Walter Isaacson, Author of 'The Code Breaker,' On Dr. Jennifer Doudna And CRISPR Gene Editing

You may know Walter Isaacson from his biographies of Steve Jobs, Benjamin Franklin, Leonardo Da Vinci, or Albert Einstein. In his latest book, the author, journalist, and professor tells the story of a new subject who has had a huge impact on the scientific community, the gene-editing field, and even the coronavirus pandemic: Dr. Jennifer Doudna. 

In this Fool Live episode, which aired March 9, Fool.com Bureau Chief Corinne Cardina interviews Isaacson about his new book titled The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race.

Corinne Cardina: Hi there, everyone, and welcome to Fool Live. I'm Corinne Cardina, bureau chief of healthcare and cannabis on Fool.com. I am beyond thrilled to welcome Walter Isaacson today. How are you, Walter?

Walter Isaacson: Hey, Corinne, thank you so much for having me.

Cardina: Absolutely. Walter, let me give a brief introduction of you. You are a professor of history at Tulane, the author of many books about great inventors and innovators. Walter has served as CEO of the Aspen Institute where he is still a distinguished fellow. He's been the chairman of CNN, the editor of Time Magazine, among many other roles, I'm sure I'm not doing your full resume justice here. But we are here today to talk about your latest book. It comes out March 9th. It is called The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race. I got a chance to read it. It totally blew me away. I'm really excited to have the chance to discuss it with you, Walter. Thank you for joining us.

Isaacson: Well, thanks. I'm glad you liked the book. Boy, Jennifer Doudna and that whole team that creates gene editing and the vaccines that we've just now gotten for COVID, it just inspires you about science as you well know from your reporting.

Cardina: It definitely does. I'm going to start by introducing Jennifer Doudna to our audience and then I have some questions for you. Dr. Doudna may be a familiar name to some of us who have followed gene editing healthcare. She won the 2020 Nobel Prize in Chemistry alongside her collaborator, Dr. Emmanuelle Charpentier for their work developing a method of gene editing called CRISPR-Cas9. But your book actually takes us back to Dr. Doudna's childhood, how she cultivated her own passion for science and describes her journey through academia, ultimately becoming a biochemist focused on RNA, which you call DNA's less celebrated sibling. So much of her career has been at UC Berkeley leading the Doudna Lab there where many of the important discoveries that you discuss have happened as well as the Innovative Genomics Institution which focuses more on the public policy side of this work. She has founded and led many other projects, conferences, even companies along the way. Walter, let me start by asking you, what inspired you to write about Jennifer Doudna and gene editing?

Isaacson: I had written about Einstein, which was the first great innovation revolution of our time, the first half of the 20th century where the atom, the fundamental particle of the atom and how it behaved, led to a revolution in physics that gives you atomic power, and GPS, and space travel, everything else with Einstein's theories. Then we get in the second half of the 20th century the next great innovation revolution, which is the digital revolution, and I wrote about that with Steve Jobs and others, Ada Lovelace, because it's us understanding that if we can take the microchip, the computer, and the Internet and all connected, we'll have a digital revolution. The next great revolution which we're in right now, and whether it's coronavirus vaccines or gene editing, it's paving the way, is the biotech revolution in which molecules are going to be the new microchips. We're going to have to know how to program them to do our bidding. Jennifer Doudna is one of those inspiring scientists who as a very young kid read The Double Helix by James Watson, and said, OK, I want to prove that women can become scientists. She pursues this notion of how life began, what happens in our cells, and becomes a expert on RNA, which is as you said, the less celebrated sibling of DNA, but it's a molecule that actually does some work. From that, she gets the CRISPR gene editing technology which will allow us to edit the genes of our bodies and of our children, and also of course, as you well know, RNA is the foundation for these new type of vaccines that are helping us get out of the coronavirus pandemic.

Cardina: Absolutely, and we'll talk more about those vaccines a little bit later on. Of course, you participated in one of those clinical trials, which is very exciting. But I do want to explain CRISPR to our audience a little bit more. There are already certain gene editing technologies before CRISPR was discovered, thanks in part to Dr. Doudna and Dr. Charpentier's work among others. The two methods you discuss in the book, one was called zinc finger nucleases, also another one was called TALENs, but CRISPR really changed the game. Can you explain briefly how CRISPR works and why discoveries by these scientists opened so many doors?

Isaacson: CRISPR is a pretty simple system. Bacteria have been using it for more than a billion years. It's how they fight off viruses, which is of course a useful talent to have as we face all these pandemics. What CRISPR is is a system in bacteria that can remember the genetic code of viruses that attack them, and then if they see that genetic code again, they take a scissors, an enzyme, a scissors that will cut up that invading genetic code. What Jennifer Doudna and her team did, they said, oh, we can turn that into a scissors that will cut our own DNA at some place we've chosen. Like if we want to get rid of a bad gene like the mutation that causes sickle cell anemia, or if we want to create healthier children, we can use this system to just take a target that we want to cut in our DNA and to use a guide that will take an enzyme scissors there and cut it there.

Cardina: Absolutely. Within the gene editing space, there is a major difference between what is called somatic gene editing and germline gene editing. I'll give you my understanding and you can check me on this. With somatic gene editing, you're altering the genes within a particular person. There's either the ex vivo method, removing their cells, engineering them in a lab, putting them back in the body, or the in vivo method in which you inject gene editing molecules into the body. Somatic, it means body. It changes the person's genes and how their body creates certain proteins, but it does not impact how they pass on those original genes to their offspring. That brings us to germline editing, also called inheritable edits, in which the edits to the gene can be passed on to the offspring. You say that germline editing holds more promise but more peril. Can you explain some of the big ethical questions that scientists are grappling with about germline editing and why it's such a big jump from somatic gene editing, which has largely already become accepted? You mentioned sickle cell anemia, plenty of trials going on with the somatic side.

Isaacson: Yes, we've already cured sickle cell anemia this past year on a patient named Victoria Gray in Mississippi using somatic editing, meaning her stem cells were taken out of her body, edited, returned to her body. We've also used CRISPR in a far more controversial way. Just two years ago, a Chinese scientist who had been to Jennifer Doudna's seminars used CRISPR to edit the embryos, what became two twin girls in China, and they had been edited so that they didn't have a receptor that allows them to get the virus that causes AIDS. By doing it in an early stage embryo, in theory, it means you're not just editing those twin girls; you're editing all their descendants. You're editing the human race. So the moral question becomes, should we hack our own evolution? It's like Prometheus snatching fire from the gods. We now have the power to design our children and all of our descendants not to have certain traits, or maybe to enhance certain traits like height or hair color or IQ, whatever you may do in the future. That becomes ethically questionable to some people. Certainly, we'd want to do it in order to fight off dreaded diseases like Huntington's or cystic fibrosis or sickle cell, but should the rich be allowed to buy better genes for their kids to make them taller and make them smarter or give them greater muscle mass? Not something we could do right now, but in the next few decades, that'll be possible. Will we want to edit out some of the diversity of our species? Behind me is my balcony overlooking the French Quarter in New Orleans. I look at the passing parade of all sorts of types of people that add to the richness of our society. If we start editing our children, are we going to lose some of our diversity? Are we going to lose this notion that we're all created equal? These are the things that Jennifer Doudna, after she makes this discovery, she has a nightmare that somebody wants to learn about it, in which he goes into the room to meet the person, in her nightmare, it's Adolf Hitler. The book not only talks about the science of this but it talks about how Jennifer Doudna went on a journey, I mean, went on a mission to enlist scientists around the world to say, what rules are we going to have in place for using this new technology?

Cardina: Certainly. That's where the role of public policy comes into the book. You discuss the very valid concerns about genetically encoding inequality. Of course, right now we have lots of financial inequality in the world. But if parents are able to go to the "genetic supermarket," it's not going to be free. You discuss references to Brave New World, 1984. How do you see the role of public policy in gene editing, and maybe how does Jennifer see it as well?

Isaacson: I think initially, Jennifer Doudna and myself flinched at the notion of creating genetically modified children. It's like we all flinch maybe the first time we talk about GMOs in our food. But like GMOs in our food, we have to figure out, when can it be good and when can it be bad? At a certain point, I began to think, and so did Jennifer Doudna, that there are certain times where it would be immoral not to use this technology to alleviate suffering, to try to stop brutal diseases like Huntington's disease. But the way we're going to have to figure it out is not just delegated to the politicians or delegated to the scientists. I think we all have to be involved in thinking this new technology through. By we, I mean you and me, Corinne, you and me, all the listeners of this show are going to have to say, we should be discussing this as a society. It's the largest moral issue we're going to face. In order to discuss it, it helps to know a little bit about it. By telling the story of Jennifer Doudna, I hope I make it very easy to understand what the possibilities are. That way, all of us can engage in this discussion, whether it's at the dinner table or in our political lives with what are we going to do with this new found fire that we've snatched from the gods.

Cardina: Certainly. It's not just scientists in labs necessarily who are doing and experimenting with gene editing. I want to talk a little bit about what you call the rebels or the troublemakers. You quote Steve Jobs, his famous Apple ad from '97 that celebrated the rebels and troublemakers who pushed the human race forward. We talked a little bit about the Chinese scientist who created CRISPR babies without getting approval from the greater scientific community. He actually got in trouble. He served time in prison. He's not allowed to do science in China anymore. Can you tell us about some of the troublemakers that you discuss in the book that have forced us into a new era of gene editing?

Isaacson: The most prominent was the scientist in China named He Jiankui, who decided in a rogue experiment to just make the first designer babies. People say, "Well, it's science fiction, it can't happen." Well, it's already happened. He pushed it forward and I think he did it in a very irresponsible way, which is why he's under house arrest in China, because it wasn't medically necessary. You can prevent AIDS in other ways, and it was done in a sloppy fashion. But the question becomes, what happens when it can be done in a safe way, and what happens when it is medically necessary? It's not that hard to do. In the book, I describe going to Jennifer Doudna's lab in Berkeley, and within two days, with just two graduate students helping me, I was able to edit human genes. Now, don't worry, we took them after I'd edited the cells, and we mixed it with chlorine and killed them and flushed them down the drain. I didn't unleash them on the world, but it's going to be something that in the next couple of decades will become easy enough for any graduate student to do, and eventually, people will be able to do it like they create webcasts in their own house. So we have to learn what the rules should be.

Cardina: Absolutely. One troublemaker that sticks out to me in your book is the scientist who was selling gene editing kits out of his garage and actually injected himself with gene editing technology. That's just one example of people not necessarily who you think of as a scientist.

Isaacson: Josiah Zayner is the Puck-like character, the Shakespeare character in my book. I have a picture of him doing that, but also of him injecting a vaccine he created using this technology that will, like an mRNA vaccine or a DNA vaccine, fight coronavirus. Sometimes, it's the misfits and rebels who, as Steve Jobs said, push us forward and even push us out of our comfort zones.

Cardina: Right. Those biohackers are certainly contributing to the democratization of gene editing that I think we'll start seeing more and more. I want to talk a little bit more about the pandemic. It seems rather fortuitous now that you were working on this book about gene editing, which has been somewhat niche before the pandemic began despite its enormous potential. Then coronavirus happened, and the technology you were researching for the book really became the upmost urgency and mRNA entered the public's lexicon. How did Dr. Doudna's work on RNA lay the groundwork for the mRNA vaccines that are not only proven effective but people are receiving them today?

Isaacson: The CRISPR work that was done involved, as I said, the system bacteria use for detecting viruses and then chopping them up. RNA becomes the most important molecule. What Jennifer Doudna does is figure out how to use RNA as a guide in order to find genetic material we may want to change. She has been able to use it as a detection technology so that instead of having these complex PCR tests that take a long time and people can't get tested will now have very simple to use CRISPR tests that'll be like pregnancy tests; you can do it at home and get the result almost instantly. She and a rival group at MIT and Harvard that were racing her to do CRISPR have also looked at ways that we can directly cure attacks from the coronavirus or the COVID disease. As for the mRNA vaccines, they go back to the most fundamental thing that RNA does, which is it acts as a messenger, taking the code from our DNA for our genes, and then going to build proteins in the cell. That was done by people starting in the 1960s with Francis Crick and others understanding this dogma of biology, and then a great team at the University of Pennsylvania that learned how messenger RNA works. But if we're going to give an award to anything, it's to the molecule of the year, and that molecule is RNA.

Cardina: Excellent. You participated in a clinical trial with the mRNA vaccine. Can you tell us a little bit about what that was like and how you decided to join that trial?

Isaacson: Well, I was fascinated with RNA, of course, because I was writing about it, and this is way back last July when Pfizer (PFE -1.05%) and Moderna (MRNA -0.34%), two great companies, Pfizer was working with BioNTech (BNTX 0.07%), a German company, figured out how to harness the use of RNA to build the antigens that would protect us from coronavirus. I said, "Wow, that's cool, I want to learn more about it." A little bit like the biohackers you talked about, which is citizen science, I thought I'd do it in a very safe way, which is get involved myself. So I went down here in New Orleans down to Ochsner Hospital, the great hospital down here, that was leading one of the clinical trials for the Pfizer exam, and I just signed up and I got the Pfizer. Initially, I got the placebo, but then they switch you over to the real thing as you keep your diary and they can figure out how this vaccine works.

Cardina: That is so awesome. Let's talk a little bit more about Dr. Doudna's response to the coronavirus. In the early days of the pandemic, she gathered experts to embark on a coronavirus hackathon. She broke people up into groups and they all chose different things to explore to urgently respond. The scientific community was really able to collaborate and set aside a lot of those patent issues that influence the CRISPR race, for instance. Can you tell us about what Dr. Doudna's coalition was able to accomplish?

Isaacson: About a year ago, last February and March, she had driven her son, a 17-year-old named Andy, to the train station to be part of one of those robotics hackathons out in Fresno, California. Then she woke up in the middle of the night, woke her husband up and said, "We got to go pick up Andy because I've been hearing about this pandemic." They bring him back, and just as they get him from there, they announced that the whole competition is canceled. She said, "That was my wake up call." So she gathers 50 researchers in the Bay Area of California and they form 10 teams to do things like new testing techniques, new techniques for vaccines or for cures of coronavirus. Likewise, the rival group who had been racing her to use CRISPR technology as a gene editing tool in humans, led by this wonderful scientist named Feng Zhang at the Broad Institute of MIT and Harvard, they likewise engaged in this competition to fight the coronavirus. The cool thing is that, as you said, they don't fight over the patents this time around. They take their discoveries, publish them as quickly as possible and open-source publishing. They say, "If you're going to use these discoveries to fight the coronavirus, you can use it royalty-free. We're not trying to own the intellectual property when it comes to fighting the coronavirus."

Cardina: Absolutely. However, those scientists definitely were competitors. If you back up before the pandemic, and we've talked about the race to not only discover CRISPR but really implement the CRISPR technology in editing human genes, can you talk a little bit about what you learned about the competitive nature in this community and how the academic institutions also contribute to that race for patents, for publications. Was that surprising to you?

Isaacson: No, it wasn't surprising. Any one of your listeners who knows anything about business, or about sports, or about anything else realizes that competition is a good thing. It spurs us to go faster, to go further, to try harder, to work on weekends until the competition to discover how to use this gene editing tool of CRISPR to edit the genes in our body, and for that matter, to make medicines and products that will be based on it and to have the patents so that you can be incented to do more research, that's generally a good thing. The cool thing about science and the cool thing about the scientists in my book is they were doing it partly for the competition, partly to win the race just like Francis Crick and James Watson were racing against Linus Pauling and Rosalind Franklin to do the discovery of DNA structure. That's what competition is about. But they were doing it for the competition. They were doing it for the acclaim. Yes, they were sometimes doing it for the patents. But they were also doing it because they felt that it was just a noble cause furthering research into how our bodies work.

Cardina: A lot of that basic science that you talk about is curiosity-driven. You talk about Dr. Doudna's childhood. She was so interested in different parts of nature. She wanted to know why certain things happened and how that basic science translates much later sometimes into applied science. Can you talk about the distinction between basic science and applied science and how they work together, especially in the context of CRISPR gene editing?

Isaacson: Yeah. The relationship between basic science and applied science is very interactive. Sometimes, we think it's like a linear model in which basic science discoveries like surface state on semiconducting materials leads to applied science like transistors and microchips. But usually, it's a mix of things, and that's what happened with CRISPR. Initially, it was curiosity-driven, some Spanish graduate student looking at weird microorganisms and how there's clusters of repeated sequences in their DNA, which he names CRISPRs. That was just pure curiosity. But then a couple of scientists at Danisco, the wonderful yogurt and cheese making company, they realize, maybe we should figure it out because we got to protect our bacteria and the cultures for our cheese. So that's applied science. But they were working together, the applied scientists and the basic scientists. Likewise, Jennifer Doudna was pursuing CRISPR out of curiosity. What are these weird little repeated sequences? How do they help bacteria fight off viruses? But as soon as she discovered the essential components of the CRISPR system and could engineer them to cut DNA at any spot she decided to target, she realized there's an important application here; gene editing. I think we all have to be open to the absolute beauties of basic science and realize that it often leads us to and works together with applied science.

Cardina: That was a big lesson for me from the book. Another really important theme for me in the book was the representation of women in science. Dr. Doudna first pictured herself as a scientist when she read The Double Helix and learned about the scientist named Rosalind Franklin that you mentioned earlier. Later on in her studies, a male guidance counselor told her, "Girls don't do science," but fortunately for the world, she was not deterred. Dr. Doudna had female mentors and colleagues throughout her career. I loved learning about them throughout her journey. It's great to see women leaders in the scientific community, but it's also important to look around and notice what you don't notice. You pointed out a lack of Black scientists in the labs that you visited. Is that same representation and mentorship that Dr. Doudna enjoyed still missing for other groups of people like prospective black scientists, and any thoughts on just how the scientific community is improving on the diversity front?

Isaacson: I think it's really important that the scientific community, especially the community of life sciences, improves on the diversity front. The information technology and digital revolutions we've just been through have, in some ways, not had as many African-Americans or others involved in a leadership role. But it's even more important, I think, that in the life sciences, we reflect the diversity of our society, and frankly, the diversity of our species. There's a long history of life sciences being used in ways that are appalling like eugenics and the Tuskegee experiments that were done on Blacks without their permission or knowledge to do biological experiments. So I feel it's crucially important that this next innovation revolution in the life sciences, we do all we can to find role models, mentors, advisors, ways of bringing African Americans into the mix. I'm on the board of a foundation, the Bloomberg Philanthropies, that has just given large grants to historically Black medical schools as one of many ways we could create more leaders from different backgrounds in the field of life sciences.

Cardina: Yeah, absolutely. I think that's so important. Another group to consider is the disabled community as we talk about the future of inheritable edits that will impact, in your book you mentioned, the Deaf community, and making sure that access in the scientific community is extended to those groups, I think, will be more and more important.

Isaacson: Yeah, I think that we have to understand what is a disability, what do we call disabilities, and whether some things that we might say are disabilities are actually society not accepting people who have different abilities to be part of society. When it comes to, say, congenital deafness, inherited deafness, that's something you could change genetically. Likewise, blindness. I think we have to figure out, allow all of society and each of us as individuals to figure out to what extent we want to use this tool to fight deafness and blindness. I think most of us would say those of us who want that should have the right to do that, but we also have to appreciate and listen to people from different communities who say, all right, that's not for me.

Cardina: Absolutely. Let's talk about the idea of "a prudent path forward." That is a phrase that is repeated throughout the book. That is what Dr. Doudna and her group of scientists are really looking for in terms of germline editing. They do not want a moratorium, which I think you call the 'M word' a couple of times in the book on germline editing. The opposite of the moratorium approach would be a prudent path forward related to germline editing. There are natural questions about the potential to edit out genes that make us susceptible to pandemics. Can you talk a little bit about the prudent path forward for germline editing in this context?

Isaacson: I think we have to say, what type of world do we want to leave to our children, and then all of us as a society to understand this so we can go step by step. It becomes less of a slippery slope if we're going cautiously step by step, preferably hand in hand. I think what we would first do is to say, here's some principles. Let's look at what's really medically necessary and that can't be done in another way, and let's start with that. Then as we go step by step, we may decide it would be wrong not to use this technology to help us fight viruses. At first, we may think that's playing God or doing something, but we've used everything ever since inoculations were done 400 years ago, or vaccines 200 years ago. We've done things to fight natural infections. So it's not a simple task but it begins by understanding the journey that Jennifer Doudna and so many others went on, a journey of discovery. Because it's fine for those of us to have strong opinions about, say, not wanting GMOs in our food, but it's actually helpful if you have that strong opinion to know what a genetically modified organism actually is. It's fine to say, we don't want to have gene editing, but it helps to know what a gene is. My book is a journey of discovery so that you can have a sense of what this is all about, and then you can join the discussion.

Cardina: Absolutely. I want to talk a little bit about entrepreneurship. Jennifer occupies a huge spectrum, from basic science researcher, and really just curiosity-driven, digging into things because she's curious, all the way to being a founder of multiple companies. So the race to develop CRISPR technology led to three companies formed by the cast of characters that you chronicled. There's Intellia (NTLA -1.42%), Editas Medicine (EDIT -4.10%), and CRISPR Therapeutics (CRSP -4.14%). Of course, there are more gene editing companies now but these are the three that we've familiarized ourselves with the founders by the end of your book. At The Motley Fool, we're investors. Many of our audience members may have heard of some of these companies and some may have invested in one or all three. What would you say generally to anyone thinking about putting their money behind companies focused on gene editing applications?

Isaacson: Well, first of all, it's both useful but also joyful to actually understand what these technologies do, and that's what my book is about, which is, what is CRISPR Therapeutics? How does that work? Now, that's a good company to invest in. It was just very successful in helping cure sickle cell anemia and a blood disease over in Europe. Likewise, things like Mammoth Biosciences, which was founded by Jennifer Doudna and her graduate students, and its rival group, Sherlock Biosciences, which was founded by the MIT Harvard people like Feng Zhang and his graduate students, those have done things like use CRISPR and RNA to detect viruses. Well, that's become very useful these days. So I think that it's always a problem when you invest based on whims and hunches. It's useful to understand the product. It's useful to understand what do these companies do, and that's why I spend a lot of time in my book showing how they form these companies and then looking at how everything from coronavirus to cancer to sickle cell are being affected by the technologies these scientists first discovered and then decided to commercialize when they formed companies.

Cardina: Certainly. My last question for you, Walter, today is, what is one lesson that everyone here today can take away from Dr. Jennifer Doudna's story?

Isaacson: Curiosity, curiosity, pure curiosity for curiosity's sake. All the geniuses I've written about from Leonardo Da Vinci to Ben Franklin to Steve Jobs to Jennifer Doudna had that one quality, which is they'd see something and they'd say, "why, how, how does that work?" They were curious not just because they thought it would lead them to something useful. Both Ben Franklin and Einstein and Leonardo were curious about why is the sky blue. They tested that out. Jennifer Doudna was curious about why does the sleeping grass curl when you touch it? Why do bacteria get to fight off viruses better than we do? So being curious is the key to creativity. It's also the key to great investing because you become curious about what people are actually doing.

Cardina: That is so true. Walter, thank you so much for all of your insights here today. I know I learned so much by reading your book, but also speaking with you, I can't wait for it to come out so I can tell everyone I know that it's a must read and I hope we'll keep in touch. Thank you again.

Isaacson: Thank you, Corinne, and thank you to everybody at The Motley Fool, one of my favorite sites from the beginning.

Cardina: That's right. Fool on. Thanks a lot.

Isaacson: Fool on, Fool on.