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Podcast: Walter Isaacson — The Science and Business of CRISPR

Walter Isaacson

Walter Isaacson

Throughout nearly the entirety of human history, we have accepted a simple truth: A person’s genetic makeup is beyond one’s choice. Until now.

In 2020, the Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of CRISPR, a method for genome editing. CRISPR may change everything — and land us in a world previously imaginable only in science fiction.

CRISPR can be wonderful and incredible. It may eliminate a child’s susceptibility to a genetic condition, such as cleft lip or cystic fibrosis or devastating disease. Imagine that. However, it also makes it possible to choose a child’s height or hair color. With these and other possibilities, the moral and ethical implications are important and immense.

The race to discover CRISPR was one of the great science tales of the 21st century, a cross-continent battle of discovery and speed. So how did CRISPR arrive? And more importantly, where might it take us?

Walter Isaacson is one to tell that story — a professor of history at Tulane, he has been CEO of the Aspen Institute, chair of CNN, and editor of Time. He has written numerous No. 1 best-selling books, including on Leonardo DaVinci, Steve Jobs, Albert Einstein, and Ben Franklin, each one of the great creators of their time, who transformed not only their fields, but also the way humans connect — offering new ways to think about and engage in meaningful human interaction.

Isaacson’s latest book is The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race. It’s part mystery, part science, part personal, and completely compelling. Isaacson details the discovery of the CRISPR method and tells the story of the groundbreaking, female scientists who revolutionized the world.

Transcript: Walter Isaacson

Chris Riback: Walter, thanks for joining. I appreciate your time.

Walter Isaacson: It’s great to be with you, Chris.

Chris Riback: I realize we are talking today because you have written a new book, singular, but I would argue that is very misleading. I think you’ve written several books: a science history, a biotech 101 tutorial, a biography, an exploration adventure story that’s like a race to Antarctica, philosophy of… I mean, the list can go on. Frankly, it’s quite a bargain for the book buyer. It’s like a six in one package for one low price. I can only assume that was your intention the whole time.

Walter Isaacson: You know, a subject like biotech and how it’s going to transform our lives, and especially gene editing and the use of molecules to fight the coronavirus. It’s a wonderful story. But I wanted to personalize it, make it a narrative, make it a storytelling thing. So you could see how a real person, in this case, Jennifer Doudna and her partner Emmanuel Charpentier, and her friend Jillian Banfield, and many others embarked on this journey of discovery. And I guess most of all, I wanted it to be a journey of discovery but if you’re doing a book about a journey, whether it’s Huck Finn or The Odyssey, you always have to have a central character that helps drive the plot. And she’s a perfect central character. She’s a delightful, smart, persistent, insightful woman who was told as a young school girl that girls don’t do science, so, she decided to do science.

Chris Riback: And like any great story, tension and obstacles, and rivals and lows, and highs and successes and failures, and it’s all in there.

Walter Isaacson: Hey, it’s real life. Sometimes we have rivals and sometimes we have competitors, but that’s what spurs us on.

Chris Riback: It’s real life. I think you would also state it’s potentially the future of life

Walter Isaacson: I mean, it really is us having for the first time the ability to hack our own evolution, to say, here’s what we want the species to be. We want us to be less susceptible to viruses and not have sickle cell anemia. And so it does look a bit into the future, but these are things we’re going to have to sort out now and figure out, okay, what are we going to do with this tool?

Chris Riback: Yes, the future is now. There’s no doubt. So let’s talk about the framing that you set up at the very start. And one of, I think the through lines: Molecules are the new microchips. You’re touching on it just a little bit in your previous answer, but what do you mean by that? When I read how you framed it, it changes the way you go into thinking about Doudna’s story and about the whole adventure.

Walter Isaacson: We grew up, you and me, in the digital revolution. And we want to make sure our kids and young students know how to code. They know how to code digitally. They know how to code microchips, or at least have some feel for what digital coding is all about. Now, the first half of the 21st century is going to be about understanding the code of life and connecting that with our technology. And by the code of life I simply mean that every cell in our body has DNA and it uses RNA in order to express it. And it has a code, they’re four letters. And there may be a billion or 3 billion base pairs in a species, like ours, but you can read that code, and in the year 2000 with the human genome project, we sequence the entire human genome. Now we’re about to enter a phase where not only can we read our DNA, we can rewrite our DNA. And so to me, this ability to recode our molecules will be about 10 times more momentous than the ability to code and recode microchips. We’ve already seen that in the past year, where we’re just coding a bit of RNA to be a messenger, to tell ourselves, build that little part of the spike protein of the coronavirus, so that if the system ever sees a real coronavirus it’ll know to destroy it. So that’s what I mean by programming a molecule.

Chris Riback: And to be clear, that part gets to the heart of the Pfizer vaccine, which you participated in that trial and other vaccines. What’s to me, among the things so important about that concept, about the importance of biotech and the role that it plays of what we should be teaching our kids or what one wants to learn about is. We know today, you need to understand computer programming if you want to go into business, if you want to go into law, if you want to be an entrepreneur, and frankly in many ways if you just want to engage in society. And you outline how biotech is that next stage. Is that right?

Walter Isaacson: In the digital revolution, you didn’t really have to know how to do digital coding. You didn’t need to know Python or C++ or JavaScript, but you did need to know what coding could do. You needed to know what a website was, how to connect things digitally to our computers. And the-

Chris Riback: How to have a conversation.

Walter Isaacson: Right. How to have the conversation. And the real value came from people like Steve Jobs who did not really know how to code computers that well, but knew how to connect computers to creativity, to connect the arts and the sciences. That’s how you make the iPod, rather than the Zune. You’re the person who understands what digital technology can do, but you’re creative. You connect it to law, to business, to science, to art, to music. And that’s what’s happening now with the digital revolution, is that the people in the frontier are the ones not doing just the coding and being engineers, but the ones connecting our digital technology to our creativity, to our medicine, to our art, to our finance, whatever.

Likewise, now that we’re going into the life sciences revolution. What can we do with genes? What would it mean if we changed certain genes? What are the moral and ethical implications? How do we use that to make vaccines? How do we use it to make detection technologies? And then they’ll be able to connect this, sort of, wonders of nature and connect it to things like business if you want to start a company. Or you’ll be able to connect it to the law, if you want to understand the intellectual property. Or you’ll be able to connect it to just your everyday moral and ethical thinking, to say, what does it mean to be a human, and what’s the essence of our species and the diversity in our species? These are conversations that are interesting to have. And one more thing, even if you’re never ever going to engage in it, there’s a joy that comes from understanding how something works, especially when that something is ourselves.

Chris Riback: This is all about understanding how we work and how we might work, or potentially could work in the future. I can’t help though, as you’re telling that story, just feel lousy for Steve Jobs and how much he might’ve been able to accomplish had he actually known how to do computer programming. It’s-

Walter Isaacson: Well you know, Bill Gates knew computer programming 10 times, a hundred times better. And I think Bill Gates is a great entrepreneur of our time, a great philanthropist of our time. But early on he didn’t have that feel for design, that feel for beauty, and early on it took Microsoft a while to make products that were as beautiful as Apple’s.

Chris Riback: How did you meet Jennifer Doudna?

Walter Isaacson: I met her about six or seven years ago as she came to the Aspen Institute where I worked. But I’d already been interested in the life sciences revolution. I’d been interested in this notion that we can both edit our genes and make new vaccines and fight cancer by understanding genetic makeup of our genes, of our molecules, of our cells. And so I met her and we did a discussion on stage at the Aspen Ideas Festival about the moral implications of this. And when I asked her about her life, about how as a young girl she picked up The Double Helix and decided, “Hey, I’m going to become a scientist.” And the guidance counselor said, “No, girls don’t become scientists.” It’s like, okay, this is a really interesting life in the 21st century. And sometimes you have heroes and heroes don’t all wear capes. Some wear white lab coats and she’s one of them.

Chris Riback: I was wondering about that, what your personal eureka moment was. You had the science interest, you knew enough about CRISPR and what its potential was, but then the storyteller in you it sounds like, heard Doudna’s personal story and maybe that was when you said, wait a minute, Isaacson, you might have your next book here.

Walter Isaacson: Well, when I was in sixth or seventh grade, my father left on my bed, The Double Helix. I still have it here in the library. It’s an old first edition with a pale red cover.

Chris Riback: The red cover you said, yes.

Walter Isaacson: Yes. And I got interested in biology, always have been. And in life, you know, what are the miracles of nature? And in some ways I wish I had studied more biology. I studied it in college a little bit. But it was good because I came at this book as somebody who was not a scientist, who was not a biologist. So it’s not a technical book. It’s not a book about biology. It’s not a textbook. But when I heard that she had gotten The Double Helix from her dad at the same time, I realized, okay, I’d like to follow her journey, what she did after she got The Double Helix, how she persisted and became a woman in science.

Chris Riback: Some of the personality components, because you do tell a story, it is a narrative and there are the human components of storytelling that help drive this book forward. One of the components that I struggled with and admired about Doudna was, one, she’s just like the rest of us. So the book opens with this. She’s fretting over a parenting decision. Did she do the right thing sending her kid to the robot building competition just as COVID is breaking out? And who among us hasn’t been talked into letting our kids do something that we, in retrospect, we’re like, “Wait, why did I do that?” She’s super-competitive and struggles with that tension between her own internal competitive nature, but her desire to make things better for humankind. She gets jealous and angry and hurt. She’s good at relationships. She’s bad at relationships. I mean, there are all these aspects where she’s just like the rest of us, and then at the same time as you said a moment ago, not all superheroes wear capes. She’s kind of nothing like the rest of us. She was able to see the fantastic potential in CRISPR. Now that you’ve spent so much time with her, you clearly admire her incredibly, did you feel that conflict between she’s both ordinarily human and simultaneously superhuman?

Walter Isaacson: This is why she was such a good subject in my mind. Because you and I, and no listener of this show are ever going to be Einstein. We’re never going to have that processing power. He was in some ways, superhuman in his ability to visualize the curvature of time and space and come up with his theories. But Jennifer Doudna is a normal person like us. She gets annoyed at her competitors. She’s fiercely fighting her rivals to make discoveries, to get patents and finally to win the Nobel Prize. And she’s very, very human. Like, “Oh, I let my 17 year-old Andy go to this competition,” and wakes her husband up in the middle of the night and retrieves him and retrieves Andy, but then said, “Okay, I’m going to gather some scientists and we’re going to turn our attention to fighting coronavirus.” So I think when you have a character like that, we can all relate to her.

It’s not as if she’s got some superhuman processing power, but she’s dedicated, she’s persistent, and she has a curiosity that you and I both had when we were in our wonder years, and some of us, it gets knocked out of us after we keep asking why does the plant curl when I touch it? Or why does a sea shell have spiral shells. And the grown-up says, “Quit asking so many dumb questions.” Well, she keeps her childhood curiosity the way that Steve Jobs did, the way that Ben Franklin did. And so I think by having a truly human person, it made it easier to make this not some outsider that we can never relate to, but somebody you would have a normal dinner with. You would think she was fascinating, but you say, “Ah, I can admire her. She’s inspiring too.”

Chris Riback: Is it fair to conclude that the most complex character, I found, was Feng Zhang. And complex in that, you clearly like him. He’s a nice and brilliant guy. But he also kept, maybe in air quotes, information from his Harvard mentor, George Church. And I know there’s debate about whether he actually did keep it or not. But anyhow, he didn’t tell him that he was working on CRISPR. He didn’t tell his mentor, Church. He cut out [Luciano] Marraffini, his collaborator from the patent application. Tell me, who is Feng Zhang, what’s his relationship with Doudna and how should we feel about him?

Walter Isaacson: Well, I liked him, as you said. Feng Zhang was born in China, but raised in Iowa. He has that corn-fed cheeriness and eagerness to please of a person who grew up in Des Moines and was embraced by the good old American heartland hospitality. Jennifer Doudna doesn’t like him because he was a competitor. He filed patent applications and paid to expedite them and ends up beating her to the patent office, so to speak. And she really, I think feels a great rivalry and feels that he was disingenuous. But I’ll let the reader decide because I spent a lot of time with him and he’s smart and he’s charming. And yes, he’s competitive. And yes, when he was hot on the heels of a discovery, he kept it secret from even the person at Harvard who had been his mentor.

But you know what? There’s worse things in the world than that. I mean, we’re looking at people who’ve done much worse things. And yes, he sort of short circuits the patent application process and actually gets a patent before she does. But life is about competition, and life is about real people. And this book is about competition and real people. And the cool thing is when coronavirus strikes, they put aside the rivalry and they both turn their attention to using these technologies to fight the virus. And they say, and we’re not going to file for patents on some of this. We’ll put it in the public domain so any researcher who wants to use it to fight COVID can do so. I didn’t want to do a fairy tale here. I wanted to do a story about real life.

Chris Riback: No, it was no fairy tale. That tension between cooperation and competition, and the way both can drive a human being forward at different times and in different ways is I guess yet another theme. And then yes, the way that they come together around COVID particularly after everything they’ve gone through.

Walter Isaacson: And I think you understand people better if you become rivals and competed. I mean, you and I are journalists. When I was a journalist I worked at Time Magazine and we stayed up very late on Friday nights and worked on Saturdays because we were competing against Newsweek. And then on Sunday night I’d have dinner with Evan Thomas, one of my close friends who worked at Newsweek.

Chris Riback: And rub it in. Right?

Walter Isaacson: And if you ever got into trouble, if there were some real problems with the news business you’d cooperate a bit against the alien invader, like coronavirus. I think anybody who’s been in business, anybody who’s tried to be successful knows how you have to balance that, and so this book is an adventure story about people who make the most amazing discoveries, but they do it as real human beings in a race.

Chris Riback: Were you following that race in real time? Back a few years ago, were you following that day by day or week by week, or did you recreate it in your research?

Walter Isaacson: Yes, that race happened in 2012, and it was basically in the back of my mind that people had developed CRISPR technology and they were fighting over the patents. But when I wrote the book I went back month by month of who did which experiments, and what they did and how excited they were, and what they filed and the personal relationships. And of course you have all of the emails, you have all of the journal entries. And so just like James Watson’s book The Double Helix is about him and Francis Crick using the work of Rosalind Franklin to beat Linus Pauling and Maurice Wilkins and others in the race to figure out the structure of DNA, that’s how science leaps ahead, and that book is a great adventure race and so is so many other science books. The Eighth Day of Creation is a wonderful book written in the ’70s that way. So I wanted to make it clear what real scientists do every day in the lab, and how they’re kind of like the rest of us. They want to win the race to make discoveries. They want to win patents and prizes. But, more than the rest of us, they also know they’re doing it as a noble mission. It has a higher calling, which is it will help humanity as we found out during this coronavirus pandemic.

Chris Riback: The biohacking and bioethics, you give kind of an outline, a gradation of how we might want to consider where we want to go with CRISPR, from helping solve sickle cell anemia down to, well, do you want to deal with height and do you want to deal with intelligence? There are ways to think about the ethics. I tried to think about that in connection with Josiah Zayner, who is a bio-hacker and a fascinating character, and a rebel genius it seems. How is it possible to thoughtfully address the bioethics that you outlined, when Josiah Zayner has shown that yesterday’s kid computer hacker can be today’s kid bio-hacker.

Walter Isaacson: And we had He Jiankui, the Chinese scientist who also was almost like a hacker. He did in his own lab, edited the embryos of unborn, what became twin girls in China. And this is a technology that is not like building an atom bomb, which you can’t do that in your basement or your garage. But CRISPR editing is not all that complicated. So somebody like a Josiah Zayner, I actually admire him. As Steve Jobs used to say, “Here’s to the misfits, the rebels, the round pegs in the square hole. Those who are crazy enough to think they can change the world are the ones who do.” Well, these bio-hackers play a role. It’s like Puck in A Midsummer Night’s Dream that’s saying, all right, all you mortals are wringing your hands but, “what fools you mortals be,” let’s just proceed with things, and they pushed the race forward as Steve Jobs said.

Chris Riback: Should I buy my kid who is interested in CRISPR, who has read Doudna’s book, who has started your book, should I buy him the DIY CRISPR kit from The Odin, a genetic engineering home lab kit.

Walter Isaacson: Yes, it’s not that expensive. You can buy it online. It’s a do-it-yourself thing. Don’t let them experiment on himself or any other members of your close family. But you can use that kit to make frogs that are stronger, and it shows you the power of genetic engineering. When I grew up I had Heathkits. You’re probably too young to remember them, but we’d solder and make ham radios and other, walkie talkies. Well, I think these type of things will be the new Heathkits for a new generation, which is, you can do biology experiments. I’d not let him do it without a bit of oversight. How old is he?

Chris Riback: He’s 16.

Walter Isaacson: Oh, okay. Well, good luck, because you don’t want to give him much oversight. But certainly he’ll be able to… I mean, my book is, anybody in high school can easily read my book and anybody can do one of those do-it-yourself kits from The Odin.

I went and did it in Jennifer Doudna’s lab, which is, I edited genes there. Of course flushed them down the drain with chlorine to make sure they didn’t escape. I think the difficult thing in doing do-it-yourself CRISPR, is not editing the cells, but the delivery mechanism. Then you get it into an embryo in IVS, or to get it into a lung cell if you’re trying to do a CRISPR edit that might affect coronavirus, so the delivery mechanisms are going to be a lot harder. And we’re not ready for prime time here. I mean, we can cure sickle cell which is a pretty simple single genetic mutation, but the notion of trying to do intelligence  or things like that, we’re decades away because that’s a complex mix of genes and there’d be a lot of unintended consequences if you start messing with Mother Nature that way.

Chris Riback: Walter, to close out, DaVinci, Einstein, Steve Jobs, Jennifer Doudna, just among the individuals that you have written about. You also write about obviously curiosity, and you write about genius. And I found myself wondering as I was thinking about your work about those characters and about those concepts, which comes first, curiosity or genius? How do they interplay?

Walter Isaacson: Curiosity. We all have curiosity. And those who really keep and curate their curiosity, they’re the ones who really can push things forward. Jennifer Doudna was just purely curious about things. And the cool thing is to be curious, curious across all of human nature. Curious about the arts and the sciences. And that’s what I think everybody from Leonardo DaVinci to Jennifer Doudna, they love both the arts and the sciences.

Chris Riback: Walter, I loved the book. Thank you for your time.

Walter Isaacson: It was great to be with you.