ON CRISPR Episode 2: The Discovery

Summary

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

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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.

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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).

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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)

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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

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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.

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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.

Transcript

[Narrator/Host]

This is an iHeart podcast. The murder of an 18 year old girl in Graves County, Kentucky went unsolved for years until a local housewife, a journalist and a handful of girls came forward with a story.

[Walter Isaacson]

America, y' all better wake the hell up. Bad things happens to good people in small towns.

[Narrator/Host]

Listen to Graves county on the iHeartRadio app, Apple Podcasts or wherever you get your podcast and to binge the entire season ad free. Subscribe to Lava for Good plus on Apple Podcasts.

[Evan Ratliff]

Sacred Scandal is back, the hit true crime podcast that uncovers hidden truths and shattered faith. For 19 years, Elena Sada was a nun for the Legion of Christ. This season she's telling her story.

[Narrator/Host]

When I first joined the Legion of Christ, I felt chosen. I was 19 years old when Martial Macel, the leader of the Legionaries, looked.

[Evan Ratliff]

Me in the eye and told me.

[Narrator/Host]

I had a calling.

[Evan Ratliff]

Surviving meant hiding. Escaping took courage. Risking everything to tell her truth. Listen to Sacred the Many secrets of Martial Maciel on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

[Narrator/Host]

In early 1988, federal agents raced to track down the gang they suspect of importing millions of dollars worth of heroin into New York from Asia.

[Walter Isaacson]

Had 30 agents ready to go with shotguns and rifles and you name it.

[Narrator/Host]

Five, six white people pushed me in the car. I'm going, what the hell?

[Walter Isaacson]

Basically your stay at home moms were.

[Evan Ratliff]

Picking up these large amounts of heroin.

[Walter Isaacson]

All you gotta do is receive the package. Don't have to open it, just accept it. She was very upset, crying. Once I saw the gun, I tried to take his hand and I saw the flash of light.

[Narrator/Host]

Listen to the Chinatown sting on the iHeartRadio app, Apple Podcasts, or anywhere you get your podcasts. Hey guys, it's Stephanie, Beatriz and Melissa Fumero. And this is more better. We are jumping right in and ready to hear from you, your thoughts, your questions, your feelings about socks with sandals. And we're ready to share some possibly questionable advice. And hot takes. God, that sucks so hard though. I'm so sorry. Can you out pet them? Can you match their pettiness for funsies? Yeah, all the things. Because aren't we all trying to get a little more better? Listen to more better on the iHeartRadio app, Apple podcast or wherever you get your podcasts. Kaleidoscope.

[Walter Isaacson]

He's looking at bacteria in very, very salty ponds. And he notices something when he's sequencing the genes because this is getting in the late 1990s, when we finally can gene sequence. But it's hard.

[Evan Ratliff]

In science, sometimes a world changing breakthrough arrives at the end of a long chain of discovery. A chain that starts with an obscure or even trivial seeming observation. So it was that in 1990, a young microbiologist named Francisco Mojica began working on his PhD in his native city of Alicante on the Mediterranean coast of Spain. A medieval port with narrow streets, colorfully painted houses, and sweeping views across the sea to Algiers, Alicante was also the home to a collection of salty ponds 10 times saltier than the ocean. Mojica's research focused on the genomes of tiny bacteria like organisms thriving in the ponds called archaeae.

[Walter Isaacson]

He keeps seeing these repeated sequences in the genes of bacteria, and they're clustered repeated sequences. And he thinks he's made a mistake. 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. But as he keeps testing it out, he sees these repeats.

[Evan Ratliff]

These repeats are also read the same forwards and backwards, like palindromes. Walter Isaacson writes, they look like tiny knots in a string of otherwise regular genetic rope. And Mojica had no idea what they were. Isaacson says that only got him more curious.

[Walter Isaacson]

He goes to the library. This is before you could Google things, before there's a database. So he goes to the library and looks up indexes. And a Japanese scientist had seen this in a bacteria. And so soon you have a few scientists saying, well, why are there these things?

[Evan Ratliff]

The Japanese scientist who had also noticed these clustered sequences was Yoshizumi Ishino. A few years before, Mojika Ishino had found the same clusters in a very different type of bacteria. In his paper on the discovery, he wrote that the biological significance of these sequences is not known. Still, the fact that both researchers had found the same pattern in extremely different organisms convinced Mojica that these clusters might have an important purpose. For years he kept experimenting with them, leading a growing international network of scientists interested in figuring out their significance.

[Walter Isaacson]

And the first thing they do is they try to figure out a name for it. And it's Francesco. Mojica, driving back from his wife, was on the beach and he was bored with the beach, goes back to his lab and he says, well, they're clustered repeated sequences.

[Evan Ratliff]

Mojica's thesis advisor had suggested the name tandem repeats. Not exactly the catchiest. A colleague in the Netherlands suggested direct repeats, but that wasn't quite it either. So Mojica kept thinking and he comes.

[Walter Isaacson]

Up with the name crispr. And he said because it's a memorable, fun name, it's not intimidating. And he then back engineers it. I think it's clustered, repeated, interspaced, palindropic, repeated sequence, whatever it may be. But it was called CRISPR just because he liked the name crispr. And it doesn't have an E, it's CRISPR without an E. So it makes it look futuristic. So 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.

[Evan Ratliff]

Mojica had no way of knowing then, but this tiny palindrome gene he'd found inside a salt loving bacteria would become the tiny engine driving a new revolution in gene editing. I'm Evan Ratliff and this is on CRISPR, the story of Jennifer Doudna. Episode 2 CRISPR. It goes back to that sort of passion and obsession over these what seem like tiny questions to us. A guy in salt ponds who's just obsessed with the bacteria that live there, which kind of goes back to the sleeping grass and really wanting to know. But this guy has no idea where this discovery is going to lead.

[Walter Isaacson]

This is the big deal, which is it's pure curiosity about some quirk of nature. And you have no idea that is going to lead to a tool to fight viruses, it's going to lead to a tool to edit genes or anything else. You're just curious, why did Nature do this?

[Evan Ratliff]

And apparently the major journals also didn't know where it would lead since his findings were initially rejected.

[Walter Isaacson]

He's a sort of unknown junior scientist, I think, and aliante Spain. And so one of the problems is you can't really make a discovery of science unless you can publish it. I mean, that's the way we put the stamp on it. And he's having trouble getting this published in a journal. And so are other people who are looking at CRISPR because like, okay, fine. And even his advisors at the university is like, fine, fine, fine. You see bacteria repeat themselves a few times, but now go on to something that's important.

[Evan Ratliff]

But Mojica suspected that there had to be a reason for these clustered sequences to keep showing up. And Isaacson says it was an instinct driven by a fundamental piece of knowledge.

[Walter Isaacson]

Nature loves simplicity. It's not going to have some complexity of repeated sequences unless there's a reason. I mean, bacteria don't have that much genetic material, so you don't want to waste it repeating yourself. So there Must be a reason that these things exist, as these basic scientists like Francisco Mojica are doing this out of pure curiosity. You have two food scientists who work for Danisko, one of these huge French food companies. It's Rodolphe Barangu and Philippe Horvath. They're both French, but one of them has moved to North Carolina to study food. And I'm thinking, this is the only guy I ever met who move from Paris to North Carolina to study food. And they make starters, cultures for yogurt and cheese. And the starter cultures are bacteria. And one problem they have is that viruses attack bacteria. You think we got a problem with viruses, man? For 2 billion years or so, bacteria have been fighting off viruses. It's the biggest battle on this planet. It's ongoing. And so these yogurt cultures are getting messed up by viruses. And you have these two scientists who are sequencing the genetic code. And the cool thing about Danisko is it's got a whole database of every culture they've had going back to 1980 or so. And so you can look at how the DNA changes. And they discover that the CRISPR sequences, or what's in between the CRISPR sequences, are mug shots of the genetic code of some viruses that attack them. And every time a new virus attacks, and every year or two or three, the bacteria that survive have some of that genetic code in these repeated sequences and clusters. And they realized this is a way that bacteria have a mug shot to know if there's a dangerous virus coming in and how will they kill, meant that in the future, the bacteria would know how to ward off those virus. So it was an adaptive immune system against viruses, which may seem pretty technical, but it was quite useful in saving the yogurt industry. And by the way, we didn't know it at the time, but understanding an adaptive immune system that could fight off viruses that came in pretty handy for humans later on.

[Evan Ratliff]

And that in and of itself, if you just told that story, that's a fascinating bit of science.

[Walter Isaacson]

It's a huge, huge thing for Danisko and for anybody who eats yogurt and eats cheese, we'd be in trouble every year. Just like maybe we have trouble with bird flu every now and then. We can't get get eggs. We'd have trouble with yogurt and cheese if the entire billion dollar industry of starter cultures was wiped out.

[Evan Ratliff]

So at this point in the story, we sort of know what CRISPR is, and we know what it does, but not how. And so that's when Jennifer Doudna reenters the picture for us in that she has a conversation with one of her colleagues that leads her down the road to crispr, because she wasn't studying CRISPR when this started, right.

[Walter Isaacson]

Jennifer Dadna had a colleague at Berkeley named Gillian Banfield. They hadn't really met each other because Berkeley is so big, but Gillian Banfield was just looking at bacteria from weird places like Yellowstone and others and noticing this crispr. And they're trying to say, how does it work? So she looks through the database at Berkeley for anybody who is studying RNA and RNA interference. And who pops up, of course, is Jennifer Doudna, because she's the RNA expert at Berkeley. And Jennifer was a biochemist, in other words, looking at the chemistry of how biology works. And there's a subtle difference because Gillian Banfield was a microbiologist, meaning she looked at small organisms. She didn't look at test tubes. She looked at real organisms and tried to figure out they work. So you needed combination of biochemistry and microbiology or biology of small things to make this work. They met one afternoon at the Free Speech Cafe. I love the name of it, because those of us who are old enough to remember Berkeley had a great free speech movement. And so there's a cafe right as you come onto the campus near the library. And Gillian Banfield has been studying CRISPR and trying to figure out, we know it tries to stop viruses that attack bacteria, but how does he do it? What's the mechanism? And she brings all these printouts and they talk about it, and Jennifer gets it and says, I'm not sure it's RNA interference, but there's a mechanism that these CRISPR sequences in the bacteria somehow another. They have a mechanism that attacks viruses.

[Evan Ratliff]

And she starts her lab looking into that question. So she's intrigued enough to get her lab looking into it, right?

[Walter Isaacson]

She kind of is not absolutely sure, but she likes Gillian Banfield when they meet at the cafe. And it's like, you're really. You're passionate about your little bacteria you found in copper mine wastelands and something that have these repeated sequences. And yeah, I've now read the papers and maybe. But she said, I don't think I have anybody in my lab who can do it. And that's when a guy, Blake Wiedenheff, walks into Jennifer's lab and wants a job. And Jennifer's interviewing, and he's one of those guys who grew up near Yellowstone, and he loves collecting bacteria. And he's sort of a microbiologist, too. And he says, I'm interested in crispr. And Jennifer says, bingo. Okay, I got this project we're going to work on. So it's a lot of serendipity. There's.

[Evan Ratliff]

Isaacson had the chance to visit Doudna's lab, and he told me that what he saw helped him understand her process when it came to translating her initial curiosity into research.

[Walter Isaacson]

I never actually knew what a scientist did every day. I mean, I knew what scientists were, but what did they do, like at 2 in the afternoon, 3 in the. And especially lab scientists. And so I got to go to the lab at Berkeley where Jennifer Doudna works. One of the things is there's long benches. It's called being a bench scientist, where you're seating there next to each other, and you have a sort of workspace that sometimes has a hood that ventilates things. And you've got test tubes and pipettes. And you have a lab director like a Jennifer Doudna, who comes up with the ideas of, what are we going to test next? Let's try putting a little bit of RNA into this mixture in this test tube and see what happens. She's got an office. She's looking at all their results, but also she's putting on the white gown and she's putting on the latex gloves and going from station to station, bench to bench, say, what are you doing with that experiment? And she had certain secrets she sometimes used. She said one of them is rna and says, 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. The other she said, was enzymes. They spark an action. They spark a neuron or a muscle twitching. And it is something that instigates things. It's like a match or a spark that allows something to happen. And she says the two things to remember when you're doing science inside of a cell or microbiology is enzymes. Rna. Those are the two keys, when in doubt.

[Evan Ratliff]

Enzymes and rna, you know, they start on this journey. They're trying to figure out how does CRISPR work, how does it do what we sort of know that it does.

[Walter Isaacson]

And.

[Evan Ratliff]

And one of the first things they do along the way is organize a conference and bring in all these other people that study it. And you could imagine it going the other way, where they say, we don't want to talk to anyone because we are. They're competitive. They might discover it before we do.

[Walter Isaacson]

One of the Things that I wanted to convey in the book is that science and discovery is a team sport and conferences really matter. You bring people together just to hash things around, just to, you know, go to Alice Waters restaurant near Berkeley and sit upstairs and compare notes. And it's dangerous because scientists are sometimes competitive. They want to get their paper published first, they want to win the prize, they want to get the patent. But if you get them together at a conference, they can't help but sharing information. And so people studying CRISPR decide, all right, it's a brand new field, what do you do? Let's start a conference. And the first one's at Berkeley. And it's done by one of the.

[Evan Ratliff]

Yogurt scientists, the Danisko researchers, who discovered that CRISPR was a kind of immune system against viruses in their yogurt cultures.

[Walter Isaacson]

The first speaker is Francisco Mojike, the.

[Evan Ratliff]

Spanish researcher who'd found CRISPR in salt loving bacteria and named it.

[Walter Isaacson]

He comes all the way over from Spain, and the rule is you get to talk about work that you haven't published, and you trust everybody not to try to steal it and to beat you into the publication. And back then, things were competitive, but it was a small enough community that they were good at sharing ideas. The conferences on CRISPR in some ways reflected Jennifer's early experience, which is getting invited to Cold Spring harbor, where James Watson was convening conferences and doing them on genetics, but doing it on RNA world. And she realized that gathering in a place like Cold Spring harbor with its Blackford bar, where people would watch the Yankees at night, but discuss, you know, biochemistry. That's why she was interested in starting this CRISPR conference with some of the yogurt scientists, with Francisco Mojico and others.

[Evan Ratliff]

And these little personal interactions are how some of the kind of light bulbs go off for people.

[Walter Isaacson]

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. And coming out of it, people say, all right, I now see things in a new way.

[Evan Ratliff]

We'll be right back.

[Walter Isaacson]

All I know is what I've been told, and that's a half truth, is a whole lie.

[Narrator/Host]

For almost a decade, the murder of an 18 year old girl from a small town in Graves County, Kentucky, went unsolved until a local homemaker, a journalist, and a handful of girls came forward with a story.

[Walter Isaacson]

I'm telling you, we know Quincy killed her.

[Narrator/Host]

We know a story that law enforcement used to convict six people and that got the citizen investigator on national tv.

[Walter Isaacson]

Through sheer persistence and nerve, this Kentucky housewife helped give justice to Jessica Curran.

[Narrator/Host]

My name is Maggie Freeling. I'm a Pulitzer Prize winning journalist producer, and I wouldn't be here if the truth were that easy to find.

[Evan Ratliff]

I did not know her and I.

[Walter Isaacson]

Did not kill her or rape or burn or any of that other stuff that y' all said. They literally made me say that I took a match and struck and threw it on her. They made me say that I poured gas on her.

[Narrator/Host]

From Lava for Good. This is Graves County, a show about just how far our legal system will go in order to find someone to blame.

[Evan Ratliff]

America, y' all better wake the hell up.

[Walter Isaacson]

Bad things happens to good people and small towns.

[Narrator/Host]

Listen to Graves county in the Bone Valley feed on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts and to binge the entire season ad free. Subscribe to Lava for Good plus on Apple Podcasts.

[Evan Ratliff]

At 19, Elena Sada believed she had found her calling. In the new season of Sacred Scandal, we pull back the curtain on a life built on devotion and deception. A man of God, Martial Maciel, looked Elena in the eye and promised her a life of purpose within the Legion of Christ.

[Narrator/Host]

My name is Elena Sada, and this is my story. It's the story of how I learned to hide, to cry, to survive, and eventually how I got out.

[Evan Ratliff]

This season on Sacred Scandal, hear the full story from the woman who lived it. Witness the journey from devout follower to determined survivor as Helena exposes the man behind the cloth and the system that protected him. Even the darkest secrets eventually find their way to the light. Listen to Secret Scandal, the mini secrets of Martial Maciel as part of the Mikeultura podcast Network on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

[Narrator/Host]

In early 1988, federal agents raced to track down the gang they suspect of importing millions of dollars worth of heroin into New York from Asia.

[Walter Isaacson]

We had 30 agents ready to go with shotguns and rifles, and you name it.

[Narrator/Host]

But what they find is not what they expected.

[Walter Isaacson]

Basically, your stay at home moms were picking up these large amounts of heroin. They go, is this your daughter? I said, yes. They go, oh, you may not see her for like 25 years.

[Narrator/Host]

Copied in between a federal investigation and the violent gang who recruited them. The women must decide who they're willing to protect and who they dare to betray.

[Walter Isaacson]

Once I saw the gun, I tried to take his hand and I saw the flash of light.

[Narrator/Host]

Listen to the Chinatown sting on the iHeartRadio app, Apple Podcasts, or anywhere you get your podcasts. It may look different, but Native culture is very alive. My name is Nicole Garcia, and on Burn Sage, Burn Bridges, we aim to explore that culture.

[Walter Isaacson]

It was a huge honor to become.

[Narrator/Host]

A television writer because it does feel.

[Walter Isaacson]

Oddly like very traditional. It feels like Bob Dylan going electric.

[Narrator/Host]

That this is something we've been doing.

[Walter Isaacson]

For, like, hundreds of years.

[Narrator/Host]

You carry with you a sense of purpose and confidence. That's Sierra Teller Ornelas, who, with Rutherford Falls, became the first Native showrunner in television history. On the podcast Burn Sage, Burn Bridges, we explore her story along with other Native stories, such as the creation of the first Native Comic Con or the importance of reservation basketball. Every day, Native people are striving to keep traditions alive while navigating the modern world, influencing and bringing our culture into the mainstream. Listen to Burn Sage, Burn bridges on the iHeartRadio app, Apple Podcasts, or wherever you get your podcast podcasts.

[Evan Ratliff]

The CRISPR conference at Berkeley in 2008, the first international gathering on the subject was a success. Interest in RNA was growing and researchers were finding new connections. But Isaacson tells me that it was also around that time that Doudna started to call into question what she was doing and why.

[Walter Isaacson]

All scientists, including Jennifer Doudna, are human. They go through a bit of a midlife crisis. She's depressed. She's working on basic research at a lab at Berkeley. And even though CRISPR has come along and it seems pretty exciting, she's like, what does that all mean? Am I really doing anything useful? And she decides, well, maybe I should just become a doctor and go to medical school or other things. And she gets recruited to a company named Genentech, a very famous company. Herbert Boyer and some of the pioneers of recombinant DNA and genetic engineering in the 70s had taken the intellectual property that they had created at universities like Stanford and Berkeley and made companies that created pharmaceuticals and other things based on recombinant DNA and genetic engineering. And so she decides, I'm going to go to Genentech and actually apply science. So it moves from the bench to the bedside of the patient, and that lasts about two months. She realizes she's made a big mistake, that she loves having graduate students. She loves the research, the hunt, the discovery. And she sits outside one night and it's raining, and she just keeps crying and crying, thinking she's abandoned her post at Berkeley. She's now in corporate America, and it's a great job, but it's not her. And the head of the chemistry department at Berkeley. I think Jennifer's husband, Jamie Cade, calls up and says, hey, Jennifer's not doing well. And the head of the chemistry department comes over and says, you want to come back to Berkeley? And she says, yes.

[Evan Ratliff]

And that seems to be that almost move that then brings her back into basic science, basic research. That itself seems to be some kind of catalyst, like, things really take off from there, Starting with the Puerto Rico meeting, and she meets sort of her intellectual and creative partner for the coming years.

[Walter Isaacson]

We talk about how meetings and conferences in Cold Spring harbor labs serve as a catalyst, like an enzyme, to spark collaboration. And that happens at a Puerto Rico conference where there's a French scientist named Emmanuelle Champantier who's also studying RNA and actually is understanding the mechanisms of rna, how it works with an enzyme to cut DNA. And she realizes that Jennifer Doudna is also doing it. And they walk along the cobblestone streets of Puerto Rico and they say, let's collaborate. And that's how this beautiful partnership. And Jennifer says to me and says to Emmanuel, when we're talking, I almost became a French teacher, and I imagine myself as, you know, being an elegant French person, and you're that person, but you're a scientist. This will be a perfect combination.

[Evan Ratliff]

But Charpentier also seemed to have a little bit of this outsider perspective that you talked about earlier, Feeling a little bit excluded, always moving from lab to lab.

[Walter Isaacson]

She was very peripatetic, still is. Never stayed in a lab more than a year or two. She was at the Max Planck Institute in Berlin, but before that, she had been in Sweden, and before that she had been in Vienna. And then she moves every two years. And in her life, she never made commitments, never got married, never had kids. And that was just something about her. In fact, there was always a slight distance, a shell around her.

[Evan Ratliff]

But when they started out, clearly they found this commonality around trying to understand crispr. Can you walk us through what it was that they jointly discovered?

[Walter Isaacson]

For CRISPR to work, it's gotta use rna, which is the thing that goes into your cell and tells the cell how to build a protein. And it can be coded to do certain things. And in crispr, the rna, the coding, had mug shots of various viruses. But the question is, then, how does it do something with it? And the answer, as Jennifer always said, if something does something, your first answer is, it must be an enzyme, a CRISPR associated enzyme.

[Evan Ratliff]

In other words, Doudna and Charpentier were focused on really breaking down and understanding the crispr mechanism, specifically how the RNA and its accompanying enzyme were able to work together. And Isaacson tells me they were far from being the only ones.

[Walter Isaacson]

Everybody is racing to figure out what are called CRISPR Cas Systems. And one of the discoveries that Jennifer and Emmanuel made is that there were actually two types of rna. One that you could consider a guide RNA that had a little code and it was a guide that told it where to go. But there was another snippet of RNA called tracer rna, which was almost like a scaffolding it. Now, this seems very technical, but you got to know exactly how it works if you're going to want to engineer it and make it a tool. So there's a race around the world of people studying CRISPR cast this and CRISPR cast that. But the breakthrough that seems small, but is the big one is to know all the ingredients and have it work in a test tube. Not just say, I can make it work against this bacteria in a yogurt culture, but say, I'm putting these three ingredients in and these three things make it work.

[Evan Ratliff]

By this point, Doudna had another researcher on the case, an RNA obsessed graduate student from the Czech Republic named Martin Yinick. Yinick was an expert in crystallography, the same technique Rosalind Franklin had used that allowed Watson and Crick to understand the role of DNA.

[Walter Isaacson]

And it's Martin Yenick, one of the graduate students, the lead graduate student in Jennifer's lab, who's working on this, who sketches out on a whiteboard, here's what the tracer RNA does, here's what the guide RNA does, and here, if you look at it and you see their chemical structure, they could actually fit together. And let's figure out what's the essential part of each and make it so that you had a fused, a single guide RNA that was as simple as possible. The reason this is important is it's not just a discovery about nature. Now you've done an invention, you've done something that can be patented. It is something that you've created and that allows it to move past just being a basic science discovery into being a real breakthrough. That's a technology breakthrough and something so.

[Evan Ratliff]

Small and so technical, there's actually so much drama in it. There's so much drama in the tracer RNA has two functions and it's. Who's going to figure out that it has two functions and then who's going to publish the fact that it has two functions?

[Walter Isaacson]

This is where we get back to the conferences. They're all Collaborating and figuring out. You do this CRISPR cast system. I'll work on this one. Maybe I'll look at this form of D. And they're sharing things. But suddenly, as they get closer, everybody wants to win the prize of how does CRISPR work? And so you have this conference in 2012, and a lot of people are racing to do the ingredients. Jennifer and Emmanuel and their two graduate students have figured out every single element of how it works. And that weekend, they're finishing off their paper. They're rushing it off to a journal because it doesn't count unless you get it published. And so they're rushing into the journal science. They're showing all of the elements, the crispr, the enzymes that cast, the tracer rna, the guide rna, and they're even showing a tool they've been able to make to combine the two forms of RNA to be a single guide rna. So in other words, it's an engineered tool that makes this simpler. And they're ready with all those elements. And everybody's at this conference. They're all trying to present. And Jennifer and Emanuel want priority. They want to be the first to publish. They want to be the first to get patents. And so the competition comes in then.

[Evan Ratliff]

And how does the competition drive the discovery without poisoning? It is one of the questions that I feel like comes in the book without creating rancor, without creating bad feelings or even bad behavior.

[Walter Isaacson]

Well, it sometimes does create bad feelings and bad behavior. And this is how science advances, which is a mix of cooperation and competition. You got to have competition, because why are Emmanuel Charpente, Jennifer Doudna and their two graduate students can stay up 24 hours a day around the clock, working in Europe and in Sweden and in Berkeley and the United States, so that they can win the race, that competition. And sometimes you're wondering, what are they competing for? Well, they're competing for the prizes that matters. They're competing for being published first. I think mainly they're competing for the recognition, but also they're competing for a lot of money because you get a patent, you know you've hit the jackpot. If you want to win the Nobel Prize, you're no longer going to be as cooperative of other people in the same field.

[Evan Ratliff]

It was at that CRISPR conference in 2021 that Jennifer Doudna and Emmanuel Charpentier finally submitted their paper on CRISPR. Cas 9, the first part of the name, referring to the repeated clusters, and Cas9 referring to the specific enzymes that essentially created these genetic scissors. Isaacson says this was A pivotal moment.

[Walter Isaacson]

At the end of Watson and Crick's paper on the structure of DNA, they do a breathtaking sentence that goes down in history, which is sort of, as I paraphrase it, it's not escaped our notice that what we have discovered by the structure can be a system for passing along genetic information. In other words, a sentence that says, hey, this isn't just about RNA being fused. This could have a big deal. So at the end of the paper that von Thier and Doudna write in 2012, they basically mimic that sentence and it says, basically. It's not escaped our notice that this could become a tool to edit our DNA.

[Evan Ratliff]

It's not escaped our notice. It's simultaneously a little bit understated, but also a little bit grandiose.

[Walter Isaacson]

Yes. Because the paper itself was just how does CRISPR form the right ingredients to cut the genetic material of a virus? Well, that's really important to know, especially when fighting viruses. But one order of magnitude more important is, say, can we make that into a tool where we can program it to edit our own DNA?

[Evan Ratliff]

Doudna and Charpentier had accomplished what just a decade ago seemed impossible. The clustered sequences that Francisco Mojica had found in the salty ponds of his hometown were now fully understood as a mechanism for gene editing. But they still needed to make the leap to turn the CRISPR Cas9 system into an active gene editing tool. And Isaacson tells me Doudna and Charpentier faced one particularly fierce competitor.

[Walter Isaacson]

The person at MIT Harvard who is racing against them is Feng Zhang. Fang Zhang originally sends an email to Jennifer Doubt and say, I've read your piece. I want to figure out how it's going to work. But they soon realize the stakes are too high and they all become more secretive and more competitive.

[Evan Ratliff]

That's next time on Doudna. On Doudna 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 Alex Zonenfeld. It was mixed by Kyle Murdoch and our studio engineer was Thomas Walsh. Our executive producers are Kate Osborne and Mangasha Tigador from Kaleidoscope and Katrina Norvell from Iheart Podcasts. If you enjoy hearing stories about visionaries in science and technology, check out our other series, based on biographies by Walter Isaacson on Musk for an intimate dive into all the facets of Elon Musk. And on Benjamin Franklin to understand how his success scientific curiosity shape society as we know it. Thanks for listening.

[Narrator/Host]

The murder of an 18 year old girl in Graves County, Kentucky went unsolved for years until a local housewife, a journalist and a handful of girls came forward with a story.

[Walter Isaacson]

America, y' all better wake the hell up. Bad things happens to good people in small towns.

[Narrator/Host]

Listen to Graves county on the iHeartRadio app, Apple Podcasts or wherever you get your podcasts. And to binge the entire season ad free. Subscribe to Lava for Good plus on Apple Podcasts.

[Evan Ratliff]

Sacred Scandal is back, the hit true crime podcast that uncovers hidden truths and shattered faith. For 19 years, Elena Sada was a nun for the Legion of Christ. This season she's telling her story.

[Narrator/Host]

When I first joined the Legion of Christ, I felt chosen. I was 19 years old when Marcia Almasel, the leader of the Legionaries, looked.

[Evan Ratliff]

Me in the eye and told me.

[Narrator/Host]

I had a calling.

[Evan Ratliff]

Surviving meant hiding. Escaping took courage. Risking everything to tell her truth. Listen to Sacred Scandal, the many secrets of Martial Maciel on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

[Narrator/Host]

In early 1988, federal agents raced to track down the gang they suspect of importing millions of dollars worth of heroin into New York from Asia.

[Walter Isaacson]

Had 30 agents ready to go with shotguns and rifles and you name it.

[Narrator/Host]

Five, six white people pushed me in the car.

[Evan Ratliff]

I'm going, what the hell?

[Walter Isaacson]

Basically your stay at home moms were.

[Evan Ratliff]

Picking up these large amounts of heroin.

[Walter Isaacson]

All you gotta do is receive the package. Don't have to open it, just accept it. She was very upset, crying. Once I saw the gun, I tried to take his hand and I saw the flash of light.

[Narrator/Host]

Listen to the Chinatown sting on the iHeartRadio app, Apple Podcasts, or anywhere you get your podcast.

[Walter Isaacson]

December 29, 1975, LaGuardia Airport.

[Narrator/Host]

The holiday rush. Parents hauling luggage. Kids gripping their new Christmas toys. Then everything changed. There's been a bombing at the TWA terminal.

[Walter Isaacson]

Just a chaotic, chaotic scene.

[Narrator/Host]

In its wake, a new kind of enemy emerged. Terrorism. Listen to the new season of law and criminal justice System on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This is an iHeart podcast.