--:-- Sean Rameswaram: Support for the show today comes from Quip Electric Toothbrush. It's like, what if someone who really cared about design made a toothbrush for you? That's the Quip. Check it out at getquip.com slash explained. Your first set of refills is free.
--:-- Sean Rameswaram: Joss Fong, you're a science reporter here at Vox. We talked with you a couple of months back about genetic engineering, and most of our conversations seem pretty sci-fi. But this week, there was news that this Chinese scientist says he's genetically engineered two human babies. Is this the beginning of the end? Is this how it starts?
--:-- Joss Fong: It's the beginning of something. I feel like, you know, in cartoons where their legs are moving so fast that the head hasn't caught up? That's how I feel about all of this right now. I did not expect to see a CRISPR baby this year. But you know maybe I should have because the whole deal with CRISPR is how cheap and easy it makes gene editing.
--:-- Sean Rameswaram: Remind the people what CRISPR is again.
--:-- Joss Fong: CRISPR is a tool for editing DNA and that can sound really abstract. Yeah. So I like to picture a Word document that has a million pages in it. Okay. And in those pages are just billions of letters. It's A's, T's, C's, and G's. That's a genome. It's all the DNA that's inside of an organism.
--:-- Sean Rameswaram: Say you want to change a few of the letters inside of it. How would you do that?
--:-- Joss Fong: Basically what CRISPR does is it adds a find and replace function to that document so that scientists can essentially type in the sequence of DNA that they want to find and then make the edit at that point.
--:-- Sean Rameswaram: So is it like something that scientists built?
--:-- Joss Fong: CRISPR is a bacterial immune system that scientists discovered inside the genomes of various bacteria. What's turned it into a tool is that researchers have figured out how to reprogram this immune system to edit DNA for our own purposes.
--:-- Sean Rameswaram: I talked to Jennifer Doudna, one of the pioneers of this, for our show on Netflix.
--:-- Joss Fong: Never thought I'd become a genome engineer. It was a result of curiosity-driven research that was aimed at it in a very different direction from where it ended up. She wasn't looking to develop a gene editing tool. They were just interested in figuring out how bacteria work, how this immune system worked.
--:-- Sean Rameswaram: Okay. And what they found is that if they grabbed it and kind of rejiggered it a little bit, it could be this immensely powerful tool.
--:-- Joss Fong: How does this tool actually work? I mean, the document analogy helps, but what are scientists actually doing? Or can like anyone do this?
--:-- Sean Rameswaram: So to edit DNA, you need a couple things. You need a way to cut the double helix. And you do that with something called an endonuclease, which is basically an enzyme that cuts DNA.
--:-- Joss Fong: Literally like slices through both strands of the DNA. There's plenty of enzymes that do that. That's not the hard part. The hard part is putting that enzyme in the right place so it's cutting the gene that you want.
--:-- Sean Rameswaram: And what was so brilliant about CRISPR is that it uses a strand of RNA as the kind of GPS system, just to layer another metaphor on here, to guide that enzyme to the segment of DNA that you want to edit.
--:-- Joss Fong: RNA is super easy to make. It's super easy to program, and that makes this tool incredibly accessible to scientists, to non-scientists. And so now basically every biology lab has the power to edit DNA in every organism that it's been tried in.
--:-- Sean Rameswaram: This works. I've been doing science professionally for about 25 years, and I have never seen a technology take off the way gene editing has. It's transforming the field of biology.
--:-- Joss Fong: You said it was cheap. How cheap are we talking?
--:-- Sean Rameswaram: Well, you can buy this DIY CRISPR kit for less than $200.
--:-- Joss Fong: Wow. What makes CRISPR better than the tools that already existed to edit DNA is that it's really easy to do, and you can do it in pretty much any living thing.
--:-- Sean Rameswaram: I talked to Neville Sanjana, who is a biologist in New York who works with CRISPR, and he compares this current era to the early days of Silicon Valley.
--:-- Joss Fong: 40, 50 years ago, when it's just becoming clear that we had this ability to program computers, it was really hard, I think, to see all the developments like the internet or computers inside everyone's pocket.
--:-- Sean Rameswaram: What will happen 20, 30, 40 years from now? It's kind of hard to look into the future and see, you know, what is the equivalent of the smartphone for biology, but that's kind of where we're headed.
--:-- Joss Fong: So how far are we away from, like, Gattaca, 1997, Ethan Hawke, Uma Thurman?
--:-- Sean Rameswaram: Ooh, Gattaca. The Gattaca question comes in when you're talking about editing the germline. Which is to say like changing human characteristics.
--:-- Joss Fong: Yeah. Germline cells are those that we pass to our offspring. Think about medicine. You're treating someone for muscular dystrophy. Those muscle cells don't get passed on through their eggs or sperm. Those eggs and sperm and embryos are germline cells.
--:-- Sean Rameswaram: And if you start editing those, what you're talking about is editing future generations.
--:-- Joss Fong: There's a scene in Gattaca that I think really highlights these questions. Ethan Hawke's parents are in a fertility clinic designing their next child. You have specified hazel eyes, dark hair, and fair skin.
--:-- Sean Rameswaram: And then the geneticist says, oh, by the way. I've taken the liberty of eradicating any potentially prejudicial conditions. premature baldness, myopia, alcoholism, and addictive susceptibility.
--:-- Joss Fong: And I talked to Jennifer Doudna, one of the CRISPR pioneers, about this. She said, when I saw that movie, it was science fiction. And now it's looking like, you know, we're almost to that world.
--:-- Sean Rameswaram: And keep in mind, this child is still you. Simply the best of you
--:-- Joss Fong: Now I want to be clear we can edit things like baldness or addiction or obesity or intelligence or athletic ability These are very complex traits That is still science fiction.
--:-- Sean Rameswaram: Yeah. But what this scene does is it highlights that there's two debates with using CRISPR in humans. The first one being, should we edit the germline? And the second is, should we do enhancements? Meaning, should we edit genes in a way that gives people some extra ability above what is quote-unquote normal?
--:-- Joss Fong: And that line is not as clear as it might seem. If you think about genes that affect your risk for Alzheimer's disease, if you have an embryo, you've screened it, and they say this embryo has a high risk of Alzheimer's disease later in life, and they offer you to switch it for the low-risk one, which is lower than the typical risk in the population, is that an enhancement? Or is it a treatment?
--:-- Sean Rameswaram: These are hard questions.
--:-- Joss Fong: And now it seems like this Chinese scientist has actually designed human babies using CRISPR. What happened? What is he claiming?
--:-- Sean Rameswaram: So this week, Antonio Regalado, who's a reporter at MIT Technology Review, found out that this scientist in China, He Jiankui, who goes by JK in the United States, was moving forward with making CRISPR babies.
--:-- Joss Fong: And then the AP released a report that two babies had actually been born, two twins that were edited to give them resistance to HIV by knocking out this gene CCR5.
--:-- Sean Rameswaram: Which sounds noble. Is this the only way to do that? No.
--:-- Joss Fong: And that's part of why everyone is mad at him right now. There's several layers of ethical questions. The first is whether these girls are okay.
--:-- Sean Rameswaram: Sure. The second layer is, you know, the procedure. Did the participants understand what they were signing up for? Did he get the appropriate ethics review?
--:-- Joss Fong: There's some allegations that he forged some documentation in order to move forward with this.
--:-- Sean Rameswaram: And then there's not a clear case that there is a strong medical need for this type of use of CRISPR.
--:-- Joss Fong: We have ways of preventing the transmission of HIV between parents and their babies. We have lots of ways of treating HIV.
--:-- Sean Rameswaram: But it was clear that he wanted to be first to make a CRISPR baby.
--:-- Joss Fong: And this is how he chose to do it.
--:-- Sean Rameswaram: Is China, like, supporting this guy's experimentation on humanity here? Or are they pissed?
--:-- Joss Fong: They seem pretty pissed. Okay. China's investigating him. The university that he worked for says they didn't know anything about this. He was on unpaid leave during the time that this experiment was conducted.
--:-- Sean Rameswaram: I think over 100 Chinese scientists released a letter condemning this work. People are really pissed at him right now. And that includes people in China.
--:-- Joss Fong: You're saying some gene in these twin babies has been altered. If I look at these twin babies, how do I know if he's telling the truth or not?
--:-- Sean Rameswaram: Yeah, we can't know for sure. It hasn't been confirmed. He didn't publish anything.
--:-- Joss Fong: When this came out, he released a series of YouTube videos announcing it. Classic way to announce you've altered humanity forever.
--:-- Sean Rameswaram: I feel a strong responsibility that it's not just to make it first, but also make it as example.
--:-- Joss Fong: And then he presented the results this week at this conference in Hong Kong about human genome editing. A bunch of scientists started asking him really pointed, really critical questions.
--:-- Sean Rameswaram: This is a red line. Why do you choose to cross this line?
--:-- Joss Fong: I'm quite interested in what happened in that conversation and how you explained what the risks were. And what evidence you have that they actually understood. How could you evaluate their potential mental health?
--:-- Sean Rameswaram: What is our responsibility as scientists and doctors to make that decision for the patients rather than allowing patients to make critical decisions seemingly on their own?
--:-- Joss Fong: What they're basically saying is like, what did you do?
--:-- Sean Rameswaram: And one of the questions they asked him is, are there more babies on the way?
--:-- Joss Fong: And he indicated... There is another one.
--:-- Sean Rameswaram: It doesn't seem like there would be a reason for him to make this up. He's an expert in DNA sequencing, and he showed his data, which seems rigorous.
--:-- Joss Fong: I think one of the reasons why we should believe that he did this is that it's not hard to do.
--:-- Sean Rameswaram: I guess what seems scariest about this is, like, there's just some random scientist in a lab deciding that he wants to alter how humans are made.
--:-- Joss Fong: And now that someone's saying he's done it, maybe another 500 scientists will be like, man, maybe I'll give that a shot too.
--:-- Sean Rameswaram: Isn't that, like, scary?
--:-- Joss Fong: Yeah, I think it really is. I mean, from the scientist's point of view, people who work in this field, they're really worried that something could go wrong.
--:-- Sean Rameswaram: You know, there's a history of gene editing trials resulting in deaths that set the field back for many, many years.
--:-- Joss Fong: And I think there's a lot of promise for human health, for other things that scientists want to make sure can move forward.
--:-- Sean Rameswaram: I think it's important to keep some perspective. We have a long trend toward using genetics more and more in human reproduction.
--:-- Joss Fong: This is a big step towards that direction, but we've been doing it for a really long time.
--:-- Sean Rameswaram: I mean, in the United States, you can walk into a fertility clinic in New York, say, I want a baby, I don't want a girl, and I want my baby boy to have blue eyes.
--:-- Joss Fong: You can do that.
--:-- Sean Rameswaram: And I think we need to remember that there are non-CRISPR questions that have to do with the way that we're using genetics to choose what kind of humans we bring into the world.
--:-- Sean Rameswaram: Coming up on the show, it might be scary, but there's still a hell of a lot of good CRISPR can do.
--:-- Joss Fong: So Hey so I just going to read a message someone sent me.
--:-- Sean Rameswaram: Hey Sean, I'm a big fan and listen to every episode. My boyfriend of 10 years, who often takes long car rides with me, is mandatorily volunteered to listen as well.
--:-- Joss Fong: So one would think, after months and months and a long car trip from Grand Rapids, Michigan to Norfolk, Virginia round trip, and to include several conversations about our very own toothbrushes, he would get the point and get me a quip.
--:-- Sean Rameswaram: So I thought with the holiday season, I would just get myself one for me. Then I saw it would be a savings if I bought two. So I did, ordered them today.
--:-- Joss Fong: You know, you think after 10 years, your partner would get the hint when you turn up the commercial.
--:-- Sean Rameswaram: Love what you do. Live long and prosper. David. Getquip.com slash explain. Don't disappoint your partners.
--:-- Sean Rameswaram: Joss, we're talking about doing this on humans, using CRISPR to alter humans, but this isn't just something that we're doing with humans, right?
--:-- Joss Fong: Right. CRISPR can edit all life forms. And so there's lots of applications in plants and animals.
--:-- Sean Rameswaram: One of the most controversial is this idea of using a gene drive, which is an extension of the CRISPR technology that allows you to kind of push a gene edit through a wild population of organisms.
--:-- Joss Fong: And just yesterday, the UN Convention on Biological Diversity considered and rejected a moratorium that would temporarily ban the release of any gene drive animals.
--:-- Sean Rameswaram: That's something that environmental activists had wanted.
--:-- Joss Fong: Any particular animals? I mean, I think one of the big ones is mosquitoes that transmit malaria.
--:-- Sean Rameswaram: The mosquito-borne disease is a ferocious foe. Despite global eradication efforts, around 450,000 people died last year.
--:-- Joss Fong: And what makes it particularly ghastly is that 70% of the people who die are little kids. They're under five years old.
--:-- Sean Rameswaram: There's been a lot of progress on malaria over the past 15 years or so, but the death rate is still unacceptably high.
--:-- Joss Fong: So how could CRISPR be a better solution for malaria than like nets and pills and bug spray?
--:-- Sean Rameswaram: So this whole concept of a gene drive where you push a trait through a population of wild animals has been around for decades. But they never had the tool to really make it work.
--:-- Joss Fong: CRISPR is that tool. And so this whole concept of engineering a self-propagating genetic modification is suddenly really real.
--:-- Sean Rameswaram: And we're talking about the last five years.
--:-- Joss Fong: So scientists want to use CRISPR to tweak mosquitoes. What exactly do they want to do to them?
--:-- Sean Rameswaram: So there's two broad approaches to using gene drive on malaria mosquitoes.
--:-- Joss Fong: There's a group called Target Malaria that's interested in kind of shrinking mosquito populations. So there's just fewer mosquitoes to carry this disease.
--:-- Sean Rameswaram: Okay. The other approach that's being worked on at some University of California institutions is changing their genetic makeup so that they're resistant to the malaria parasite.
--:-- Joss Fong: Okay. So the females don't pick it up from people and carry it to another. That's a different set of genes that you can change to create that resistance.
--:-- Sean Rameswaram: How far away are any of these organizations from realizing this dream?
--:-- Joss Fong: So I worked on this story with another Vox reporter, Dylan Matthews, and we did a whole bunch of interviews for this.
--:-- Sean Rameswaram: And some of those interviews were with the scientists that are actually engineering these gene drives.
--:-- Joss Fong: And our question for them was, when is this happening?
--:-- Sean Rameswaram: There was a lot of talk about this in 2014. We're now, you know, 2018. How long will it take?
--:-- Joss Fong: Yeah. And they said that their mosquitoes could be ready for field testing within a couple of years.
--:-- Sean Rameswaram: Wow. Which is amazing. Like these real live mosquitoes. Live mosquitoes. Will be ready to go to Africa?
--:-- Joss Fong: Yeah. They did some preliminary tests. They had immense success. They've been working on these mosquitoes to make them better and better.
--:-- Sean Rameswaram: And the next step is to test them in a field trial.
--:-- Joss Fong: So that would be a large cage out in the wild or on a very remote island where the chance of them spreading to the mainland is very small.
--:-- Sean Rameswaram: If so many people are dying of malaria right now in Africa, why haven't these modified mosquitoes been released?
--:-- Joss Fong: It's a good question. The science is not quite finished, But I think at this point, the real delay is going to be getting the approval from a wide patchwork of African countries, some of which have more robust governance than others.
--:-- Sean Rameswaram: This is completely unprecedented. Right. We're talking about changing a wild species of animals that crosses borders, crosses continents in some cases.
--:-- Joss Fong: There is no regulatory structure for this. And so it's going to be a while before that structure is in place.
--:-- Sean Rameswaram: Right now, the science is far ahead of it.
--:-- Joss Fong: Is there some group of scientists or environmentalists or politicians or anyone out there fighting this? Someone who's hesitant to mess with nature like this?
--:-- Sean Rameswaram: Because we're messing with nature, right?
--:-- Joss Fong: Yeah, this is a drastic extension of human power over nature.
--:-- Sean Rameswaram: This technology has arrived remarkably quickly. With gene drives, you know, a small group of biologists could change a wild species. That's huge.
--:-- Joss Fong: I talked to Dana Pearls, who's part of Friends of the Earth. We have safe and less risky ways of addressing problems on this planet that aren't about permanently altering nature.
--:-- Sean Rameswaram: So I think it really important that governments do environmental assessments to see what role these mosquitoes play inside of these ecosystems and what the potential ripple effects of doing this could be
--:-- Joss Fong: But the question becomes what unintended consequence could be worse than hundreds of thousands of little kids dying every year?
--:-- Sean Rameswaram: I haven't found a good answer to that question.
--:-- Joss Fong: And Dylan interviewed an MIT scientist, his name is Kevin Esvelt. And while they were having this conversation, Kevin just stopped to highlight the urgency of this.
--:-- Sean Rameswaram: And he said, There's a strong ethical argument of doing something now today because so many children have died just in the time that we've been speaking.
--:-- Joss Fong: I would say at least 20. We don't want to rush this. It needs to be very methodical because if there is a controversy, if there is a backlash, the cost of that is just immense.
--:-- Sean Rameswaram: Every two minutes, malaria is killing somebody's baby.
--:-- Joss Fong: And if this becomes really politicized I think what we've learned from the climate change debate is that science can really outpace the rate at which humans get their shit together.
--:-- Sean Rameswaram: It would be unfortunate to see that kind of politicization create delays when the cost of an action is so clear and so direct.
--:-- Joss Fong: I feel like it's inevitable that this is just like self-driving cars or Facebook and Cambridge Analytica. Like, we won't have the conversation until people die, until something goes terribly wrong.
--:-- Sean Rameswaram: Yeah. And one of the things that Doudna is really worried about is that something will go wrong, and it will create a backlash against gene editing writ large.
--:-- Joss Fong: My biggest fear, honestly, is that we'll see the use of gene editing getting ahead of itself, an application that causes harm or the perception of harm and fear in people that creates a backlash against a technology that I think has really the potential to be incredibly positive.
--:-- Sean Rameswaram: That would be a tragedy because this is a technology that has the potential to cure diseases. Save children. Millions of children.
--:-- Joss Fong: How do we balance these two things? You've got this push to use CRISPR on mosquitoes, which seems to have some really broad support and could save millions and millions of people.
--:-- Sean Rameswaram: And then this guy out there in China who's using CRISPR to change humans, which I think people find to be a lot more scary.
--:-- Joss Fong: Yeah, I think we're reckoning with the reality that our species has come to a point where a single person or a small group of people can make, you know, very targeted changes to the DNA of living things, not just one individual organism, but, you know, the descendants of that organism.
--:-- Sean Rameswaram: Yeah. And so I think it's going to be really important that we evaluate each application individually.
--:-- Joss Fong: So it's not, you know, CRISPR is bad or CRISPR is good.
--:-- Sean Rameswaram: Yeah. But, you know, we as a society have decided that this use of CRISPR has greater benefits than harms and these do not.
--:-- Joss Fong: Right. And, you know, the really difficult problem and really scary problem with that is that we're simply not going to agree about which of these applications are okay and which aren't okay.
--:-- Sean Rameswaram: And we're talking about technologies that transcend borders, and we're going to have countries that have different values and different opinions on what should move forward.
--:-- Joss Fong: We're going to have scientists that have individually different ideas about what we should be doing.
--:-- Sean Rameswaram: I think we're going to see a patchwork of different approaches, and that means that in different places, the human genome is going to look different.
--:-- Joss Fong: It's going to continue to diverge as countries and cultures and individuals take different stances on what we should do to our own dna
--:-- Sean Rameswaram: No big deal what you're saying is what it means to be a human has begun to change it has
--:-- Joss Fong: Joss Fong reports on Science for Vox. You can find her work all over Vox's YouTube channel. It's youtube.com slash Vox. She also made a sick episode about this very subject for Vox's Netflix show. It's called Explained.
--:-- Sean Rameswaram: I'm Sean Ramis from this show is called Today Explained. And this is our 200th episode. To mark the occasion, I'm going to shout out the names of the outstanding people who make this show 200 times. Starting with... Irene Noguchi.
--:-- [200 times repeating Irene Noguchi's name]
--:-- Sean Rameswaram: Thanks again to Quip for supporting the show all week. Quip electric toothbrushes. If you haven't heard, they start at $25. Your first set of refills is free at getquip.com slash explained.
--:-- Sean Rameswaram: Anil Dash, you are the host of Function with Anil Dash, but your producer, Bridget Armstrong, sent me a rundown of upcoming episodes and episodes that already exist, And I said, we have to talk about this particular episode because you are making an episode of your show about podcast ads.
--:-- Anil Dash: Yeah. You know, it is a fascinating story about how the economics and the advertising world of podcasts is totally different than any other media.
--:-- Sean Rameswaram: It doesn't work like TV. It doesn't work like newspapers. And to talk to creators who make great shows and have them say, you know what, this actually gives me more freedom.
--:-- Anil Dash: It makes me feel less like a sellout if I just had dropped some ads in.
--:-- Sean Rameswaram: I thought that was fascinating. And it's one of those things that I feel like you can really only hear on Function.
--:-- Anil Dash: Function with Anil Dash wherever you find your podcasts. Please use our promo code when you check out.
