Sean Carroll's Mindscape: Science, Society, Philosophy, Culture, Arts, and Ideas - 8 | Carl Zimmer on Heredity, DNA, and Editing Genes

Episode Date: August 6, 2018

Our understanding of heredity and genetics is improving at blinding speed. It was only in the year 2000 that scientists obtained the first rough map of the human genome: 3 billion base pairs of DNA with about 20,000 functional genes. Today, you can send a bit of your DNA to companies such as 23andMe and get a report on your personal genome (ancestry, health risks) for about $200. Technologies like CRISPR are allowing scientists to edit genes, not just map them. Science writer Carl Zimmer has been following these advances for years, and has recently written a comprehensive book about heredity: She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity. We talk about how our understanding of heredity has changed over the years, how there is much more to inheritance than simply listing all the information we pass down in our DNA, and what the future might hold in a world where genetic manipulation becomes widespread. [smart_track_player url="http://traffic.libsyn.com/seancarroll/carl-zimmer.mp3" social_gplus="false" social_linkedin="true" social_email="true" hashtag="mindscapepodcast" ] Carl Zimmer is a leading science writer whose work regularly appears in The New York Times, National Geographic, The Atlantic, and elsewhere. He is the author of thirteen books, including a university-level textbook on evolutionary biology. He has been awarded prizes and fellowships by the National Academy of Science, the American Association for the Advancement of Science, and the Guggenheim Foundation, among others. He teaches as an adjunct professor at Yale University. Home page Matter column in The New York Times Yale home page Wikipedia page Amazon author page Talk on Science, Journalism, and Democracy Twitter Download Episode

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See Lowe's.com for details. Visit your nearby Lowe's on West Pico Boulevard in Los Angeles. Hello everyone and welcome to the Minescape podcast. I'm your host, Sean Carroll, and today we're going to be talking about heredity. This is, of course, a very old idea, the idea that there's something inside us, some properties, some features that get passed down through the generations. So we inherited something from our ancestors and we send something down to our descendants. Back in the day, there used to be the thought that royal blood was handed down,

that the right to be the king or the queen or the emperor depended on who your parents were. I suppose there's still countries in which that is the case. But we know a lot more about how heredity really works now than we used to. We know that all of our cells have a little molecule in them called DNA, and that DNA is a little code. It's a chain of letters, AG, CT, that the arrangement of those letters tells us what makes up who we are. Or at least there's a simplistic version of it where you think of DNA is kind of like a blueprint

that if you knew what the DNA was, you could predict exactly what the organism was going to be, maybe even, you know, what kind of food they would like or what kind of occupation they would have later in life. Today we know it's a little bit more complicated than that. There's more going on than just our DNA to make up who we are. Not only nature versus nurture,

but even the nature part is very complicated. There's epigenetics and development factors, there's mitochondrial DNA, there's the expression of different parts of the genes that we have. And so we're in a very, very rapid state of evolution, as it were, in terms of how we think about how heredity works. These days, you can get your genome sequenced. You can send it into a company, pay some money, and they'll tell you something about your genetic heritage. On the horizon, we see the ability to edit genes. We can do it in some ways now, and the ability to do that for human beings. probably is not very far away. So it's natural to imagine, you know, can we design what the next generation of human beings is going to be like? Can we design the animals and plants that make up

the rest of our ecosystem? These are important questions as well as fascinating ones. So we have today Carl Zimmer as our guest. Carl is one of the very best science writers working out there. He's been working and writing about this area of genetics and heredity and DNA for a very long time. You may know Carl through his blogging or his Twitter account, his New York Times column, where you may have heard him on NPR. Now Carl has a major new book out called She Has Her mother's Laugh, The Powers, Perversions, and Potential of Heredity. It's a doorstopper. It's a big one, but it's full of fascinating individual human stories as well as the deep science behind what we know about heredity. So we're going to talk about how heredity works, what we do and don't know about,

it, and most importantly, where the new knowledge that we're gaining every day might take us. It seems very plausible that what we're learning these days might dramatically change how we think about being human beings. So let's go. America's first pledge was freedom. Jeep still carries that fighting spirit. With a Jeep Declaration of Deals, we're pledging our allegiance to the American people with great deals on the luxurious grand Cherokee, with available three-row seating premium craftsmanship and tech that turns every drive into an adventure. Or Jeep Rangler with legendary four-by-four-four capability and open air freedom because freedom deserves the vehicle built to carry it. Jeep,

there's only one. Hurry into your local dealer for the Jeep declaration of deals. Jeep has won more awards over its lifetime than any other SUV branch. Even the Jeep Grill or registered trademarks of FCAUS LLC. Carl Zimmer, welcome to the Mindscape podcast. It's great to talk to you. So now we've known each other virtually, at least online, you know, since the early Halcyon Saladays of the blogging world, right? Isn't that how I got to know you reading your blog and you read mine? Absolutely, yeah, back when blogs were the future. Blogs, yes. Now we're in the future and no one writes blogs anymore.

They delivered us here. Exactly. The future is a journey. We've been through the future and now we're in the post-future. So I couldn't help. You've written this gigantic, magisterial book about heredity, inheritance. She has her mother's laugh and the subtitle, of course, The Power, Perversions and Potential of Heredity.

And while reading it, I can't help but think as a physicist, you know, my goodness, how lucky I am that what I do for a living doesn't really matter to people's lives. Because this is a kind of science that everyone has feelings about, right? Does that come through in your work? Oh, I think that everybody clings to heredity in a profound way. And I see that when I give talks about my book, I mean, I have learned to keep my preparer. remarks fairly short because people just have tons of questions and the questions come from the fact that we use heredity to define who we are and also what is our connection both to the past and to the future. I mean, you can't ask for anything more intimate than that.

Yeah, so the future in terms of our children, our descendants you mean? Sure, absolutely. And also, like, what if we tamper with the heredity of other species? then what is what is left after we're gone? Well, you know, heredity will carry on those sorts of changes into the future. So I think, you know, everyone who is involved in this conversation right now knows a little bit, right? You know, we're not entering and we're not telling people something that they've never heard before, that there's something called DNA in our, you know, cells and it carries some information. So let's try to remember what it was like before we knew that, right? People still had an idea of inheritance and heredity and things being passed down through the blood

even before Darwin and Mendel came along. Right. I mean, it's kind of hard to reconstruct the way people fought in the past, especially when they didn't use the concepts and the words that we use today. And yet, you know, we can start to get some clues about it just by looking back and and trying to piece together. You know, for example, there were ideas about blood, as you say. You know, we still use the word blood to talk about, you know, what we really mean by genes. You know, there's blue blood, for example, you know, like blue blood is something that is like, well, you come from a blue blood family.

In other words, somehow like that is inherited down through the generations, your sort of status. I mean, the irony is, of course, that the. phrase actually comes from a particular time in a particular place. It was in Spain in the 1500s when people in Spain were trying to distinguish themselves from Jews and Muslims. So this is where and this is where the whole issue of race comes from. I mean, literally the word race starts to be used in Spain in this way. And so, you know, when are you talking? What century you said? 1500s, 1400s and into 1500s. And the, so the idea with Blue Blood was that if you were, you know, racially pure,

then someone could see your veins through your translucent skin. And so, you know, you can kind of get these ideas about how in Western society, there were these ways in which we started to define ourselves as, as, being sort of made up of something that was being passed down through the generations. But, you know, really, you know, it wasn't until the 1800s that people like Charles Darwin actually like framed it as a scientific question. Like, okay, there's something, something molecular that is being passed down through the generations and explains why people have these traits that seem to run in,

family. So what is it? So yeah, I mean, Darwin wouldn't have said the word molecular, right? But we know what you mean. There is something that is being given from parents to children. What did, but without genes, without DNA or anything like that, with this basic idea that we inherit from our mothers and our fathers, did anyone ever wonder about the fact that why aren't we always just exactly halfway in between our mothers and our fathers in every trait? There, there clearly seem to be variations around that. Do people in pre-Mendell and DNA worry about this fact? Yeah, I mean, they could see for themselves that these patterns of Haredity were not simple.

They really puzzled over them. Mendel was just in a long line of people who were scratching their heads. And, you know, these were plant breeders. These were animal breeders. In the 1700s, someone named Bens. Bakewell in England became legendary because he created a new breed of sheep. And he did it by carefully breeding different kinds of sheep together and coming up with these rules of his own for how to breed them.

And it was an incredible accomplishment, you know, because, you know, people would breed animals and, you know, like their offspring would be all sort of a mess. They would be like, you know, all this variation when, you know, if you're breeding animals, you all, you want them all to be the same. You know, if you want a particular kind of meat from an animal, you want them all to have that same taste. You want a kind of wool, you want the same wool. So it was a huge puzzle and struggle, and the stakes were enormous. I mean, you know, by the 1700s and 1800s, countries were actually looking at breeding, in other words, heredity as part of their national wealth. You know, if you could breed new crops,

and new livestock, you are going to make your country rich. I love the practicality of it. It reminds me of how thermodynamics, which can be a very abstract and theoretical subject, arose from trying to get better steam engines, right? This is definitely an era where there was a give and take between people with boots on the ground, trying to make better products,

and trying to understand the world better as scientists. Yeah, it is interesting. I mean, because, you know, we assume that everybody must have thought about heredity the way we do and wondered about it the way we do 500 years ago or a thousand years ago, but they just didn't. And it wasn't really until some practical questions drove people to really think carefully about this. And, you know, the other people, in addition to breeders, were psychiatrists in the early 1800s, particularly in France, and also to some extent the United States and elsewhere, psychiatrists were trying to understand

madness. Then they were struck by the fact that when they would do questionnaires for their patients, their patients often had people in their family or more distant relatives who also were institutionalized or maybe they had something that seemed. like a form of madness. And so they said, hmm, so is this a hereditary disease? And if so, how on earth could this be passed down through the generations? And so Darwin actually read a lot of psychiatry when he was developing his own ideas of our heredity. So this connection between heredity and intelligence and madness and thought was there from the very, very beginning. Yeah. A lot of the things that we're talking about right now, people were talking about,

150 or 200 years ago with just as much loudness and passion and conflict. Maybe not just as much because now we have Twitter and they didn't have that there. So that's an amplifier that they didn't have. Yeah, but they had pamphlets, you know? Pamphlets? Yeah, a lot of this stuff would get circulated in things like pamphlets where, you know, you get a new pamphlet every day. Like I feel like Twitter is just an extension of the old traditions of,

pamphlets. So maybe blogging is the past more than the future. There you go. I don't know where podcasting fits in, though. So then we did get to genetics, right, to real genetics, to Mendel. Mendel, by the way, I have to always say this. I went to an Augustinian university, Villanova, and Augustinians have a slight inferiority complex compared to the Jesuits, who are, you know, wonderfully intellectually, have this wonderful intellectual tradition. But we have two really important Augustinians in history. One was Gregor Mendel and the other was Martin Luther. So they weren't always, you know, the best Catholics, but they did affect the world an important way. So Mendel, among other things, he helped sort of pinpoint this discreetness, right, of heredity,

that there could be like, you get this feature or you don't. So there must be somehow, it wasn't just a blending of your two parents. There was some, piece of information, a quantum, a physicist would call it, as being handed down through the generations. Right. Mendelden called them genes. Sometimes the terms he used get translated as factors. So there would be some kind of factor that was in a plant. And there was an almost mathematical beauty to how these factors combined in new offspring and then produced a trait. So just an example that people may recall from high school is that peas can be wrinkled or they can be smooth. And if you cross two wrinkled pea plants together, you're going to get nothing but wrinkled peas.

If you cross two smooth peas together, you might get nothing but smooth peas, and then the next generation after that, smooth peas and smooth peas forever. on the other hand, if you cross a smooth pea and a smooth pea together, you might be surprised to suddenly have a quarter of the peas being wrinkled. And so the fact is that that wrinkled factor can hide because it's what we would now call, well, actually, Mendel called it too, recessive. So, yeah, so that was the first recognition that there was a sort of thinking about heredity with these two kind of distinct parts, the invisible factors that get carried on through the generations and then sort of what you see, what's dynist called the phenotype. This June, the world comes to Los Angeles.

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correct me if I'm wrong, but there was already this new synthesis of genetics and evolutionary biology, natural selection, Darwin. And so the DNA was just sort of figuring out, not just, but it was figuring out what the mechanism of that was. Yeah, that's a beautiful distillation of like 80 years of really rough science. Yes, exactly, yeah. You know, people had known about DNA, really, since the 1800s, but they were kind of like, what is this weird stuff? Sorry, just to make that very clear.

They knew that there was a molecule called DNA. Exactly. If you pulled apart cells, you would find different components. So you'd find some molecules that are known as proteins, that all had a similar chemical composition, and then you would find this stuff that they called nucleic acid, and people just didn't really know what it was for. And actually, even in the mid-1900s,

a lot of people thought proteins were what genes were made of. And it took some elegant experiments to demonstrate. No, actually, if you transfer DNA from one microbe to another, you transfer that trait. The proteins don't matter. And so then once we figured out the structure of DNA, then all of a sudden we can get down to the molecular details of how genes make heredity. possible, in other words, that it's almost like genes are like texts. They're made up of these units where they're like letters made up from a four-letter alphabet. And we have over three billion letters in our DNA and change the letters or cut and paste chunks

of text and you get changes to us. And those changes can be passed down if the DNA is being faithfully copied. Right. And so three billion, three billion base pairs, right, in the human DNA. But we talk about only having like 20,000 genes. So I'm going to ask every biologist I ever talked to on the podcast to explain this because it took me a long while to get it right. But explain the relationship between the base pairs and the DNA and what we call genes. Yeah, it's kind of messy. But, you know, biology is messy. Yeah. So, so, so the, the way that people traditionally think about genes is

a stretch of DNA that encodes a protein. And so, you know, every, every protein is, is encoded by a gene. It is true, although sometimes you get proteins that are made by combining genes together and all sorts of stuff we don't need to get into. But in any case, um, we have, as you say, 20,000 of these protein-coding genes. And they only make up about 1% or 1% or 2% of the human genome. So then the big question is, well, what's all the other stuff? Yes. Yeah.

So some of it, you know, maybe 10% of it has functions of its own. So actually some of them are also genes. It's just that they don't go the full process towards making proteins. You have thousands of genes, we don't know how many, that actually encode RNA molecules. Okay. So you may be used to thinking of RNA as part of the process to make protein. Right.

So RNA, yeah. Go ahead. You got a gene made a DNA. you make a copy an RNA, which is a single-stranded version of DNA, basically. And then you use that RNA as a template for building proteins out of a different set of molecules, called amino acids. And that's true. But it turns out that sometimes our cells will make an RNA molecule, and then that's it.

And that not only that's it, but that RNA molecule has a really important job to do. So for example, in women, women have two X chromosomes. they need to keep one of them shut off or they're going to basically poison themselves with too many proteins from the X chromosome. Men only have one X chromosome. So there are, so there are these RNA molecules that basically wrap around the X chromosome, one of the X chromosomes in women and silence it. And so, you know, we know that at least some of these RNA molecules play an important job. So that's, those are most. more genes, but that still leaves you with a lot of the rest of the genome.

So some of that DNA is really important as kind of genetic switches for turning on and off genes elsewhere in the genome. And then the rest, you know, a lot of it is probably what scientists would scientifically call junk. A lot of them are dead genes. They're genes that have mutated and just are useless now, and we just carry them along. Some of them are actually descend from viruses. So viruses infect our DNA and make copies of themselves that get passed down and just spread all over our genome and bulk it up with all sorts of stuff that we don't actually use.

They also could be codes that were injected by aliens millions of years ago to be activated at some point in the future, right? Yeah, right. Now, I haven't seen the papers on that yet, but maybe you've seen a preprint. I'm giving you jewels here, Carl. You should write the paper. All right. I'm going to get on. I'm going to have the scoop of the century. But it's a good reminder that, you know, we're not intelligently designed. The cell is kind of a mess that has been put together over billions of years. And DNA doesn't care that its job is to encode genes into proteins.

It does whatever it wants to do. So whatever it needs to do to make things function. So some of the DNA is making proteins, some of it's making RNA that will do something, some of it's just going along for the ride because it keeps getting copied all the time, right? Yeah, I mean, it's hard to believe that the cell is a lot sloppier than we think of it as being. You know, a lot of DNA actually is used by ourselves to produce RNA molecules, and then the cell just immediately shreds all that RNA, because those were just sort of accidental. They were just not, they didn't really have any function.

So you can have junk DNA shooting off RNA molecules, but they don't serve any purpose. So they just, you know, the cell just sort of like manages this chaos, you know, by having certain proteins that kind of go around and say like, are you supposed to be here? And, you know, if not, then they just shred them and just recycle it to make more RNA. molecules. So yeah, it's not, it's, it's, if you really get to know cells, intelligent design

becomes kind of laughable. And so, okay, so we have this idea that the coding parts, there, there are parts of the DNA, stretches of DNA, many, many base pairs at once that will code into a protein. There's probably an informal and incorrect idea. I'm sure none of our extremely sophisticated and well-educated mindscape listeners would have this idea, but some people might think that there's a direct map from a gene to a trait to, you know, how big our nose are, what color our hair is, or how, you know, charismatic we are. But it's more complicated than that, right? For the most part, yeah, it is more complicated. I mean, you know, we, it's good to learn about Mendel in high school, but, you know, I do think that it's going to be important for, you know,

for schools to take students beyond Mendel, now that people are getting their DNA tested by companies like 23 and me, you can't really understand those test results if you're just relying on P-plan experiments. Right. You know, you're, you know, your blood type, sure, it's like, you know, there's one gene

and there are different versions of the gene and that can determine your blood type. Okay, no problem. But for most of the terms, that we actually really care about or think about. And even seemingly simple ones like height, they are influenced by many, many, many, many, many different genes. And so that, yeah, you can't say that, oh, I have, do I have the tall gene? It's just meaningless. So we brought ourselves up to about, as you infer, imply, the level of high school biology, you know, what people sort of

remember we have a DNA, we pass it along. And I think that even if there's some complicated, nonlinear map from the genes in our DNA to our traits, people still have this idea that basically there's a molecule, the DNA. And from the molecule, that's us. That just makes us, right? But we know a lot more than that now also, right? I mean, there's various ways in which the thing that we turn into is more than just what's encoded in our DNA. any straightforward way. Is that an accurate statement? Yeah, yeah, definitely. And, and, you know, when we, I mean, I, it's funny, you know, like, if, if you say to someone, oh, you have two eyes,

you must have gotten your two eyes from your parents. They're going to look at you funny. Like, what? That doesn't make sense. You know, and the fact is that you do get, you did get your two eyes from your parents. But when we, when we talk about, oh, you got this, you got that from your parents, we're really more interested in the things that are different between people so that we can say like, oh, you are tall and your great uncle Bertie was tall. So you must have gone in from him, even though, of course, Bertie is off to the side. Whatever. My point being that we just get kind of confused about what it is that we're talking about when we talk about. about these traits. And the fact is that, you know, you might be tall like your uncle Bertie is tall. Sure, partly because of the genes you inherit.

But, you know, maybe you and your uncle Bertie also had the privilege of growing up in an affluent society, an affluent family. You had good diets. You got medicine when you were a kid. and so that you have the opportunity to grow to be tall. Because the fact is that all over the world, the average height of people is several inches higher than it was a century ago. And that's not because we are now inheriting a different set of genes. It's just that in that respect, the world got to be a better place.

And so you have to sort of take into account the, the combined influences of genes and environment, or actually, as Shakespeare once called it, nature and nurture. We'll get there, but I think that even at the level of nature, even at the level of our inheritance, our genetic inheritance, I'm learning about, from your book, among other places, how complicated that is.

For example, the idea of mitochondrial DNA, right? We have these little sort of genetic stowaways in every single one, of our cells and we hand them down to subsequent generations. That's right. That's right. So, yeah, even if you just limit yourself to genes, heredity can be a lot more complicated and strange than we learned about. So mitochondria, we have dozens or hundreds of them in every cell, and we depend on them for our survival. They're the little factories that generate fuel for our cell, you know, using oxygen and various nutrients to build, to build fuel that we then burn.

They do lots of other stuff, too. So we're great. Yeah, absolutely. And the weird thing about them, well, several weird things. One is that they've got their own DNA in them. That's aside from the DNA that's tucked away in the nucleus. So they've all got their own DNA. And if you look at a cell, you can actually watch mitochondria divide on their own.

And they make new copies of their own DNA for those new daughter cells. And you might say like, whoa, that doesn't make sense. That sounds like bacteria. And it's like, yeah, guess what? They're bacteria. Exactly. Like about 1.8 billion years ago when we were single cell, the ancestors of mitochondria somehow ended up inside of ourselves and maybe some kind of symbiotic relationship.

Kind of like, you know, cleaner fish that go inside the mouths of bigger fish. And then they became basically permanent residence so that they couldn't live outside of ourselves anymore. And as if that wasn't weird enough, you know, when a sperm approaches an egg, it's swimming furiously. And it's using that mitochondria to generate that fuel to swim. So the only way you can get to an egg is to use its mitochondria, and then it reaches the egg, and it dumps in its chromosomes, but then it also destroys its own mitochondria. It just rips them apart. So both the sperm and the egg have separate mitochondria from dad and mom.

Right. And the sperm do not deliver their mitochondria into the egg. Lazy bastards. Well, it's puzzling because, you know, we are, when you look at our chromosomes, we are a 50-50 split between our parents. But you look at our mitochondria, it's all mom, it's just all mom. So mitochondrial inheritance is not sexual reproduction? Exactly, exactly. For some reason, we keep out one of the from that process. And it's interesting because what that means is that, you know,

your mitochondria is extremely similar to your mothers and your grandmothers and so on and so on and so on. Because, you know, with your chromosomes, in every generation, the pairs of chromosomes, they shuffle some of their DNA together. Right. And so they swap pieces in this process called meiosis. And so after several generations, you know, your chromosome number two doesn't really look all that much like your great, great, great, great grandmother's chromosome two. But mitochondria basically the same.

And so they're really powerful for tracing genealogy, for example. You know, you can say like, aha, well, this person has to be the child of this woman. I mean, there's just, you know, two ways about it. And, and yeah, it's a, it's a, you know, scientists who are just looking at the basic questions about heredity. You're like, why, why is this? Why would the sperm not give the mitochondria? Why is it only the mothers? And there are some interesting theories about it.

I mean, one theory is that if you have two batches of mitochondria inside a person coming from different people, they're going to not play well together, that they're going to operate differently and that could actually cause problems. I mean, that makes sense, right? When we, when we, when meiosis happens, meiosis is the splitting of this cell into, a little sexual reproduction cell, right? So, you know, we split our genome in half, and then they're going to recombine with the half from the other parent, and the mitochondria kind of aren't participating in that process. So it's, you know, dad's mitochondria and moms are just there separately,

and they might come into conflict, like you say. Right, right. And, you know, there are, there are, there are, it's interesting, you know, we think of sort of mom and dad's genes as, you know, playing nicely in our own genome. But, you know, there are conflicts between the genes in our parents, evolutionary conflicts. Sometimes there's conflicts between our actual parents, too.

Yeah, and now think about it inside our DNA, you know. You know, sometimes there'll be like, you know, dad's genes are maybe sort of driving kids to grow faster because that's good for the father's long-term evolutionary benefit. The mother, meanwhile, if the mother has to carry the children, like it has to be pregnant, like too much growth is actually like can really drain her resources and may mean that she has fewer children over her lifetime. And so you will actually find that the man's copy of a gene is turned on, a woman's copy

is turned off inside the child. So it's like this tug of war going on. Sure. just to try to, that finds a sort of optimal thing. And then sometimes you actually find, there are genes or pieces of DNA that basically just totally break Mendel's law completely and just sort of override that sort of 50-50 kind of split between which chromosome ends up, you know, in an egg or a sperm.

this was illustrated with a discovery once of certain kinds of flies, certain strains of flies that were, they would almost always produce daughters. And scientists are like, what's going on here? And it turned out that there was a gene that was basically hijack, was sitting on the female chromosome in flies and was sort of basically ensuring that these flies, did not have any sons because if there were just daughters, I would spread this gene further,

sort of the ultimate selfish gene. Well, this makes sense, right? I mean, maybe it makes sense. Maybe I'm leaping ahead too far. But we have this kind of game theoretic way of thinking about not just the struggle to survive as organisms, but we can, in the selfish gene way of thinking, think of it as the individual genomes trying to pass themselves down. And, you know, mom has a genetic set of information, and so does dad.

And they both want to win. And in human beings and mammals, there's this rough equilibrium that we've reached where children are 50, 50, male and female. But that's certainly not universal across the animal kingdom. There's a sort of different equilibrium you might imagine reaching where the struggle plays out in different ways. Sure. And actually, there are some animals that adjust the ratio of their offspring.

just depending on what their environment kind of looks like. So there are birds that, you know, in effect, what they're doing is looking around and saying, like, I think I need a lot of daughters to stick around and to help me raise, you know, my other chicks. And voila, incredibly, they produce more daughters and sons. And then there are other situations that they produce more sons than daughters, you know, and then the sons fly off. So, yeah, I mean, it's, we, you know, we like to think about, we like to take biology and put it into categories and try to come up with absolutes. So, you know, Mendel's observations become Mendel's law.

Or males and females become these sort of absolute categories that, you know, you could never have any exception to. I mean, we keep doing that. I think we just have very, you know, brains that really like categories, but, you know, heredity just does not work like that. Yeah. And, you know, yeah, there are some patterns that kind of repeat themselves a lot, but a lot of times those patterns are this sort of a stable balance produced by competition that sort of works out into this almost like a daint.

Well, I talked with Alice Drager in episode three of the podcast. and we talked about intersexuality and how the fact that the idea there's two sexes, right? That's a convenient fiction. It's very useful. It's a good approximation, but if you're going to try to be a little bit more careful,

there's a whole bunch of stuff in between and different ways you can be in between. And this reflects, I think that philosophically, this is just a really important point that you're bringing up, that we organize the world, be human beings for our comprehension because it's easy for us.

But as we try to be more and more accurate, all those complications are going to become more and more relevant to a better understanding. Yeah, and I noticed that a lot of times people will justify these absolute categories by saying, like, well, look, like, this is just nature. You know, this is biology. You have to just accept biology. And I'm like, whoa, like, you want to talk about biology?

Let's take a little tour, shall we? Through my 600-page book on inheritance. Absolutely, absolutely. I mean, the fact is that heredity itself, works very differently in a lot of different organisms. And, you know, the irony is that like this is one reason why Mendel was forgotten, actually. So this is one of these incredible ironies is that Mendel studied peas. And he was like, oh, my gosh, look at this mathematical thing that's happening.

And he wrote to one of his mentors and his mentors like, hmm, that's, interesting. I'm not sure what to make of this, but why do you see if you can replicate this? You know, like if this is what you say it is, then you ought to be able to find it in another plant, right? So Mendel, I guess, agreed with that. Anyone studied another common garden plant? And it turned out that this other one, hawkweed, I think, I forget the name now. It doesn't reproduce in the neat sort of sexual way that peas do. It has pollen. And pollen is sort of like the plant equivalent of sperm.

So they have male and female gametes. And you have to have fertilization. But in these other plants, once fertilization happens, the ovules, the eggs, as it were, just basically just kick out any male DNA. They don't use it. So they do myosis, you know, within their own genes. And so they're kind of like clones, except that they're sort of shuffling their DNA with every generation.

So, you know, like, boom, like those lovely three to one patterns that Mendel saw with peas, they're just not there at all when it looks at another species. And then it's like, huh. And, you know, you imagine if he had picked another species that was very neat about, you know, worked like peas did, that he might have gained more traction. But no, I mean, he was forgotten for basically 50 years. It's good to know that the deflationary role of mentors has not changed in academia over the centuries. I think I've done that to my students sometimes.

So I love the idea that mitochondria as important as they are, these stoaways. I mean, they're basically living their own lives. right, they're handing down their own genetic inheritance, and it's part of what makes us who we are and so forth. Are there other examples of that? I mean, I know that we carry around a whole microbiome, a whole set of little monocelular organisms that function in us. But my impression is that we kind of build those up throughout our lives. We don't actually get those from mom and dad. Well, you know, that is a big question right now.

And, you know, there are people who are trying to really nail that down at the moment. Because, you know, it is true that you pick up microbes every day. You're picking them up off your keyboard and your doorknob and you're shaking hands or, you know, you're having yogurt. I mean, like, we're just, yeah, we're just swimming through a microbial ocean. And by you, you don't mean me in particular. You mean all of the listeners out. It's not my keyboarded. that is worse than average, right?

Well, I've heard things. No. So the thing is that we also know that there are lots of species that pass down certain microbes as faithfully as they do their own genes. And my favorite example is cockroaches. Okay. So cockroaches actually depend on. one species of bacteria to help them to eat food because the bacteria can actually make some of the

compounds they need for proteins out of their food. The cockroaches don't have the genes to do it. So they totally depend on these bacteria. In fact, they actually build special little organs for these bacteria to live in. And the bacteria actually like embedded inside the cockroach's own cells in this organ. And when it comes time for the female, male to produce her eggs, something incredible happens. Some of these cells that carry these microbes, they just start crawling and they make their way through the cockroach's body to the cockroach's eggs. And then they open up and they basically deliver these bacteria into the eggs. And so after these eggs get fertilized by a male cockroach, then the cockroach is born with these

bacteria ready to go, just like we are with our mitochondria. Biology is very scary. It's mind-blowing. And the best book on all of this is Ed Young's book, I contain multitudes. For me, what interests me in particular about this is to think about this as another form of heredity, another channel of heredity. It's like you've got your own genes, quote unquote, but then you have these bacteria. Yeah.

Now, we don't have anything quite like that except for mitochondria that we know of. We know of. Right. But maybe there is something like heredity in the way that some of our bacteria end up inside of us. Scientists are trying to figure out, for example, are human embryos sterile when they're in the uterus? The evidence is not clear. What is clear is that as a baby moves through the birth canal during delivery, it gets slathered in bacteria. And some of that bacteria goes into its gut. And there are certain forms of bacteria that the mother encourages to grow in the birth canal.

And not only that, but the mother. mother's milk contains bacteria as well, as well as bacteria food. In other words, sugars that in the milk that babies can't digest themselves, but bacteria can't. So there is a debate right now, whether there might be, you know, certain species that are being put into babies early on and sort of are kind of define our own species that way. It's a very romantic picture you are painting, the miracle of childbirth. is so enhanced by our scientific understanding. It's really great. Well, but it raises some very practical medical questions.

Sure. Cesarian sections are exploding in countries like the United States. And so, you know, so those babies are not getting that exposure. And so there's a question of like, well, does that matter? You know, can you still pick up those species just by being handled by your parents and other people? Or does that not getting that seeding at the beginning, is that a problem? Because, you know, if your microbiome isn't quite right when you're young, that can lead to problems throughout your life. Your immune system may not work properly, for example. Is it still thought to be true that the number of unicellular organisms in our microbiome is more cells than human cells in our body?

Actually, no. I heard rumors that that had gone away, that thought. Yeah, yeah. So, you know, I and other people had, when we'd write about the microbiome, we always say, like, you know, your microbes outnumber your own cells by 10 to 1, which, you know, it's always fun to say. It turns out probably not to be true. It's just, it's probably more like one to one. So we have about 37 trillion cells of our own, or quote unquote, own human cells. It might be around the same, you know, I don't know, 30, 40 million bacteria.

You know, I don't, that doesn't count the viruses and the fungi and all the other fun critters that are living inside of us. So, you know, the final number of the full microbiome might be higher, but it's not a tend to one thing anymore. But a body, a biological body, is a complicated open system. It's a, it's a ecosystem all by itself. It's a, we're a little bus that is carrying around, you know, a whole world of little critters talking to each other and evolving and doing their own things. Yes, but it's not a totally random collection of critters. You know, like the same species and the same strains tend to turn up again and again in people. And I mean, your microbiome is going to be

different than mine, but not too differently. You know, and so you can, like, if you look at human microbiomes compared to like a chimpanzees, they're going to be a lot more similar to each other than chimpanzees are. And it seems like there are, we have filters. Right. You know, so not everybody gets to see it in the bus. then there's also the idea that we're learning more and more that just the information in our DNA, even just getting back to the sort of genetic part of inheritance, there's more to it. There's more to how we pass information down. There's the whole story of epigenetics and so forth.

I hear that you're advocating that people take epigenetic yoga classes so they can pass down new things that they learn to their children. is that right? Many people are saying that. Right. No, I'm... I hear people saying it. Yeah.

Yeah, right, right. No, I think you should, you know, take epigenetic yoga if you like it, but don't think that your kids are going to be better for it. But the idea is that we can learn something and pass it down, right? Yeah, that we could have an experience that alters how our genes work, and that alteration can get passed down to future generations. That's the crux of epigenetics and heredity. And it's tricky.

And I explore it in my book. And there's definitely good evidence for it happening in plants. It's good evidence for it happening in little teeny tiny worms. When you get to mice, there's some very ten. analyzing experiments. I mean, so for example, there was one experiment where scientists would expose male mice to a certain odor and then give them a shock. And then they learned us to associate the odor with the shock. And then they took sperm from the mice and used it in vitro fertilization and then produced mouse pups. And it seems like the mice in the next generation kind of responded

oddly to that same odor. And so the claim was that somehow that learned memory, that learned association about that smell got passed down to the mouse pops. You know, and when that paper came out, the journal put Lamarck on the cover. Remind us who Lamarck is, Mr. Lamarck. Mr. Lamarck.

So, right, so Lamarck was a French biologist who proceeded. Darwin. He was most active in the early 1800s and came up with his own theory of evolution, which depended a lot on what's known as the inheritance of acquired traits. And so he had a classic example that giraffs stretch their neck to reach leaves. There's some sort of nervous fluid. that causes their necks to get a little bit longer. You can think about it, that like building up muscles. And then those giraffes would pass down that longer neck to their descendants.

And so then over many generations, the drafts would adapt their environment by getting a longer neck. And so, you know, the claim, I guess, is that, well, mice, you know, are adapting to their environment by learning about. you know, the risks that they face and that their osping are inheriting that knowledge. Right. So that's the basic idea. And how would this work sort of at the molecular level for the mice? Is it pups? You call them mice pups, mice babies or puppies?

Okay. I learned something. So it's a matter of obviously the DNA are not being altered as you, as you smell something. Your DNA is still your DNA. But somehow there's information being passed down to the next generation. that is not in the DNA. It's somehow in the chemical makeup of what goes into making a little puppy. Yeah, yeah.

I don't think, if you call them mouse puppies at a biology conference, people will probably look at you funny. You think that people will see through me and not realize I'm not a biologist? There's an imposter in our ranks. That's a cosmologist, get him out. yeah. So, we know that genes are attended to by lots of molecules in the cell. You know, genes just don't take care of themselves. And so there are proteins, for example, that will clamp on to genes and they can essentially shut them down. There are other places that protein, genes latch on to DNA and they can switch on a gene. You can coil DNA around spools and then basically

anything that gets coiled up, any gene just can't be used to make a protein because it's just all tucked away. And so, and those changes can be very long lasting. Like when a cell divides, those same controls will, in effect, be inherited by the two new cells. So that's why your skin cells, when they divide, they make skin cells. They don't, you know, make brain cells or tooth cells or something. You know, like, so we know that epigenetics really matters a lot. There's no question about that. And so the question is, could these kinds of processes, you know, change the way that genes

are being used? And then could those changes, you know, those proteins and those coils or whatever, get passed down through the generations. We don't know. The mechanism for it, especially for mammals, it's kind of hard to figure out how the mechanism would actually work.

And you look at a mouse experiment. I mean, the critics of this kind of researcher says like, whoa, so you're telling me that there's this change that is happening in the mouse's brain, the daddy mouse's brain, And that somehow then that is getting communicated into Daddy Mouse's sperm. And then somehow that is then making its way through fertilization, through the development of an embryo, through the development of a brain,

and then somehow it's getting plugged back into the brain in the same circuits that Daddy had being altered. And a lot of scientists just say like, whoa, that doesn't make any sense at all. Right. But this is something that's being studied. We'll try to figure it out. Yeah, but in the meantime, there's epigenetic yoga. Like, you know, there are literally like psychiatrists who will help you to undo the epigenetic trauma of you that your grandparents pass down to you. Like, this has totally saturated pop culture.

And I don't honestly know how it happened because, you know, epigenetics is messy and complicated and the language is totally inscrutable. And yet, you know, when I get a lot of it. give talks, like half the questions I get after the talks are, what about epigenetics? Look, I'm writing a book about quantum mechanics. So the idea that crazy, abstract ideas are going to be hijacked by popular culture is not foreign to me. Any tips? Well, quantum epigenetic yoga might be a bestseller, right? Oh my God. That's it. Throw dark energy in there and we'll be buying yachts any moment. So, okay, we need to, we need to patent that idea right now. Okay. Author, I will edit this out with the podcast, so no one hears it and steals our great idea.

It sounds like, though, even in principle, if you handed a computer a complete list of the three billion base pairs in our DNA, the GCTA letters in our alphabet, a computer with perfect knowledge, that would not be enough to predict what the organism would look like. I mean, it would be missing the mitochondrial DNA. It would be missing all sorts of chemical signals that could be passed down through the body. But, I mean, so it sounds like we're learning how much of the organism is predicted by that. Probably a lot, right, but certainly not the whole thing. Yeah. And in a way, this is one of those deep questions in the history of biology. You know, how much of an organism is basically determined

at the very beginning and how much of an organism's end result is just the emergence through development, you know, through, and, you know, it, you know, as always the answer is both, but it's complicated, you know, in the sense that you, there are a lot of things that you can predict based on DNA. Those predictions may, are not like, you know, I can't like predict what color shoes you're wearing right now today based on your DNA, Sean. But I bet if I looked at your DNA, I could get a pretty good idea what your eye color is. And I might be able to, you know, make some very crude predictions about the influence of your genes on your height. I couldn't tell you how tall you are, because I don't know if your parents, you know, fed you properly.

But, you know, there are things that you can predict out of DNA. But then there's this, you know, the DNA makes, you know, the cells make proteins and RNA molecules from the genes, and the cells are talking to each other, and they're taking in cues from the environment, cells are migrating through the body, and all sorts of crazy stuff is happening. And the genes are responding to all of that. And that is how we end up the way we are. So, yeah, so, you know, if someone, you know, I had my genome sequence.

I'm sure nobody could make any predictions about me from that. Right. I do want to, that's right, I remember this from the book. So when you say you had your genome sequenced, so like you're special here because you really had the full blown treatment. If people do Ancestry.com or 23 and Me or any of these things, they, get a little bit of information about their genome, but they do not get a list of three billion ACGTs, right? I mean, they get some sub-knowledge of that. Do you actually have a printout of, you know, all three billion base pairs in your DNA? I do not have a printout. I have a hard drive.

Okay. Metaphorical. I was being metaphorical. Yeah. Well, if I printed it out, it would, you know, fill up, you know, dozens and dozens of books. I mean, it would be a fun art project, but... You can use a small font, it's okay. Yeah, right. And it would be kind of hard to, you know, do a search function on that. So I prefer to have it on that hard drive because then I can take it to scientists and say like, okay, you know, let's play around with this data here, which just so happens to be my genome.

And show me how you discover things in human genomes by analyzing this sort of data. And it's been a fascinating experience. but it is a very different thing than getting your DNA sequence from a place like 23 and me. What 23 and me your ancestry does is they do something called genotyping. So basically they look at maybe a million markers, a million spots throughout your genome, and they try to, they look at see, well, which variant do you have at that particular spot? And so it's, you know, it's kind of a high-level survey of your genome, but you can learn an awful lot. One of the reasons you can learn an awful lot is because we pass, we tend to, like, share similar stretches of DNA.

So if you've got, you know, a string of variance all in a row, chances are that that whole segment of DNA is identical to somebody else that has those same variants. And so you can infer a lot about what's in between those markers. When you get your whole genome sequence, that means that you're trying to figure out as best as you can every single letter in your genome. And with that, you can discover all sorts of deeper things about your genome. Well, and one of the deeper things you could discover is that you are susceptible or even almost inevitably going to have some disease that might affect you at a certain time of your life. And so there's this question of, what do we want to know?

Like, if you could, the philosophers would come in and instantly say, the version of the question to ask is, if you could know you were going to die on exactly a certain day, would you want to know that? Is that information you want? Some much cruder version of that might be available through this looking at our genomes. That information is really only available to a small fraction of the people who get their DNA genotyped or get their genome sequenced because the genes that really have a strong impact on your health. Let's say we're talking about genes that cause hunting disease or genes that raise your risk dramatically. of getting early onset Alzheimer's,

genes that dramatically raise your risk of getting certain forms of cancer. These are rare. Right. You know, natural selection is not fond of these genes. For all these reasons. So therefore they're rare. And so, you know, when I got my genome sequence, the first part of it was doing it.

I did it as part of a conference. And I think there were like 40 people who were going to this conference who also got their genome sequenced. They weren't getting the raw data, but they were getting these interpretations from clinical geneticists. And there were like 40 of us. And if I recall correctly, maybe like five people were told like, okay, you know, we're going to sit down with a genetics counselor and make some plans for you to talk to your doctor because there's something you need to know about. How's your life insurance plan looking? Yeah, right, right. I mean, for the rest of us, it was like, man, you know, like you don't have anything that really,

you don't have anything that really jumps out, you know, is what they would say. You know, there's nothing where it's like, hey, that gene, that's big trouble. Now, you know, I have plenty of genes that have been associated with, you know, raising my risk of this disease or that by some modest amount. But that doesn't mean that I'm going to die of any of those. diseases. I mean, also have variants that lower the risk for certain diseases, too. And so, um, so, so, you know, and that's, you know, that is going to be how most people are going to, uh, find what that's most people are going to find when they, when they get their DNA sequenced.

And it's going to be, um, either, you know, there, a lot, I'm concerned that people not make one of two mistakes. One mistake is to be like sort of angry and irritated that they didn't find anything in their genome. You know, it's like, really? Like my genome is much more interesting than you're making it out to be. Yes. Well, you know, like this isn't like a status thing. Like it's not like you want to go to the doctor's office and get terrible news, you know, and like it's not like you feel like you're, you should feel happy if they say, oh, you're fine. See you later. And also, the flip side of that is that sometimes people will get in these reports or maybe do their own research and discover they have a gene that is associated with some disease.

Let's just say like colon cancer. And they say, oh, my God, that's it. I'm going to dive colon cancer. Like, no, no, no. You like think you have to dig down that extra level and say, like, well, what exactly did this study find? you know, like, do you, do it find that like people who had this variant had, you know, a slightly higher risk of this disease? Yeah.

And also, like, how big was the study? Like if a lot of these studies, when they're preliminary, it's just like 100 people. They're tiny. And, you know, tiny studies are often wrong. And so there are plenty of mutations that were thought originally to cause diseases that we now no, do not. So, you know, you've got to think about all these things when you're looking at these results. And that kind of gets back to me and my, how I feel that like our high school, grade school genetics has just got to step up its game because these things are not just

abstractions that you learn about in high school, never think about again. People are getting these results in their email inbox. Right. But also, isn't it, isn't it maybe an antiquated kind of worry because recently I bought new running shoes. So I went to the Nike website and they let you actually customize your own shoes. Like what color is the front and what logo is on the bottom and stuff like that. So within a couple generations, we'll have a website for doing that for our babies, right? We'll just be able to pick what different features we want them to have, edit the DNA and get whatever baby we want. I am sure that there will be people who are offering that. if the laws allow.

I don't think that you will get the baby of your dreams. I think your baby will just be your baby and will be subject to all the vagaries of experience and biology and all the rest of it. But we already have all sorts of companies out there that are offering really dubious claims based on looking at your DNA. They'll look at a few variants and they'll say,

aha, like here's your special, you know, exercise program. Or here's your special DNA diet. Or there's even a company that called Vynome. I don't know if you've seen them. No. They will recommend wine to you based on your DNA. Sorry, how do you spell that? I actually have to look this up.

Yeah, yeah, please do. I-N-O-M-E-V-O-M-E. All right. Could be a podcast sponsor down the road. I like it. Well, yeah. You may not want to play this episode because, I mean, when I saw a video for it, I just thought, well, this is, wait, is this the onion? I'm, this, this can't be real, but it was.

And, you know, like, I mean, all these companies seem to be doing as far as I can tell is, you know, looking. looking in the scientific literature and saying like, you know, oh, do, you know, here's a variant where people who had it tended to report a stronger sensation for bitter tastes than people who didn't. Right. And then going from that to saying like, here, take this peanut noir. And, you know, with exercise, it's a very similar thing. I mean, yeah, sure.

There are genes that are associated with all sorts of aspects of exercise. you know, the power in your muscles or how much oxygen you take in and so on. And I'm sure that, like, there is a genetic element to great athletes being great. But, you know, when I got my genome sequenced, the company that gave me that first sort of, first layer of results before I took matters into my own hand, they actually said, like, your muscles are. built for power. I was like... Sorry, I do not mean to laugh. I was laughing at something completely separate

that was happening here in the room. I'm sure, I'm sure. No, it's okay, Sean. I mean, you've bet me. And I mean, like anybody who has met me knows that my muscles are not built for power. I mean, it's just not the case. And, you know, but what they were doing

is they were just looking at this one variant in these limited number of studies and not taking into account all the other genes that influence our muscles, many of which we don't really understand. So, yeah, there's, so I do worry about, you know, letting, letting folks like that who run these companies do the same thing with, you know, designing babies. Well, tell us a little bit, though, about CRISPR and the reality of gene editing. It is something that is rushing at us very, very quickly, right?

Yeah, yeah. I mean, I only became aware of CRISPR maybe six years ago or something. And I can remember thinking, I mean, at first, I was sort of puzzled by it because actually CRISPR was, it's natural thing. What it is is basically an immune system for bacteria. They make molecules that can essentially store information about virus. and then use that information to create new molecules that could zero in on particular stretches of virus DNA and cut it. And I thought, wow, that's cool.

I mean, microbes never cease to amaze me. But then some scientists said, hmm, well, we could use that. And we could maybe cut whatever DNA we want. And lo and behold, they could. They could zero in on particular stretches of DNA and make cuts. and then substitute in new DNA. And all of a sudden, they had this very powerful new molecular tool at their disposal. You know, scientists use CRISPR all the time now to do experiments.

You know, they might say, like, we want to know, you know, which cell, I'm sorry, we want to know, you know, which genes in a cancer cell are essential for it to survive as a cancer cell. So they would just use CRISPR to systematically cut out. every single gene in individual cell lines and just see which one survive as cancer. You just couldn't do that before. I mean, so the impact is unbelievable. And then people are starting to say, like, well, can we use this to alter the genes of crops or of animals?

And the answer is, hell yeah. And so the next step is, well, what can we do for people? And one of the things you can potentially do for people is treat hereditary diseases. So if someone has sickle cell anemia, you take some of their bone marrow cells out, these stem cells that can make blood. You tweak their DNA so that they can now make hemoglobin that they need, you know, the proper kind of hemoglobin because sickle cell anemia is caused by a misshaping kind of hemoglobin. And you put the cells back in.

into people and they make healthy blood cells. That's the hope. And there are clinical trials that could start very soon on that. And then the big frontier, the one that, you know, understandably everybody gets excited and scared about is what if you could use these on embryos and change genes in embryos and then you are creating an inherited change that will be passed down through the generations. Right. Yeah, they're going to do it, right? It's going to, I mean, so there's no, you know, I have kind of an extremist point of view

on this because people say, people raise this question that you just raised. You know, can we genetically edit what's going on in embryo and therefore change what the person is going to be like? And there's a sort of instant reluctance, right? It's like, well, of course, that would be bad, or at least it might be bad. We should think about it. We should really be very careful. But I'm not quite sure where the reluctance comes from other than a sort of squickiness, right?

A sort of feeling that we're messing with nature. And what I suspect is that some people will feel that way. Some people will not feel that way. And it's absolutely 100% going to happen. And 100 years from now, the idea of just making a baby by, randomly picking half of the DNA from mom and half the DNA from dad and hoping for the best will seem hopelessly barbaric. Well, you know, you and I are going to have to, you know, hope that, you know, life extension

anti-aging drugs advance really quickly so that we can make a bet and see if it pans out, you know. Yeah. But, you know, I have thought about these. scenarios a lot. Partly they're just fun to think about. And it's and you know, it's, it's, it's what science fiction writers do so well.

And, you know, I, there are a lot of questions I have. I mean, I don't, I, I, I'm not as sanguine, maybe is the word, as you are. Like in the sense that, so for starters, like CRISPR, like, CRISPR is, is indeed revolutionary, but it's turning out to have some problems. Because it's, it's, it's, it's, it's, people call it gene editing, but it's editing that

involves chopping DNA. And that is a pretty radical thing to do to DNA. And cells don't like it. I mean, the cells actually have all sorts of defenses against chopping up DNA because it can lead to all sorts of damage that can ultimately cause a cell's descendants to become cancerous, for example. And not only, so, you know, there are concerns about just how safe CRISPR would be in terms of, like, creating a line of cells you'd want to put in your body through CRISPR.

Like, you don't want to put in cells that are going to be more prone to cancer. That's problem number one. Problem number two, there's a recent study. that showed that sometimes when scientists try to cut one particular segment of DNA out, they cut out a long stretch that includes that particular target. And so you might be cutting out pieces of DNA that you really need. And maybe when the DNA is getting repaired, it gets kind of shuffled around in ways it could be a problem.

So, okay, so there's the safety issue and then, then also there's kind of like the logistics issue, you know, like, you know, if you're saying, I mean, you know, you're saying like, oh, this is barbaric. So you're imagining a world where, are you imagining a world where all, say, nine billion people all get in vitro fertilization? You know, I mean, feature fertilization is a very difficult drawn out process right now. It could get a lot better in the future, but, you know, maybe not. Maybe there are some inherent sort of limits to do this. It's not, so my point is like, Chris, it wouldn't be Chris, you wouldn't have, CRISPR alone would not deliver you into that science fiction future. You'd have to have all sorts of other advances in reproductive technology and stem cell research and all the rest of it before this could even be possible. But I have talked to biologists who say, you know, we're going to look at, we're going to look at CRISPR like vaccination in the future.

Right. Yeah. So I think I get absolutely the fact that it's not within the next five years or ten years, right? We will have to extend our lives if we're going to see this thing come true. And I'm also not sanguine in the sense that I think that it's going to be an unalloyed good. I look at, you know, this editing of our children's genomes as something. It's a technology. It's like cars or Twitter, right? There's going to be good parts about it or bad parts about it. I just think it's inevitable. I just think that it's like we have jumped off of a pier into the ocean. And as we

fall in, we're debating should we get wet or not. And that's just not a debate that is very reasonable to have. We can have other debates. Should we swim for shore? Should we try to climb back up the pier? should we fight off the sharks? But I think it's going to happen and people are going to be trying to alter their children's intelligence and skin color and size of their noses and everything. And I think that we're kind of dropping the ball

a little bit on dealing with what the implications of that really are going to be. Well, I mean, I guess the question becomes, you know, if people really are going to try to do this if they can, then, you know, should we pass laws to prevent that? Or do we have, do we put regulations in place to allow certain uses of it for certain things? And then really you're shifting from a scientific question to a social or a political one.

You know, for example, with, we're dealing with that right now, actually. I mean, people don't realize it, but, you know, genetically engineering humans has already begun. because, you know, some, we were talking about mitochondria before. Like, so mutations can cause mitochondria to become defective. And so women can pass down defective mitochondria to their children, and you can get these mitochondrial diseases, which can be quite devastating. There are all sorts of different ones that emerge from faulty mitochondria. So some years ago, people thought, well, what if we were to,

do a transplant, an egg transplant, take the DNA in the nucleus of an egg and put it into a donor egg that has good mitochondria in it. Obviously, you take out the nuclear DNA out of the donor egg first. But anyway, so basically you're just, now you have an egg that has the mother's nuclear DNA, the chromosomes, and another woman's mitochondria and then fertilize that. People call that three parent babies, which is unfortunate, but it's stuff. But anyway, well, we can debate about what it means to be apparent. But in any case, you know, in the United States, that has been banned. I mean, there's no way that's going to happen in the United States.

There's no way there's going to be research or evaluation of it. Forget it. That is dead in the water right now. and, you know, there was a case of a doctor in New York who had done some research on this who actually went to Mexico to treat a couple who the mother had a mitochondrial disease. And so they, Mexico doesn't have any laws one or the other about it. And so they did it kind of, you know, secretly. And but meanwhile in Britain they talked about this. They very quite explicitly.

They had discussions in Parliament and they said, you know what? These diseases are so devastating. And we feel that, you know, this combination of mitochondria from one woman and chromosomes from another woman, we're okay with that. You know, we don't think that violates sort of human dignity. and we're going to allow this to go forward under a lot of regulation. And so there's a university in Britain that has gotten a license. They're open for business.

And so they will start, probably babies will start being born soon through this technology. So, you know, I wonder, like, what's going to happen with CRISPR? Right. Will it be the American version, total ban? Will it be the Mexico version? Like, it's all kind of an, you know, unregulated. black market or is it going to be out in the open carefully, explicitly regulated, you know, under the guidance of government?

Well, and I think that's, I'm being a little intentionally provocative here because I think that people are, there's a tendency for people either to just sort of ask rhetorical questions and leave them hanging without quite answering them or there's this other tendency which we in the United States love so much is just to ban it first and, ask questions later for something like designer babies, if it does become possible, and obviously there's enormous scientific technical hurdles to getting there. But, you know, I could easily imagine that it's banned here. And so, okay, someone sits up a clinic in Mexico or the Cayman Islands or whatever. And rich people go there and design their babies and poor people can't do it.

Or even if it doesn't get banned anywhere, like you alluded to earlier, there's just, okay, you can do it. It costs a million dollars, right? That's just how much the, the effort is going to require. And so that's a kind of inequality socially that is going to be hard to deal with. It's a little bit, it hits home in a way, you know, the ability to make sure all your children are, you know, tall and beautiful that other kinds of inequality might not. I have a problem with these arguments against CRISPR based on inequality because they all make it sound like we are living in a paradise of equality today. Wait, what? We're not.

You know, like, you're, you know, if you're, if you are concerned about inequality, like, it's time to get started now, because it's not as if genes are the only thing that can influence the success of children later in life. And so, you know, and this raises, I do think that this also raises difficult questions because, you know, if you say, okay, well, it's wrong to let parents use CRISPR to make their children, let's say, you know, tall, beautiful or whatever you want to dream that you could do with CRISPR. I don't think that would happen, but let's just pretend you could do that. Anyway. Okay. So what about all the other advantages that children.

of wealthy parents have that help them to get ahead in life. Do we make those illegal? Should SAT prep classes be banned? Yeah, no, I think this is very real, but I still think the analogy is not quite perfect. I mean, I get it, and I think that we are a terrible society at treating people equally right now. That point is very, very well taken.

But in America at least, you know, people grow up with this idea that someday, no matter where you come from, you could be a millionaire, you could be president. But no one grows up with the idea that, you know, 20 years from now, my DNA will be better. So it's this kind of obvious in your face difference between people, which I suspect people will react to very viscerally. I agree. And, I mean, I think part of it is that, well, you know, part of the problem here is that we think of gene. means as being the sort of absolute definition of who we are. It's not. But we also think about heredity in the sense that like these kids will then pass down

these traits to their kids and so on. And that really like strikes a chord, I think, because like I was saying before, like heredity is such a profound thing to us in terms of how we define ourselves. And so to be tampering with heredity seems like one of the great transgressions. And that, I think, colors are our discussion of this. And you can see this. And, you know, the debates people have. You know, scientists who developed CRISPR actually have just in the past few years,

like had a series of international meetings to figure out, like, well, what's right? What's wrong? What should we do with this? the overriding issue, it seemed, was what is this going to do to heredity, which is so striking to me because it really tells you where our concerns are located. And I think it's a good question, but, you know, on the other hand, I mean, I just, I don't, some people say like, oh, we're going to turn ourselves into two separate species. You know, you'll have the rich people who, can afford CRISPR who will become their own species and the poor people will become a different

species. This sort of reminds me of, you know, the time machine. It's very HD Wells. Yes, exactly. That's right. You know what I'm talking about. Yeah. But, you know, like, but people, but like that just, people just don't work that way. Like animals in general don't work that way. Like, you, like, people have sex, lots of sex. And like, people don't respect these sort of arbitrary boundaries when they're having sex. Like whatever genes might get introduced into some rich person will either disappear entirely from the human gene pool eventually because that's what happens to most gene variants, or will just kind of diffuse around all over the world after a while because of just the way

that people have kids together. So, you know, I just find some of these science fiction scenarios that people are talking about, as if they're like real ethical questions to be silly, frankly. I think actually, so I'm going to go on the other side. I think that even if they're wildly unrealistic and not mapping out the future, I'm glad people are envisioning the craziest most extreme scenarios. I think will help us sort of be prepared a little bit for the brave new world yet to come. Well, but no, but but you have to then, but, okay, we can talk about these scenarios,

but then we have to take the next step and say like, well, okay, but here's the basic, here are the basic facts of science that tell you that this is not even something worth considering, you know? You know, like, for example, like I wrote an article for the Times recently about studies on DNA and the link between genes and how long you stay in school. There is a connection there. We don't really know why there's a connection there and may have to do with genes that influence certain things in our brains or maybe even our parents' brains, we don't know. But there's an

association there. It's interesting. It's worth studying. And you can actually like look at, you know, these million variants in people's DNA and actually come up with a score, a sort of education score, which sounds very fancy, like, oh, well, I could use that to, you know, test some kindergartner and say, like, you're never going to make it to college. So we're just going to put you over here in this track. And, you know, you just be content with your lot. And that would be a ridiculous thing to do because this score, you know, it only predicts a small amount of the variation in how people do in school.

So chances are that your score would be very wrong. So, you know, lots of people with a high genetic score who drop out early from school, there are a lot of people with a low genetic score to go into grad school. Like it's just one variable among several. So, you know, for people to say like, oh, okay, well, clearly we're going to have this future where everybody's fate is predetermined. Well, no, no. And it's not a scenario worth talking about just because of the basic statistics of what we're talking about. So, you know, I'm all for talking about scenarios, but you have to be willing to,

to throw some out. No, I completely agree on that. I mean, that idea that you just said about sort of predicting people's educational attainments on base of their DNA makes no sense to me. It's like taking a preseason power pole in some sports league and then saying, well, we don't need to play the games now. We figured out who's going to win. But playing the games actually matters also.

So Carl Zimmer, or as we say around here, Carl Built for Power Zimmer. Thank you very much for a, wonderful conversation so always great to talk to you oh it's good talking to you again john all right bye bye bye