Making Sense with Sam Harris - #77 — The Moral Complexity of Genetics

Episode Date: May 22, 2017

Sam Harris speaks with Siddhartha Mukherjee about the human desire to understand and manipulate heredity, the genius of Gregor Mendel, the ethics of altering our genes, the future of genetic medicine,... patent issues in genetic research, controversies about race and intelligence, and other topics. If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe.

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Starting point is 00:00:49 Siddhartha Mukherjee is an oncologist and researcher. He is an assistant professor of medicine at Columbia University and a cancer physician at Columbia University and NYU Presbyterian Hospital. He's a former Rhodes Scholar. He graduated from Stanford, the University of Oxford, where he got a PhD in studying cancer-causing viruses. And he got his medical degree from Harvard Medical School. His laboratory focuses on discovering new cancer drugs. He's published articles and commentary in such journals as Nature, the New England Journal of Medicine, Neuron, and in publications like the New York Times and the New Yorker and the New England Journal of Medicine, Neuron, and in publications like the New York
Starting point is 00:01:25 Times and the New Yorker and the New Republic. He won the Pulitzer Prize for his book on cancer, The Emperor of All Maladies. And his most recent book, which is the topic of our conversation, is The Gene, An Intimate History. And now I give you Siddhartha Mukherjee. I am here with Siddhartha Mukherjee. Siddhartha, thanks for coming on the podcast. Yeah, my pleasure. Well, listen, you have a great job, it looks like. You're doing amazing things in the world on at least two fronts. I just want to start, before we get into your book, I want to start by getting you to describe what it is you do and how much of your time is spent in each of these two careers. You have a career as a physician and as a writer,
Starting point is 00:02:17 both at very high levels. So describe what you're doing? So I'm a physician scientist, and the particular area I work on is the, is in the clinical realm, I work on leukemias. I'm an oncologist, so I treat cancers. I see patients with cancer. My area within cancer is leukemia and lymphoma, basically cancers of the blood cells, although I certainly see other cancers as well and treat other cancers as well. So that's one aspect of my physician scientist life. The other part is I do laboratory research. I do basic cancer research.
Starting point is 00:02:55 Our laboratory has really a couple of major fronts. We can talk about them, but I work on cancer genetics. We've discovered genes that are implicated in cancers, particularly blood cancers. And we try to use that information about cancers to try to figure out how to make new treatments and then bring all of that stuff back to the clinic to sort of make a difference in human lives. So it's been called a bench to bedside, but of course, it's a long and complicated route. So that's the world I live in. I have a laboratory actually across the street from where I see patients.
Starting point is 00:03:32 So in a rather physical sense, I'm in the road in between. So now I cut you one job short. You have three jobs. You're a physician, you're a scientist, and you're also a writer. And how much of your time is spent writing these books we're about to talk about and your New Yorker pieces? The time is spent, it's very uneven. So my primary life is as a physician scientist, but then when the books come, the birth of a book is like the birth of a baby.
Starting point is 00:04:06 The books take over your life for a while. Though sometimes bloodier. They take over for a while, and then they go out into the world, and eventually they sort of take on a life of their own. One thing that's nice is that for the first book, Emperor of All Maladies, I then collaborated with Ken Burns and a bunch of other people, cancer geneticists and cancer biologists on making a documentary. So that book sort of acquired a second life,
Starting point is 00:04:33 if you will. And that's going to happen with the gene as well. Ken Burns is again going to do a PBS documentary on the gene. So it's a somewhat, it's like a sine curve. It goes up for a while, then it dies down for a bit, then goes up for a while, et cetera. And, you know, the New Yorker is not the only outlet that I write for. I write for the New York Times Magazine, actually, I've written much more for them in the past. And also for other places like Vice, where I do also some editorial work. But really,
Starting point is 00:05:08 it's all focused on questions. I write pieces not because I'm on salary at any of these places, but because I am interested by when a topic interests me, or when the editors want to excerpt things from the book is when those pieces appear. They're either book excerpts chosen by the editors, or they're topics that I initiate because I'm interested in them. Right, right. Well, I want to talk about The Gene in particular, your more recent book. I have some questions about cancer I'd like to ask you at the end. Unfortunately, I have not read Emperor of All Maladies, for which you won the Pulitzer, but I've read The Gene, and that's your more recent book, and that gets to some
Starting point is 00:05:46 really fundamental science, obviously, but fundamental questions of human existence and public policy and ethics, and this is as rich a topic as anyone can find in the 21st century. And I want us to move through it fairly systematically, because I can assume a fairly, or even a very, educated audience on this podcast. And in other episodes, I would be happy to use a term like phenotype without bothering to define it. I would just assume that people can look it up if they're confused. But in this conversation, I think we should do our best not to leave anyone behind on anything, because the topics are so fundamental and important. That would be great. And stop me when you think that, you know, the whole point of the book is to minimize jargon. Now, that involves some simplification,
Starting point is 00:06:39 necessarily. So we'll try to cut the right balance, but that's a tough thing to do, because the audience, as you're saying, is simultaneously very sophisticated. But some of the issues here are so fundamental that if we gloss over them, I suspect we'll lose sight of very important issues. Yeah, and they're just interesting facts that jump out of even the definition of a word that you are quite sure you understand and use without any self-consciousness. Let's start where you, the path you take through the book, is very much of a historical tour of our understanding of the basis of life and inheritance. So you trace it from its beginning in philosophical speculation. You start with
Starting point is 00:07:28 Pythagoras and Plato and Aristotle, but then it wasn't until Mendel that we arrive at a crucial understanding of the atomic and information theoretic aspect of inheritance. So just remind people about the significance of what Mendel did. Well, if it's okay with you, let's start with a little before Mendel. Let's start with people that you mentioned, Pythagoras, Aristotle, Plato. The question of human heredity, why is it that we look like our parents, why do we look unlike our parents, is a question that really obsessed people, scientists, thinkers, philosophers for generations, and twinned to that idea—and it's very important to make it very clear—is that even in Plato,
Starting point is 00:08:13 even in Aristotle, you have simultaneously the desire to understand heredity and a desire to manipulate human heredity. Those things come hand in hand. That's one of the messages of the book, is that no sooner have we begun to understand the principles of heredity, because of the aspirations that we have as humans to, it's some ancient desire, clearly, but to guarantee the best for our children. Heredity does not live in abstraction even for a minute. It immediately becomes concrete.
Starting point is 00:08:49 It jumps to life, literally, and begins to work its way into fundamental questions about who are we, what do we want to transmit, how do we aspire to see ourselves, how do we aspire to see our children? Aristotle wrote about this. Plato wrote about this. They didn't understand what heredity was necessarily in current scientific conception, but they had strong ideas about it. And those ideas were powerfully twinned to the notion that they would change human beings if they could manipulate it.
Starting point is 00:09:16 Well, then we're going to get to the topic of eugenics, but I think the punchline I take away from what you just said is that eugenics on some level is unavoidable. I mean, we all begin attempting to practice it the moment we start thinking about genes. That's exactly the point. The point is that the aspirations to manipulate genes come directly out of some ancient human desire, which is very related ultimately to, you know, as I said, wanting the best for yourself and your children. And we see this pattern recurring over and over again in this book. In fact, it's obviously one of the drivers in this book, is to realize that, you know, it's not as if in 2017, we've all of a sudden ascended to some kind of higher plane
Starting point is 00:10:06 where we've been able to somehow divorce or cut our understanding of genetics from our desire to manipulate it. In fact, it's only been amplified. We'll come to these topics, but it's important to underscore them right from the beginning. So on to Mendel. Mendel is an important, interesting character in this book. The first version of the book didn't begin with Mendel, but I thought that and I'll talk to you about how I reorganize some of these issues.
Starting point is 00:10:36 But Mendel is, of course, the is a very for me, the most the most obvious way to begin this story. very, for me, the most obvious way to begin this story. And that's because even though Mendel didn't coin the word gene, he performed experiments that allowed him to get to the concept of the gene. Now, who was Mendel? Mendel was a monk. We know, I've been to Bruneau, I've looked through, you know, whatever papers there are on Mendel, some of them in translation, some of them I had translated from the original Germans.
Starting point is 00:11:16 Mendel was a monk. He lived in what is now the Czech Republic, most of his lifetime in a city called Brno, which was a city center, a relatively active place. He lived most of his life in a monastery, and attached to that monastery was a garden. Mendel, the monk, like many other monks, people who certainly were part of the clergy, was interested in questions of natural science. He was also a natural scientist. And he was an Augustinian. In fact, many Augustinians trained in botany, they trained in biology, they trained in geology, and Mendel carried this tradition forward. And the question that Mendel asked was a very simple question, which is, if you take hereditary traits that move across generations, what is the pattern of that movement? Is it that these traits, once you mix them together, do they blend like a wearing blender? Or is there something about them that is something different about them?
Starting point is 00:12:26 Now, interestingly, you know, the dominant theory in Mendel's time was this wearing blender kind of theory, this idea that, and in fact, it makes some intuitive sense. You know, your height is some kind of average between your mother and your father. The shape of your nose or the color of your hair is often some kind of average. So it makes a lot of intuitive sense. But of course, it doesn't make entire intuitive sense, because if that was true, you couldn't explain gender. Gender is not the average of your two parents. Every generation somehow seems to retain the information about male physiology and female physiology,
Starting point is 00:13:10 male anatomy and female anatomy, and then seems to be able to regenerate this information. So even the most obvious, if you think about it for a second, there was a problem there. You had to explain these two peculiar contradictions. Mendel doesn't write about these contradictions. He went straight into the experiments. And his experiments, Mendel's genius was to
Starting point is 00:13:29 boil the experiment down to a very simple idea, which is, you know, if you take two traits and you bred them to be true in an organism, two strains of organisms, what happens when you mix them? What happens in the first generation? What happens in the second generation? And what he found was astonishing. What he found was that if you did this experiment with peas, that these traits seem to behave in a very odd manner. First of all, they did not blend. One trait became dominant over the other. The second thing was that as they moved through the generations, the traits didn't go away. They had the capacity to be retained in some kind of indivisible or, you know, we struggle for analogies, atomistic form.
Starting point is 00:14:18 It couldn't be split apart. They didn't sort of, the wearing blender didn't blend them all away. They remained true to their original essence. And then he also found that they acted independently of each other. They were really somewhat like particles. Now, there's a lot of debate looking back at Mendel, whether he was solving the problem of duality in general, whether he was interested in plant hybridization, so the smallness of his experiment. I happen to believe, having read Mendel over and over again, that he was very aware that his experiments had something important to say about how organisms create their form and function.
Starting point is 00:14:57 So he, of course, didn't use the word gene. If you read his papers, and perhaps this is the way to read them in contemporary times, if you read the papers, you do get the sense of his idea that information is involved. He codes the idea of a gene. He called it a big A and small a, for instance. So I don't know how history will sort of eventually solve the question of how much Mendel knew about what he had eventually found. But certainly, to my reading, there's a strong hint that, number one, Mendel understood that what he found was very consequential, that traits did not move in this wearing blender form, but in fact had a kind of, again, we struggle with modern words for this, but had a kind of atomic quality about them. They were indivisible. They were particulate. And they moved across generations in whole, in wholesome, in a kind of whole form. And that was
Starting point is 00:15:59 the basic, and they followed, and this is an important piece as well, they followed mathematical laws and ratios, which would be very tough to capture if you were just sort of blending everything together. Well, there's one way to solve that problem. We can clone some of that DNA that was left on those manuscripts and raise the resulting human being in a monastery near a pea garden, and then ask him what he's thinking. Well, to me, what's interesting about all of this is that, you know, I was at a conference recently, and one of the things that I tried to do was to
Starting point is 00:16:31 remind people of the exact dimensions of that garden. And of course, it is strikingly small. You know, it's about the size of three rooms. And from those three-room springs, all of this discussion today about gene cloning and ethics and et cetera, et cetera. Yeah, it's remarkable. So let's talk a little bit about what we now know that Mendel didn't, and essentially the basics of information flow in biological systems. So you have genes to RNA to amino acids to proteins. Just remind listeners of that sequence a little bit. There are two ways you can think about the information flow.
Starting point is 00:17:10 One way is that genes encode instructions. They usually encode instructions by, they instruct the formation of RNA. This RNA itself can give rise to important functions in cells and bodies. But also this RNA then gets translated into proteins, which are strings of amino acids, can be even further chemically modified, but are fundamentally strings of amino acids. And these strings of amino acids ultimately are responsible for much of the form and function that we see in living organisms. So there's information transfer. You can think about genes as the master code of instructions, the RNA as a kind of soft
Starting point is 00:17:56 copy, although, as I said, it itself has important functions. It itself can carry out much of the important functions. And that RNA is translated into proteins, which are responsible for most of what we know about features and functions of organisms. So, you know, the color of your hair, the color of your eyes, the signals that go between cells that instruct cells how to be and what to be. Many of these are either proteins themselves, or they are products that are created by proteins. There is both the protein product of genetic transcription, and then there's just the fact that some of these products also regulate the function of genes as well.
Starting point is 00:18:39 So that's an important piece. The regulation of genes is a crucial piece, and it was known for a while that— so the question, of course, is, you know, the cells in your eye and the cells in your retina and the cells in your blood have essentially, give or take some exceptions, the same genetic information, the same DNA. How is it that the cells in your eye or your retina are very different from the cells in your blood? And it turns out that genes are regulated. So the analogy that I use is that although the symphonic score, if you were, if you were to use that analogy, the musical score is the same in the eye and in the blood, the eye cell chooses to play out certain parts of that score.
Starting point is 00:19:34 And in doing so, picking out certain bars, picking out certain sections, it obviously, the output of the genetic output that it has in RNA and proteins is different, and that is partly responsible for the difference between your retina and the cells in your blood. And there's really no clear boundary between species. When we're talking about genes as information, there's no DNA that is intrinsically human, and there was no first human. Both of those are correct, and they're very important consequences. So the fact that there is no, that the genetic code seems, for the most part, there are a
Starting point is 00:20:21 few, you know, there could be minor quibbles with that sentence, but for the most part, the genetic code is identical between blue whales and bacteria and humans. First of all, that is a powerful, powerful argument for evolution. We'll set that aside for a second. But in fact, the flow of information has been conserved across organisms, across the entire biological world. And you're right, there is nothing fundamentally human about human DNA. If you were to put, as experiments have shown, you can put a yeast gene into a human cell.
Starting point is 00:20:59 And for the most part, the human cell will take that yeast gene and make RNA and proteins out of that yeast gene. You can take a viral gene and put it into a bacterium, and for the most part, the virus will take that viral gene, make RNA and protein out of that viral gene, and there's nothing intrinsic to one versus the other. Again, there's some minor sort of scientific quibbles about what I just said, but that's for the most part true. And again, with respect to species, the boundary between species is blurry in time, too. There was no moment where, in the primate line, if you had a time machine, you could go back and point to the first human being. They're exactly right. You know, it depends on what we mean by blurry. In a genetic sense, there's continuity. But of course, as you know very well, part of the formation of species is
Starting point is 00:21:58 reproductive isolation, and thereby leading to the formation of species. So, in a genetic sense, you're absolutely right. There's continuity, but that itself, you know, doesn't make species. Species formation is, I mean, I discussed it a little bit. It's not the central subject of the book, but species formation is a little bit more complicated than just genetic continuum. but species formation is a little bit more complicated than just genetic continuum. Yeah. So I want to just touch on this topic of eugenics because you can't avoid it for long. And as you just indicated, this is just part and parcel of understanding what genes are,
Starting point is 00:22:37 or even attempting to understand them. And this idea that... Now, obviously, eugenics is a highly stigmatized word for good reason, given fairly recent human history. And we can talk about that. But just this basic issue of caring about how the next generation turns out as a possible parent. I mean, if you marry a person because they're smart and beautiful and not too crazy and you think they'll be a good parent and you wouldn't select them as a mate if they weren't these things, this seems to amount to a very crude form of eugenics, doesn't it?
Starting point is 00:23:19 Well, eugenics has a, you know, kinship and mate selection, et cetera, are topics of their own. I mean, the way I like to think about eugenics, you're right. There's a, there's a, there's, it seems that there's an ancient desire that we have, which is ultimately related to the idea of, you know, how to best create the best future for our children. That's a, that's, that's an, that's an ancient desire. Eugenics has to do with, there's a, so it's important to distinguish between those aspirations, which are present in multiple cultures, present in ancient cultures. Eugenics is a kind of deliberation on that idea. It brings it to a particular kind of self-consciousness. And it is the idea that we can deliberately, prospectively, intentionally manipulate human heredity
Starting point is 00:24:10 in order to create the best humans in the next generation. And in doing so, improve the human race or species, these were Victorian words, but we have to use them here, in general. So the forward march, as it were. I mean, look, the reason we're having this entire conversation, I think, is that we're at a pivotal moment in history. We'll talk, I'm sure, more about this. But as you know, just to give the listeners a
Starting point is 00:24:38 kind of advanced flavor, three or four months ago, the National Academy of Sciences wrote a document saying that for the first time, it would be permissible under extreme circumstances, under conditions where there's a disease that causes extraordinary suffering, to intervene on the human genome in a manner that would make that information perpetually, permanently heritable in humans. In other words, in sperm and egg forming cells. Right. So-called germline genetic or genomic modification. Everyone who's listening to this should know or will know that this is a momentous point in history. We are essentially saying that we are a machine that has begun to learn to read and write its own instructions. So therefore, the question arises, you know, when in the past,
Starting point is 00:25:29 when have we, what has happened when we've been tempted to read and write our own instructions? And just to point out, there's an ancient drive in here. You know, the writings go back to Plato and Aristotle, but the self-consciousness arises particularly in the late 18th and 19th and 20th century. So the word eugenics is coined by Francis Galton, a cousin of Darwin's. And Galton imagines that he and others can manipulate human heredity to produce better human beings and thereby improve the human condition in general, alleviate suffering and improve the human condition in general. And in fact, one of the things that's important about eugenics in this first phase is that it is embraced by many Victorian progressives. It is thought to be a progressive idea. It's thought to be an idea which we should be subscribing to because what other better way that is there to improve the human condition
Starting point is 00:26:26 than take the horns and the reins of heredity in your own hands? Many, many famous Victorian progressives sign on to this. You can list them. They're listed in the book. And then there's a second phase. The second phase is that eugenics then moves to the United States. So it undergoes a kind of manic adolescence in the United States. This is a time from around 1910s to the 1930s, when it is also
Starting point is 00:26:54 the rage in the United States. The Eugenics Record Office is soon set up. And in England, eugenics meant selective breeding. In America, the twist was placed on it. Eugenics became the possibility of selective sterilization, that if you were an imbecile or a moron or had genetic or what was perceived to be genetic or hereditary problems— We should remind people that those were technical terms, imbecile, moron, idiot. In fact, yeah, I point that, you know, it's pointed out in the book, but I'm using these, and they were loosely used, but they were powerful technical terms invented to sort of service the
Starting point is 00:27:37 eugenic engine. You know, if you had a particular level of intelligence, you were called an imbecile or a moron or a high-gradeon, low grade moron, etc. But the point was that very soon, by the late 1920s and the early 1930s, even the courts in the United States had agreed that, in fact, men and women who had these kinds of hereditary traits should be sterilized by state mandate and thereby, again, in the hopes of improving human heredity. Many men and women were in fact sterilized based on these grounds. The story that I tell in the book is that of Carrie Buck, a young woman who was falsely probably found to have a hereditary condition of imbecility, as I said, most likely because of really manipulation of information by the state.
Starting point is 00:28:37 And she was forcibly sterilized. The case rose to the Supreme Court, and Oliver Wendell Holmes, the so-called judicial moderate, said three generations of imbeciles is enough. That word enough signals something, a kind of impatience with, you know, let's just get on with it. You know, this is a time when better babies contests were part of, you know, a. You could go to a railroad fair or on the playground, and there'd be a better babies contest to select the best babies, etc. There were films about sterilization in the United States. So that's the second phase. And the third phase is the one that we're most familiar with, is that the idea then metastasizes to Germany, most familiar with is that the idea then metastasizes to Germany, where from selective breeding and selective sterilization, it morphs into selective extermination. If in England,
Starting point is 00:29:33 you know, we could breed the better humans. In the United States, we could sterilize them and thereby prevent their births. Then in Nazi Germany, the logic was extended. Why not just exterminate them? And on that grounds, initially, the German scientists began to exterminate, again, following the United States, those that are considered genetic defectives. This is their terminology. And very soon that morphed into the idea that, you know, genetic defectives, well, why not then exterminate racial defectives? And thereby that ultimately launched what we know as sort of racial eugenics in Nazi Germany, the extermination of Jews and other races as well.
Starting point is 00:30:17 Yeah, well, one clear variable here is just the means of intervention available to us. here is just the means of intervention available to us. So in a world where the only choice is between selective breeding, forced sterilization, and exterminating people, well, clearly those methods are so crude that they would only tempt people who are either fundamentally deranged by some ideology or lacking in compassion to a degree that is just pathological. What's interesting — let me interrupt this, though — what's interesting is that I agree and disagree with that. And that's the point of the first part of this book. In fact, when the Victorians were speaking — or I should say when Gorton and his associates were speaking about human heredity in this manner.
Starting point is 00:31:09 One thing I should say, I think I spoke a little too loosely in grouping selective breeding with the other two. I mean, I can see how selective breeding is tempting for people. we should remember and remind ourselves that this history was a gradual stepping into blood, as it were. In fact, it's not as if the Nazis all of a sudden one day woke up and said, oh, this would be a nice way to improve the human race. They followed the road to health through the best genetic intentions of the progressives of the 1890s and 1900s in the United States and in England. Yeah, yeah. And again, it comes down to the technical means available. So for instance, if the question is whether or not a person with a heritable disability should be allowed to have a child that will have that disability or will likely have that disability,
Starting point is 00:32:11 that's a very interesting and difficult ethical question depending on what the disability is and the likelihood that some as yet unborn child will inherit it. But it becomes a trivially easy question to answer in favor of intervention if the intervention is trivial to apply. So if you told me that, well, this aspiring mother who doesn't want the state to meddle in her life at all, you know, stands a 99% chance of giving birth to a deaf child, say. But if she'll simply take this vitamin that's otherwise harmless, you know, twice during her pregnancy, the risk of this will be removed. Well, then, yeah, the state has an interest in
Starting point is 00:32:59 ensuring she takes that vitamin, right? It would be criminally negligent on her part not to take that vitamin. And there's a continuum from that, you know, harmless and trivially easy intervention to the removal of her uterus, right, by a state. So, again, absolutely correct. But to remind ourselves, and we're fast-forwarding a little bit, but it's important to keep reminding ourselves that in reality, the genetic information in%, but turn out to be, you know, something like 20%, 30%. And some of these diseases are very dependent on other genes that that child would inherit, so the context, and on the environment. Just to give you a very concrete example, and this is a very intimate example, because it happened to me recently. I was giving a talk on cancer genetics. And after that, a woman with a BRCA1 mutation, BRCA1 mutation, with a terrifying history of breast cancer, came to me to talk to me afterwards.
Starting point is 00:34:18 And she said her mother and her grandmother had died of breast cancer. She had had two children. She was thinking of having another one. The question she was asking is, should she and could she eliminate the BRCA1 gene mutation forever from her lineage? And the answer is, if not now, very soon. Basically, we have the technologies to allow her to do that. We have the technologies that,
Starting point is 00:34:45 you know, she could do that by selectively implanting an embryo, which lacks that genetic variation. And if in the future, we might be able to do that by selectively changing the genomes of her sperm and egg carrying cells or making cells. So, but remember in her case, the child will not have a 99% chance. We Actually, what's interesting about it is we can't really predict. We can predict that the child who was born with the BRCA1 gene mutation will have a multiply higher risk of having breast cancer in her future and other cancers, but breast cancer in her future. But we cannot, looking at her genome or looking at her, tell you whether it's going to be at age 30,
Starting point is 00:35:28 at age 60, at age 70. Is it going to be an indolent variant of cancer? It's going to be likely very aggressive. Where it's going to spread? All of this information is weirdly hidden from us. We can tell you that there is risk and there's propensity for risk. Is it a tenfold risk or something around there?
Starting point is 00:35:43 You actually don't know what the newest numbers are for BRCA1, but let's say tenfold. Well, so unless the BRCA gene confers some other benefit that I'm unaware of, what would be the argument against eliminating it? Well, the argument, there's some arguments against eliminating it. BRCA1 is an intermediate example. I'll give you another more extreme example in a second. But the arguments against eliminating it right now are we don't know
Starting point is 00:36:07 exactly whether we can use these technologies in a predictive way. If you think about, it's in the doing, as it were. If you think about the intervention into sperm and egg forming cells, when we do these genetic interventions, we're doing these in the lab with other genes, not with BRCA1, but with other genes that we've discovered. When we're doing this in the lab, you know, these interventions, these technologies allow us to do powerful genetic interventions in stem cells, but they're, you know, they sometimes miss and they reach a different target. They're off-target effects. So that's one. The second one is that the interventions that we're doing often, as I said, occur in the context of other genes. So we know very little about how other genes and
Starting point is 00:36:59 environments influence it. Sure, BRCA1 will be an example of a genetic variation where we will and are already and will allow genetic interventions in the future. And insofar as it gets simpler, if you go to something like cystic fibrosis, then it's a pretty easy decision, isn't it, to eliminate it? It is an easy decision to allow the elimination. Socially speaking, it's an easy decision to allow the elimination because of the fact that the disease that it's linked to causes extraordinary suffering. Whether an individual woman chooses to or not to exercise that decision, I think, should be left up to her. And the point is that one of the things that the history is teaching us, I think,
Starting point is 00:37:48 is that state mandates are not very successful here because they end up intervening on individual liberties. So the states can provide guidance. They can provide the options of what would happen. States can provide guidance. They can provide the options of what would happen. But it seems to me that once the state got into the business of forcing a woman to have only one prescribed kind of genetic lineage, I think for me that steps a little too far. But now, is that intuition of yours technology-dependent? I think you're picturing kind of a forced in vitro conception as opposed to a natural one. Whereas if the intervention could be as easily applied as taking a harmless pill, then do you still feel the same way about it? Again, I'm talking about cystic fibrosis. I think I would feel the same way, but I don't think it's intervention dependent.
Starting point is 00:38:43 I think I would feel the same way, but I don't think it's intervention dependent. I think it has to do with allowing humans the liberty to choose what kind of heredity they choose to transmit. And there's some historical precedent for this, which is that the state provides guidance as to what the life of a child with Down syndrome may be like. And even there, we very, very, very much know there's a wide spectrum. I mean, you know, Down syndrome has a wide spectrum. But of course, there are important medical consequences of Down syndrome. The state provides guidance, but it doesn't go and tell women that, you know, you can't have that child. Right. It seems to me that cystic fibrosis is a clearer case, maybe not the clearest possible, but getting there both in the simplicity of the underlying genetics and in the cloud without a
Starting point is 00:39:41 silver lining outcome. And then when you try to map it on to other ethical imperatives, so for instance... Just a reminder, I mean, this is a side note, Sam, but it's an important reminder. Just a reminder to remind us that we think that the cystic fibrosis gene variant that now causes disease was likely selected at a time when gastrointestinal disease like typhoid
Starting point is 00:40:03 were rampant throughout Europe, and that gene variant likely protected people from dying. Now, I'm not trying to be wax eloquent about a history that's long past. Most countries in the West do not have these threats of typhoid. But just a reminder that these gene variants were, in some cases, selected for very particular environmental conditions. Yeah, yeah. Well, that's a great point that I actually want to get to in a slightly different context, because that presents a fascinating limitation on our ability to use this technology, even if we get our heads straight ethically. But I'm just thinking back to this particular intervention, the feeling that I should oblige my children to wear seatbelts, whether they want to or not,
Starting point is 00:40:52 and whether I want them to or not, and that the state has an interest in my doing that, because it's not much fun to see needlessly injured or dead children show up at the ER day after day when they could have just been wearing a seatbelt. Why isn't there a... Why isn't there a seatbelt law for genetics? Yeah, seatbelt law for unborn children on some level. Again, when the... I think that you're pointing out exactly the reason. Because seatbelts are... We do not... Our aspirations and personhood are not linked in the same way to seatbelts as they are to heredity.
Starting point is 00:41:29 And that may be because of vast cultural reasons. It may be because of an enormous, a particular interest in heredity. But we have carved out a special place within ourselves, within our cultures, that says, look, the autonomy that we have around heredity is an autonomy that should be respected unless there are truly extraordinary circumstances. And even when there are extraordinary circumstances, you know, I've taken care of many children with Down syndrome who have leukemia. In fact, this is one of the terrifying things that happens. And so there is no doubt that that is an extraordinary circumstance and there's extraordinary suffering involved. But even
Starting point is 00:42:15 in such cases, we've decided, partly because of the history and partly because of the special place we've carved out for our aspirations around heredity, to provide strong guidance, but not step beyond the lines of strong guidance. We've left it to individuals. It's just a fascinating area ethically, which I haven't thought as much about as I would like, because just in hearing you say that now, it really is what we're privileging the aspirations of the parents over the experience of their future children in a way that wouldn't make a lot of sense if the children already existed. Well, so, you know, there are several philosophers and biologists and geneticists who are grappling with this question now. So, you know, to what extent you have to take into account the unborn voice of the child. It really is a fascinating and important
Starting point is 00:43:09 debate. But the point here being that, I've given you my perspective on this, but the point here being that this debate will become increasingly central, increasingly central as we learn to read and write genomes more and more. Right now, we are in a kind of learning phase, a steep learning phase of reading and writing. We are like a child who's just begun to discover the world. If you'd like to continue listening to this conversation, you'll need to subscribe at SamHarris.org. Once you do, you'll get access to all full-length episodes of the Making Sense podcast, along with other subscriber-only content, including bonus episodes, Thank you. you

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