ON CRISPR Episode 1: Beginnings

Summary

Podcast Summary: ON CRISPR Episode 1: Beginnings

Podcast: ON CRISPR: The Story of Jennifer Doudna with Walter Isaacson
Hosts: Evan Ratliff & Walter Isaacson
Release Date: September 10, 2025
Producer: iHeartPodcasts and Kaleidoscope

Overview:

Episode 1, “Beginnings,” launches the story of Jennifer Doudna—the Nobel Prize-winning scientist pivotal to the development of CRISPR gene editing. With in-depth discussion between acclaimed biographer Walter Isaacson and journalist Evan Ratliff, the episode traces the roots of the CRISPR revolution, placing it in the context of history’s major scientific breakthroughs, and explores Doudna’s journey from curious child in Hawaii to world-changing biochemist. Woven throughout are themes of scientific curiosity, mentorship, gender, and the transformative—and sometimes perilous—potential of altering the very blueprint of life.

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Key Discussion Points & Insights:

1. CRISPR in Action: The Human Stakes

• The episode opens with a story: doctors use CRISPR to treat baby KJ, who has a genetic disorder (urea cycle disorder), with a personalized gene therapy that showed dramatic early results.
  • "Just a few days after his first injection, KJ starts showing signs of improvement. It's totally miraculous... After two months, the doctors described him as growing and thriving with no side effects from the treatment.” (Walter Isaacson, 03:27)
• This story is used to underscore the human urgency and potential of gene editing, emphasizing that the breakthrough represents “30 years of biological research.” (Walter Isaacson, 04:07)
• Isaacson situates Doudna’s work as foundational to these new therapies.

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2. The Third Scientific Revolution

• Isaacson frames CRISPR alongside landmark scientific revolutions:
  • Atomic era (Einstein),
  • Digital age (Steve Jobs),
  • Now: “the age of a life sciences revolution.” (Walter Isaacson, 06:31)
  • Isaacson set out to add to his “pantheon of books about great geniuses and the scientific revolutions they were creating,” identifying Doudna as the quiet revolutionary leading this new age.
  • “She wasn't just cloning sheep. She was pushing through technologies that are life changing.” (Walter Isaacson, 06:54)

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3. Jennifer Doudna’s Early Life: Curiosity and Barriers

• Growing up in Hilo, Hawaii, young Doudna became fascinated by nature’s mysteries, e.g. “sleeping grass” and coral shapes—exhibiting a trait Isaacson sees in all great innovators: passionate curiosity.
  • “She became deeply curious about every little secret of nature… That was something other great innovators had: this passionate curiosity about everyday things.” (Walter Isaacson, 07:43)
• A life-changing moment: her father leaves the book The Double Helix on her bed. Initially thinking it was a detective story, Doudna soon realizes it’s the real-life hunt for DNA’s structure.
  • Doudna draws inspiration, particularly from Rosalind Franklin—a rare female scientist depicted in the story. Rather than noticing the dismissiveness toward Franklin, young Doudna was simply amazed “that a girl could be a scientist.” (Walter Isaacson, 09:49)
• With few female role models and after being told by a guidance counselor “no, girls don’t do science,” Doudna’s determination only increased.
  • “Then I'm going to become a scientist… We have to realize the importance of mentorship and also realize that sometimes science is not something that everybody gets to be a part of. There's a lot of underrepresented groups in Science, including women.” (Walter Isaacson, 10:39–11:49)
• Early mentorship from Don Hemmes, a local biology professor who guided her via beach walks and lab time.

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4. Formative Years & Breadth of Talents

• Doudna’s interest in both science and French literature is discussed; a French professor at Pomona encourages her to pursue biology.
• Her time in Jack Szostak’s Harvard lab shapes her commitment to “basic science”:
  • “You're not supposed to be just trying to invent a new microchip...you're supposed to be marveling at the basic beauty of nature.” (Walter Isaacson, 13:21)
  • The “big question” Szostak gives Doudna: “the origin of life,” catalyzing her lifelong fascination with RNA.

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5. Contextual Foundations: Darwin, Mendel, Watson & Crick

• A brief, lively history of genetics:
  • Darwin’s natural selection, Mendel’s peas and hereditary patterns.
  • Discovery of DNA’s double helix (Watson & Crick, with pivotal input by Rosalind Franklin).
  • “The big breakthrough around 1950 or so is when James Watson and Francis Crick...figure out the DNA structure… Three billion pairs of code to code you and me.” (Walter Isaacson, 20:34)
• Transition to Doudna’s era, where the focus in her lab is on RNA rather than DNA.

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6. RNA: The Underdog Molecule

• Isaacson explains the roles of DNA and RNA:
  • DNA: Stores genetic information, stays guarded.
  • RNA: The active messenger—reads DNA, makes proteins, catalyzes reactions, and “actually does more work.”
  • "...like a lot of not famous siblings, it actually does more work." (Walter Isaacson, 21:34)
• Doudna’s key scientific focus: exploring RNA’s self-replicating properties and its possible role in the origin of life (“the RNA world”).

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7. Early Recognition & Challenges

• Doudna presents her work on RNA’s structure at Cold Spring Harbor Laboratory, invited by James Watson himself—a powerful full-circle moment.
  • Signifies joining the “chain of discovery.” (Evan Ratliff, 24:46)
• About the Human Genome Project:
  • The sequencing of human DNA held initial promise, but at first proved more descriptive than prescriptive.
  • “We could read the code of life, but we couldn't do anything with it. You couldn't rewrite it. You couldn't edit it.” (Walter Isaacson, 26:16)
• Doudna, along with other women scientists, shifted focus toward RNA, an undervalued research field.

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8. Women, RNA Research, and a New Direction

• Isaacson highlights how the Genome Project was an “alpha male exercise;” many women scientists, Doudna included, “ran to where the ball was going to be”—RNA.
  • “A lot of women who were not part of the Human Genome Project started studying RNA, the less famous molecule… In the end, it turns out that RNA is a lot more useful to understand because it's the one that goes and does work.” (Walter Isaacson, 27:38)
• These women—Doudna, Gillian Banfield, Emmanuelle Charpentier, Kati Korichko—are now pivotal figures in the field.
• RNA’s expressive power is now central to technologies like the COVID-19 mRNA vaccine.

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9. Visualizing Biomolecules: X-ray Crystallography

• Doudna uses x-ray crystallography, akin to Rosalind Franklin, to “figure out the folds and twists of the three-dimensional structure” of RNA.
  • “She's doing things about the structure of rna, trying to crystallize it. That's the way scientists are able to figure out what does it really look like...” (Walter Isaacson, 30:02)
• Personal moment: As Doudna solves RNA’s structure while her father is dying, she explains her findings to him—a demonstration of both scientific achievement and her capacity for accessible explanations.

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10. Toward CRISPR: The Next Big Breakthrough

• Introduction of the CRISPR story: A young Spanish scientist finds odd repeating sequences in bacteria—an obscure, fundamental clue.
  • “He keeps seeing these repeated sequences, but nobody knows why they exist. And that's when the hunt begins.” (Walter Isaacson, 31:47)
• The episode ends teasing coming topics:
  • The global race to develop CRISPR technology.
  • The potential for both enormous benefit and evil.
  • Doudna's own anxiety, as dramatized by a nightmare featuring Adolf Hitler seeking her invention.
    • “She realizes, of course, that in the wrong hands, this tool could be not just powerful, but evil.” (Walter Isaacson, 32:59)

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Notable Quotes & Memorable Moments

• Isaacson, on the paradigm shift CRISPR represents:
  • "Now...we do [have the ability to change the fundamental chemical nature of who we are]. And what do we do with that?" (Podcast Host, 05:16)
• On the mindset of breakthrough scientists:
  • “She became deeply curious about every little secret of nature...That was something other great innovators had: this passionate curiosity about everyday things.” (Walter Isaacson, 07:43)
• On mentors and belonging:
  • "We have to realize the importance of mentorship and also realize that sometimes science is not something that everybody gets to be a part of." (Walter Isaacson, 11:49)
• On the necessity and power of basic science:
  • “You're not supposed to be just trying to invent a new microchip...you're supposed to be marveling at the basic beauty of nature.” (Walter Isaacson, 13:21)
• On the limitations of the Human Genome Project:
  • “We could read the code of life, but we couldn't do anything with it. You couldn't rewrite it. You couldn't edit it.” (Walter Isaacson, 26:16)
• On the danger and excitement of gene editing:
  • "Not only will we be able to cut DNA, we'll cut and paste just as if we were using a word processor." (Walter Isaacson, 32:28)
  • Doudna’s nightmare: “She realizes, of course, that in the wrong hands, this tool could be not just powerful, but evil.” (Walter Isaacson, 33:02)

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Timestamps for Key Segments

• CRISPR/KJ’s Story: 02:43–05:16
• ‘Third Great Revolution’ Framing: 06:31
• Doudna’s Childhood & the Double Helix: 07:43–09:49
• Role Models and Guidance Counselor: 09:49–11:49
• College, Szostak, and RNA Focus: 12:17–14:00
• DNA/RNA 101, Watson & Crick: 20:34–23:14
• Women Shift to RNA, Marginality in Science: 27:38–29:40
• Crystallography & Personal Loss: 30:02–31:23
• Origins of CRISPR Discovery: 31:47–32:12
• CRISPR’s Double-Edged Sword (Doudna’s Nightmare): 32:28–33:05

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Tone & Style

The episode melds story-driven narrative with Isaacson’s reflective, sometimes awe-filled tone. There’s a sense of wonder and urgency, but also historical skepticism and humility about the pace of discovery. Isaacson and Ratliff conversationally break down complex scientific concepts for broad audiences while foregrounding the very human stories behind the science.

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Closing Thoughts

“Beginnings” is as much about the building blocks of discovery—curiosity, mentorship, perseverance—as it is about base pairs and enzymes. By chronicling Doudna’s path from a curious Hawaiian schoolgirl to a Nobel laureate, the show roots the CRISPR revolution within familiar human struggles and triumphs, setting the stage for future episodes’ deep dives into the global, ethical, and competitive drama of gene editing.

Transcript

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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 me in the eye and told me 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.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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. 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 Podcasts or wherever you get your podcasts. Kaleidoscope.

[Evan Ratliff]

Last year in Philadelphia, the mother and father of a baby boy experienced any newborn parents nightmare. They discovered that their son KJ had been born with a rare genetic disease called urea cycle disorder. Causing him to have abnormally high levels of ammonia in his blood. The prognosis was devastating. And the only conventional life saving treatment option was a liver transplant. A treatment that KJ might not be able to obtain or survive. But then a pair of doctors at the Children's Hospital in Philadelphia approached KJ's family to discuss the possibility of trying a treatment that had never been tried before. They would try using a technology called CRISPR to correct the specific genetic flaws that were creating KJ's condition.

[Walter Isaacson]

So it takes about six months and the doctors developed a drug that was designed to target baby KJ's genetic variant specifically targeted to that one letter mess up in his DNA. And just a few days after his first injection, KJ starts showing signs of improvement. It's totally miraculous. The color returns to his cheeks and for the first time he can tolerate protein in his diet. His parents are overwhelmed. After two months, the doctors described him as growing and thriving with no side effects from the treatment. And with every month the hope has grown that the world's first personalized gene editing treatment has been a complete success. Now you may think that therapy was developed over six months, but it was actually the product of like 30 years of biological research. I mean, there was a lot of technological development that went into this. And the race to arrive at this moment is just a great story of ambition and competition and collaboration and triumph because the work and the results are extraordinary. And much of it was fueled by the quiet determination of a biochemist named Jennifer Doudna. While that name may not be at the tip of your tongue like Elon Musk or Steve Jobs or maybe Benjamin Franklin, who work might be the thing that saves your family like it did for kj. Or maybe it already did, like with the COVID vaccine. You know, we've never had in the.

[Podcast Host / Narrator]

Past the ability to change the fundamental chemical nature of who we are in this way. Right? And now we do. And what do we do with that?

[Walter Isaacson]

The discovery is both a tale of pure curiosity driven basic science as well as functional science.

[Evan Ratliff]

This is the third time I've sat down with Isaacson as part of an ongoing conversation we're having about his subjects. The kind of people who change the world by the force of their intellect. In the first season, we talked about Elon Musk and Isaacson's 600 page biography of him, the tome that launched a thousand hot takes. In our second, we focused on a less polarizing inventor, Benjamin Franklin, whose life and thinking helped us make sense of today's turbulent times. The origins of our third sit down trace back to 2012, when the world first heard about a new gene editing tool called crispr, A breakthrough that would allow us to modify our own genes, copying and pasting them like a sentence. Isaacson, when he learned the news, saw it as something more than a singular invention. To him, it represented, as he's written, the beginning of the third great revolution of modern times, followed by the revolutions in physics and information technology.

[Walter Isaacson]

I was trying to create a pantheon of books about great geniuses and the scientific revolutions they were creating. Einstein, who brings us into the atomic era, Steve Jobs, who brought us into the digital age. But also we're entering an age of a life sciences revolution. And I wanted to find somebody who represented this revolution. He was this brilliant, understated person, this woman who wasn't mercurial or cantankerous like Steve Jobs or Elon Musk, but was quietly leading a revolution. She wasn't just cloning sheep. She was pushing through technologies that are life changing. And I thought, hey, I need to spend time with her.

[Evan Ratliff]

I'm Evan Ratliff and this is on crispr. The story of Jennifer Doudna. Episode one Beginnings for Isaacson, the tale of how Jennifer Doudna delivered CRISPR has its deepest roots in her childhood in Hilo, Hawaii.

[Walter Isaacson]

She's in Hawaii and she's looking at things like sleeping grass, where if you touch it, it curls up. I remember that. I remember touching ferns. They curl up. But I didn't sit there and obsess. Like, how does the leaf know how to do it? Does it have a motor inside? What causes it to move? And she became deeply curious about every little secret of nature, about the corals and about the curves of the shells and why they're done in a certain way. And I realized that was something other great innovators had is this passionate curiosity about everyday things.

[Evan Ratliff]

Walter says that around that time, Jennifer received a particular book from her father.

[Walter Isaacson]

Her father knew she loved to read and used to buy used paperbacks on the way home and leave them on her bed for her to read on Saturday. And one day he left the paperback of the Double helix. And it looks like a detective book in a way. Now, if you know the Double Helix, it's a wonderful book. It's Jim Watson's personal account of how he and Francis Crick and others discovered the structure of DNA, that little double helix. And it's about their sprint to do it and to beat other researchers to make this discovery. But of course, Jennifer didn't know that when she Found the paperback on her bed, and she said, oh, I thought it was a detective's tale. And I saved it for a rainy Saturday. And when I started reading, I realized what actually is a detective tale. It's about somebody on the hunt to try to figure out how do genetic information work. That seems like a pretty elevated thing, but the way that James Watson wrote that book, it made it feel like a detective story.

[Evan Ratliff]

When Doudna was reading the Double Helix as a kid, she was captivated not just by the discovery or even the detective's tale, Isaacson says, but by one character in particular.

[Walter Isaacson]

One of the interesting things about the Double Helix is there's a character in it named Rosalind Franklin, very to us in the science world. Famous because she takes the photographs that allow Watson and Crick to figure out the double helix structure of DNA. And she doesn't get much credit. And in the book that Watson writes, he dismisses her a bit. He calls her Rosie, even though he takes her science seriously. And I asked Jennifer about that when she read the book, did she notice the dismissiveness? She said, no, because I was so surprised that a girl could be a scientist. And that's what I took away from the book was I did not know women were scientists.

[Evan Ratliff]

So she didn't find early in her life role models.

[Walter Isaacson]

She said she had two role models. One was Rosalind Franklin in this book, and the other, she read a childhood book about Marie Curie. And she had always wanted to be a French teacher, and she was doing literature even in high school. And so she told her guidance counselor at school, I think I want to be a scientist. And the guidance counselor in Elo, Hawaii, said, no, girls don't do science. Well, it was a good thing that he said that, because if you know Jennifer and you read the book, that's going to get her back up. And it does. And she says, then I'm going to become a scientist. She was very lucky to have a mentor. There was a guy named Don Hemmes who taught biology at the local college in Hilo, Hawaii, and he would go on walks on the beach with her and collect small organisms and show the crustaceans and how they worked and allowed her to indulge her interest in science. And even in the summer would bring her into the lab where she could look at the shelves under a microscope. And we have to realize the importance of mentorship and also realize that sometimes science is not something that everybody gets to be a part of. There's a lot of underrepresented groups in Science, including women.

[Evan Ratliff]

And it seems like once she got to college, she did start to, you know, she had a real aptitude for science. But even then she almost was a French, wanted to become a. An expert in French literature instead.

[Walter Isaacson]

Yeah, she goes to Pomona, which has a great chemistry department. A smaller college in California. She's really out of place because she's from Hawaii and doesn't know anybody. And she's finding the chemistry hard because she didn't know enough math. And she tells her French teacher at college, I think I'm going to change majors to French. I've always wanted to be a French. And fortunately, the French professor says something. She says, you know, if you become a French major, that's great, and you may become a French professor, but if you become a biology major, that's probably more open to you.

[Evan Ratliff]

It's true. It's true. The job prospects are significantly different. So then she ends up at Harvard. She ends up in Jack Szostak's lab. And this seems like another sort of pivotal moment in the sense that he conveys to her something about doing basic science and why you're doing it and what you're trying to capture.

[Walter Isaacson]

Two things. He conveys the importance of basic science. In other words, you're not supposed to be just trying to invent a new microchip or invent a gene editing tool. You're supposed to be marveling at the basic beauty of nature. And secondly, he said, asked the big questions, and she said, what's the big question? And he says, the origin of life. How did it happen? And that's when they start looking at rna, a molecule that's not as famous as its sibling DNA.

[Evan Ratliff]

And in the book, you take us through some of the history of how these discoveries were made, and we don't have to go through the whole history of it. But, you know, Darwin to Gregor Mendel.

[Walter Isaacson]

Oh, let's do.

[Evan Ratliff]

We can. We certainly can.

[Walter Isaacson]

Well, you gotta start with Darwin and Mendel. Both in the same period, you know, the mid-1800s. And what Darwin figures out by going on the voyage of the Beagle to the Galapagos and others is different species adapt as their environment changes. He looks at the beaks of the finches and like, oh, maybe they had a drought. And the beak becomes something that can open up nuts. So he's trying to figure out, how does this information, this survival of the fittest, lead to changes in the genetic information. And at the same time, unbeknownst to him, there's a priest in brno, which is the Czech Republic. Now, who is breeding peas? And he would say, okay, I like the peas with the purple coat. And when I mix them with the peas with the white coat, they don't sort of blend purple and white. They'll have a dominant gene, so most turn out purple, but one will turn out white in the second generation. So all of that information comes together and they finally discover around 1900, there just must be some chemical in our body that transmits this genetic information. And that's where the hunt begins for how does genetic information get transmitted?

[Evan Ratliff]

Coming up after the break, we dive into the Human Genome Project and why some scientists, notably women, didn't get the chance to work on it.

[Walter Isaacson]

All I know is what I've been told and that to have truth is a whole lie.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

Took a match and struck and threw it on her. They made me say that I poured.

[Walter Isaacson]

Gas on her.

[Podcast Host / Narrator]

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.

[Walter Isaacson]

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

[Podcast Host / Narrator]

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 pulled 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.

[Podcast Host / Narrator]

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 Sacred the Many Secrets of Marciel Maciel as part of the My Cultura podcast Network on the iHeartRadio app, Apple Podcasts, or wherever you get her podcasts.

[Podcast Host / Narrator]

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

[Evan Ratliff]

We had 30 agents ready to go.

[Walter Isaacson]

With shotguns and rifles, and you name.

[Podcast Host / Narrator]

It, but what they find is not what they expected.

[Walter Isaacson]

Basically, your stay at home moms were.

[Evan Ratliff]

Picking up these large amounts of heroin.

[Walter Isaacson]

They go, is this your daughter? I said, yes. They go, oh, you may not see her for like 25 years.

[Podcast Host / Narrator]

Caught 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.

[Podcast Host / Narrator]

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. It was a huge honor to become a television writer because it does feel.

[Walter Isaacson]

Oddly like very traditional.

[Podcast Host / Narrator]

It feels like Bob Dylan going electric, that this is something we've been doing for hundreds of years. 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, influence, 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 podcasts.

[Walter Isaacson]

The big breakthrough around 1950 or so is when James Watson and Francis Crick get together in Cambridge University, England, and they figure out the DNA structure, which is it has two strands and it's like a spiral staircase. And the rungs are four different letters. We'll call them for chemicals, A, T, C, G. And it can pull itself. It pulls apart and replicates itself. And those letters. Three billion pairs of code to code you and me. That encodes the genetic information that gets transferred generation to generation.

[Evan Ratliff]

This string of findings from Darwin to Watson and Crick were the foundation for the study of DNA. But fast forward two decades later, and Jennifer Doudna and her mentor at Harvard, Dr. Jack Szostek, were paying attention to another important but more neglected molecule, rna.

[Walter Isaacson]

The different molecules we have in our body, proteins being among the most famous. But there's also what are called nucleic acids, and there are two of them, RNA and DNA. And DNA is what encodes our heredity, our genes. They're encoded in this four letter code that can replicate itself because the strands of DNA can pull apart and, and then create an identical new set of DNA strands. That's how we transmit genetic information. But the real question is, what makes that work? And that's what RNA does. It's not as famous, but like a lot of not famous siblings, it actually does more work because the DNA just sits there in the nucleus of your cell curating this information. It doesn't go anywhere. It carefully guards it. But RNA goes into the nucleus, reads that blueprint, reads that information in the DNA code and then goes to the outer area of the cell where proteins are made. And it will make a protein based on the information it got from DNA. And that's all life is, is proteins getting made. Whether it's your fingernails, your hair, or the neurons in your brain, or the muscles that twitch, those are just different forms of protein that use the code in our genes. And it's RNA that says, all right, we're now going to build a molecule that's a hair follicle.

[Evan Ratliff]

In that lab, Doudna and her colleagues were focused squarely on rna.

[Walter Isaacson]

DNA knows how to replicate itself. That's its strong suit. That's why it's DNA. RNA they figured out could also replicate itself and help create proteins. And so it could have been the original molecule that gets life started. And indeed, they do a paper about self replicating RNA and set the groundwork for what is now called the RNA world, which is how did life begin? Well, there was a stew of a lot of chemicals and four of them get together and they start replicating. And it made her always want to look at basic science and the big questions of life.

[Evan Ratliff]

Is that the paper that landed her at Cold Spring, giving the talk at age 23?

[Walter Isaacson]

Absolutely. The research with Jack Shostak into the RNA world and how you could have RNA replicate itself and do all these amazing things. She gets invited by the great James Watson, whose double helix she had read as a kid, to Come to Cold Spring harbor lab on Long island, where they have scientific conferences because Jack Szostak couldn't come. And so she gets to present their work with James Watson sitting in the front row. And this is a seminal experience for her.

[Evan Ratliff]

Isaacson tells me that for Doudna, the Cold Spring harbor conference was not just a full circle moment, but a signal that she was joining this historical chain of discovery, a generational project aimed at ultimately unraveling how our genes work. But Douda wasn't alone. There was an expanding group of researchers who were turning their attention to rna. It feels like when Doudna is sort of starting to come of age as a scientist, she's, you know, she's working in different labs. There's this next big development going on, which is the Human Genome Project, and that's sort of what's hovering over everything. But she goes in a different direction. Maybe you can explain what the Human Genome Project was doing and why she kind of went the other way.

[Walter Isaacson]

So in the 1950s, when Watson and Crick discover the structure of DNA, the hunt becomes, well, let's look at each of those letters and decode where in our DNA it codes for hair, height, whatever may be encoded for. And that was called the Human Genome Project, which is map the human gene. And one of the leaders was James Watson. And Francis Crick was very involved, too. It culminated in the year 2000. More than a thousand researchers across six.

[Podcast Host / Narrator]

Nations have revealed nearly all 3 billion.

[Walter Isaacson]

Letters of our miraculous genetic code.

[Evan Ratliff]

I congratulate all of you on this stunning and humbling achievement.

[Walter Isaacson]

I was at Time magazine and we put Francis Collins and Craig Ventner on the COVID They were rivals trying to decode the gene. We were going to just do Craig Venter. The little thing was that the vice president was Al Gore, and he was insistent. He even called and said, you also have to put the National Institutes of Health person, the government person. Yeah. He called and said, you can't just put this privateer who's doing it? And so we put them both on the COVID and we thought it was the biggest thing in the world, that all of human life would now change because we could read the blueprint of the discovery of our human genome. It was a big deal back then, and Dolly the sheep was being cloned, and everybody thought that DNA was going to be a revolution. And like a lot of revolutions, it actually started slowly. Why? Because we could now read the code of life, but we couldn't do anything with it. You couldn't rewrite it. You couldn't edit it.

[Evan Ratliff]

But there was this sense then that, well, now we have command of this thing. We know now we'll just figure out what all the genes do and then we'll be able to manipulate them down the line. We'll be able to cure diseases. But everyone was forgetting about another element, which was rna.

[Walter Isaacson]

It was quite nice to be able to say, oh, that's the part of the gene that does this, but let's say it's the letter in the gene that's messed up, that causes sickle cell anemia. That was fine to know, but there wasn't much useful that came out of it. And that's when RNA and the women who were focusing on RNA entered the story. One of the things that happened is the Human Genome Project and decoding DNA is mainly an alpha male exercise. Jennifer Doudna, when she played soccer as a little kid in Hawaii, she said all the boys used to run to the ball, but I always wanted to run to where the ball was going to be. And so a lot of women who were not part of the Human Genome Project started studying rna, the less famous molecule. And those were people like Gillian Banfield, Emmanuel Charpentier, Kati Korichko and of course Jennifer Doudna. In the end, it turns out that RNA is a lot more useful to understand because it's the one that goes and does work, reads the DNA and then has the protein made. It also can be a messenger to make any protein you want, which is quite useful when you're trying to invent a COVID vaccine and you want to make a fake spike protein in people's cells. So a lot of women were doing rna and after the Human Genome Project, it became important to say, well, what are we going to do with all this information? We have to be able to manipulate it, we have to edit it, we have to do things with it. And that's where RNA becomes the tool. Just like in our body, it's a tool for applying the code of DNA to the making of protein. In science and the basic research, it becomes the tool for understanding what we can do with our genetic coding.

[Evan Ratliff]

Isaacson says that in order to really understand how to harness the abilities of rna, Jennifer Doudna realized that she had to use some of the same techniques deployed by Rosalind Franklin to uncover the structure of DNA, namely an imaging technology called X ray crystallography, which, as Isaacson writes, she could use to figure out the folds and twists of the three dimensional structure of cell splicing.

[Walter Isaacson]

RNA she had understood from Jack Showstack the importance of RNA and how RNA explain the origins of life. So she's doing things about the structure of rna, trying to crystallize it. That's the way scientists are able to figure out what does it really look like? You know, how can I shine light into it? Is what Rosalind Franklin did for DNA so that we can see the structure and the shape.

[Evan Ratliff]

And it seems like Jennifer Doudna, she really, she had that maybe that soccer player moving to where the ball is going to be sense of there's something here that we're gonna need to know. And there's basic science to be done here. And I feel like the first time she sort of has a public profile is like a little story that you found. When she's at Yale, she's working on the structure of rna and there's a very moving scene where she's trying to resolve this question. And her father is dying at the.

[Walter Isaacson]

Same time her father was dying. And her father was this great influence. It always pushed her to be a scientist. And he kept saying, even though he was fighting cancer, he kept saying, explain it to me, explain what you're doing. And that becomes one of Jennifer Doudna's superpowers, is being able to explain what was happening.

[Evan Ratliff]

What she explained to her father was her first taste of real scientific discovery. A picture of the three dimensional folded shape of an RNA molecule. But for Doudna and her expanding orbit of colleagues, nailing the structure of RNA was just the beginning. To figure out how to harness that structure, she would need to piggyback on an obscure breakthrough from across the ocean in Spain.

[Walter Isaacson]

A graduate student, young scientist in Spain, and he's looking at bacteria in very, very salty ponds. And he notices something when he's sequencing the genes. And he keeps seeing these repeated sequences, but nobody knows why they exist. And that's when the hunt begins.

[Evan Ratliff]

Coming up this season on crispr, there's.

[Walter Isaacson]

A race around the world. 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. Not only will we be able to cut DNA, we'll cut and paste just as if we were using a word processor. Jennifer had a nightmare, and it was that somebody wanted to meet with her about this new technology. And she opens the door to the room, the person looks up and it's Adolf Hitler. And she's taken aback. And she. She realizes, of course, that in the wrong hands, this tool could be not just powerful, but evil.

[Evan Ratliff]

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 Kyle Murdoch and our studio engineer was Thomas Walsh. Our executive producers are Kate Osborne and Mangash Hatikador from Kaleidoscope and Katrina Norvell from iheart Podcasts. If you enjoy hearing stories about visionaries and science and technology, check out our other seasons based on the biographies that Walter Isaacson's written on Musk for an intimate dive into all the facets of Elon Musk and on Benjamin Franklin to understand how his scientific curiosity shapes society as we know it. Thanks for listening.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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, Alena Sada was a nun for the Legion of Christ. This season, she's telling her story.

[Podcast Host / Narrator]

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 me in the eye and told me 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 Marcial Maciel on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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.

[Podcast Host / Narrator]

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 Fumaro. And this is More Better. We are jumping right in and ready to hear from you, your thoughts, your questions, your feelings about Sox sandals. And we're ready to share some possibly questionable advice and hot takes. God sucks so hard though. I'm so sorry. Can you out petty 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. This is an iheart pod.