ON CRISPR Episode 5: The Conversation

Summary

ON CRISPR Episode 5: The Conversation

Podcast: ON CRISPR: The Story of Jennifer Doudna with Walter Isaacson
Episode: 5 – The Conversation
Date: October 8, 2025
Host: Walter Isaacson
Guest: Jennifer Doudna
Moderator: Evan Ratliff
Recorded at: New Orleans Book Festival at Tulane University

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Episode Overview

This final episode presents an in-depth live conversation between biographer Walter Isaacson and Nobel Prize-winning biochemist Jennifer Doudna. Four years after the publication of Isaacson’s biography, they reflect on CRISPR’s emergence as a game-changing technology, its multiplying medical breakthroughs, and the ethical, practical, and political complexities that have followed. The episode highlights Doudna’s personal journey, the collaborative nature of scientific discovery, the global implications of gene editing, and the challenges facing science in the US today.

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Key Discussion Points & Insights

1. Early Inspiration and Overcoming Barriers

• Doudna’s upbringing in Hilo, Hawaii, her exposure to science through literature, and first awareness of women in science.
  • “My father was a literature professor. He gave me a copy of the Double Helix… That book really showed me that science is a process of discovery.” (04:01 – Jennifer Doudna)
• Influence of Marie Curie and referencing the dismissiveness toward Rosalind Franklin in "The Double Helix."
  • “Of course, she was doing important experiments.” (05:07 – Jennifer Doudna)
  • “Up until then you hardly knew that there were women scientists.” (05:15 – Walter Isaacson)

2. Pathway Into Science: Chemistry to CRISPR

• A pivotal high school chemistry teacher (Ms. Wong) who taught science as problem-solving rather than rote memorization.
  • “Science is about solving puzzles and not memorizing facts…” (05:37 – Jennifer Doudna)
• Her draw to the interface of chemistry and biology.

3. The Origins and Mechanism of CRISPR

• Initial collaboration with Jill Banfield at Berkeley, sparked by Banfield’s curiosity about bacterial immunity.
  • “She Googled who at Berkeley works on RNA. My name popped up and she called me, and that's literally how we got together.” (07:59 – Jennifer Doudna)
• The role of curiosity-driven ('basic') research over lab work with direct applications.
  • “It was pure curiosity driven science.” (09:40 – Jennifer Doudna)
• Clarifying what CRISPR is: “It's a series of repeated sequences of DNA... where I'm storing information about viruses... a genetic vaccination card.” (13:53 – Jennifer Doudna)
• How CRISPR systems serve as a kind of genetic “mug shot” archive, protecting bacteria from viruses.

4. Gene Editing: Discovery and Global Impact

• The eureka moment: understanding CRISPR-Cas9 as a programmable “scissors” guided by RNA to cut DNA.
  • “When we looked at the data, we realized that we had in our hands the knowledge of how to reprogram these Cas9 proteins so they would cut DNA where we wanted.” (17:19 – Jennifer Doudna)
• The promise for treating genetic diseases—sickle cell as the archetypal example.
  • “With CRISPR, it's now possible to override that mutation and give patients back a normal blood supply…” (19:20 – Jennifer Doudna)

5. Ethical Questions and Global Scientific Responsibility

• The boundary between treating existing patients and editing inheritable genes (germline editing). Reference to the case of He Jiankui in China and global consensus-building against heritable editing.

  • “There's very little information about how genome editing would actually work in embryos, to the point where it's really not, I think, technically safe…” (21:20 – Jennifer Doudna)
  • Discussion of broad ethical questions—should we edit out diseases and “enhance” future generations?
  • Reflections on patient stories (e.g., David Sanchez with sickle cell) and questions of identity and resilience.
    • “…what is it that truly makes us individuals, makes us who we are? …his disease had… helped to shape him as a person and that he would be different without it.” (23:13 – Jennifer Doudna)

• “Once you do this and you have this tool, you start worrying about these questions...” (25:19 – Walter Isaacson)

• Reference to the Asilomar Conference as a model for responsible self-regulation in science.

  • “We actually contacted Paul Berg and David Baltimore, two of the scientists who were some of the leaders of those original group discussions in the 1970s, and they came to an early conference we had… to discuss the ethics of CRISPR…” (26:29 – Jennifer Doudna)

• Importance of international cooperation and aligning standards globally.

6. Science Funding and US Scientific Leadership

• Concerns about reduced NIH/NSF funding and the “seed corn” of future innovation.
  • “Companies are not going to be able to invest in the kind of curiosity-driven science that does provide that pipeline, but does so in a way that is kind of open ended. And if we cut that off, I guarantee that we're going to see a big change not only in this country, but around the world.” (38:16, 38:53 – Jennifer Doudna)
• Loss of the US as a global magnet for top scientists due to funding cuts and tighter visa restrictions.
  • “Science is really international... If we stifle that, it's going to be a disaster.” (40:50 – Jennifer Doudna)

7. Translating Research into Solutions: Academia & Industry

• Need for academia-industry partnerships, challenges in commercialization, and training scientists for entrepreneurship.
  • “Academic labs are really not appropriate [for global deployment]. We don't have the funding... This is where companies are necessary.” (33:18 – Jennifer Doudna)
• The creation of the Innovative Genomics Institute as a bridge between discovery and application.

8. Expanding Applications of CRISPR

• On human health:
  • Future of CRISPR in treating not just rare genetic disorders “but increasingly... to prevent disease and to cure diseases that affect many people” including cancer.
    • “We’re looking at opportunities with programming the immune system... and also thinking about ways that we can provide preventative changes in DNA that will protect us from disease.” (43:07 – Jennifer Doudna)
  • Possibility of CRISPR-enabled "cancer vaccines."
• On climate change and agriculture:
  • Using CRISPR to edit the microbiome of cattle to reduce methane—a major greenhouse gas.
    • “Imagine that we could reprogram those microbes to not produce methane and in fact to use that energy to make more meat or more milk...” (47:46 – Jennifer Doudna)

9. Science Communication and Public Trust

• Barriers caused by misunderstanding, misinformation, and “anti-science” sentiment.
  • “Scientists are not good at... being public intellectuals... We have to be educating students to be not only great at what they do in the lab, but also thinking about how they explain the importance of what they do.” (46:26, 46:53 – Jennifer Doudna)
• Importance of pairing science with humanities, for ethical, societal, and practical navigation of new technologies like gene editing and AI.

10. Intersection of CRISPR and AI

• Use of AI (e.g., AlphaFold) in biological research to rapidly predict protein structures and suggest experiments.
  • “It accelerates the pace of science... we're seeing this more and more with other kinds of AI-driven approaches.” (57:50 – Jennifer Doudna)
• Potential for AI to design better therapies, vaccines, and tailor clinical approaches quickly.

11. Challenges to Equitable Access

• High cost of gene therapies such as CRISPR-enabled sickle cell treatment (up to $2M per patient).
  • “Why isn't everybody with sickle cell disease able to get this?... in large part, it's for technical reasons...” (59:44 – Jennifer Doudna)
• The technical bottleneck is delivering genome editors to the right cells—solving this would democratize the technology.

12. Advice to Aspiring Scientists

• Importance of following one’s passion and not being deterred by those who discourage ambition.
  • “You have to figure out what you're really passionate about and pursue it just sort of doggedly and not be dissuaded by naysayers.” (62:00 – Jennifer Doudna)
• On explaining your work simply:
  • “I want you to be able to say in one sentence to your grandmother, you know, why you're doing what you do and why it matters.” (47:19 – Jennifer Doudna)
  • “Rewriting the code of life to protect us from disease.” (47:26 – Jennifer Doudna)

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Notable Quotes & Memorable Moments

• Walter Isaacson:

  • "Jennifer is the intersection of being a good person and a brilliant scientist and probably the person most defining our future with biotech." (03:21)
  • "Oppenheimer, the movie, is somewhat about it, which is the Prometheus problem, and that we have snatched a technology from the gods, and who knows what we're going to do with it." (25:19)
  • "You have that in history with great advances in science. The Double Helix being... whatever you may think of Jim Watson, just a wonderfully written book." (52:44)

• Jennifer Doudna:

  • "With CRISPR, it's now possible to override that mutation and give patients back a normal blood supply, which means that they're free of these repetitive crises." (19:20)
  • "It's going to require a better effort between scientists and technologists and then the rest of us to work that out." (56:40 – on bridging science and humanities)
  • "If we stifle that, it's going to be a disaster." (41:20)

• On Science Funding:

  • "If you were an enemy of the United States and you wanted to destroy its future, one thing you would be doing is say, you know, they did the Internet, they did all these things... let's pull all these away so that China can be doing it." (39:28 – Walter Isaacson)

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Important Segments & Timestamps

• Early Aspirations, Science Inspiration: 03:21–06:40
• Origin of CRISPR Collaboration: 07:37–09:47
• CRISPR Mechanism Explained: 13:12–14:44
• Gene Editing Discovery Moment: 17:19–18:28
• Sickle Cell Treatment Story: 19:05–19:59; Moral boundaries, heritable editing, and the story of David Sanchez: 20:16–23:54
• International Ethics Consensus (“Asilomar 2.0”): 26:29–27:54
• Debate on Science Funding and US Leadership: 37:58–41:20
• CRISPR Applications for Disease and Climate: 43:07–49:58
• Challenges of Communication and Anti-Science: 46:26–47:19; 55:33–57:04
• Future of CRISPR, AI, and Lowering Costs: 57:04–61:35
• Advice for Students: 62:00–62:36

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Tone and Language

The episode strikes a tone of optimism, responsibility, and humility—reflecting Doudna’s sense of scientific wonder and caution, as well as Isaacson’s energetic, accessible curiosity. Their language is direct and vivid: Doudna explains technical details with clarity and draws real-world connections, while Isaacson frames the moral and historical stakes.

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Conclusion

This rich conversation spans the personal, scientific, and societal dimensions of CRISPR. From Doudna’s emergence as a science pioneer overcoming social barriers, to the technical and ethical puzzles of gene editing, to policy, access, and the urgent need for cross-cultural and interdisciplinary dialogue, the episode threads together the frontiers—and fragilities—of modern biotechnology. It closes with practical wisdom for the next generation: follow your curiosity, communicate your discoveries, and contribute with both rigor and humanity.

Transcript

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[Jennifer Doudna]

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[Jennifer Doudna]

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[Jennifer Doudna]

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[Liberty Mutual Advertiser]

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[Ryan Seacrest]

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[Jennifer Doudna]

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[Jennifer Doudna]

Class.

[Evan Ratliff]

This is on crispr the story of Jennifer Doudna. I'm Evan Ratliff. For our final episode, we're bringing you something a bit different. It's a conversation that Walter Isaacson and Jennifer Doudna had at the New Orleans Book Festival at Tulane University earlier this year. It's a fascinating exchange that shows how four years after the book's publication, the medical breakthroughs brought on by CRISPR have only multiplied. Isaacson and Doudna also touch upon how recent cuts in science funding and researcher visas have shaken the field, putting at risk the very kind of work that created CRISPR and is now saving lives. If you've listened and enjoyed the series so far, thank you. We would be grateful if you could take a moment to rate and review the podcast on your platform of choice. It really helps us reach more people. Here's the conversation.

[Walter Isaacson]

Thank you, thank you, thank you. And Jennifer, thank you so much for being here. As somebody who's written biographies, I tried people say, who's the nicest one? I said, there's only one I've written about. Well, Jennifer is the intersection of being a good person and a brilliant scientist and probably the person most defining our future with biotech. When you were a kid, you were in Ilo, Hawaii. I think you had a guidance counselor who once said, girls don't do science. How did you end up thinking, okay, there are women scientists. I can do this?

[Jennifer Doudna]

I think when I, you know, I think back to my upbringing. My father was a literature professor. He gave me a copy of the Double Helix, a book about the discovery of the structure of DNA, when I was probably 11 or 12 years old. And that book really showed me that science is a process of discovery. And I was fascinated by. By that description of how scientists could figure out the mystery of something in biology by doing experiments. And then I learned about Marie Curie's work and was inspired by her story. And together, I think those two ideas really spurred me on to thinking about a career in science.

[Walter Isaacson]

One of the things in James Watson's book, the Double Helix, is he kind of minimizes and dismisses dismissively a bit. Rosalind Franklin, who did the great photograph that helped helped Watson and Crick understand the structure, calls her Rosie. Most people, when they read that book, they say, oh, you know, it was dismissive. But when you read the book, what did you think?

[Jennifer Doudna]

When I read the book, I thought, that's ridiculous. Of course, she was doing important experiments.

[Walter Isaacson]

And that a woman could be a scientist.

[Jennifer Doudna]

Yes.

[Walter Isaacson]

Which you told me at one point that up until then you hardly knew that there were women scientists.

[Jennifer Doudna]

That's True.

[Walter Isaacson]

Exactly. So from there you decide to go to not be a French teacher, but go into biochemistry and chemistry mainly. Why did you choose that? That's not a usual path on chemistry.

[Jennifer Doudna]

Well, I think it started with my chemistry teacher in 10th grade. She was Ms. Wong In Hilo. She taught us kids that science is about solving puzzles and not memorizing facts in textbooks. I thought that was so interesting. I thought to myself, wouldn't it be am understand the chemistry of life? So that was really the first inkling I had that really what I wanted to do was be working right at that intersection between chemistry and biology.

[Walter Isaacson]

Now, on the power of books your father leaves on your bed. The double helix. I think it was the old vintage paperback.

[Jennifer Doudna]

Penguin, Penguin Books.

[Walter Isaacson]

Penguin, Penguin. Sorry. And if I remember, you thought it was a detective story because it looked like that, right? And then you find out it wasn't, and then you found out it was.

[Jennifer Doudna]

Yep, that's right. I thought it was a detective story of one type. And in fact, when I read the book, I realized it is a detective story. It's just about something very different than I expected.

[Walter Isaacson]

Tell me, growing up, you'd taken hikes, and you're seeing things in Hawaii that we kind of have here, too, out in the. You know, which is weird grasses that if you touch them, they curl up. And one of the things I like about you, Leonardo da Vinci and others, is a curiosity about things that we all see every day, but we don't go, oh, my God, why is that? And when you touched, I can't remember the name of the grass, and it curled, you just become fixated on how does that happen, Right?

[Jennifer Doudna]

Yeah. I think when I was in Hawaii, I was amazed by all the plants and animals that had adapted to that island environment. So you're mentioning sleeping grass. That's one of the organisms that I was fascinated by. But we also had blind spiders that lived in lava tubes. And this was something that I just found myself drawn to. That question of why, when we get.

[Walter Isaacson]

You get to Berkeley after a while, through a long thing, through Harvard, but when you're there, you weren't doing RNA CRISPR type stuff. I mean, it was not yet a full field. How did you end up starting to study that? I mean, who called you and said, let's do something?

[Jennifer Doudna]

Well, this is the great thing about doing research is that ideas come out of all sorts of directions. In our case with crispr, the first indication that there was something very interesting going on in bacteria known as CRISPR systems was the work of Jill Banfield, who studies bacteria in their native environment. I think she was really one of the first people that noticed that bacteria can acquire immunity to viruses that infect them in real time. And she wondered how that works and why. And she had a hypothesis that involved molecules of rna, which are the chemical cousins of DNA. She Googled who at Berkeley works on rna. My name popped up and she called me, and that's literally how we got together.

[Walter Isaacson]

And this is why Great Research University is so good, because you have a lot of people together and somebody says, okay, I need to know about this molecule.

[Jennifer Doudna]

And.

[Walter Isaacson]

And you form a partnership, right?

[Jennifer Doudna]

That's right, collaboration.

[Walter Isaacson]

And one of the problems nowadays is so much of that is funding of basic research, not applied research, just funding for curiosity's sake that the federal government under Vannevar Bush starting in 1945, made part of what we as a nation do, which is curiosity driven basic science. So when Jillian Banfield calls you up and says, I've got this molecule, I know you're interested in it, but maybe it has something to do with the sequences and bacteria. Were you all thinking of an applied application or were you just basic research?

[Jennifer Doudna]

Oh, certainly not. It was pure curiosity driven science.

[Walter Isaacson]

And what was it you were trying to figure out?

[Jennifer Doudna]

Well, the question at that time for me was, well, first of all, I guess I was amazed that bacteria would have an adaptive immune system. We're all familiar with our own bodies working that way, but nobody had any inkling that bacteria could do something like that. So I was fascinated by that possibility and also by the role of molecules of rna, which are thought to be some of the most ancient molecules on our planet and perhaps even the source of life on Earth.

[Walter Isaacson]

Wow. Source of life. So we're all trying to figure out how did life begin? You had a great. Tom Cech was his name, right? Or who did the origins of life and figured the RNA world thesis that you worked on.

[Jennifer Doudna]

Well, Tom Cech was one person who I worked with in the past, but also my graduate advisor, Jack Szostak, was very interested in this question.

[Walter Isaacson]

And it was. He said, ask big questions, right?

[Jennifer Doudna]

He did.

[Walter Isaacson]

And what was the big question?

[Jennifer Doudna]

Well, the big question was, where did life come from and can we study it in the lab?

[Walter Isaacson]

And why does it.

[Jennifer Doudna]

The answer is yes, but you have.

[Walter Isaacson]

To do a chicken and egg riddle to get there. Right? Which is, we thought it was DNA that becomes a code for replicating species, but you can't have. How did you figure out that chicken and egg thing?

[Jennifer Doudna]

Well, the fundamental question is DNA is the code of life, yet it is replicated by proteins that are encoded by DNA. So sort of sets up this conundrum of which came first. And some scientists think that, in fact, neither one. It was really RNA molecules that might have had the ability to both encode information, which they do, but also copy information originally, and that that union of activities in one molecule could have given rise to early life.

[Walter Isaacson]

Yeah, I mean, the main thing is to be able to replicate itself, I guess, is what distinguishes a rock from life.

[Jennifer Doudna]

Right?

[Walter Isaacson]

Yeah. And so one of the things I say in the book, but you've pushed back on, but I'll let you do it again, is when you look at when you were doing that, say, in the 1990s, approximately all the men, including dear Francis Collins, who I think I see here, and others, they're doing the Human Genome Project. Eric Lander. Anyway, it's a very alpha male thing to figure out DNA and to sequence it by 2000. And yet, if I look, there were almost no women on that project, but women like you, Gillian Banfield, Emmanuel Charpentier, all are focusing on the sibling or cousin molecule rna. Why is that? And was that a gender thing or just happenstance?

[Jennifer Doudna]

No happenstance.

[Evan Ratliff]

Okay.

[Walter Isaacson]

But you played soccer and you said you always knew to run where the ball was going, not where the ball was. And I figured that was part of what you got you in rna.

[Jennifer Doudna]

I think what got me into RNA just, frankly, was just curiosity and this question about its role possibly in evolution that I found so fascinating also in the crispr.

[Walter Isaacson]

Well, now that we're talking about crispr, I'll start to give it. Which means it's clustered repeated sequences that are in the bacteria.

[Jennifer Doudna]

You almost got it right.

[Walter Isaacson]

Yeah, well, I'm not going to do clustered repeated interspersed palindropic, by the way. It was a. Whatever it's called where somebody comes up with a name and then tries to come up with the words that will spell the name. Wasn't it true that he said, okay, I'm going to call it crispr? And then he had to figure out what would the cri.

[Jennifer Doudna]

You want a nice acronym?

[Walter Isaacson]

Yeah, it was a nice acronym. It's called a backronym or something where you go backwards to get the acronym. But what it is is repeated sequences in the genetics of a bacteria. Explain why bacteria would waste a lot of time repeating sequences.

[Jennifer Doudna]

Well, what's interesting is that it's really, as you said, it's. It's a series of repeated sequences of DNA. So you probably all know that DNA is a four letter code and it is spelling out all kinds of molecular information that are required for cells to function. But how do cells mark a particular set of sequences so they know what to do with them? This is what happens in CRISPR sequences is that there's a repetitive region in the DNA that tells the cell this part is special. This is where I'm storing information about viruses that are infecting me over time. So it creates a genetic vaccination card.

[Walter Isaacson]

It's a little bit like mug shots. They say, hey, this one attacked me before.

[Jennifer Doudna]

Exactly.

[Walter Isaacson]

And we didn't quite know we might need that as a human species while you were doing it. Right. I mean, that we were going to be hit by viruses that way.

[Jennifer Doudna]

Well, we always get hit by viruses, of course, but humans don't have a CRISPR system. They do immunity differently. But in bacteria, this is a very effective way in real time for cells to acquire immunity to viruses and then use it to protect themselves.

[Walter Isaacson]

Well, they've been at it longer than we have, meaning bacteria have been fighting viruses for 4 billion years or so.

[Jennifer Doudna]

Roughly. Yeah.

[Walter Isaacson]

And so is this an evolutionary thing that the smart bacteria figured out?

[Jennifer Doudna]

Yeah.

[Walter Isaacson]

And so where did. So Gillian Banfield calls you up, take the story from there.

[Jennifer Doudna]

Yeah, she called me on the phone. This was in the days before we were all, you know, texting each other.

[Walter Isaacson]

Group chats, we call it.

[Jennifer Doudna]

Yeah, yeah, yeah. And we met at the Free Speech Movement Cafe at Berkeley, kind of a quintessential place. And she arrived with a big, you know, stack of papers. And she said, jennifer, I've got. We just noticed something fascinating in these bacterial genomic sequences, and we don't know what it means, but she showed me these signatures of repetitive DNA elements that flanked unique sequences that came from viruses. The question was, why? Why would bacteria be storing little pieces of viral DNA in their genome? That was the question. And she was so passionate and so excited about this that I couldn't help but be drawn to it.

[Walter Isaacson]

And how did that start leading to a gene editing tool?

[Jennifer Doudna]

Well, that led to a whole project that initiated in our lab biochemically to figure out how these sequences might be protecting bugs. And what we figured out, and this is the royal we with other people working in the field as well, is that these CRISPR sequences in encode molecules of RNA that provide the molecular zip codes that tell proteins that are also part of the CRISPR pathway where to go and what to cut. And so what they do in these cells is they cut up viral DNA that gets into the cell and prevent it from causing an infection.

[Walter Isaacson]

So these are proteins, sometimes called enzymes in this case. Right. That know how to cut. They're just like scissors, but they're made of molecules. Right. And so you see, it cuts DNA. When does it occur to you, oh, wait, if I can cut and paste DNA, I can edit genes?

[Jennifer Doudna]

Well, you know, Walter, I remember this morning sitting in my office in Berkeley when Martin Yinick, who was the scientist in Berkeley working on this project, came into my office and he said, jennifer, we figured out that this protein called CRISPR Cas9 is an RNA guided enzyme that has the ability to recognize viral DNA that matches the little letter sequence in these RNA molecules and make a double stranded DNA cut just like you would cut a rope. When we looked at the data, we realized that we had in our hands the knowledge of how to reprogram these Cas9 proteins so they would cut DNA where we wanted. And if one could do that, you could trigger DNA repair in other cell types, like plant or animal or even human cells to make targeted changes in the genome. This was really the synthesis of a lot of other scientists work in the field. But realizing putting all of those pieces together with our knowledge of this CRISPR enzyme made us recognize that we were probably sitting on a very powerful technology.

[Walter Isaacson]

What did you think at first that this ability to edit DNA, DNA in humans would be good for all kinds of things.

[Jennifer Doudna]

I mean, people were already able to use earlier forms of genome engineering to make targeted changes in DNA. So imagine that you could perturb a gene and understand its function, or maybe perturb a whole set of genes. But even beyond that, what if you could actually change a DNA sequence to correct a disease causing mutation? I think that was really one of the things that first attracted our attention.

[Walter Isaacson]

Well, give us, I think what may be the simplest, which is sickle cell anemia, is just a one letter mess up, right? A typo.

[Jennifer Doudna]

And.

[Walter Isaacson]

Your technology has done what with that? Right.

[Jennifer Doudna]

Well, this is a disease that's been characterized or understood for a long time at the genetic level. But it was impossible to cure it, certainly, and not trivial to treat. And of course, if you know anyone with sickle cell disease, you know that it's a terrible disorder that causes repetitive cycles of crisis where patients have to get blood transfusions. That's really the only way they can be treated up until CRISPR came along. But with crispr, it's now possible to override that mutation and give patients back a normal blood supply, which means that they're free of these Repetitive crises.

[Walter Isaacson]

How big of a deal is it to cross the line between doing that in a patient and doing that in the. I'll say, the inheritable genetics of a patient so that the children and grandchildren will have been edited?

[Jennifer Doudna]

Well, now you're talking about something that I think is really interesting and fundamental about a technology like crispr, which is that it enables making targeted changes in the DNA of an individual, as is being done currently for sickle cell treatments. But in principle, it could also be done in embryos, where it creates a change in DNA that can be passed on to future generations. We call that a heritable change. And to me, that's really kind of in a different category.

[Walter Isaacson]

One guy who has done it in China, He Zhuang Qi, who visited some of your seminars out at Cold Spring harbor, he's the only person who has crossed that line, right? Or the only person we know, that we know of. And even China punished him. It's like, okay, because you helped get a consensus around the world, let's not cross the line of inherited or heritable gene editing. Do you. Do you think that should tell me about that line and how it can hold?

[Jennifer Doudna]

Well, I think the current state of the field, and this is true even now, is that there's very little information about how genome editing would actually work in embryos, to the point where it's really not, I think, technically safe to use it in that setting. So many scientists think that it's irresponsible to proceed with that kind of an application until we have really vetted the technology and also determined under what circumstances and which conditions would it really be the right way to proceed.

[Walter Isaacson]

But in some ways, that begs the larger moral question, which is, suppose it was something you could technically do. As you can easily imagine that in five or 10 years, we'll be able to do it without, you know, mistakes or hallucinations, as we call them in AI. Well, actually, let me tell you a story. When I was doing it, the book about you and gene editing, there was a young kid. I'm blanking on his name. His picture is in the book. And he loved playing basketball, except for when he crumpled over on the floor because he had sickle cell.

[Jennifer Doudna]

David Sanchez.

[Walter Isaacson]

David Sanchez. And so he's working in the Bay Area being treated, and one of them says, you know, we'll be able to edit this out someday. In fact, we'll edit it out so that neither you nor your children or anybody, grandchildren will ever have it. He said, that's great. And then he comes back and he says, well, wait, shouldn't that be my child's decision? They said, well, didn't you hate to have it? He said, yeah, but there were things I learned, including resilience and getting up off the floor when I fell down, that maybe we should be careful about editing for future generations. So that seems to me the larger issue than can we technically get it right?

[Jennifer Doudna]

Yeah, I agree. It's a really moving section in the story of David. David. His story was told in the film Human Nature, a documentary. And it's a fascinating reflection that he has, even as a young boy, about what is it that truly makes us individuals, makes us who we are? And I think he, you know, really appreciated the fact that, you know, his disease had, you know, was a terrible, terrible disease. And I'm sure he wouldn't wish it on anyone. But he also reflected that it had helped to shape him as a. As a person and that he would be different without it. So, you know, it raises an interesting challenge.

[Walter Isaacson]

Yeah, but we've always had those. I mean, I'm not sure Jonas Salk or Sabin people would say, wait, if Franklin Roosevelt hadn't gotten polio, he would have remained an Upper east side playboy. So let's keep polio.

[Jennifer Doudna]

Interesting example.

[Walter Isaacson]

Yeah, it's from Doris Kearns Goodwin, who's one of my next interviews here, because she did the polio's effect on Franklin Roosevelt. But do you. Let's go back to sickle cell. You can change the letter so the cells aren't sickled in theory, I know we haven't done. In practice, you could probably change it so that the cells carry more oxygen rather than less more oxygen than on average. And you could edit so that your children would win the Olympics or be sprinters. Is that morally acceptable?

[Jennifer Doudna]

Well, let's just first point out that you could only do those things if you knew which genes to edit and which mutations to make. But if we say, for the sake of argument, suppose you did know those things, I think you're right. It brings up a very important question we all have to grapple with, because I think this technology will be capable of making those kinds of changes in embryos in the probably not distant future. And we have to decide is that, are we okay with that?

[Walter Isaacson]

And one of the things I admired about Jennifer and why I wanted to pick her as the subject, I didn't know you were going to win the Nobel Prize, which helped the book a bit, but was that once you do this and you have this tool, you start worrying about these questions and in the history of science, we have so many examples. Oppenheimer, the movie is somewhat about it, which is the Prometheus problem, and that we have snatched a technology from the gods, and who knows what we're going to do with it. And early on in biotechnology, I'll call it a bioengineering, there was a group called the Asilomar Group in California that said, okay, this could be dangerous. And they met a few times and said, we don't want government to regulate it. We don't want to let the genie out of the bottle. And they did that process. And what impressed me about you is that when you got this discovery and technology right, you almost replicated the Asilomar process. So you said, okay, let's try it again for this.

[Jennifer Doudna]

Well, I really admired that scientists in the 70s had grappled with these sort of fundamental ethical questions about biotechnology. In that case, they were looking at examples of modification of bugs that live, you know, bacteria that live in the human body, and wondering whether there could be health risks to making those kinds of modifications that had become possible. So we actually contacted Paul Berg and David Baltimore, two of the scientists who were some of the leaders of those original group discussions in the 1970s, and they came to an early conference we had in, I think it was 2014, to discuss the, you know, the ethics of CRISPR and how we should think about it and how we should proceed as a scientific community.

[Walter Isaacson]

And how did you enlist it? Because if it was only us scientists curtailing it, then we'd fall behind. It's like the AI argument. Let's not curtail it here because China will do it. How did you try to make it international?

[Jennifer Doudna]

Well, we reached out to scientists in other countries, including in China. We got the scientific academies involved. And this was, I think, really critical to bringing together a global community of people who could think together about how to proceed.

[Walter Isaacson]

And what lines have you sketched out or drawn on the use of this technology that have been agreed to or at least a consensus?

[Jennifer Doudna]

Well, I think one of the real challenges with something like this is that it's. I mean, you know, we didn't say this earlier, but maybe folks here understand this already. But, you know, the thing that's so powerful about CRISPR, really, is that it's not difficult to. And so that's meant that it could take off very quickly as a powerful tool. But the flip side is that it's kind of readily deployable for these other purposes. And in the case of the meeting that we had in California to discuss the early days of CRISPR and the ethics of it. We really wanted to make sure that scientists would get on board with the the responsibility that we thought we all had. And so our approach has been to publish articles about this, to get the World Health Organization involved in creating a registry where scientists can be very transparent about work that they're doing, and also to get the scientific journals involved in ensuring that work that gets submitted for publication is reviewed with a lens on ethics.

[Walter Isaacson]

Thanks.

[Evan Ratliff]

Coming up after a break, Isaacson Adowda discuss what it takes to keep doing scientific research in a fraught political moment and how AI and CRISPR are joining forces. Stay with us.

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[Walter Isaacson]

Lenovo.

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[Jennifer Doudna]

Limu is that guy with the binoculars.

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[Walter Isaacson]

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[Walter Isaacson]

How worried are you? Or is there a reason to worry about what's happening now in Washington, both with Robert Kennedy Jr. At HHS and the government in terms of. First of all, let's talk about regulations and science.

[Jennifer Doudna]

Well, it's, you know, it's an interesting thing. I mean, you know, there's kind of two sides to that coin. On the one hand, I think we appreciate the importance of regulations and especially when we think about approving, improving drugs that are going to be used in us or our kids. We want them to be safe. We want them to be effective. And that's the job of the Food and Drug administration in the U.S. the flip side is that if you have too many regulations or regulations that don't really make sense, then that can slow down the process. And I think we've all. I certainly have seen both sides of that. So it's a delicate balance. How do you get the regulations so that they do what you want them to do and protect us but not impede progress?

[Walter Isaacson]

And give me some examples where you've taken it from the lab to the bedside in a way, by creating commercial companies to develop drugs?

[Jennifer Doudna]

Well, this is the thing. I mean, companies play a very important role in that pipeline. Academic scientists are great at innovation. We love our students coming in with their ideas and having the freedom to pursue things. And that's really, I think, what gave rise to something like crispr. But when, when it comes to expanding on an idea to the point where it can be globally accessible, academic labs are really not appropriate for that. We don't have the funding to do it. We don't have the resources and the personnel to do it. This is where companies are necessary. I've long believed that there's a really important partnership between academics and companies, and we have to figure out how to forge that effectively.

[Walter Isaacson]

And Berkeley is very good at allowing people to commercialize and to start companies with the intellectual property, right? No.

[Evan Ratliff]

Okay.

[Walter Isaacson]

Not as good as Tulane. I mean, but yeah.

[Jennifer Doudna]

They could be better.

[Matt Rogers and Bowen Yang]

But you know how.

[Jennifer Doudna]

Well, I think there are a number of challenges. You know, as we just said, universities are not set up to be companies. And that means that intrinsically, and I'll just speak for my own institution, I don't know about Tulane. Tulane may be much better at this, but, you know, really figuring out, really figuring out how to foster that connection, how do you, for example, how do you train scientists that are coming out of academic labs that are trained as academics to be good business people? How do you do that? There's no sort of easy answer to that. How do you de risk an idea so that investors are now willing to put money into it where they think they're going to get a return? That's also not easy. So these are not unique to any one institution, of course, but this was part of the motivation for us to establish the innovative genomics institute 10 years ago, which is a partnership between different campuses of the University of California that's expressly focused on this kind of smooth pipeline between discovery and application.

[Walter Isaacson]

That's something that's happened in a few places over the past 50, 60 years. I mean, I teach history of technology course here, which is when MIT and Harvard resisted the commercialization of the things. Stanford University under Frederick Terman, who was the provost, encouraged graduate students, starting with Hewlett and Packard and ending with Larry Page and Sergey Brin, that if you had a good idea, form a company. To what extent do you think that process can be improved?

[Jennifer Doudna]

Well, again, I think that we need to do better. I'm speaking to myself here, really, we need to do better at giving our students the training that they need to be effective in business. One thing that's very interesting is that, and I see this in my own lab, that people that are coming out of our labs, some of them are very focused on the science and they want to stay that way. Others want to take a different lens to it. They are willing to or maybe even happy to let other people do the actual science. What they really want to do is they want to think about the business model around it. How do you expand it, how do you develop it in ways that will solve real world problems. And frankly, you need both.

[Walter Isaacson]

I ask all this because we are at Tulane trying a bio innovation zone, a two lane innovation institute. All of this is happening now. And when you discovered this, you had two or three really great graduates. I think Lucas was one of them. And you said, okay, we're going to just call the company Mammoth and we're going to make T shirts. And they knew how to form a company. Last time I was coming in from the San Francisco airport, there's a huge building that says Mammoth Pharmaceutical. So explain how you picked the graduate students and said you can form a company and I'll be, I guess, scientific advisor.

[Jennifer Doudna]

Well, they kind of are self selecting. These are often students who recognize that that's their interest and that's what they want to do. And I feel like my job is to help them get there. I love working with people in the lab, helping them figure out what they're really good at and then do more of that. In the case that you mentioned with Mammoth Biosciences, that was a wonderful situation where there were two graduate students in the lab, Lucas Harrington and Janice Chen, who were working together on a project. They both recognized that was an opportunity to commercialize it. They wanted to be part of that. And they teamed up with another, a third student coming out of Stanford. Maybe the only history of a Stanford.

[Walter Isaacson]

Berkeley partnership successful like Tulane, lsu. Can be done.

[Jennifer Doudna]

Can be done, but rare. Yeah. And so they started Mammoth Biosciences and they're going strong.

[Walter Isaacson]

Getting back to the policy challenges we have now. We talked a little bit about regulation and trying to get the balance right. The more pressing ones. I'll start. Well, there are two of them I can think of, but I'll start with this. NIH funding being cut radically and other NSF funding being cut. Is that destroying the seed corn for the future, inventions like crispr?

[Jennifer Doudna]

It's not a good idea. You know, I mean, thank you.

[Walter Isaacson]

You're not quite as forceful as Tony Fauci was. He used stronger language than not a good idea.

[Jennifer Doudna]

Well, let me expand. So you may appreciate that in the United States, we are a leader around the world right now in science and technology. Why is that? It's because taxpayer money for decades has gone into funding the kind of science that we're talking about here. Curiosity driven science that is asking questions about how nature works and then taking those key insights that come out of that kind of work and turning them into applications. Companies aren't going to do that. Why not? It's too risky. Companies are not going to be able to invest in the kind of curiosity driven science that does provide that pipeline, but does so in a way that is kind of open ended. And if we cut that off, I guarantee that we're going to see a big change not only in this country, but around the world. Because right now the United States really drives the discovery of all of the, not all, but many of the medicines that we take and the kinds of technologies that have had such a huge benefit.

[Walter Isaacson]

I would think that if you were an enemy of the United States and you wanted to destroy its future, one thing you would be doing is say, you know, they did the Internet, they did all these things. AI all because of these science grants. Even Larry Page and Sergey Brin are on National Science Foundation Grants when they were graduate students. And you'd say, let's pull all these away so that China can be doing it. Do you worry that competition, a country like China will end up being in the fore if we keep this path?

[Jennifer Doudna]

I not only worry about it, it's already happening. I mean, it's.

[Ryan Seacrest]

Oh, wow.

[Walter Isaacson]

Explain. Give me some examples.

[Jennifer Doudna]

Well, I think we're already seeing scientists being recruited to other countries. They've been very, very proactive already about reaching out, even to people in my lab, about job opportunities. We're seeing that some universities in the US are already cutting back on their graduate training programs due to NIH cuts or anticipated cuts. And it's not going to get better unless there's a real change in the approach in Washington.

[Walter Isaacson]

And one of the related things is this, I'll call it crackdown on visas. And people who are on student visas sometimes getting arrest. I mean, so having foreign students studying here, that's going to be harder for them. Have you seen any problems with that yet?

[Jennifer Doudna]

Well, you know, science is really international. And it's international not just in the sense that there are people all over the world working on scientific problems, but it's international here in the United States in the sense that we recruit many of our scientists and our trainees from other countries. Why is that? Well, again, it's because the US has been a real magnet for them. Right. It's attracted them to come here because of the wonderful opportunities that they have had. And if we stifle that, it's going to be a disaster.

[Walter Isaacson]

Have you seen stories of researchers who now are afraid because they're not. They're on visas that they may lose?

[Jennifer Doudna]

Well, sure. I think that's happening all over. And we're seeing some frightening examples of students even being pulled off the street, which is really shocking.

[Walter Isaacson]

And does that have a ripple effect even at Berkeley?

[Jennifer Doudna]

Oh, sure. I mean, I think it creates an atmosphere of fear.

[Walter Isaacson]

What would you do to try to make sure we became a magnet for the best around the world?

[Jennifer Doudna]

Became, you mean?

[Walter Isaacson]

Yeah, well, yeah. Regain. Make sure we stay a magnet.

[Jennifer Doudna]

Well, I wouldn't be proceeding the way we are currently as a country. I mean, I think we have to be welcoming to people from other countries. We have to be willing to support science with taxpayer funding in ways that have been so valuable in the past. I didn't mention before, Walter, but our very first grant that supported CRISPR research in my lab was actually from the National Science Foundation. The NSF supported our work long before anybody appreciated that there was going to be human health value to it.

[Walter Isaacson]

And they did that just out of curiosity. Yes, thank you.

[Jennifer Doudna]

Yes.

[Walter Isaacson]

Going back to Chris, when we talked about sickle cell, there's many other applications. Tell me in humans first. I know there's for agriculture, climate and other things, but in humans, how will it be applied? Maybe even in cancer research?

[Jennifer Doudna]

Right. Well, you know, I think one of the things that's very interesting about CRISPR is that as the first applications are coming to the fore, we mentioned sickle cell disease, but there are also several therapies for liver diseases that are already in the last sort of third phase of clinical trial testing that are looking very promising. These are all for genetic diseases that are relatively rare in the population. But I think that what we're going to see over the next decade of CRISPR is increasingly this technology being deployed to prevent disease and to cure diseases that affect many people. You mentioned cancer. I think there we're looking at opportunities with, with programming the immune system in ways that allow targeted cancer therapies and also thinking about ways that we can provide preventative changes in DNA that will protect us from disease.

[Walter Isaacson]

Are you suggesting something akin to a cancer vaccine?

[Jennifer Doudna]

I think that's a possibility, yeah.

[Walter Isaacson]

And how would that work?

[Jennifer Doudna]

Well, the idea would be to program immune cells in a person so that those cells could find and destroy tumor cells before they form a tumor or before they metastasize.

[Walter Isaacson]

Amazing.

[Jennifer Doudna]

Yeah.

[Walter Isaacson]

And explain. It works, let's say messenger RNA and guide rna. The guide RNA is what you did for gene editing. Messenger RNA is what we use for the vaccines. But it tends to tell ourselves make this protein or something. What are the implications of that? Of saying, okay, let's code our molecules the way we code microchips?

[Jennifer Doudna]

Well, what's interesting about using RNA to do that kind of therapy is that it's a transient thing. That means that it happens briefly. And so with crispr, if we were to use MRNA for example, just to as was used in the COVID vaccine to deliver CRISPR molecules, then you could imagine a short term production of the genome editing molecules that could make targeted changes and then go away, which is kind of ideal. So then you'd have the protective change made, the editor goes away and a lasting treatment.

[Walter Isaacson]

But people looking at the MRNA vaccines, who are the anti vax people and whatever, and some of them in government now have been implying that messenger RNA or some guided thing like that will totally change your DNA and is a permanent thing. How do you. How could one get across the fact that no RNA doesn't Even go into the nucleus of the cell. If it's building a protein, it just programs the outer. I mean, it's complicated to make people believe that they're not getting reprogrammed.

[Jennifer Doudna]

I think this is where we scientists have to do better at explaining our findings. Right now, there's zero evidence that there's any permanent changes that are made with MRNA use. So there's just no data that would support that conclusion.

[Walter Isaacson]

Yeah, you just said something interesting to me, which is we scientists are not good at. I mean, one of the reasons I wrote this book and others do is. Wait, let's explain. Scientists used to be better at being public intellectuals, explaining from the old days of Carl, Carl Sagan and others, what should science, instead of blaming it on the people who don't get it, to what extent are scientists. Should they be doing more to communicate?

[Jennifer Doudna]

Oh, it's critical. I think it's incredibly important. I tell my students this regularly, and I'm sure you do, too, in your class. Right. You really have to. We have to be educating students to be not only great at what they do in the lab, but also thinking about how they explain the importance of what they do. I tell my students, I want you to be able to say in one sentence to your grandmother, you know, why you're doing what you do and why it matters.

[Walter Isaacson]

In one sentence to your grandmother, what are you doing now, and why does it matter?

[Jennifer Doudna]

Thank you. Rewriting the code of life to protect us from disease.

[Walter Isaacson]

And you're doing it good.

[Jennifer Doudna]

I do. Okay.

[Walter Isaacson]

And say, and what about rewriting it to protect us from climate change?

[Jennifer Doudna]

Well, I'd like to do that, too.

[Walter Isaacson]

How?

[Jennifer Doudna]

Well, you know, here's the thing. So, you know, CRISPR is a powerful technology in part because it works across all of biology. We know that it works in bacteria, but it also works in humans, as we've been discussing, and it works in plants because, you know, fundamentally, they are all using DNA to encode their properties. And so we realized in thinking about that fact that CRISPR could actually be used to make changes in plants, but also, frankly, in the microbes that support agriculture that will be beneficial in terms of protecting the climate. So I'll give you an example. Cattle are harboring microbes in their gut, in their rumen, that are important for digestion, but they also produce a lot of methane. Methane is one of the most powerful greenhouse gases. And it turns out that when you look at methane produced from animal farming around the world, it's about a third of the global methane that's released around the world. Imagine that we could reprogram those microbes to not produce methane and in fact to use that energy to make more meat or more milk. Great for farmers, great economically and the right thing to do for the climate. So that's what we're working on.

[Walter Isaacson]

And tell me how close you are and how that would happen.

[Jennifer Doudna]

Well, this is where we brought on board a third partner, campus partner at the Innovative Genomics Institute, University of California, Davis, one of the world's great agricultural universities, with experts working on this methane problem in cattle. And they had shown that you could change the cow diet to control methane product. But it was clearly not an affordable or sustainable solution to the problem. So we got together and we said, look, let's take your knowledge of cattle and rumen microbe biology and combine it with the CRISPR technology for reprogramming and make changes in the microbiome of cattle that could be permanent and could reduce the release of methane. And that's what we're working on right now.

[Walter Isaacson]

Now, how do you feel in this current climate, not just the politics in Washington, about saying, all right, we're going to use RNA guided things to edit the biomes of our cows, etc. Do you think there would be a backlash or you're going to have trouble getting people to understand that it seems like it would be demonized right away.

[Jennifer Doudna]

Well, I think we have to be proactive. I mean, we have a big public impact team at the Innovative Genomics Institute to work on the communications about this, to explain the technology, to show the data that we have for the technology and to really invite a partnership. You know, you talked about scientists needing to be better kind of ambassadors. And I think that has to be not through lecturing, it has to be through reality, partnership with our communities.

[Walter Isaacson]

I'm going to talk about myself for a second. What is it like? I mean, I had to trail you for a couple of years. I was in your lab all the time, in your hair all the time, so to speak, rubber gloves, trying to learn how to do things. What's it like to have books and other things written about you? Does that you're not an out there person trying to get public?

[Jennifer Doudna]

Well, I'm still stunned that it got done. Do you remember, Walter, that you called me? So it's kind of an interesting backstory because Walter and I had met at the Aspen Ideas Festival where we did a chat like this a few generations ago now it feels like. And Walter, a few months later called me up one day and he said, I'm thinking about writing a book. And I said, oh, that sounds great. You're always writing books. And he said, no, I mean about you. And I said, well, that'll never happen. I couldn't imagine that it would come to pass. But, you know, Walter is very, very persistent. And one thing led to another. And I think what's been great about the book, Walter, is that I think you did a wonderful job of telling a compelling story. It's kind of a bit of a. Could be its home, but it's not. It's a kind of a page turner, actually. And you did a great job of interviewing a lot of the people who were involved in the story, telling their sides of it, talking about the way that science really works, the way it really gets done. And there's competition, there's collaboration that both plays into the things that actually happen in the laboratory. So I think it's a great way for people to. To try to really understand the science that goes into a new technology that you might read headlines about, but you don't have any idea where it emerged from.

[Walter Isaacson]

I mean, you have that in history with great advances in science. The double helix being. Whatever you may think of Jim Watson, just a wonderfully written book. I mean, it is colorful, even if it's maybe too colorful at times. Do you see a role at igi, Berkeley, Tulane, whatever it may be, of just training science communicators, not people going to be great scientists. But when people ask me, how do I go into journalism, whatever, I say it's a tough time to go into journalism, but pick a particular field, like maybe science. Do you think Berkeley and others should have a science communication program?

[Jennifer Doudna]

I do. I think that's very important. I also think that it's important to encourage people that. That we're coming into contact with to pursue those ideas. I think that one example from my own lab is a scientist named Sam Sternberg, who was a former graduate student. You know, Sam. You've interviewed Sam. And when Sam was finishing up his PhD, he's a wonderful scientist, incredibly talented. I asked him, what do you want to do next in your career? And he said, well, you know what? I think I want to write a book. And I said, really? You want to write a book? And he said, yeah, I want to write a book about the work that went into the discovery of crispr, because I've lived through it in your lab. And I think it's just an extraordinary story. And so, again, I sort of thought, well, that'll probably not happen. But it did you know, he did.

[Walter Isaacson]

It'S called a crack in creation and you should buy it, right? Or no, you're talking about a crack in creation. Yeah.

[Jennifer Doudna]

And so he took a year off from his research and he spent time, hold up, you know, writing this story. And it was a struggle. I mean writing is tough, you know.

[Walter Isaacson]

And editing genes is tough. Writing ain't that hard. I've done both.

[Jennifer Doudna]

I think writing is very. I've done both too. And it's. I think writing is very hard either way.

[Walter Isaacson]

But I did edit, I think it was human kidney cells, right?

[Jennifer Doudna]

Yes, you did.

[Walter Isaacson]

And I was able to edit in her lab these cells so that they would phosphoresce or glow in the dark. As I'm not a scientist and I thought, okay, I'm now Dr. Frankenstein. And they made sure that we poured large amounts of chlorine and killed it. So it's a type of thing though it would be better if labs like yours or here or whatever could say to kids, come in and just go to the bench and have a pipette.

[Jennifer Doudna]

And a test tube testing experience. Maybe like you said, they don't have to professional scientists in the future, but understanding a little bit about how science actually works, I think it's very valuable. And then communicating that to people is critical.

[Walter Isaacson]

Yeah, we have an anti science movement seeming to happen now. But it also comes at a time when humanists are intimidated by science. There's a two cultures system that been written about. How important is it to sort of connect the sciences and the humanities?

[Jennifer Doudna]

I think it's very important again for the same reasons. I think these are fundamental ideas that we're all grappling with. How do we use technologies? And we haven't brought up AI yet. But artificial intelligence I think is the same kind of thing where it's powerful, it's complicated really. Understanding how these models, like large language models are actually working is non trivial. And then to evaluate, you know, what's the safety of these things, what's the appropriate way to regulate them. These are non trivial things to figure out. And so I just think that it's going to require a better effort between scientists and technologists and then the rest of us to work that out.

[Walter Isaacson]

But I feel that humanists who care about the morale, they're going to be left out of the equation if they don't make the effort to learn some of the science. That if you're clueless about the science, it's going to be hard to discuss should we do heritable gene editing and.

[Jennifer Doudna]

That'S why I love that you asked me if you could come to the lab and work with crispr. It was great.

[Walter Isaacson]

The two great historic advances of our time in science. Just like 100 years ago was the age of electricity and then the digital revolution revolution. We're seeing two revolutions happen at once that I think are going to be the most transformative of the past 500 years. The life sciences revolution, meaning gene editing at the core, and the AI revolution, meaning artificial intelligence. We saw the Nobel Prize this year being awarded both in physics and in chemistry to AI because that combination. Tell me what happens in your lab and your work and in your, your thought when you combine the power of the AI revolution to the power of the genetic revolution.

[Jennifer Doudna]

Well, when the work was done, that was recognized by the chemistry Nobel this year, which is a program called AlphaFold that allows prediction of protein 3 dimensional structures in a very accurate way. Our lab and many, many others began using it almost immediately because it instantly provides a tool that we can use to predict the functions of proteins, how they might interact with other molecules. And that's very valuable. It used to be incredibly time consuming to work out individual shapes of proteins experimentally. And we still do that, but we don't have to do it nearly to the extent that was required previously. As a result, it accelerates the pace of science, and we're seeing this more and more with other kinds of, of AI driven approaches in technology approaches, is that we can do experiments faster, we can increasingly predict the right experiments to do and not waste time on the others. And I think we're just going to continue to see this acceleration of the pace of discovery. It's very, very exciting, but it's also, it's a little bit scary too.

[Walter Isaacson]

Give me a very specific concrete way we get our heads around and maybe take vaccine where, where you use AI to totally say, handle a huge database that humans could never have coped with and discover something that could be a vaccine.

[Jennifer Doudna]

Well, it means that you can quickly evaluate all the molecules that are being produced by a virus or a bacterium that's infectious and try to figure out what are the ways to neutralize it.

[Walter Isaacson]

And how might it work with cancer or something?

[Jennifer Doudna]

Well, similarly with cancer, same thing. Cancer cells often produce molecules on their surface that are not found on normal tissues. So imagine that you could figure out what those are and what they look like and then how to target them.

[Walter Isaacson]

One of the problems with CRISPR is that it costs a whole lot. I mean, doing sickle cell, I mean it's millions. So you can't really do it. What is the reason the cost is so high? And what could you do with delivery systems to get that cost down?

[Jennifer Doudna]

Yeah, thanks for bringing that up, because that's a very important point. So. Right. A drug, Casgevi, that's approved by the FDA we mentioned earlier for sickle cell disease. And it's extraordinary. I've met one of the patients who was treated in the first trial using that therapy, and it's completely changed her life in a very positive way. So why isn't everybody with sickle cell disease able to get this if they want it? And the reason, at least in part, is the cost. So it's about $2 million a patient right now for this therapeutic. Yeah. Not good. And why is that? Well, it's again, in large part, it's for technical reasons. It's because it's not easy to get those genome editors into the cells that need editing, namely the cells in the bone marrow that are the source of our blood supply in our bodies. Imagine that you had a way to do that kind of targeted delivery into blood stem cells in the bone marrow by a simple injection, or even maybe someday it's a pill that somebody could take that would be incredibly valuable and we change the whole field. And it would also make it possible to use CRISPR for lots of other types of diseases. So that's really one of the core mission goals of the IGI, is to figure out how to change the. The technology around genome editing delivery so those kinds of applications become possible.

[Walter Isaacson]

So, final question. You're at Pomona College, you're thinking of being a French teacher, maybe, but you're also holding the chemistry things, and it's kind of fascinating you and you figure out a path that takes you to the Nobel Prize. For my students here, what should they be doing that will get them, if not a path to a Nobel, a path to helping our society?

[Jennifer Doudna]

Well, all I can say is when I asked my French teacher about switching my major from chemistry to French, she said, no, stay with chemistry. So it's probably good advice, but I always tell my students, you have to figure out what you're really passionate about and pursue it just sort of doggedly and not be dissuaded by naysayers. You have to be able to identify what you really want to spend your time on and then go after it wholeheartedly. And I really see this over and over in my own lab, is that when students do that, they are successful.

[Walter Isaacson]

Jennifer Doudna Melci Bohto.

[Evan Ratliff]

On crispr, the Story of Jennifer Doudna is a production of Kaleidoscope and I Heart. This show is based on the writing and reporting of Walter Isaacson. It's hosted by me, Evan Ratliff and produced by Adriana Tapia with assistance from Alex Zonneveld. It was mixed by Kyle Murdoch and our studio engineer was Thomas Walsh. Our executive producers are Kate Osborne and Mangashti Tigdor from Kaleidoscope and Katrina Norvell from iheart Podcasts. If you enjoy hearing stories about visionaries in science and technology, check out our other seasons based on the biographies that Walter Isaacson has written on Musk for an intimate dive into all places facets of Elon Musk and on Benjamin Franklin to understand how his scientific curiosity shapes society as we know it. Thank you for listening.

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[Jennifer Doudna]

Dad, the cousins in Mexico have a surprise for you.

[Walter Isaacson]

You.

[Jennifer Doudna]

And enjoy the gift of staying connected. Switch and start saving today. Get four Samsung Galaxy S25 phones with Galaxy AI on us and four lines for just 25 bucks per line plus non stop talk, text and data between us and Mexico. Visit a store t mobile.com or call 1-800-T-Mobile- 1-800-T MOBILE. See details@t mobile.com this is an iHeart podcast.