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

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.

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)

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)

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

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.

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.