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 Crisper to correct the specific genetic flaws that were creating Kj's condition.

So it takes about six months, and the doctors developed a drug that was designed to target Babykj's genetic variant, specifically targeted to that one letter mess up in his DNA.

In 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 thirty years of biological research.

I mean, there was a lot of technological development that went into this 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 Dowdner.

And 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 a different kJ or maybe it already did, like with the COVID vaccine.

You know, we've never had in the 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?

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

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 changed the world by the force of their intellect.

In the first season, we talked about Elon Musk and Isaacson's six hundred page biography of him, the tone that launched a thousand hot takes.

In our second we focused on a less polarizing inventor, Benjamin Franklin, whose life in thinking helped us make sense of today's turbulent times.

The origins of our third sit down traced back to twenty twelve, when the world first heard about a new gene editing tool called Crisper, 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.

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 at are life changing.

And I thought, hey, I need to spend time with her.

I'm Evan rightlift.

And this is on Crisper, The Story of Jennifer DOWDNAT Episode one.

Beginnings for Isacson.

The tale of how Jennifer down a delivered Crisper has its deepest roots in her childhood in Hilo, Hawaii.

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 farnes.

They curl up, But I didn't sit there and obsess like, how does the leaf know how to do?

It?

Does 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 hat is this passionate curiosity about everyday things.

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

Her father knew she loved to read, and used to buy used paperbacks on the way home and leave them on her bed for 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 to 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.

When Daltna 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.

One of the interesting things about The Double Helix is there's a character in it named Rosalind Franklin, very to us and 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 book, was I did not know women were scientists, so she.

Didn't find early in her life role models.

She said she had two role models.

One was Russell and 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 Ilo, 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 Hemis who taught biology at the local college in Helo of Hawaii, and he would go on walks on the beach with her and collect small organisms and show the crustaceans and how they work and allowed her to indulge her interests in science, and even in the summer, would bring her into the lab where she could look at the shells 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.

And it seems like she 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 an expert in French literature instead.

Yeah, she goes to Pomona, which has a great chemistry department and a smaller college in California.

She's really out of place because you know, she's from Hawaii and I don'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 major.

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, there's probably more open to you.

It's true, it's true.

The job prospects are significantly different.

So then she ends up at Harvard.

She ends up in Jack Shostak'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.

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 tools, to be marveling at the basic beauty of nature.

And secondly, he said, ask 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.

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, oh, let's we can, we certainly can.

Well, you gotta start with Darwin and Mendel, both in the same periods on the mid eighteen hundreds, and what Darwin figures out by going on the voyage of the beagles of 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 Burno, 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 piece with the white coat, they don't sort of blend purple and white.

They'll have a dominant gene, so most turnout purple, but one will turn out white in the second generation.

So all of that information comes together and they finally discover around nineteen hundred 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?

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.

The big breakthrough around nineteen fifty or so is when James Watson and Francis Kraik get together in Cambridge University, England and they figure out the DNS structure, which is it has two strands and it's like a spiral staircase, and the wrongs are four different letters we'll call out chemicals ATCG 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.

This string of findings from Darwin to Watson and Crick with a foundation for the study of DNA.

But fast forward two decades later and Jennifer DOWDNA and our mentor at Harvard, doctor Jack Showsteck, we're paying attention to another important but more neglected molecule, RNA.

The different molecules we have in our body, proteins being among the most famous, but there's also what they're called nucleic acids, and they're two of them, RNA and DNA.

And DNA is what encodes our heredity, our genes.

They are encoded in this four letter code that can replicate itself because the strands of DNA can pull apart 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 alike 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 can't go anywhere.

He 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.

In that lab, Downa and our colleagues were focused squarely on RNA.

DNA knows how to replicate itself.

That's its strong 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 which it's 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.

Is that the paper that landed her at Cold Spring giving the talk at age twenty three.

Absolutely the research with Jack shaw Stack 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, who's 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 Showstack couldn't come, and so she gets to present their war with James Watson sitting in the front row, and this is a seminal experience for her.

Isaacson tells me that for DOWDNA, 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 Downa wasn't alone.

There was an expanding group of researchers who were turning their attention to RNA.

It feels like when DOWDNA 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 Geno Project was doing and why she kind of went the other way.

So in the nineteen fifties, when Watching and Krick discover the structure of DNA, the hunt becomes, let's look at each of those letters and decode where in our DNA it codes for air 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 two thousand.

More than a thousand re searches across six nations have revealed nearly all three billion letters of our miraculous genetic code.

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

I was at Time magazine and we put Francis Collins and Craig Ventnor on the cover.

They were rivals trying to decode the gene.

We were going to just do Craig Ventor.

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 cover, 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 re write it, you couldn't edit it.

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.

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.

In decoding DNA is mainly an alpha male exercise.

Jennifer Dowd and 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 Jillian Vanfield, Emmanuel Scharpancha, Katti Carichko, and of course Jennifer Daudna.

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's 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.

Isaacson says that in order to really understand how to harness the abilities of RNA, Jennifer Downer realized that she had to use some of the same techniques deployed by Roslin 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 self splicing RNA.

She had understood from Jack show Stack the importance of RNA and how RNA explained 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 in the shape.

Mm hmm.

And it seems like Jennifer Downas 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 going to need to know, and there's basic science to be done here.

And I feel like her first 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 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, kept saying, explain it to me.

Explain what you're doing.

And that becomes one of Jennifer down his superpowers is being able to explain what was happening.

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 DOWDNA and her expanding orbit of colleagues, kneeling 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.

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.

Coming out this season on Crisper.

There's 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 will 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 Adolph Hitler, and she's taken aback and she realizes, of course, that in the wrong hands, this tool could be not just powerful, but evil.

On Crisper, The Story of Jennifer DOWDNA is a production of Kaleidoscope and iHeart.

This show is based on the writing and reporting of Walter Isaacson.

It's hosted by me Evan Ratliff and produced by Adrianna Tapia with assistance from Alex Zonaveld's.

It was mixed by Kyle Murdoch and our studio engineer was Thomas Walsh.

Our executive producers are Kate Osbourne and Mangashatigador from Kalidoscope and Katrina Norvell from iHeart Podcasts.

If you enjoy hearing stories about visionaries and science and technology, check out our other seasons.

Bates 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.