StarTalk Radio - The Code of Life and CRISPR with Jennifer Doudna and Walter Isaacson

Episode Date: April 5, 2021

Designer babies? On this episode, Neil deGrasse Tyson and Chuck Nice sit down with biographer Walter Isaacson to explore Neil’s interview with Nobel Prize-winning biochemist, Jennifer Doudna, about her pioneering work with CRISPR technology. NOTE: StarTalk+ Patrons can watch or listen to this entire episode commercial-free here: https://www.startalkradio.net/show/the-code-of-life-and-crispr-with-jennifer-doudna-and-walter-isaacson/ Thanks to our Patrons Miguel Santana!!, Cristina Magistrali, Phillipe Dewindt, Toren Wallengren, Eric Huffman, Christopher Sukhanenya, Dmitry Pugachevich for supporting us this week. Image Credit: Tim Tim (VD fr), CC BY-SA 4.0, via Wikimedia Commons Subscribe to SiriusXM Podcasts+ on Apple Podcasts to listen to new episodes ad-free and a whole week early.

Welcome to StarTalk, your place in the universe where science and pop culture collide. StarTalk begins right now. This is StarTalk. I'm Neil deGrasse Tyson, your host and your personal astrophysicist. And I got with me today my co-host Chuck Nice. Chuck. Hey Neil, how are you? Always good to have you, Chuck. And you got with me today my co-host Chuck. Nice, Chuck. Hey, Neil. How are you? Always good to have you, Chuck. And you're always cheerful and got a nice smile. It's all a lie, Neil. It's all a lie. It's just a facade. I'm very well media trained. So today we've got really a hot topic. Oh my gosh. We're going to talk about CRISPR, the gene editing tool.

We're going to talk about the origin of life and what role RNA did or did not play in that. And I have no expertise in this at all. So we're going to feature an interview with Jennifer Doudna, who is an expert in this. In fact, she's a co-invented CRISPR and, in fact, was recognized by the 2020 Nobel Prize. Yeah, the Nobel Prize for that. And not only that, I'm bringing in somebody. He's actually an old friend. Not old, old friend, but a recent acquaintance,

Walter Isaacson. Walter, welcome to StarTalk. Hey, it's great to be with you, Neil. Yeah, Walter, I mean, your bio, if I went through your bio, we have no room for the show. So let me cherry pick it, if I may. Author, journalist, professor of history at Tulane University. And you co-host Amanpour and Company with Christiane Amanpour and formerly the CEO of the Aspen Institute in Colorado. That's a place where very deep thinking people go to have deep thoughts.

And one time editor of Time Magazine, chair of CNN. So you've got the pedigree, but more important for this program, you're a biographer of really important thinkers who have shaped our understanding of this world and civilization. You've got the best-selling biographies of Leonardo da Vinci, Einstein, Steve Jobs,

Benjamin Franklin, and Benjamin Franklin, I think of him as a scientist, even though many think of him as a founding father. And surely you got all up in that story. But you've also become the biographer of Jennifer Doudna. Oh, my gosh. In a new book called The Codebreaker.

And I thought I'd get to you before this book sailed away. It hit number one on the Times bestseller. So you don't even need this PR. So I'm just saying, you know. Doing it for the greatness and fun of being with you. Yeah, okay. That's great. So let me ask you, did you start this sort of work as a biographer of Jennifer Downer?

I had to have well before the Nobel Prize was announced. So what was the trigger here that got you into it? Because I think she's the only one of your people you have biographied that was alive at the time the book came out. Well, yes, by recent biographies, that's true. And I wanted to be able to take on the life sciences revolution. You know, through Einstein was able to do the physics revolution of the first half of the 20th century, and then through Steve Jobs, do the digital revolution. But I think even more consequential will be this revolution where molecules have become the new microchips. We can reprogram them to do our bidding, to make the proteins we want.

If we need a vaccine against COVID to be the guide that will help us chop up our DNA and maybe edit it and add things to our genome. So to me, that's like the most consequential revolution of our time. And Jennifer Doudna was a perfect central character. She's somebody who starts off by marveling on DNA, but then she does the structure of RNA. She co-discovers the CRISPR technology, the gene editing technology you talked about. She's been involved with the COVID, fight against COVID. She wins the Nobel Prize. And she even more importantly, in some ways now, is gathering the scientists, the politicians, the ethicists to say, when should we be using these gene editing tools?

So what a wonderful central character she is. And she shared the Nobel Prize, my notes show here, Emmanuelle Charpentier, a French biochemist. Is that right? Absolutely. They met in Puerto Rico at a conference and bonded together like two chemical compounds. And I flew on over to Berlin, which is where Emmanuelle Charpentier's lab is, and spent a lot of time with her. It was a wonderful collaboration the two of them had,

and Jennifer's had other collaborations along the way. But it was the first time two women scientists alone have won a Nobel Prize like that. So it was pretty fortuitous, both for the book, but I think for the time we're in, to have Jennifer Doudna and Emmanuelle Charpentier suddenly become world heroes. Now, Nobel's rules are that you can award up to three people in one category in any given year. In that year, it only went to those two, right? They didn't even bring in anybody else into that list.

Wow. A little surprising, a little surprising to me. I set my alarm for 4 a.m. so I could watch the live stream, thinking it was a bit too early for the CRISPR technology to win a Nobel, but I let out a shout when they said these scissors will rewrite the code of life and change science into a new epoch. And then I waited for the names, and it was Emmanuel and then Jennifer. I thought it was going to be Feng Zhang as well, the competitor they have at the Broad Institute of MIT and Harvard. But in some ways, what he did was show how it can work in human cells, and I'm hoping maybe someday he and George Church

win the Nobel Prize for medicine. You're telling me you woke up at 4 in the morning to listen to... Look, who does that? Well, I mean, I was writing a book about Jennifer Doudna and Emanuel Charpentier and all the other players. Oh, I get it. So you let out a shout. You know who let out a bigger shout? Your publisher.

You know who did not let out a shout? Who's that? Jennifer Doudna. She slept through it. She did not wake up. And when she wakes up finally, there's all these missed phone calls from Stockholm. Wow.

Now, I've never had that experience of seeing missed phone calls from Stockholm on my cell phone, but that was pretty amazing. Yeah, that's what we call a baller move. Oh, yeah. Yeah, where you're so confident, you're like, yeah, I'm going to go to sleep on this. And I'm badass, and they can wait. You know, Stockholm can wait. Stockholm can wait, yeah.

Well, her career began studying RNA and origin of life, we think, possibly began with RNA. So I chatted with her about her origins. Let's check it out. Well, this takes me back to when I was first starting my graduate work. And my advisor, Jack Shostak, was fascinated by the question of the origin of life. Jack Shostak was fascinated by the question of the origin of life. And he and a few other people at the time wondered whether RNA molecules might in many ways hold the clues to life's origins on Earth by providing the link between DNA, which is now the material, the genetic material that is used in all cells, as far as we know. There are viruses that use RNA in some cases as its genetic material.

For example, the coronavirus, the virus that causes COVID-19 is an RNA virus. And the fascinating thing about RNA and the reason why I got interested in it is because it's a molecule that has fundamentally the ability to not only encode genetic information, but also to do chemistry. So that means that RNA molecules have the ability to form three-dimensional shapes that allow them to do things like cut and paste other molecules of RNA. And some people think that that might have even allowed very primitive forms of RNA to make copies of themselves.

And that would potentially have formed the basis for a self-replicating RNA-based system or world early on in the origin of life. So that was how I originally got interested in it. And what's happened over the last few decades, really since I did my graduate work in the 80s, how I originally got interested in it. And what's happened over the last few decades, really since I did my graduate work in the 80s, over the last few decades, scientists studying RNA have come to realize that RNA is doing all sorts of really interesting things in cells that we didn't know about at the time. So we know now that RNA molecules are helping cells decide when and where to make proteins.

They're helping cells decide how to regulate different parts of the chromosome. And they're also involved in things like CRISPR that help cells protect themselves from viruses. And I'm sure there's a lot of other things that haven't yet been discovered about RNA. Okay, so then, all right, so if RNA is the contractor, the construction contractor, oh, we need some of these, I'd fold this way, or we need some of that, do this chemistry. Is there any insight into how you get the RNA itself?

How you go from organic molecules to RNA? Where are we on that frontier? Well, we certainly know how RNA is made in modern cells. We don't really know where it originated from. If we're going to rewind the clock, if we had a time machine, we could go back and see what was going on. I'm working on that time machine. You come back.

Please do. Yeah, please. Okay. I want a ticket. But yeah, I think understanding how RNA came into existence in the early years of the earth is very much a mystery. It's not known. Some people think, so Francis Crick, who is one of the co-discoverers of the structure of DNA, who was one of the co-discoverers of the structure of DNA,

came to feel that life might have been seeded from outside of our Earth, and that maybe RNA came in from somewhere else. So some people think that might be the case. So the answer is that we don't know. It's a mystery right now. Yeah, so if we came from Mars, that would mean we're all descendants of Martians. That would be kind of fun.

Perhaps some people are more descendant than others of Martians. Yeah, so she was talking about, that's basically, we say in astrobiology, the panspermia hypothesis. But if life on Earth came from Mars, then you still have the question of how life on Mars began. So, Walter, here she is getting all into RNA, but recent memory tells me that her whole world, her scientific community, was all about DNA and the Human Genome Project and recombinant DNA and gene therapy. So how does she end up swimming upstream against all of that to end up focusing on RNA? When I wrote about her childhood, she said she loved playing soccer, but unlike the boys, she wasn't always running to the ball. She liked playing positions where others weren't playing

and getting a sense of the whole field. So in the 1990s, when a lot of the alpha males that you know so well, Neil, were part of the Human Genome Project sequencing DNA, she was there, as she said, with Jack Shostak studying RNA. And it turns out that RNA is pretty simple. And if it jostles together and those four letters of RNA, it can replicate itself, as Jennifer showed, and maybe that just started replicating itself. So those four letters you're referring to,

the amino acid letters, the letters of our... Which are similar to the DNA four letters, but there's a one letter difference just to make sure that biology students are staying awake. Okay, good. And gene editing as an activity has a very high precision with CRISPR. I can imagine without that level of precision, it's kind of like a crapshoot. Or if it's not a crapshoot, there's risks involved that are minimized with CRISPR. Is that right? Yeah. And you can still have off-target edits. But the great thing about CRISPR technology is it's advancing in leaps and bounds. And so when we talk about a Nobel Prize, I think David Liu at Harvard might also win one from Madison because he's created things like base editing and prime editing where if CRISPR is like a scissors that can cut DNA these are fine pencil points that can do it

exactly right and then even edit in a sequence and even do multiple genes so really in the 10 years since Jennifer Doudna and Emmanuel Sharpenjay made their discovery, we keep advancing on that genetic editing front. So to make sure we're all on the same page and all of our listeners, I actually got Jennifer to describe precisely how CRISPR works. So let's check it out. It's quite amazing. It's a system that evolved originally in bacteria as a way that bacteria fight viral infection. So in the natural world, there's a lot of viral infection going on all the time in bacteria. So there's a lot of evolutionary pressure to develop ways to fend off these viruses. And one of those pathways is called CRISPR. And what it does is provide cells a way to steal snippets of virus DNA and store them as a record of that virus and then use that molecular information to fight the

virus if it shows up in the cell. And so by studying how it works, and in particular, a protein that's called Cas9 that allows bacteria to program Cas9 with these little snippets and its job is to cut DNA in a way that in bacteria leads to destruction of the viral DNA. But in our cells or plant or animal cells, it can be used to make cuts that will trigger cells to change the DNA sequence during the process of DNA repair. And that's fundamentally how gene editing works with CRISPR. Wow. Wait, wait. So what you're saying is we're finally as smart as bacteria because they've been doing this for a billion years. I wouldn't go that far, Neil. So, Walter, I'm told that they allowed you to edit a gene yourself. Did they really let a journalist into a lab to do this? Oh, man, it was so exciting to be in the lab with Jennifer

and a couple of her graduate students. And, you know, I like to learn to do by doing. And the way we did it was we first edited a bacteria cell, which is sort of what happened in the 2012 paper that Jennifer and Emmanuel did that won the Nobel Prize. And then the next day, we took the step that Fong Zhang, Jennifer Doudna, George Church do, and see if he could do it in a human cell. So I did it in a human kidney cell. And it was pretty easy in the lab, which was probably the most frightening thing about it. But I don't want you to worry, Neil.

We took it afterwards and mixed it with chlorine and poured it down the drain and flushed it. So my edited cells are not part of the planet Earth. There's not some new creature crawling out from under the rock. I was going to say, somewhere in the sewer right now, there's a chlorine monster. Chlorine? There's a chlorine monster somewhere in the sewer that is just now getting its legs. So I checked with Jennifer to see how far away we are from this process possibly editing more complex human traits than what might simply be encoded in a single gene. So let's check it out.

as a surprise to many people that, in fact, there isn't a single gene for musical ability or, you know, astrophysical inclinations or, you know, things like that, that we can put our finger on. And in fact, it's, you know, by far typically the case that for human traits, there are probably dozens, if not hundreds, or even more genes that are involved. And so the reality of genome editing to create people that have particular intellectual capabilities, for example, is, I think, a distant possibility. However, again, you know, just circling back to what is possible, I think, you know, already on the horizon, we have the potential to manipulate individual genes that are known to either directly cause disease or, you know, give people a sort of a propensity to develop disease. And I'll give you a couple of examples. So, you know, I think many folks are familiar with a disease called sickle cell disease or sickle cell anemia. So that is a very well characterized genetic disease that results from a single mutation in a single gene in the human genome. And CRISPR is capable of correcting it or making an ameliorating change elsewhere in the genome. And that's actually already being done in patients and it's already been shown to be effective. So, you know, it's

extraordinary and it's kind of already giving everybody in the field the sense that, you know, we're on the verge of being able to provide potentially a cure for that type of genetic disease where there's a single gene that causes a disorder. And, you know, another example is muscular dystrophy, cystic fibrosis is in this category, and there are quite a few others. So I think, you know, that's where CRISPR is going to have a real impact. Yeah, Walter, it's not surprising, I guess, that DARPA took interest in this technology, the Defense Advanced Research Projects, what does the A stand for in that? Agency.

So what is it that they, what are they going to do with it? You know, first of all, a malevolent actor or enemy power could decide to use CRISPR to do anything from creating gene drives that will change mosquitoes so that they can carry deadly pathogens, or as Vladimir Putin said to a youth conference in Moscow, maybe we'll use CRISPR to create soldiers that don't feel pain or don't feel fear. Oh, that's laddy. He's such a romantic. And so you can imagine the Defense Department is one of the biggest spenders in this area.

They've come up with, and a person who's been working with Jennifer was part of it, something called anti-CHRISPR, which is pretty much what it sounds like. And just like we may have ballistic missile systems and Russia may have them, we develop anti-ballistic missile systems. Russia may have them. We develop anti-ballistic missile systems. So I think we have to guard against, you know, bad actors using this technology. So science fiction becoming science.

That's how this goes. It always happens, doesn't it, Neil? Yeah, that's what it is. The thing about really great science fiction is that half of it's already happened. Wow. We're going to take a quick break, but when we return, we're going to address the philosophical and ethical implications of CRISPR. Hey, I'm Roy Hill Percival, and I support StarTalk on Patreon. Bringing the universe down to earth. This is StarTalk with Neil deGrasse Tyson.

We're back. StarTalk. Chuck Nice, co-host Chuck. Hey, Neil. Tweeting at Chuck Nice comic. Thank you,

sir. Okay. I like, I like your, your occasional posts there. They, they make me Chuck. Hey, Neil. Tweeting at Chuck Nice Comics. Thank you, sir. I appreciate it. Okay, I like your occasional posts there. They make me smile. Uh-oh. Thank you. But sometimes they're like making fun of other people, and I guess that's still okay sometimes.

I am a comedian, and so... That's how that works. And that kind of comes with the territory. That's how you roll. So we're talking about gene editing. Oh, my gosh. And we're featuring my interview with biochemist Jennifer Doudna and recently winning, sharing the Nobel Prize in this very subject.

And Walter Isaacson, the one and only biographer of genius out there, as well as other things he's done in his career, of course. And I want to talk about the ethical challenges that this technology brings. And let me actually begin with a clip of Jennifer Doudna addressing the difference between somatic editing and germline editing in the CRISPR technology. So let's check it out. the CRISPR technology. So let's check it out. Germline means changing DNA in embryos or other kinds of germ cells like eggs or sperm, basically cells that can produce an entire organism. And if DNA is altered in those cells, then those changes become part of the entire organism. And furthermore, they can be inherited by future generations. So

it's a heritable change to the DNA, which is very different in my mind from somatic cell editing, which means editing cells that are already fully developed. So they're not going to be able to produce a new organism or pass their changes on to future generations. They might make new cells that have those changes in an individual, but they won't be inherited by future individuals. And that's fundamentally different than germline editing to me because it remains localized in one individual rather than being passed on to future generations. Okay, so that's good or bad.

For example, if I have sickle cell or Tay-Sachs, less likely Tay-Sachs, but if I have one of these that you have identified the gene and I'm a full human being, you can remove those disease symptoms from me and the disease entirely, but I still carry that into my offspring, correct? Indeed, yeah. So why wouldn't you want germline editing? Well, you might want to, right? I mean, I think there may come a time when we decide that it would be unethical not to do that in the germline for certain types of disease. I don't think that time is now. I don't think the technology is where it needs to be for one thing. And also, I don't think that time is now. I don't think the technology is where it needs to be, for one thing. And also, I don't think that, you know, society is ready for this. Like, how do we ensure equitable use, affordable access, all of those sorts of things. possibility that in the future, the technology is robust and we decide that we meaning, you know,

I don't know who we is really here, but, you know, maybe a parent would decide that, you know, I would really like to not pass this trait on to my children. And furthermore, I don't want my children to have to deal with it when they come around time for them to have kids. And so I'm just going to get rid of it once and for all by editing the germline. That could happen in the future. Walter, most conversations about CRISPR are not so much about the innovative science of it, but about the ethical and moral implications. And you devote justifiably a significant real estate in your book addressing these issues. Can you help us through how bad it could get relative to how good it could get?

Well, I think most of what will happen will be really good because every creature large and small on this planet uses every trick in its playbook to say, okay, how can I thrive? How can I survive? And I think humans can and will and should do that. The question is when you start doing things that could be problematic. One thing that would be problematic is if we just let this be a free market thing where rich people can buy better jeans for their children and make them taller or make them boost you know, boost whatever their muscle mass, whatever they want to do.

And not only will that increase the inequality in our society, it will encode it permanently in our species, which would just be a eugenic horror show, you know, like Brave New World or the movie Gattaca. We don't want that to happen. The other thing is that one of the really important things about the species that makes it creative, but also makes it, you know, resilient, helps it survive, is that we have a lot of diversity in this species. People tall and short and fat and skinny and gay and straight and trans and, you know,

different hues and different backgrounds and different personalities. And if all of a sudden parents are saying, here's the model child we want, we won't have a great diversity in our species. I think those are science fiction-y in the moment, meaning we're talking 20, 30, 40 years away. But when Jennifer says, we should decide this, but then says, who is we? I'll answer that question. We is me and you and everybody listening to this podcast.

We ought to be somewhat familiar with all these problems that are going to happen. We're all screwed. Walter just showed us if it's up to us as a society, we're, oh, well. Wait, Walter, it is inevitable that if we can remove bad traits, that we can add good traits. So you'll say that's not good, but what's going to stop it? How's that going to... Are you imagining a realistic future here rather than a utopian future?

Oh, yeah. I mean, I think there are all sorts of medical procedures that either get approved or don't get approved. Oh, okay. Whether they're drugs or pharmaceuticals. It's an approval list. There it is. That's what it is.

And, yeah, and I think we have international conferences. Jennifer Doudna, in my book, I travel with her, and she gathers people from around the world. And so the Chinese Academy, one of the characters in my book, is Zhuang Qingpei, who is one of the people at the Chinese Academy. Robin Lovell Badge at the Royal Academy in England. All these people trying to figure it out. And once you

have an international consensus and things get regulated, sure, some people will be using off-target pharmaceuticals. Some people will be trafficking in elephant tusks. But we can try to minimize those things by saying they're not legal.

I was going to say, once you do have a roadmap as to what is indeed ethical, inevitably what you will have created is a black market for those who want to circumvent those ethical guidelines and create

whatever the hell they want to create. That's what he just said about the Tusks. That's what I'm saying. But it's easy. My point, and this is my question. It's easy to find the person who was trafficking in Tusks. How do you find the person who made my kid LeBron James when both my parents are white, but yet somehow here I am, LeBron James,

the greatest basketball player ever. Like, we don't have any idea how that happened. Like, how would you even police that? You can't do that on a street corner. Right. It would have to be. Well, you know, a lot of things are kind of hard to police, but, you know, we can't stop at all.

I think we're going to be able to save our species if we make sure that maybe 1% of the cases sneak through because people engage in medical tourism or they find some back channel way to have gene editing in the next 30, 40, 50 years. But I think we as a society are pretty good at saying these are the things we aren't going to do, whether it be through regulation or just social shame. Well, Chuck, we have a sort of example of that because back in 2018, there were scientists in China that used CRISPR to actually edit the embryos, unborn human embryos, to make them HIV resistant. And basically they're the first designer babies.

I had to ask Jennifer about that and get her reaction to what it means in the present and in the future. Check it out. This story was, you know, probably the most shocking so far with CRISPR, honestly, because in this situation, a scientist had actually used CRISPR in human embryos, not just for research, which has been done in other labs, but for the purpose of implanting those embryos to create a pregnancy. And in fact, that did occur and those children were born. And as you mentioned, Neil, the stated purpose of that work was to protect those kids from future infection by HIV using a CRISPR-based approach where their cells were edited so they couldn't express a protein that's necessary for HIV infection.

So while that might sound like a good idea at a high level, it turns out that there are already very well-known, you know, other ways of treating or preventing HIV infection for kids that are born to parents that might have a pre-existing HIV infection. And also, I think in this instance, it was absolutely irresponsible and frankly, just flatly unethical to use it in this way, because for many reasons, but one of them is that the parents, I don't think, could really understand the technology or just how experimental it was and how untested it was. I mean, to do this on your children is kind of the most extreme use of something like this. And also just that I think even the data that were published for that particular application showed that the technology itself is just not ready for that kind of use.

We don't have enough control over it yet in embryos to use it safely. Right, but so how do you regulate it then? Do you just make it so socially and ethically objectionable that there's cultural pressure against it? Or do you need actual laws, governmental laws and international treaties or regulations surrounding it? What's that going to take? Well, I certainly think the former is probably the most, you know, the most realistic strategy right now. And that means basically creating a, you know, a culture around the technology that supports what I would call responsible use and really, really makes a very strong statement against unethical or just, you know, uninformed,

frankly, uses of the technology. And that's what happened after that announcement in 2018, I think there was a really interesting kind of international rejection of that work. It was not published in, you know, I think in the end, I don't really think that a manuscript reporting that study was published anywhere, you know, in any kind of a peer-reviewed journal, even though it had been submitted to those journals. But those journals said, we're not going to support this. We're not going to publish it. It was not done in an ethical fashion. And this is just simply not work that we're going to publicize.

So that would be scientists policing ourselves in that sense. Yeah, yeah. And that has tremendous value. It does. I think it's very important. I think it's, you know, the reality is that is, and you have seen this in other fields, you know, that it's very difficult for governments to, first of all, even to draft, you know, legislation that would be suitable for controlling technology. And I look at the challenges with things like social media, right? Very difficult to police it.

How do we do that appropriately? It's not... They don't even know what questions to ask. Right. That's it. It's very difficult, right? It's very hard. And then even if you could draft legislation, how would you ever enforce it?

And how would you enforce it globally? I think it's unrealistic. So to me, the better approach or just the more realistic approach is frankly, just to really engage the, you know, the scientists and the technologists in this and create a culture around the technology that very strongly supports the, you know, the, I would call it the appropriate and ethical use of the technology. Walter, just a moment ago, you were referring to you, me, Chuck, and others, common folk, to have a say in the ethical use of this technology. But it wasn't that long ago, really,

when eugenics was sort of sweeping sort of the Western world as a way of improving the human species, breeding out the bad traits, breeding in the good traits. And there were panels and committees, and surely at that time they considered homosexuality something you're going to have to breed that out because that's deviant. So what kind of thinking have you done about what might be the evolution of a morality from one time to another? Yes, it's a great question.

And in the book, I talk about the fact that, yes, we had state-sponsored eugenics, whether it was in the United States in the early 1900s and, of course, in Nazi Germany. But I think we also have to get our minds around what could be happening if you had a free market, and maybe a free market eugenics. You talk about homosexuality. I think nowadays people would be appalled at the notion that we would try to edit our sexual orientation of our child

or change it in some way. But if you left it to every parent and to the free market, who knows what choices individual families may make. And yet, in our system, in the United States in particular, we tend to leave reproductive choices to the individual or to the family. And so this is where we're going to get into some conflict in figuring this out, because I think sometimes it changes

if you're in a fertility clinic and it's confidential and nobody knows what you can pick. You might pick the gender. You might pick the gender orientation. You might pick anything as your design. Behind closed doors. Behind closed doors.

And so I think that's why our whole morality has to change. We have to say, what are true disabilities, such as having Tay-Sachs or sickle cell, and what are things that we may, that society may cause to be disabilities, but shouldn't be. And I think we have to make sure that we don't label things as bad

just because society has prejudices. Because as you said, there were prejudices 20, 30, 40 years ago we would find abhorrent. But here's my prediction. 20, 30, 40 years from now, people will look back at us and find our prejudices abhorrent.

Well, two things. One, hopefully the first thing that they're able to edit out completely is asininism. That's what's happening. So, you know, if we can get rid of asininism, a lot of that stuff will take care

of itself. So that's a gene for that. That's a gene. That guy's an a-hole. We found a gene. We found a gene to get rid of him. The second thing, though, that I will say is somewhat frightening is that even now, very recently, there is a world power government that was very much involved in the fertility decisions of its citizens. So, you know, what happens when governments say, you know what, for these reasons, we need to do thus and so. So perhaps there needs to be treaties immediately worked upon to make sure that with this technology, governments themselves don't take actions to interfere with people's decisions in these areas. Absolutely. And I think there are one way to help

push back in that in the long run is for individuals, for real people to understand this technology, figure out what they're comfortable with. And even in authoritarian regimes, if the people truly have a sense of morality about something, the leaders will eventually have to follow them. And so I had to ask Jennifer about sort of the fear factor involved in designer babies. Let's check out her reply. Is the fear factor justified? Yes and no. I think it's important to be, you know, realistic about what the technology can

and cannot do right now or even in the future. Is it going to allow us to create super soldiers, for example? No, I don't think that's happening anytime soon. But, you know, does it have the potential to allow parents who are using in vitro fertilization to make tweaks to their children's DNA? Yes, it does. And so that does bring along, I think, very important questions, ethical and otherwise, that have to be addressed. And so that's where I sort of feel that, you know, having that conversation now, even while the technology is still developing, is very important. That's really good so that it doesn't bite us in the ass when it's too late.

Yeah, I hope that's the case for sure. For sure. So what I'm going to do, let's take a quick break. And when we come back, I want to learn from you, Walter, what role CRISPR may have played in the race to find a vaccine for this virus, this pandemic that we're in, when StarTalk returns. We're back. StarTalk. We're talking about gene editing. We're talking about CRISPR.

And in this segment, we're bringing COVID into the mix. And we're featuring my interview with Jennifer Doudna, a biochemist who invented CRISPR. Somebody had to do it. There she was with some close colleagues of hers. And we've got the person who has served as her biographer in this modern time, Walter Isaacson. Walter, it's always good to see you,

and always good to hear what you have to say. And, of course, Chuck Nice. Oh, it's a pleasure. It sounds like, oh, and Chuck Nice. Of course, because that's exactly what it was. I mean, here I am. Let's be honest. I'm sitting here with the world's most renowned science educator

and the world's most renowned biographer. Of course, it's going to be, oh yeah, and Chuck Nice. Chuck. We love you, Chuck. Jennifer, if you only just joined us, Jennifer actually won the Nobel Prize in 2020.

Walter, she won it in biochemistry. Why didn't she win it in human physiology? Because that's a whole other category, and it seems like that would be appropriate. Were they saving that category for more rewards for this discovery? It was a basic discovery in science. It's how the chemistry of this tool works. And it was done in labs and done in test tubes.

And so I think it was appropriate that it was the chemistry prize. I do think people are now applying it to humans and using it as a medical tool. And I hope eventually that some of the people doing that, including George Church and Feng Zhang, who first showed how it could be used in human cells, and David Liu, who's creating new ways to use CRISPR technology for editing in humans, that someday they may win the prize in medicine. Okay, so this is the right way this would happen, because there are conduits that connect branches of science that are in nature that does it all the time. And it's kind of artificial that we even do it at all. So the fact that you have a basic chemistry discovery that gets exploited in the service of the human condition,

that makes perfect sense, Walter, just the way you describe that. Let me ask you, tell me about competition in science and what you've discovered as a biographer of her work, Jennifer's work. You know, competition is a good thing, in my opinion. And she's a competitive person. And some people say that, I think, meaning it to be slightly insulting. And I say, yeah, she's very competitive. Isn't that great?

And when she heard footsteps in 2012, when she and Emmanuel Charpentier were doing this discovery about CRISPR, but there were Lithuanian scientists working on it. There were people in different labs. She pushed hard to get it done fast. And competition, as you know, that's what causes us to work weekends. That was what caused Jennifer Doudna in California and Emmanuel Charpentier in Europe to work around the clock by handing things off to each other when sunset happened in one place or the other. So I think that competition was good. But at the end,

when COVID struck, they decided the labs around the world to put aside some of the competition and to make discoveries out in the open, sharing the information and not asserting patent rights. out in the open sharing the information and not asserting patent rights. Oh, okay. So this is duty rises above what was otherwise the competitive spirit. Personal glory takes a back seat. It's good to know that that still exists.

And you make an excellent point, Walter, about competition in science where initially you might think of it as some kind of a dig on someone, but almost everything else we do in this world thrives on competition. You go to sporting events, you go to a track meet, you want to see who wins,

and the runners want to win, right? So, and you celebrate that and the struggle that gets you there. So there's no reason why science shouldn't be any different, especially if in the end, the results are valuable discoveries. So what precisely did they do to help COVID? You know, when COVID struck about a year ago in March of last year, Jennifer Doudna had dropped her 17-year-old son off at a robot building camp.

son off at a robot building camp. And she woke her husband up at two in the morning and said, we got to go back to Fresno and pick up Andy because I don't want him there in this convention center now that I hear about this pandemic. And Andy's an only child. He's rolling his eyes. But as they leave the parking lot, they get a text message saying, robot competition canceled. And that's when Jennifer decided to gather people throughout the Bay Area, the scientists, and focus their attention on turning their tools to fighting coronavirus. Likewise, Fong Zhang and the people at the Broad Institute in Cambridge, Mass. did the same. And what they do are multiple things. One is you can easily use CRISPR, as we've talked about, as a detection technology to detect the genetic material of coronavirus. And testing was a real cock-up during this pandemic.

Now we're going to be able to have at-home testing kits at work instantly. Secondly, we can fight coronavirus the next time around the way bacteria do, which is not by stimulating our immune system, which is kind of a messy process, but just by detecting the virus in our system and cutting it up and killing it. And thirdly, that whole notion of using RNA as something you can code, which goes back to Jennifer Dowden's graduate work. That's what we're doing with the Pfizer and Moderna vaccines, which is we're coding RNA to be a messenger to tell our own cells what little proteins to produce that will create immunity to the virus. So is it fair to say

that without the CRISPR technology, we might still be reaching for vaccines at this point? Well, no, I think the vaccines come out of the earlier work we've done on RNA, which is that you can code it to be a guide, which is what CRISPR is, or you can encode it to be a messenger telling our cells to build proteins. And it was the latter that's involved in these Pfizer and Moderna vaccines. But if it's going to be the treatments, the treatments that don't even involve vaccines, that'll even be better. That's going to be CRISPR directly chopping up the virus. So it formed an important motivating force to further expand the power of CRISPR over our destiny. Is that a fair characterization of this?

And it also showed, as we said at the beginning of the show, that RNA is the miracle molecule. It's the star of my book, along with Jennifer Doudna. And it's like having a microchip. If you can code RNA to do your bidding, you can make vaccines and you can make gene editing tools. And how long did it take you to write this book, The Code Breaker? You know, for seven or eight years, I've been gathering string on it because I've been wanting to write

about the health sciences. I was finishing up Leonardo, but I kept meeting Jennifer Doudna. And I also met George Church, who you know, and I've met Feng Zhang and Eric Lander and many other people in the book. And Eric Lander, you can't just go by his name that quickly. Eric Lander is now the very first cabinet science post ever in

the history of the country. Eric Lander, a biologist. A really good choice by Joe Biden. Secretary of Science for the first time. Exactly. And it's a great choice because what Eric Lander has shown is his magnetic ability to bring together talent. And he built the Broad Institute into the best place on the planet for translating genetics into medicine. And he's, you know, people talk about competitive.

He's as competitive as they come. He competed against Jennifer Doudna with his team, but they all know that they were part of a more noble mission and a higher calling. Can I ask a question that is unrelated, but I'm just got to know? Okay. Okay. We can always cut this, I think.

Yes, we can. Yes, we can. We can always cut it, all right but it's killing me i gotta know this from walter all right because i'm preparing to die no no no okay so check it out so all these brilliant people that you have chronicled their lives and their accomplishments who do you like best okay well you know as a, there's nobody more likable than Jennifer Doudna. And I tell you, I've written about some people, and I knew Steve Jobs pretty well. I was spending a lot of time with him when I was doing that book.

Steve Jobs was brilliant. He drove people crazy. He drove them to distraction. He also drove them to do things that they never dreamed they would be able to do. But nobody said he was the coziest, warmest, fuzziest person they had ever met. Jennifer is cozy and gentle and loves to mentor people. And so I would put her and Benjamin Franklin as the two people who seem just the person you want to have dinner with or be with. And by the way, I share those same sentiments. When we laid down

the tracks of the interviews where we've just cut in, I said I just want to stay on for like three hours. Of course, she's busy. She's got other things. But it was just a delight to just be educated by her and just to have her do all the talking.

That was great so i had to ask jennifer what did she see what might be in the future of crisper because will that pave the way for curing cancer and other diseases that have been a blight on our civilization well in a hundred years we look back in the primitive 2020s and say, oh, look at all the diseases that our species once had. So let's see what she has to say about this. So Jennifer, what's the future of the science of CRISPR? Will it just get cheaper and faster, and now you can do it in your kitchen? And what else are you working on? I don't know about doing it in your kitchen, but it's certainly going to get cheaper and faster and better over time.

It already is. And yeah, I think we're going to see, you know, increasing uses in clinical medicine. I think we're going to see, we didn't talk about this today, Neil, but a big, big area of impact for CRISPR is in agriculture. We have a big effort right now at the Innovative Genomics Institute that I founded a few years ago to use CRISPR to address climate change. And I think that's going to be, you know, a very interesting kind of area of development of this technology.

And for myself, yeah, I mean, we're continuing to do fundamental research in my academic lab on CRISPR molecules, understanding how they work, on CRISPR molecules, understanding how they work, and also really digging into the ways that this technology will become affordable and widely available in the future for solving real-world problems. You know, Walter, you said earlier that you were worried about the inequality gap growing if only the rich people can afford CRISPR

and touch up their offspring and the poor people can't. But if it becomes very affordable, like, for example, let's just look at smartphones. Even poor people have smartphones. So the technology, though it's still costly, it wasn't out of reach of people who were not otherwise rich. So is there a future where it is accessible to everyone and therefore you can't invoke the inequality argument? You can't play that card anymore.

That's what we should be aiming for. And it's a great question, Neil. And it's a great comparison to digital technology, which had the ability to create a digital divide and probably did during this pandemic, you know, when people were having to, students were having to study from home, there was somewhat of a digital divide. But as you said, we've been able to try to make digital technology widespread, and the cost keeps going down because the cost of microchips keeps going down. Now, when it comes to CRISPR, that should be our goal. I was in Jennifer Doudna's lab with a guy named Fyodor Yurnov, about one of the most colorful characters in the book, and his job there is bring the cost down. Because when Victoria Gray got cured last year of sickle cell, that was about a million

dollars, that treatment. But if you could do it in the body rather than extract the stem cells and have to reinsert them, you can bring the cost down dramatically. And so that should be our goal for the next phase of CRISPR, is say, let's make this health part of this technology, the one that cures bad disabilities, let's make it as available as possible. So is it possible that we'll get to a place where instead of, in the truest sense of manipulation, we're just trying to make things better? In other words, this is what we already see you do well.

We've identified that. You do this well, you do that well. What we're going to do is augment that to the best of your ability. I mean, how do you feel? I'm asking you too, Neil. How do you guys feel about that ethically as a means of manipulating gene expression? I think one thing about that, Chuck, that would be good is that it preserves the diversity and respects the individuality of people. And it says, well, you know, you joked, I think you were making me into LeBron James. Well, you know, that ain't going to be me. But I think every person can, first of all, have the disabilities, things that are true disabilities, you know, muscular dystrophy, that's a disability, or even problematic, you know, genetic conditions you have.

Let's remove those so that every person can flourish to the extent their abilities and their desires lead them to. It seems to me there would always be this sort of fuzzy boundary between what anyone is declaring should be fixed and what shouldn't be. Absolutely. The boundary is fuzzy. And in my book, I try to make us open our minds a bit to say, are true disabilities and what are things that are disabilities only because society doesn't accommodate them well and those of us in the hearing-enabled community we may say we want to make sure our kids don't have congenital deafness but if you're in the deaf community you might say we're adding a lot to our society. I don't think there's easy answers to things like that even David David Sanchez, as I mention in my book, says, well, those of us who have sickle cell.

You know, sickle cell drove Miles Davis to drink. It drove him to drugs. It probably drove him to death. But it also drove Miles Davis to do Bitches Brew or Kind of Blue, some of the greatest jazz albums ever. Jazz albums ever. Jazz albums ever. And so we have to march down this path by understanding, yes, you know, Franklin Roosevelt was forged by polio,

but that doesn't mean we're going to quit using the polio vaccine. Sickle cell may have forged Miles Davis, but what does that mean? Should we be editing out sickle cell? Should we be editing out deafness, shortness? These are not easy answers. But in my book, I walk through talking to people in all the communities, including what we sometimes call the disabled community, and say, hey, let's open our minds a bit. Because this is an interesting ethical journey we're about to go on.

The differently abled community that that is. So, Walter, I think I have the solution. You do edit out the sickle cell gene, but you edit back in the gene for jazz. And that way, everybody's aware all around. You're talking to somebody in New Orleans. In New Orleans, your home base. That balcony overlooks Royal Street, and at the moment, Doreen Ketchins is playing her clarinet, and I want to edit that gene in because I've learned.

I would love to play clarinet. I used to play it pretty well, and I want that gene so I can play it again. Well, I'm glad you didn't play so that you can write these books. Walter, it's great to have you on the landscape among mortal other folk. And thanks for agreeing to this interview on StarTalk. And Chuck, always good to have you, dude.

Always a pleasure. Neil and Chuck, thank you. All right, we got to call it quits there. This has been StarTalk. I've been your host, Neil deGrasse Tyson, your personal astrophysicist. As always, bidding you to keep looking up.