Siddhartha Mukherjee is an oncologist and researcher. He is an assistant professor of medicine, at Columbia, University and a cancer position at on the university in 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 is nature. The New England Journal of Medicine Neuron and in publications like the. New York Times and the new Yorker, 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 said: are the Mukherjee I am here with the dart. The Mukherjee said Arthur thanks for coming on the podcast yeah, my pleasure. Well, isn't you are? I have a great job, it looks like you're doing amazing things in the world on at least two front. I just want to start before we get into your book. I want to start by getting you to describe what it is do and how much of your time is spent in each of these two hope. You have a career as a physician and as a writer, both at very high level, so describe what you're doing so. I'm physician scientist and the particular area I work on is the the is the clinical realm my work on Leukemia Simon oncologist, so I treat cancers. I see patients with cancer might

area within cancer is leukemia and lymphoma, basically cancers of the blood cells, although I certainly see other cancers as well and feed other cancers as well. Much of a so so that's one aspect of my the physicians I just like the other part is: I do live research, I do basic cancer, research or laboratory has really couple of major fronts. We can talk about them, but I work on. Cancer genetics we've discovered jeans genes that are implicated in cancers, particularly blood cancers, and we try to use that information about cancer is to try to figure out how to treat that make new treatments and then bring that all of that stuff back to the clinic to sort of make a difference in in human lives. So it's seven that you know it's been called advanced to bench to bedside, but it's a it's a long and complicated out. So that's the world I live in. I I have a laboratory actually across the street, from where I see patients. So, in a in a rather physical sense, I

I'm I'm in the road in between. So now I cut you one job short, you have three jobs here, a physician, you're, a scientist and you are also a writer and how much of your time is spent, right in these books were about to talk about an your new Yorker piece is the the time is spent uh uh, it's very uneven uhm. So you know my we live is as a physician scientist, but then, when the books come they may you know that the birth of a book is like the at the birth of a baby. The books take over your life for a while, though sometimes bloodier, take it for awhile and then and then they go out into the world and and eventually they sort of take on a life of their own. One thing: that's nice is that for the for the first of all maladies, I then collaborate with KEN Burns and a bunch of other people that I am cancer geneticist and cancer biologists on making a documentary. So I was that that book master required a second life. If you will,

and that's going to happen with the gene as well. We're going to KEN Burns is again going to do a PBS documentary on the gene. So it's it's a somewhat. It's like a sign curve you it goes up for awhile. Then it dies down for a bit then goes up for a while, etc and so the New York is not the only outlet that I write for. I write for the New York Times magazine, actually written much more for them in the past and also for other places like vice, where I do also some editorial work, but really it's all focused on questions. I 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 want to excerpt things from the book is when, when those pieces appear that 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 I have some questions about cancer. I'd like to ask you, at the end, unfortunately, not red emperor formalities for which you won the Pulitzer. But I've read the g and that's your more recent book and that gets to some really fundamental science, obviously but fundamental questions of human existence and public policy and ethics, and this is as rich, topic is anyone can find in the 21st century, and I want us to move through it fairly systematically, because even a very educated audience on this podcast and, in other episodes, be happy to use a term like phenotype, without bothering to define it. I would just just assume that people can look it up if they are confused, but in this conversation I think we should do our

best not to leave anyone behind on anything because of the topics are so fundamental and and important that be great and stop me when you think that you know when, when the the whole point of the book is to minimize jargon now that involves some simplification, yeah necessarily so we'll try to try to cut the right balance with that that that's a tough thing to do, because the audience as you're saying is simultaneously very severe. I get it, but some of the issues here are so fundamental that if we, if we don't we gloss over them, I suspect will 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

Oracle. Tour of our understanding of the basis of life, an inheritance, so you trace it from its beginning in really philosophical speculation, you start with Pythagoras Plato and Aristotle, but then it wasn't until Mendel that we arrive at a really a crucial understanding of the atomic, an information theoretic aspect of inheritance, so it just remind people about the significance of what mental did if, if, if it's? Okay with you, let's start with the a little before mental, let's start with with people like you mentioned, but had recessed all the data, the question of human heredity. Why is it that we look like our parents, why we look on, like our parents is a question that really obsessed people, scientists, thinkers philosophers for generations and and and cleaned to that idea, and it's very important to do to make it better to

is that even in Plato, even in Aristotle, simultaneously, the desire to understand Aristotle, 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 you have we begun to understand the principle of her of principles of already because of the aspirations that we have as humans do yeah it's some ancient desire clearly, but to guarantee the best for our children. It will the the the minute that the red does not live in abstraction, even for a minute, it immediately becomes concreted immediately. Becomes it jumps to life literally and makes 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 you spy to see our children or Aristotle wrote about this Plato wrote about this? They didn't understand what reality was necessarily in current can scientific conception, but they had strong ideas about it and those ideas were powerfully twinned the notion that they would change human beings if we could, if they could manipulate it. Well, that we're gonna get to the topic of eugenics, but I think the punch line I take away from what you just said is that eugenics on some level is unavoidable and we all begin attempting to practice at the moment. We start thinking about genes that that that's that that that's exactly the point, the point is that the aspirate

it is to manipulate genes, come directly out of some ancient human desire, which is very related, ultimately need to. You know, as I said, wanting the best for yourself and your children, it's so so that, and and- and we see this pattern recurring over and over again in in in the in this book and packets- it's always the one. The one of the drivers in this book is that is to realize that you know it's not because if in two thousand and seventeen we've always had an ascended to some kind of higher plane, where we've been able to somehow divorce the or cut our understanding of genetics from our desire to manipulate. In fact, it's only been amplified will come to these topics, but it's important to under

them right from the beginning, so on to mend the mental is an important, interesting character in this book. The beef, the first version, the book didn't begin with Manta, but I thought that and and and I'll I'll talk about how it re organize some of these issues, but mentally is, of course the. It is a very for me, the most the most the most obvious way to begin this story, and that's because, even though mental didn't coin, the word gene he performed experiments, that allowed him to get to the concept of Jane Mental Mental was a monk we know. I I've been to Bruno. I've looked through the you know. Whatever papers there are on and some of them in translation, some of them I had translate from the original Germans mega was a was a monk. He lived in what is now the the Czech Republic most of his lifetime in a city called Bruno,

which was a a city uh it relatively active place, the he He was uh. He lived most of his life in a monastery and attached to that monastery was a garden with a monk like many other monks, parsons, naturally, uh people, who certainly were part of the of the clergy, was interested in questions of natural science. He was also NASH. Scientist and he was an Augustinian. In fact, many Augustinians trained in botany they trained in biology. The train in geology and metal part was a was. It was carried this tradition forward, and the question

in that man lost was a very simple question, which is, if you, if you take her medically traits that are that I'm that move across generations. What is the pattern of that movement? Is it that these traits, once you mix them together today, blend like a like a Waring blender, or is there something about them that it's always something different about them, not a interesting? He. You know that the the dominant theory in Mendel's time was this way, England in Lander kind of theory. This idea that that that, at the end, if I could make make some intuitive sense, you know your your height is some kind of average between your mother and your father. Your

the shape of your nose are the color of your hair. Is off and I'm 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. You know gender is not the average of your of your two parents. Every generation produce somehow seems to retain the information about male physiology and he female physiology, male anatomy and female anatomy, and then seems to be able to regenerate this information to even the even the most obvious, if you think about it, for second. There was a problem that he had to explain these two peculiar contradictions, mental right about these contradictions. He went straight into the experiments and his experiments. Members 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 bred them to be true in in in in an organism to strains of organisms. What happens when you mix them? What

in the first generation what happened? The second generation and what he found was astonishing in what he found was that if you did this experiment with peas, that you would that these traits seem to behave in a very odd manner. They did first of all, they did not blend one trade became dominant over the other. The second thing was that, as they move through the generations, that rates didn't go away. They had the capacity to be retained and, in some kind of You know indivisible, or you know we struggle for analogies, atomistic form that it couldn't be split apart. They didn't sort of Waring Blender didn't blend them all the way they remained true to their original essence, and then he also found that that that they acted independently of each other really lie somewhat like particles, a lot of debate, looking back, add mental, whether he was solving the problem of generality in general, whether he was interested in

launch hybridization, so the smallness of experiment. I happen to believe having, get mental 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 so of course didn't use the word gene. He if you read his papers and perhaps the way to read them in in in contempt re time to read the papers. You do get the sense of his idea that information is involved. He codes the idea of a gene. He called in to be a big and small, a for instance. So I I don't know how his history will will sort of eventually solve solve the question of how much metal new about what he had eventually found, but certainly attempt to my reading. There's a strong hint that number one Mendel understood that what he found was very consequential that traits

I did not move in this Waring blender form but in fact, had a kind of again. We we struggle with, with with modern words for this, but had a kind of at Tommy quality about them. They were indivisible, they were particular and they across generations in hole in wholesome in in a kind of whole form and, and that was that the basic and they followed and is an important piece, is widely followed. Math local laws in 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 an raise the result in human being in a monastery near p garden and then ask him what he's thinking well need to me what's interesting.

All of this is that you know I 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 and, of course it is strikingly small. You know it's it's it's about the size of three rooms and from those three rooms springs. All of this discussion today about gene cloning and ethics and etc, etc. So 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 of new jeans to RNA to amino acids, to proteins just remind listeners of that sequence. A little bit there. Two ways you can think about the

mission flow. One way is that genes in code instructions date, usually in code instructions by by the they instruct the formation of irony. This rna itself can can give rise to important functions in cells and bodies, but also this on it and gets translated into proteins which are strings of a minor acids, can be even further chemically modified but are fundamentally string the line acids and it needs that string them on assets ultimately are responsible for much of the foreman from and that we see in living organisms. So there is a if they there's there's information transfer. You can think about Jane's as the at the monster code of instruction

the army as a kind of soft copy, although, as I said it itself has a has important functions, it itself can carry out much of the important functions and that our name is translated into proteins which are responsible for most of of what we know about features and tions organism, so that you know that the color of your hair, the color of your eyes, the signals that go between cells that instructs cells, how to be, and what to what to be many of these are either proteins themselves or their 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 jeans as well. So that's an important piece that the regulation of genes is and isn't is. It is a crucial piece, and it was. It was known for a while that that so the question, of course, is you know the cells in your eye

and the cell as any of the cells in your right now, and the cells in your blood have essentially and give or take some exceptions the same it. Kinetic information, the same dna. How is it that You know, I, I all your retina very different from the cells in your in your blood and it turns out that jeans are regulated. So it's so it the now did you that I use is that, although the at 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 d? I said to this to play out certain parts of off that score and in doing so picking up certain bars speaking out certain sections it. Obviously, the output of the genetic output that it has in our own in proteins is different, and that is part.

Responsible for the difference between your eye right now and your the cells in Europe and the sounds of the cells in your blood and then there's really no clear boundary between species. Well, my we're talking about DNA that is intrinsically human and there was no first human. Both of those are correct where they are very important consequences. So the fact that there is no that the genetic code seems for the most part there are few. You know that it could be minor quibbles with that sentence, but for the most part, the genetic code

denticle between blue whales and bacteria in humans. First of all, that that is a powerful, powerful argument for evolution. We'll set that aside for a second better, but in fact that that there's a there's, the the the flow information has been conserved across organisms across the entire biological word and and you're right, there's nothing fundamentally, human about human DNA, the D a if you were to put as we as as experiments have shown you can put a yeast gene into a human cell and for the most part the human cell will take that use gene and make RNA and proteins out of that e chain. You can take viral gene and put it into into a bacterium and for the most part, the virus will take that viral gene.

Arnie and protein out of that, but gene and there's nothing intrinsic to one versus the other again that they will be there. Some minor sort of scientific quibbles about about what I just said but backs for the most part and again, a s t with respect to species the boundary between species is is blurry in time to there was no. There was no moment where, in the pro Metline, if you had a time machine, you could go back and point to the first human being. Yeah exactly right there. If you know it depends on what we mean by by blowing into genetic sense. It is a contest continuity, but but of course, as as, as you know, very well part of the formation of speakeasy's reproductive isolation.

So, and and there, by a leading to the the the formation of species, so so in a genetic sense, the actually right there's a good as there's good continuity, but that itself, you know, doesn't make species species formation. As I discussed a little bit, it's not the central subject of the book, but it's easy for me to live a more complicated than than just genetic continue yeah. So I want to just touch on this topic of eugenics because you can't avoid it for a long and, as you just indicated, this is just part and parcel of under standing with jeans are or even attempting to understand them, and this is this idea that now, obviously eugenics is a highly stick ties word for good reason given fairly recent human history, and we can talk about that. But just this basic issue

caring about how the next generation turns out as a possible parent. Maybe 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 you, Jay Next doesn't well. Eugenics has a kinship and made selection etc. Are topics of brown. I mean the way I like to think about eugenics that you're right there's a there's, a there's. It seems that there is an ancient desire that we I have, which is item. Did it do the idea of you know how to best create the best future for our children? That's that that's that's and that's an ancient desire. Eugenics has to do with the.

There's a so it's important to distinguish between those aspirations which are present in multiple cultures present in ancient cultures, huge This 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 set. When the next generation and in doing so improve the human race or species victorian words, but we have to use them here, I'm in general, so he ate in the forward March as it where I mean. Look the reason we're having this entire conversation, I think is that is that, where can pivotal moment in in history will talk I'm sure more about this, but, as you know, just to give it give give give the listeners a kind of advanced flavor, three or four months ago, the National Academy of Sciences and wrote a document saying that for the first time it would be put MR,

under extreme circumstances, under you know, conditions where there is a disease that causes extraordinary suffering, to intervene on the human genome in a in a man, I know that would make that information perpetually permanently heritable in humans, in other words, in sperm and egg forming cells, so called Germline genetic 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. It arises when, in the past, when we, what has happened when we've been we've been tempted to read and write our own instructions and and and just to point out- is that there's that there's a name drive in here? Did you know that 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 war

eugenics is coined by Francis Galton, a cousin of Darwin's and imagines that you know, if that he could, that he can. He and others can manipulate. And heredity, to produce better human beings and thereby improve the human condition, in general, they leave it 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 progresses. It is thought to be a progressive ideas, thought to be an idea which should be subscribing to because what else? What what other better way that is there to improve that improve the human condition then take the you know, take the horns and the rains of of heredity in your own hands. Many many famous victorian progresses sign on to this. Then you can list them in the bed they listed in the book and then there's a second phase. The second phase is the track. 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 the rate in the United States? The offices of the eugenics record office is soon set up and in in in the in in England, eugenics meant selective breeding in America. The twist a twist was based on an eugenics, became the possibility of selective stay realization that if you were an embassy, lawrimore on or or had genetic, what was perceived to be genetic. Their hereditary problems. We should remind people that those were technical terms, so more on that yeah there will be a big factor. I point that a you know. It's pointed out in the book, but I I'm you using these and they were they were. They were loosely used, but there were powerful technical terms invented to sort of service the eugenic engin.

You know if you had a particular level of intelligence, you were calling him a seal or more on a high grade, more low grade, morbid sector. But but the point was that very soon by the by the late nineteen twenties and the early nineteen thirties, even the courts in the United States HI 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 in in the in the hopes of improving human heredity and

Any men and women were in fact sterilized based on these grounds, and the story that I tell in the book is that of Carrie Buck, a young woman who was falsely probably found to have a the reading fee, a condition of imbecility, as I said most likely because of of really manipulation of information by the state and she was forcibly sterilized. The the case rose to the Supreme Court and all rental homes. The so called traditional moderate said to three generations of imbeciles is enough. That would be enough signals something a kind of impatience with with you know, let's just let's just get on with it. You know this is

a time when better babies contests what part of a you know a bit about fair you, you can go to at at a railroad fare on the playground and and a bit better babies contest to select the best baby that separate what films about sterilization in in the United States. So that's the second phase, and the third phase is the one that will be most familiar with. Is that that the I get then metastasize to Germany, where from selective breeding and selective sterilization it marks into selective extermination? If you you know, if it, if in England, you know we we, we could breathe the better humans in the United States, we could sterilize them and thereby prevent them. That birds, then, in in in Germany, is that the logic was extended. Why not just extra and on that grounds, initially, the german scientists began to initially

eight again following the United States, those that are contained considered genetically genetic defect of this is their terminology and very soon that morphed into the idea that you know you newegg defective as well. Why don't you know why not then extremely racial defectors and thereby the ultimately launched we know is a sort of racial eugenics in Nazi Germany, the extermination of Jews, an other races as well yeah One clear variable here is just the means of intervention available to us, so in a way world, where the only choices between selective breeding, four sterilization and exterminating people well. Clearly, those methods are so crude that they would only tempt people who are either fundamentally deranged by some idea. Maji or lacking in compassion to a degree that is just Pathologie.

Well, that's interesting it, but let me interrupt this there. Well, it's interesting is that is that I I agree and disagree with that and that's the point of part of the first part of this book when, when the when the Victorians were speaking or I should celebrate, Galton and his associates were speaking about human heredity in this manner. 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't see how select reading it is exactly that that that that that that, in fact the the we should remember very remind remind ourselves that this history it was a gradual stepping into into blood as it were, and in fact that it's not as if not these 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. They followed the road to the road to Hell through the best genetic intentions of of

of the progress is of the eighteen nineties and nineteen hundreds in the United States and and in in England, yeah yeah and again a it. It comes down to the technical means available, so, for instance, if If the question is whether or not a person with a Parrot Obel disability should be allowed to have a child that will have that disability or it will likely have that disability. That's a very interesting and difficult ethical question. Depending on what the disability is an 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 metal in her life at all, you know stand

eight, a ninety nine percent chance of giving birth to a deaf child say, but if you'll simply take this vitamin, that's otherwise harmless twice during her pregnancy, the risk of this will be removed. Well then, yes, yes, the state has an interest in in sure, and she takes that vitamin right. It would be criminally negligent on her part not to take that vitamin and so there's a continuum from that. You know harmless and trivially easy intervention. The removal of her uterus right by state so so again absolutely correct, but but good to remind ourselves up and live with fast floating a little bit, but it's important to the to keep keep reminding ourselves that in in.

Reality, genetics. The genetic information in humans has turned out to be more complicated, thereby raised the specter of more complicated questions again, use your analogy to good and run along the stretch of analogy for many diseases The odds turned out not to be ninety nine percent, but turn out to be something like twenty percent, thirty percent and some of these diseases very dependent on other genes that the child would inherit. So the text and on the environment. Just to give you a concrete example- and I and this is very intimate exactly because it happened to me recently. I was that I give it give me a talk on cancer, genetics and after after that, a woman with the Brca one mutation back, a limitation with the terrifying hits you breast cancer came to me to talk to me afterwards and she said her mother and her grandmother had died of breast cancer. She was she had had two children. She was

of having another one. The question she was asking is: should and could she eliminate the Bracker one gene mutation forever from her lineage, and the answer is, if not now very soon. Basically, we have the technology to allow her to do. That we have the technologies that you know she could do that by selectively implanting an embryo which lacks that future, we might be able to do that by selectively. Changing the genomes offers sperm and egg carrying cells or making cells. So who but remember in her case the child will not have a ninety nine percent chance. We actually what's interesting about it. If you can't really predict, we can predict that the child was born with the Rachael one. Gene mutation will have a and as MIKE Dibley higher fold risk of having breast cancer in her future and other cancers, but

breast cancer in the future. But we cannot looking at her genome or looking at her, tell you whether it's going to be at eight hundred and thirty at eight hundred and sixty at eight hundred and seventeen going to be an indolent variant of cancer can be likely very aggressive where it's going to spread all this info, and is weirdly hidden from us. We can tell you that there is risk and there's propensity for risk. This is a ten fold risk or something around there the newest numbers after back a one, but at the eight let's say ten fold also and less the bracket gene confers some other their benefit that I'm unaware of what would be the argument against eliminate it. Well, the arguments at the some argue But then again still I mean a bracket. One is an intermediate example I'll give you another more extreme examples in a second but

was against eliminating it and right now. I we don't know exactly what we can. We can use these technologies in a productive way. If you think about the the it's it's it's in the doing as it were. If you think about the, if you think about that the d intervention into sperm and egg forming cells when we do these genetic interventions, we were doing these in the lab it with other jeans, not with Racker one, but with other jeans that we've discovered when we it is in the lab. You know that, bit with these intervention, these technologies allow us to do powerful genetic interventions in stem cells, but there they, you know they they sometimes miss and they reach a different target. They off target effects, that's one. The second one is that the interventions that we are with that weird doing often, as I said, occur in the context of other other jeans, so we know very little about how other genes and environment influence it sure.

Track. One will be an example of a genetic variation where we will an hour you are already an will allow genetic interventions in the future so far 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 it what it is: an easy decision to allow the elimination, socially speaking, it's an easy decision to allow the elimination, because of the, because the fact that that the disease that it's links do causes extraordinary suffering, whether an individual woman chooses to or not to exercise that decision, I think, should be left up to her and and- and you know so, the point is that it one of the things that the history is teaching us, I think, is that that that state mandates are not

may not be successful here, because they end up intervening on individual liberties, so misstated the states can provide guidance. They can provide the options of what would happen, but it seems to me that that once the state got into the business of of for supporting it, a woman to have only one, you know a a prescribed kind of genetic lineage. I think, for me, that's the absolute too far, but now is the intuition of yours technology dependent, I think, think you're picturing kind of a forced in vitro conception as opposed to a natural one, whereas if the inter mention could be as easily applied as taking a harmless pill, then did you still feel the same way about it again? I'm talking about cystic fibrosis, I I I think I would feel the same way, but I don't think it's intervention dependant. 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 his store, president. For this you know. Obviously down syndrome is a is a is a good is an important historical precedent for this, which is that the the state provides guidance as to what the what what what the life of a child with down syndrome maybe like and even there- and we were very, very, very much so there's a wide spectrum of you know down syndrome is is has a wide spectrum, but of course there are important medical consequences of down syndrome. The state provides guidance, but it doesn't going tell women that you know you can't have that shot right. I I it seems to me this is the fibrosis is a clearer case maybe not the clearest possible, but getting they're both in the simplicity of the underlying genetics and in the cloud without silver lining outcome and then

when you try to map it on to other ethical imperative, so, for instance, just remind them. This is a side note sound, but it's an important reminder, just in my set a reminder that we think that the cystic fibrosis, gene variant that now causes disease was likely selected, at a time when gastrointestinal diseases like typhoid, were rampant throughout Europe and that gene variant likely protected people from dying now, is not that I'm not trying to be is so. You know wax eloquent about history. That long because we are the most countries in the United Day in the west- do not have these threats of type for, but with it, but just a reminder that these gene variants were, in some cases selected for very particular and by

mental good conditions. Yeah yeah. Well, that's a great point that I actually want to get to and 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 making data back to the to this particular intervention the feeling that I should apply to my children to wear seatbelts or whether they want to or not, 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 seat belt. Why isn't there a wide their seat belt law for genetics? Yes the law for unborn children on some level. A again when the I think, the, if you're pointing out exactly the reason, the the the because seat belts are, we do not, and we are aspirations and- and he personhood

are not linked in the same way to seatbelts as they are to do heredity, and that may be because of vast cultural reasons. It may be because of of an enormous a particular interest in ready back back to, but we had we, we have carved out a special place. I within ourselves, within our culture, is that says: look at the the the autonomy that we have around here at eighty is an economy that that should be respected unless they are truly extraordinary. Sir, stances, and even when their extraordinary circumstances, you know I've taken care of many children with down syndrome who-

of leukemia. In fact, this is one of their terrifying things that happens, and so there is no doubt that that is an extraordinary circumstance and there is extraordinary suffering involved. But even in such cases, we've decided, partly because of the history and partly because of the special place we've carved out for aspiration's around reality to provide strong guidance. But not step beyond the lines of strong guidance. We've left it to individuals is just a fascinating area, ethically, which I haven't thought as much about it, as I would like 'cause just in hearing. You say that now it really is what we're privileging the aspirations of the parents over the experience of their fee, your children, in a way that

make a lot of sense. If the children already existed, you know they have several philosophers, and biologists and geneticists would grappling with this question now. So you know to what extent you have to take into account the unborn voice of the of the child. It really is, and it's a fascinating and important debate, but the point here being that I've, given you my perspective on on this, but the point being that it being that is this the it will become increasingly central. Interestingly central as we learn to read and write genomes more and more right now and we are in a kind of learning, phase at steep learning phase of reading and writing. We are like the tide was just begun to discover the language so again to remind ourselves if your, if your genome was written out in in in standard print, you

gene on SAM would be seventy or eighty full sets of the Encyclopedia Britannica. It would be enough for your whole house. We are beginning to learn. Of course, you now know to gene sequencing that in fact, the active parts of that inside the beating up the insight and guidance I could get, but the active parts of the inside to be a you. Can you can obtain the sequence or for about two thousand dollars? The first one, the full sequence, but the first unit was was about three billion was in two thousand and one the prediction I just came back from a conference in Seattle Prediction is that will fall down to about three hundred dollars per person, not the full genome, but the active parts of the genome so reading and writing that information reading it in the sense understanding what that code predicts for the future and and writing it understanding how and where to intervene.

Can I change one word in that seventy seven cyclopedia is going to be the central question, one of the central questions that our children will face and the conversation we just had to what extent should we mandate to extension, we dictate are going to questions that are children rapper, with this will and I and I keep making his point. These technologies to intervene on human heredity was seen will make the technologies that we seem to be obsessed with today. Like social media center seem like absolute child's play, they will brushed them aside, like a like a like a fly on a summer day, because they will get to the good Gandhi's human aspirations about controlling our children and ourselves. Yeah I just to Point out the technological trend you just sketch there that's three billion down to three, where dollars to sequence a genome in about what twenty years that's a ten. Million fold reduction in the cost. It's incredible

and and the one thing I I will add to this- and maybe that will have time to discuss this, but just to just to just to keep people current. We are currently using computational tools and human tools to inspect genomes, to read and right and the amount of data that we've collected is quite small compared to the total amount. There is so you know tens of thousands of and maybe go going into, the hundreds of thousands of individual human genomes, but imagine now on increasing that that that parents data set and then on leasing tools like deep learning on on on on that data set and picking up patterns that would not be apparent to the human eye or potentially to even standard computational ways to mine information. Imagine now for every human being being able to create a kind of predictive algorithm about their future. It really distort

and has has an effect on how we think of ourselves. I'll give you one very concrete example: another woman, with keeping on Breast cancer theme, another woman with the bracket. One gene mutation has two daughters and she told me the story. She was very concerned and got herself sequence for Bracco One and her two children. The two daughters are eleven and nine so, and one of them turned out to be positive for the carrying cation. So the question which is with me the race to me was you know these children have not even develop breasts, they are in their in their adolescence and yet already the mother's relationship with one of them and both of them has fundamentally changed. She does not see her two daughters as

same anymore. Now. Imagine doing this not across one gene but across the you know several thousand jeans that human beings have parsing r us in these kinds of propensity's parsing. Us in these kinds of probability probabilities even if their probabilistic well that that's that's a point worth flagging, because people will need to learn to think about probability in ways that are far more insightful and and ethically relevant than they have been led to thus far. We we are we're terrible about thinking about the implications of probability and, and you can give people the same, abilities in different guises. You know the probability of a loss versus the the problem is have a gain and and their feelings about the scenarios completely shift and they've been given the same information

and that in the end that's been documented in psychological study up or psychological study that same idea, but but yes absolutely getting that central point of of of this, which is to say that- and let me be very clear about something and it's very clarified in the book many times and let me be clear about it yet again that in most cases for most human features, jeans are not autonomous. They interact with their environments; they interact with chance to produce the ultimate feature. Most human features that we commonly see are the products of multiple jeans into gene variants, interacting with each other. Interacting with environment, interacting with chance. So not only is there the probability of how to the combinatorial business of the genome, which gene going to inherit in what combination. But, of course, there's a role for the environment which is which has to be factored in and may be factored in in the future and roll for chance which may be factored in in the future and there's

this additional problem which you just raised a moment ago, which is that there is no clear boundary. But I mean what's wrong with us and what's right with us, it was the end of the point you actually spell out in your book and some like the genes that make people creative, for instance, could be some of the same jeans and and seems rather likely, that some of them are that predispose people to conditions like bipolar disorder, and David there's there's evidence. I, I think, with respect to intelligence as well that that some of the genes that are highly correlated with intelligence are also correlated with certain diseases like torsion dystonia. So it could just be, it may be that some in the end, engineering solution by which we can get around this, but it could be that there will always be trade offs here that, if you're going to grab the dial that can be turned in the direction of slightly more intelligence or even much greater intelligence or probability there of you.

Your hand on the same dial that is increasing the likelihood that your child will be in a wheelchair. Well, let me the examples that we know best. I gave you a couple of cystic fibrosis is one of them that gene variant was selected for in. We think in condition where endemic typhoid was rampant. Sickle cell anemia is another one that gene where it was selected for because it protects. If you have one, if you have one copy, protect from and and potentially cerebral, malaria, and and so that you know that there are. There are more and more isolated examples of this over time and with what we know- and I I try to describe this very clearly in in the book, which is at an idea which, with medical geneticist, began to have in the nineteen sixties and nineteen seventies, particularly as we began to understand the

genome in terms of medical genetics, it won him. When did you know, and when did you do in genetics was an abstraction. You know bacteria. This is what happens in this. Is our regulation happens, an abstraction things that seem somewhat simpler, but once you cut came into the human genome, all the things that you and I talked about began to be true began to read. Most human traits are not the product of single genes that are multiple genes. Our capacity to manipulate multiple genes is fundamentally constrained, although changing will come to that in a second. The capacity predict future FINA type of future traits. Future characteristics from a single genome remains in its infancy and maybe fundamentally constrained because of environmental and John's effects, and the possibility that there are trade offs in in it. When you select for something that you inherently

Toggle switch in one direction and toggle the switch in the wrong direction, for something else may be true for certain gene variants. Again the moment you start talking about this, you feel the presence of various taboos all around you and there's just this fundamental fact that people are uncomfortable hearing about the genetic basis of of many things, and certainly certainly mental traits and things like mental illness, because they they assume that spelling this out likely produces suffering in people and likely would lead to social policies that are counter to what we, what we want, ethically and politically, but I think we should also noticed ways in which it can alleviate suffering in a very straightforward ways. He take that a condition like schizophrenia, and- and this is something you discussed in your book- it used to be believed that this condition was produced by bad parenting and and that you had this notion of a a schizophrenic Jan.

Like mother and now we know that jeans play an enormous role in this disease and I think the concordance between identical twins is something around eighty percent. Just imagine having been among this generation of mothers. Who are blamed for the mental illness of their children and blamed in terms of a psychosexual mythology. It was more or less invented out of whole cloth. By Freud, I mean it seems like a genetic understanding of a condition like schizophrenia. Is it just a huge ethical gain and the gain arrives almost immediately correct It's so did the, although yet you actually correct, we, we understand so much more and and really have involved a kind of a sense of a deeper understanding of schizophrenia, but also the Dig Temple of schizophrenia is reminded us that in schizophrenia

particularly in in familiar schizophrenia, and the kind of my family has were yet to find powerful genetic mechanistic understanding of the disease. It will come, I believe, but in fact yes, it's alleviated the kinds of ways of thinking about schizophrenia that we're very incriminating and and ultimately destroyed, families and souls? I want to mention on the set in a in your TED talk, I believe, which struck me as fairly flabbergasting. Said of the estimated one million physiological pathways in the human body that can be targeted by medical therapies or cures for diseases? We can currently target about two hundred and fifty of them

I'm became came from an article which I can send you at some point of time. Always it's a it's a little bit against work there. So someone tried to estimate the number of biological Bob ways for which they are top the target to exist, and that number is increasing. But yes it, I would say ballpark. That sounds right to me on his face as a very depressing ratio, although that the flip side is that it said guests and almost limitless promise of medicine in the future I mean what we're doing now is just the tiniest tiniest fraction of what could conceivably be done with more less the technology we already have, which is to say you know, pharmacology, you can see it one of two ways: it's either, US and or or at a picture of of limitless promised to- and this is one one one important piece to intervene on that, which is that the the the the the denominator problem, which is that the the the parts of that equation that are responsible for disease

or can we uh manipulate for enhancement, maybe a tiny fraction to start with. In other words, much of the much of the much of these. Ways these proteins, these special cogs and wheels. Much of them might be sort of the bedrock on which human, physiology and structure and form are built, and there intervening on them. Wouldn't I would neither enhance nor nor cure disease. It would basically either created dysfunctional human email or or or or not at all. So we don't know what part what fraction it's a denominator problem. We don't know what fraction all those men cogs and wheels as it were? What fraction of

am I relevant in human pathology and what fraction can be manipulated for if you're interested in and have spent what fraction can be manipulated for enhancement that what's the state of genetic medicine at the moment? And perhaps you want to talk about crisper here and and and whether you think it will fulfill its promise to genetic medicine is a very wide time. So it was probably better to be a bit narrower about it because you know some people with the same. Every medicine is in all kinds of medicines, United Medicine. So you know to Lee Diseases act on proteins and pathways which are themselves the product of jeans. So you could make the argument. So, let's talk particularly about gene therapy, maybe that's a natural way to restricted. So there are a couple of ways to imagine gene therapy, but the big bright line distinction is between so called somatic

therapy and germ line gene therapy and and input. It goes I'm involved in in in in in quite a lot of somatic gene therapy works. So so so let me just a walk us through these trends. Systematic comes to the word Selma, which means body. So this is gene therapy in which your I we're introducing a gene for engine for material or any kind of genetic material into a cell, often into a stem cell in a human body, and that cell divides replicate so maybe doesn't divide nonetheless contains that all could genetic information and thereby changes its function and and start doing a different functions. So a classic example would be in attempt to put the functioning version of a functioning version of a clotting factor, gene in

people who have a hereditary problem with blood clotting such as hemophilia, so that is a distinct from so called germ line. Gene therapy, in which what what what the attempt is is to change the genetic information in a cell. That's capable of producing sperm and eggs, I'm an ultimate once it once it does. Produce from an exit basically now carries on, goes on to the next generation and then in perpetuity. It carries on forever. So that's the right line, distinction being somatic and germ line gene therapy and until the nineteen nineties, two thousands first, attempts were in germline gene therapy using things like viruses, so viruses can carried you material into cells, particular viruses They have evolved over millennia to carry genetic material into cells. You can manipulate those viruses, you can instant

new genes into them and then thereby allow those viruses to bring genetic material into human cells and that's one kind of gene therapy, and then this this word was turned somewhat upside down by the discovery of new technologies. To change Ed genetic information and the one that much that is hidden that but more people will want to know about, is a technological crisp and has nine. Now you want me to go into the technology a doctor or tell you what the what the? What the upshot of the the the the upshot is: a wow. How detailed you want to get it? You could make a gloss on the on the actual mechanics of it, but more. The upshot, I think yeah, so so the the the glossing over the mechanics of it. The upshot is that the Crispin cast nine is an ancient, our parts of an ancient bacterial system that allow us to make intentional in a genome of choice, and why is that? Why is that relevant? Although again to return to

encyclopedia analogy you could go into you know the encyclopedia and say, go to page three hundred and forty seven volume, sixteen and and cut the word ATG City there, and hopefully only there will come back to that in a second but only their spelling everything else and if you combine it with some other techniques, not only can you make the cut there, you can replace that ATG Cc with a c t, g c c or DTG cc. So obviously do you know what, if that is the back of one gene, what? If that's the cystic fibrosis gene and what, if you make those changes, not in a cell, that's a somatic cell, but a germ line cell, a cell that is sperm and eggs, so crisper and nine, among other things, in these kind of back to the system? That order did that they're, not they're really systems are technology.

Is that allow us to make intentional deliberate changes in genomes and that we couldn't do easily, with with the kind of viral based gene therapies that we had in the past, so they allow a an unprecedented level of being able to manipulate genomes and actually not only GINO's of other organisms, mosquitoes parasites, pests, crops, etc, but also, of course, the human genome, and- and if you buying these technologies. But what we're learning about stem cells, sperm and egg producing stem cells, then, all of a sudden you have the kind you have a really unprecedented power to be a manipulate the germ line of organisms and humans in the future. That's the option, yeah and obviously

The bright line between the somatic therapy in the germ line is that all future descendants now inherit whatever changes you make as opposed to the single person you have provided the therapy to, but you know I guess in in certain cases that strikes me, he is a very easy decision and in others and impossible one it does come down to just the probabilities in Alvin. How sure we are. We know what the effects will be of our of our intervention right, she's, a nest of questions, their nest of ethical questions, and it is an ester biological questions or technical question, of course, they're interrelated discuss with each other and you're pointing out all all of them. So some of them are biologically technical questions. You know one of the off target effects. What is the likely that we'll get it back, particular what an encyclopedia and, by most

did not erase another word on page four hundred and seventy six. So that's those are technical, biological questions, but then, of course there other questions, like you know, under what circumstances should we allow this, and this goes brings us back full circle with, as I said, the National Academy. Report, which other other academies other panels around the world will eventually produce their own versions of this, but it, but it did back. In that case and and and and in the gene we I got if I try to identify some circumstances where we're beginning to open up this germ line technology, there's also some ethical questions surrounding this work that really just go to the the sociology of science. I guess first, all their their patent fights between the developers of crisper right. I think it's the broad institute and and Berkeley and then there's just this whole phenomenon of having in government funded work that is in fact

fact privately owned and becomes hugely profitable, and then you, basically you have the public paying twice for the results of this work. How do you view the ethics of enriching yourself based on research that was taxpayer funded in Hey? It is or something interesting to sort there. Yet many interesting these things to sort out there. I I've written a little bit about the patent issues around genetics in in in the gene. You know it's it's so new This arena is that the courts are still trying to figure out how to how to make sense of it. And yet just the case to point out was the Bracco one. Gene mutation with the was there was an attempt to patent the testing for that gene mutation because after all that was the product, discovery of of of scientists. But on the other hand you could say well, why is the bracket one gene mutation any different from your nose? It's a part of your

maybe it's a part of the human body. So where is the invention there? So it was a series of complicated debates that ensued, but, of course this has been carried to its next level with with the debates around gene editing, these technologies that allow you to intervene on on genetic information in a deliberate manner, and the two sides of the debate are sure tools. I borrowed from the microbiological what it's a back to invented that really to evolution back to. They were refined and changed and program and reprogrammed by individual scientists. So this is still one concern. One concern is: should these be patentable at all question one? The second question is: who made the discovery first, what's the evidence that anyone of the teams made the discovery first and the third set of questions which is

is if the discovery was in fact paid for through government dollars? Should individuals or companies be allowed to use at the same kinds of the tools to sell them back to us as it were? I tell you my views on on all three of these questions, but of course they differ. So in reverse order, should should should they be allowed. I think you know, I think, as I think it's important to keep the cycle of innovation alive. I think it's important to give important incentives, substantial incentives to scientists as they bring their products of their science into human lives. Cancer is one example that I see on a daily basis. I think most people would feel that the structure of an eighty eight off incentives cut currently it has been- has moved the needle has tipped way too far I'm speaking for myself and that we need to be able to identify inventions that are that for which, where the

line of credit and substantial substantial conference it is given and when that line gets crossed. So it's a case by case question, as you can imagine, this is the rich lead, the hotly contested there's no one formula here. I think it's the hotly contested an arena, people, including myself, feel that the first movers, the original inventors should be given substantial rewards, the come later and and so the pylon to them. The meat twos should be given much less. I also feel that the patents should not be extended indefinitely, based on you know, creating new applications for them, but much of the what should come up front, but once you're done you're done so these are these are sort of the gory details as it where they set the second, the third question along so quickly in the interest of time that the second question was a one question was

Should these be patentable, I think in the case of Christmas, has nine the amount of human intervention that went into the process after the initial discovery is substantial. A lot of things had to be done, things that we hope to gather at the b, but the biological system, invented by microbes by bad bacteria, was designed to kill. Viruses. Did John Baird genomes in DNA up, we've redesigned it to focus it on the human genome and in a programmable way. So I think there's a good case. We made that there was a substantial innovation involved. I should say that anyone who wants to patent my nose is free to do it. It's broken at least once and I consider it Creative commons knows so, if it's in my mind, is not the ticket back to minus, I'm I'm happy to give it up. So I'm I I have one bone to pick with you. I wasn't necessarily planning to bring this up, but it's become a sore spot for me personally in my life and you sort of bumped into it. I recently had Charles Murray on the

cast yeah and now, as you might predict, being attacked as a racist in certain circles for merely having had a perfectly cordial conversation with him and many listeners. In anticipation, of this podcast with you have reminded me that you were more crit full of Murray in your book than I was when I had him on the podcast, and so they want us to discuss this. So. I you know, I don't we don't have spent a lot of time on this and it wouldn't have to spend a lot of time on Murray. We can talk about that. Just a general question of intelligence, but I read obviously what you wrote your book and I went back and read the relevant chapters in the Bell curve, and it seems to me that, like nearly everyone who writes about Murray, you seem to feel under considerable pressure to distance yourself from his reputation and in my view this leads you to make at least a couple of obvious mistakes. But to really get into this, I would have to read the passages from your

look out loud on the podcast, which I'm not going to do, and I would have read a fairly long passage from Murray. I can summarize, I can summarize our differences and, I think they're not. I don't think there was thanks. I think they. Let me just let me flag once I know, there's one difference which I do want to talk about, which is not necessarily mistaken. It's definitely a point of valid debate. There were a couple of moves you made there that struck me at the very least sloppy, and I just want to fly them for you and and listeners so that so that they can go look at both books if they there and you can go back and look at what I'm talking about, because I feel like I'm going to take just one example the use you made of there's a transracial adoptees study, there's a study of kids that had one or two biological parents who are black and they were adopted by white parents right, and so this was a only by scar and Weinberg, and you cite this study pointing out that the adopted children had a mean iq of one hundred

fix, that's even higher than the white average, and you single this out. As some of the strongest evidence that the IQ testing was was biased. But. Scar in weinsberg did a follow up study, which is again described in the same paragraph in Murray's book that Significantly muddy the waters that should show that racial like he was stratified in their follow up study, and you don't cite that study right, which is when you go to look at Murray after reading your book. This seems like a fairly Aaron oversight, at least, but this again is something it's hard to parse without just reading the text. I should say honestly: this is not a topic that has ever posted me as I got I I simply want to talk to Marie after I saw what happened him at Middlebury and where I realized, with some degree of shock that I had always assumed

that where there was that much smoke, there had to be fire, and I assume that when, when you have people like Richard Nisbett, calling you a racist and a pseudo pseudoscientist, you must be guilty of something. You're now I have nisbet calling me, or at least insinuating, that I'm a racist and a suit a scientist as Recently is twenty. Four hours ago he published a piece in VOX magazine which is completely confused. Responding to the podcast I did with Murray's actually listened is that I have listed the forecasted, maybe let me tell you what I think they substantive issues are and I'll. Try to summarize and then, but not because he was just finish this. The final point- that because of my interest here, is not in the genetics of intelligence and certainly not in racial disparities, intelligence, J.

Headache or otherwise. I've always felt that looking for racial differences in anything is a dubious thing to do, or at least I haven't heard a good justification for it. But what I'm very interested in is in the way in which it's becoming impossible to talk about facts when they brush up against these taboo rails, and The toxicity of this is just very difficult to digest in one's life. I want to look at them. I can't imagine how Murray has felt these last twenty three years. This is a man who has been treated incredibly unfairly Leanne and again, I would argue that or by no means a glaring example of this. But even in your case, I feel, if you go back and look, you will discover that he was not hiding the ball. The way you claimed he was hiding the ball and that you that you are not making a totally fair, so what was in his book. So I just invite you to go. Look at that again

but let's talk about not only have I read Charles, but actually I've had correspondence with Charles in the pre publication stated this book, so so uh uh sometimes happy to share that, and it was you know it was. It was an extremely civil correspondence. I wanted to get to the heart of the issue. The point that you're making about this car Weinberg Study and in subsequent studies, is exactly right. They were muddy studies and the the the central point in in the gene is to point out number one, that there were many studies and to draw strong conclusion from Alistair studies in either direction is, is unwarranted. That is the point I leave in the book is this, which is to say that so it's it's a non. It's unfair to say that did I do

in you know. This is this. Is that, and that is the the the the counter. So let me give you what I think is is that that the three questions and I'll tell you my thoughts about them. I think Charles is thoughtful about these. I I I worry that he that to get you know he has. He has over interpreted money studies, that's not a crime, that's not a criminal thing to do. It is the job of a very thoughtful journalists to try to interpret my studies, but it's equally important to remind us that the studies are inconclusive on several aspects. Let me just split. The question did three questions, but before you did, I just I just want to get it. We got to be. Forgive me if, as a host, I begin to speak a little more defensively here, but we're recording this podcast really just like as a tsunami of criticism, is breaking over me for my podcast with Charles. So yes, some Studies are certainly muddy and the data is not in on everything, but there are some findings where the

jury really is no longer out. So the next yeah so interrupt me. If you think that the job that I'm, that I'm mudding Mudding studies that are not fine, so the question- One question number one is: does the iq test predict? Is it? Is it a great surrogate for intelligence, so I would say the following, which is that this is this issue has been studied. Although much is to be done in the future, it depends on who you ask so if, if, if you're, if, if it's about certain aspects of performance short predicts certain aspects of performance in this world- but it actually is- is a relatively poor predictor of other aspects of performance, including aspects of academic. So in some cases it correlates highly with with how

perform in the world. In other cases, it it college it's poorly with how how perform in the the. I think, that's what the jury jury. That's that's the general case of what the jury says. Would you agree that, with that yeah, this is a great way to proceed? Let's just go point by point. So, in certain cases, that's true, but that's a slightly tendentious way of describing and so, for instance, I queue for certain things is necessary, but not sufficient or having a high iq is necessary, but not sufficient to other things. Clearly, like motivation, an ability to to for pleasure right, you did it and and and set goals. A maze of these are are features that don't aren't necessarily tide to IQ and have a lot to do with in terms of explaining differential success between people, but if you're going to tell Maine, what's your prospects of success as a theoretical physicist, with a an iq of a hundred, not great, but the point. I agree with that, but the point here is to Clara,

by and say say that the world is not made of theoretical physicists. The word is very, very different some people who you know it's me, Lee Krasner is and to replicate this this and the people who are athletes and and Queen Elizabeth. I'm sorry other way of saying that is that intelligence is not the only thing we value or they will get you good outcomes in life. But there is you have a quiz with how we define intelligence- which I think is right at the heart here so talk about the problem in defining this- notion of general intelligence by correlating the outcome of an iq test with differential success in life, because you talk about that yeah. I I'm I'm, I'm a cancer scientists and the genetics is one of the things that I'm always looking for is is is what's called a you can call it a gold standard, or what what's the standard by which it will be judged

when we measure something, what are we trying to correlate that? What what? What? What is the end point of that by which the it? What is an independent or a non dipper, and and that we can use to judge whether what we're measuring is worthwhile, measuring or not and the but the. But the point is that, when we use the word intelligence, that is a powerful, culturally loaded word were so I'm very much about we're. Not talking about the performance on a test culturally loaded, word and so on. My point here is that it would be helpful if I I'll be a counter example. If it turned out that the I q test was correlated a hundred percent with a performance in diverse activities in the world aging from you know the Bron James to Queen Elizabeth, I would say fine, you know, that's the that's a good test. Currently, the the the current format of the test seems to predict something about our capacity to process information it, but

take it away what it's used in the war in the real world is, I'm not so sure about, and that's what that's that's. The first thing, I'm saying about the the the you know the don't confuse the I q test with the word intelligence. Well, actually, I think you say something different in your book, which is seems to be great hunting, that there is a fairly strong correlation between the results of an iq test and six in areas where general intelligence is valuable, so friends instance, exactly correct: canonical writing articles justice, in other words, this there's a circular in this test which which does not apply to the broad real world. So, let's see we agree on on on these disagreements. Guy going to the second piece, because it's a new threat before you do that there seems to be a bit of confusion here, because it does apply to the broad.

The world is just that the broad real world has been made by the same people who make I q tests some to to make this simple, like it's of an iq test, puts great weight on the side. Size of a person's vocabulary, and we find that people with big vocabularies succeed in academia? This is a circular justification, because that is this. The same people in academia. We were taught that that's the that's the point that I make several times in the book. I do with a hundred percent. Yes, okay. I just want to make that clearly stated so. The second question which is relevant here is where they're testing on the I q test is heritable or inheritable. So it's a very important point, and so it and then pointed to stick shooting those towards heritable an inheritable. So when we talk about something being heritable, we're asking the question: is there a powerful or not powerful, moderate genetic compl?

Do it when we come with something mean inheritable asking the question: how likely is it that that set of genes work or components marches across generations in intact form so clearly understood yeah? So the way we measure her the question of whether something is heritable or not is to twin studies, and I very clearly point And I in fact this I I owe this to discuss. One is with Charles Murray, in which it is. I think it is very believable that the results of the I q best armor it too highly heritable, in other words, twins share concordance in such in such affairs. Also know, based on studies of identical versus, fraternal twins that multiple g means and gene environment interactions are probably involved, because no single gene is seems to be highly correlated individually. There are certain genes that have been looked at and we talked about some of them so

direct. Consequence of that is that IQ is a very is, is one of the many human features which is heritable but not easily inheritable right, So I agree with that, but I just to give some context here. We are now speaking in a contest. Swear Murray, and now I get attacked for saying that IQ is significantly Myrtle and when this is in fact one of the most consistent findings in behavioral genetics. In fact, Robert Plomin men colleagues just published an article, I think three months ago, titled the top ten replicated findings in behavioral genetics and the heritability of IQ is one of them. So this is like this. One of the things that is rap for that. But but that's correct I mean you know, so I I think that you, at least with me out with with the GNU con, find fault with the stink shun between heritability inheritability. I think people use

language incorrectly. We should be using that language correctly. Heritability is not the same as heritability and when you say something is heritable you're not say Something is inheritable, that's that's just because those two words have similar data, But if people want to engage in this debate with you and Charles and other people, they should look at the literature. And the answer is yes, and just to spell at another point here again, this is what's so crazy. Making about this is that most of the criticism I see of Murray and certainly most of the criticism I have seen of my conversation with him relies on asserting that we claim things that we didn't and ignoring things that we in fact said so. One point to make here is that, even if something like intelligence is highly heritable,

eighty percent say heritable, you don't know to what degree an individual's intelligence was the product of environmental influence. The mistake at a clear case if it is not charged- and it's a case that I brought up with Marie something like. Height is unambiguously heritable and if we found an island of people, who were you- know five feet tall just knowing that there are five feet tall, wouldn't tell us that they don't have the genetic ability to be as tall as the Dutch, because we have to find out whether there are being systematically stunted say by malnutrition. You don't know based on the outcome whether there is a medic explanation for what you see and- and in fact I eat- this- is the very example that I I use in the gene. You know when you look at a plot. I use the word. I used a blanket of human being when a blind is grows to a certain size. You don't

know whether that size is the product of nutrition or the soil well or the environment or its genes. Yes, okay, we agree about that. It seems perfectly yes, sir, so I eat I'm sorry again about the flat, but it seems to me that there's a fundamental misconception about the difference, heritability an inherent ability. You won't find any big beef with me. I think in asserting that Gee and what what what the IQ test measures and you have to you and I have some exactly it measures, but what it measures is heritable, but not easily inheritable. So let's talk about what it meant because I agree with you that there is clearly some cultural construction I I'd so so want to go back to the point we were. We were discussing a few moments ago, which led me to finish the third question. I wanted well what sure yeah the first question which which we can also spend a lot of time. So, first, let me ask is

what is IQ measure, what its relationship with the real world is in the circularity of that argument. The second question is the distinction, but heritability an inherent ability of off like you, we we, I I agree with Charles about this. In fact it's it would be hard to find that data against this. The third question is the is the racial genetics, so we agree. We talk about the first two. To what extent is is race then has has to do with question? Does it have to do with, like you know, things that are heritable, but not inheritable tend not to running in races, even if you construct them, for the simple reason is because of of mendelian Genetics two is that the gene- spends a lot of time, questioning the id yeah. What erases the victorian idea of race is being run rapidly, reconstructed today rapidly and dramatically, being reconstructed and is being reconstructed in terms of geographic distributions, so

The the old ideas of of dividing races, we've turned out genetically speaking, are likely to contain lump people into categories where they fundamentally don't belong because of their background, and because particular their racial and genetic- sorry, not the racial they geographic background. So this is just to say that extr ordinary claims demand extraordinary evidence and the first attempts to answer the third question my mind have not risen to that extraordinary evidence in implicating or or cross segregating, races with IQ, because the the term race itself is being redefined right now but in my understanding all of these data, I think there is a lot you can view it as agnostic. With respect to the reality of race or the or the actual race of any of the subjects, but it's just based on how people self identify with respect to raise their enough that stuff I dedicate

could be circular. But yes fair enough, so I mean you: have we have a tradition of people self identifying with respect to the race? They think they are whether or not race is a valid concept and then we're getting a persistent and incredibly annoying difference in the mean performance on IQ tests on sat tests on tests of everything in this area, and this is the thing that is so toxic to talk about it's not, toxic to talk about once we realize what the limitations are at least to me: it's not toxic drop, but once we realize, as we've done now, sequentially realize what the fundamental limitations an advantage. There's of each of these individual components. Are it's not toxic talk with long as we understand the pieces of the puzzle that allows. I think us to think about questions like how circular is his death. How much does it rely on particular constructions of tests? How much is the in

his motivation, a factor in someone taking a test or not is? Is the self identification of race real? The the point is that bear it to me I I know this is not true for Charles, but to me the each of these individual components. If you were to think about this as a vast machine, each of these individual components seems to have enough fuzziness to it that making a can vision about the vast machine and then making social policy conclusions about the big machine it is, is more suspect than I think Charles thinks it is. This is to say that these are you know these are important questions, but they are that they would be. You know, there's an end in incredible amount of fundamental slippage in vocabulary- and I hope again by having this conversation at least we're getting through some of those slippages vocabulary yeah, I don't think

is guilty of the slippage that is attributed to him about. The problem, for me is that there is this fictional version of his work and a and of the man that has been manufactured in risk, wants to the Bell curve, and then you have everyone reacting to that fiction, and you, you know he's someone who is still can't stand up. Diversity and give a talk without some reasonable threat of violence. I could you might tell you my own, because once it might was extremely civil yup we talk, we can hardly talk to be exchanged, letters and thought about genetics, and I told him about you know some of these fundamental concerns or disagreements. I have one last piece that I'm gonna tell you, which I think is important to all of this, and that is that that goes into a kind of philosophical question, is not about data crunching, but is

a philosophical question about what we look for in the human genome, when we my argument, which is actually the most important argument in that section of the gene, when we look for performances in particular test, the more we define the test as a surrogate for whatever it might be chances are that we will find genetic determinants of that so loud. I give an example if we, if we decide it does a society that beauty was having blue eyes and sure enough. You'd find a gene or a set of jeans that were correlated with the blue eyes, and you decide that you do use genetic. This again gets to the whole point which you are trying to make, which is my fundamental beef with all of this is not the validity of the heritability of the test. My fundamental problem is that these us, better business secularity in these arguments and if we meet the genome is not. This is reflected if we look for narrow traits will find no trace in the genome

I believe that if we define athletics in a very narrow way as the as the capacity to run a particular distance for a particular amount of time, there will be genetic coral. It's of that idea. And you and I can then have a discussion about you- know what the world would be like if we all of a sudden widened the definition of mathematics to include playing chess or definition of sports to include playing some other game that has nothing to do with, with with the particular definition that we have today. My point here is the following, which is that, as we enter, what is clearly a toxic arena, we just have to be very careful in dissect

methodically key in a clear eyed manner. Without assigning blame ascribing blame what parts of the machine I have data that is powerful and functional, which is what parts of the machine I have data out, which is which is more suspect because of a vast historical, cultural and, frankly, racist apparatus that is surrounded this country to other countries for years. That's all I'm trying to say so. I want to press on this point just for a couple more minutes, and then I think this will be the last thing we talk about on this topic and then a guy I don't want to. I know your time is getting short as is mine, and I do want to ask you a few questions about cancer, but this is. This is just too interesting to leave right here. I take your point that we could make arbitrarily narrow definitions of n saying and then test for them, and then we would find that there was a Jeanette

vantage in one group or another for that thing, and that would be a strange thing to do, but the definition of something like intelligence and even the athleticism, I think, is a perfect analogy or or it was a very good one- is ends as arbitrarily circumscribed. As all of that to take athleticism our notion of that of what it is to be a great athlete is based, rather obviously on the various ways we can interact with the world and there are clearly attributes rather generalizable attributes like strength and speed and agility and hand eye coordination, and probably even things like body symmetry right and the underlying genetics of all of that. That correlate with success, not only in basically every sport, you can name but everything you could conceivably of invent. Let me

copyright there I know where you're going and there are some tradeoffs right. So if you want to be profound tradeoffs that profound traders, a weightlifter in a marathon runner there. If you are into sports, not just athletes, a chess player versus you know how long jumper, okay, but again you can only this is only so elastic your because, yes, we can understand those trade offs with into a larger caught a footprint of what it means to be a great athlete. But when you take someone like Bo Jackson, okay, who for those who don't recall and he's one of the few people who played to professional sports right he to be played football and baseball at the highest level. Now it is not a stretch to say that what ever that, if you came up

definition of athleticism that excluded him, you've got a pretty weird definition. I know it he's not gonna be the world's greatest marathoner I buy. I would doubt that, but the space of all possible sports there is very unlikely to be a sport where I'm going to be better than Bo Jackson. You know if you've got us at the same age and gave us the same training in the new sport. I'm not saying I'm going to specially terribly athlete, but but I'm just saying, there's a ok. Ok then he then Bo Bo Jackson is going to beat you at this new sport if it all all relies on will see, the wood is turned away from that you know. Basically, we are finding less and less all such general sportsman Bo Jackson would do terribly. Against a very average kenyan marathoner. He would do terribly instead, relatively average basketball player. I would imagine today, I don't know, I don't know the particulars, but the point there is that the world has become, and it's in its newness in israel-

I meant in its diversity. Would you like it or not you dislike it? You do whatever might be the idea, in fact, of the general sports. Man has become less and less relevant today, but it's well not completely irrelevant, and it's still it's still highly relevant. Again, I mean I Just say that I would bet on Bo Jackson again this morning, for the sports would go check out who's running marathon today, how many general sportsman in the marathon, but that's an extremely unique phenotypic case- that's not emblematic of most sports right and then it things to be seen whether such tradeoffs exist- and this could be where the the and I she breaks down, I'm not so sure. There's such tradeoffs with respect to intelligence, and once we build Super intelligent machines, right. Imagine, building a machine, that's better than us at everything. We can plausibly call a cognitive task. Well then, in the presence of such a machine, this conversation were

it is going to seem pointless. I met with them what what we it's gonna, be like chess, all the way down right, the machines just better than a than us at facial recognition, memory, arithmetic, chess and everything else we can name is not clear. You're going to get the kenyan marathon or trade off where will be able to point to the thing that the machine can do and will never do yeah, I don't I don't doubt it that doesn't convince either direction, I mean one thing: we know a little bit about taking a little bit about machines and machine intelligence in medicine, the one. What we know is that when you have a machine, maybe this is relevant. When you have a machine, that's been partially trained on one algorithm, it tends to do better on other algorithms you, but you can read that as the cup half full half empty, the cup half full would say that sure that you know there's there's some kind of

general ability, that's been acquired by this machine that now allows it to to to do to find another other than what we're not there. Yet with machines. I mean it's, it's good. It's clear that we're just there's nothing like general, more intelligence emerging in machines, even though we do have some general purpose- algorithms. It's not I mean they're still general within the machine in now. She doesn't help me very much because I don't know enough. We don't know enough about the structure of the way of knowledge, acquisition, skill acquisitions and put Julie reason, acquisition in in machines that will learn, but I I'm not sure we know enough take another machine who that that we do know a little bit about you. Take someone like John VON Neumann right and so any definition of general intelligence. That Exc, who did John VON Neumann or where he didn't rank extort really high, would be a bad definition. Given the man's talents and it's hard to

see a lot of trade offs there. That was he the world's greatest poet, probably not, but it's well. You just gave an example, but The idea that he would be a bad poet seems rather far fetched. Did he write any poetry? I have no idea Thetical so anyway I mean you know, but every example that you come up with has exactly these kinds of endemic problems right. So my point is we didn't arrive at our definition of intelligence, pure. Only by accident or by Wim, it's not like. We just got faster with blue eyes and blue on her and said: that's that's beauty for all time, but we did it I, and by by eight, by a process of historical and cultural mechanisms- and my point again is my point again, that there's a circularity there and that's all, I'm I'm not saying that. I'm not, but you know I will grow, can. Then I have granted stew

people who've measured these qualities that in fact the qualities correlate their highly highly correlated with actually highly through life. It doesn't not like they're stochastically Van incoming adventure. That would be even bigger problem, but they don't get more correlated through life, so all of this accepted, I think, might be. I just do not cause on the all the x. I didn't listen to that particular podcast, but I think I feel bad. Dad that that you know you're being blamed for something you know people are listening to that. Okay, saying all of that said my mom, you know this is that a relatively small section of the zine Beckham My argument will be that has been that there is a circularity and narrow things are often found in the genome. If you define the narrowly and those narrow definitions arise, you're right highly by whim, but by a comment

in all of our historical circumstance, which is worth questioning- that's all I'm so, okay. Well, it was nice first. I just wanna apologize to have ambushed you with this particular topic, because it's just the weird conjunction of of what you wrote and what is happening on other podcasts. To me I was not aware it entirely, but that yeah I was at a book signing, and someone said you know you gonna talk about this, and I said I only for the people and not just. I think this is six pages of a six hundred page book, so while you're you're a good sport here- and I appreciate you to get into the weeds with Maine, but obviously one of the things- we want intelligence for insofar as we've defined it is for people like you to cure cancer. Sooner rather than later- and I just want to take a few minutes to talk about cancer

forty! This is not informed by my having read your much celebrated book, the emperor of all maladies on the topic, but it it's probably safe to say that everyone listening to this PA the cast has either had or will have some encounter with cancer there either going to get it or someone close to them. Will. I have a close member of my family who just went through a major ordeal with it. It amazingly he seems to be someone who is among the tiny percentage of people who seems to have successfully treated or been treated for stage four pancreatic cancer. First, I want to ask you: Why does cancer have this unique status and why? Why are people left battling cancer? You don't hear, People battling heart disease. Is this based on the the range of treatments that that exist for it or how You think of this person very diverse disease.

Disease of enormous diversity, genetic diversity and there's not one cancer, but many cancers. It is these, unlike heart disease, unlike most other diseases with the level of genetic diversity, is enormous and now we're beginning to understand, is not just generic diversity. There's also component powerful component revolution here. Cancer cells are constantly valving and their evolving by creating their own environment. Don't micro environments, they defy the immune system through a process of selection and evolution, etc. So it's a very different kind of battleground, as it were compared to heart disease. Does it make sense to keep

find cancer in terms of their organs of origin like long and breast and prostate. Is that or or is our thinking change in a Huff wait a half a moment about that? It certainly made sense initially from from the standpoint it, but now that the other genetics is is redefining back so basically of it to my kind of that, your brain cancer could share some jeans with with with the breast cancer, not that I said when we tried it seats based on these kind of new genetic times. Those are still not very successful in part, because somehow the other cancer so seems to remember it's tissue of origin, so son, the truth is somewhere in between interesting and finally is: is there any important difference between childhood and adult cancer? It seems to me that there is some fundamental differences between them. They started cancer center to be more responsive to many chemotherapy's

and the quick answer. Is we don't exactly why all right? I am sorry to have given one of the most important diseases, such short shrift, in the presence of one of the most important writers and thinkers on the topic. This is just going to justify another podcast before we all get cancer set Arthur. Thank you so much thanks. Thank you. If you find this podcast Bible. There are many ways you can support it. You review it on Itunes or Stitcher or wherever you happen to listen to it. You can share social media with your friends, you can blog about it discuss it on your own podcast or you can support it directly and you can do this. I subscribe in through my website at SAM Harris, DOT, org and there you find subscriber only content, which includes my ass, anything episodes, you also get access to advance tickets to my live events as well as streaming. Video of some of the

events, and you also get to hear the bonus questions from any of these interviews. All of these