The Code of Life and CRISPR with Jennifer Doudna and Walter Isaacson

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.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:01Neil deGrasse Tyson?

  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.

• 0:23Chuck Nice?

  Hey Neil, how are you?

• 0:25Neil deGrasse Tyson?

  Always good to have you Chuck. And you're always cheerful and got a nice smile.

• 0:29Chuck Nice?

  It's all a lie Neil.

• 0:30Neil deGrasse Tyson?

  It's all a lie. It's just a facade.

• 0:33Chuck Nice?

  I'm very well media trained.

• 0:36Neil deGrasse Tyson?

  So today we've got really a hot topic. Oh my gosh, we're going to talk about CRISPR, that 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 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.

• 1:20Neil deGrasse Tyson?

  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,

• 2:02Neil deGrasse Tyson?

  you're a biographer of really important thinkers who have shaped our understanding of this world and civilization. You've got the bestselling biographies of Leonardo da Vinci, Einstein,

• 2:15Speaker 02

  Steve Jobs.

• 2:17Neil deGrasse Tyson?

  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's hit number one on the Times Bestseller. So you don't even need this PR. So I'm just saying, you know.

• 2:45Speaker 02

  Doing it for the greatness and fun of being with you.

• 2:49Neil deGrasse Tyson?

  Yeah, okay, that's great. So let me ask you. Did you start this sort of work as a biographer of Jennifer Doudna? 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.

• 3:12Speaker 02

  Well, yes, about 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

• 3:58Speaker 02

  Starts off by marveling on DNA, but then she does the structure of RNA. She co-discoveries the CRISPR technology, the gene editing technology you talked about. She's been involved with the COVID, uh, fight against COVID. She wins the Nobel Prize. And, uh, 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.

• 4:27Neil deGrasse Tyson?

  And, and she shared the Nobel Prize, uh, my notes show here, Emmanuel Charpentier, a French biochemist, is that right?

• 4:35Speaker 02

  Absolutely. They met in Puerto Rico at a conference and bonded together like two chemical compounds. And, uh, I flew on over to Berlin, uh, which is where Emmanuel Charpentier's lab is, and, uh, 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, uh, it's 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, uh, to have Jennifer Doudna and Emmanuel Charpentier suddenly become world heroes.

• 5:15Neil deGrasse Tyson?

  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.

• 5:27Speaker 02

  Wow, a little surprising, a little surprising to me. I set my alarm for 4:00 AM 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, uh, will rewrite the code of life and change science into a new epoch. And, uh, then I waited for the names and it was Emmanuel and then Jennifer. I thought it was gonna be Feng Zhang as well, the, uh, competitor they have at, uh, 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, uh, win the Nobel Prize from Madison.

• 6:10Neil deGrasse Tyson?

  Uh, you telling me, you woke up at four in the morning to listen to, um, who does that?

• 6:17Speaker 02

  Well, I mean, I was writing a book about Jennifer Doudna and Emmanuel Sharpanche and all the other players.

• 6:23Neil deGrasse Tyson?

  Oh, I get it. So you let out a shout. You know who let out a bigger shout? Your publisher.

• 6:28Speaker 02

  You know who did not let out a shout?

• 6:31Neil deGrasse Tyson?

  Who's that?

• 6:33Speaker 02

  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. Now, I've never had that experience of seeing missed phone call from Stockholm on my cellphone. But that was pretty amazing.

• 6:50Chuck Nice?

  Yeah, that's what we call a baller move. You know, where you're so confident, you're like, yeah, I'm gonna go to sleep on this.

• 6:59Neil deGrasse Tyson?

  And I'm badass and they can wait. You know, Stockholm can wait.

• 7:02Chuck Nice?

  Stockholm can wait, yes.

• 7:04Neil deGrasse Tyson?

  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.

• 7:14Speaker 03

  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. 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.

• 7:57Speaker 03

  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.

• 8:42Speaker 03

  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.

• 9:23Neil deGrasse Tyson?

  Okay, so then, all right, so RNA is the contractor, the construction contractor. "Oh, we need some of these, I'd fold this way. Or you 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? Is there, where are we on that frontier?

• 9:45Speaker 03

  Well, we certainly know how RNA is made in modern cells. We don't really know where it originated from. If we're trying to rewind the clock, if we had a time machine, we could go back and see what was going on and...

• 9:57Neil deGrasse Tyson?

  I'm working on that, time machine.

• 9:58Speaker 03

  Right, yeah, please do.

• 10:01Neil deGrasse Tyson?

  Okay.

• 10:03Speaker 03

  I want a ticket. But yeah, I think, I think understanding how RNA came into existence in the early, you know, early years of the Earth is very much a mystery. It's not known. Some people think, so Francis Crick, 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, you know, 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.

• 10:39Neil deGrasse Tyson?

  Yeah, so if it came, if we came from Mars, that would mean we're all descendants of Martians. That would be kind of fun. Or perhaps, perhaps some people are more descendant than others of Martians.

• 10:53Neil deGrasse Tyson?

  Yeah, so she was talking about, that's basically what 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?

• 11:28Speaker 02

  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 in 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 a far more interesting molecule. And when you ask about where did the RNA come from, how did life begin? Just as the primordial soup of chemicals four billion years ago, RNA is pretty simple.

• 12:10Speaker 02

  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.

• 12:20Neil deGrasse Tyson?

  So those four letters, you're referring to the amino acid letters, the letters of our...

• 12:26Speaker 02

  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.

• 12:33Neil deGrasse Tyson?

  Okay, good. And gene editing as an activity has 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, it's, there's risks involved that are minimized with CRISPR, is that right?

• 12:49Speaker 02

  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 Lu at Harvard might also win one for medicine 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 Sharpanjay made their discovery, we keep advancing on that genetic editing front.

• 13:27Neil deGrasse Tyson?

  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.

• 13:35Speaker 03

  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

• 14:18Speaker 03

  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 of information that help these proteins find viruses. And if they find them, what Cas9 does is to cut. And its job is to cut DNA that, 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

• 15:00Speaker 03

  of DNA repair. And that's fundamentally how gene editing works with CRISPR.

• 15:04Neil deGrasse Tyson?

  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.

• 15:12Speaker 03

  I wouldn't go that far, Neil.

• 15:17Neil deGrasse Tyson?

  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?

• 15:27Speaker 02

  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 Jang, 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.

• 16:11Speaker 02

  So my edited cells are not part of the planet Earth.

• 16:15Neil deGrasse Tyson?

  There's not some new creature crawling out from under the rock?

• 16:17Speaker 02

  I was gonna say, somewhere in the sewer right now, there's a chlorine monster.

• 16:21Neil deGrasse Tyson?

  Chlorine!

• 16:22Speaker 02

  There's a chlorine monster somewhere in the sewer that is just now getting its legs.

• 16:26Neil deGrasse Tyson?

  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.

• 16:38Speaker 03

  This probably won't come 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, you know, genome editing to create people that have, you know, particular intellectual capabilities, for example, is, I think, you know, a distant possibility.

• 17:20Speaker 03

  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

• 18:05Speaker 03

  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.

• 18:37Neil deGrasse Tyson?

  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?

• 18:51Speaker 02

  Agency.

• 18:52Neil deGrasse Tyson?

  Agency. So what is it that they, what are they going to do with it?

• 18:54Speaker 02

  Uh-oh. 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."

• 19:18Chuck Nice?

  Oh, that laddie, he's such romantic.

• 19:20Speaker 02

  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-CRISPR, 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. So I think we have to guard against, you know, bad actors using this technology.

• 19:50Neil deGrasse Tyson?

  So science fiction becoming science. That's how this goes.

• 19:53Speaker 02

  It always happens, doesn't it Neil?

• 19:54Neil deGrasse Tyson?

  Yeah, that's what it is.

• 19:56Speaker 02

  The thing about really great science fiction is that half of it's already happened.

• 20:00Neil deGrasse Tyson?

  We're gonna take a quick break, but when we return, we're gonna address the philosophical and ethical implications of CRISPR.

• 20:19Speaker 04

  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.

• 20:38Neil deGrasse Tyson?

  We're back, StarTalk. Chuck Nice, co-host Chuck. Hey, Neil. Tweeting at ChuckNiceComic. Thank you, sir. I appreciate it. Okay, I like your occasional posts there. They make me smile. Oh, thank you. But sometimes they're like making fun of other people and I guess that's still okay. I am a comedian and so... That's how that works. And that kind of comes with the territory.

• 21:01Neil deGrasse Tyson?

  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.

• 21:42Speaker 03

  Germ line 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

• 22:27Speaker 03

  that have those changes in an individual, but they won't be inherited by future individuals. And that's fundamentally different than germ line editing to me because it remains localized in one individual rather than being passed on to future generations.

• 22:44Neil deGrasse Tyson?

  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?

• 23:06Speaker 03

  Indeed, yeah.

• 23:06Neil deGrasse Tyson?

  So why wouldn't you want germ line editing?

• 23:10Speaker 03

  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 germ line 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, you know, society is ready for this. Like, how do we ensure equitable use, affordable access, all of those sorts of things? But, you know, if we set all that aside for the moment, I think what you just said is a very real 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

• 23:54Speaker 03

  to my children. And furthermore, I don't want my children to have to deal with it when they come around the time for them to have kids. And so I'm just going to get rid of it once and for all by editing the germ line." That could happen in the future.

• 24:09Neil deGrasse Tyson?

  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?

• 24:33Speaker 02

  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 genes for their children and make them taller, or make them, 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

• 25:14Speaker 02

  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.

• 25:59Speaker 02

  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 gonna happen.

• 26:12Chuck Nice?

  We're all screwed. Walter just told us, if it's up to us as a society, we're, oh, well.

• 26:20Neil deGrasse Tyson?

  Wait, 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 gonna stop it? Who's, who, how's that gonna? Is there, is there? Are you imagining a realistic future here rather than a utopian future?

• 26:42Speaker 02

  Oh, yeah, I mean, I think there are all sorts of medical procedures that either get approved or don't get approved.

• 26:47Neil deGrasse Tyson?

  Oh, okay.

• 26:47Speaker 02

  Uh, whether they're drugs or pharmaceuticals.

• 26:50Neil deGrasse Tyson?

  That's what it is.

• 26:50Speaker 02

  And, yeah, and I think we have international conferences. Jennifer Doudna in my book, we, I, you know, 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 Drang Ching-Pei, who is one of the people at the Chinese Academy. Uh, Robin Lovell-Bedge 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, you know, pharmaceuticals. Some people will be trafficking in elephant tusks. But we can try to minimize those things by saying they're not legal.

• 27:27Chuck Nice?

  I was gonna say, but doesn't that, I mean, if, once you, 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, those ethical guidelines and create whatever the hell they want to create.

• 27:46Neil deGrasse Tyson?

  That's what he just said about the tusks.

• 27:47Chuck Nice?

  That's what I'm saying. So what, you know, so, uh, but it's easy. My point, that's my question. It's easy to find the person who was trafficking in tusk. 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 do you, how would you even police that?

• 28:16Neil deGrasse Tyson?

  You can't do that on a street corner.

• 28:18Chuck Nice?

  Right.

• 28:18Neil deGrasse Tyson?

  It would have to be.

• 28:20Speaker 02

  Well, you know, a lot of things are kind of hard to police, but, you know, we can't stop it all. I think we're gonna 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 gonna do, whether it be through regulation or just social shame.

• 28:50Neil deGrasse Tyson?

  Well Chuck, we have a sort of example of that because back in 2018, there was a scientist in China that used CRISPR to actually edit the embryos of 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.

• 29:18Speaker 03

  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, you know, edited

• 30:03Speaker 03

  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, you know, the parents, I don't think, could really understand the technology or just how experimental it was and how untested it was.

• 30:48Speaker 03

  I mean, to do this on your children is, you know, kind of the most extreme use of something like this. And also, just that, you know, I think even the... 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.

• 31:11Neil deGrasse Tyson?

  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?

• 31:31Speaker 03

  Well, I certainly think the former is probably the most, you know, the most realistic strategy right now. 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,

• 32:14Speaker 03

  I don't really think that that, 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, you know, those journals said, you know, we're not, 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.

• 32:37Neil deGrasse Tyson?

  So that would be scientists policing ourselves in that sense? And that has tremendous value.

• 32:43Speaker 03

  It does, you know, 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 technologies and I look at the challenges with things like social media, right, very difficult to police it. How do we do that appropriately?

• 33:10Neil deGrasse Tyson?

  They don't even know what questions to ask.

• 33:13Speaker 03

  That's it, right? 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 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.

• 33:45Neil deGrasse Tyson?

  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?

• 34:29Speaker 02

  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, you know, 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

• 35:11Speaker 02

  families may make. And yet, in our system in the United States in particular, we tend to leave reproductive choices

• 35:20Speaker 02

  To the individual or to the family. And so this is where we're gonna 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's know what you can pick. You might pick the gender, you might pick the gender orientation, you might pick anything as your design.

• 35:42Chuck Nice?

  Behind closed doors, yeah.

• 35:43Speaker 02

  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.

• 36:22Chuck Nice?

  Well, two things. One, hopefully the first thing that they're able to edit out completely is asinineism. That's what I said. Okay, so, you know, if we, if we can get rid of asinineism, then we, a lot of that stuff will take care of itself. So there's a gene for that? That's a gene, there's a gene. That guy's an a-hole, we found a gene. We found a gene to give him. The second thing, the second thing though that, 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.

• 37:06Chuck Nice?

  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.

• 37:32Speaker 02

  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.

• 37:55Neil deGrasse Tyson?

  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?

• 38:07Speaker 03

  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? Uh, 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

• 38:51Speaker 03

  while the technology is still developing, is very important.

• 38:54Neil deGrasse Tyson?

  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 gonna 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.

• 39:43Neil deGrasse Tyson?

  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, 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.

• 40:13Chuck Nice?

  Oh, it's a pleasure.

• 40:14Neil deGrasse Tyson?

  It sounds like, "Oh, and Chuck Nice."

• 40:16Chuck Nice?

  Of course, because that's exactly what it was. Yeah, 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 gonna be, "Oh, yeah, and Chuck Nice."

• 40:34Neil deGrasse Tyson?

  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. Or are they saving that category for more rewards for this discovery?

• 40:55Speaker 02

  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 a 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.

• 41:32Neil deGrasse Tyson?

  Mm-hmm, mm-hmm. 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 described that. Let me ask you, tell me about competition in science and what you've discovered in your, as a biographer of her work, Jennifer's work.

• 42:06Speaker 02

  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 Sharpanj 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 Sharpanj in Europe to work around the clock by handing things off to each other when sunset happened in one place or the other.

• 42:47Speaker 02

  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.

• 43:04Neil deGrasse Tyson?

  Oh, okay, so this is a, this is an, uh, this is duty rises above what was otherwise the competitive spirit.

• 43:13Chuck Nice?

  Personal glory takes a backseat.

• 43:15Neil deGrasse Tyson?

  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 the end, if in the end, the results are valuable discoveries. So what precisely did they do to help COVID?

• 43:52Speaker 02

  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. And she woke her husband up at 2:00 in the morning and said, "We gotta 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.

• 44:35Speaker 02

  Likewise, Feng 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 CRISPRs, 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,

• 45:21Speaker 02

  which goes back to Jennifer Doudna'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.

• 45:37Neil deGrasse Tyson?

  So is it fair to say that without the CRISPR technology, we might still be reaching for vaccines at this point?

• 45:47Speaker 02

  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.

• 46:16Neil deGrasse Tyson?

  Oh, so it formed an important motivating force to further expand the power of CRISPR over our destiny. Is that a fair characterization of this?

• 46:27Speaker 02

  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.

• 46:47Neil deGrasse Tyson?

  And how long did it take you to write this book, The Codebreaker?

• 46:49Speaker 02

  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 Fang Zhang and Eric Lander and many other people in the book.

• 47:06Neil deGrasse Tyson?

  And Eric Lander, you can't just go by his name that quickly. Eric Lander is now the very first, the very first cabinet science post ever in the history of the country, Eric Lander, a biologist.

• 47:20Speaker 02

  A really good choice by Joe Biden.

• 47:23Neil deGrasse Tyson?

  Secretary of Science for the first time, yeah.

• 47:25Speaker 02

  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.

• 47:54Chuck Nice?

  Can I ask a question that is unrelated, but I'm just gotta know?

• 48:00Chuck Nice?

  Okay.

• 48:01Neil deGrasse Tyson?

  And we can always cut this, I think.

• 48:03Chuck Nice?

  Yes, we can. Yes, we can. We can always cut it, okay?

• 48:06Neil deGrasse Tyson?

  All right.

• 48:07Chuck Nice?

  But it's killing me, I gotta know this from Walter.

• 48:09Neil deGrasse Tyson?

  All right.

• 48:09Chuck Nice?

  Because...

• 48:10Speaker 02

  I'm preparing to die.

• 48:11Chuck Nice?

  No, no, no, it's... Okay, so check it out. So, all these brilliant people that you have chronicled, their lives and their accomplishments, who do you like best?

• 48:24Speaker 02

  Well, you know, as a person, 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, cuddliest 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 beer with.

• 49:04Neil deGrasse Tyson?

  And by the way, I share those same sentiments. When I... 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... It was 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 might be in the future of CRISPR? Because will that pave the way for curing cancer and other diseases that have been a blight on our civilization? Will in a hundred years, we look back in the primitive 2020s and say, "Oh, look at all the diseases that our species once had."

• 49:49Neil deGrasse Tyson?

  So let's see what she has to say about this.

• 49:53Neil deGrasse Tyson?

  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?

• 50:02Speaker 03

  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 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 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,

• 50:43Speaker 03

  and also really digging into the ways that this technology will become affordable and widely available in the future for solving real-world problems.

• 50:57Neil deGrasse Tyson?

  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?

• 51:36Speaker 02

  That's what we should be aiming for. 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, uh, 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. Uh, I was in Jennifer Doudna's lab with a guy named Feodor Yornov, about one of the most colorful characters in the book, and his job there is bring the cost down.

• 52:20Speaker 02

  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.

• 52:49Chuck Nice?

  So is it possible that we'll get to a place where instead of, like, i- i- i- in the, in the truest sense of manipulation, we're just trying to make things better? In other words, this is what you, we already see you do well. We've identified that. Like, you do this well, you do that well. What we're gonna do is augment that to the best of your ability. I, I mean, how, how do you, 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?

• 53:22Speaker 02

  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 or somebody. Well, you know, that ain't gonna be me. Uh, 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, uh, problematic, you know, genetic, uh, uh, conditions you have. Let's remove those so that every person can flourish to the extent their abilities and their desires, uh, lead them to.

• 54:06Neil deGrasse Tyson?

  Uh, 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.

• 54:16Speaker 02

  Absolutely, the boundary is fuzzy and in my book, I try to make us open our minds a bit to say what 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 Sanchez, as I'll 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 Bitch's Brew or Kind of Blue, some of the greatest...

• 54:59Neil deGrasse Tyson?

  Jazz albums ever.

• 55:00Speaker 02

  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 gonna 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."

• 55:43Neil deGrasse Tyson?

  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...

• 55:53Speaker 02

  Everybody's a winner.

• 55:54Neil deGrasse Tyson?

  Everybody's a winner, all around.

• 55:57Speaker 02

  You're talking to somebody in New Orleans...

• 55:59Neil deGrasse Tyson?

  In New Orleans, your home base.

• 56:01Speaker 02

  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.

• 56:16Neil deGrasse Tyson?

  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 people, mortal other folk. And thanks for agreeing to this interview on StarTalk. And I'm Chuck, always good to have you dude.

• 56:31Chuck Nice?

  Always a pleasure.

• 56:32Neil deGrasse Tyson?

  Neil and Chuck, thank you. Alright, we gotta 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.