Opinion | Humanitys Awesome, Terrifying Takeover of Evolution – The New York Times

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Im Ezra Klein, and this is The Ezra Klein Show.

So over the past couple of years, theres been this worry stalking my own work. What if Im just wasting my time covering taxes and public options and Donald Trump and filibuster reform? What if the thing, the only thing that really matters right now is CRISPR, that everything else comparatively is just a sideshow CRISPR. Over the past few decades, scientists have studied this enzyme bacteria used to recognize viruses and just cut them apart. It is wild how this works. So bacteria, they fight off viruses by snatching fragments of the viruss own DNA and then loading these sequences into these enzymes. And these sequences they then program the enzymes to patrol the cell looking for a viral match, like looking for that virus again. And when it finds it, the enzyme cuts the viral DNA and saves a cell from infection. But heres the thing that won Jennifer Doudna and Emmanuel Charpentier a Nobel Prize in chemistry in 2020. They figured out, along with many, many other scientists, how to code these enzymes with whatever genetic sequence we want, and then we can make these incredibly precise cuts wherever that sequence is located, and we can actually replace that sequence. We can replace it with new genetic information of our choice. We can make these very precise edits in genetic code and not just our code but the code of mice, of plants, of pigs, of mosquitoes. Were learning how to take control of not just human evolution but arguably every species evolution with a precision we have never had before. Weve had the ability to shape genetics by breeding plants together, dogs together, doing this very crude genetic editing in recent decades, but nothing like this. Whats becoming possible now is everything from carrying genetic diseases like sickle cell anemia and Huntingtons all the way up to imbuing humans with characteristics weve never had before making us stronger, faster, smarter, giving us better memories, allowing us to see in new light spectrums. We really dont know whats possible here, but it seems like the answer is a lot a lot a lot. There are still technical problems. Its expensive, and there are issues to work out. But we are talking when, not if, for all of this. And so for years now theres been this part of me that thought, I just need to drop everything and try to understand CRISPR and its moral and political and human and economic, I guess, implications. Short story, I didnt do that, but luckily Walter Isaacson did do that. Isaacson is the former editor of Time magazine, the former head of CNN, one of the great living biographers. Hes written biographies of Leonardo da Vinci and Einstein and Steve Jobs, and his new one is called The Codebreaker Jennifer Doudna, Gene Editing, and the Future of the Human Race, which sounds like a biography of Jennifer Doudna, who Ive had on an older iteration of the show before, but this is really a biography of the scientific process that led to CRISPR and the people trying to answer the questions it poses. So now I get to ask him all the questions Ive wanted to spend the time to answer myself. As always, my email is ezrakleinshow@nytimes.com. Heres Walter Isaacson.

Ive heard you talk about there being three technological revolutions, atoms, bits, and genes. Tell me what those were and why I should see genes on that list.

These are the three fundamental kernels of our existence, the atom, the bit which are binary digits that can encode information and the gene. So you get the first half of the 20th century, its a revolution driven by the atom and Einsteins theories. Everything from the atom bomb to space travel to semiconductors come out of that. Second half of the 20th century I grew up in was the digital revolution where computers, the internet, and the microchip all combine so that we can process anything in digital bits. And now were about to enter the age of the genetic revolution where the code of life, the genetic code will replace the digital code as being the core thing were going to program, and well be programming molecules, not just microchips. And I think this is going to have even more of an impact than being able to get an iPhone or a personal computer. Its going to allow us to rewrite our own genes and certainly cure genetic diseases.

How well do we understand the coding language here? When were coding software on a computer, weve created these languages. We have a sense of what the computers can do. Obviously coding requires solving some hard problems, but its within a universe we understand pretty well. How well do we understand the coding instructions we might want to give something like CRISPR or some of these other technologies?

As you know, we have about 3 billion pairs of letters that make up our DNA. And beginning in the late 1990s, groups of scientists, including the US government, decided, all right, lets sequence the entire human genome. Now, that didnt get us too much. You needed another step to say, all right, each three-letter sequence usually has some meaning to it. Lets try to map, out of the 3 billion letters, what each of these sequences might do. Like one might help make a hormone or a neuron or make your hair blonde and mine brown or something. We can map the human genome pretty well now. This is particularly easy for single-gene properties or, for that matter, mutations like sickle cell. Sickle cells just one letter off, and we know exactly where that letter is in the human genome. And if it switches from one letter to another, youve got a real bug in the system, not just a bug but a very dangerous and deadly bug in the system. Likewise, muscular dystrophy, cystic fibrosis. Those are pretty easy to spot the little flaws in the 3 billion base pairs we have. If you want to get to something more complicated, you can just move up the gradation. Muscle mass is pretty easy to regulate. Height is pretty well determined. But those are multiple sequences that do it, and we dont understand those very well. And then you get to the most complex of all where things like schizophrenia, bipolar disease. What predisposes us to that? What predisposes us to have a high IQ? Is that mainly genetic or mainly environmental? So those are the parts of the genome we dont fully understand.

So it sounds to me theres almost a ladder of programming complexity here. Theres, as you say, a set of conditions that we understand. There is a mistake in the code, and we can look at it. We can look at normal code. We can look at code that has this error in it, and then you say, OK, were going to just change that little mistake. Then there are things where we pretty well understand how it works, like, say, muscle mass. We know there are certain things we can turn on and off because weve watched it happen in people. Then there are things we know people currently have like bipolar disorder or schizophrenia or high IQ, but we dont really know how it works. And then I assume there are things that people dont currently have. You bring this up in the book. Like one can imagine in the future us understanding how to give people capabilities they dont currently have through genomic editing. But because we cant currently look at people and see that, we dont know how to do that, that coding. Is that a reasonable way of framing the ladder?

Absolutely, and the interesting thing about the ladder is we could create new things for human capabilities, maybe even to hear different frequencies or be able to see colors that are off the normal visible spectrum. But the important thing you put your finger on is we say its not in the wild. In other words, nobody really has it. And so its far safer to edit the human genome to create a genome that already exists in other people in the wild form. But if youre going to edit something thats never existed before, I think weve got a few decades before were going to try to cross that line.

So as you gesture towards, weve had the capacity to do some level of genetic editing or changing for some decades now. What did CRISPR add to our capabilities here? What made CRISPR different?

What made CRISPR different is its not just recombining DNA or even using the old, clunky tools we used to have that could try to cut DNA and make an edit known as ZFNs or TALENs and things like that. What made it different is that its easily reprogrammed. You can say, OK, I want to do it right here at this sequence. And so you have this guide RNA, and the guide RNA can just be much more precise, and it can be done much more quickly. Its like the Johnson & Johnson vaccine, which is a really great one, but thats an engineered virus that carries a gene to help do it. I got the Pfizer. That meant it just used messenger RNA. And if the spike protein continues to mutate in ways, it is much quicker to just reprogram that messenger RNA to build a fragment of the new shape of the spike protein when youre using something thats an RNA-programmed device, whether it be a CRISPR tool or a vaccine.

And tell me if this is wrong, because it probably is going to be, but I think its actually good to use the vaccines here because people have a lot of familiarity. One of the issues is the way the Johnson & Johnson vaccine works is you really have to grow this sort of semi-inert virus to do it, whereas the mRNA vaccines are much more of a programming challenge. I mean, very famously I think Moderna made theirs in like a weekend. And so theres this capacity really not just to treat this as life but to treat it as programming. Is that fair or is that an unbelievably poor way of putting it?

No, its exactly fair, and the fact that you can do it over a weekend makes it a lot better than growing or doing genetic engineering or recombinant DNA or growing a virus or a whole bunch of viruses. Those are the type of vaccines weve had in the past. With the genetic vaccines, as you say, it was done by Moderna over a weekend. Once they got the sequence from China, what the spike protein looked like, it was pretty fast to do it.

So whenever I have a conversation with anybody who knows anything about CRISPR, I will hear them explain it, and it will sound like we can do absolutely anything we want. And then youll ask them if we can do these amazing things. Theyll say, well, no. Its not safe. It makes mistakes. Its very expensive to do something like, say, curing sickle cell anemia in somebody. So what makes using CRISPR hard? What are the difficulties? What can go wrong?

Well, the hardest thing is the delivery system. Now, you talk about sickle cell. It actually has been done. It was done finally five or six months ago in a woman named Victoria Gray from Mississippi. She becomes the first patient where they used CRISPR to edit her genes so she no longer is producing sickled cells, and shes now producing healthy blood cells. What made it difficult was not the editing of her cells but you have to take the stem cells and take it out of the blood and some bone marrow, and then you have to put it back into her system. So thats what cost a whole lot, just as any stem-cell transplants would do. What Jennifer Doudna, the hero of my book, is doing is gathering a group of people saying, well, how can we do it much faster and easier? Well, the first, simplest way to do it much faster and easier is dont take the cells out of the body and then have to reinsert them in the body. Lets do it instead of in vitro, as its called when you do it out of the body, do it in vivo, which means make the edits in the body. Now, thats a year or two down the road, but that brings the cost down exponentially. But as you can see, the editing weve done it. A Chinese doctor did it in embryos. Take out the receptor for HIV, the virus that causes AIDS. Weve done it now in clinical trials in Portland to do it in eye cells for people who have congenital blindness, to reverse those. So the actual editing is not only easy. It has been done. The difficult for medicine is you got to get it in the right cell. For example, CRISPR comes from a system that bacteria used to kill viruses. Well, thats something we would love to have. And so you could say instead of having an immune system or the human immune system be jacked up and kicked into orbit by vaccines, which is a tricky thing to do, why dont we just have pills or inhalers or something that say whenever that virus comes in, chop it up and kill it? That would be a simpler, safer way to do it, and we will have that in a couple of years. But the difficulty is not doing that through CRISPR. The difficulty is getting it into the right cells in the lungs or the right cells in the body where the virus may exist. So thats the less exciting frontier, but the important frontier is delivery systems.

You talk in the book about this biohacker who on a live YouTube stream or something injects himself with the CRISPR edit that would allow for radical increases in muscle mass, but it doesnt really work, and you didnt expect it to work because youd have to be doing that over a long period of time. Why would you have to be doing that repeatedly? Why cant you just hit yourself with that injection and all of a sudden youre The Rock?

Because our cells in our body tend to replenish themselves. They tend to regenerate. And if you get new ones that havent been edited, that means the treatment wears off. Now, some cells in the body arent that way, including our eye cells. We dont make new eye cells. So once you edit the eye cells for congenital blindness, its once and done, like your Johnson & Johnson phrase. When it comes to sickle cell, now if you do it in STEM cells, that may work, and it may be permanent in the sense that once the stem cells are edited, the new blood cells will all be sickle free. The only way to make it permanent and Im about to cross an ethical line here is to do it in all the cells of the human body, which means doing it in early-stage embryos is the easiest way to do that or in reproductive cells, like sperm or eggs, at which point all cells in the body have the edit and you dont have to worry about refresher courses.

And just to ping on this for another second this is going to become real important in our conversation later on this is the germline-somatic distinction.

Bingo. Germline means youve done it so that its in reproductive cells. Youve done it before a patient is born. Youve edited the eggs of the sperm or very early-stage embryos. And that means not only will it be every cell in the body will carry the edit, if you do it right, it means that children will have those edits, and all descendants will have those edits. So once you cross the germline, meaning the line of inheritable edit, youve edited the human species. Somatic simply means in the body, like Victoria Gray down in Mississippi. It was done in her body, but it wasnt done for reproductive purposes. Now with sickle cell, were already talking about, well, lets edit it out. Lets say Victoria Gray wants to have more children. You could edit it out of her fertilized eggs or reproductive cells, and so her children would have inheritable, good blood cells rather than sickle cells.

Lets say you had unlimited money and few ethical strictures. What could CRISPR actually probably do right now?

Right now, its best at single-gene mutations. But if you really had a doctor in a clinic somewhere with no ethical guidelines, certainly there are things that clearly predispose height, for example, or muscle mass, as we talked about with our friend the biohacker. Thats just a myostatin regulator. And certainly, by the way, if we can make cells so that they arent sickled in the blood and carry more oxygen, that might make muscle mass or blood or endurance much better. And then obviously the type of diseases we have Tay Sachs, muscular dystrophy youd edit those out of your children if you wanted to.

What are you pretty sure then that we will be able to do at a price point available to, say, non-billionaires in the next 25 years?

Oh, in the next 25 years we could certainly do things like hair color, eye color, skin color. You could probably enhance memory, and you could get perilously close to things like neurons that give you faster mental processing power which, combined with better memory, may get you close to what we call intelligence. Those are the things that I think would be simple enough if youre giving a 25-year horizon.

It is at least plausible that in the next 25 years we will face a question of if you could make an edit so your children would have lets just call it photographic memory should you?

Yeah, you could, and the answer would be no. One of the joys of my life is I dont have a photographic memory, so I dont remember if youve ever written anything bad about me in your life. In fact, theres a wonderful book I just read about the joys of not having perfect memories. But I say that not just jokingly. I think its a be careful of what you wish for phenomenon. For example, muscle mass is pretty easy, as we said, and its already been done in cattle and in mice and double muscling and stuff. So you could do that for kids, and then youd have athletes who had better muscle mass and better twitch movement, and would that destroy athletics where, instead of admiring the athlete, were admiring their genetic engineer? Likewise, if you decide on height, I mean, thats an interesting one to think about because lets suppose and it wouldnt be that hard genetically to do it that you get edit a gene so somebody could be taller, eight inches taller. That would be really good if your kid, instead of being 5 foot 8, was 6 foot 4 or something and youd say, all right, I got a basketball player in the family. But suppose everybody did that. Its actually only a positional benefit or relative benefit because if everybody, if every kid in 40 years starts being eight inches taller, thats not going to help anybody. And given the size of airline seats, its really not going to be good for anybody. It would just help carpenters who have to raise doorjambs. So you have to decide, what is good for all of society? such as maybe editing out receptors for viruses. That could be good for all of society. You could even argue making people have better memory or better mental processing power, that could be good for all of society even if not everybody gets it. But there are certain things that if the rich can buy it and the poor cant, it gives a positional advantage. But if everybody can get it, it doesnt help society as a whole.

There are ways of thinking about CRISPR, which is that it is a frightening but remarkable new technology, and we want to put the strictures on it for it to be rare. And then theres another way of thinking about it, which is that it is a remarkable new technology which can do all these things and we want to wrap it in a politics, a distributional politics such that it could be common because what were afraid of is that the people who have wealth and privilege now will use it to create a genetic elite. And those are really, really quite different approaches, and I hear a lot more of the first, being afraid people are going to get out ahead of their skis on it, but I dont see too many people wrestling with the second and trying to think of this question of, OK, we want this, but what we want is for it to be widely available so the children of the rich and poor alike can be taller, can have better memory, or whatever it might be.

Yes, you should have George Church on your podcast because

I would love to have George Church on my podcast.

Yeah, we will work on this. I will call George. Hes been very helpful since the book came out because hes one of the main characters in the book and was at Harvard when Jennifer Doudna was a young student there. And George Church will say, excuse me, whats wrong with adding some IQ points or adding some strength or muscle mass or enhancement so that you can see infrared light if you want to? And then he would agree that the main ethical problem is the distribution problem in the sense that if its unequally distributed, you get to Brave New World, that science fiction. You get to the time machine. You get to the movie Gattaca if theres a genetic elite that can afford to have their kids enhanced and a subspecies thats not genetically enhanced. But thats not a problem with the technology. Thats a problem with our policy and our politics. [MUSIC PLAYING]

So I just did a podcast with the science-fiction writer Ted Chiang, and we were talking about artificial intelligence and the attraction to the question of itll take all the jobs or it will kill us all. And I was asking him what he thinks of this, and he said that one of the problems when people discuss technology is that they often speak as if theyre afraid of technology when what theyre afraid of is capitalism. And I actually dont think thats a great argument on A.I., but I think its a very good argument on CRISPR, which is to say that a lot of the questions on CRISPR are a little bit less about CRISPR or at least what some of the ones I worry about most than they are about capitalism, which is to say how it will be distributed.

Yeah. In the book I dont use capitalism because both its a loaded word and a more complex world, but I talk about state eugenics creating the master race where the governments were doing it. And this is the Nazis and, for that matter, at Cold Spring Harbor in the early 1900s in the US. And I say thats not the big fear now. I mean, were not going to have government-mandated child editing like in Brave New World. The fear is what I would call a free-market eugenics, and thats probably what youre calling the capitalist eugenics. And by free market, I mean as Robert Nozick writes about this, everybody can go to the genetic supermarket, and they can buy what they can afford. And companies will market cool things that you can get if you go to your fertility clinic and youre given the shopping list from the genetic supermarket. And in the privacy of that genetic clinic and they shut the door. They promise not to tell people what you chose. They say, what skin color do you want? What sexual orientation do you want? What height? What eye color? What IQ? And youd be a good moral person, Ezra, and so would I. I would make sure Id check off no bad genetic diseases, and Id wrestle with maybe congenital deafness because I would consider that a disability. But Id pause and think, well, people in the deaf community dont consider it a disability. Maybe its an interesting thing for our species. And as we go down the list, I wouldnt dare choose some of the things that other people might choose. But as it got more and more private and its a free-market choice, you may have more and more people saying heres the sexual orientation I want my kids. Heres the gender I want. Heres the height I want, the skin color I want, and these sort of things. And they wont be free, and so the rich would be able to buy taller children and whatever other types of things they would want. So we would do two things that would be bad if you had free-market gene editing, or as you might call it, capitalist gene editing. A, we would let the rich not only get better genes but they would encode it into their families so that you would have families with a genetic elite and families without it. And the second thing you might do if you had a free-market eugenics like this is you might edit out diversity. You might find there would be a lot fewer deaf people or fewer people who are short or fat, and you could go down the list where people may not want to go where you just let the free market edit out the diversity of our society. And as I sit here in New Orleans Im sitting on the balcony overlooking Royal Street. I look at all the diversity. I see people gay and straight and trans and tall and short and fat and skinny and Black and white and Creole and caf au lait colored. And people from Gallaudet University were by, and they were sign languaging. And I think, well, the diversity of the human species makes it really creative. Its really the wonderful, colorful thing about our species. And by the way, not being emotional about it, its also a good thing for the safety of our species, the health of our species that we have a lot of genetic diversity. And so you could march down a path of free-market choice and free-market eugenics with gene editing that would give us a genetically encoded elite and edit out the diversity of our species. Those are the two things I most worry about in the future of gene editing, both of which could be solved by policy. Its not something you need to solve by shunning the technology.

Well, theres so much here. So one concern here that the I think gesturing towards is you get into like a human monoculture, right? Weve done this with agriculture many, many times where we begin to select for, say, a kind of potato thats very good at growing in a particular condition, and weve gone now from hundreds of kinds of potatoes to one. And then a particular kind of blight comes, and it turns out that weve edited out the genes that we didnt think were doing anything but that gave us potatoes that were resistant to this blight. But I also want to touch on this question not just of diversity but of what we think of as disabilities. While preparing to chat with you, I read this editorial by Sandy Sufian and Rosemarie Garland-Thomson, who are two scholars who live with conditions of a sort that many would be excited to use CRISPR to eliminate. And they write and I want to quote this. Our genetic conditions are not simply entities that can be clipped away from us as if they were some kind of misspelled word or an awkward sentence in a document. We are whole beings with our genetic conditions forming a fundamental part of who we are. Still, many Americans, including medical providers and even some people with genetic differences, consider lives such as ours as not worth living as they are. Thats the end of the quote. And so this gets into really tricky territory of who is the deciding agent. The choice a parent may make on behalf of an unborn child may not be the same choice that a child would make for themselves.

Absolutely, and I quote them in the book and use them in the book because thats really an important thing about what we as a society or we as parents at the genetic supermarket with free markets would choose as disabilities. One of the most interesting ethical philosophers in my book is a kid named David Sanchez. Now, hes only 17 years old, and he loves playing basketball, but hes got sickle cell. And so out at Stanford where hes being treated they say, all right, we can edit this in you and fix it. And then they tell him, and by the way, we can edit it probably so that by the time you have children, we can make sure weve edited it out of your reproductive cells and your children will not have sickle cell anemia. And he first says, oh wow, thats wonderful. That would be great. Then he has a second thought. And he says, maybe it should be up to the kid later on after the kid is born to decide that. And you say, well, what do you mean? Would you want your kid to have sickle cell? And he says, well, probably not, but sickle cell forged me. It forged who I am. Its part of who I am. It made me empathetic more than most of my friends are. It made me resilient. I know how to get up off the floor. So Im not sure we should edit it out of my children before they decide whether they want that or not. And Im going, whoa, holy cow. Hes as good as the professional bioethicist you just quoted. And I talked to him later. Months later I get back to him, and I ask him again. Youd really want to not edit it out so that your kids might be born with sickle cell? He said no, and its like on third thought. I dont want him to have sickle cell. So yeah, Id do that. I said, well, what about the empathy? Well, he said, Id try to teach them empathy, but I dont want them to have to suffer the pain Ive suffered. And my point here is that we have first thoughts and second thoughts and maybe third thoughts. And so we have to figure out, what is it that we call disabilities? and do those forge our characters in ways that we want to keep? and who makes that decision? Is it the parent? Is it society? Can you wait until the kids already born? Well, no, not really if its a bad genetic disease. And so I hate to tell you Im going to spoil my book sales here. I dont have a last chapter that says heres the seven easy answers. We go with David Sanchez and other people hand in hand and I hope have first, second, and third thoughts, especially when it comes to making inheritable edits about things we call disabilities.

I want to bring up, say, an obvious objection even maybe a charge of hypocrisy here against myself. So Im pro-choice, within reasonable boundaries, and isnt there something odd about worrying over giving parents control of genetic questions that are marginal compared to the question of whether a child exists or not? And then one step beyond that, people now do a lot of genetic testing. And I mean, theres been lots of reporting on this. People often abort children who show up with Down syndrome on the testing. So arent we doing a lot of this in broader, cruder ways already?

Yeah, were doing it in broader, cruder ways like aborting kids that might have Down syndrome or even preimplantation genetic diagnosis, meaning you create in an IV clinic fertilized eggs and then you can sort of screen them to say which ones dont have Huntingtons or something and implant the ones that are healthy. Thats very crude, and its very if youre trying to produce a whole lot of fertilized eggs and you have multiple characteristics, its almost impossible to do. But yeah, we faced these types of things before, and youre right. Our default when I say our I mean yours and mine and probably 70 percent of your listeners. Our default is choice, parental choice, individual choice. Abortion, that should be a matter of the mothers choice. And so when it comes to reproductive decisions, we generally, especially in this society and especially after the eugenic horrors of the 20th century, we say lets leave that to individual families to make their own reproductive choices. But then you get to the point where you say, oh, and lets hand them this shopping list at the genetic supermarket and see what choices they might be able to afford. Does that take us into a brave new world, or is that just the same as weve had before but just a little bit more than weve had before? I think were getting into a brave new world now that we can make a whole lot of edits rather than just abort or not implant Down syndrome.

But I think choice rapidly becomes I dont want to say its irrelevant, but it is not free. So life is positional, and life for your children is really positional. And so if the other parents are making their kids taller and smarter and able to run further and you dont, you are setting your kid up for a much harder life. I also think about this in terms of international competition. If China decides that as part of their national destiny they want to begin enhancing Chinese children and they want that to be something that is encouraged, theres going to be pressure on other countries simply to keep up as a geopolitical stratagem. I mean, imagine if this was going on during the USSR-America competition of the Cold War. And so I dont know that choice is going to be as relevant here as what other people are doing. Our choices are very structured by the context in which they happen and the people and countries were trying to compete with.

Well, we see it all the time like college-admissions scandals. All right, well, I dont necessarily want to fake my kid as a lacrosse player, but other parents are doing it, and Ive got to get her into Princeton or something. So yeah, if you look at what parents will go through in order to get their kids into what they think are elite universities, imagine what theyll do if theyre handed a shopping list at a genetic supermarket and societal pressure is, hey, youve got to keep up. You cant let your neighbor have a kid whos six inches taller without buying your kids the genes to be six inches taller. Now, you could also then say, well, maybe societal pressure can work the other way, which is we dont allow this type of genetic enhancement. We allow it for fighting diseases only. And lets say that we can make this into an international accord, just like we might do on athletic doping. Say, OK, were going to have international rules that say these are the things that society just doesnt want to have happen. And some people are going to sneak off to clinics in the Cayman Islands and try to do it, but generally its like smuggling of elephant tusks or shoplifting at the corner store. We have a whole lot of restrictions against it, and well keep it in check. Those are the things I think we can decide as a society as a whole because when you get to the question of choice, as you pointed out, at a certain point, youre pressured to make every possible choice you can for your children. Now, let me give the counterargument, which is every species on this planet for a million years at least, great and small, have done whatever they could to make sure that their offspring survive and carry on genetically. So why should we be any different? Why shouldnt we produce super kids that will end up taking over our species? Well, Im uncomfortable with that, and I think we should try to keep these genes or genie in the bottle.

Yeah, I want to play with the flip now. I want to take the super-kid-advocate position because, Walter, how dare you? How dare you tell me that if my child has the capacity to not grow up with, on the one hand, maybe just like the level of anxiety that I and many of the people in my family have been wracked with thats an almost I dont want to say an easy one. But then why shouldnt the human race get smarter such that it can do more to invent renewable energy yeah, the George Church argument and the argument of many ethicists. I mean, we have big problems. We have made the human race smarter again and again and again. If you dont think putting kids in school every single day in ways that are pushing on their analytical intelligence and then putting them in a context where that changes which genes express themselves I mean, were way better at solving abstract problems and way better at knowing which direction were walking in than we used to be or then sort of hunter-gatherer societies that we see even in existence now are. We are changing gene expression all the time. We are changing humanitys capabilities over time all the time. And this idea that we should stop or that we should tell families or tell the race that weve come this far and no further, theres an argument that thats a crazy decision to make.

I agree that things that can make the human race better and smarter and healthier, thats a good thing. We should move forward on it. I think what we have to guard against is what we get back to the free-market-eugenics part, which is it helps the human race if everybody gets a bit smarter. It might help if everybody got a bit taller, although thats more of a positional advantage than a societal advantage. But certainly it would be societally good if everybody were a little bit smarter. Wed solve climate change and do some good things. The problem comes if you say a genetic elite of 10 percent of the privileged families on Earth get to have children that are twice as smart as the rest of the species. You get to exactly where we got in Brave New World or in the movie Gattaca, and do we really want to have subspecies that are genetically inferior?

Yeah, but this speaks to this idea that then what were afraid of is not CRISPR but capitalism.

And same is true. Yeah, I agree that my fear is not on CRISPR once we make it safe. I think you got a lot of unintended consequences. You start making somebody have better memory and God knows whats going to happen. But let us say weve determined that these genes are in the wild, that the people who have these genes are doing just fine. Therefore well try to give everybody the gene to have intelligence. And certainly you might start by saying, all right, instead of making everybody taller, lets make people who have the disadvantage of being very short, give them the eight inches first. In other words, if youre going to be born at 4 foot 4 inches tall, OK, we can give you the height. And then we give it to positional advantages for people who want to be taller. Likewise IQ. Certainly most people would say if youve got a birth defect or genetic defect thats going to affect your mental processing power, it would be great for all of society if we could fix those in a way that was healthy and safe. Then if you say maybe we can make all of society a little bit smarter, that becomes, as you said, a distributive-justice question, not a is this technology good? question.

One of the other kinds of competition here, or at least questions here, comes from the other kind of code were editing. I kept reading your book thinking theres always something poignant that we were learning how to edit genetic code at the same time as were getting pretty close to creating if not life than intelligence through code with A.I. And whenever I tap into that conversation for five minutes, people are worried that humanity is going to become more and more occupationally obsolete. But so that might then create this pressure to augment humanity because were almost creating our own competition at the same time.

Well, Im one of those people who believes that artificial intelligence will not actually succeed as fast as augmented human intelligence, which is sort of the Ada Lovelace, Doug Engelbart, Steve Jobs school is that if you combine our computational power and our enhanced mental processing powers that the combination of machines and humans with good interfaces so that they can share information and interact as seamlessly as possible, that will always do better than trying to invent machines that off on their own develop artificial intelligence and leave us behind. So I think the second half of the 21st century and this book is only about the first half of the 21st century will be about augmented intelligence in which the symbiosis between the A.I. of our machines and the augmented intelligence of ourselves try to get integrated seamlessly by a continuous process of better human-computer interfaces, which now were looking at graphical point and clicks on a screen. But if it can all be done by voice and telepathy or whatever, we can meld more seamlessly with our machines. But youve now taken me on a path thats far beyond either my pay grade or my imagination. [MUSIC PLAYING]

One of the things that is implicit in the conversation were having here, though weve questioned it a few times in a to-be-sure way, is whether or not we will understand what it is were doing. And there are no massive technological leaps humanity has made without tremendous unintended consequences, and thats particularly true when were dealing with things as complex as genetics, as our own brains. And so one thing that seems true to me here is that it may be real fun to be part of the humanity that exists on the other side of the long period of CRISPR trial and error, but it may really not be fun to be part of the humanity that exists in the middle of it when were trying things and we think we understand them. Like lets say we turn down the genes for anxiety, and it turns out people in that class not that anxious but really unmotivated, like really unmotivated and lethargic. Theres a real chance for CRISPR screwups that we thought things were doing one thing and we didnt understand as you say with memory, that its actually a really important part of creating a psychologically coherent person that you can reshape your memories to fit a cohesive story about your own life in which you are the hero and not just the villain. Thats a pretty scary piece of all this to me.

I think the unintended consequences is the good Pause button we should have each step of the way down this slippery slope because youre right. When you start editing out anxiety, how many fewer podcasters will there be on the planet? Or if you edit out depression, how many fewer Hemingways will there be on the planet? We dont want to go marching in a direction unless we think through and even test out what are some of the consequences going to be. And so that, to me, argues for the cautious and go slow approach, which is first lets do things that we truly know are health issues that are legitimate like sickle cell or Huntingtons. And lets do them carefully so we dont mess around with other genes. And as we go step by step, preferably hand in hand, we can avoid doing a massive cock up like an invention of a Facebook, something thats supposed to connect us but turns out to divide us, and has some genetic unintended consequence.

But I think theres another step there that we need to think about societally. So lets take the vaccines that were all dealing with now. Were not in a free-market vaccine world. I mean, theres no doubt that rich people who understand how to game systems and have people like clicking on the Refresh button, that richer people are getting vaccinated at a somewhat faster rate than poor people. That is happening. But nevertheless, we did not do this such that you can just walk in and if youre willing to pay 10x the vaccine cost or 200x the vaccine cost, you get it. Instead, its being apportioned out to state governments, and they are apportioning it out according to some criteria, and people are arguing over the criteria. But broadly, thats creating some curbs on the system. I mean, does this argue for a world where these sorts of advances come out more like that? If, for instance, if we dont have enough supply, if the price is too large, then maybe this doesnt get accepted by the FDA. Or if we do have it, it gets rolled out to certain people in certain cases. In California right now, they are apportioning double the vaccine allotment to counties that are lower on their Healthy Places Index. Maybe you actually have some level of reverse distribution. If were going to come out with something here that seems like it has a potential to increase inequality, you actually roll it out in a way where more disadvantaged communities get more access to the treatment. Now, obviously this would be easier within a nationalized or a single-payer health-care system, but I feel like this actually forces you into questions like that, much more structural questions than even just safety and cost questions.

Yes, absolutely, and the good thing about this vaccine rollout is weve been able to wrestle with these questions. And I think in some ways its been very good because despite the fact that you say maybe some rich people can get it first I just talked to one of the richest people I know yesterday, David Rubenstein, and he lives in Maryland. He said, I finally got my first dose of the vaccine, and hes chair of the board of more hospitals and colleges than you can imagine. So generally we have made it so that fewer people have jumped the queue by greasing the palms and spending money than you might have expected if you had guessed six months ago how is this going to happen? We can do these things by policy. Weve just learned if we decide we have the political will to have distribution of the societys goods done not simply by bidding it up and then eBay of a free market but doing it by some sense of distributive justice that we decide politically to do. Our problem is not that it cant be done. Our problem is our politics doesnt always allow it to be done this way, which is why I push back against what I call the free-market genetic supermarket of getting enhancements. Its no, lets have society decide how were going to allocate these resources when it comes to something so basic as the capabilities of life.

This actually brings me to something bigger Ive been reflecting on and struggling with. There are a series of technologies that we can see coming right now. CRISPR is one of them. A.I. is one of them. I think a lot about lab and clean-based meats. I think a lot about some of the climate and transportation technologies. And it seems to me we have to have political ideologies that are a little more oriented to how we want to think about these. And so let me ask the question this way. Youre a broadly progressive guy, but youve spent years now writing biographies of technologists and scientists, going back to da Vinci but also to people in the modern era like Steve Jobs and Jennifer Doudna too. How would you characterize the way todays liberalism thinks about technology and technologists?

I think unfortunately, whether its on the left or on the right, theres been a few things happening. One is a knee-jerk antiscience sometimes or antiexpert thing. Secondly, we dont revere the scientific method as much. Its something why I admire you and your work in your podcast is you say, OK, lets actually analyze the evidence and revise our theories rather than have an ideology that gives us our theory and then we cherry pick evidence, which is the way its been happening so much now. And when we get into a world in which even wearing a mask or using a vaccine or climate change becomes an ideological issue rather than something that should be assessed using the scientific method of having a theory, gathering evidence, revising the theory when the evidence tells you to, thats a huge problem of our society. And then we get to the problem sometimes of modern liberalism. Theres either the neoliberal problem, which is lets let the market figure out some of these issues such as what genetic enhancements which kids can have. Theres also the antimarket sentiment that can say we dont want companies and corporations to have patents and to advance these things, at which point you really crush the advancement of turning basic science discoveries into inventions and products that could improve our lives. So it comes to me to be more of an argument for a nonideological infusion into our body politic where we all pause a little bit from our positions and say lets be guided by some evidence before we decide that Florida is doing something wrong or right or California is or New York is or whatever. Lets gather more evidence and have some more theories.

I agree with you on the examples you just gave, but Im going to shatter your nice conception of me. I think Ive moved to wanting a more ideological infusion in the body politic when it comes to politics, and I mean that in this way. I am at least circling the theory that progressivism has become a little bit antitechnic because it isnt imaginative enough about changing the context in which technologies are driven and funded but then also rolled out and distributed. And so when people see the story of technology being that some founder, usually like a young white guy, makes a bazillion dollars and rolls something out, and then their incentive is always to get bigger and bigger and bigger. And then the world has more concentration of power, and you have people like Mark Zuckerberg and Jack Dorsey making these tremendously consequential decisions about who can speak and who cannot. It drives a kind of turning away from technology, not just from technologists. But at the same time, almost everything I care about from health-care quality and access to climate change to animal suffering to economic dignity, the politics get a lot easier if we really get the right technological advances and we get them quickly and we distribute them well. And so one of my concerns is I think you want a kind of techno-optimistic progressivism but one that really thinks then about the distribution and the regulation, and instead what youre getting is a kind of techno-pessimistic progressivism because there have been such disappointments on the distribution and the regulation.

And I think the reason is people have become convinced that government is the problem, that it screws things up at all times. And my hope, my fervent hope, is not just Joe Biden but its in Jeff Zients and Ron Klain and whoever he may be bringing in that might actually say were going to actually triple the amount of vaccines we have out by next month. Were actually going to deliver it in ways that are fair. And if people see that government and politics can work again I think government and politics is just as important as technology. We should celebrate them both. We should be techno optimists, but we should also be political optimists. Meaning if we have the will as a society, we should have the political tools to implement what we do, and thats been knocked out of us since the age of Reagan, not just on the right but on the left. And so Im looking for us to believe that our politics can work again to solve the big issues youre talking about, which mainly are issues of equity and climate change and justice and distribution of societys goods.

Lets do some book recommendations before I lose you here. You, I think, have become one of the great biographers of our time. What is your favorite biography?

Favorite biography out now is The Bully Pulpit by Doris Kearns Goodwin, which I dipped into again because I find that Teddy Roosevelts progressivism and trying to do a Square Deal for the American people and making into a bully pulpit and then the schisms youre having in the Republican Party of how to fight it seem so timely now.

How about your favorite book about your hometown, New Orleans?

The Moviegoer by Walker Percy, which is a gentle little fable talking about a man in the neighborhood I grew up who is on a search and looking for clues not a search for great scientific discoveries or the next stock tip but a search for why are we here? and what are we doing? and what is our role in this cosmos?

Whats the book you read with the most professional envy?

Not too envious because the person is no longer with us, but when I read Horace Freeland Judsons The Eighth Day of Creation, I almost paused in writing the book that I just finished because it was so damn good as a journey of discovery in which he inserts himself a little into the tale but not in a bad way. And I say, man, that was a great style he wrote in.

And then finally, always our final question, what is your favorite childrens book?

Oh, by far its Winnie-the-Pooh, and Im still very nostalgic about the last one when Christopher Robin decides he has to put the teddy bear, Winnie the Pooh, away forever, and he holds his paw and tries to explain. I even get choked up thinking about it now. And you always think that somewhere on that enchanted forest a boy and his teddy bear will always be playing.

Walter Isaacson, what a pleasure.

Ezra, thank you so much. [MUSIC PLAYING]

The Ezra Klein Show is a production of New York Times Opinion. It is produced by Roge Karma and Jeff Geld, fact checked by Michelle Harris, original music by Isaac Jones, and mixing by Jeff Geld.

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