Siddhartha Mukherjee is an oncologist and researcher. He is an assistant professor of medicine at Columbia University and a cancer physician at NYU Presbyterian Hospital. His lab 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 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 he writes for The New York Times and The New Yorker, among other publications. In this episode, we talk about what it s like to be a physician, a scientist, and a writer, and how much of his time is spent in each of these roles. He talks about how he balances his work as a physician and writer, as well as his research and lab work, and why he thinks it s important to have a second life in addition to a life in the world. He also talks about his new book, The Gene, an intimate history, which he wrote with Ken Burns, about the evolution of the human gene, and his new documentary on the gene as a tool for understanding human life and the process of becoming a better human being. We don t run ads on the podcast, and therefore it s made possible entirely through the support of our subscribers. So if you enjoy what we re doing here, please consider becoming a supporter of the podcast by becoming a subscriber. We re made possible by our listeners, not by our sponsors, by our creators, Sam Harris, and by our editors, by the wonderful people at The Making Sense Podcast. We ll be making sense of this podcast by you, Sarah Goodey, and we re making sense by you all by listening to the Making Sense podcast by Sarah Goodie, and you ll be helping us all make sense of the world by listening and listening to us all of the making sense in the podcast and we all get a better of it by listening, and they get it all of it, too much of it in the morning, and more of that, and it s a good day, too good of a good thing, and all of that and more, and so much more, thanks, and good things, and that s a real thing, good of it too, etc., etc., and so on, etc. etc., et cetera. Thank you for listening.
00:09:35.080The point is that the aspirations to manipulate genes come directly out of some ancient human desire,
00:09:42.340which is very related, ultimately, to, you know, as I said, wanting the best for yourself and your children.
00:09:49.500And so, and we see this pattern recurring over and over again in this book.
00:09:55.780In 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
00:10:06.420where we've been able to somehow divorce or cut our understanding of genetics from our desire to manipulate it.
00:10:14.180And in fact, it's only been amplified.
00:10:15.640We'll come to these topics, but it's important to underscore them right from the beginning.
00:10:21.480Mendel is an important, interesting character in this book.
00:10:27.480The first version of the book didn't begin with Mendel, but I thought that, and I'll talk to you about how I reorganized some of these issues.
00:10:36.260But Mendel is, of course, the, is a very, for me, the most obvious way to begin this story.
00:10:44.180And 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.
00:11:08.400He 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.
00:11:26.400The, he was, he lived most of his life in a monastery, and attached to that monastery was a garden.
00:11:31.640Mendel, the monk, like many other monks, parsons, natural, people who certainly were part of the, of the, of the clergy, was interested in questions of natural science.
00:11:47.460He was also a natural scientist, and he was an Augustinian.
00:11:51.100In fact, many Augustinians trained in botany, they trained in biology, they trained in geology, and Mendel was, was, was carried this tradition forward.
00:11:59.840And the question that Mendel asked was a very simple question, which is, if you, if you take hereditary traits that are, that are, that move across generations, what is the pattern of that movement?
00:12:15.640Is it that these traits, once you mix them together, do they blend like a, like a wearing blender?
00:12:21.960Or is there something about them that, or is there something different about them?
00:12:26.200Now, interestingly, you know, the, the, the dominant theory in Mendel's time was this wearing blender, blender kind of theory, this idea that, that, that, and in fact, it makes, makes some intuitive sense.
00:12:40.120You know, your, your height is some kind of average between your mother and your father.
00:12:45.020Your, the shape of your nose or the color of your hair is often some kind of average.
00:12:49.140So, 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.
00:12:58.460You know, gender is not the average of your, of your two parents.
00:13:02.480Every generation somehow seems to retain the information about male physiology and female physiology, male anatomy and female anatomy, and then seems to be able to regenerate this information.
00:13:14.800So, even the, even the most obvious, if you think about it for a second, there was a problem there.
00:13:19.860You had to explain these two peculiar contradictions.
00:13:22.640Mendel doesn't write about these contradictions.
00:13:24.160He went straight into the experiments.
00:13:26.200And his experiments, Mendel's genius was to boil the experiment down to very simple, very simple idea, which is, you know, if you take two traits and, and you've read them to be true in, in, in, in an organism, two strains of organisms, what happens when you mix them?
00:13:43.300What happens in the first generation, what happens in the second generation?
00:14:20.420They didn't sort of, the wearing blender didn't blend them all away.
00:14:23.540They remained true to their original essence.
00:14:27.000And then he also found that, that, that they, they acted independently of each other.
00:14:30.760They were really like, somewhat like particles.
00:14:32.760Now there's been a, there's a lot of debate looking back at Mendel, whether he was solving the problem of gerality in general, whether he was interested in, in plant hybridization.
00:14:44.620So the smallness of the 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.
00:14:57.200So he, of course, didn't use the word gene.
00:15:00.780He, if you read his papers, and perhaps this is the way to read them in, in, in contemporary times, if you read the papers, you do get the sense of his idea that information is involved.
00:15:14.500He called it a big, big A and small A, for instance.
00:15:17.120So I, I don't know how history, history will, will sort of eventually solve, solve the question of how much Mendel knew about what he had eventually found.
00:15:28.400But certainly to, to my reading, there's a strong hint that number one, Mendel understood that what he'd found was very consequential, that traits did not move in this wearing blender form.
00:15:41.500But in fact, had a kind of, again, we, we struggle with, with, with modern words for this, but had a kind of atomic quality about them.
00:15:52.300And they moved across generations in whole, in wholesome, in a, in a kind of whole form.
00:15:58.280And, and that was his, that was the basic, and there were, and they followed, and this is an important piece as well.
00:16:03.680They followed mathematical laws and ratios, which would be very tough to capture if you were just sort of blending everything together.
00:16:09.880Well, there's one way to solve that problem.
00:16:12.560We 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.
00:16:22.860Well, to me, to me, what's interesting about all of this is that, you know, I, I was at a conference recently and I, I, I, one of the things that I tried to do was to remind people of the exact dimensions of that garden.
00:16:33.900Um, and of course it is strikingly small, uh, you know, it's, it's, it's about the size of three rooms and from those three rooms springs, uh, all of this discussion today about gene cloning and ethics and et cetera, et cetera.
00:16:48.620Yeah, it's remarkable. So let's talk a little bit about what we now know that Mendel didn't and essentially the, the, the basics of information flow in biological systems.
00:17:00.180So you have, you know, genes to RNA to amino acids to proteins. Just remind listeners of that sequence a little bit.
00:17:06.900There are two ways you can think about the information flow. Um, one way is that genes encode instructions. Um, they usually encode instructions by, um, uh, by the, they instruct the formation of RNA.
00:17:21.300This RNA itself, uh, can, can give rise to important, uh, functions in cells and bodies, but also this RNA then gets translated into proteins, um, which are strings of amino acids.
00:17:34.820That can be even further chemically modified, but are fundamentally strings of amino acids.
00:17:39.640And these, uh, strings of amino acids ultimately are responsible for much of the form and function that we see in living organisms.
00:17:46.960So there's a, there's, there's information transfer. You can think about genes as the, uh, the master code of instructions.
00:17:54.480The RNA as a kind of soft copy, although, as I said, it itself has, uh, has important functions.
00:17:59.980It itself can carry out much of the important functions and that RNA is translated into proteins, which, uh, are responsible for most of, of what we know about, um, features and functions of organisms.
00:18:13.000So that, you know, the, the color of your hair, the color of your eyes, um, the signals that go between cells, uh, that instruct cells how to be and what to, what to be.
00:18:22.920Many of these are either proteins themselves or they are products that are created by proteins.
00:18:28.100There is both the protein product of genetic transcription.
00:18:33.420And then there's just the fact that some of these products also regulate the function of genes as well.
00:18:39.700So that's an important piece. Um, that the regulation of genes is an, is an, is a, is a crucial, uh, piece.
00:18:44.640And it was, um, it was known for a while that, that, so the question of course is, um, you know, the cells in your eye and the cells in your, the cells in your retina and the cells in your blood have essentially, give or take some exceptions, the same, uh, genetic information, the same DNA.
00:19:04.360Uh, how is it that the, the cells in your eye are, or your retina are very different from the cells in your, in your blood?
00:19:10.400And it turns out that genes are regulated. So it's, so it, uh, the, the analogy that I use is that, um, although the, uh, 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, in the, in the blood, the, uh, eye cell chooses to play out certain parts of, of that score.
00:19:33.800Um, and in doing so, um, picking out certain bars, picking out certain, um, sections, it, uh, obviously the output, uh, of, uh, the genetic output that it has in RNA and proteins is different and that is partly responsible for the difference between your, uh, retina and your, um, the cells in your retina and the cells in your blood.
00:19:53.760Hmm. And there, 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.
00:20:11.040Um, both of those are correct. And they're very, very, they're very important consequences. So the fact that there is no, uh, that the genetic code seems for the most part, there are a few, uh, you know, that could be minor quibbles with that sentence, but for the most part, the genetic code is identical between blue whales and bacteria and humans.
00:20:28.800Um, first of all, that's, that is a powerful, powerful, um, um, argument for evolution. Um, we'll, we'll set that aside for a second. Uh, but, but in fact that, that there is a, there is a, there is a, the, the, the flow information has been conserved across organisms, across the entire, uh, biological world.
00:20:46.540And, and, and, and you're right, there is nothing fundamentally human about human DNA. Um, if you were to put, as we, as, as experiments have shown, you can put a yeast gene into a human cell.
00:20:59.000And for the most part, the human cell, um, will, uh, take that yeast gene and make, uh, RNA and proteins out of that yeast gene.
00:21:07.880You can take a viral gene and put it into, into a bacterium. And, uh, for the most part, the virus will take that viral gene, make, uh, RNA and protein out of that viral gene.
00:21:17.880And there's nothing intrinsic to one versus the other. Again, there, there will be, there's some minor sort of scientific quibbles about, about what I just said, but that's for the most part true.
00:21:27.160And again, as the, with respect to species, the boundary between species is blurry in time too.
00:21:35.200There was no, 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.
00:21:44.360They're exactly right. Um, you know, it depends on what we mean by, by blurry. In a genetic sense, there's a, there's continuity, but, but of course, as, as, as, as you know, very well, uh, part of the formation of species is reproductive isolation.
00:21:59.560So, so, and thereby leading to, uh, the, the, the formation of species. So, so in a genetic sense, uh, the, you're absolutely right. There's a, there's, there's continuity.
00:22:11.760Um, but, um, 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, than just genetic continuum.
00:22:23.560Yeah. So I, 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 or even attempting to understand them.
00:22:39.960And this, 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.
00:23:02.280I mean, if you, if you, if you marry a person because they're smart and beautiful and not too crazy and you think there'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?
00:23:19.220Well, eugenics has a, you know, kinship and mate selection, et cetera, um, 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.
00:23:32.280Uh, that we have, uh, which is ultimately related to the idea of, you know, how to best, uh, create the best future for our children. That's a, that's a, that's a, that's an, that's an ancient, um, desire.
00:23:45.220Eugenics has to do with, there's a, so it's, it's important to distinguish between those, um, aspirations, uh, which are present in multiple cultures, present in ancient cultures.
00:23:56.360Eugenics is a kind of deliberation on that idea. It, it brings it to a particular kind of self-consciousness and it is the idea that we can deliberately, prospectively, intentionally manipulate human heredity in order to create the, the best human, humans for the second, in the next generation.
00:24:15.240And in doing so, improve the human race or species. These were Victorian words, but we have to use them here, um, in general. Um, so the forward march, as it were, um, I mean, look, the reason we're having this entire conversation, I think, is that, is that we're at a pivotal moment in, in history.
00:24:33.560We will talk, I'm sure, more about this, but as you know, just to give, give, give, give the listeners a kind of advanced flavor, um, 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, you know, conditions where there's a disease that causes extraordinary suffering, to intervene on the human genome in a, in a manner that would make that information perpetually, permanently heritable in humans.
00:25:00.320In 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, uh, point in history. We are essentially saying that we are a machine that has begun to learn to read and write its own instructions.
00:25:18.880So, therefore, the question arises, you know, when in the past, when have we, what has happened when we've, when we've been tempted to read and write our own instructions?
00:25:29.400And, and, and, and just to point out, there's a, there's a, there's a, there's an ancient drive in here. You know, the, the, the writings go back to Plato and Aristotle, but, uh, the, the self-consciousness arises particularly, um, in the, uh, late 18th and, uh, 19th and 20th century.
00:25:45.500So, the word eugenics is coined by, uh, Francis Galton, a cousin of Darwin's. And, uh, Galton imagines that, you know, if, that, that he could, that he can, 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.
00:26:06.880And, in fact, one of the things that's important about eugenics in this first phase is that, um, it is embraced by many Victorian progressives. Um, it is thought to be a progressive idea. It's thought to be an idea which we should be subscribing to because what else, what, what other better way that is there to improve the, improve the human condition than take the, you know, take the horns and the reins of, of heredity in your own hands.
00:26:30.760Um, many, many, many famous Victorian progressives sign on to this. You can list them in the, they're listed in the book. And then there's a second phase. The second phase is the, is that eugenics then moves to the United States.
00:26:44.560So 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 the rage in the United States offices of the eugenics record office is soon set up. Um, and in, in, in the, in, in England, eugenics meant selective breeding in America, the twist, a twist was placed on it.
00:27:08.720That eugenics became the possibility of selective sterilization. That if you were an imbecile or a moron or, or had genetic, uh, or what was perceived to be genetic or hereditary problems.
00:27:21.060We should remind people that those were technical terms, imbecile, moron, idiot.
00:27:24.880In fact, yeah, I point that, you know, it's pointed out in the book, but I'm using these and they were, they were, they were loosely used, but they were powerful technical terms invented to, to sort of service the eugenic engine.
00:27:38.720Um, uh, you know, if you had a particular level of intelligence, you were called an imbecile or a moron or a high grade moron, low grade moron, et cetera.
00:27:46.280But, but, but the point was that very soon by the, by the late 1920s and the early 1930s, uh, even the courts in the United States had, uh, agreed that in fact, uh, uh, men and women who had these kinds of hereditary traits, um, should be, uh, sterilized by state mandate.
00:28:05.220Um, and thereby again, in, in, in, in the, in the hopes of improving human heredity and, um, many men and women were in fact sterilized, uh, based on these grounds.
00:28:15.980And, um, the story that I tell in the book, um, is that of Carrie Buck, a young woman who was, um, falsely probably found to have, um, uh, uh, uh, hereditary, uh, condition of imbecility.
00:28:29.980As I said, most likely because of, of, um, really manipulation of information by the state and she was forcibly sterilized.
00:28:38.840Um, the, the case rose to the Supreme court and Oliver Wendell Holmes, the so-called judicial moderate said, um, three generations of imbeciles is enough.
00:28:48.820That word enough, um, signals something, a kind of impatience with, with, you know, let's just, let's just get on with it.
00:28:56.440Um, you know, this is a time when better babies contests were part of, uh, you know, a, a, a, a fair, you, you go to a, a, a, a railroad fair or on the playground and, and there'd be a better babies contest to select the best babies, et cetera.
00:29:11.440There were films about sterilization, um, in, in the United States.
00:29:17.960And the third phase is the one that we're most familiar with is that, that the idea then metastasizes to Germany,
00:29:23.820where from selective breeding and selective sterilization, it morphs into selective extermination.
00:29:30.700If you, you know, if, if, uh, in England, you know, we, we, we could breed the better, uh, humans in the United States, we could sterilize them and thereby prevent them, their births.
00:29:40.580Then in, in, in Nazi Germany, the logic was extended.
00:29:45.580Um, and on that grounds, um, initially, uh, the German scientists began to exterminate again, following the United States, um, those that are considered genetically genetic defectives.
00:29:59.680And very soon that morphed into the idea that, you know, genetic defectives, well, why not, you know, why not then exterminate racial defectives?
00:30:07.120Um, and thereby the, that, that ultimately launched, uh, what we know as, um, sort of racial eugenics in Nazi Germany, the extermination of Jews and, and other races as well.
00:30:17.640Yeah, well, one clear variable here is just the, the means of intervention available to us.
00:30:24.860So, 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
00:30:45.560or lacking in compassion to a degree that is just pathological.
00:30:50.840Well, what's interesting, but let me interrupt this, though.
00:30:52.900Well, what's interesting is that, is that I agree and disagree with that.
00:30:56.840And that's the point of part of, of the first part of this book.
00:31:00.440In fact, when, when the, when the Victorians were speaking, or I should say, when Gorton and his associates were speaking about, uh, human heredity in this manner.
00:31:09.940One thing I should say, I think I spoke a little too loosely in grouping selective breeding with the other two.
00:31:15.560I mean, I, I, I can see how selective breeding is tempting for people to see.
00:31:17.520The point is exactly that, that, that, that, that, that, that, that, in fact, the, the, we should remember, um, and be very remind, remind ourselves that this history, uh, was a gradual stepping into, into blood, as it were.
00:31:30.200Um, and, and, and in fact, the, it's not as if the Nazis all of a sudden one day woke up and said, oh, you know, this would be a nice way to improve the human, human race.
00:31:38.300Um, they, um, they followed, um, the, the, the, the road to, uh, the, the, the, the road to health through the best genetic intentions of, um, of, of, of the progressives of the 1890s and 1900s in the United States and, and in, in England.
00:31:53.940Yeah, yeah. And, again, it, it, it comes down to the technical means available.
00:31:59.640So, for instance, if, 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,
00:32:11.300that's a, a, 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.
00:32:23.680But it becomes a trivially easy question to answer in favor of intervention if the intervention is trivial to apply.
00:32:33.440So, 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, a 99% chance of giving birth to a deaf child, say.
00:32:48.060But if she'll simply take this vitamin that's otherwise harmless, you know, twice during her pregnancy, the risk of this will be removed.
00:32:56.680Well, then, yeah, she, the state has an interest in ensuring she takes that vitamin, right?
00:33:02.280It would be criminally negligent on her part not to take that vitamin.
00:33:06.900And there's a continuum from that, you know, harmless and, and trivially easy intervention to the removal of her uterus, right, by a state.
00:33:20.820But, but to remind ourselves, and we're fast forwarding a little bit, but it's important to, but to keep, keep reminding ourselves that in, in, in reality, genetics,
00:33:29.960the, the genetic information in humans has turned out to be more complicated and thereby raised the specter of more complicated questions.
00:33:36.880So, again, to use your analogy, to run along the structure of analogy, for many diseases, the, the, the odds turn out not to be 99%, but turn out to be, you know, something like 20%, 30%.
00:33:49.540And some of these diseases are very dependent on other genes that the, that, that, that child would inherit.
00:33:57.140So, the context and on the environment, just to give you a very concrete example.
00:34:01.720And, and, and this is a very intimate example, because it happened to me recently.
00:34:05.720I was giving, giving a talk on cancer genetics.
00:34:09.060And after, 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.
00:34:18.960And she said her mother and her grandmother had died of breast cancer.
00:34:24.980She was thinking of having another one.
00:34:26.920The question she was asking is, should she and could she eliminate the BRCA1 gene mutation forever from her lineage?
00:34:36.920And the answer is, if not now, very soon.
00:34:40.240Basically, we have the technologies to allow her to do that.
00:34:43.440We have the technologies that, you know, she could do that by selectively implanting an embryo, which lacks that genetic variation.
00:34:50.140And 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.
00:35:00.300So, but remember, in her case, the child will not have a 99% chance.
00:35:04.800We, actually, what's interesting about it is we can't really predict.
00:35:07.220We can predict that the child who was born with the BRCA1 gene mutation will have a multiply higher fold risk of having breast cancer in her future and other cancers, but breast cancer in her future.
00:35:21.640But we cannot, looking at her genome or looking at her, tell you whether it's going to be at age 30, at age 60, at age 70.
00:35:29.880Is it going to be an indolent variant of cancer?
00:35:31.700Is it going to be likely very aggressive?
00:36:02.740I'll give you another more extreme example in a second.
00:36:04.540But the arguments against eliminating it right now are we don't know exactly whether we can use these technologies in a predictive way if you think about it's in the doing, as it were.
00:36:16.100If 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.
00:36:30.060When we're doing these in the lab, these technologies allow us to do powerful genetic interventions in stem cells, but they sometimes miss and they reach a different target.
00:36:45.680The second one is that the interventions that we're doing often, as I said, occur in the context of other genes.
00:36:56.520So we know very little about how other genes and environments influence it.
00:37:00.620Sure, BRCA1 will be an example of a genetic variation where we will and are already and will allow genetic interventions in the future.
00:37:11.060And 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?
00:37:21.340It is an easy decision to allow the elimination.
00:37:25.540Socially 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.
00:37:33.300Whether an individual woman chooses to or not to exercise that decision, I think, should be left up to her.
00:37:42.180And, you know, the point is that one of the things that the history is teaching us, I think, is that state mandates are not very successful here because they end up intervening on individual liberties.
00:38:02.080They can provide the options of what would happen.
00:38:05.660But it seems to me that once the state got into the business of forcing a woman to have only one, you know, a prescribed kind of genetic lineage, I think for me that steps a little too far.
00:38:18.300But now is that intuition of yours technology dependent?
00:38:21.680I 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?
00:38:37.680Again, I'm talking about cystic fibrosis.
00:38:39.900I think I would feel the same way, but I don't think it's intervention dependent.
00:38:43.740I think it has to do with allowing humans the liberty to choose what kind of heredity they choose to transmit.
00:38:55.060And there's some historical precedent for this.
00:38:57.040You know, obviously, Down syndrome is a good, is an important 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.
00:39:13.740And even there, we very, very, very much know there's a wide spectrum.
00:39:18.300You know, Down syndrome has a wide spectrum.
00:39:22.220But, of course, there are important medical consequences of Down syndrome.
00:39:26.640The state provides guidance, but it doesn't go and tell women that, you know, you can't have that child.
00:39:30.820It seems to me that cystic fibrosis is a clearer case.
00:39:34.700Maybe not the clearest possible, but getting there both in the simplicity of the underlying genetics and in the cloud without a silver lining outcome.
00:39:43.900And then when you try to map it on to other ethical imperatives, so, for instance...
00:39:49.520I mean, this is a side note, Sam, but it's an important reminder.
00:39:52.160Just 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 were rampant throughout Europe.
00:40:06.320And that gene variant likely protected people from dying.
00:40:10.040Now, this is not...I'm not trying to be, you know, wax eloquent about a history that's long past.
00:40:15.720We are...most countries in the United...in the West do not have these threats of typhoid.
00:40:20.560But just a reminder that these gene variants were, in some cases, selected for very particular environmental conditions.
00:40:29.120Well, 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,
00:40:39.360even if we get our heads straight ethically.
00:40:42.300But I'm just thinking, back to the...to this particular intervention, the feeling that I should oblige my children to wear seatbelts,
00:40:51.240whether they want to or not, and whether I want them to or not, and that the state has an interest in my doing that
00:40:57.040because 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.
00:41:14.720I think that you're pointing out exactly the reason.
00:41:18.340Because seatbelts are...we do not...we...our aspirations and personhood are not linked in the same way to seatbelts as they are to heredity.
00:41:29.980And that may be because of vast cultural reasons.
00:41:35.360It may be because of an enormous particular interest in heredity.
00:41:39.820But 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.
00:41:57.560And even when there are extraordinary circumstances, you know, I've taken care of many children with Down syndrome who have leukemia.
00:42:05.940In fact, this is one of the terrifying things that happens.
00:42:08.800And so there is no doubt that that is an extraordinary circumstance and there is extraordinary suffering involved.
00:42:14.840But even 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.
00:42:31.020It's just a fascinating area, ethically, which I haven't thought as much about as I would like.
00:42:37.640Because 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.
00:42:57.280Well, so, you know, there are several philosophers and biologists and geneticists who are grappling with this question now.
00:43:02.800So, you know, to what extent do you have to take into account the unborn voice of the child?
00:43:07.940It really is a fascinating and important debate.
00:43:10.400But 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.
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