Pod Insights Short Wave Your DNA is changing all the time. Here’s why About this episode We tend to think of the DNA strands that contain our genetic code as consistent, stable units. But in reality, the cells that make up our bodies are constantly replicating and changing. Even as you read this sentence, in fact, the genes within your cells are mutating. So, what causes these mutations and what’s the impact? Science writer Roxanne Khamsi examines the answers in her new book, Beyond Inheritance https://roxannekhamsi.com/beyond-inheritance/. Today on the show, she gets into how scientists examine these mutations, how they’ve shifted our understanding of disease and what the future of genetic therapy could entail.
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Transcript Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
0:00 Speaker 00 This message comes from Mint Mobile. Ditch overpriced wireless and get premium wireless for less. Go to mintmobile.com/switch to see which plan works for you.
0:12 Emily Kwong? You're listening to Short Wave from NPR. Shortwavers, I'm going to take us back to high school biology, the genetics chapter. You may have learned that the human body is made up of trillions of cells, and inside those cells are DNA molecules, those strands that contain the genetic code that makes you you. But here's something that may surprise you and you may not have learned in school. That DNA is not the same for every cell. And that's because DNA is constantly changing.
0:44 Speaker 02 There's actually trillions of mutations happening in your cells every day.
0:47 Emily Kwong? This is Roxanne Comsey. She's a science journalist and a contributing writer at The Atlantic.
0:52 Speaker 02 We're just constantly in flux, partly because there's just wear and tear. Like genes will get turned on and sometimes things will break. And then enzymes will come in and try to fix it, but they won't always do the best job fixing it. So we are kind of a landscape of genetic diversity, each of us, just by nature of all the DNA changes, all those errors that pile up over the course of our lives.
1:15 Emily Kwong? By the way, scientists have known for decades that our genes mutate. It's just that in the last decade, DNA sequencing has gotten so much more powerful and precise. The scientists can now read the genetic code of individual cells.
1:28 Speaker 02 There's been this possibility to kind of do a census of the cells in a body and figure out which ones have which mutations that the other cells don't have. So then here we are grasping this diversity, this genetic diversity that exists inside us.
1:43 Emily Kwong? And it turns out there is a lot of genetic diversity going on inside us, so much so that Roxanne wrote an entire book about it called Beyond Inheritance: Are Ever-Mutating Cells and a New Understanding of Health?
1:56 Speaker 02 People hear the word mutation and they immediately think about something negative. But there's also good things that can happen with mutation.
2:06 Emily Kwong? So today on the show, genetic mutations like you've never seen them before. Out of the trillions of mutations happening inside us every day, yes, trillions, which ones matter? What do scientists know about them? And if our DNA is always changing, then who are we really? I'm Emily Kwong. You're listening to Short Wave, the science podcast from NPR.
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3:30 Emily Kwong? This election season, let the NPR Politics podcast save your time and your sanity. We'll help you understand key races, which polls you can safely ignore, and what might happen if power shifts in Congress. Our short daily episodes come out every afternoon, so you can spend less time scrolling through each chaotic news cycle. Make NPR Politics your hub for midterm election coverage. Follow our podcast on the NPR app or wherever you get your podcasts. Roxanne, so usually when we talk about genetic mutations, it's because something extraordinary arises from it, like the formation of an entire species eventually, or an inherited disorder. But in your book, you say mutations are ordinary. They're as common as salt. They are happening all the time.
4:16 Emily Kwong? What kinds of mutations are happening all the time?
4:19 Speaker 02 So yeah, I guess I could have called this book like Everyday Mutations. I mean, you and I are mutating as we're having this conversation.
4:24 Emily Kwong? Wow.
4:25 Speaker 02 People listening to this are mutating as they're listening. It's something kind of ongoing. It's kind of the background noise, if you will, of our lives.
4:32 Emily Kwong? Because the cells are copying and just making errors all the time?
4:35 Speaker 02 Yeah, so there's cell turnover all the time. Like, our skin cells, you wouldn't believe how many skin cells we shed. Our blood is turning over constantly. And it has implications for our health, even these smaller-scale mutations, because...
4:50 Speaker 02 There's a lot of mutation happening and a lot of it doesn't matter in our cells. But every once in a while, there is something that happens and it's not going to cause a new species. It might be an evolutionary dead end because we're not going to pass it on to the next generation. But for the vast majority of the mutations in our bodies, what matters is where it falls in the genome. And if it falls in a place that matters and that that cell reproduces or replicates itself, that's when you get into a situation where, you know, a spontaneous event can have really profound impacts on our health.
5:27 Emily Kwong? Are there any specific environmental factors or behavioral factors that trigger certain kinds of mutations?
5:34 Speaker 02 So we know that things like sunlight obviously cause our skin cells to mutate. That's what's linked to skin cancer, for example.
5:40 Emily Kwong? Okay.
5:41 Speaker 02 If you have good quality sleep, if you sleep well, that is actually linked to fewer mutant cells. But what I found really striking is that we now have the ability to dissect our mutations so much that scientists can actually look at the signature of your mutation, so where they fall in the genome. And actually tell you if you have been smoking tobacco or chewing tobacco. Like, that's how, that's how refined a picture we're getting of how our behaviors affect our cells. So in the past, people might have said, oh, don't smoke, it gives you cancer. Now we're actually saying, okay, don't, don't chew tobacco or don't smoke tobacco because these are the actual kinds of mutations you're going to get that may then precipitate something down the road.
6:26 Speaker 02 So, yeah, behaviors cause cancer, and then sometimes it's just, you know, chance.
6:33 Emily Kwong? Hmm, say more about that, chance.
6:36 Speaker 02 Well, what I think is really interesting is that when embryos are dividing cells, so like, you know, we all start with as one cell for the first 24 hours of our life and then we're two cells and by day five, we're 100 cells with this hollow center. That's one of the most active places of cell division in the course of our lives. It's this embryonic development. And I spoke with this family that 13 years ago, their youngest daughter was born and like immediately taken to the ICU, the neonatal ICU. And they were trying desperately to figure out what was going on with her. And what they thought she had was this condition called long QT syndrome. But then they kind of looked and her parents didn't have it, which was strange because
7:21 Speaker 02 this was thought to be an inherited disorder. And what they found is that indeed she did have those cells mutated in her heart. And the thinking is that since she didn't have the mutation throughout her body, it was in that early, kind of really dynamic embryonic cell division that a mistake was introduced in her DNA and then passed on to part of her body.
7:41 Emily Kwong? Just by chance.
7:42 Speaker 02 Just by chance. So it has shifted our perspective of certain inherited diseases to be not just inherited, but also spontaneously occurring. And I think it's important for people to be aware of this if they want to kind of understand what's going on with their health.
7:59 Emily Kwong? Let's, let's talk about this more. Instead of assigning a value judgment to like good mutation, bad mutation, there's just like mutations and, and there's different pathways there. In chapter six, you talk about auto corrections where the human body by chance is mutating and like fixing itself. What is an example of that?
8:19 Speaker 02 Back in the 1990s, there were these two boys that should have not survived a condition that they were born with. So they were born with something called ADA SKID, which is an inherited immune deficiency. And one of the boys actually had, had a brother that had passed away from it before he was born. But these kids were doing fine and the doctors in New York couldn't understand it.
8:45 Speaker 02 Then they decided to look at the DNA of these boys more closely. And what they found out is that in addition to having the inherited disorder, so the mutation that would have caused their immune systems to malfunction, they actually had second corrective mutations that were actually allowing their immune systems to function well. And this isn't just a fluke. So that was with one immunodeficiency, but they found it in patients like, I don't know if people are familiar with Duchenne muscular dystrophy. Now, this is a disorder that's kind of a progressive muscle disease. It's tragic. It's extremely tragic because people die so young. There was a case that, again, in like the 90s,
9:26 Speaker 02 where there was a patient who just wasn't progressing as they thought that he would. And it was very interesting because it was one side of his body was doing better than the other. And then they did the kind of cellular analysis and they found that actually earlier in his development, one of his cells had actually acquired spontaneously a corrective mutation that essentially fixed the muscular issues that would have happened. And it's kind of interesting as case examples, but what you have to understand is that like this then points to new treatments. Some people have called it natural gene therapy.
10:03 Emily Kwong? Oh, yeah, yeah, yeah. Your book talks about natural gene therapy in the context of skin disorders, muscular disorders and anemia, these kinds of spontaneous corrective mutations.
10:11 Speaker 02 It's amazing, right? I mean, I look at our bodies as just completely dynamic. Like, we are not static in any way. It's almost like we're constantly playing the lottery in our cells. And sometimes we get lucky. And I think what we can now do, because we have the DNA sequencing technology, is we can learn from that luck and we can replicate it. And in fact, you and I, our immune systems, benefit from the process of mutation. That's one area in the body where mutations are critical to our health instead of Detrimental.
10:45 Emily Kwong? Yeah, that's a good point. I mean, vaccines are really capitalizing off our ability to mutate, right? They wouldn't work if our cells couldn't do that.
10:51 Speaker 02 Yeah.
10:51 Emily Kwong? So you you write in a different chapter called "The Next Generation," quote, "Most of the time when doctors talk about the risk of genetic problems in parents' reproductive cells, they focus on egg cells. An embryo, of course, comes from an egg cell and a sperm cell when they come together. But scientists have started to look also at sperm cells and how their genetic mutations could shape the embryo. What has research found there?
11:15 Speaker 02 You know, first of all, I want to back up and say, I am a woman who had a child at age 42. And I got a lot of concern amongst the doctors about my age.
11:24 Emily Kwong? Yeah.
11:25 Speaker 02 And it's true that chromosomal abnormalities do increase. So chromosomal abnormalities refer to like the big bundles of DNA that happen in our cells. And sometimes they don't sort so perfectly well if an egg is from a woman who's older.
11:37 Emily Kwong? Yeah.
11:37 Speaker 02 The bulk of new mutations that occur in the reproductive cells that that form our kids, 80% are actually traced to the sperm, not the egg.
11:48 Emily Kwong? 80%? That is a lot. That's like four out of every five mutations.
11:52 Speaker 02 Yeah. And that's because, in part, sperm are not quite as good at defending against mutation as egg cells, it seems, from what scientists have kind of uncovered. So I mean, at the risk of sounding like the doctors who talk to me about my age and my fertility.
12:07 Emily Kwong? Yes.
12:08 Speaker 02 The sperm of a 25-year-old man is the result of around 350 cell divisions. And in contrast, the sperm of a 45-year-old man traced back to more than 750 cell divisions. So it's almost, it's like more than twice the number of cell divisions. And every time there's a cell division, there's opportunity, again, for those mistakes to happen.
12:31 Emily Kwong? Yeah.
12:32 Speaker 02 So the the end story is, the older a man is, the more chance that he has all those mutations. So I think it's more just shifting. The focus not just from women and just kind of placing on everybody to say, "Look, everybody, as they get older, have more mutations in their reproductive cells."
12:49 Emily Kwong? I mean, given that the number of genetic mutations increases with age for everybody, there is kind of an effort by some people to slow down mutations themselves, like, slow down the aging process. How does that work?
13:03 Speaker 02 Well, first of all, I want to mention again what I said earlier, which is like, sleep seems to like, slow down the rise of some mutant cells in our bodies.
13:11 Emily Kwong? So you're like, "I have a very futurist idea to propose to you all. Let's get enough sleep. That could be a really good thing."
13:17 Speaker 02 Yeah, but like, put that aside. There are people who are looking at factors that contribute to longevity. And how is mutation playing a role in that? So, interestingly, centenarians, so people who live 100 years or more, have been found to have like, certain variants of the Cert6 gene, which is involved in DNA repair. So there's companies now looking at all this data and actually trying to kind of explore the idea of slowing our mutation down.
13:50 Emily Kwong? Yeah, I'm curious what you think, because right, you write about these companies in the UK and in the US that are looking at these anti-aging therapies that look for and correct genetic mutations. Do you think that is a worthwhile enterprise for all?
14:04 Speaker 02 I love the idea of having DNA that is repaired. My concern is, how specific can it be? Because, as I was alluding to, our immune cells require mutation in order to make new antibody shapes. So every time we get sick, you might be able to hear, "I'm coming over a cold." So this happened in me recently. I got some kind of bug from my kid who's in daycare. And I'm sure, because I know how the immune system works, that my immune cells were essentially doing that lottery thing. They were pulling that lever, reshuffling their DNA inside them, and coming up with new antibody shapes to fight this pathogen. So my point, going back to the aging question, is that if we slow down mutation in the body,
14:49 Speaker 02 can we be specific enough so we can slow down mutation where we don't want it, but then keep it where we need it? Keep it in the immune cells that are doing DNA changes in order to come up with antibodies that are new? Because that's what we need to truly survive.
15:05 Emily Kwong? Uh huh.
15:05 Speaker 02 We're now grasping that spontaneous mutations in the body
15:09 Emily Kwong? Yeah.
15:10 Speaker 02 are affecting our health. And we're going to just feel so much more empowered when we want to get a handle on this.
15:18 Emily Kwong? Roxanne, this conversation may have changed how I see humans, us. This has been really fantastic.
15:24 Speaker 02 Well, it's been a pleasure mutating with you throughout it.
15:26 Emily Kwong? Oh, the pleasure's mine. I've literally came away changed. This episode was produced by Hannah Chin. It was edited by Rebecca Ramirez and fact checked by Tyler Jones. Jimmy Keely was the audio engineer. I'm Emily Kwong. Thanks for listening to Short Wave, the science podcast from NPR.
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15:52 Emily Kwong? This message comes from Found. Found provides modern business banking with built in bookkeeping, invoices, contractor payments, and tax tools. Categorize expenses, track receipts, invoice clients, and send payments right where you bank. Join the hundreds of thousands who have already streamlined their finances with Found. Open a Found account for free at found.com. That's F-O-U-N-D dot com. Found is a financial technology company, not a bank. Banking services provided by Lead Bank, member FDIC.
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