--:-- Sean Rameswaram: Hello, Sean. Connecting via WhatsApp today. I know. The last try, I think, right? What are you doing today? Cleaning up. Lots to do. Hmm. Sounds like you've got to move forward with your day. Yes. You know who else is moving forward? Uber. Yep. They're listening to feedback so they can improve and get better with every trip. Yes. Building new features to take the stress out of your pickup and working on ways to keep you better protected and connected throughout your ride. You can find out more by going to uber.com slash moving forward. Like me, I am more forward. I was married for donkey's years. Now I am more forward.
--:-- Sean Rameswaram: Bill Gates offered up millions of dollars to kill off mosquitoes this week. And the foundation he runs with his wife Melinda has pledged nearly $2 billion more. It seems like Bill will do anything to get rid of some mosquitoes. Now malaria is, of course, transmitted by mosquitoes. I brought some here so you could experience this. We'll let those roam around the auditorium a little bit. He'll do anything to get people to care. I am the mosquito. He's even made a bunch of Funny or Die style comedy videos. The greatest killer of all time. Yet I do not feel great. One of them features a guy in a giant mosquito costume walking around some beach town getting shunned by everyone. I just sprayed myself with a whole can of off to keep myself off myself.
--:-- Sean Rameswaram: Bill Gates has a very good reason for wanting to kill all these mosquitoes. and he's got a pretty nifty weapon in his back pocket. And no, it's not a guy in a giant mosquito costume. Joss Fong, science reporter here at Vox. Does Bill Gates want to kill all the mosquitoes?
--:-- Joss Fong: So there are over 3,500 species of mosquitoes in the world. Bill Gates has a beef with just a handful of them, the ones that transmit a parasite that causes malaria. The mosquito-borne disease is a ferocious foe. Despite global eradication efforts, around 450,000 people died last year. 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. What's being done now? Is it just like nets and bug spray?
--:-- Joss Fong: Exactly. It is a curable disease. It's curable with drugs. In Sub-Saharan Africa, it's often hard to give people the drugs that they need to treat the disease. And so the approach there has been a lot of bed nets, a lot of insecticides, making sure that people are covered at nighttime, which is when the female mosquitoes like to bite.
--:-- Sean Rameswaram: Okay, so what does Bill Gates want to do?
--:-- Joss Fong: Bill Gates wants to use CRISPR to modify the mosquito population in a way that shrinks their population. So there's just fewer mosquitoes around to transmit malaria.
--:-- Sean Rameswaram: What is CRISPR?
--:-- 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. Okay. 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. 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.
--:-- Joss Fong: 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. 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.
--:-- Sean Rameswaram: How does this tool actually work? I mean, the document analogy helps, but what are scientists actually doing? Or can like anyone do this?
--:-- Joss Fong: 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. Literally like slices through both strands of the DNA. There 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.
--:-- Joss Fong: 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. RNA is super easy to make. It's super easy to program. And that makes this tool incredibly accessible to scientists, to non-scientists.
--:-- Sean Rameswaram: There's a community of biohackers who have really taken to CRISPR because it's incredibly cheap to manufacture an RNA sequence. And so now basically every biology lab has the power to edit DNA in every organism that it's been tried in.
--:-- Joss Fong: 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.
--:-- Sean Rameswaram: You said it was cheap. How cheap are we talking?
--:-- Joss Fong: Well, you can buy this DIY CRISPR kit for less than $200.
--:-- Sean Rameswaram: 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. The ease of use of the CRISPR system has enabled it to really spread like wildfire through the scientific community.
--:-- Joss Fong: 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. 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 could CRISPR be a better solution for malaria than like nets and pills and bug spray?
--:-- Sean Rameswaram: What CRISPR does is it lets you create something called a CRISPR gene drive. And that is a tool that lets you alter a wild population. We're not just talking about animals inside a biology lab. We're talking about a wild population of insects.
--:-- Joss Fong: And this 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. CRISPR is that tool. And so this whole concept of engineering a self-propagating genetic modification is suddenly really real. And we're talking about the last five years.
--:-- Sean Rameswaram: So scientists want to use CRISPR to tweak mosquitoes. What exactly do they want to do to them?
--:-- Joss Fong: There are two broad approaches to using gene drive on malaria mosquitoes. The team that Bill Gates is working with is called Target Malaria. And they're interested in just shrinking mosquito populations. So there's fewer mosquitoes to carry this disease. 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. So the females don't pick it up from people and carry it to another.
--:-- Sean Rameswaram: How far away is Bill Gates or 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. And some of those interviews were with the scientists that are actually engineering these gene drives. And our question for them was, when is this happening? There was a lot of talk about this in 2014. We're now, you know, 2018. How long will it take? Yeah. And they said that their mosquitoes could be ready for field testing within a couple of years. Wow.
--:-- Sean Rameswaram: Which is amazing. Like these real live mosquitoes. Live mosquitoes. Will be ready to go to Africa? Yeah, they did some preliminary tests. They had immense success. They've been working on these mosquitoes to make them better and better. And the next step is to test them in a field trial. 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.
--:-- Joss Fong: If so many people are dying of malaria right now in Africa, why haven't these modified mosquitoes been released? 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. There is no regulatory structure for this. And so it's going to be a while before that structure is in place.
--:-- Joss Fong: Right now the science is far ahead of it. Is there some group of scientists or environmentalists or politicians or anyone out there fighting this? Someone who hesitant to mess with nature like this?
--:-- Sean Rameswaram: Because we're messing with nature, right? Yeah, this is a drastic extension of human power over nature. 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. And what she was saying was, 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's 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? I haven't found a good answer to that question.
--:-- Sean Rameswaram: Dylan interviewed an MIT scientist. His name is Kevin Esfeld. And while they were having this conversation, Kevin just stopped to highlight the urgency of this. 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. I would say at least 20.
--:-- Joss Fong: 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. Every two minutes, malaria is killing somebody's baby. 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 inaction is so clear and so direct.
--:-- Joss Fong: In a minute, what happens when we're through editing mosquito DNA and turn this CRISPR technology on ourselves?
--:-- Sean Rameswaram: This is Today Explained. Hey, there's one thing about Uber I haven't told you yet this week where we've been talking about Uber. What's that?
--:-- Joss Fong: Uber has service in more than 600 cities around the world. Did you know that?
--:-- Sean Rameswaram: No, I did not. And they're apparently increasing their efforts in community service and partnering with organizations that make a difference.
--:-- Joss Fong: I spoke to Therese again yesterday about Uber. Your friend Therese. She loves Uber.
--:-- Sean Rameswaram: What about Today Explained? Does she love Today Explained?
--:-- Joss Fong: She listens to you if I recommend any episode that she's interested in.
--:-- Sean Rameswaram: Thanks for nothing, Therese. Well, she's a busy person. Thanks for hanging out with me all week and talking about Uber.
--:-- Joss Fong: Oh, you're welcome. Mom, I love all your listeners. Okay, great. Wow. You don't know a bunch of them, though.
--:-- Sean Rameswaram: I know, but they listen to you. I love them. Wow. Back to Snapchat. All right, Mom. Take care. Love you. All right. Take care. Bye. Bye. Today. Today Explained. Today Explained.
--:-- Joss Fong: Joss, what happens when we turn this CRISPR technology on ourselves? The mosquitoes are almost out of the lab. How far away are we from gene editing humans? How far away are we from Gattaca?
--:-- 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. Yeah. Germline cells are those that we pass to our offspring. Yeah. 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. 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. 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.
--:-- Sean Rameswaram: And I talked to Jennifer Doudna, one of their 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. 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. Yeah. But what this scene does is it highlights that there 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?
--:-- Sean Rameswaram: And that line is not as clear as it might seem. If you think about genes that affect your risk for Alzheimer's disease, there are some genes that increase your risk and some genes that decrease your risk. So think about 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?
--:-- Joss Fong: These are hard questions. Because obviously this would just be accessible to a very small portion of society, I imagine?
--:-- Sean Rameswaram: Yeah. There are lots of countries that have laws that say this cannot happen. And these are mostly European countries that have had these in place since the 90s, saying it's illegal to modify the human germline. The two countries where CRISPR research is most active are the U.S. and China. And in those two countries, there aren't laws against germline editing per se, though there are restrictions right now.
--:-- 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. 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.
--:-- Sean Rameswaram: 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.
--:-- Joss Fong: That would be a tragedy because this is a technology that has the potential to cure diseases. Save children. Millions of children.
--:-- Sean Rameswaram: Do you think any of the scary sci-fi potential in all of this might actually get in the way of using CRISPR to do stuff that most people think is good, like put an end to malaria or some other disease?
--:-- Joss Fong: If you look at the organizations that are speaking out against gene-derived research now, they are in many cases the same organizations that are opposed to the use of genetically modified organisms in agriculture. So I think there is a risk that the kind of politics of that can sort of port over here.
--:-- Sean Rameswaram: If there are conspiracy theories about these mosquitoes that pop up, if there's misinformation that these genetic modifications could somehow jump to humans and make humans infertile, I could see that creating a kind of backlash that would stop this technology dead in its tracks.
--:-- Joss Fong: So that's why I think target malaria and the scientists that work on this are moving more slowly than some people would like to make sure that you don't get a backlash because everybody is in agreement about what they're trying to do and what it will take to get rid of this disease.
--:-- Sean Rameswaram: Joss Fong makes videos about science at Vox. You can check out our work at youtube.com slash Vox. I'm Sean Ramos from this is Today Explained. The show's executive producer is Irene Noguchi. Our editor is Bridget McCarthy. Noam Hassenfeld and Luke Vanderplug produced the show. Afim Shapiro is our engineer. Catherine Wheeler and Bree Seeley are the interns. And we had some extra help this week from Paige Flager, Katie McMurrin, and Jillian Weinberger. The Infectious Breakmaster Cylinder makes music for us. And Today Explained is produced in association with Stitcher. And we're part of the Vox Media Podcast Network. It's the weekend. If you've got some extra time, rate and review the show on Stitcher or Apple Podcasts. Thanks. One last shout out to Uber for supporting the show this week. Uber has turned the page and is moving forward. The company's goal is to improve the experience for both riders and drivers. They've been listening to feedback, working on ways to keep you better protected and connected during your ride. So they can get better with every trip. And one other last note, the people behind the political gab fest, they practically invented the political podcast. The political gab fest dissects everything from the Mueller investigation to the big cases currently facing the Supreme Court to the future of public unions and sexual harassment in Congress. The three hosts, they're veteran journalists. You might know them, Emily Bazelon with the New York Times Magazine, David Plotz of Atlas Obscura, and John Dickerson of CBS This Morning, and The Atlantic. They're funny, they're real, they're super wicked smart. Subscribe to the Political Gap Fest wherever you get your podcasts and you'll automatically get new episodes every Thursday.
