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December 18, 2018

At long last, we’re doing genetic editing. What’s the deal with the recent news about CRISPR babies? What does a future full of human genetic editing look like? And how might CRISPR change the food we eat?


Further Reading:

Paper mentioned in the Policygenius ad: “National culture and life insurance consumption

Flash Forward is produced by me, Rose Eveleth. The intro music is by Asura and the outtro music is by Hussalonia. The episode art is by Matt Lubchansky.

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That’s all for this future, come back next time and we’ll travel to a new one.



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Rose: Hello and welcome to Flash Forward! I’m Rose and I’m your host. Flash Forward is a show about the future. Every episode we take on a specific possible… or not so possible future scenario. We always start with a little field trip to the future, to check out what’s going on, and then we teleport back to today to talk to experts about how that world we just heard might really go down. Got it? Great!


This is the last episode of the season! Whoa! Seasons for Flash Forward are very arbitrarily 20 episodes long, and then I take a break because my human brain needs rest. So starting now, there’s going to be a bit of a break! The show comes back in March of next year, and I’ve got big things planned for 2019 that I’m really excited to tell you all about.


In the meantime, you can keep up with some behind the scenes stuff for the upcoming season by becoming a Patron! Go to patreon.com/flashforwardpod. And, while I’m gone, I’d love for you lovely weirdo listeners to keep in touch and keep talking about the future. So I’m opening up the special secret Flash Forward listener Facebook group to everybody. For a while this group has been only available to Patrons, and we discussed episodes, weird future news, and all sorts of other stuff. If you want to join the group, just search Flash Forward Podcast on Facebook. It’s a closed group, so you have to ask for access, but I’ll add you! Only good bots are allowed, and remember, the future is for everybody so be nice.


Also! At the end of this episode there’s a little bit of a bonus thing. Remember waaaay back in April when we talked about exercise pills and I ordered a drug on the internet and said I was going to try it? Some of you got very mad at me for that, but I did it anyway, and if you want to hear how it went, there’s an update at the very end of today’s episode, after the credits. If you don’t want to hear about it, all you have to do is turn the show off during the credits. I’ll warn you again at the end just in case!


Also, and this is the last little announcement before we go to the future, I … Rose Eveleth… the person who makes this show… actually do make work that is not Flash Forward related. I know… this is kind of like seeing your teacher at the mall or something, but it’s true! And if you want to keep up with what I’m up to in non-Flash-Forward-land I’ve just started a newsletter for that. You can find that by going to roseveleth.com/news.


Oh! And one last last thing. There is a single f bomb in this episode. 99% of Flash Forward episodes are totally clean and cursing free, and I know some of you listen with the kiddos or students, so I just wanted to give folks a heads up that you will hear one curse word in this episode. Use that information however you like.

Okay! That’s all the updates I have for you. Let’s go to the future! This episode we’re starting in the year 2073.




Geneticist: Your extracted eggs… Maria, have been fertilized with… Antonio’s sperm and we have performed an analysis of the resulting pre-embryos. After screening we’re left with two healthy boys and two very healthy girls.  Naturally, no critical pre-dispositions to any of the major inheritable diseases. All that remains is to select the most compatible candidate. First, we may as well decide on gender. Have you given it any thought?


Maria: We would like Vincent to have a brother… you know, to play with.


Geneticist: Of course you would, hello Vincent.


Vincent: Hi


Geneticist: You’ve already specified blue eyes, dark hair and fair skin.  I have taken the liberty of eradicating any potentially prejudicial conditions – premature baldness, myopia, alcoholism and addictive susceptibility, propensity for violence and obesity–


Maria: We didn’t want–diseases, yes.


Antonio: We were wondering if we should leave some things to chance.


Geneticist: You want to give your child the best possible start.  Believe me, we have enough imperfection built-in already. Your child doesn’t need any additional burdens.  And keep in mind, this child is still you, simply the best of you. You could conceive naturally a thousand times and never get such a result.


/end scene


Rose: Okay, so, today we’re talking about gene editing, and, more specifically, about something called CRISPR. And I will confess, I had this episode basically done. And I was really excited that I had finished an episode a tiny bit early, and then… this happened.


News Anchor: Controversial claim that the world’s first genetically edited babies were born in China.


News Anchor: Now to a fascinating and perhaps troubling claim from a Chinese scientist who claims he’s made a major breakthrough that’s sparked controversy around the world.


News Anchor: It’s the claim that shocked the world, a scientist in China announcing that he’s created the world’s first genetically engineered babies.


News Anchor: The scientific community has reacted with shock and skepticism, and American professor is now being investigated for his possible role.


News Anchor: These researchers are walking an ethical tightrope, reaction from the scientific community it has been harsh, saying this work seriously violates academic ethics and standards,


Rose: So, let’s just start there with this pretty big news. I’m guessing a lot of you have heard about this already but on November 25th, news broke that a Chinese scientist named He Jiankui had successfully used CRISPR on two human embryos. And the way this news broke was sort of chaotic.


Sarah Zhang: There was supposed to be a international summit about how we should go about using gene editing in humans.


Rose: This is Sarah Zhang, a reporter at The Atlantic


Sarah Zhang: And then on Sunday Night, a story appears in MIT Technology Review that a Chinese scientist is already using CRISPR in embryos and those embryos had been implanted into women and there will probably be babies. A couple hours later we will learn the babies have been born, and then we learn that there are two girls.  


Rose: Shoutout to Antonio Regalado at MIT Tech Review by the way, for breaking this story and kind of scooping He who had planned to announce this work at that summit Sarah mentioned. Antonio figured out what he was up to first, and published this piece, and sort of forced He to announce exactly what he’d done before he had planned to.


Sarah: And what he did was he had so what he did was actually very controversial as you can imagine, the gene that he targeted was something that is supposed to give these two baby girls resistance to HIV. And their father was HIV positive. And so the idea is that he had tinkered with this particular gene using CRISPR so that when they were born they were supposed to be resistant to HIV.  


Rose: So He basically announced that he had used CRISPR to edit the genes of these two little girls, and that these girls had been born, and were now living in China. He made the full announcement via a YouTube video, which you can find in the show notes.


He: Two beautiful Chinese girls named Lulu and Nana, came crying into the world as healthy as any other babies a few weeks ago. The girls are home now with their mom Grace and their dad Mark.


Rose: In case it’s not… already obviously to you, this is … a HUGE DEAL. Nobody has ever taken CRISPR editing all the way through to birth in humans before. And a lot of people were really mad that He had done it, basically in secret. The summit he was planning to announce this work at was supposed to be about whether or not you even SHOULD do this kind of thing.


Sarah: And here you are, he’s like raced ahead with this secret study and already done it and these kids have already been born.


Rose: And there are plenty of reasons that people are really mad about this. Some of them are big picture ethical questions about the future of humanity and the nature of choice and control. And some of them are comparatively smaller questions about what might happen to these two little girls specifically. And to understand all of this, we have to back up a little bit and go over what he actually did and what CRISPR actually is.


CRISPR, that’s C-R-I-S-P-R, stands for clustered regularly interspaced short palindromic repeats. There will be no quiz at the end of this so don’t worry about remembering that. What you need to know is that CRISPR is really a tool, it’s a technique, for editing DNA.


Sarah: Yeah so CRISPR is likened in a lot of time to a pair of molecular scissors, and what you can do with it is you can cut DNA. So basically what you do is you give it a code that says I want you to go to this piece of DNA that says oh maybe like ATCGCC or something and it will go right there and will cut the DNA.


Rose: Once the DNA is snipped, you can then do a couple of different things.


Sarah: Maybe there’s a gene there and now that you’ve cut it that gene is disabled, or maybe you want to put a new gene in and now you can insert a gene in that place.


Rose: Or, maybe you want to change a few of the letters.


Sarah: Maybe you can change an A to a T or a C to a G.


Rose: If that sounds simple, it kind of its. That’s the beauty of it. There have been plenty of gene editing techniques in the past that have been able to do this DNA cutting, but CRISPR uses a bacteria that is is a lot cheaper and easier than most of the previous methods.


Sarah: It was originally discovered in bacteria and it was for a long time just kind of like obscure cooky thing, this weird thing bacteria do. And it wasn’t until scientists realized you could, you know, easily give it that code and you could actually do it programmed to do whatever you want that it became, it spread like wildfire through labs. It’s just like, it went from a weird obscure thing to like everyone in the world trying to use it.


Rose: To give you a sense for how easy this is, and how fast this all happened — CRISPR was first described as a tool in 2012. And now, just six years later, we have CRISPR babies. It only took He a few years to get the expertise and tools to make this happen.


That super speedy timeline also means that it’s still early days and there are still questions about just how precise you can be with these genetic scissors and what the side effects might be. Any time you edit the genome, you have to worry about what are called “off target effects,” basically you might think you’re editing one thing, but actually your little bacterial snippers have gone and edited something else too. Or maybe, the gene you thought JUST did this one thing… actually also does something else really important that we didn’t even know about.


And here is where we get back to the dangers of He’s work.


Sarah: What if it’s in the middle of a gene that was supposed to suppress cancer. Well now you cause cancer. Or if you’re doing it in an embryo, you know, one cell if it’s causing these random mutations like the embryos could have these mutations in every single cell when that baby grows up to be a person. So we really don’t know what the effects of those are.


Rose: We just don’t know what the risks are yet, because nobody has done the studies. What He did hasn’t been fully worked out in animal models yet, or even in a embryo in a dish, and he jumped right ahead to doing it in humans, and bringing those humans into the world.


And in this specific case, the risk almost certainly is not worth the reward for these two girls. He’s editing targeted genes related to HIV transmission from parent to offspring. But that’s something scientists can already do without CRISPR.


Sarah: It’s actually pretty easy to prevent HIV transmission and father to child. So there’s lots of ways we can do it. We know lots of ways of preventing HIV that are fairly easy and well tested and not as risky as this thing has never been done before.  


Rose: After He announced these two CRISPR babies, he did still go to this big gene editing conference. And, unsurprisingly, people had a LOT of questions for him.


Sarah: There was one woman who asked him a question about, have you thought about what these girls what their lives are going to be like. Because one of the twins seems to, based on the genetic changes they’re able to identify, maybe is more resistant or more likely to be resistant to HIV than the other. And she was asking you know how do you think how they will perceive themselves as you know of scientific experiments or how will they be treated differently in the family because one that might be susceptible or not.


Rose: He didn’t really have an answer to that question. It’s unclear to me, based on what I’ve heard him say to other reporters, whether or not he’s thought deeply about the ways that his decisions might emotionally impact these two real human beings down the line. For the record, I did reach out to He to see if he’d come on the show to talk about all of this, and he didn’t answer. Oh and by the way you might have heard in the news that He is missing or has been detained by Chinese authorities, that’s not true. I’m not sure where that story came from, but He’s been responding to emails from journalists since this happened, and there’s no evidence that he was ever missing or under arrest.


So I couldn’t talk to He himself, but I do happen to know someone who is actually in line for a CRISPR therapy, someone who might, in a few years, have CRISPR edited genes injected into her eyeballs.


Greta Johnson: Do I think I’m going…


I mean [sigh] if I mean if I know it’s safe if my dad does it and it works for sure 1,000 percent. I’m going to do it. I mean even now, I mean. I’m anxious every time I have to go to the DMV to renew my driver’s license I’m anxious before going to the doctor to get my contacts renewed. You know it’s like, I don’t think my vision has gotten much worse but it’s also just like it’s so scary for me. You know like it’s it’s it looms in a way that like is really awful. And so if there is a way that I can be freed from that and know that I can like see the world. Fuck yeah.


Rose: This is Greta Johnson


Greta: I’m WBEZ’s weekend anchor and I host a podcast here also called Nerdette.


Rose: Greta has something called Best Disease, otherwise known as premature macular degeneration. Which is… not actually the best, at all. Basically, Great has a glob behind her retina that will eventually destroy her central vision.


Greta: I got glasses when I was four yeah. And that was when they first noticed it in me too they were like “oh yeah you have this thing!” And the way the way they described the glob behind my retina is they said it looks like a fried egg yolk and and when there’s no damage to my vision it’s just like a perfect yellow circle. But if that egg yolk starts to scramble that’s when I start noticing problems with my central vision. And so right now my yoke is like a little scrambled in some spots but for the most part it’s still intact. It’s still like, a lovely sunny side egg. [laughs]


Rose: But eventually Greta’s lovely sunny side egg is going to scramble – it’s inevitable. Best Disease is genetic, and Greta’s dad has it too. Although for most of Greta’s life he didn’t actually know he had it.


Greta: We thought it skipped a generation in our family because it was undetectable in my dad at the time and my grand, his dad, my grandfather had it and his got pretty bad by the end.


Rose: But at one point Greta went to see a specialist to check on how her eyeball yolks were doing.


Greta: like I’ve always been so resistant to going to specialists because like, you sit around in a waiting room for hours and hours, you go in for 15 minutes, they’re like “yup you have best disease. Good luck with that. You know we got nothing for you. See ya!”


Rose: At that appointment, she happened to mention to the specialist that it had skipped a generation in her family, and that her dad didn’t have it.


Greta: And he was like ya no, that’s not how this works. If you have it your dad has to have it. So I actually called my dad and told him that he had it.


And I as a result of that actually, I think he’s a lot more freaked out about it than I am because of that. In a weird way like his is getting worse also which has to be scary, but also like I’ve known about this thing since I was 4.


Rose: Today, Greta’s dad, whose name is Jim, is noticing his eyeball yolks scrambling.


Greta: His vision has gotten a lot worse in the last couple of years. You know he used to play softball. He can’t anymore because he used to play outfield and he just like couldn’t see the ball coming in and it just started really scaring him.


Rose: But Jim Johnson is the kind of guy who doesn’t just let stuff happen to him. He wants to know everything about everything.


Greta: I mean he’s the guy who like we had a dictionary at the dining room table just in case we needed to look something up when we were kids like he. His enthusiasm about the pursuit of knowledge is just unparalleled.


Rose: So when he found out he had Best disease he started doing a whole lot of Googling and emailing.


Greta: Ue was reaching out all over the place, like any retinal specialist he would get in touch with. And like I remember he was thinking about going to Iowa for a while. it was just sort of like wherever anyone might be interested in this thing and have a solution for me I’m going to do it.


Rose: But Best disease is really rare. And it’s not life threatening. So there just aren’t that many people working on it. So Jim just kept striking out. And then, on a whim, he looked at what was going on at UCSF.


Greta: I think it was just sort of like oh well let’s see what’s happening in California like there are smart people at the University of California San Francisco


Rose: And at UCSF, he found Bruce Conkin’s lab.


Greta: I can’t remember what the Google search was it was some ridiculous like oh like gene blah blah blah retina thing


Rose: So Jim emailed Dr. Bruce.


Greta: Within two hours they had responded and were like oh we’re so interested in talking with you. And it was totally because this disease happens to have the perfect potential for CRISPR application.


Rose: It turns out that Best disease is caused by a mutation on a specific gene located on chromosome number 11.


Greta: So with us they want to just delete something they want to take out the bad gene which in my case is my dad’s and in my dad’s case it’s his dad’s, right?


Rose: So Greta and her dad gave blood samples to Dr. Bruce and with those samples


Greta:  they can figure out our genome and like where the bad genes are and then they can just like scoop them out of the cells essentially


Rose: And if you can scoop out the faulty genes, you can cure Best disease. Just like that.


Right now, Dr. Bruce is working with samples of Greta and Jim’s cells in petri dishes, trying to design the perfectly shaped pair of scissors to go in and do this.  They’re still a couple of years away from injecting CRISPR into anybody’s eyeballs, but if they do get to human trials, Jim Johnson is basically first in line. Which Jim is super excited about! And his wife and eye doctor are… less excited about.


Greta: He was mentioning to his eye doctor he was like “yeah it’s so cool they’re doing this thing this is what’s going to happen.’ And even the. Doctor was like “You know, you maybe shouldn’t be the first person to have CRISPR.” And he was kind of like whoa, you know, like you could tell that he was like, that he hadn’t really considered like the possible risk of it at all hardly. And then hearing the doctor say that my mom was sort of like “oh wait a second.”


Rose: Both Greta and her dad have a few years before they have to really decide whether they’re going to be some of the first people to be treated for something with teeny tiny genetic scissors. And there’s a lot to consider.


Greta: I mean part of me is just really relieved that my dad is so gung ho about it because that means they will try it on him first, you know? And I think partly the reason why he is so enthusiastic is partly because he wants his vision to not get worse but also like if there’s any way he could help me. I mean gosh like that’s like what an amazing thing for a parent to be able to do to help their kid.


Honestly I think maybe I’m a little more selfish about it. I like the implications of CRISPR are potentially terrifying right. But for me it’s like, man if I knew that I could drive for the rest of my life. You know. If I knew that I’d be able to read books until I was an old lady like, that would be really wonderful.


Rose [on the phone]: You mentioned that you think that maybe your dad is like impart a among all the other reasons that he is excited about it is also in part thinking about you. Is that like, a lot of pressure?


Greta: On me?


Rose [on the phone]: Yeah!


Greta: Ummmmm, gosh that’s so funny. I never thought of it that way. I think I will say no because it’s his fault [laughs]. He passed it on to me. You know what I mean like those are his genes. So and I mean you know it’s not like I blame him or anything. Obviously like you know it’s it’s all roulette. I’m so lucky in all of the ways, I have you know I have no resentment towards him. No I don’t feel now that such a fascinating question I totally have never thought of that. I don’t know. I mean isn’t that partly all of a sudden now I’m thinking of the most recent Star Wars movie When Yoda is talking to Luke about how like the student has to surpass the teacher. You know like that’s just how it works. Like you pass what you can along and you hope the next generation does better than you did. And you know like I don’t think I feel any additional responsibility other than just the fact that like you know the world is on fire and it’s up to us to figure out how to fix it. You know.


Rose: If you want to learn more about the quest to CRISPR Jim Johnson’s eyeballs, Greta did a whole episode of her podcast Nerdette about it, which I’ll link to in the show notes. Definitely check it out, you get to hear Jim react to being called the John Glen of eyeball CRISPR, which he loves. But since that episode came out, Greta did find out one new thing from Dr. Bruce.


Greta: Yeah so I was just talking with Bruce Conklin earlier this morning, Dr. Bruce as we called him in the episode and he says they’re looking at probably two to three years for my dad and then another four to six for me is what it sounds like. And you know the other update he gave me is actually hilarious.


Rose: One part of the process in making a set of specialized CRISPR scissors for Greta and Jim involves taking samples from them and generating something called IPS, which are a type of stem cells that can be formed from adult cells.


Greta: And apparently my dad’s stem cells are much better behaved than mine.


Rose [on the phone]: What does that mean?


Greta: I think it’s like, I think it’s the process of like holding them in status and turning some into retinal cells, but then having the rest just sort of like chill in that kind of intermission period is just like, his are much more willing to be manipulated than mine are which I think is so funny. Because like my obstinate ass I’m like nuh uh!


Rose: In many ways, Best disease is the least controversial version of CRISPR applications in humans – consenting adults are making a choice about whether they want to undergo a treatment that they understand the risks of. But when you start to look at other uses of CRISPR technology, and other ways that people talk about using CRISPR technology, it gets a lot more ethically complicated.


Alice Wong: I do feel like there is so much optimism and enthusiasm for this technology. And you know, yes, I’m not, a Luddite, much of my life is dependent on technology, my life is better thanks to technology but I think we also have to really be skeptical and mindful of the consequences of our usage of technology.


Rose: And when we come back we’re going to talk about the ethics of human gene editing from the perspective of disability activists. Plus, humans aren’t the only organisms that can be CRISPR’d, and the world of agriculture might be about to see a huge CRISPR boom of its own. All that and more, after a word from our sponsors.




Rose: For the last six years of CRIPSR development, scientists seemed kind of hesitant to talk deeply about the ethics of human embryo editing. They seemed to think that actual CRISPR babies were really far away, far away enough that they didn’t really have to engage with questions about the ethics of editing an embryo’s genes for a while. Remember, that conference that He announced his work at was supposed to be about these ethics. Obviously, they had their timeline a little bit wrong.


What this means is that a lot of the reporting and research on CRISPR hasn’t really grappled with the thorny questions of who gets to decide what kinds of genetic edits are acceptable, and what kinds are not.


Alice Wong: You in a lot of the reporting around human germline modification and about the magical powerful possibilities of CRISPR as a technique, a lot of that conversation is about the removal of suffering, and pain, and disease. So, whenever I hear stuff like that, I’m like, they’re talking about people like me, people that are in my community.


Rose: This is Alice Wong, the founder and director of the Disability Visibility Project.


Alice: For the listeners out there, I’m somebody who’s a full time wheelchair user, I rely on personal assistance for almost every aspect of my daily activities. For those of you who are listening to the sound of my voice, I’m wearing a mask over my nose that is attached to a ventilator. So, people look at me and think “oh my god this person is just, you know, I cannot imagine living like that.” And these are the kind of pervasive attitudes that are ableist .


Rose: For Alice, there’s a huge difference between someone like Greta choosing to undergo a CRISPR derived therapy to stop her eye yolks from scrambling, and scientists deciding what kinds of bodies are and are not desirable at the embryo stage.


Alice: For people to elect to do this to their own bodies, hey, more power to you. You know I think that’s, that’s a choice that everybody hpefully would get to make for themselves if it is available. But I do think that you know, the kind of preemptive elimination, or alteration of certain genes are based on fear. They’re based on the imagination of non-disabled people about what living with a disability is like. So I think that to me is the difference.


Rose: To be explicit here, some of the conversations about editing human embryo DNA circle around the idea of elimination. Elimination of bad genes. And that’s where Alice and other disability advocates get nervous because “elimination of bad genes” is sort of another way of saying… eugenics.


Alice: You know when we talk about the removal of diseases, especially through human genetic editing, that’s forever. That’s going to be a change, a modification, that would be passed on to future generations. So that’s actually, you know, genocide is a form of eugenics where certain lived experiences are seen as undesirable and unimaginable.  


Rose: Often when you hear people talk about using CRISPR to eliminate disability, you hear people talk about how the removal of certain genes can make children’s lives easier. Wouldn’t it be easier for a child to live without a disability? And perhaps that’s true. But there are plenty of things that are easier to live with or without — it’s scientifically proven that the lives of white, straight, cis, men are easier than everybody elses. But to suggest that we should engineer babies to all be white, straight, cis, men is clearly bad, right?


Disabled people have rich communities and languages. So when well-meaning scientists talk about editing them out of existence, they’re talking about removing entire cultures and ways of seeing the world that contribute to a world where there are lots of perspectives. In an essay called “Please Don’t Edit Me Out,” in the Washington Post, Rebecca Cokley writes: “Where is the line between what society perceives to be a horrible genetic mutation and someone’s culture?”


Alice: I think the idea of who decides what is suffering, who to decides what lives are unbearable, I think that’s what’s really concerning to me as a disabled person.


Rose: Like she said earlier, Alice isn’t a luddite. She relies on technology, she likes technology, she likes science, and she’s interested in ways that we can make the lives of disabled folks better. And she’s not saying that living with a disability doesn’t include suffering. But she does point out that one of the hardest parts of her disability isn’t the physical element — it’s the way she’s treated. Ableism often inflicts far more suffering than any disability on its own.


What Alice and other disability advocates want is for geneticists and scientists to think long and hard about what they’re actually saying when they say things like “we want to eliminate disability.” And for them to invite actually disabled people into those discussions instead of assuming they know what people want and need. Because right now, scientists aren’t talking to advocates and activists.


Alice: There are all these silos that are in place.  And that there in’t enough recognition that people who are actually living with these chronic illnesses, disabilities, and diseases have something worth saying and that we should be taken seriously.


Rose: Of course, there are class and race issues at play here too.


Alice: What happens to people who don’t want this? What happens to people who can’t afford it? What kind of future is that going to look like for the new haves and have nots? If we’re talking about future of building better healthier or stronger people. And I’m using that not literally but like, you know, that is basically what this technology is trying to do, is trying to create a superior human body. Which I think is pretty creepy!


Rose: And there’s another key thing here that I think often gets overlooked, which is that … it’s not actually possible to eliminate disability or even suffering. Even people who CAN afford this technology, are never going to be able to actually succeed at only having babies with the precise bodies and minds that they had hoped for.


Here’s the thing about genetics: it’s really complicated! There is no one gene, or even a few genes that determine things like intelligence or even physical fitness. Whenever people talk about the future of human gene editing, they tend to reference the movie GATTACA, as an example of a world where human embryo genetic editing is pervasive. Which, in fact, you heard a clip from in the intro to this episode. Here’s another clip.


Vincent: Like many others in my situation, I moved around a lot in the next few years, getting work where I could.  I must have cleaned half the toilets in the state. I belonged to a new underclass, no longer determined by social status or the color of your skin.  


Boss: Welcome to GATTACA gentlement!


Vincent: No, we now have discrimination down to a science.


Boss: Alright, there’s your cleaning material, start from the front and clean all the way back!


Rose: Often when you hear people talking about or referencing this movie they stop there, and talk about a world where some people are actually better than others, thanks to engineering.


But the point of the movie is that those who are not genetically engineered might indeed be just as capable and smart as their super human counterparts. Our main character in the movie is not genetically engineered, an invalid as they say in the movie, but he proves that he’s just as smart and strong as his brother, the valid.


And if we ever did wind up in a world where there were unscrupulous and unscientific companies telling people that they could genetically engineer their kids to be smarter — which seems plausible, considering all the pseudoscience on the market now — this is the world we would be in. One where in fact, there is, for example, no intelligence difference between these two groups, but people THINK there is. The same way that today, some people THINK there is a difference in intelligence between men and women, or white people and not-white people, when that’s not true at all. Of course, this is the world Alice already lives in.


Alice: So you know I’m already living in a present where there is this hierarchy around different bodyminds. Right now clearly people with my bodymind are lower in the ladder, and I could very easily see post human genetic editing how this would just widen the idea of what bodies are ideal and, you know also expand the bodies that are not ideal, and all the pressures of people to be towards the center.


Rose: A world of CRISPR babies isn’t going to be a world where some kids are ACTUALLY superior to their peers. It’s a world where people just think that’s the case. And I think that’s a crucial distinction because in the weeks since the He’s CRISPR baby announcement I’ve seen a lot of debate online that assumes that we can and will successfully engineer humans for intelligence or even sexuality and gender identity. And we won’t. We can’t really. Most things aren’t like Best disease, where there’s a little mutation on one chromosome that causes it. Most things can’t just be snipped out or popped in.


Of course, that doesn’t mean that this fake distinction doesn’t have real impacts… we see that now with racism and sexism… but it is important to be realistic when you’re talking about potential dystopias so we can fight them properly. And this is why I think talking to disabled folks about CRISPR is extra important. It’s way more likely that gene editing will increase social stigma and suffering for disabled people, than actually decrease the number of disabled people.


So… I’m going to take a hard right turn now. Before the He news broke, a full half of this episode was about non-human uses for CRISPR, and I want to make sure we have enough time to talk about that a little bit here at the end. Anything that has genes, can be the subject of gene editing. Which means that animal and plant genomes can be snipped and rearranged and fiddled with in all sorts of ways. And humans have been messing with the genes of animals and plants for a really, really long time.


Alison Van Eenennam: That’s what breeders try to do is bring useful genetic variations into their into their breeding programs.


Rose: This is Alison Van Eenennaam, a researcher at UC Davis


Alison: So you know in the case of Ruby Red grapefruit they mutagenized the heck out of it and then they got this bizarre red grapefruit. They’re like “oh cool I bet this is awesome!” And now it’s a thing right and there’s like literally thousands of plant varieties that have been developed that way.


Rose: What CRISPR and other gene editing techniques can offer is a more efficient way of introducing traits into an animal or plant. Instead of having to breed individuals over and over and then pick the ones that have the traits you want, you can stack the deck in your favor and make sure that all the offspring have the thing you want, and not the things that you don’t.


So take for example horns. The type of cow that is most commonly used for dairy production naturally has horns. But farmers would prefer that they didn’t.


Alison: Because they can hurt each other with the horns and they can hurt their human handlers.


Rose: Today, dairy farmers cut the horns off of baby cows by hand.


Alison: That’s routinely done to the I don’t know nine million or so dairy cows that we have in the United States.


Rose: This process has been called out by lots of people as a form of animal abuse, and honestly, farmers don’t exactly enjoy it either. So what if you could use gene editing to make it so that the cattle never grow horns in the first place.


Alison: The idea was well can we use editing in this case TALENs to introduce the illegal or form of the horned gene that doesn’t grow horns so that they’ll be genetically dehorned


Rose: TALENs are another form of gene editing, a bit like CRISPR. They’re a way to snip out, or add in, genes. Now, you could try to eliminate horns through traditional breeding.


Alison: So a lot of beef breeds, for example Angus are naturally genetically dehorned. You could cross that bull over the top of a of a dairy cow there the black and white ones typically and produce this kind of F1, so they wouldn’t grow horns but they’d also inherit the other three billion base pairs from that sire that isn’t ideally suited to milk genetics.


Rose: Gene editing allows you to keep all the things you like about dairy cows, which have been bred for specific traits for hundreds and in some cases even thousands of years, and just cut out the thing you don’t want. Or, in other cases, you can add the thing you DO want. Right now, Alison is working on a project that would introduce a gene into beef cattle, that would make them all male.


Alison: Males are a lot more efficient at producing gain from feed, in other words beef from corn, if you will. And they also get to market weight more rapidly, and so that’s quite attractive from a production standpoint


Rose: To make all male cattle she’s using a gene called SRY, which is usually found on the Y chromosome. But mouse studies have shown that if you take that SRY gene, and you put it into a mouse with two X chromosomes, that’s enough for the mouse to develop into an animal that physically presents as a male. So the resulting mouse, with two X chromosomes and this inserted SRY winds up being functionally male.


Alison: And so we’re testing whether that same gene has the same effect in cattle.


Rose: And this isn’t the only project where researchers are trying to use CRISPR in animal agriculture.


Alison: There’s groups in Australia that are working to produce female only chickens, and so that’s actually my counterpart. So I’m a girl working to make all boys, and he’s a boy am working to make all girls. [laughs] So obviously for the laying hen industry where only the female produces product, the males ideally wouldn’t be part of that production system. And so if you could only produce females you’ve removed an animal welfare concerns in terms of disposition of the males, and also if you think about it you’ve kind of doubled the efficiency because you only need to hatch half as many eggs to get the same number of female laying hens.


Rose: There’s another group trying to use gene editing to produce pigs that never sexually mature. Sexually mature male pig meat apparently does not taste very good, so to keep the meat tasting the way they want, farmers prevent male pigs from maturing. This is something that, like the dehorning of cattle, is achieved on farms right now through physical means.


Alison: They’re typically castrated to prevent that from happening and that’s an animal welfare issue, and so if you could genetically prevent them from basically going through sexual maturity then you avoid having to castrate those pigs


Rose: Then there’s research on how to use gene editing to snip out genes that make animals susceptible to certain diseases. So for example, there’s a disease in pigs* and it’s basically a virus that attacks a certain protein in pigs, and that protein is encoded on a really specific bit of pig DNA.


Alison: And if you knocked out that exon, on that virus no longer has access to that pig.


Rose: Other researchers are hoping to use CRISPR to be able to replace the genes of inferior animals, with the genes from the so called “elite sires.” These are special males that are considered the best of the best of the best of the breed


Alison: If you could use editing and knock out basically the germ line of those inferior sires and replace it with a germline of the best sire in the breed, if you will, you basically reduce artificial inseminations to bulls on legs that can go actually deliver that elite genetics out in the field.


Rose [on the phone]: So you have a bull that’s maybe like not the top tier bull, you have a sort of regular bull, and he’s going out and he’s like “yes, I am making babies I am spreading my genes” and in fact he is not.


Alison: [laughs] No he’s spreading the genes of the very best bull in the breed.


Rose [on the phone]: That’s so tragic!


Alison: I think that’s going to be some confused cows. We’re going to have some explaining to do.


Rose [on the phone]: The Maury Show, you are not the father!


Alison: That does not look like my child! And it’s like, no I swear you’re the only bull I ever slept with!


Rose: So there are tons of applications for CRISPR when it comes to agriculture. But right now, it’s really, really hard to actually get any of these applications on the market, especially in the United States.


The regulations surrounding genetically modified organisms are different all over the world. In the United States, as of March of this year, the USDA considers any plant or animal that could have been developed through traditional breeding fair game. So if you just used gene editing as a shortcut to get to something that you could have created through traditional breeding techniques, you’re good, no need to regulate you extra. But if you couldn’t have gotten there the old fashioned way, then… it gets more complicated. And it’s not super clear exactly what kinds of CRISPR edits the USDA will consider a form of faster breeding. The USDA has a whole form for people to fill out to get an answer to the question “Am I Regulated?”


In cases where these edits don’t fall under the “could have been made traditionally” umbrella, the US historically has viewed them as if they’re new drugs. Which means going through years of expensive drug trials to make sure that they’re safe. This regulation applies to the genetically dehorned dairy cows, and to Allison’s all male cattle. According to the US regulators, these all have to be tested as if they’re a new animal pharmaceutical drug.


Alison: And so it becomes well, what is what would be the novel kind of drug attribute of being being a boy when half the population already expresses that drug, if you if you want to use that terminology, because that’s basically what their Y chromosome tells them to do. And So it’s this kind of sticky area where it’s like, what has it is that we’re regulating here being a boy? And if so are boys dangerous to eat? And if so then should we not eat boys? So I guess that’s the kind of the questions that you run into when you start working in this field.


Rose: In case it’s not obvious to you, Alison thinks that right now, these laws make no sense at all.


Alison: I guess I’m not onboard with DNA being a drug, I think that you know chemical that you take Sudafed for example is a drug.


Rose: Now, you might not agree, and you might have your worries about gene editing in animals. But even if you yourself personally don’t want to eat a genetically modified animal, I think it’s still safe to say that the rules here are pretty confusing. Things might get kinda weird while the various regulatory organizations are trying to figure out the best way to oversee this stuff.


Alison: And I think that there’s going to be a lot of trade issues brought around by the fact that there’s not regulatory harmony between the different countries and different countries are taking really different approaches as to how they’re going to regulate the products of genome editing for food animals.


Rose: In other countries the rules are different – places like Brazil and Argentina are taking a much more relaxed regulatory standpoint on gene editing. That might mean that these countries develop techniques that American farmers would love to import, but aren’t aren’t allowed to.


And it’s not just animals who could be CRISPR’d.


Sarah: So maybe you can tinker with the taste of vegetables maybe you can tinker with the look of vegetables make them more enticing or interesting or exotic.


Rose: That’s Sarah Zhang again.


Sarah: And I think one of the first that was kind of not publicly was this mushroom that doesn’t brown when you leave it out. There are efforts to for example make soybean oil a bit healthier. Love or oil comes from soybeans and to make it more like olive oil than traditional soybean oil.


Rose: All of this stuff hinges on being able to convince people and regulators that farmers should be allowed to edit the genes of the food we eat. And that’s not a given, right? Despite that, Alison is continuing to do her work on all male cows.


Alison: Well we’re transferring transferring embryos on the 20th but I won’t know whether we get pregnancies for about a month and a half so I’m not going to scoop you, you’ll be okay.


Rose: Some of you might be excited to hear about the results of Allison’s experiment. Some of you are already composing an angry email to me in your heads about GMO’s. Here’s what I’ll say: the scientific evidence we have right now says that GMOs are safe to eat. At the same time, many of the companies behind the biggest and most well known GMO’s have shown themselves to be unethical monster corporations. Like so much technology, it’s complicated and largely depends on who wields the power here. There are indeed questions we should ask about safety and knock on effects of gene editing in the food we eat, and scientists should absolutely do those studies. Gene editing also has the potential to make our food systems more humane and efficient, which I think is overall a good thing.  


In the next few years, we’re going to see some big debates around this kind of technology – on both the human and animal side. Right now, we’re kind of in a CRISPR gold rush. There’s this incredible excitement and energy surrounding this technology, and it can sometimes feel like the possibilities are endless. But before you get toooooo carried away, I should probably note one, uh, speed bump.


Sarah: Yeah sure it’s almost kind of poetic isn’t it ,especially as we’re talking about like the hubris of humans.


Rose: CRISPR might actually not work on every human, or cow, or plant.


Sarah: So as I said earlier CRISPR is actually a protein that comes from bacteria. And you know we’re encountering bacteria all the time and it is the job of our immune systems to kill these bacteria so our immune system is primed to recognize bacteria proteins and try to neutralize them. So it seems like that in a fairly substantial number, or percentage of the population our immune systems are able to recognize this one particular CRISPR protein called CAS9 and that means that if you put a, you know if you inject a raw cascade protein into your bloodstream something bad, either something bad could happen or nothing would happen.


Rose: Our bodies, it turns out, are really good at stopping stuff from meddling with our genes! So for a lot of us, our immune systems are going to see those little Cas9 bacteria carrying their little scissors and be like “um hello excuse me where do you think you’re going with those?” like you’re a child who was about to go give your cat a haircut against its will. Just… inside your body.


CRISPR companies right now are pretty much all trying to find ways around this, and Sarah thinks they’ll probably be successful. But it’s not quite as simple as people once thought.


So before you invest all your money in some CRISPR startup, it’s worth looking into just how successful they can actually be with their technology, and thinking long and hard about what kind of vision of the future you’re throwing your money at.


[music up]


That’s all for this future, and for this season! You’ll hear from me again next year, with a brand new set of futures we can travel to together. Thank you all so much for listening this season, without you I am nothing.

Flash Forward is produced by me, Rose Eveleth. The intro music is by Asura and the outtro music is by Hussalonia. Special thanks to my guests this week: Sarah Zhang, Greta Johnson, Alice Wong and Alison Van Eenennaam. You can read Sarah Zhang’s work at The Atlantic dot com. You can listen to Greta Johnson’s podcast Nerdette wherever you get your podcasts, and I’ll link to their CRISPR episode in the show notes. You can also hear Greta every weekend on WBEZ. You can find Alice Wong’s work and podcast at Disability Visibility. And you can read about Alison Van Eenenaam’s research at UC Davis, I’ll link to studies from her in the show notes. The episode art is by Matt Lubchansky.


If you want to suggest a future we should take on, send us a note on Twitter, Facebook or by email at info@flashforwardpod.com. We love hearing your ideas! And if you think you’ve spotted one of the little references I’ve hidden in the episode, email us there too. If you’re right, I’ll send you something cool.


And if you want to support the show, there are a few ways you can do that too! Head to www.flashforwardpod.com/support for more about how to give. But if that’s not in the cards for you, you can head to Apple Podcasts and leave us a nice review or just tell your friends about us. Those things really do help.


And now… the results of my 516 experiment. So if you don’t want to hear about it, turn the show off now!


[music out]


Rose [VO]: Okay… so here’s how I set up this experiment. And let me just say, that it’s not a good experiment. I’m an n of one, and there was only so much I could control and I only wanted to take the drug for so long. Also, we had a huge fire in Northern California in the middle of it, so that messed up some of my timing. But the plan was as follows: First I had my boyfriend Robert taste the 516 and go find something that could reasonably be considered a control substance.


Rose: When you push it the light goes on


Robert: Yes it does, I can see that


Rose: So I am now recording  


[mic handling noise, Rose handing the mic to Robert]


Rose: Thank you, you’re going to do great.


Robert: Alright time to poison myself! [Rose laughs in the background]


Robert: Take my dose… I guess on the tongue is probably going to give me the best flavor so we’ll do that…


[sound of liquid]


Yeah it’s like an extremely burney alcohol… yeah… I mean that’s pretty simple nothing too flavorful in that.


Rose [VO]: Then I ran three individual miles on a track, spaced out a week and a half apart. The first one I ran as a baseline, not taking anything.


Rose [at the track]: Okay, so we are at a track. There’s a lovely soccer game going on. Highschool girls. The track is bigger than I remember it being from running? I might cry. I’m hoping to keep it under 10 minutes, that’s my goal.


Robert: I think you can do it. Do you want me to cheer you on?


Rose [at the track]: I don’t want you to cheer me on. I want you to draw no attention to me. Alright let’s see what happens…


… okay [panting] so my time was 7:48, it’s less actually the time than how bad that felt, like that felt really bad.


Rose [VO]: Then I took a half a ml from one of the bottles for 10 days


Robert: To properly science this I’m going to flip a coin and see which one you get first. It’s a heads!


Rose: And that means what?


Robert: That means green


Rose: Great! And now I get to taste it, well not taste it, take it. They say you’re supposed to wash it down with water but I’ve already opened this Pacifico beer so I’m going to wash it down with beer…. It tastes horrible! Um, it just tastes like rubbing alcohol, which I think is probably what it is.


Rose [VO]: And ran a second mile.


Rose [at the track]: Okay we are back at the track, mile number 2, it’s a beautiful sunny day. We did pass a sign that said drug free zone though so… technically in violation.


Robert: Did you bring the container?


Rose: No I didn’t.


Robert: So it’s inside of you.


Rose: I think that still counts


Robert: I don’t think that counts! You can be high in a drug free zone. You just can’t sell in a drug free zone.


Rose: Are you allowed to be high in a drug free zone okay well, good to know, I’m not in violation I’m not going to be arrested. Okay I’m going to go run a mile now and probably feel just as bad as after the last one.


[panting] Ugggghhhhh 7:19.


Robert: How do you feel?


Rose: Just as bad as last time! I hate it!


Rose [VO]: And then I took a half a ml every day from the other bottle for 10 days, and ran a third mile.


Rose [at the track]: Okay, this is run number three, our last, my last, you’re not running, run. My last run for this experiment. It is the Friday after Thanksgiving so I am very full and it is raining and cold. Now I’m just stalling for time because I don’t want to go do it. Allright I’ll see you in a little bit and I’ll let you know how it goes.


[panting] It started really raining. I forgot to start my timer properly but I listened to the same song twice… times two so that’s eight minutes! Terrible! It felt worse.


Robert: It felt worse?


Rose [at the track]: Yeah. Alright, well, I’m going to stop this, and cry.


Rose [VO]: In case you weren’t keeping track that was a 7:48 baseline mile, a 7:19 second mile and then an eight minute third mile. But really, the time wasn’t the key thing here. All the accounts I read about 516 focused on how much it made cardio FEEL different. Easier, more effortless, getting winded less quickly, all that stuff. And I have to say, I did not feel any of that. Honestly I didn’t feel any effect at all. I also didn’t lose any weight, which is something some people reported on 516.


So, which one was 516? Did it make me run faster? Drumroll please.


Rose: I suspect that the 516 is the green cap, that’s the clear stuff, and this is some kind of extremely terrible alcohol that you bought.


Robert: The notes, where I wrote it down… and the answer is… purple cap, 516, green cap, Fleischmann’s vodka.


Rose: Ooohhhhh


Robert: I asked the guy “what is the worst alcohol you have” and it was that.


Rose [VO]: I love the idea that Robert walked into a liquor star and was like hello what is the worst possible thing I could buy and the guy was like “oh yeah, I gotchu, no problem dude.”

Okay so… this doesn’t really mean much, but the miracle effects of 516 that I read about definitely didn’t happen to me. Maybe I didn’t take enough, or for long enough, but I was kind of disappointed! Which made me wonder if what I had was even 516 in the first place. So I sent the rest of the bottle to a guy with a lab, who you also heard on that episode… my dad.


Dad: Hi Rose it’s Dad.


Rose [on the phone]: How’s it going.


Dad: I’m alright how about you?


Rose [on the phone]: Eh, I’m alright I’m a little sick so if I sound funny that’s why.


Dad: Oh dear


Rose [on the phone]: I thought I’d try to catch you before you get on your bike


Dad: Yes well you caught me before I got on the bike so…


Rose [on the phone]: Okay good. Um, so do you have, did you get the answer?


Dad: I did, I have the report sitting in front of me and I can email it to you. I had a guy at a company that I know who has a, they do small molecule synthesis and analysis and I asked him to analyze it and he wrote me up a little report that is sort of for people who have a little bit of chemistry.


Rose [VO]: I will post this report on flashforwardpod.com so you can read it if you want to.


Rose [on the phone]: So… is the stuff in my little bottle what I thought it was? Did I buy fake stuff or did I buy real stuff?


Dad: Um, there is, there is GW501516 in your bottle.


Rose [on the phone]: Woo!


Dad: Yeah, and because of the fact that we know what we’re looking for and we’re looking for exactly that, and we detected, or the analytical chemist detected a molecule of exactly that molecular weight and furthermore there’s a way you can check on these things with many molecules, and that is that the process of doing a mass spec is a fairly harsh process so the molecules tend to break down in the system and they break down in predictable ways. That is you can look at a structure and you can predict that you’re going to break it here and here and those products have their own distinct molecular weights. And in the case of your molecule we, or the analytical chemist also detected one of those breakdown products. So it’s pretty much a lock that yes there is GW501516 in that sample.


Rose [VO]: So I did get 516! There’s also other stuff in there too, but the way that this kind of chemical analysis works they can’t necessarily say WHAT else is in there. You have to look for something specific here, and if you know what you’re looking for you can find it, but otherwise you just know the molecular weights of all the other stuff.


Dad: There are at least four other unique compounds in the mixture, and they have molecular weights of mostly smaller than the one that you’re interested in but some larger so there’s a 346, there’s a 470, there’s a 498 and there’s a 482.


Rose [VO]: Again if you’re a chemist who’s interested in digging into the results, I’ll post the information I got from the analytical chemist on the site. But I had one last question for my dad, who got really interested in the chemistry of 516 after I interviewed him for that episode.


Rose [on the phone]: You’re not going to take the 516 are you?


Dad: No. No.


Rose [on the phone]: Okay, you thought about it!


Dad: No I’m not. You know, it’s a great proposition in the sense that 516 and its related molecules generate a lot of excitement in a lot of people because the desirable biological effects were very good. I mean, the evidence that it actually does what bodybuilders are taking it to do, inasmuch as you can conclude things from animals which is, there’s a big big big big grain of salt that you need to put on that because humans and animals don’t behave the same way, but based on the animal work, the evidence that 516 does what it is, what bodybuilders take it to do is very good. The problem is the animal evidence that it also causes cancer is very good. So… um, yeah.


Rose: So that’s what happened with my 516 experiment. This is not an endorsement to take it. Some of you emailed me after the episode asking where you could get it and I will not tell you that because I don’t want to be sued! Okay, see you next season!


*An earlier version of this episode stated that the disease here is called PERVs. That is incorrect, it is actually called PRRS – porcine reproductive and respiratory syndrome virus. Rose regrets the error and the bad joke she made about PERVs as a name.

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