Walter Isaacson on CRISPR and the People Behind the Revolution

; Abraham Verghese, MD; Walter Isaacson, MA

Disclosures

June 18, 2021

This transcript has been edited for clarity.

Eric J. Topol, MD: Hello. This is Eric Topol for Medscape's Medicine and the Machine, with my co-host, Abraham Verghese. We're especially delighted today to welcome Walter Isaacson, one of the great biographers of our time. His most recent book is The Codebreaker, which is about CRISPR and genome editing. Walter, welcome.

Walter Isaacson, MA: Thank you so much, Eric. I'm a big fan of both of you. It's an honor to be on your show.

Topol: We are thrilled to have you. I thought I'd set the stage because the medical community — our Medscape audience — certainly knows a bit about CRISPR. It's a true life sciences breakthrough. We don't use that term lightly. I wanted to read two passages in your book that are striking to set the stage. They are like "A.C." and "B.C.," where "C" is CRISPR. You captured it. You're a man of words, of course. Here's the first one I wanted to highlight.

The issue is one of the most profound we humans have ever faced. For the first time in the evolution of life on this planet, a species has developed the capacity to edit its own genetic makeup. That offers the potential of wondrous benefits, including the elimination of many deadly diseases and debilitating abnormalities.

And the other passage, from the book's introduction, is also telling. You wrote:

There was a sense that we had crossed the threshold into a whole new age, perhaps a brave new world, like when Adam and Eve bit into the apple or Prometheus snatched fire from the gods.

These are pretty profound statements. Can you give us an overview, because you really delved into this. You're not a genomicist. You're not a hard-core scientist. Yet you actually did CRISPR in the lab. You did a deep dive.

More Consequential Than the Computer?

Isaacson: I do think that we've seen certain revolutions in our time in the early 20th century — the physics revolution, much of which came out of the work of Einstein and others at the very beginning of the century. And likewise, in the second half of the century, we saw the computer, the microchip, and the internet combine to create a digital revolution.

Now we're on the verge of what I think is going to be a far more consequential revolution, one in the life sciences and biotechnology. It has many components and it begins to some extent with the sequencing of the human genome at the turn of this century, but also with genetic engineering and recombinant DNA.

CRISPR takes us into an entire new league because we can not only read the human genome and try to engineer things, we can actually make ever more precise edits to human or, for that matter, the DNA of any organism.

Just out of curiosity, I think people should want to know this, but also because they'll probably have to wrestle over the next 10 or 20 years with some of the implications of this. And by the way, it's just beautifully exciting to understand how something works, especially when that something is ourselves. I want to thank you, but also all the graduate students and various labs in Berkeley and the Broad Institute and other places that went through the process with me of understanding exactly what the tracer RNA and the guide RNA do, and how you engineer a single guide, and all the things that I try to make exciting in this book.

The Cast of CRISPR Characters

Abraham Verghese, MD: I want to echo what Eric said. It's just a tremendous book and a very compelling read — it almost read like a mystery — it just seemed to evolve on the page, which was wonderful. My question is, as a writer and biographer, when you approached this, you must have had an infinite number of choices as to how you would tell the story. I'm curious to hear how you arrived at the particular structure that you used.

Isaacson: That's a great question, Abraham, because I did spend a lot of time trying to sort through the process of the best way to tell the story. I have a natural proclivity to biographical narrative. I don't think that's anything new; I mean, that's how the Bible tells interesting stories and makes moral points. It's got a great lead sentence, which is "In the beginning (comma)."

So I tend to try to write chronological narratives with main characters that help bring it along. Biographers sometimes can distort history by making it seem like a guy or a gal goes into a garage or a garret and has a light-bulb moment and innovation happens, when we know that it's a collaborative effort, a team sport. I've written a couple of books, including one called The Innovators. That was about a whole group of people without a main central character. I thought of doing that here.

And there have been many good books on CRISPR. Kevin Davies has one called Editing Humanity. Hank Greely has a great one called CRISPR People that brings you through all the people involved in this revolution. I spoke to a lot of people who could have been central characters, including George Church, Feng Zhang, and Jennifer Doudna. I flew to Berlin to spend time with Emmanuelle Charpentier and Francisco Mojica. Many people, like Rodolphe Barrangou, were involved in this story. As my writing and thinking evolved, it seemed that as a narrative writer, it's often useful to have a driving central character. And secondly, writing through Jennifer Doudna as a central character had certain advantages, especially because she began her career, so to speak, in middle school when she read The Double Helix and became absolutely fascinated with the notion that the structure of a molecule is a key and a clue to figuring out what it can do.

She wanted to become a scientist but a guidance counselor said no, girls don't do science. She was inspired by a character named Rosalind Franklin in the book. And then she spent the 1990s under Jack Szostak and, to some extent, Tom Cech, doing the structure of various types of RNA, including self-replicating introns that answer the big questions, because Szostak had taught her to always ask the big question. She said, "What's the big question?" And he answered, "How did life begin?"

While a lot of the other scientists in the field (especially the men) were chasing the Human Genome Project and sequencing DNA, a lot of women, including Jennifer Doudna, Jillian Banfield, and Emmanuelle Charpentier, were focusing on RNA, which turned out, at least in our time, to be a more interesting molecule. It actually does work. It becomes a messenger to tell ourselves which proteins to build, and that's why we have the vaccines we now have. It became a guide that can take an enzyme and cut in a specified place, and hence we have CRISPR.

Telling the story through Jennifer offered the advantage of having a narrative that brings us through the history. She then turned her attention to the ethical and moral issues, and along with David Baltimore and others who led the Asilomar conference in the 1970s, she used a similar process to figure out what to do with gene editing. Then, as you'll see if anybody gets to the end of the book, she pivoted to get groups of people in the Bay Area to take on coronavirus using both CRISPR and other forms of molecular biology. And so she became a very good narrative thread.

As you flip through the book, even just looking at the pictures and certainly reading the chapters, you'll see pictures of many of the graduate students and young investigators and researchers. You'll see Virginijus Šikšnys, Martin Jinek, Prashant Mali, and Jennifer Hamilton. I wanted not only to get the stars of the CRISPR story to be main characters, meaning Feng Zhang, George Church, Emmanuelle Charpentier, and Jack Szostak, but all the principal investigators, because I wanted to show that creativity is a team sport when it comes to science.

The Importance of Curiosity-Driven Innovation

Topol: I thought it was remarkable how you bridged genomics and computer coding, even in the book title The Codebreaker — all the things that you brought out with respect to the likeness of biotech with CRISPR and the digital internet. It's a symbol of the movement toward biotech.

This was a basic science breakthrough that had been around for a billion-plus years. It's the way bacteria protect themselves against viruses, and it took basic scientists to discover this. Can you put these two things into perspective — one, the connection with the digital world and coding, and the other, the importance or the essentiality of basic science?

Isaacson: When growing up, we all figured that we had to learn how to code. I knew C++ and Pascal and a few others. We made sure our kids learned how to code. It's going to be particularly important to have an appreciation not just for C++, but also CTG and A, the letters of genetic coding, because molecules have become the new microchip. Whether it's with the mRNA vaccines or CRISPR, we were able to code molecules pretty quickly. As soon as we saw the sequence of a spike protein of a coronavirus we decided we wanted to target it. We have to get in the mindset that we're going to be coding and reengineering in order to create fast vaccines.

To your point about basic science, that's incredibly important to me. I've written about it in The Innovators and other books — the Vannevar Bush concept of the linear progress of innovation, which is that basic science that leads to discoveries, which leads to inventions, and useful products that can help the economy. Vannevar Bush wrote that in Science: The Endless Frontier, which in 1946 became the model for the National Science Foundation, the National Institutes of Health, and many other things.

And in CRISPR, you see that quite a bit in the curiosity of Francisco Mojica and various other early CRISPR pioneers who were looking at a more than a billion-year-old system that archaea and bacteria have created, and puzzling over these repeated, interspersed sequences in the DNA of these microorganisms. They were doing it purely out of curiosity, like Leonardo da Vinci. They weren't trying to create a gene editing tool. But that basic curiosity eventually leads to the understanding of the components of CRISPR and then an understanding of how we can take this bacterial system that's been around more than a billion years and repurpose it to edit genes in ways that we target them, including in our own human species.

That said, it's not a pure example of the linear model. A lot of people have questioned the linear model, and I think rightly so, saying that it's more of an interactive dance between the applied scientist and the basic scientist; between the purely curious and those trying to do translational research, or for that matter, business people. In the linear model that Vannevar Bush talked about, people studied the conduct of electrons on the surface of semiconducting materials and figured out the quantum mechanics of it. They did that out of just pure basic research, but we ended up with the transistor and the microchip.

Well, yes and no. We end up with the transistor at Bell Labs because Bardeen and Shockley and some of the theoretical physicists are sitting there with experimentalists like Walter Brattain. But even business people are saying we have to amplify a phone signal between these two codes. We have to have pole climbers with grease under the fingernails who know how amplification works and that interaction creates a transistor.

Likewise with CRISPR, you had Horvath and Barrangou working at a yogurt and cheese company (Danisco) and they were looking at the sequences of bacterial cultures that were getting destroyed. They noticed from the historical record of these cultures that the viruses that had attacked them, a mug shot of those viruses, had been put in the clustered repeated sequences. So even in CRISPR, you see this beautiful dance between basic curiosity-driven research and applied and translational research.

Patents: Problem or Pace Setter?

Verghese: One of the fascinating side stories of the book is the necessity or the trend toward these scientists making links with the business world, patenting the technology, and starting companies. I'm puzzled that Stanford, for example, embraced the idea of commercializing and capitalizing on these discoveries, whereas Berkeley was initially reluctant. Now it seems like everybody's starting a company while in academia — pretty much everybody embraces it. Can you talk a little bit about that trend, how it's evolved, and where you see it going?

Isaacson: That's important. I discuss it both in this book and in others. You're sitting there at Stanford as we speak, Abraham. In the 1970s particularly, under Fred Terman, who was then dean of the School of Engineering at Stanford, people like Hewlett and Packard, who were coming up with great ideas and intellectual property out of Stanford, were encouraged to commercialize them and to get patents. This happened not only at Stanford but with recombinant DNA and Herbert Boyer and the people who started Genentech. When you look at the valley in which you're situated, Abraham, you have companies that started it off, such as Hewlett Packard, Genentech, and others that come out of Stanford and the other universities there. On the East Coast, you have Harvard and MIT, which had up until then been at the forefront of digital technology by creating the routers for the internet and everything else.

But there's a condescending attitude toward commercializing content at all sorts of traditional universities. So Stanford helped them get a leg up and they became amazingly successful, whether it's for recombinant DNA patents or I assume Hewlett and Packard for that matter; Google spins out of grad students Larry Page and Sergey Brin at Stanford. They're encouraged not to finish their doctoral dissertation but to get out there and find a garage somewhere and create a company.

Now I'm at Tulane University. We're in the third wave, meaning we've watched Harvard, MIT, and the University of Washington, like so many other universities, catch up with the Stanford approach. Now, whether it's the University of Texas, Vanderbilt, or Tulane, we're trying to create these centers that will have patent attorneys, venture capitalists, and innovation centers.

That can go a bit too far. In my book, the war between Berkeley and the MIT/Harvard folks over the CRISPR patents gets a bit unseemly at times. It reminds me of the story of Jack Kilby and Bob Noyce, Texas Instruments and Intel fighting over the microchip. Finally, Noyce calls up Kilby and says, "Let's quit fighting over divvying up the proceeds until we finish robbing the stagecoach" and they just cross-licensed their patents. I kind of hoped that Broad and Berkeley would do that.

But patents are an important part of the process. Just like competition for prizes, they drive people to stay up late at night and to work on weekends and to have the funding to do other things. There's a backlash against patents, especially in the era of COVID vaccines. But even with my daughter, who is of the generation that is not as much in favor of intellectual property, I defend the desire to commercialize and patent things as long as those patents are used the way Bell Lab used its patent on the transistor — to help spark, rather than suppress, an industry.

You Don't Have to Be an Einstein to Understand Science

Topol: I knew of Jennifer Doudna's work, but you traced it from her 6th-grade reading of Watson's book all the way through to the Nobel Prize. I was struck by how you got this remarkable access to her, because she had to confide in you and spend a lot of time with you to bring you along. She almost was a French major, which is kind of amazing, but became a chemist who did extraordinary work in RNA, and then with Emmanuelle Charpentier, with the cells showing how CRISPR works, certainly not in human cells, which is a bit of a gap. Doudna is obviously very competitive, which is a good thing. And now she's into human diseases and trials, plus companies, ethics, and public policy. How she went from being a chemist all the way to the big picture of the universe is pretty transformational. Can you comment on that?

Isaacson: It's important for scientists to do what you do, Eric, which is also be in public policy; intellectuals also engage in education. There has been a problem with science over the past century and a half. I wrote about Benjamin Franklin. He loved science and he would have thought you were a philistine if you were not involved in science, if you didn't know the difference between an integral and a differential equation, or if you didn't understand gravity or the Gulf Stream or botany. It was the same with Thomas Jefferson.

But then Einstein came along and science became a bit intimidating. People think you have to be an Einstein to understand it. It became slightly frightening. We saw a picture of Einstein on the cover of TIME magazine with a nuclear bomb cloud behind him. When I was growing up, we were living in C.P. Snow's two cultures where those who were humanists would be unashamed to say, "I don't understand science" or "I can't do math." When I went to college, I loved science and I studied biology and physics. But as somebody who wasn't majoring in the hard sciences, I didn't feel all that welcome going to physics and biology classes. Whereas if you were majoring in molecular and cell biology and you took a Shakespeare course, you'd feel perfectly welcome.

Scientists are sometimes formed into a priesthood; they don't popularize or they even look down upon popularizing what they do. This leaves a role for Jennifer Doudna to become a public policy intellectual, the way a David Baltimore did, the way you have, Eric. It also leaves room for people like myself who are not bench scientists to say, "Let me hang around the bench, and teach me what you're doing so I can translate it into something that the public will not only understand but be able to discuss and appreciate the beauty in."

Remember When That Chinese Scientist Edited Baby Genes?

Verghese: One of the most exciting parts of the book, because most of us were following that dramatic episode, was the Hong Kong conference when the Chinese scientist reluctantly presents his data on editing the genes of those babies. Can you talk a little bit about that? Are we entirely safeguarded from that sort of thing based on the guidelines that Baltimore and others have set up? What are your fears about CRISPR technology going forward?

Isaacson: My fears are overwhelmed by my hopes for it. Every day, people send me a picture of their daughter or their son who has a monogenic disease saying, "Can you put me in touch with the people in your book? My son is going to die in 3 years and he can't walk." My heart goes out to them. I keep saying, let's make sure before we tap on the brakes too fast here, we understand the promise of this, especially for horrible genetic conditions, including common ones like cystic fibrosis, muscular dystrophy, etc.

Will people start designing babies? I go through the case studies in the book that I worry about. We look at what Jiankui did in Hong Kong, what he announced, and we were all appalled by it. He made inheritable germline edits in early-stage embryos. But when you look at what he did, he did it to knock out a receptor for HIV, the virus that causes AIDS. Coming out of the pandemic, there might be people who say, well, remind me again why it would be bad if we learned 20 years from now how to very safely reduce the number of receptors for viruses and study the unintended consequences and maybe find a way to fight viruses?

I think the research should progress. I do worry about rogue scientists. In the book, Jennifer Doudna described a nightmare in which somebody says, "I want to learn about your technology." She goes in the room and the person looks up and it's Adolph Hitler. We can have the nightmare about state-sponsored eugenics. The Russians may use it for super-soldiers or whatever. It's more likely that we're going to have free-market libertarian eugenics, meaning we allow parents, 20, 30, or 40 years from now, to buy better genes for their children. The rich can afford to make their kids more muscular, have better blood cells that carry more oxygen or maybe even better memories or certain synapses with more processing power. These are well into the future. But it might be a system in which the rich get to buy better genes for their kids and in which we start editing out the diversity of the species.

One of the more interesting bioethicists in my book is a 17-year-old kid named David Sanchez. He loves playing basketball, except for when he doubles over in pain in the center of the court because he has sickle cell disease. I think it's at Stanford where he's being treated. They told him that we may someday be able to edit your sperm cells or reproductive cells so your children won't have the sickle cell defect (if you want to call it a defect). And David said, "That's great. That would be wonderful." And then a little bit later, he said, "Well, maybe that should be up to my kid, after my kid is born." And I ask, "Do you want your kid to have sickle cell?" He said, "Well, no, but sickle cell taught me a lot. It taught me persistence. It forged my character. It taught me how to get up off the floor when I fell down. And maybe we shouldn't edit that out without the permission of the kid." Later I asked him again and he said, "No, I've decided I don't want my kids have sickle cell." I said, "What about persistence?" He said he'd try to teach them empathy and persistence, but he didn't want them to feel the pain.

I use this example not to say there's a right answer, but that we all should have first thoughts, second thoughts, and third thoughts about what things we design in or out of our species.

Step-by-Step Makes a Slippery Slope Less Slippery

Topol: The points you're making regarding somatic vs germline editing are crucial, and you develop that fully in the book. To close the chapter about the CRISPR babies, I didn't even realize until I read your book that Jiankui was convicted and is in prison for 3 years with a very large fine. That was quite interesting. I knew he was in trouble in China, but I didn't know he got into that much trouble.

The somatic thing is really hot right now. You gave us a preview. My friend Sek Kathiresan and his Verve Therapeutics treatment that was just reported in non-human primates has the ability in one shot to knock out the PCSK9 gene and get LDL-cholesterol down to what you would want for a lifetime to prevent coronary disease, no less the effects with David Liu's base editing on progeria. And yet recently in Nature, there was a study about a one-shot CRISPR base editing cure for sickle cell disease in mice, not in people. But this approach is accelerating, with people looking at Huntington's disease, sickle cell, and possibly the other monogenic conditions; there is extraordinary excitement that we can see in the short term. We're already seeing it. That's why it's so important now to not get hung up on the germline. That's where it gets dicey. Would you agree with that?

Isaacson: It's extraordinarily important that people understand the promise of this, as well as perhaps the potential perils down the road — and that we're not near germline edits that could be widespread. Even though Jiankui did that in China, we can go very slow on germline edits.

In the meantime, we should celebrate what David Liu is now doing at Harvard with base and prime editing, and all the studies with congenital blindness, blood diseases, and cholesterol are going to be a great boon to society.

I did want to start the conversation, though, and that's why I say let's go step by step with what inheritable editing we do, because 10 to 20 years from now, we're going to have to have a consensus on what we're going to allow and what we're not going to allow. We ought to start having that discussion.

I can see why we would want to do germline editing at some point. For example, Victoria Gray was the first to be cured of sickle cell disease. She's from Mississippi and that was last year, but that cost more than a million dollars. It was a stem cell extraction and transplant, and then the editing in order to do that. If, as in the case of David Sanchez, we can edit so that we knock sickle cell out of the human species, that's going to be affordable.

When the Senate held a hearing on this after Jiankui did it in China, Jennifer Doudna, George Church, and others were there and they were waiting for the Senators to want to ban CRISPR editing. The talk turned instead to how it can be done more cheaply so we're not going to break the bank every time we have anything from cholesterol problems to sickle cell. We have to go carefully down what is a slippery slope. But if you do it step by step, hand in hand, it becomes less slippery.

CRISPR and the Democratization of Science

Verghese: Walter, you did a wonderful job of conveying the excitement of science and the adventure. I walk down these corridors at Stanford and I always wonder just exactly what's going on in the labs here. No one ever hears about most of it until the researchers publish. And even then, if you don't understand the jargon, you're going to miss it. So I loved all the compelling stories about individual scientists. But I confess, the one that I love the most and felt I would have loved to hear more of was George Church. He sounds like a fascinating sort of renaissance man in the midst of hardcore scientists. Can you talk a bit about some of your favorite characters in the story?

Isaacson: George is certainly one of them; he's a main character in the story. In his book Regenesis, he talks about attempting to resurrect the wooly mammoth using gene editing. He's been in the gene editing trade for a long time. It's not just CRISPR. He goes back to zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) and other techniques. He looks a bit like the wooly mammoth himself, which may be in kinship, with his bushy beard and wild halo of hair. He's very provocative. He's the one in the book who, when I say we don't want the rich to be able to buy better genes for their kids, said, "What's wrong with some rich people making their kids smarter?"

He could have been a central character in my book and has been in other people's books. He is very close to Jennifer. In fact, when prizes were given out and George was not included, she invited George to be her guest and donated the prize money to the foundation called Edge that George started with his wife that educates people about genetics.

Another character who is particularly interesting to me (and I just had drinks with him in New Orleans a few days ago) is Josiah Zayner. You may remember him. He's the biohacker with ODIN who, in his garage, is doing his own CRISPR things, making his own DNA vaccine, and injecting himself with the CRISPR treatment that will regulate myostatin so he can have bigger muscles.

Talking about the Stanford area, Abraham, I'm old enough to remember the Homebrew Computer Club, when the hackers and hobbyists like Steve Jobs, Paul Wozniak, and Bill Gates took over the use of microchips from the big corporations and created the first personal computers; how hackers and hobbyists and phone phreakers were at the forefront of democratizing the digital revolution. That's not easy to do in the biotech revolution, because if you're sitting in your garage like Josiah Zayner, concocting CRISPR and vaccines and other things, it's a little bit more dangerous than hacking into the Bell system to make free phone calls.

But there is something good about democratizing science, with all due respect to the two of you, pulling it out of the castles of Stanford and other places. I grew up here in New Orleans. My father was an electrical engineer. I grew up in our basement soldering circuits. I felt I could have hands on. So I like Josiah Zayner and he's going to be part of the ethical debate because when we ban CRISPR for certain things, people like Josiah Zayner are going to be selling it on the internet out of their garages. He pops up just like Puck in A Midsummer Night's Dream every now and then to say "What fools these mortals be!" He's the provocative character who's the wise fool.

So, I like him and George Church a lot. And I fell in love with Emmanuelle Charpentier, but that's a different subject.

Collaboration, Competition, and Conflict

Topol: To me, the most heartwarming part of the book, which is riddled with conflicts between different people, is when you brought together Jennifer and Emmanuelle, who were about to get a Nobel Prize together, but they were at odds. You went on a mission to get them to renew their friendship. Can you tell us about that? I thought that was masterful.

Isaacson: It was not fully intended, but it just evolved that way. And like the Heisenberg principle says, sometimes we observers affect the things that we observe. I love the science and intellectual relationship between Jennifer Doudna and Emmanuelle Charpentier, who spent time in Berlin in the Max Planck lab. Emmanuelle is a genuinely wonderful person but very guarded, with a shield around her. Jennifer was going to be a French major, so she loved Emmanuelle Charpentier and they had a great bond when they were working together, but then they drifted apart.

It reminded me that these are human stories — just like the story of Steve Jobs and Bill Gates — where people compete, collaborate, and then they drift apart for reasons neither side quite knows. Jennifer is a very sincere person, open and self-aware. She would say to me, "When you talk to Emmanuelle, tell her I'd love to get together with her, but we seem to have drifted apart. Is she annoyed with me?" There was some annoyance like the Crack in Creation book, written in the first person, that Jennifer did with Sam Sternberg, and Emmanuelle said she was thrusting herself out too much. People get a little jealous or a little rivalrous, but there was no reason they should have fallen apart.

There was a virtual CRISPR conference coming up at Cold Spring Harbor last year. I had just come back from Berlin and Jennifer said to me, "What can I do to try to restore my friendship with Emmanuelle?" I said, "Why don't you invite her to present at this CRISPR conference?" And she said, "Well, that's a good idea." So Jennifer talked to Maria Janssen and others and invited Emmanuelle. I urged Emmanuelle to do it. She said, "No, I'm too busy," which seemed somewhat odd. It's a 3-day Zoom conference. It was clear she didn't want to do it.

I was puzzled. I said, "Why? How about if you, me, and Jennifer get together right after the conference ends on Sunday? I need it for my book. It begins with a scientific journey with you and Jennifer, walking down the cobblestone streets of Puerto Rico." I said, "I need to have some closure here. Why don't I have a joint interview about your relationship?" And surprisingly, Emmanuelle said, "I would love that. That would be really important to me." And Jennifer also said she would love it.

It was a Zoom screen with the three of us. I had a list of questions so I could guide the conversation. But the minute they both get on Zoom, they started asking each other, "How's your son Andy?" Or "What's happening there?" I just turned off my video. So it was the two of them together and they talked for 45 minutes. To me it wasn't a necessary part of the book, but it did show that these are human endeavors.

Topol: You not only wrote a book but brought these two phenoms together. That was a great contribution.

Isaacson: Let's admit it, the Swedish Academy did more to bring them together a month or two later.

Topol: But it might have been the Cold Spring Harbor stuff that got them back together.

Isaacson: For those of you who are in the medical field, the Cold Spring Harbor conference this year is in late August and it is virtual again. The keynote speaker is Emmanuelle Charpentier, with Jennifer Doudna. So all is right with the world. Tune in.

Topol: I don't remember a book that had as much impact. Of course, it's a field that I follow closely. The way you told the stories and brought out all the characters; the human side, no less the science side, is really quite extraordinary. I hope that our Medscape audience gets into this book because they will appreciate the importance of this discovery. It isn't just a prize-winning thing. As I said in the outset, the impact of CRISPR will probably be the most profound of our lifetime. I can't imagine, in terms of life science, that there will be a breakthrough like this for some time to come.

Isaacson: I set my alarm in New Orleans to 4:00 AM so I could watch the livestream Nobel Prize ceremony on the off chance that CRISPR would win the Nobel Prize this past October. And when the Nobel Prize secretary began reading and said this was not only for a discovery but for bringing science into a whole new epoch, a whole new era, I realized it was going to be CRISPR because that's what's happened. As you said, there was a "before CRISPR" and "after CRISPR."

What I wanted to do is show ordinary people what happens in labs and research institutes like yours. I don't think people get how the scientific method works these days, and that's so important in different fields. But also, what do people do in a lab? How are they driven by curiosity? And by the way, how are they driven by patents and prizes and priority of publication?

I admire so much what people in the medical research community are doing that the small chance to make it more understandable to a wider audience was not only an honor for me but a joy.

Verghese: Walter, it's just a wonderful contribution. Your great skill is telling the story in such a compelling way and connecting all these dots. So thank you so much for giving us your time and allowing us to share the experience of this wonderful, wonderful book.

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