CRISPR Scientist's Biography Explores Ethics Of Rewriting The Code Of Life

Mar 8, 2021
Originally published on March 8, 2021 11:48 am

The Pfizer and Moderna COVID-19 vaccines are the first vaccines to be activated by mRNA — and would not have been possible without the invention of the gene editing technology known as CRISPR.

In his new book, The Code Breaker, author Walter Isaacson chronicles the development of CRISPR and profiles Jennifer Doudna, who, along with Emmanuelle Charpentier, won the 2020 Nobel prize in chemistry for their roles in developing the technology.

CRISPR has already led to experimental treatments for Huntington's disease and sickle cell anemia, as well as certain cancers. Isaacson likens its technological capabilities to "Prometheus snatching fire from the gods — or maybe Adam and Eve biting into the apple."

"The very secrets of life — our DNA — is something that we can not only read these days, but we can write. We can rewrite it if we want to," Isaacson says. "It made me think that all of us should understand and marvel at and be excited about this notion."

But, Isaacson warns that gene editing also raises a host of moral and ethical questions — especially as the technology becomes more developed.

"In the future, you might be able to do more complicated things — change hair color or muscle mass or memory cells in a human being," he says. "Like any technology, [it] is only as good or bad as we are. ... So that's [why] we ought to have the discussion: What type of genes do we want to edit?"


Interview highlights

Simon & Schuster

On how gene editing is next science revolution

I think in our modern times we've had three great revolutions: The first was the physics revolution. And it sort of starts at the beginning of the 20th century with Einstein's papers — and based on that fundamental kernel known as the atom. And from that, we get the atom bomb, and space travel and G.P.S. and semiconductors.

The second half of the 20th century was also based on a very small kernel of our existence, called the bit — meaning a binary digit. And it meant that all information could be coded in zeros and ones and binary digits. And that leads you to the internet and the microchip and the personal computer. And so that gives us the digital revolution, which dominates the second half of the 20th century.

This part of the 21st century, I think, will be a biotech revolution, a life sciences revolution in which we'll be able to rewrite the code of life. - Walter Isaacson

Now we've come to another particle, a fundamental particle of our existence, which is the gene. And in the beginning of this century, in 2000 or so, we sequenced the entire human genome. And now with Jennifer Doudna and the things that she and her colleagues have invented, we found ways to rewrite that genome. And so this part of the 21st century, I think, will be a biotech revolution, a life sciences revolution.

On how the gene editing technology CRISPR mimics what the immune system does to bacteria

Whenever viruses attack certain bacteria, those bacteria do something very clever: They take a mugshot and they put it in their own genetic material of the bacteria. ... So that when the virus attacks again, the bacteria remembers it and uses a little guide RNA and a pair of "scissors" (an enzyme that acts as a pair of scissors) and cuts up the invading virus. So that allows the bacteria to have an adaptive immune system, meaning every time a new wave of virus comes along, it takes that mug shot and will be able to fight it off the next time. And that's just what we, of course, need in this day when we're being attacked by wave after wave of viruses. ...

What we can do and what Jennifer Doudna ... discovered is that we can engineer this system that bacteria have and say, OK, we'll code in the place we want the DNA cut. So we can take this billion-year-old tool that bacteria have and reprogram it so we can aim at any sequence of DNA we want to change in our own bodies. If we want to change a gene, we can do so.

On CRISPR home testing kits, soon available to the public

There's going to be these wonderful CRISPR-based home testing kits that build directly on the discovery that [Jennifer Doudna and Emmanuelle Charpentier] won the Nobel Prize for, which is using this old technology that bacteria have, called CRISPR, to say, "I can spot any virus, just by reading the genetic code of things in my body." And so [eventually], we'll be able to have these [tests] in which, just in a minute, you can detect not only viruses or flu, you can detect bacteria, you could detect cancer, you can do your gut microbiome. That's going to be a great platform: these CRISPR home-based tests upon which people will build all sorts of wonderful medical tools. ... These home testing kits will help bring biology into our home and bring us into a whole new era where we can do easy self-diagnosis of the things happening in our body.

On why the U.S. Defense Department funds research on gene editing

A lot of the research into CRISPR and genetic engineering has come from the Defense Department, usually as a defensive mechanism, like how would you make it so that radiation wouldn't be as harmful to your cells? That's just a genetic issue. Can you make cells that are more resistant to radiation? Can you make them more resistant to other forms of poisons or whatever?

Walter Isaacson visited Jennifer Doudna's lab at UC Berkeley while researching his book, The Code Breaker. Isaacson's other books include Steve Jobs and Leonardo da Vinci.
Simon & Schuster

The Defense Department also helped Jennifer Doudna and the people around her at Berkeley in the Bay Area create something called anti-CRISPR — because you could imagine a bad actor using this gene editing technology to do something harmful, to try to edit our genes, to do bad things. ... Vladimir Putin was talking about CRISPR's gene editing technology to a youth group at one point and he said, "We might use it to make better and stronger soldiers that don't feel pain." So that you can realize, some of our enemies might be doing things. We got to figure out how to counteract it.

On gene editing getting into the wrong hands

I think that CRISPR and other gene editing technology are easy enough that it could be used by people who aren't playing by the same rules as a research scientist. ... So I can imagine people saying, "I want to create tools that will help my memory [or] increase my muscle mass." But like any drugs or any tools, we hope that there'll be some types of regulation [and] that the Food and Drug Administration and others will say, "Here's what you can use it for and here's what you can't." ...

When Jennifer Doudna first helped create [CRISPR] she had a nightmare and she walked into a room with somebody who said, "I want to understand your new technology." And the person looked up and it was Adolf Hitler. And this made her realize that if it got into the wrong hands, somebody might use it for eugenics purposes, might want to create a "master race," might want to create people who were stronger as soldiers. And she decided to gather scientists from around the world to say, let's figure out ... the wonderful things this gene editing technology can do, but let's also try to limit things that would be inheritable or things that would not be as easy to control. And so she's been one of the leaders that said this is an important and good technology — let's make sure we don't misuse it.

Sam Briger and Seth Kelley produced and edited this interview for broadcast. Bridget Bentz, Molly Seavy-Nesper and Deborah Franklin adapted it for the Web.

Copyright 2021 Fresh Air. To see more, visit Fresh Air.

TERRY GROSS, HOST:

This is FRESH AIR. I'm Terry Gross. The Pfizer and Moderna COVID vaccines are the first vaccines to be activated by mRNA. These vaccines build on the breakthroughs of the gene-editing technology known as CRISPR. This technology is also being used to treat people who have sickle cell anemia, certain cancers, Huntington's disease and congenital blindness, and will likely be used to treat many other diseases in the future. There are many other CRISPR-related breakthroughs on the horizon and a lot of moral and ethical questions to deal with about the editing of the basic element of human life.

One of the developers of CRISPR is Jennifer Doudna, who shared a Nobel Prize last year for her discoveries about gene editing. Doudna and the story of RNA-related scientific breakthroughs are the subjects of Walter Isaacson's new book, "The Code Breaker." While writing the book, he became part of a double-blind trial of the Pfizer vaccine. In other words, he was given the vaccine but wasn't told whether it was actually the vaccine or a placebo. Then he was monitored for symptoms of COVID and for side effects of the vaccine. Isaacson is also the author of biographies of Ben Franklin, Steve Jobs, Albert Einstein and Leonardo da Vinci. He's a professor of history at Tulane and was formerly the CEO of the Aspen Institute, chair of CNN and editor of Time magazine.

Walter Isaacson, welcome back to FRESH AIR. It is a pleasure to have you back on the show.

WALTER ISAACSON: Terry, it is so great to be back with you.

GROSS: So let's start with the vaccine. How did you have the option of participating in the Pfizer vaccine study? And why did you want to do it?

ISAACSON: I was fascinated about the science and the thrill that we might have a vaccine. And I really believe that we should all participate in science a little bit more, not be intimidated by it. So when I heard they were making vaccines and testing them that used RNA, I just went online at Ochsner Hospital down here in New Orleans and volunteered to be one of the participants in the clinical trial. And, boom, the next day, I got called up. And they gave me a shot, made me close my eyes to make sure I couldn't guess whether it was the real thing or the placebo. But it made me feel I was a participant in helping us figure out how to fight COVID.

GROSS: So when was this? This was last summer?

ISAACSON: It was July 31.

GROSS: OK (laughter) - memorable day. What was it like for you not knowing whether you got the real thing or a placebo?

ISAACSON: It was important not to know because I didn't want to change my behavior. You know, I still wore masks and did social distancing. But they monitored my blood. They made sure it was all going well. And they did tell me that at the end, if I'd gotten the placebo, they'd switch you over and monitor you with the real thing. So I was just waiting to see.

GROSS: How did they unblind you? In other word, how and when did they let you know what you really got? And what did you get?

ISAACSON: Well, it was six months later, after you do your final blood test. And then they unblind you. I had gotten the placebo. But at that point, they were rolling out the real Pfizer vaccine anyway. So I was able to get the real thing.

GROSS: Well, that's great. Did you have side effects to report?

ISAACSON: No. In fact, I was kind of worried. Even with my second shot, I kept thinking, everybody's got side effects. Maybe they gave me the placebo again. But nope.

(LAUGHTER)

ISAACSON: I didn't really have any side effects.

GROSS: Before we get deep into the science of the vaccine itself, let's do some background science and background history of RNA so it'll make it easier to understand the science of the vaccine. So we're talking here about RNA or, more specifically, mRNA. RNA is a sister of DNA. We know what DNA is kind of. I mean, we know that we can submit our DNA through saliva and find out more about our genealogy. We know if there was a crime, they could take DNA samples and trace who the criminal is through a DNA databank if you're lucky and the DNA is already in the databank. So what is RNA compared to DNA?

ISAACSON: You're right. DNA is the famous sibling. It's the one that gets on the magazine covers. And we talk about the DNA of an organization, of a society. But like a lot of famous siblings, DNA doesn't do a whole lot of work. It just sits there in the nucleus of our cell guarding our genetic information. The real work is done by RNA. The RNA goes in there, takes copies of a particular gene that might be needed and then goes to that region of the cell where you make proteins. And it's the RNA that oversees the making of the protein. And that work of taking the code from in our cell's nucleus from the DNA and going to make protein, that's called the messenger work of RNA. And that's why these little snippets are called messenger RNAs. And when everybody was trying to race to study the human genome and do the sequencing of DNA, there were some scientists who said, let's look at this more interesting molecule, which, by the way, turns out to be able to replicate itself. And so - lo and behold, it's the beginning of all life on this planet. So RNA turns out to be far more interesting than its brother, DNA.

GROSS: And a recurring theme in your book is that nature is beautiful and that RNA is beautiful. What's beautiful about it?

ISAACSON: RNA is beautiful because it's so simple, which is a four-letter code. It can build any protein that's in our body. It was the molecule that started replicating itself three, 4 billion years ago in this stew that was on our planet. And that's how life begins on our planet. And RNA can serve as a guide to help cut up pieces of DNA, which is what gene-editing technology is all about. Or it could serve as a messenger to say, hey; build this protein in the cell because that mimics a spike protein on a coronavirus. And that way, the person will be immune to coronavirus. And so RNA can do all these things, act as a guide for scissors, act as a messenger to build proteins. And it really does the daily work every, you know, time we need proteins built for anything, whether it's our hormones or our hair or our eyes or the little things that - the neurons in our brain.

GROSS: So CRISPR - spelled C-R-I-S-P-R - is an acronym for a big scientific term that I don't think you even need to mention because no one will understand what it means (laughter). But anyway, so CRISPR is a gene-editing tool. Before we get to how that uses RNA, what does it mean to be a gene-editing tool? What are some of the ways that's being used now?

ISAACSON: If you want to change the genes in our body, you can do it just by snipping them out and sometimes putting in a replacement. So let's say somebody has sickle cell anemia or Huntington's. That's a simple single-gene mutation. And so you can change it with a gene-editing tool. In the future, you might be able to do more complicated things, change hair color, a muscle mass or memory cells in a human being. And so what we do with gene-editing tools is we can fix diseases. And a little bit more controversially, we can edit the embryos of our children and make permanent changes in the human race.

GROSS: Yeah. And we'll talk about that a little later when we get to the moral and ethical questions surrounding this new genetic technology. So you describe CRISPR as an immune system that bacteria adapted when they get attacked by a new type of virus. So what's the relationship between the bacteria immune system and the gene-editing tool known as CRISPR?

ISAACSON: Whenever viruses attack certain bacteria, those bacteria do something very clever. They take a mug shot, and they put it in their own genetic material or the bacteria. And so in these bacteria, you see these clustered, repeated segments of DNA. And that's where the name CRISPR comes from.

So that when the virus attacks again, the bacteria remembers it and uses a little guide RNA and a pair of scissors - an enzyme that acts as a pair of scissors - and cuts up the invading virus. So that allows the bacteria to have an adaptive immune system, meaning every time a new wave of virus comes along, takes that mug shot and will be able to fight it off the next time. And that's just what we, of course, need in this day when we're being attacked by wave after wave of viruses.

GROSS: So how does that apply to gene editing?

ISAACSON: What we can do and what Jennifer Doudna, the hero of my book, discovered is that we can engineer this system that bacteria have and say, OK, we'll code in the place we want the DNA cut. And so we can take this old, billion-year-old tool that bacteria have and reprogram it so we can aim at any sequence of DNA we want to change in our own bodies. If we want to change a gene - clip - we can do so.

GROSS: You actually tried your hand at genetic editing (laughter) just to see, like, how it's done, how hard is it. Would you describe your experience as a non-scientist trying to do a genetic edit?

ISAACSON: I was in Jennifer Doudna's lab at Berkeley, and I figured out, all right, if I'm going to really write about this, I should learn to do by doing it. And so a couple of graduate students spent a couple of days with me, and we had test tubes and pipettes and those little centrifuges that spin things around. And we were able to take CRISPR and edit a human cell, put in a little phosphorescent gene in it so we could see it glow. And it wasn't really all that hard, which was a little bit exciting to me, but also a bit unnerving.

Now, don't worry, Terry. When we finished, we mixed it with chlorine and poured it down the drain so it didn't escape. But that's why we all have to be thinking about what are we going to do with these gene-editing tools because they're not all that complicated.

GROSS: Let's take a break. If you're just joining us, my guest is Walter Isaacson. His new book is called "The Code Breaker." We'll be right back after a break. This is FRESH AIR.

(SOUNDBITE OF TODD SICKAFOOSE'S "TINY RESISTORS")

GROSS: This is FRESH AIR. Let's get back to my interview with Walter Isaacson. His new book is called "The Code Breaker: Jennifer Doudna, Gene Editing And The Future Of The Human Race." So let's get to the new mRNA vaccines, the COVID vaccines. And we're talking about the Moderna and the Pfizer vaccines here. How is mRNA used in these vaccines?

ISAACSON: The most basic thing that RNA does on this planet is it serves as a messenger to take a piece of genetic code from the DNA that's in the nucleus of our cell and say build this protein. And the way it works in the vaccine is we know that the coronavirus has certain proteins that, if we can disrupt them, they ain't going to work anymore, such as the spike protein that's on the surface of the coronavirus. And so we can now just program in the genetic code that tells a snippet of RNA to go make a part of that spike protein so it becomes a facsimile of it, like a mug shot of it.

And then our immune system says, OK, I'm going to kick into gear whenever I see this thing, and I'll knock it out. And so that's what the vaccine does, is it stimulates our immune system to make sure that if that spike protein - the real thing - ever comes along, it's already got the antibodies to knock it out.

GROSS: So for people who are afraid that if they get vaccinated, they're going to get COVID - which they're not - what's the difference between what you're being inoculated with - the mRNA that you're being inoculated with and the actual virus, DNA or RNA?

ISAACSON: It used to be when we did vaccines, we would take the whole virus that we wanted to knock out, and we'd give the patient an inactivated version of that virus, so one that was a weakened version of the virus, whether it be polio or measles or mumps or rubella. And, you know, people feared, well, I'm getting a little of the virus in me. Is that going to be bad? It never was bad, but this is much safer.

You're not getting the real virus. You're just getting a tiny blueprint that tells your cell how to make a small bit of a protein that exists on the surface of the real virus. Now, that little protein that gets built - that's not going to hurt you. That's not the virus. That's just a tiny component of the virus. But it tells your immune system, if you ever see this little thing, this tiny component, knock it out. And that's the way your body learns to knock out the real virus.

GROSS: Now, some people do get some side effects, like they feel, like, headachy or a little flu-ish (ph) the next day, especially after the second dose. Some people get a rash after the first dose. These are not - these go away. They're not - having COVID or dying of COVID, that's far worse than having a problem for a day or two. But why would you get a reaction if you're not really getting a virus?

ISAACSON: Your immune system is starting to kick in. Your immune system is saying, all right, I'm going to fight off this tiny little piece of protein that the vaccination is telling my body to make. And whether it's a flu vaccine or any vaccine, when your immune system jumps into action, it can cause a bit of a headache or a little bit of a swelling. But you don't have the real virus. You just have your immune system getting to work. In fact, it's a good thing. When my wife got the second shot, you know, she had a headache for a few hours, a little bit of swelling. And I didn't. And I thought, oh, wow, her immune system's a lot better than mine. It's kicking in fast. So you actually want to feel a little something because that says, hey; your immune system's working.

GROSS: So since you're explaining the science behind the vaccine - with all these new variants coming our way, variants that - some of them are more contagious or, you know, more infectious or possibly more lethal. And the question is, how good, how effective will these new vaccines be against these new variants? So with the mRNA vaccines, the Pfizer and the Moderna, what's the science behind how well they would adapt to a new variant?

ISAACSON: They've adapted very well, these mRNA vaccines, to the new variants that have come along because all of these variants still have the spike protein. And that's like a big barn door that the RNA vaccines and some other vaccines say, hey; watch out for this spike protein. And knock it out if it comes along. So - so far, we haven't seen variants that don't get affected by these vaccines. These vaccines are pretty effective. But here's the cool thing, Terry, these RNA vaccines are easily coded and recoded. In other words, it's just like rewriting a word document or recoding a program.

If we have a major new variant of the coronavirus that has a spike protein that's a different shape, it's real simple just to say, all right, let's take the genetic code of this new variant of the coronavirus, and let's program a messenger RNA that will build its spike protein. And that would take, maybe, two or three days to just do the recoding. And so it's not all that hard. And then it would take a few weeks to start manufacturing the new vaccine. So what we've seen this past year is a major shift in the balance of power between us and viruses because we can just recode. Every time the virus mutates and changes, we can pretty quickly recode these messenger RNA vaccines so that they'll go after each new variant. Fortunately, we don't need to do so much yet because the current vaccines are very good at the variants that we are now facing.

GROSS: I thought some scientists weren't so sure about, for instance, the variant in Brazil and how effective the vaccine was going to be against that.

ISAACSON: Well, we've seen that it's proven so far to be pretty darn effective. But as I say, all coronaviruses, they mutate a lot. There'll probably be thousands of variants that will change. And at some point, we might get one that will totally evade the vaccinations we have. And that just means we'll have to have booster shots that we do pretty simply just by redoing the code for the messenger RNA we're using.

GROSS: So it's interesting that recoding the vaccine isn't hard. You can change the formula, so to speak, in a couple of days by rewriting the code. But then the manufacturing and the distribution becomes the issue. How quickly do you think they can gear up for that for boosters?

ISAACSON: Well, as you say, molecules are the new microchips. We can recode them pretty simply. Then, of course, you do have to make the solutions and put it in the vials and distribute it. But now that we've gone through this process of doing it, we know it can be done in months rather than years. And so I think we'll be prepared just like we are every flu season when we create new versions of the flu vaccine. We'll be prepared to do booster shot and new variations of our vaccines as a coronavirus emerges, which is why I do think that this is a turning point in the hundreds of millions of years that organisms on this planet have been fighting off viruses.

GROSS: We've talked about the Moderna and Pfizer vaccines. Is the Johnson & Johnson vaccine also related to RNA?

ISAACSON: The Johnson & Johnson vaccine is more of a genetically engineered vaccine. It has a gene that will once again create a immunity towards the spike protein of the coronavirus. But it's not done using RNA. It's done using the entire gene of a particular coronavirus.

GROSS: Let's take a short break here, and then we'll talk some more. If you're just joining us, my guest is Walter Isaacson. His new book is called "The Code Breaker: Jennifer Doudna, Gene Editing, And The Future Of The Human Race." We'll be right back. I'm Terry Gross, and this is FRESH AIR.

(SOUNDBITE OF KENNY BARRON AND DAVE HOLLAND'S "DR. DO RIGHT")

GROSS: This is FRESH AIR. I'm Terry Gross. Let's get back to my interview with Walter Isaacson. He's written biographies of Einstein, Da Vinci, Steve Jobs, Ben Franklin and Henry Kissinger. His new book "The Code Breaker" tells the story of scientific and medical breakthroughs through new understanding of RNA. The book is part science history and part biography of Jennifer Doudna, who won a Nobel Prize last year for her RNA-related discoveries about gene editing, which led to the gene-editing tool known as CRISPR. Her breakthroughs in our understanding of RNA also paved the way for the mRNA COVID vaccines created by Moderna and Pfizer.

When Jennifer Doudna, who as you say is the hero of your book, started researching RNA, it wasn't to make a vaccine or to create a gene-editing tool; it was just to see what RNA could do, like what is RNA, because it was DNA that was getting all the attention. Tell us more about why she was so interested in RNA.

ISAACSON: That's one of the beautiful things about science, is that basic curiosity without any particular point - it's not like you're trying to invent something - but you're just basically curious about something in nature. It often leads to an amazing thing. And so Jennifer Doudna was just curious about how does RNA work? What is its shape like? How did it help begin life on this planet? And so she became interested, too, in how you could use RNA as a tool, as a guide, to help edit genes. And when she saw that's how the CRISPR system worked, it suddenly dawned on her - wow, this is not just basic curiosity; this could be a very useful tool in the medical toolbox we have. It's what we call moving something from bench to bedside - in other words, a bench in the lab to the bedside of the patient.

GROSS: And she had been an academic. She was at the University of California, Berkeley, and had a lab there. And at some point, she wanted to kind of get her research out of the lab, like you're saying, and make it a practical tool in the real world. What was her first step in that direction?

ISAACSON: After she discovers how CRISPR can be used as a tool to edit genes, she forms a couple of companies. One is called Mammoth, and it becomes a detection technology for viruses. Well, you know, that's pretty useful these days. She formed it five or six years ago. But soon they'll be producing home kits that will test us for any virus. She also helped form a company called Caribou which uses this gene-editing tool as a therapy to help fix diseases and genetic diseases. So one of the things I like so much about Jennifer Doudna is she's interested in the basic science. She's excited about the beauty. She's curious about how nature worked. But she also likes to take the next step and say, after we've discovered something, how can we make it useful? How can we apply it to our own lives?

GROSS: Are the home testing COVID kits that are going to be available soon - or maybe already are available; I've kind of lost track - are they building on her science?

ISAACSON: There's going to be these wonderful CRISPR-based home testing kits that build directly on the discovery that she won the Nobel Prize for, which is using this old technology that bacteria have called CRISPR to say, I can spot any virus just by reading the genetic code of things in my body, in which just in minutes, you can detect not only viruses of flu, you can detect bacteria, you could detect cancer, you can do your gut microbiome. That's going to be a great platform, these CRISPR home-based tests, upon which people will build all sorts of wonderful medical tools.

It'll be like your iPhone helps you bring apps into your home - these type of CRISPR-based home testing kits, being done by people at MIT and Harvard, but also by people who work with Jennifer Doudna out at Berkeley - these home testing kids will help bring biology into our home and bring us into a whole new era, where we can do easy self-diagnosis of the things happening in our body.

GROSS: Well, let's back up a second. You mentioned cancer in this list. We're going to be able to diagnose if we have certain cancers?

ISAACSON: Yeah, cancer tumors have genetic code, just as everything does, in terms of living things, just like coronaviruses do or bacteria do. So once you're able to develop a technology that can just go in and check to see if a particular piece of genetic code is around, then you'll be able to sequence tumors. You'll be able to sequence coronaviruses. And you'll say, hey; I want a tool that will detect it. It won't be a home kit to detect tumors by the end of this year, but in the lab, that's already being done.

GROSS: Yeah, you describe, like, gene editing and the discovery of how mRNA works as being the equivalent of a new revolution in science. Give us your short summaries of the three revolutions with gene editing, with, you know, this kind of biology being the third.

ISAACSON: I think in our modern times, we've had three great revolutions. The first was the physics revolution, and it sorts of starts at the beginning of the 20th century with Einstein's papers, and it's based on that fundamental kernel known as the atom. And from that, we get the atom bomb and space travel and GPS and, you know, semiconductors. Second half of the 20th century was also based on a very small kernel of our existence called the bit, meaning a binary digit, and it meant that all information could be coded in zeros and ones and binary digits. And that leads you to the Internet and the microchip and the personal computer. And so that gives us the digital revolution, which dominates the second half of the 20th century.

Now we've come to another particle, a fundamental particle of our existence, which is the gene. And in the beginning of this century, in 2000 or so, we sequenced the entire human genome. And now with Jennifer Doudna and the things that she and her colleagues have invented, we found ways to rewrite that genome. And so this part of the 21st century, I think, will be a biotech revolution, a life sciences revolution, in which we'll be able to rewrite the code of life.

GROSS: Let's take a short break here, and then we'll talk some more. If you're just joining us, my guest is Walter Isaacson, and his new book is called "The Code Breaker." We'll be right back after a break. This is FRESH AIR.

(SOUNDBITE OF ALLEN TOUSSAINT'S "EGYPTIAN FANTASY")

GROSS: This is FRESH AIR. Let's get back to my interview with Walter Isaacson. His new book is called "The Code Breaker: Jennifer Doudna, Gene Editing, And The Future Of The Human Race."

So early on for Jennifer Doudna, when she was working on RNA and gene editing, she got a contract from the Defense Department to study if gene editing could be used to treat radiation sickness that would be caused by, you know, a nuclear device, an atomic weapon of one sort or another. That seemed really remarkable to me. I mean, I grew up in the shadow of, like, nuclear terror (laughter), you know, post-World War II, like, nuclear terror.

And the thought - and there are so many movies that have come out where people are suffering from radiation sickness, you know, like, what-if-there-was-a-nuclear-bomb kind of movies, where you watch people for the whole movie, like, suffer nuclear radiation sickness. And the thought that it's possible that gene editing could be used to cure that just seemed absolutely remarkable to me. So I don't know how far she got with that. Like, where do we stand with that aspect of her research?

ISAACSON: A lot of the research into CRISPR and genetic engineering has come from the Defense Department, usually as a defensive mechanism. Like, how would you make it so that radiation wouldn't be as harmful to your cells? That's just a genetic issue that - you know, can you make cells that are more resistant to radiation? Can you make them more resistant to other forms of poisons or whatever?

And the Defense Department also helped Jennifer Doudna and the people around her at Berkeley and the Bay Area create something called anti-CRISPR because you could imagine a bad actor using this gene-editing technology to do something harmful, to try to edit our genes to do bad things. And so you want to say, how do we reverse the process? So a lot of the money has come from the National Science Foundation. A lot comes from these foundations that support research into bad diseases, like Huntington's and sickle cell anemia. And then some of it comes from the Defense Department that wants to help defend against people who might use gene editing to attack us or to help make people less resistant to other forms of attack.

I mean, you know, Vladimir Putin was talking about CRISPR as a gene-editing technology to a youth group at one point, and he said, well, we might use it to make better and stronger soldiers that don't feel pain. So that's - you can realize, all right, some of our enemies might be doing things; we got to figure out how to counteract it.

GROSS: So let's talk more about nefarious and unethical ways that this new technology can be used. One of the concerns you bring up in the book is biohacking. Describe what that - what those concerns are.

ISAACSON: Well, I think that CRISPR and other gene-editing technology are easy enough that they could be used by, you know, people who aren't playing by the same rules as a research scientist. It could be done in garages. So I can imagine people saying, hey; I want to create tools that will help my memory, increase my muscle mass. But like any drugs or any tools, we hope that there'll be some types of regulation, that the Food and Drug Administration and others will say, here's what you can use it for and here's what you can't.

GROSS: Are there other, like, nefarious uses that scientists are worried about?

ISAACSON: When Jennifer Doudna first helped create this tool called CRISPR that allowed you to do gene editing, she had a nightmare. And she walked into a room with somebody who said, I want to understand your new technology, and the person looked up and it was Adolf Hitler. And this made her realize that if it got into the wrong hands, somebody might use it for eugenics purposes, might want to create a master race, might want to create people who were stronger as soldiers.

And she decided to gather scientists from around the world to say, let's figure out what the promise and the wonderful things this gene-editing technology can do, but let's also try to limit things that would be inheritable or things that would, you know, not be as easy to control. And so she's been one of the leaders that said, this is an important and good technology; let's make sure we don't misuse it.

GROSS: So describe what inheritable means in this context and why scientists now are kind of drawing the line at that kind of work.

ISAACSON: It's easy to use gene-editing technology to fix problems in a living patient. For example, just this past year, a woman in Mississippi who has sickle cell anemia had her genes edited so that she no longer suffers from sickle cell anemia. Nobody would be against that - that a patient knew what she was doing, gave informed consent. But also, a couple of years ago, a doctor in China in an unauthorized experiment edited early-stage embryos of what turned out to be two twin girls, and he used those edits to make it so that the twins, the designer babies they were, didn't have a receptor that allowed them to get the virus that causes AIDS.

Now, you can see why some people say, well, that's great; we could help wipe AIDS, you know, from the human species. But the problem with that type of use of CRISPR is when you do it in reproductive cells, like early-stage embryos or eggs or sperm. It affects every cell in the body, and thus it's inherited by the children and all the descendants of the edits you've made. And that's a line you don't want to cross lightly, is making the type of edit that will not only affect a patient but also affect the entire human species and all their descendants.

One of the people in my book - a wonderful young kid named, you know, David Sanchez - has sickle cell anemia. And he's being treated for it, and they tell him about CRISPR and how it could make it so his children won't have sickle cell anemia. And David says, wow, that's really cool. But then he says, but I think it should be up to the kid to decide. And they said, well, what do you mean? Wouldn't you want to make sure your kids didn't have sickle cell anemia and that all their kids didn't? And he said, well, I think it should be up to each person to decide because even though sickle cell anemia has been really brutal to me, it taught me a lot of things. It taught me character. It taught me persistence. It taught me empathy and patience.

And so he, even as a 17-year-old, is able to make this distinction between using these wonderful technologies to cure patients who give their consent and want to have their genes edited to cure the disease and then crossing the line to make inheritable edits. Well, that's a line, as I say, that we don't need to do now and maybe we should be careful about ever doing.

GROSS: So I want to get back to the Chinese scientist who edited the genes and embryos of two twins so that they wouldn't be able to get HIV, they would be immune to that. He thought he would be a hero. He ended up with a big fine and a three-year prison sentence. What went wrong with his experiment that teaches us a lesson about what could go wrong with these kinds of things?

ISAACSON: Well, first of all, what the Chinese scientist did was unsafe. We're not ready yet to make these type of edits. And in fact, the children he produced are called mosaics, meaning some of their cells were edited and some weren't. So that's obviously a bad thing. The second thing is we don't know the unintended consequences. You get rid of that receptor that allows you to get the virus that causes AIDS, but maybe it means you're more susceptible to malaria, or West Nile virus. So we want to know what the intended and unintended consequences are.

But the real question is, once we figure out how to make it safe and that it's going to be reliable, then we still may want to pause and say, do we really want to make designer babies, to edit our kids? In my own personal opinion - and in the book, we go through it step by step because I think we all have to think through the cases and how it would work. Jennifer Doudna, the hero of my book, other people, myself, we each discuss each of the cases you'd do it.

I think you'd probably would want to make inheritable edits when it comes to things like Huntington's disease or sickle cell anemia or Tay-Sachs, especially if there's no alternative that's an easy medical fix for those things. But if you're just doing it to enhance children - say you want to make them taller or you want to change their hair color - that's where I think we have to draw the line for the time being at least.

GROSS: You live in New Orleans and teach at Tulane University. Last year in New Orleans, as I recall, there was a big spike in the coronavirus after Mardi Gras. What was that period like for you?

ISAACSON: I remember sitting on my balcony on Mardi Gras a year ago, and my balcony is in the French Quarter overlooking Royal Street. And it was a wild time. There were people - nobody had died at that point from coronavirus in the United States, but we knew about the pandemic. And some people were dressed up with Corona beer bottle costumes and viral heads and masks, making fun of the coronavirus. And boom, about three weeks later, it really hits the United States. There's a spike throughout the country, and we realize, OK, we're in a whole new era.

GROSS: Walter Isaacson, thank you so much for talking with us.

ISAACSON: You know, it's always great, Terry. I hope someday we'll be back in Philadelphia together.

GROSS: That would be great. I look forward to that. Walter Isaacson is the author of the new book "The Code Breaker: Jennifer Doudna, Gene Editing And The Future Of The Human Race." After we take a short break, Ken Tucker will review the new expanded version of Hailey Whitters' 2020 country album "The Dream," which he says is proof of how important she's become. This is FRESH AIR.

(SOUNDBITE OF ERROLL GARNER'S "IT'S ONLY A PAPER MOON") Transcript provided by NPR, Copyright NPR.