♪ ♪ (theme music plays) DAVID: Hello, I'm David Rubenstein, I'm in conversation today with Walter Isaacson who is a professor of history at Tulane University and has previously served as the CEO of Aspen Institute, the chairman of CNN, he's also served as the editor of Time Magazine.

So very impressive roles.

Walter, thank you very much for coming today.

WALTER: Thank you, David, it's great to be with you.

DAVID: So we're gonna talk today about your new book, The Code Breaker, Jennifer Doudna, Gene Editing and the Future of the Human Race.

So my first question to you is this, when you write books, do you often write books about people that some people would say are geniuses.

So you've written books about Steve Jobs, uh, Albert Einstein, Benjamin Franklin, Henry Kissinger, among others.

Uh, and I assume you would put Jennifer Doudna in the genius category as well.

Uh, what is it that these geniuses have in common in your observation?

WALTER: One thing they have in common is curiosity.

I mean when Jennifer Doudna is growing up in Hawaii, she touches things like the curling grass and figures out why does it move when you touch it, or why are there the same spirals in these seashells that I see elsewhere.

And that fascinated me, because Leonardo da Vinci asked those same questions, even drew the same spirals, and so people with this curiosity about nature.

And Einstein, his whole life, trying to figure out why does a compass needle twitch and point north when nothing is touching it.

You know, what's an electromagnetic field?

That passionate, obsessive, and very playful curiosity.

It's somethin' you see in Steve Jobs, Einstein, Leonardo da Vinci, and, of course, in Jennifer Doudna.

DAVID: Jennifer Doudna grew up in Hawaii.

Where did she go to school and where was she getting her training, uh, post-school?

WALTER: She grew up in Hilo, Hawaii, a small uh, volcanic town on the big island.

And it was interesting, because she was an outsider.

She was a tall, lanky, blonde girl, but the whole school in the small village were Polynesians.

And so she grew up knowing what it's like to be a bit of an outsider, which I think has helped a lot of people from Leonardo da Vinci to Steve Jobs in terms of creativity and, you know, having imagination.

And she grows up there, she's, sort of, loves science and nature.

But she grows up with, sort of, teachers who say, "Well, you know, girls don't become chemists, they don't become scientists."

So she goes to Pomona, a great liberal arts college in California, and decides to major in chemistry.

And she has a really good French teacher, and she thinks well maybe I should major in French.

And the French teacher says, "No, if you major in French, you'll be a great French teacher, but if you major in chemistry and biology, someday you'll be able to affect, you know, our lives, affect the human race."

So she does that, she gets, uh, into Harvard.

And that's where she starts working on the structure of RNA, somethin' other people weren't looking at.

But as an outsider, she said it was, like, when she played soccer as a kid.

She tried to play the positions that other kids weren't playing, and so she's always a little bit of an outsider.

And then, of course, after she's been at Harvard and Yale as an assistant professor, she gets recruited to go to Berkeley, and she likes the idea of being at a public university.

And so ever since then, for the past 15 years or so, she's been, uh, a professor at Berkeley.

DAVID: Was there, uh, discrimination against Jennifer Doudna as she was rising up in the science world as a woman in science?

WALTER: Absolutely, and this book is about the underappreciated role of women in technology and science.

When Jennifer Doudna was in the sixth grade, her dad left on her bed a copy of The Double Helix, James Watson's book about DNA.

And she was so fascinated, she thought it was, like, a detective story, and she decided she wanted to become a scientist.

And her guidance counselor at her high school said, "No, girls don't become scientists."

And that really prodded her along, especially because one of the main characters in Watson's, The Double Helix, is Rosalind Franklin, whose images are so crucial to figuring out the structure of DNA, but who doesn't get the credit in history that she deserves.

And so this was, uh, to me, she overcame the obstacles, Jennifer Doudna did, that had faced Rosalind Franklin.

And even as, uh, all the male scientists in the 1990s, and you know half of 'em, David, they were all pursuing the human genome project, they were all sequencing DNA, and the women weren't very involved in that.

And so women like Jennifer Doudna, Jillian Banfield, Emmanuelle Charpentier, focused on RNA, which is, sort of, the molecule that actually does the work in ourselves.

It's the one that actually builds the proteins.

And as we now found out, RNA is the more interesting molecule.

It's helped us create the vaccines we have for the coronavirus and it helped create this gene editing tool.

DAVID: So, for those who aren't experts in genes, let's go back a bit.

Um, uh, who was Gregor Mendel and, uh, and what did he do that was so enormously important.

WALTER: Yeah, um, Mendel and Darwin lived in about the same time, they both produced most of their work in the 1850s.

And Mendel was an underemployed, uh, monk in, uh, what is now the Czech Republic in Central Europe.

And he couldn't really get a job being a teacher.

He was not a very good pastor, 'cause he was so shy.

So he spent his time in the garden cultivating peas.

And then he would breed the peas so that the ones that had purple were were bred with the ones that were white, and the tall ones, and the short ones, and he kept track of 'em all.

And between what, uh, Mendel's peas and then the beaks of Darwin's finches, 'cause Darwin was looking at the finches in the Galapagos, it becomes apparent when you put those two things together that there's some particle in our body that is the unit of heredity, and that becomes known as the gene.

And so from Darwin and Mendel, we get to this concept of we have genes that we pass on to our kids.

DAVID: Now the, the structure of a gene, or the structure of DNA, that was discovered by, uh, which individuals, and when was that?

WALTER: The structure of DNA was discovered by James Watson and Francis Crick, and that was The Double Helix book I mentioned that Jennifer read when she was in sixth grade.

And it was a great competition, 'cause he was racing against Linus Pauling who was trying to do the same thing in California.

And, also, at the University of London, was Maurice Wilkins, sort of working both in collaboration and competition with Rosalind Franklin, the person who was taking the images of DNA.

So in the 1950s we finally figure out, not only do we figure out that DNA is a molecule that helps encode the gene, but we figure out the structure of it, and it has four letters, and how those four letters code everything you need to know about the life of any species.

DAVID: And then after that there was someone, Paul Berg, who also won a Nobel Prize for, uh, discovering how to, split DNA.

Is that right, through recombinant DNA?

Can you explain what that is and why that was so significant?

WALTER: Recombinant DNA that Paul Berg and others do, Herbert Boyer turns into a great company called Genentech.

Uh, what they've done, is recombinant DNA, which means you take the genetic material from one organism and you combine it with a genetic material from another organism, and you make some new organism.

And you can do it with viruses and bacteria, or, or anything.

And so that became the first chance we had at what's now called "Genetic Engineering."

It's where, sort of, molecules become the new microchips.

Instead of programming microchips, you can reprogram molecules by genetic engineering.

DAVID: So that, uh, launched the biotech revolution as we know, and it's been goin' on for quite some time.

So, why do we need any other inventions?

We have everything, we can split genes.

So, uh, what is it that, is actually discovered by, um, Jennifer Doudna?

And can you explain before you answer that, what actually is CRISPR?

WALTER: Well, CRISPR is a system that bacteria have been using for more than a billion years to fight viruses.

And as we go through this pandemic, you'd say, "Okay, that's a good idea to understand how bacteria fight off viruses."

And what bacteria do, is every time a virus attacks them, they, sort of, take a snippet, almost, like, a mug shot of the, the genetic material of that virus, and they store it in these clustered repeated sequences now known as CRISPR.

So if the virus ever attacks again, the bacteria can take a pair scissors, an enzyme that acts as a pair of scissors, and direct it to cut up the attacking virus.

So it's an adaptive immune system, just what we're trying to do in order to fight COVID.

Now what Jennifer Doudna does is we have this idea of genetic engineering, and we know what a gene is like, and she knows how RNA works, and can be a guide to get to a particular part of DNA.

So what she does is she replicates the system bacteria use, called CRISPR, and says, "I can use it to target a very specific gene."

We got three billion base pairs in our DNA, but we can target to just the gene we want.

Maybe the gene that's causing sickle cell anemia, or cystic fibrosis, or Huntington's.

Or maybe the gene that's giving us a receptor that allows us to get the virus that causes AIDS, or the virus that causes COVID.

And she and Emmanuelle Charpentier, her partner in research, discover a way to take CRISPR, figure out its simple components, it's very, very simple.

You just got a guide, RNA, and it's got, uh, scissors.

And take that and you say, "We can edit the DNA of anything at any spot we want to, cut out any gene we don't like, and maybe insert a gene we do like."

DAVID: This particular discovery that, uh, that the two of them came up with, or invention you might say, uh, how long did it take them to work on this?

WALTER: Well it took a long time and a whole lot of people to figure out CRISPR, starting with a wonderful graduate student in Spain named Francisco Mojica, who, kind of, discovered these weird things in the microorganisms he was looking at.

It also took people who worked for Danisco, the yogurt company, the two great scientists there.

It's, like, that's a billion dollar industry protecting the bacteria and yogurt culture, so they're figuring it out.

But then when Jennifer Doudna and her partner, Emmanuelle Charpentier, do it, it really only takes them about eight months of work.

And what they're trying to do is just isolate exactly what are the components that make this CRISPR system work?

And there is almost an eureka moment, 'cause they're doing it in a test tube, and they're doing it by Zoom, and Skype, and Dropbox 'cause Emmanuelle is in S, um, Sweden, and her graduate student's in Vienna, and Jennifer Doudna is in Berkeley.

And there's a moment when they get their component exactly right and they're able to cut a gene exactly where they want to.

And that was an eureka moment because not only did it make the CRISPR system work, but it made 'em realize we could turn this into a tool that could edit our own genes.

DAVID: So, uh, when somebody like Jennifer Doudna, uh, has a lab, and she works in a lab, what is a lab?

Is it two or three people, is it ten people?

Who supports its, where's the money come from?

WALTER: Well, the lab is at Berkeley, you know, it's a huge academic room that has rows after rows of benches where researchers, and graduate students, and investigators sit with their little test tubes.

And they figure out what experiments they want to do and they all do it during a day.

It's funded in an interesting way.

Part of it, you know, Berkeley, it's a, you know, public university, it's being funded.

A lot of the money comes from the government, the National Institutes of Health.

And for that matter, DARPA, the Defense Department's research agency, trying to figure out CRISPR.

So they give grants to universities to figure out specific things.

And this is why American science is so good, is it's done in academic labs, sometimes funded with philanthropic dollars, like, the Gates Foundation and, Priscilla Chan, Mark Zuckerberg's Foundation put money into Jennifer's lab.

But then the third thing that happens, which is somewhat controversial, but I think is an important part of the process, is you get patents, and you get a patent on what you've discovered.

And so Stanford University made hundreds of millions of dollars when you talked about recombinant DNA.

And Paul Berg, and then Herbert Boyer and others, there's a patent on it, that returns a lot of money to universities.

DAVID: Okay, let's suppose you're, uh, a scientist, a bench scientist, or the head of a lab, and your lab discovers, uh, fire, or you invent the wheel, uh, do you get any credit for that unless it's published in an academic journal?

What is the obsession with publishing these things in academic journals?

Why is that so significant?

WALTER: It's very important to be published and to be peer reviewed, meaning you write up a paper, you describe exactly what you did, and then great journals such as Science, or Nature, or Cell, send it around to other scientists and they review is this worth publishing?

And once you've published, they just put your marker down.

When Jennifer Doudna and Emmanuelle Charpentier published in the middle of 2012 their CRISPR paper, that means they won the race.

It wasn't just that they did the experiment first, they got it published first.

DAVID: Okay, so they published in a journal their discovery, but their discovery didn't actually prove that you could do this, kind of, gene editing in humans... WALTER: Right.

DAVID: It proved you could do it in a test tube.

So, there are somebody else at another place that was trying to prove they could do it in humans.

Who was that and where was that other place?

WALTER: Well Feng Zhang Is the other researcher.

He was born in China, raised in Iowa, and then is at the Broad Institute of MIT and Harvard with his great patron, the brilliant Eric Lander, who's now become the chief science advisor to President Biden.

And this is a great controversy in the book, because Jennifer Doudna and Emmanuelle Charpentier, indeed figure out exactly how CRISPR works in a test tube.

And then there's a six month race between the middle of 2012 to January 2013 where Jennifer Doudna's lab, Feng Zhang's lab at the Broad Institute of MIT and Harvard, and a couple of other labs, all racing to say we now read this paper, how can we make it work in a human cell?

And there's still a patent battle going on, and a battle for credit because, as you said, somebody like Jennifer Doudna could say, "Well it's obvious," and I mean that almost in a legal sense, as a, uh, legal term called obviousness when it comes to patent law.

"It's obvious that if it worked the way we said it would, it would also work in a human cell."

And, of course, the people at the Broad Institute, including Feng Zhang and the lawyers for them say, "It's not obvious at all, it takes a lot of effort to make it work in humans."

So that's part of the competition in the book.

Who gets the credit, who gets the patent?

Now the Nobel Committee has decided who gets the Nobel, but who gets the real credit and the intellectual property that comes from making it into a medical tool that can work in humans.

DAVID: So the Broad people, Feng Zhang, uh, filed for a patent and they were awarded a patent, uh, initially, but now it's still in litigation is that correct?

WALTER: That's a very simple version of a very complicated thing.

But, yes, the fight is going on, and at some point I hope they all just shake hands, and say we're gonna cross-license, and we're gonna get back to our benches.

Because, uh, there's a old saying that, "We ought to quit fighting over divvying up the proceeds until we finish robbing the stagecoach."

DAVID: Now in October of 2020, the Nobel, uh, Committee came out.

I guess it's the, uh, chemistry, uh, award was given to, uh, the two women that had done the original work, the pre-human, let's say, work.

WALTER: Mm-hmm.

DAVID: Um, was that controversial or surprising?

And what was the reaction in the Broad Institute, uh, for not winning the, uh, the Nobel Prize alongside, uh, Jennifer Doudna?

WALTER: I think it was not surprising that CRISPR, the inventors of CRISPR won, and it's not surprising that they picked Emmanuelle Charpentier and Jennifer Doudna.

The, there were a few surprises to me.

One is, I thought CRISPR was gonna win, but I didn't know it would happen so quickly.

The same group of Nobel Prizes last October.

Sir Roger Penrose won in physics for a discovery he had made 50 years ago.

So, usually the Nobel waits, you know, a decade or two before saying this is Nobel Prize worthy.

But what they say is, this is not just a discovery, this changes everything.

This rewrites the code of life, this brings us into a new era is what they say.

So, the surprise to me is it happened so quickly.

The other surprise is usually there are three.

You know, the Nobel is awarded to three people, most of the prizes, and they usually don't throw away one of 'em, they give it to three people.

I was a little surprised they didn't give it also to Feng Zhang, but instead just gave it to Jennifer, uh, Doudna and Emmanuelle Charpentier.

But I think it's because it was a chemistry prize.

It was a prize about the basic science.

And in the end, the basic science all comes from this amazing eureka moment that Jennifer Doudna and her team had in 2012 when they said, "We can target genes and cut them."

DAVID: Now, uh, with the ability to change genes in people before they're born, uh, you could, as you point out in your book, take some of the worst diseases, sickle cell anemia, for example, or Huntington's disease, and you could create a human that would not have those genes.

Um, who decides whether it's a good idea to do that or not?

WALTER: We've already used CRISPR in this past year, just a few months ago, it was finally successful, to cure a patient of sickle cell anemia.

That's not controversial.

That's a living patient, she gave her consent, they edited her STEM cells, uh, for her blood, and she now is cured of sickle cell.

The controversial thing is let's do it an embryo or a reproductive cell.

So we're designing a baby that will have these genetic traits, such as not have sickle cell anemia, or any other trait you want to put.

And once you do that, those are inherited by all the children of that person and all of their descendants, so you basically edited the human race and that's real controversial.

The question of who gets to decide, well it's difficult, but that's one reason I wrote this book, is we all have to think this through.

This is gonna be somethin' society has to figure out.

So if we're gonna think this through, it's useful to understand how it works, not be intimidated, 'cause it's a really, um, amazing, wonderful tool, but also know, like any tool, we don't want to misuse it.

DAVID: Now you point out in the book that some scientists, a scientist in China did actually try to edit, uh, genes in an embryo.

He did so, and what happened to him, and what did he actually do?

WALTER: Well he did.

He edited the embryos of what turned out to be twin baby girls that were born in November 2018, you know, a couple years ago, in China.

He had been to some of Jennifer Doudna's seminars, he had, uh, talked to all of these people doing CRISPR, and he uses the tool of CRISPR, that Jennifer Doudna and others created, to edit these embryos.

And what he did was, he edited the children so that they would not have the gene that produces a receptor that allows you to get the virus that causes AIDS.

And at first it's announced, and Jennifer Doudna is there at a Hong Kong summit, it's announced, and there's a moment of awe and then a moment of shock.

And, you know, it's, like, "Whoa, we've actually now snatched fire from the Gods."

We're like Prometheus and we've become a species that gets to edit our future, that gets to hack our own evolution.

And it was controversial, of course, and it was a messy thing because he didn't really need, 'cause there's other ways to prevent people from getting AIDS.

So everybody decided that this was a bad thing, even the Chinese government.

And a few weeks later, he was put, he was, uh, arrested and put on trial, and he's now under house arrest for having done this.

DAVID: So, um, just to go back to what's gonna be the impact on the human race.

Uh, theoretically we could say to a parent, "If you want to have a tall basketball playing, uh, child, we can do that for you.

If you want to have a child that is a fast runner we can do that for you."

Uh, why would humans not do that at some point, uh, 100 years from now, or even 50 years from now, and just, you know, change what God gave us and just... We move forward.

Why would that not happen?

WALTER: Well, one of the things that God gave us was a mind to be able to figure out how to use CRISPR.

So people say it's unnatural or, you know, it's tryin' to play God.

And, and whether it's nature or nature is God, it's evolved a creature that's given us these tools to do things.

So it's a good question.

Why wouldn't you do it?

People, including Jennifer Doudna, she said she recoiled at first of the notion of this being used, but the more you think about it, maybe we should have it be used.

Now you gotta make sure it's safe.

You know, we can figure out the genes that cause, sickle cell anemia, or cystic fibrosis.

It's a little bit harder, but not impossible to get the genes that stop our muscle growth at a certain time.

We've done that in, in mice and cattle, where you can double muscle it, animals to be, uh, greater muscle.

We could eventually do that with our children.

You know in ten, 20, 30, 40 years, it's a question of what other genes you could edit.

Certainly easy to edit eye color, or skin color, or hair color.

Even memory, we've done that in mice, you could do that.

And then you have a moral question, which is, well, why not do it?

As George Church, at Harvard says, "Well, if we start making people who are taller, and stronger, and have a higher IQ, what's wrong with that?"

Here are a couple things that I think are problematic.

One is, it's not gonna be free, all these offerings at the genetic supermarket.

And so do we want to make it so that the rich can buy better genes for their children until the inequalities in our society, not only exist the way they are, but they get, you know, heightened and even encoded.

So we have sub-species of those who are genetically enhanced, like in the movie, Gattaca, and those who aren't.

Secondly, I think you have a diversity problem.

You know, I sit on the balcony right behind me, it overlooks Royal Street in New Orleans.

We just went through a truncated Mardi Gras.

But even then, I'm lookin' on that balcony and there are people tall, and short, and fat, and skinny, and, you know, light, and dark, and in between, and gay, and straight, and blue-eyed, and brown-eyed.

And that wonderful diversity makes us strong as a society, makes us strong as a species.

And if we allow everybody to edit out anything that they might consider to be away from the norm, I think that's bad for society too.

So I hope we use this to make our kids smarter, to make our kids healthier, but I'm not sure we should use it to enhance kids in a way, uh, that destroys the diversity and the notion that we're all created equal.

DAVID: Okay, well Walter thank you for a very, very fascinating conversation.

Uh, thank you for being with us today.

WALTER: Thank you David, it's was great to be with you.

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