For years, Walter Isaacson had immersed himself in the world of Jennifer DOWDNA and the other Crisper pioneers.

In hours of conversations.

He'd work to capture the stories behind the invention.

But at a certain point he decided he needed to approach Crisper from a different angle to understand it in a more pans on way.

So he traveled to Downa's lab on the tree lined campus of UC Berkeley, sat down on a lab bench alongside a couple of grad students, and got to work editing genes from a human kidney cell.

You're sitting on a bench in front of a lab table usually has a big hood on top so that it, you know, exhausts the air and there's not a lot of fumes.

And you have some test tubes in a little rack, just like he used to have in chemistry class in eighth grade, and you pipe pets, and those pipe pets allow you to put tiny drops of things into the test tube.

In the case of editing with Crisper, there would be some preprogrammed RNA targeted thing with an enzyme, meaning a protein that can cut or do other things.

A spark reactions attached to it.

Both Gavin Knott and Jennifer Hamilton, who had graduate students in the lab, hovered over me with my pipets and my glasses and goggles and latex gloves on and showed me how to mix the different ingredients we had, put it into a test tube, and then look and see whether I had edited in a gene that would make it glow green, sort of a phosphorescent gene.

And after a while you get to put it into a centrifuge, or you get to put it under microscopes, and you'll get to see were your cuts actually made.

They said, here it is, and there, indeed was the gene spliced in.

Isaacson tells me that one of the things that struck him most during the process was discovering how with crisper gene editing was relatively easy to do with a little help.

I was surprised that even I could do it.

I know, I had a couple of graduate students hovering around and helping, and I realized that this is going to be a technology that's not only easy to use, but it's easy to reprogram.

I didn't actually program the guide RNA.

Somebody else had done it for me.

But if I decided I wanted to make a cut in the parts of DNA that show my eye color, or the parts of the DNA that grow hair, whatever it may be, I realized that it wouldn't be all that hard to program the molecule.

Isaacson's realization mirrors one that Dowdna had herself, as the technology behind cris Burg continued to spread.

After Jennifer Dowdner and Emmanuel Shoppenjay publish their paper, Jennifer had a dream or 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, sort of in a pig's head, and she's taken aback.

And she realizes, of course that eugenics, I mean, this is what the Nazis were trying to do to edit the human race.

That in the wrong hands, this tool could just be not just powerful, but evil.

And she realized at that point that she would have to want to gather scientists from around the world because it had to be international to say, let's think through the implications of this.

There is the Prometheus issue, which is Prometheus snatches the technology from the gods, fire from the liver of the gods, and it becomes problematic, it's harmful.

That, of course, is written large with the atom bomb project.

And if you've seen the movie Oppenheimer, you know he's called the American Prometheus.

And so you have to wrestle with the moral implications of the technology you've created.

From the atom bomb to gene editing, scientists have long had to grapple with the risks that their own inventions present for society.

They've been forced to search their consciences and at times to galvanize their colleagues and efforts to contain those risks.

As Isaacson writes, for decades, widespread human genome editing had lived in the realm of science fiction.

Now with Chrisper, it's arriving, and the question is are we ready?

I'm Evan Ratliffe and this is on Crisper, the Story of Jennifer Downa.

This is episode four Franken Monsters.

DWNA wasn't alone in thinking about the ethical repercussions of gene editing.

Isaacson notes that the field of biotechnology has always been right with these questions.

One of the first groups to wrestle with the biotechnology ethical issues was a group that had Paul Berg and Herbert Boyer and the people in the nineteen seventies who had done the original genetic engineering of recombinant DNA in producing new types of organisms by fusing things together and had patented them.

And this was causing a problem that maybe commercial labs are going to create Franken monster.

And they go to a conference center in California known as Asilomar, and they decide to discuss the ethics of it and the rules of the road.

And the second year was a big conference.

It's called a Silomar too, and they made a series of guidelines to allow the technology to proceed.

They called it a prudent path forward was their watchword.

And they worry mainly about the safety, like how do you keep these things from escaping the lab.

They didn't worry enough about the moral implications of genetic engineering.

And this is not yet human gene editing like Christopher does, but it's a type of genetic engineering where you can create new microorganisms that might be good at fighting diseases, and they also might be pathogens that escape and are really bad.

So even if the question and the technology surrounding gene editing had changed down to return to the early organizational efforts of her colleagues as a framework.

When Jennifer decides to start this process of dealing with the ethical implications of Chrisper gene editing, she goes back to the nineteen seventies conferences of a Sillomar where Paul Berg, Herbert Boyer, Jim Watson, and David Baltimore had all gathered together do the rules of the road and create this prudent path forward for genetic engineering.

And she even gets some of the original players.

She gets David Baltimore, she gets Paul Berg to be sort of honorary chairs of this process she starts, and she goes to not a Sillomar but another resort in California, and they gather people for a series of meetings that discuss not only the safety issues but the moral issues.

I should we be making gene edits and especially inheritable gene edits so that we're not only fixing sickle cell anemia and a single patient, but we might want to make permanent genetic edits that are inheritable so that their children and nobody in their family will ever have any of their descendants, we'll ever have sickle cell again.

And that's a line across It's called the germ line, but it's like a red line, which is all right, we're not just doing it in one patient and if it doesn't work, well, that's bad for the patient, but the species survives.

What if we're now doing it in something that will change the human species?

And what was their general conclusion coming out of these meetings?

One of them was, don't make inheritable gene edits.

We're just not ready for that.

We don't know how to do it, but we also don't know the moral implications.

That gets blown away when one of these men, they're about to go to Hong Kong to have another session because they're doing internationally, and suddenly word comes forth that a little known Chinese scientist, Ju juang Qi, had made inheritable gene edits to twin girls in China by editing them when they were embryos, so all of their cells are edited and all of their descendant cells will be edited to make it so they didn't have a receptor for the virus HIV, which sounds like a good thing to do, but it crossed that line, and so that shakes everybody up.

The scientist Jo Jianqui had actually personally reached out to Daudna to tell her about his feet.

Isaacson says that gene editing researchers didn't receive the news the way jan Qui expected.

He sends her an email and the subject is baby's born and she looks at it and she's a gas.

She realizes, oh my god, this guy is edited embryos and made these genetically altered, inheritable changes in babies.

And she calls David Baltimore and they're supposed to be meeting in Hong Kong for one of these conferences, and Jennifer says, I'm catching an earlier plane.

Meet me in Hong Kong because Han Shuang key was going to be there.

He was supposed to just talk about his ears on some panel, and he wasn't planning to talk about doing an inheritable gene edits.

In fact, he didn't want to.

He was trying to keep it secret.

And they decide they have to let him present what he has done, and it's all very awkward in this hotel in Hong Kong, where he'd keep sending messages to Jennifer's room saying, I've got to talk to you, you know, I've got to save my reputation, and she's saying, you have to do this presentation and you have to answer questions.

But then the questions were sort of technical, not very interesting questions, and it was kind of messy.

They never confronted the deep issues, and then Jojuan Ki kind of walks off stage and leaves and goes back to China.

He thought he was going to be world famous, like the person who cloned Dolly the Sheep, or you know, one of those big breakthroughs.

And he had hired an American public relation specialist who had set up sort of embargoed private interviews with the Associated Press that would be released when he did his scientific paper and videos.

He made five videos that were held until they were going to all be released on the same day, and then the paper comes out and all of a sudden, people realize, well, he's not going to be celebrated.

This was actually a crossing of an ethical line.

Still Doubna and some of our colleagues believed that what happened with Hojenqui shouldn't dictate the rules of the field, but more so serve as a warning and tells me that crisper researchers were trying to walk a delicate line between enforcing appropriate rules and potentially stunting their own research.

They wanted to make sure that people didn't just run away with this saying, but they also wanted to make sure that governments, regulators, and people didn't try to stop research on it.

And so Jennifer, unlike Eric Lander and some others, fights the notion of having a moratorium or a ban, and we ended up not having a moratorium on crisper gene editing, and we're still trying to find this prudent path forward.

So they think that maybe they can put the genie back in the bottle or keep Pandora's box closed, And so far there hasn't been a runaway efforts to do inheritable gene edits.

And the Chinese even cracked down on this scientist, put him under house arrests, took his license away.

But the moment, the rules of the road are being respected.

And you describe a little bit how doubt does thinking did evolve over time when it came to, you know, not necessarily favoring a moratorium, but like feeling stronger at one point about putting harder lines.

And what changed over the course of a few years for her.

She originally wanted a whole lot of restrictions on the use of Crisper and said it was kind of dangerous to go too fast.

But it conferences and in other places I'd see people come up to her, they pull out a photograph say, this is my daughter and she has this genetic thing.

She's going to die in a year a year and a half.

It's degenerative.

Can you save her life please?

And Jennifer would have to say, we're going to try to do that someday with crisper, but no, it's not going to be ready in six months a year.

And also she began to realize all the suffering that could be stopped with crisper, so she began to be a little bit more open about the potential and wanting to make sure that too many restrictions were not put on it.

Her ideas changed.

Also.

Another thing causing to evolve was, of course, the coronavirus and COVID were suddenly were confronted with a viral attack.

Among many things, COVID brought to the forefront the importance of RNA technology.

Isaacson tells me that from the beginning of the pandemic, DOWDNA and her colleagues understood that they needed to get to work creating testing materials and eventually a vaccine.

Jennifer Dowd, who had been working on Crisper, all of a sudden realizes when COVID hits, how nature had created in this way of fighting viruses, and how relevant suddenly to our own lives, because we have to fight a virus just like bacteria did.

And in some ways nature is amazing that way that something that starts as a pure curiosity of what weird bacteria from salt ponds do become so central to our own lives when we get attacked by viruses.

It's really just a week or so into the first news of the pandemic and they start forming teams with or organizing it.

Like one team that's going to build a testing system, another team that's going to build the next generation of testing using Crisper to test for the viruses.

Another team that's going to try to do a Crisper based vaccine for the virus.

And so these teams start to work, and some of it is very mundane, like just testing everybody in the Bay Area she who has COVID because they didn't have good COVID test back then.

Teams were doing things that are still ongoing, like using Crisper for a vaccine that will guard against any form of coronavirus.

And even as they got together and informed these teams some of what they were doing, including the testing, it sort of outpaced the government's ability to process it.

Like they had tests ready, but they needed to jump through all these hoops to get the tests approved because no one had anticipated that this would even be possible.

We have to remember how meshy the original response to COVID was.

People will have heard, you know, the COVID vaccines, the modernic vaccine, the Pfizer vaccine are RNA related.

Can you explain to what extent Crisper itself played a role in the vaccines that we know now versus treatments that may come down the line.

The new vaccines that most of us had against COVID, known as mRNA vaccines meaning Messenger RNA.

That is not exactly the same as CRISPER, but it still uses the notion that RNA is this miracle molecule and it can be programmed to do things.

So that's how RNA technology more than just Crisper technology, but RNA as a messenger, as a molecule that could tell the cell to do something and be programmed by us to tell the cell to do something we wanted to do.

That's in the realm of the world of RNA and CRISPER, but it's a particular type of thing called messenger RNA.

Throughout this race to understand how the COVID nineteen virus worked and how RNA and CRISPER could work together to stop it, Isaacson tells me old rivalries into the forefront, but this time the goal was one that transcended personal recognition.

You have Jennifer's lab racing to do it, Fung Jang's lab racing to do it.

And this time, even though they're sort of competing, they know the stakes for society are huge, and they're working together more and not trying to beat each other to patents is the way science should work.

There couldn't have been a more a stronger moment to illustrate the value of the basic research than what happened right as they are developing these these technologies.

Yeah, I mean, I'm writing this book and thinking I'm a bit of an arcane field, which is what's RNA doing?

And I was even wondering, how does the book come to some you know, relevant conclusions so people don't think they're just reading the book about, you know, a gene editing tool.

And it was interesting because COVID is just so at the core of what the book is about, because it's about organisms that have to fight off viruses and as I said, bacteria have been doing this for billions of years.

It's the biggest war ever happened on this planet.

And the fact that out of pure curiosity we could learn something about how bacteria fight viruses and apply it to ourselves just at the moment when we're getting a viral pandemic with a spike protein, we can even mimic using messenger RNA.

I think that helped show how relevant and exciting but also important the science can be.

Coming up after the break, we dive into a middle of the night call to DAWDNA one that we confirmed she had embarked on the right research path all along.

In the middle of all this, in October of twenty twenty, Jennifer Dowdner gets a call in the middle of the night.

Yeah, she's in a conference, the first in person conference she's been to.

I think it's down in Palo Alto, you know, an hour down from Berkeley.

And in the middle of the night, the phone rings and she doesn't answer.

It's on vibrate, but finally she answers, and it's a reporter at four am SEC.

What's your reaction to the Nobel Prize?

She says, who won the Nobel Prize.

The reporter says, you did, and with Emmanuel looks at her phone and she sees a lot of miscalls from Stockholm, Sweden, and she says, oh, okay, I'll call you back.

I stayed up that night even if Jennifer dowdan didn't.

I was here in New Orleans, and I set my alarm for whatever it is, three am, four am for when it was going to be announced in Stockholm, and they start announcing it and they said, this year's prize goes for the tool that will help us with the secrets of life and edit our genes.

And I go, yes, it's crisper.

And all of these labs at this point have to some extent turned their attention or part of their attention towards commercializing these technology, towards finding through companies, finding the treatments that will actually bring them into human use, and that creates all these other dilemmas, ethical dilemmas that arise out of it.

And I want to talk a little bit about that.

Can you run us through some of your thought experiments on the implications of crisper being used in a variety of different ways.

I think the big ethical issues are when is it okay to edit our genes?

And in the book, I start with a whole lot of cases, and so we got to go slowly, step by step, because slopes are less slippery that way, and this could be a slippery slope.

And so you can look at things that are debilitating conditions like sickle cell, and it's a simple edit, and you can do it in effect only the individual involved, not reproductive cells.

And that's a no brainer to me.

There is a person in the book, David Sanchez, who's a sweet, wonderful kid, was seventeen when we were doing the book, and he loves playing basketball except for when he doubles over in pain on the floor because he has sickle cell.

And so he becomes part of one of the experiments to treat sickle cell, and they tell him, with crisper, we can cure this, and we can even with crisper if we do it in reproductive cells or embryos, make it so that your children will never have sickle cell, and all of your descendants will never have sickle cell.

And David says, that's great, and then he pauses this in a documentary he was being interviewed for and says, but maybe I should let my kid decide that.

Maybe that should be their choice.

And I said to him, wait a minute.

You know you doubled over in pain.

Do you want that to happen to you kid?

He said, well, I learned a lot from sickle cell.

I learned perseverance, I learned how to get up off the floor.

And so maybe we shouldn't just edit it out of the human species, but use it as treatments at times.

And I thought, well, that's amazing for a seventeen year old have been this morally thoughtful about it.

And I asked him again later and he said, now that I think about it, I probably want my kids to be edited so that they'll never have sickle cell.

I said, what about perseverance?

He said, I want to teach him perseverance, but I don't want him to feel the pain that I felt when I crumple up up playing basketball.

So these are complicated ethical things.

Then you get to the next step of thinking on this slope we're going down, and you say, well, you know, if we can edit for sickle cell so that the blood cells are not crumpled and does carry less oxygen, and we can fix it.

What if we get edited so they carry a little bit of extra oxygen, like fifty percent more oxygen each cell.

I could edit my kids and all of my descendants to be amazing Olympic athletes.

Is that ethically worse than curing sickle cell?

I would say yes, that's a difference between making a cure for a bad disorder or making an enhancement to the human species.

I asked George Church.

He says, what do you mean, what's wrong with enhancing the human species?

What if we can edit IQ and make it better?

All of us want our kids.

Maybe we can make our kids taller.

Tell me what's wrong with trying to enhance your kids and make them more powerful?

So I asked Jennifer, we all have to think about it.

One thing that's wrong with it is if these genetic treatments will be costly, and they will be, you could have it so the rich can buy better genes for their kids than poor people.

You don't want to have two species, the genetically you know, that's the brave New World issue, the genetically enhanced part of the species and the genetically inferior part of the species.

Secondly, if you let each individual decide, they can go into a clinic and you give them as if it's the genetic supermarket.

Here's the list.

What do you want?

Blond hair, blue eyes?

Do you want brown hair?

And you can secretly, with no knowing, you can check off what do you want?

What would people check off?

At the end of the book, I talked about sitting on the balcony here in New Orleans and Royal Street in the French Quarter, and all sorts of things are happening.

There's a funeral for Leah Chase, a great creole of colored cook, and there's a naked bicycle race for safety traffic safety.

There's a gay pride parades, and you look at the diversity to people tall and short and straight and gay and trans, and black and white, and people from Gallia Day University sign language, and you think, what if we could edit out all deafness, What if we could edit out so every parent could choose sexual orientation, skin color, would we hurt the beautiful diversity of our species?

These are the moral issues that Jennifer and then at other places I was trying to wrestle.

With, and it raises to return to sort of you know, the big questions.

One of them you've touched on here, which is you write about how with something like deafness or autism, if that could be you know, quote unquote treated.

It also raises a question like what is a disorder?

What is a disability?

One person's disability is not necessarily another person's disability in this world?

And how do we decide which things even if you forget about enhancements, what are things that we're even able to treat right?

And if we in society as a whole make decisions, we'd probably say, let's not edit out being gay, Let's not edit out even you know, being on the autism spectrum.

But if you leave it to each individual parent, they might say, I don't want my kid to ever suffer from depression.

I don't want them to be even in a small part of the autism spectrum or aspergers or whatever they want to call it.

And maybe you're editing out the hemming ways.

You're editing out van Go, You're editing out people who had either psychological or personal or whatever, or editing out Helen Keller, you know from being deaf?

Was the world better off without van Go and Helen Keller?

No, If you're a mother and father and say your kid will be born deaf, but we can easily change that, would you say, yeah, please change it.

I'll let you think.

Would you do it?

And you know in the book there's somebody there who's a deaf couple and they're about to have a child.

They want to make sure their child is deaf because they want to keep that' subculture alive.

How much of this should be individual choice or how much should be society as a whole saying you're not allowed to do some of these things.

The ethical considerations around Crisper cast nine will likely only grow as the technolog He continues to advance the news around Baby kJ renewed mainstream interests in the field and what it can accomplish, but Isaacson tells me there's still a long way to go.

We're not quite as far along as I thought we might be.

It's been ten years, but we have cured sickle cell in patients Victoria Gray, she's pictured in the book, part of the experiment.

But now they're the private companies Crisper Therapeutics of Emmanuel Sharp and Jay, who have a cure for sickle cell.

And there are four or five other type syndrums that we can now fix.

The big one about to happen in clinical trials is cancer treatments, where you can use Crisper to change some of the immune system so that you're cancer fighting treatments or the cancer cells can be defeated.

That's a shorthand of it.

But yet we're about to have we have very personalized cancer treatments targeted to your particular tumor, and Crisper can make it so that that type of treatment can work more easily.

It did strike me that you end the book on really a note of optimism about both Crisper but also the sort of like understanding and connection to science that people were having because of the mRNA vaccines at that moment in COVID, and it feels like that has all gone a little bit south or a lot south since that moment.

So I'm wondering how you feel, first of all, about the way people view science today and how that connects up with how people view what crisper can do.

One of the great tragedies of our time has been over the past few years, a backlash against science, just part of the larger backlash against expertise and establishment.

So, you know, a book, like a book on Jennifer Dowd can explain what is it a messenger RNA does and when people say the mRNA vaccine is going to destroy my DNA and change me forever, No, no, no, understand it.

It doesn't even go into the nucleus of yourself.

It's just an RNA.

It's on the outside of your you know, the outer part of your cell making protein, so it doesn't change your genetic code.

Now that may not, you know, be an easy cell, but it's a beautiful thing to understand the science, And I think it's a shame that after COVID and the great advances that we've had using RNA to make a vaccine within a year, pretty much knocking back the dangers of COVID and using these treatments to cure sickle cell.

I think it's important for people to marvel at and understand how these work so that people can be inspired, like Jennifer was when she read The Double Helix, to become scientist, or even if you're not going to become a science be odd and inspired by what science can do and the beauty of understanding it so that you can make your own informed judgments about what treatments you may want.

It feels like that backlash towards science, towards expertise is either enabling or fueling this current attack on basic science, the funding for basic science to begin with.

And you spend a lot of time in the book describing the way these very basic questions of curiosity lead down the road to changes in our lives, positive changes in our lives.

How are you feeling in this moment when a lot of basic science feels like it's under threat.

For eighty years, since the end of World War Two, we've had a system that has made the United States the powerhouse in innovation.

It was a system set up by Beneva Bush, who is somebody who ran science for the government during the war, including the Adam Baum project, but also had been a provost at MIT and started a company rightly, and he said, we're going to have a system where government funds basic science research and does it at university labs, and then allows it when it's successful and turns into a tool we can use to be commercialized by companies.

If we stop funding that basic research, that means like we're destroying the seeds that will become innovations in the future.

And China, which is doing huge amounts of basic reat search, whether it's on life sciences or gene editing or AI, will totally surpass us, and so will other places.

So there's nothing worse you could do for the future of America.

You've written about this sort of your view of the revolutions, the revolution of atoms, followed by the revolution of bits and the digital era, and now comes the revolution in biology.

Do you feel like your perspective on that has changed at all, that they could be slowed down or stopped.

I think the revolution in the life sciences will define the first half of our century, the next twenty five years or so, I think it will be combined with the revolution in artificial intelligence.

In fact, if you look at the Nobel Prizes, if you look at Demis Hosipus who just won it, it was for applying AI to how proteins fold and how the folding of proteins determines what they can do.

Because James Watson taught us in a double helix, and as Jennifer taught us about RNA, the structure of a molecule helps make it a key that can unlock certain things.

So as we have AI do protein folding, and as we have AI and machine learning go through databases of everybody's genetic code and what type of things work and don't work, this whole revolution of life sciences combined with AI technology has unbelievable potential.

In the next episode of On Crisper, we listen to a conversation between Isaacson and Jennifer Downer at the New Orleans Book Festival at Tulane University.

You won't want to miss it on Crisper.

The Story of Jennifer Downa is a production of Kaleidoscope, and iHeart this show is based on the writing and reporting of war Walter Isaacson.

It's hosted by me Evan Ratliffe and produced by Adrianna Tapia with assistance from Alex Janenveldt, who was mixed by Kyle Murdoch, and our studio engineer was Thomas Walsh.

Our executive producers are Kate Osbourne and Mangashatikadur from Kaleidoscope and Katrina Nobel 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 has written.

On Musk for an intimate dive into all the facets of Elon Musk and on Benjamin Franklin to understand how his scientific curiosity shaped society as we know it.