ON CRISPR Episode 2: The Discovery

Podcast: ON CRISPR: The Story of Jennifer Doudna with Walter Isaacson
Host: iHeartPodcasts and Kaleidoscope
Date: September 17, 2025

Episode Overview

This episode delves deep into the untidy, competitive, and collaborative origins of the landmark CRISPR gene-editing technology. With Walter Isaacson and host Evan Ratliff, listeners are taken from obscure beginnings in salt ponds in Spain to the heated academic races in top U.S. and European labs. The central theme: how curiosity, teamwork, and competition—and the stories of a cast of unexpectedly intertwined scientists—drove the revolutionary discovery that now enables us to edit genes as easily as text.

Key Discussion Points & Insights

1. The Serendipitous Discovery of CRISPR (02:46–06:23)

• Francisco Mojica's Obsession
  • Mojica, a Spanish microbiologist, studies salty ponds filled with archaea. He stumbles upon puzzling repeated sequences in bacterial DNA, initially believing it's a mistake, akin to "typing a story in Microsoft Word and the paragraph keeps repeating" (03:43, Walter Isaacson).
  • Palindromic repeats intrigue him, and his curiosity only grows when he learns, via library research, that a Japanese scientist, Yoshizumi Ishino, has observed similar repeats (04:25).
  • Mojica coins the term "CRISPR" simply because the name feels “memorable, fun, not intimidating…makes it look futuristic” (05:46, Walter Isaacson).
  • "He's the guy who first understands that bacteria have these repeated sequences and he names them, but nobody knows why they exist. And that's when the hunt begins." (06:17, Walter Isaacson).

2. Real-World Importance Emerges through Yogurt Science (08:11–10:58)

• A Yogurt Factory Problem Solved
  • French food company Danisco, with scientists Rodolphe Barrangou and Philippe Horvath, discovers that these CRISPR sequences contain genetic “mugshots” of viruses that attack bacteria. This acts as an adaptive immune system for bacteria, saving yogurt and cheese from viral attacks (09:06).
  • "It's an adaptive immune system against viruses, which…was quite useful in saving the yogurt industry. And…understanding an adaptive immune system that could fight off viruses…came in pretty handy for humans later on." (10:53, Walter Isaacson).

3. Jennifer Doudna Enters the CRISPR Story (11:17–14:29)

• A Meeting of Brains at Berkeley
  • Gillian Banfield, a microbiologist at Berkeley, connects with Jennifer Doudna, leading to their collaboration. Banfield studies bacteria from exotic locations and finds CRISPR, while Doudna is the RNA expert (11:38).
  • Their meeting at the "Free Speech Cafe" symbolizes not just the beginning of a long partnership but the necessary merging of microbiology and biochemistry (12:06–12:45).
  • "You needed combination of biochemistry and microbiology or biology of small things to make this work." (12:51, Walter Isaacson).

4. The Realities of Laboratory Life (14:39–16:32)

• Inside Doudna’s Lab
  • Walter Isaacson describes the physical and intellectual environment of a modern lab—test tubes, pipettes, and serendipitous problem-solving.
  • Doudna’s go-to investigative secrets: “What’s the RNA doing?” and looking for the right enzyme: “Those are the two keys when in doubt.” (16:20, Walter Isaacson).

5. Teamwork, Competition, and Conferences (16:40–19:21)

• The Power of Collaboration
  • The CRISPR conference at Berkeley, initiated by yogurt scientists and attended by early researchers like Mojica, fosters sharing and innovation: “Science and discovery is a team sport and conferences really matter...go to Alice Waters restaurant near Berkeley and sit upstairs and compare notes.” (16:54, Walter Isaacson).
  • Conferences spark key ideas: "We talk about enzymes being a protein that sparks things that are a catalyst. And in some ways, these conferences, these are catalysts that spark ideas." (19:00, Walter Isaacson).

6. Doudna’s Personal and Professional Turning Point (24:30–26:45)

• A Midlife Crisis and a Return to Science
  • Despite excitement, Doudna feels lost, considers leaving academia for Genentech, but ultimately returns after a period of depression and self-doubt: “She realizes she's made a big mistake, that she loves having graduate students. She loves the research, the hunt, the discovery.” (25:20, Walter Isaacson).

7. Spark of Partnership: Doudna and Charpentier (26:45–28:35)

• The Puerto Rico Meeting
  • Doudna meets French scientist Emmanuelle Charpentier — both fascinated with RNA mechanisms (27:02–27:47).
  • The partnership is “a perfect combination”, as Doudna jokes, “I almost became a French teacher...you’re that person, but you’re a scientist.” (27:41, Walter Isaacson).

8. The Race to Understand and Engineer CRISPR (28:35–34:47)

• Breaking Down the CRISPR Mechanism
  • Doudna, Charpentier, and their students discover roles for two messages: guide RNA (for targeting) and tracer RNA (for structure). They engineer a simplified system—a breakthrough that moved from basic science to an invention and patentable tool (29:10–31:57).
  • Competition becomes fierce, with labs worldwide vying to publish and patent. The "drama in the tracer RNA" is, as Evan Ratliff says, surprisingly compelling (31:57).

9. Publishing Breakthroughs and the Meaning of "Discovery" (34:47–36:25)

• The Seminal Paper & Nod to History
  • At a 2012 conference, Doudna and Charpentier’s teams rush to submit their paper describing "genetic scissors" (CRISPR-Cas9), paralleling Watson and Crick’s landmark DNA paper.
  • Memorable moment: “It's not escaped our notice that this could become a tool to edit our DNA.” (35:50, Isaacson, referencing their Science paper’s conclusion).

10. The Next Phase: A Race for Application (36:51–37:16)

• The Competitive Edge
  • MIT-Harvard’s Feng Zhang emerges as a rival. What began as open collaboration becomes close-lipped as stakes (Nobel Prize, patents, recognition, and fortunes) rise (36:51).
  • “The stakes are too high and they all become more secretive and more competitive.” (37:16, Walter Isaacson).

Notable Quotes & Memorable Moments

• “It's like if you type a story in an old version of Microsoft Word and the paragraph keeps repeating, you think, well, I didn't do that, that's a mistake.”
  (03:43, Walter Isaacson, on Mojica’s first observation)
• “It's an adaptive immune system against viruses, which...was quite useful in saving the yogurt industry. And...came in pretty handy for humans later on.”
  (10:53, Walter Isaacson)
• "You needed combination of biochemistry and microbiology...to make this work."
  (12:51, Walter Isaacson)
• "When somebody's doing a big experiment and they can't figure out what's happening, she'll just say, 'what's the RNA doing?' And she said, that's always a clue that opens things up."
  (16:10, Walter Isaacson, on Doudna’s lab wisdom)
• “Science and discovery is a team sport and conferences really matter...”
  (16:54, Walter Isaacson)
• “She realizes she's made a big mistake, that she loves having graduate students. She loves the research, the hunt, the discovery.”
  (25:20, Walter Isaacson, on Doudna’s return to academia)
• “It's not escaped our notice that this could become a tool to edit our DNA.”
  (35:50, Walter Isaacson, paraphrasing Doudna/Charpentier’s game-changing line)

Key Timestamps

• 02:46 – Mojica's initial discovery in salt ponds
• 05:46 – Origin of the name "CRISPR"
• 09:06 – CRISPR’s real-world use in the yogurt industry
• 11:38 – Doudna and Banfield’s first meeting at Berkeley
• 14:39 – Inside Jennifer Doudna’s lab
• 16:54 – The importance of scientific conferences
• 24:30 – Doudna's career crisis and move to Genentech
• 26:45 – Doudna and Charpentier meet in Puerto Rico
• 29:10 – Discovery and engineering of the guide/tracer RNA
• 35:50 – The “it’s not escaped our notice” breakthrough

Episode Flow & Takeaways

The episode effectively weaves scientific technical detail with the human drive for understanding—and recognition. Isaacson and Ratliff structure the narrative around pivotal people, places, and conversations, illuminating how dogged curiosity, teamwork, rivalry, and personal struggle together ignite revolutions in science. As the episode closes, the stage is set for the next chapter: turning the CRISPR discovery into the gene-editing tool that would forever change biology, medicine, and the future of humankind.

For science enthusiasts and newcomers alike, this episode offers both clarity and dramatic pacing, showing not only how ideas ripen, but how careers, personalities, and the thrill of the chase shape technological history.