^B00:00:14 >> Shari Werb: Hi, I'm Shari Werb. So, when was the last time you visited a library, and why did you go? Maybe to check out a new crop of books? Or do a little research on a topic that interests you. Maybe you've even utilized your local library's resources, digital or otherwise, during the pandemic. Well, here at the Library of Congress, we want to be of use to you too. It's not only our aim to connect you with our wide ranging collections, ample services, and knowledgeable experts, but to invite you to engage contemporary authors, ones who are broadening our perspectives, and enriching our world. For that reason, I am excited to introduce today's events, which features a celebrated writer and biographer, Walter Isaacson, and takes on a very timely topic, gene editing, and its role in our lives. Many of you may not be aware that gene editing tools are responsible for the first COVID-19 vaccines. This means that we are not so far from complex scientific accomplishments as we might think. In fact, Walter Isaacson has gone to great lengths to demystify the gene editing machines used in the global vaccine effort. His new book, The Code Breaker, Jennifer Doudna, Gene Editing and the Future of the Human Race, has at its center a special hero. A prize-winning scientist, who developed a special technology Crispr, that has applications in fields far beyond science. Our interviewer is the acclaimed science writer, Katherine Eban. Eban's work focuses on public health issues, and she has taken on big topics like gun trafficking and pharmaceutical counterfeiting. She is the perfect person to help us understand the story behind Isaacson's new book. So, without further adieu, please help me welcome Walter Isaacson and Katherine Eban. >> Katherine Eban: Congratulations on your new book, The Code Breaker. I'm a science journalist, and I'm going to just jump right in here. The science of Crispr that you describe in your new book is incredibly complicated. How difficult was it for you to understand and explain it, and can you explain it to the audience? >> Walter Isaacson: Absolutely. I don't find it that complicated, because bacteria have been doing it for a billion years, and they're not much smarter than we are. What Crispr is is simply a system they use to fight viruses, which is quite useful for us these days. Whenever they get attacked by a virus, they take a mugshot of that virus. A tiny snippet of the genetic code of that virus, and they put it in these clustered, repeated sequences, and they're all in genetic material. And that way, these clustered repeated sequences, Crisprs, serve as a way that they can spot the virus if it comes back, and then they can chop it up with an enzyme. And so, it's a system that adapts to each new wave of virus, which is what we're trying to do. What Jennifer Doudna and her team did was they figured out a way to repurpose this Crispr system in bacteria so that it would cut our own DNA at a targeted place we tell it to cut. In other words, if we want to change a gene in our genetic code, the Crispr system can just edit the gene, and so that's what Jennifer Doudna and her team did in 2012, is take this old system from bacteria and say, let's re-engineer it to make a tool to edit human genes. >> Katherine Eban: So, it turns out that sometimes nature had the best ideas, and maybe sometimes it didn't. So, let's talk a little bit about that. ^M00:04:12 Presumably, you started working on this book before the COVID pandemic struck, but there must have been a moment for you at the very beginning of the pandemic, when you thought to yourself, wow! This is even more relevant than I thought. Do you want to talk about that a little bit? >> Walter Isaacson: Absolutely. I knew that understanding the life sciences, and the way we can treat molecules, as if they were microchips, and recode them, I knew that was an exciting story of adventure, with colorful characters. But then, when COVID struck, I realized, it hit home. It's even more important. It's affecting our lives every day. And to just talk about what happened to Jennifer Dowden and my own hero in the book, it was about a year ago. It was last March, when her son, she had sent her 17-year-old son off to a robot building competition in Fresno, California, and at 2:00 in the morning, Jennifer wakes up her husband, Jamie, and says "We've got to go pick up Andy from the Robot building competition, because this pandemic is starting to spread, I don't want him to be in a conference center. You know, Andy is an only child. So when they go there, at about 5:00 in the morning, he's like, rolling his eyes, like oh mom, what are you doing? But as they left the parking lot, they got a text that said robotic competition canceled, every kid go home. And that's when it hit home to Jennifer, and to me, because I was talking to her and working with her at the time, that this was going to be a big deal, and so that next day, a Friday, she rallies not only about 20 scientists from her own lab, but 50 scientists from the home bay area of California, and then she says alright, we're going to have to turn our attention to the coronavirus, and start focusing on it. And arrivals, the competitors she has at the Brode Institute at Harvard and MIT, led by this wonderful scientist, Fong Chang, he did the same thing, and they started creating detection tools for coronavirus, ways to directly kill the coronavirus, and many other things. So, it really brought home that the tools I was describing in this book aren't theoretical, you know. I went up and signed up for the Pfizer vaccine, right through that period, and so last July, I became the very week of the clinical trial of the vaccine, because it's something that's run by RNA, and that's the hero molecule in my book. ^M00:06:56 >> Katherine Eban: Mm-hm, that's right. You know you've, you've obviously moved in the worlds of journalism and in the world of science, and you describe in very compelling ways the competition to be first among scientists, and I kept thinking as I was reading that, about, you know, the pressure in journalism not to lose the scoop. I'm wondering if you could talk a little bit about that competition and what it was like to have a ringside seat to the scientists putting that aside for the benefit of humanity. >> Walter Isaacson: It's a great question, and you and I as journalists know what it means to have the scoop, and we compete to do it, and certainly scientists do, and for that matter, I think almost any competitive field people want to be first. In science, there are a few things you want to be first. You want to win the patent. You want to win the prize, especially the Nobel prize, and you want to publish, first. And so there was a bitter competition between Jennifer Doudna's team, and the team at MIT Harvard, for all of those things. But, as I mentioned a year ago, they all turn their attention to the coronavirus, and they started publishing openly online, on servers, not worrying about peer-reviewed publications coming first, and they didn't assert patent rights. They said anybody who wants to use this latest discovery that we have for detection technology is free to do so in order to fight the COVID pandemic. So, I think this pandemic helped remind everybody including the scientists involved, that yeah, you do it for patents, you do it for prizes, you do it for publications, but also we do it for a higher purpose, and that higher purpose is helping humanity. >> Katherine Eban: Right. You know, something that struck me as I was reading the book is, given your past work, this is your first book that has a female protagonist at its heart, and it was also striking to me that it was women who pioneered RNA science, really, and advanced it. I'm wondering why do you think women led the events in this particular area of science, and also, what was it like for you as a writer, really for the first time, drawing such a detailed female character. Was it a different sort of writing job? >> Walter Isaacson: Yeah, when Jennifer Doudna was in sixth grade, she came home, and her dad had left The Double Helix, James Watson's book, about DNA, on her bed. And besides understanding what a wonderful competition in joining the discovery of that as, she realized there was an under-appreciated character in the book named Rosalind Franklin, who did the imaging work that led to the structure of DNA. And she realized, okay, girls can become scientists. And at her high school, her guidance counselor later on said no, girls don't do science. But that kind of drove her, all the more so, to do science. ^M00:10:17 And in the 1990s, when she was in graduate school, most of the men doing biology were focused on what was called the human genome project, which was the effort to sequence the entire DNA of humans. And it was a pretty--it was a definitely male-dominated endeavor. Now, Francis Collins, and Eric Lander, and Craig Venter, and James Watt were all involved, very few women, if any, were involved. And Jennifer, and some other women, started paying more attention not to DNA, but to the molecule that actually does the real work, RNA. RNA is sort of the forgotten sibling, but it's a one when DNA just sits in the nucleus of our cells, RNA goes out and makes proteins, based on that code, or it can be a guide to have enzymes that cut up DNA at a targeted spot, and Jennifer told me that when she was a young girl growing up in Hawaii, she loved playing soccer. But most of the boys always ran to the ball and Jennifer liked playing positions on the field that others didn't play as well, and she would be able to see the whole field. And so, what she does, along with Jillian Banfield, one of her colleagues, and then Emanuelle Charpentier, who she meets at a conference in Puerto Rico, they are focusing on RNA, and as you learn by reading the book, RNA is the one that's turned out to be incredibly useful these days. >> Katherine Eban: Right. And just speak a little bit about whether it was a different kind of writing challenge for you to put female protagonists at the center of the book. >> Walter Isaacson: I don't think so. I mean, I guess I'll let you or others be the judge, but in working with Jennifer Doudna, you know, she told me, "I don't think of myself as a woman in science, I think of myself as a scientist, and I'm a woman," so I don't try to overplay this. I mean, it would have, you know, this is not a book about how women endure in science. But it is how they're somewhat different. How they, how Jennifer and Emanuelle and Jillian Banfield had a certain collegiality that helped them form certain types of teams. And I don't try to be preachy in this book. This is just a storytelling book. And I spent, you know, four or five years by Jennifer Doudna's side, in her labs, with her colleagues, you know, with her, or in the past year, in her Zoom meetings and her [inaudible] channels, and I just describe how she operates and I think it's up to the reader to say you know, well that's different than the way a man would operate. >> Katherine Eban: Right. Let's talk about some of the implications of the science here. I think just, at least speaking for myself, I think that the science of Crispr really broke into public consciousness in 2018, with an announcement out of China that raised a lot of very thorny ethical questions. Can you talk a little bit about that? And also its impact on Doudna? >> Walter Isaacson: Right. What happened was a Chinese scientist edited the early stage embryos of what became twin girls, and he did it so that they didn't have the receptor for HIV, the virus that causes AIDS, and it caused a lot of shock and consternation, because the edits he made by doing it in very early-stage embryos would be inheritable. In other words, he just wasn't simply editing a patient, he was editing all of the children and all of the descendants of the embryos that he edited. In other words, he was editing the human race. >> Katherine Eban: Right. >> Walter Isaacson: And I don't think we're ready to make inheritable edits in the human species. There's so much we can do with Crispr in patients, living patients, like cure them of sickle cell, or Huntington's, or Tay-Sachs or cystic fibrosis, in ways that you do in the patients' body. It's called somatic editing, where it doesn't affect the reproductive cells. And so even if something goes wrong, it's bad for the patient, but it's not bad for the whole species. And so that's what happened in 2018, that made, just like coronavirus, the urgency of what I was writing about, home; this also brought the urgency of us figuring out do we want to make inheritable edits, and what are the rules going to be? >> Katherine Eban: So you had a front-row seat, then, for when Doudna was able to really sort of consider and live the implications of some of her discoveries. Can you talk about what her reaction was? >> Walter Isaacson: Well, her first time that she really realized the implications were going to be huge were shortly after she and Emmanuelle Charpentier, and others, invented this gene editing tool that we call Crispr. And she had a horrible nightmare. And it was that somebody had summoned her to a room saying "I want to understand this technology you've developed," and when the person looks up, it's Hitler. And so she decides if this falls in the wrong hands, this is bad, we don't want it to be used for Eugenics, or state-sponsored Eugenics. So, she starts gathering, from around the world, scientists, religious leaders, politicians, to have these conferences and summit meetings to try and hammer out the rules of the road. It was in the middle of this process, though, that the rogue Chinese scientist edited the early-stage embryos, going against the guidelines that were being developed. And that's when Jennifer sort of redoubled her efforts. She flew to Hong Kong, right that next morning, to meet with the Chinese scientists and this international meeting that was occurring there, and they now have gotten most of the National Academies of Science in countries, including China, the UK, Europe, America, to be part of a process to say let's not do this unless it's medically necessary and let's not do it in a way that's inheritable. Let's start with the thousands of things we can do that are incredibly important to make our kids healthier, to help us fight cancer, to help us fight off or avoid genetic diseases, and so that's what they're doing right now, is trying to institute these guidelines. >> Katherine Eban: You are perhaps best known for writing about geniuses who have been long dead, and here you are writing about somebody who is very much alive. So I'm wondering if you could talk about sort of the difference in the writing process, as you know, what that difference is, and you know, really what is more challenging? You know, in journalism, when you find out that somebody who needs to comment is dead, you maybe feel a little relief, it's one less phone call to make-- >> Walter Isaacson: I love making those phone calls. I love being by somebody's side. And twice, I've had that experience. I spent years by Steve Jobs' side, you know, and up until he was very sick. I was, you know, got to sit with him day after day or work with him in his design lab. Likewise, with Jennifer Douden, I spent much time in her lab, and as I said, you know, during the coronavirus pandemic, you know, in her Slack Channels and Zoom meetings. And you get to make it a real-time journey if you're doing it that way. In other words, you're by their side, so you get to tell a story that feels more like a page-turner, or detective story as opposed to a piece of history. Because even I, when I was reporting it, did not know how it was going to turn out, you know? I'd be there for experiments, not know what the results would be. I'd be there at conferences, not know what they'd agree to. So, I could write it in real-time, as if I were going hand in hand with the scientists involved, in making the discoveries or understanding things in real-time as they did. And in fact, that was the case. >> Katherine Eban: When did you start work on the book? And did you know right away that she would be your main character? >> Walter Isaacson: No, I started work on the book six or seven years ago, knowing I wanted to do the life sciences, that the life science revolution and the genetic revolution were going to be bigger than the digital revolution. I wanted to describe it. And so I met a whole lot of scientists in the field. But the more I spent time with Jennifer, I realized that she was a good main character. So the book evolved over the few years I was working on it, and is not just purely a biography of her, it's partly a biography of her, and partly a narrative story of discovery in which she's the main character. Just like, you know, in any--most books. Whether they be fiction or non-fiction, you can have a narrative, and the narrative can have many players in it. But sometimes it helps to have a narrative thread that is following one particular character that holds it all together. And she was perfect for that. ^M00:20:30 Because as a young girl, she's reading about DNA, when she's in school, she decides to become a scientist, she's the one who understands the structure of RNA early on, and then she starts asking the big questions like, how did life begin on this planet? And she and her thesis adviser show how RNA was the cause of life beginning on planet earth. And then she does this gene editing tool, and then turns her attention to coronavirus, and to the ethical issues. So, every part of the tale, you know, she's there. And so by riding alongside her, we can make it a more exciting narrative. >> Katherine Eban: That's great. Francisco Mojica is a fascinating character. I felt drawn to him, in part because he was so low-key about his own work. He was sort of like this backyard tinkerer, but it also raised another question in my mind, which is who is it that winds up winning a Nobel prize, and how important is sort of ambition and self-promotion essential to the kind of recognition that Doudna achieved? >> I don't think that she achieved it from self-promotion. She and Emmanuelle Charpentier are not real self-promoters. But you're right, you're asking a question of how do you award a prize to two or three people when maybe 20 or 30 people all made great contributions to Crispr. And that's why I think the prizes and patents sometimes distort science. They try to make one person or two people to be the discoverer or a particular thing. That said, the Nobel prize, I was hoping that before my book came out it would be awarded to Crispr. But I didn't think it would be, because Crispr is rather new. We're only talking about something that was discovered 8 or 9 years ago, and sir Roger Penrose won the physics prize this past year for something he discovered 50 years ago about black holes. But I set my alarm for 4:00 a.m. so I could watch the announcement that October morning from Sweden. And once they said it's for rewriting the code of life and bringing science into a whole new era, I let out a cheer, because I was--it's going to be Crispr. Then I held my breath to say okay which three people will they give it to? Now, I thought they were going to give it to Jennifer Doudna and Emmanuelle Charpentier, because they made the key discovery of what is the components of the system and how do you re-engineer it to edit genes? But I thought Francisco Mojica might be a good third choice, because the Nobel usually gives it to three people. He's the one who was a graduate student in Spain, in the 1990s, and first noticed these clustered repeated sequences, and he's the one who gave them the name Crispr. Delightful guy, wonderful time talking to him. And there are others. There's two yogurt makers, you know, worked for [inaudible]-- >> Katherine Eban: [Laughs] >> Walter Isaacson: And they discovered by looking at the genetic sequences of the bacteria in starter cultures, what happens when bacteria get hit by viruses? And then there was Fong Chang, the wonderful researcher at the Brode Institute at Harvard/MIT, who is the first to cross the finish line, along with George Church, on how do you make it work in human cells? So, then, I was somewhat surprised that the Nobel committee, instead of picking a third winner, decided to just leave it at two winners. My book is about Jennifer and about Emmanuelle, but is about all 20 or 25 heroes that I think help make Crispr and gene editing the technology it is. >> Katherine Eban: I have to say as a yogurt lover myself, I was stunned to see how much high-level science seems to go into it all. And speaking of high-level science, you know, one question that I had, and it's really about the future, are we going to see the woolly mammoth come back in our lifetime? Are we going to see the Northern White Rhino be rescued? And what are the implications? >> Walter Isaacson: Yeah, well that's a wonderful question, because there are a lot of implications for how you could use gene editing, and one of them involves the woolly mammoth. About the most colorful character in my book is George Church, whom I'm sure you know, is a Harvard biologist. And he has been a leader in gene editing. He was the one along with Fong Chang who made Crispr work in human cells in January 2013 first, and he's trying to bring back the woolly mammoth. If you look at George you might think well, he's doing it out of a sense of kinship. Well there's this huge, bushy beard, and wild hair, he kind of looks like a woolly mammoth-- >> Katherine Eban: [Laughing] That's true, he does, yeah! >> Walter Isaacson: And so, he's saying alright, we can take elephants, and others, and we know the DNA sequences of the woolly mammoth. Let's edit it, and try to re-create the woolly mammoth. Now, that gets you into Jurassic Park territory. >> Katherine Eban: Right. >> Walter Isaacson: I'm not sure I'd want to go to Jurassic Park in real life, but I assume that George, who is a very, very careful scientist, will do this carefully. >> Katherine Eban: So, you know, you have spent a great deal of your professional life sort of documenting genius, and to some extension, lionizing genius, but obviously there is a dark side to it as well which you touch upon in the book, and you talk about Doudna's sort of mid-life mini breakdown, and you talk about sort of depression among some other scientists. What can you say about whether that just seems to come along with the kind of brain who can, you know, achieve the things you write about? >> Walter Isaacson: Yeah, and the other thing all of us feel like outsiders at times. Certainly all of my characters, Jennifer Doudna growing up as a lanky blonde girl in a class in a small town in Hawaii with only kids of Polynesian descent, but certainly Einstein as a Jew in the 1920s, or Steve Jobs being adopted, or Leonardo Da Vinci being born in a small village, and being born out of wedlock, and gay, and left-handed. They all feel, "how do I fit in?" They all had a certain curiosity about everything. And also, you know, before we go around curing psychological disorders, we have to realize too that sometimes the type of psychologies we have lead us to a certain darkness, or lead us to a certain depression, but may also lead us to a certain creativity. So, before we start messing with these things, I think we have to appreciate the complexity of nature, and that's why I would start with a very simple genetic problem like sickle cell or Tay-Sachs or muscular dystrophy. >> Katherine Eban: Mm-hmm. As you, I mean, I assume you went into the recording and writing of this book with certain expectations, but there must have been things along the way that really surprised you and were not what you expected. What might those things have been? >> Walter Isaacson: Well, first of all, how easy it is to use Crispr to edit human cells. I mean, I did it in a day with just one graduate student helping me through it. You can buy the substances you need online, including the Crispr cast 9 solutions that you can do--now, it's hard to deliver it into human beings. It's something that takes a lot of medical technology to do. But the fact is, this is a pretty easy technology. And frankly, I found the science both more beautiful and less daunting than I thought it would be. I mean Crispr really only has three molecules, and you know, it has got a guide RNA, another type of RNA that's used through it, and an enzyme, that cuts DNA. And this you don't have to--is not like trying to understand Einstein's general theory of relativity, where you need to know certain types of tensor calculus. So, I found that nature is really beautiful. Nature has all these wonderful phenomenon, that out of curiosity we try to learn. But then that curiosity ends up leading to things that are useful, such as messenger RNA vaccines to defeat coronavirus, or Crispr systems, so that we can edit out genetic defects. ^M00:30:04 >> Katherine Eban: And if the science is, in fact, simple to do or to understand, can you talk about why it was so challenging to uncover? >> Walter Isaacson: Well, I think that it was only in the 1990s that we started to be able to sequence DNA. In other words, the whole genome of organisms. So not until the year 2000, 2001, that we sequenced the entire human genome. And so when Francisco Mojica, who you mentioned earlier, the Spanish graduate student, in the 1990s, he's sequencing the DNA of small organisms, like bacteria. And he notices these clustered repeated sequences. Well, what does he think at first? Not, oh, I've discovered an amazing new thing in nature, he thinks, I screwed up the sequencing. Sequencing is hard. We didn't have, you know, sequencing machines, the way in a biology lab you now have. So, he keeps trying to redo it, and he keeps finding that he gets these repeated sequences. And so it takes until about the year 2001, 2002 to understand that okay these really are repeated sequences. And then you need the yogurt makers and everybody else to say, well, let's look at the history of bacteria in our, you know, starter cultures, and let's figure out why these repeated sequences exist. And then, in the year 2012, Jennifer Doudna and Emmanuelle Charpentier say here is the three molecules that make up the system, and if you tweak the RNA guide, you can make it cut wherever you want. So, really, within the course of 15-20 years, you've discovered, you've gone from a curiosity of nature that seems mysterious, into tools to edit human genes. So, I think it happened pretty fast, in some ways. >> Katherine Eban: You know, it's interesting because one of the things that is very compelling in your book is tracing the sort of early lives of some of these scientists and the way in which they were able to use their kind of native talents and abilities to get recognition, and within the, you know, scientific community of American Universities, really find a way to apply those talents. What is striking to me is that [chuckles], even with all of this sort of fertile ground for American science, we are also at a moment where science is incredibly under threat. We've just been through a, you know, catastrophic pandemic response, in which science was almost positioned as the enemy. How do you reconcile those two things, and what do you see as the future here, not just for American science, but really science in the world? >> Walter Isaacson: Well, one of the reasons I wrote this book is to celebrate the fact that nature is beautiful, that understanding nature is a joy, and understanding nature also turns out to be useful. So if you understand nature, you can figure out how you can take a messenger RNA and defeat a coronavirus. This is totally amazing. That within a year of us having this virus pandemic hit us, scientists now have and manufacture and send around the world these new types of vaccines that are showing an amazing efficiency at defeating or knocking back the coronavirus. So I mean, some people will be skeptical of science, but first of all, once they think about it long and hard, most people are going to say I think I want that vaccine. And if they care at all, they're going to be somewhat curious about how does that vaccine work? And I've got a couple of chapters on how fun and easy it was to do the inner workings of that vaccine, and I think that, if we're going to come out of this pandemic in better shape, it's because we start appreciating the wonders that science has done for us. And yeah, there's still an anti-science sentiment. There's still an anti-vax sentiment. There's still an anti-mask sentiment. There's still sentiment that, you know, denies climate change. You're not going to fix all that. But I think the success of scientists in finding a vaccine and detection technologies for this virus, and the way that myself and many others were right about the joy of discovery of how it all worked will, I hope, shift our minds a bit to be a bit more appreciative of the beauty, as well as the usefulness and the nobility of basic scientific research. >> Katherine Eban: Right. So, let's go back a little bit, to your earlier sort of career, and how you decided to, I mean, maybe we didn't know at the time that you were embarking on a series of books about [inaudible], but how did that decision come about? Are you--are you a failed scientist [laughs], or a successful writer, or failed scientist, or both? >> Walter Isaacson: Well, I love science, I always have. Just like Jennifer Doudna, my dad gave me The Double Helix when I was in middle school. I still have the old pale red, you know, first edition, with the messed up dust jacket, and all my scribblings in the margin defining words I didn't understand, like biochemistry, and you know, my father was an engineer. My uncle was. My brother is. So, I've always loved science and engineering and studied the history of science, and I guess it began in terms of writing about it when I wrote a biography of Benjamin Franklin. I was interested in Benjamin Franklin for a whole variety of reasons, but as I researched him, I realized he was the greatest scientist, and especially experimental scientist, of that era. And that a single fluid of electricity was hugely important, as was the lightning rod, as was things like the batteries, and other things he invented. And so I realized that Franklin would have thought you were a Philistine if you didn't appreciate the sort of fun and joy of science, and I--other people had written about Franklin--hadn't written much about his science. >> Katherine Eban: Mm-hmm. >> Walter Isaacson: But he was, you know, the first rate scientist of our country. And so then, I wanted to de-mystify science, because people of my generation got afraid of science partly because of people like Einstein, who made it feel like you had to be an Einstein in order to understand physics. So I wanted to do a biography of him to make the science comprehensible. And now, when I did Steve Jobs, it wasn't simply because I wanted to do a science book, but I think it's important as we sit here on our computers or flicking our iPhones to have some sense of how do they make this? What went into this product? Otherwise we feel alienated from our technology, just like some people feel alienated from science. And so I would say out of the course of a career, I wanted to write about creative people. I wanted to write about people who were imaginative, and thought out of the box, and part of that is being creative in all fields of endeavor. Just like Leonardo, you know, we think of him as an artist, but his title, in the Court of Milan, was Artist, Scientist, and Engineer, to the Duke of Milan. So, I wanted to write about people who understand the beauties of the humanities, as well as the sciences, of the arts, as well as technology. >> Katherine Eban: Let's talk a little bit about your process. Because it's possible that most people don't realize how incredibly difficult it is to make a complex book easy, and how hard it is to make a book with so much information and so many characters, a page-turner. What is it that you do to help you get to the finish line, how do you structure your work, if you could talk about that a little bit? >> Walter Isaacson: I always structure my work as if I were a storyteller, which means it's chronological, it's a story, it follows the narrative line. I had a mentor here in New Orleans named Walker, he said there are two types of people who come out of Louisiana, preachers and storytellers. He said, for heaven's sake, be a storyteller. The world's got too many preachers. And by that, he meant, just the way the Bible does it, if you're going to explore moral issues, if you're going to do anything, you do it as a narrative that's chronologically driven. I mean, the Bible has the best lead sentence of anything, you know, "In the beginning," comma, and so, whenever I structure something, whether it's a biography or a narrative tale like the codebreakers, or you know, the innovators, I do it chronologically because everything that happens builds up to the next thing that happens, and when you're telling it as a story, it's more accessible, especially if you're doing it for a human. So, my process is, I try to learn everything I possibly can, and interview everybody possible, and then hang around them, and then put all my notes in absolute chronological order, and then I say to myself, "In the beginning," comma. >> Katherine Eban: God, that is excellent, excellent advice. ^M00:40:22 And is there a sort of secret sauce for how long a book like this takes to create? >> Walter Isaacson: Not really, I mean, some take longer, for me at least. But I find that in five or six years, if you're really focused, you know, you'll probably get the research done and you know, take another year or so to write, but often I'll be gathering for a book for many, many years. I mean I've been gathering string for twenty or thirty years just on biochemistry and life sciences, thinking someday I'm going to write a book about it. And with Steve Jobs, you know, even in the 1990s, when I was at Time Magazine, I was gathering things on him because I thought he would be a good subject. So, sometimes it takes about 10 years of sort of in the back of your mind accumulating thoughts, and then five or six more years to write a book. >> Katherine Eban: Have you started your next book? >> Walter Isaacson: No, and I don't know what it will be yet. >> Katherine Eban: Uh huh, and--and are there, are there projects where you've thought to yourself, I'd like to do something completely different. I'd like to try something that I have not done before. Or do you feel like, you know, staying in the kind of universe of innovators, for transformative innovators, is where you want to be? >> Walter Isaacson: Well, I tend to like innovators, and people who are creative, and transform things. Because I'm interested in how creativity occurs. And how imagination becomes a sort of child of curiosity. And that's always been fascinating to me. So, I don't write about war heroes, you know, generally or sports figures, and you know, even not a presidential historian, you know, I don't say, okay let's do James Monroe next. But perhaps too, I like people whose curiosity extends over many fields, the way Leonardo was curious about everything you could possibly know about every field that was knowable. So was Benjamin Franklin. So, it helped them see patterns across nature. >> Katherine Eban: You know, in my background as an investigative journalist, often there are--you spend a lot of time looking at conflicts, investigations, law suits, and you touch on that, maybe a little bit more than touch on it with this sort of patent disputes, the disputes about who got there first, who deserves the credit, and I was struck that you even sort of just say to the reader, "Well, here's my take. I looked into it, and here's my take," which was generous. Do you ever feel compelled to sort of get to the bottom of it, or do you feel that you have? And were you struck by the conflict surrounding the science? ^M00:43:51 >> Walter Isaacson: Well, there are a lot of conflicts over who did what first, who deserves credit, who deserves a patent. And I try to tell it through the eyes of all the players. Not only Jennifer Doudna and her side, but Fong Chang was incredibly generous, he's the rival. And you know, I've spent time at Legal Seafood, you know, at Kendall Square, and time in his lab, time at the Brode Institute. And so I was with him up in Canada once, eating charred seal meatloaf [laughter], you know, I try to give his side, as well. And then I don't try to say and here's the answer. I mean, at the end of my book there's no answer saying exactly it. But I do--because I've spent so much time looking at it, I think after I get all the storytelling, so that the reader can judge, ah, I think this person deserves this credit or that, I kind of try to be very casual and say, and for what it's worth, here's where I come down on this particular dispute, and I don't try to say here's the right answer, but I just say, I have given you everybody else's opinion, and here's my general opinion, which is usually that it's kind of hard to know, but on balance, I tend to feel this way. ^M00:45:09 >> Katherine Eban: One sort of classic challenge for a journalist is trying to get access to people. Do you face that challenge, or do the people you contact say hey, Walter Isaacson wants to talk to me, maybe he's going to put me in the book. Come on over to my laboratory! ^M00:45:29 >> Walter Isaacson: The first thing I learned as a journalist is, no matter who you are as a journalist, that tends to happen. I work on the Times piece here, in New Orleans, I call up somebody, even somebody involved in a crime, whatever it may be, and it always surprised me that if you call and you knock on the door, they want to talk to you. You know? Even when they probably shouldn't. You know? When you're doing an investigation. And I think many young journalists don't fully understand, you're supposed to knock on doors. You're supposed to make the phone calls, and if you do, people are just natural. It's ingrained in the human psyche, they're going to want to tell you their side of the story. Now, obviously, as you point out, as my career has progressed, and I worked at Time Magazine, and I worked at CNN, and written books that people have read, when I call, you know, I tend to be able to get through, probably faster than a 24-year-old just starting out in the business, but I would tell the 24-year-old, you're going to get through too if you call and you knock on the door and you seem genuinely interested in asking questions and learning the answer, as opposed to I want to ask a few "gotcha" questions and see if I can make a sensation out of this. >> Katherine Eban: So just, I know that we are pretty much out of time, so just my closing question for you, as you had said, you weren't sure who your main character was going to be--was there a moment when you informed Doudna, hey, you know, you're the codebreaker, this book is sort of centrally about you--and if so, what was her response to that? ^M00:47:08 >> Walter Isaacson: You know, it evolved as we worked together, and I worked with some of the people who were her rivals, or her colleagues, and as it evolved, I was always incredibly up-front and honest. I, you know, and I hoped she felt, and all the other characters, I mean, Fong Chang, I was meeting with him, and I had to say to him you know, I'm thinking more and more that Jennifer Doudna, your competitor, is going to be the main character of the book. That was a harder, you know, thing to say, because I think Jennifer was quite happy to be the main character, but I wanted to be honest with Fong Chang, and George Church, and Emmanuelle Charpentier, that even tough I was flying to Berlin to spend time with Emmanuelle Charpentier, that Jennifer Doudna was going to be the main character. And it kind of evolved so that she became more and more the narrative thread, because she's just so interesting, and you know, you can tell things through her eyes. It makes it easier for the reader, because she's discovering things, as we watch her, and go hand in hand with her, then it makes the science less intimidating. So, I just kept her informed as my thinking evolved, but it didn't evolve all the way to saying I'm just going to do an absolute pure biography only on Jennifer Doudna. >> Katherine Eban: Right. >> Walter Isaacson: It's a collective story of 20 or so amazing scientists, but like many, you know, whether it's a play, or a movie, or a novel, you know, you can have a main character or two, and many other players, and you kind of balance how the narrative works. >> Katherine Eban: Well, I have to say, it's a remarkably compelling read. It was hard to put down. I read sections of it aloud to my husband on a car ride, and he didn't want me to stop. So, it's a tremendous read. And I must say, it also left me with a hankering for a woolly mammoth comeback. >> Walter Isaacson: We will have it. >> Katherine Eban: My name is first on the adoption list [laughter]. >> Walter Isaacson: Well, thank you, and it's great to be interviewed by a great scientist and journalist like yourself, so thanks. >> Katherine Eban: Thanks. A lot of fun. >> Shari Werb: Thank you, Walter and Katherine, for that provocative conversation about the brave new world of biomedicine. I hope you enjoyed it as much as I did. Thank you, also, to the staff of the Library of Congress, Science and Business Technology Division, for their assistance with this event. The Library offers many literary programs each year, and you can see what we have in store, as well as catch up on programs you may have missed, by visiting LOC.gov/engage. ^E00:49:55