health and environmental exposures. So I looked at all this and I thought, well, if all else fails, maybe think about genetics. And that the critical thing was to identify those families and then to try to trace first just epidemiologically what exactly had happened to all of the women in those families in terms of their cancer histories.
And then to use the tools of genetics that existed at the time, which were increasingly the capacity to try to locate genes on chromosomes. A chromosome is a physical reality. A gene is a physical reality. Every gene has an address on a chromosome or in mitochondrial DNA.
If one can find that address, even if one doesn't know the sequence of the gene, a situation that now would not obtain because we would know the sequence immediately, but in those days, of course, we didn't, one will have shown that that gene has to exist.
So what my contribution was in all of this was that realization, that you could use what was then called linkage analysis in families and chromosome mapping as an epistemological tool to prove the existence of the physical reality of a gene, even though the Genome Project was more than a decade away.
You know, I've talked to a lot of researchers about intuition and the importance of following their intuition and hearing this story where you're sort of breaking out from the pack here, right, with this idea. What's your take on that, the importance of going with your gut in science?
I think intuition is extremely important, extremely important. And I worry now that we aren't... encouraging intuition enough in our students and even in our postdocs. I think clearly there are tremendous advantages to team science, but I think one of the disadvantages to team science is that everyone has a small part of a huge problem
And the opportunities to indulge your intuition are far fewer in that context.
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