Season 01, Episode 02

Gattaca's Designer Baby Astronauts:
Editing the Murder Gene

About the Episode: 

In this episode, we watched Gattaca, a science fiction movie from 1997 that asks the question: what if we could alter our destiny with a little genetic engineering? Graduate Student Sasha Luks-Morgan helps us understand how exactly genetic editing works, what the heck CRISPR stands for, and whether or not we can actually splice super powers into our DNA.

 

The full English transcript for this episode, which includes time-points and links to relevant segments, can be found below!

 

About Sasha Luks-Morgan:

Sasha Luks-Morgan is a Neuroscience graduate student at the University of Utah. Her research is focused on the role that oxytocin neurons play in pain. Originally from Pennsylvania, she attended Hampshire College in Amherst, Massachusetts. She is currently serving as a Society for Neuroscience Early Career Policy Ambassador. She is also the President of the Young Democrats of Utah, which allows her to spend time supporting candidates who support science. Previously she was the logistics director for the Salt Lake City March for Science, and the director of volunteers for the Utah Pride Festival. She does not believe in free time.

Read the Transcript:

ANNE: So I, I just imagine you in lab being like, “is this a fish?” and it’s like, a pen. [Laughs; note from transcript editor: this is actually more true than you think].  Like, your research is just , can you identify fish?

SASHA: I’d like to think I would have graduated by now if that was the case…

HEIDI: Welcome to Cinema Science, a podcast in which we interview professors, professionals, and graduate students using pop culture references as a talking point. We’ll discuss the science behind your favorite movies, games, and TV shows! Each episode will feature a new topic and guest who will answer questions from you guys, our wonderful listeners! I’m Heidi and as always I’m joined by Anne.

INTRODUCTION

ANNE: Hi guys!

H: How’s it going?

A: Good, good.

H: And today we have Sasha Luks-Morgan

SASHA: How’s it going?

H: Thank you for joining us today

S: Thank you for having me on the podcast.

H: So you are a grad student, correct?

S: Unfortunately, yes.

H: Fighting the battle like the rest of us. And you are in… whose lab are you in?

S: I’m in Dr. Adam Douglass lab in the Department of Neurobiology and Anatomy at the University of Utah.

H:  And can you give us a little shpiel about what you do?

S: So our lab is interested in how brains form circuits that drive behavior. So one of the things that we’re basically trying to do is…we know that fish  have certain behaviors, they swim in certain kinds of ways, and we know that certain things that you do, the fish will make them swim in a certain way, you scare them, they swim in one way, and it’s the idea of taking that behavior and putting together a diagram going from the thing that scared the fish to  the way that the fish tells its muscles to swim away in a certain direction. And so we’re interested in certain kinds of neurotransmitters that change the system and how everything works together.

H: I see. That’s very cool research, but we are  not talking about that today.

S: No we are not. [laughter, crosstalk]

MOVIE SUMMARY [2:26-19:42]

A: We have you here as our expert on the movie GATTACA, and gene editing.

H: Great movie. Very retro.

A: I’ve heard it’s amazing, I have not seen it.

H: [crosstalk] … you didn’t watch the movie…

A: I didn’t do my homework… I’m sorry… I knew this was gonna come up because that’s literally what the whole podcast is gonna be about.

H: It’s on amazon!

A: I can’t pretend like I’ve seen, you guys are gonna know so… I just thought I’d come out and say it. I haven’t seen the movie. I have seen the trailer …all three guys… and it looked the same. So I have no idea what the movie is about…

S: Well, two of them are supposed to look the same. That’s a plot point.

A: Ah, I see. So…

H: Yeah… and the other one is his brother [crosstalk]

A: Okay, so it sounds like I’ve basically have seen the movie. [laughs]

H: Sounds like you’ve figured it out.

A: Sounds like I’m the new expert here [laughter]. On this movie I’ve never seen [more laughter]. No, if you guys could catch me up just a little bit though, that would be great.

H: So GATTACA- which, fun fact, GATTACA is built using base pairs of DNA, which we’ll talk about later- in GATTACA, which takes place in the near future, babies are  genetically edited so that we can…

S: Make genetically preferential children.

H:  Yes! I was trying to think of a way to say that piece of info [laughter]

A: So we have these  genetically perfect…

S: Yes. You can guarantee that they won’t have a risk of mental illness or heart disease…

A: Interesting

S: … or be short. [laughter, crosstalk]. You can make sure there are no short people. And we can select…

A: All babies are short! [laughter]

H: You can have tall babies! That’s terrifying

A: We have the technology [laughter, crosstalk]

H: Finally a tall newborn baby!

A: The not-so-distant future

S: That’s not right [laughter, crosstalk]

A: Okay

S: So they are able to genetically engineer children, but obviously not everybody has been genetically edited,  and so it basically creates a subclass of people called Invalids, and those are the people whose parents didn’t or couldn’t afford to have them be genetically perfected.

And so our hero in this movie, his parents just… “accidentally” knocked up his mom….

H: “conceived him in love”, they said

A: Oh

S: ….so he is born and they’re like, “oh shit, your kid’s kind of normal and maybe he has a heart murmur… and he’s not gonna be tall”

A:  So he hasn’t had these upgrades that are…

S: He’s just like a normal shitty human

A: Just like the rest of us.. garbage people [laughter]

S: So his parents decide they wanna have a second kid, and this kid…they get all the bells and whistles, all the modifications, and so, he’s taller than his younger brother, and faster and smarter and better at everything and doesn’t have a heart murmur and his dad loves it more.  So we have to have childhood feelings about our parents, not loving us And then, what winds up happening is Vincent, the older brother, decides that he wants to go to space, but instead, he’s just like, washing windows in the… basically like SpaceX before SpaceX was invented.

H: ‘Cause in this society,  basically your genetics determine what types of jobs you can have. ‘Cause they don’t really interview you for a position, they just look at your genetics and like, “alright your genetics say that you’re gonna be really smart, so you’re probably good for this position”

S: The most implausible thing about all of this is the rate at which they can do whole genome sequencing

H: Oh yeah!

S: It’s like, they take a Q-Tip and stick it in your mouth and stick it in a machine, and it’s like 12 seconds later, like, they can look at your entire genetic code

H: I mean, they do that in CSI.

S: I wish it was how it worked

A: Could you imagine how nice that would be if research moved at that speed?  [crosstalk, laughter]

A: So I don’t know much about this movie, but I do know it came out in 1997, and the Human Genome wasn’t even completely sequenced until 2003.

S:  Exactly

H:  They didn’t even…

A:  That was still not even a real thing…. at the point that movie came out.

S: Well and in one scene.. it’s not really that important but one of the characters goes and gets somebody else’s is genome sequenced, without their knowledge because she wants to find out if he’s gonna be good to make babies with, because that’s totally normal, and healthy. And… they give her a printout of his genome. And it’s like… like a poster-sized piece of paper, maybe? And it’s like.. the human genome is way longer than that. If you wanted to write out the entire thing, you would need reams and reams and reams of paper and she is just like, walking out with this dainty little roll of paper

H: I also love that she’s just looking at it [crosstalk]. Like, that’s nice!

S: Like, she knows what that is

A: So it’s like, A G C… There’s no…

S: Yeah

A: Oh,… okay

S: It’s cute

A: …Great [mumbling in the background]

S: So… He’s completely estranged from his family, he’s working as a custodian and wants to be able to go to space to be like, an engineer that designs the trajectories of these spacecraft going to Titan. But nobody’s gonna give him a chance, because he’s Invalid and he has the genes that indicate he’s probably gonna drop dead of heart problems at like 31.  So he basically goes to the underground black market and meets a sketchy guy who’s like, “I know a guy who is Valid who has these genetic modifications, but he fell off a horse and broke his back So, he can’t work and doesn’t have any money, but you kinda look like him and you can pretend to be him, and then you can go get a job and give him lots of money and everyone will be happy.” Except being him is really complicated. So there’s this elaborate system where he has to make false fingertips that has that guy’s blood in them, so when they do a blood sample at work every morning, he reads as this other guy.

A: Oh, so he used to scan in as is on the person.

S:  Yeah, yeah.  Jude Law is the guy who is paralyzed, and Ethan Hawk is the guy pretending to be Jude Law. So you’re…

A: They do look alike. [laughs, crosstalk]

S: Two dudes look-alike problem is really legit

A:  I was just thinking… they can sequence and edit genes, but not solve paralysis.

S: Yes

A: Okay

S: That one’s hard. Apparently

A: Sure

H: What I also loved is that… So every time they collected a sample from a person to show up if they are Valid or Invalid.. with all of this technology they have….

S: the photography!  [laughter, crosstalk]. It’s like… do you have a Costco Card?

H: Yes! Oh yeah!

S: It’s like a Costco Card level of bad picture. [crosstalk, laughter]

A: Like, three pixels?

H: Yeah, it’s really bad. And that’s really the reason why he can get away with this is because… I mean Sasha is gonna get to this… but they flash this guy’s picture because he gets suspected is something later on the movie and they’re like, “we can’t find him” and it’s like… “yeah ‘cause you have three pixels of this guy’s face! Of course not!”

S: But we can sequence a genome with something the size of an Iphone….

H: Yeah…

S: …on the side of a highway… in three seconds….’causa that’s…

S: Anyways. So he is pretending to be… Ethan Hawk is pretending to be Jude Law, and he’s doing all these elaborate things like leaving hairs and eyelashes on his desk so that if anybody is like checking they think it’s his DNA… and he is really careful to not leave any of his own genetic material around but only to leave stuff from to  Jude Law. So, Jude Law has this crazy room full of blood and urine samples, and nail clippings, and hair…

H: As you do

S: …. just.. dead skin and just really normal stuff

A: You just wanna fill up an extra room… those are the sort of things you put in there.

S: I mean, what do you keep in your basement?

H: Yeah, I guess

S: And in the course of all this, Ethan Hawk’s character Vincent has to… he realizes that he is four inches shorter… two inches shorter…

H: I think it’s two inches yeah.

S: …than Jude Law,  and so they have to go in and basically break his legs and put in metal plates, to make him taller. [crosstalk. Heidi: this is just some guy on the street who does this. more crosstalk] . And then…

A: If they are just going by the genome though, why… ? [crosstalk]  I guess maybe he stands out ’cause he’s so short if everyone else is so tall.

H: Yeah, I think the… They do check them periodically. I can’t remember if he visits a doctor every week or every day. [crosstalk]. They do check them like, up and down.  

S: So then… he’s at this space company and one of the bosses, gets murdered. And everybody’s like, “Oh how could this be? None of our employees have been screened to have violent tendencies” , like, “things like this don’t happen here”

H: “No one has the murder gene!”

S: No one has the murder gene! Because clearly there is just a murder gene.

H: Clearly!

S: Clearly

S: Don’t pass that on to your kids! So Ethan Hawke accidentally leaves an eyelash at the scene of the crime, and a detective picks it up and scans it, says there is an Invalid. Spoiler alert, the detective is his brother. [everyone gasps and does over dramatic music]

A: So he knows immediately…

S: He does! So he is like… “Oh shit that’s my brother”

A: And he shouldn’t be working here

S: Well he was on  record of having worked as a custodian, in the company a couple of years earlier. But it doesn’t make sense that they’d be like just finding an eyelash now.

A: Yeah,

S: So it turns into this whole thing, where the old grizzled detective who’s the brothers buddy cop partner who basically just spends the entire movie yelling “ I’m too old for this shit.”…

A: Oh my god is that where that came from? [laughter] Is this just a GATTACA reference?

S: It’s just such a good… It’s such a good trope [crosstalk] [To Heidi]: Do you wanna… pick it up from here?

H: Yeah so from here, Ethan Hawke’s DNA is found at the scene and like Sasha said, he is immediately the first suspect because Valid don’t have the murder gen of them. So clearly, I have to be the Invalid who did the murdering So at this point Ethan Hawk is panicking and he’s trying to convince to Jude Law  that he should probably just get out, like “I’m not gonna do this anymore” but Jude Law convinces him that like, “No you’ve come this far.” He’s supposed to actually go into space later that week. Oh, an important note the guy who’s murdered was super against this space launch going on. But of course they ignore that, and obviously, a custodian will want to probably murder the director ’cause that makes sense. [crosstalk]

S: Oh yeah that’ right, he beats his head into the keyboard.

A: Wait.. so who did it? [laughter, crosstalk S: we are not at the end of the movie yet!] … I should just watch it then [laughs].

H: So while all this investigation stuff is going on, Ethan Hawke.. you know even though he’s terrified starts dating a girl who sequenced his whole genome because.. she thought he was a good match. And so they go on some really awkward dates. Like, one of the dates they go and watch this piano player who’s been genetically altered have six fingers on each hand so it makes it amazing at piano [laughter] “this piece can only be played with 12 fingers”.

S: Oh he is on a date with Uma Thurman who has really bad eyebrows.  

H: Oh yeah she did!

A: Eyebrow were bad in the 90s.

S:They all suffered through that.

H: Oh yeah, and also Uma Thurman’s character also has a heart murmur. It is a heart condition. So, they found each other. So they go on a couple of awkward dates and…. we don’t have to go through all the details but Ethan Hawke’s brother is chasing them around trying to figure out whether or not his brother actually did this. So there are a couple of opportunities for them to actually to actually collect DNA from Ethan Hawke, but Ethan Hawke is just so goddamn clever he outsmarts them at every turn. So eventually they do find the killer, and it turns out that it was not Ethan Hawke- spoilers- it’s actually Ethan Hawke’s boss who worked under the director but was also called the director? Like, I don’t really understand what his role was.

S: They never really explain… like the whole… organizational flowchart [crosstalk]. He was just like, old cranky boss man who like, shows up  at scenes periodically but he really wanted the space launch to happen so he… beat his boss to death with a keyboard.

A: So they do find out who did it

H: And in the process of all of this Uma Thurman does figure out that Ethan Hawke is not who he says he is.  But she stands by her man, you know. She doesn’t question it, until… I think she questions, questions it for 10 minutes and then he says he’s sorry, and then she forgives them, even though she doesn’t know for sure that he’s not actually the murderer at that point, but…

A: You know, no one’s perfect [laughter]

S: Just… a little murder keeps that spark in the relationship [laughter]

H: So… Ethan Hawke…. It’s the end of the week, he’s getting ready for his trip.  Jude Law reveals that he has collected enough samples for Ethan Hawke to basically live as him for two life times. And so then Ethan Hawke is heading towards GATTACA, gotta get on the ship, and then there’s  one last test, he has to give one last sample. And he didn’t bring any of his…Jude Law’s DNA. And so he’s doing his urine sample, or his finger print, I can’t remember, and the doctor is talking to him and it’s like “You know my kid really looks up to you, he really loves you. My kid, he doesn’t think he can make it here.” … Is he invalid? I can’t remember.

S: He… They didn’t completely screen out everything and the kid has some genetic…

H:  Yeah

S: Something

H: Yeah. So, when Ethan Hawke’s face comes up, the doctor just looks at it and changes it to Jude Law’s face.

A: He knew…

[crosstalk, some mumbling]

H: [Jude Law] incinerates himself

S:… It’ just like. So they have an incinerator shower in their apartment, because that’s normal

H: That’s really weird [crosstalk]

S: He just like, climbs in the shower and turns it on

A: And then the other guy… goes and just.. leaves out his dream life?

S: Well they don’t really.. show what happens. They just show him going to space and he is like “Well my heart might give out now that I’m in space, who the fuck knows…” [crosstalk]

A: Astronauts do go through a very extensive physical test, and I assume there’s reasons behind that besides perfect genetics…There’s legitimate reasons why you wouldn’t like a heart… something

H: We are in the future Anne!

A: Yeah…  [laughs]

A: That’s for the sequel GATTACA. [laughs]. Does his heart murmur kills him in space [laughs]

S: [crosstalk] Maybe they should not make a sequel. Please, movie producers do not make a sequel. Just leave it as it is.

A: They could reboot it.

S: It would be a Netflix series

H: Yeah, probably!

A: But it’s just someone doing PCR [laughter]. Because that is more realistic

S: Just a team of crying graduate students

A: [laughter] Exactly. Being like, “this is so unrealistic…”

H: “My arms hurt. Can I stop yet?”

A: “We don’t have the right primers” [crosstalk, mumbling].  So I guess it’s good that they took some scientific liberties for the sake of the movie.

S:  ‘Cause otherwise… it would be… We would still be watching it? Having started in 1997? [laughter]

WHAT ARE GENES?  [19:42-21:00]

A: So… there’s some like… there’s some scientific basis to this movie. I guess we were hoping for you to just tell us more about the science.

S: The science? Um…

H: Yeah, let’s start  with one of the basic questions. So, what exactly are genes and how do they make us who we are?

S: So… every cell in your body has a full set of genes in it, and what genes basically are is basically… you can think of it like a computer code. In a computer code you have zeroes and ones, and in genes you have four base pairs: A,T,C and G.

H: [whispers] GATTACA

[laughter]

S:  And through that combination of four letters, it basically writes out the entire sequence of every protein in your body. And so it’s the full set of instructions.  So, every cell in your body has the full set of instructions – in theory- to make a full copy of you. And so, if you leave… if we’re going for the like CSI angle if you leave one cell at a crime scene they should be able to pick up that one cell and look at your genes in it, and sequence it and then say, because the genome is so long and there’s so much variation that can happen,”oh, this genome can only belong to Sasha Luks-Morgan, and there’s no way it would belong to anyone else.

WHAT IS GENETIC SEQUENCING? [21:00-21:31]

A: So we’ve been talking about sequencing and stuff, but just to sort of define that I guess, sequencing is when you would take all of the genetic data essentially, and have the base pairs written out. Is that correct?  

S: Yes.

A: Okay.

S: So, there’s different ways of doing that, that you probably don’t want me to go into the details of…. but it’s a way of taking your genetics from a cell and getting a computer print out.

GENETIC EDITING [21:31-27:21]

H: Okay, cool. So we can sequence the genes in our body but can we actually manipulate them? Can we actually edit them like this movie is suggesting?

S: So it’s not really a thing that people are doing in humans so much, just because there’s a lot of things that can go wrong when you’re manipulating genes, but it is something that in my lab we’ve been able to do really successfully in zebrafish. So for us, there’s two main kinds of changes that we do, we either add something to the genome or we delete something from the genome.

A: And I imagine though, that one of the reasons you can do this is because zebrafish’s genome is so much simpler than the human’s. Is that right? Or is it just better studied?

S: Part of it is that it’s better studied, but at this point we have a complete sequence of both the zebrafish genome  and the human genome. But the main reason why people do a lot of genetics experiments in zebrafish is that, unlike humans, baby fish develop outside the fish’s body so they’re just eggs that sort of float around in a tank of water So it’s really, really easy to go in and basically inject whatever DNA you wanna add into the genome right into the… into the cell. With people that’s a lot harder. [crosstalk]

A: Yeah, that’s fair. So what… I guess, how are you doing this? What sets of tools…?

S: For… One set of tools when we add DNA is called Tol2, and it’s basically an enzyme and you put it into the zebrafish embryo with some DNA that you wanna add, maybe you wanna make it so that the zebrafish will glow bright green, and so you would take that green fluorescent protein and this enzyme, inject  them into the embryo, and then what the enzyme will do is it’ll take two spots on the zebrafish and basically flip in the gene for the green fluorescent protein and then that gene is permanently part of the zebrafish’s genome, and all of its children will express that gene, and they’ll all be bright green.

So, for when we wanna cut things out of the genome… So I work on a gene called oxytocin, and so one of the first things I did during my project was to start working to develop zebrafish that didn’t have any oxytocin. And so to do that, our lab and then Florian Engert’s lab at Harvard, and Jimmy Gagnon’s lab, he just started here at the U, we all collaborated on working together to use a tool called CRISPR to take this gene out of the genome. So CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats”, okay?

A: That’s a mouthful.

S: Yeah, I have it written down. So,  basically what CRISPR is it’s a way you take some genes from bacteria that make enzymes that chop up DNA in a certain way and you basically hijack them and get them into other cells that you wanna change and you give them basically RNA instructions. So you say, “I really care about this one tiny stretch of the genome, and I want you to go chop out a piece of it”  and so, you take your CRISPR enzyme and your.. they’re called guides, and you put them all into the same cell and they form…they all sort of bind together into a complex, and then it’s basically scissors that match up to a template and then just chop out that part of the genome. And that sounds really easy, because it is really easy. The kind of thing that you could pretty easily do in your house without too much trouble.

H: Interesting

S: Which you should not do in your house! [laughter]. Don’t be a biohacker, please. We are not condoning that. [crosstalk]

H: So, CRISPR has been really popular in media right now…

S:  it is, and it has been… So it’s a pretty new technique for genome modification. It was developed by Jennifer Doudna, and there’s a whole other set of stuff with competing claims for who invented it…. It was totally Jennifer Doudna [laughter].

So one of the reasons it’s been in the news a lot is that people have started to get really excited about the possibility of using CRISPR on people.So there are actually some clinical trials that are getting underway, in the United States. There’s some in China that are going, but there’s some real ethical and scientific concerns about them from what I’ve read. But the two in the United States that  people have been excited about, one is a clinical trial for cancer, and so, finding ways to… especially if it’s a cancer where you know the genetic cause it’s like one specific gene that’s causing the problem, being able to go in, delete that gene out and then cure that person of their cancer. And the other one that’s currently paused by the FDA was to treat sickle cell disease. So it’s another disease where we know the genetic cause and we’d be able to go in and make these changes.

H: So are these changes being made in adults are they being made in babies?

S: So these would be in adults. So, this is gene therapy rather than genetic modification/designer babies. So it’s a little bit different, but in theory, the techniques that you would use for making modifications for something like sickle cell disease or cancer, you could just use in a human embryo, and then have your designer baby. There are obviously ethical issues with that, however

STIGMA AROUND GENE EDITING [27:21-36:15]

H: So, speaking about the ethics of genetic editing, we actually have a question here from one of our many listeners. @MichaelCPace asks : why do you think people shy away from gene editing technology and how can we decrease the stigma surrounding it, especially for when proven and safe therapies are developed to using it?

S: I think that’s a huge question, but I also think it’s one of the more interesting questions about working in genetics right now. People are scared of the unknown. And gene editing is unknown. So you see it ….one of the places right now that people think about when they think about genetic modifications, is  GMO foods. GMO foods are safe. People are terrified of them because they think that it’s gonna be something that’s bad for them or bad for your families or bad for the planet when it’s like, there are all these amazing possibilities and if people are scared of genetically modified soy beans like we’ve got a long way to go before people are gonna be comfortable with genetically modified humans.

A: Not only are the GMO foods safe, they’re often better. That’s the whole purpose of them oftentimes. They need less water… or they produce more…

S: … abundant crops…

A & H: yeah….

H:  Yeah, so there they’re more disease resistant.

S: Yeah, they have like….  the yellow… the golden rice they’ve been trying to develop in nations where famine is a problem with vitamin C.

H: Right

A: But you’re right, if someone’s gonna get upset about rice… [crosstalk] they’re gonna be scared about designer babies! Even if it is just sickle-cell anemia, something that is life threatening, but if you could cure it somehow it would be obviously a very beneficial thing. I think it’s more of where the line is.

S: Exactly. And that’s the question, is… what becomes a disease that’s bad enough that we should be able to…. You know, I have a friend whose  son has a one… a single base pair mutation that caused him to entirely not develop an immune system and he’s almost died like several times. So if they could have gone in and fixed that one… I think he has a T instead of a C on one gene on his Y chromosome.

A: But that’s the sort of thing CRISPR can do.

S: That’s the one thing CRISPR can do really easily right now. I joke that I’m just gonna CRISPR her kid sometimes. [laughs] He’s cute.

H: I’ve seen pictures, he’s cute.

S: So that’s a really obvious one for people, they’re like… well, that’s, that’s obviously, that’s just a mistake, we should just go fix that. And then the place where you start to get into more difficult ethical quandaries are things like Down syndrome where people with Down syndrome live healthy and fulfilling lives, but a lot of families don’t wanna raise a child with Down syndrome, so you  will see cases where people will do… if they are doing in-vitro fertilization, pre-implantation genetic screens, and if they notice that this potential child , this embryo would develop Down syndrome, they’ll be like “ehh… not that embryo.” So we’re already a little bit living in that world of GATTACA where people are able to pick selective characteristics.

H: Right.  So, in GATTACA, they’re not only editing the genome to decrease the possibility of certain disease states, they’re also changing some aspects of people that are a bit abstract. So for example, personality,  we’re joking about “getting rid of the murder gene.” How possible is that?

S: Well, how possible is it, do you think, that we will actually be able to pin down one gene that’s “the murder gene”?

H: [laughter] Very good question.

S: I would be shocked if we were able to get to that point. I don’t think we’re gonna get to that point with personality traits. Personalities are too complex, and brain development is too complex, and it’s not just genetics, it’s also environment. But that becomes the question of,  if we’re willing to do genetic modifications for diseases that people would consider really, really debilitating, well… what if we determined that there’s a single gene for asthma? Are we gonna be okay with making genetic modifications so that kids don’t have to have asthma? Asthma can be really bad for some kids. And so I think one of people’s fears is that  it’s a slippery slope, and we start off with sickle cell diseases and we wind up picking our babies’ eye colors.

H: Right, right

S:  And it’s only a thing that rich people can do, which is the other part of the concern.

A: Well, one of the things about CRISPR, you said it’s  being used in clinical trials right now, it’s being used in adults. Is that correct?

S: Yes

A: So one of the things with CRISPR though is you have to introduce it into the cells, and so if you had something that was more than just your blood cells, if it was something that was delivering CRISPR basically to every single cell in an adult is much, much more difficult than delivering a CRISPR tool into something that’s just a single cell, or something like that.

S: It’s much harder to modify a whole organism than to modify like, one embryo… one single cell, ‘cause you only have to go in and  make that cut in the genome once. One of the other concerns with CRISPR is that depending on how carefully your guides are designed,  how similar the piece of DNA you’re trying to edit is to other parts of the genome, you can have off target effects where you think you’re only making changes in one gene, but you might actually be making changes in a dozen other places. So that’s another reason that I think people can be really wary of making these modifications in people.

H: Right. What are some ways that we can help  get rid of this stigma or approach it?

S: So I think one of the most important things that scientists can be doing right now is actually to be getting really involved with policy and politics, actually.  We have so many legislators that we hear talking about issues of science and there are the people making rules and laws and guidelines around this, who I don’t think could pass a high school biology class. And so the only way that we’re gonna get people thinking about these issues better and get regulations that make sense and that are actually scientifically sound is if scientists start meeting with their representatives and start going to lobbying days on the hill and yeah, running for office and and getting involved and that’s sort of been my push recently. But please register to vote, and then do that. Have you ever heard the Science and Technology,  sub-committee talk about things?

H: I bet that’s terrifying… That sounds terrible.

S: One of them,  I think the chair, maybe three or four weeks ago  said that the reason we’re seeing the rise in sea levels….

A: Oh, I heard about this

S: Which, spoilers, the answer is global warming, was was because there were a lot of rocks falling into the ocean and it was making the water seem higher because there were more rocks.

A: So I think maybe it was a lot of ice breaks, melting into the… [crosstalk, laughter]

S: Anyway, these are the people who are making these decisions about how and whether we’re allowed to genetically modify babies and  treat cancer with these incredibly advanced techniques and they shouldn’t be.

H: Yeah. One of the other issues too, is that a lot of scientific information is just not available to the public so the public isn’t necessarily getting educated on these things, too. There aren’t very many outlets for the public to be like “Allright, let me look at this paper and see what is CRISPR. Oh cool! ”

S: Well, and even if you can track down a copy of the paper, which is hard enough, scientific papers are not written in an accessible style. There are times where, if I’m reading a paper from slightly outside of my field of expertise, I have to really like, pause and be like, “okay, yeah, I’m gonna be googlin’ some stuff.” Because it’s almost like it’s written in a foreign language.  

H: Exactly, yeah, part of being a grad student is learning how to read scientific papers, and  I can’t imagine not being in grad school and trying to read a scientific paper without being trained in it at all.

S: Without having it beaten into your head.

A: But I think that emphasizes your point of then how are we gonna teach people about CRISPR? Well, scientists need to get more involved in politics, because  we can’t rely on someone who doesn’t speak the language, to be making logical decisions. We need someone who is able to speak the language of genetics and then make informed decisions, so that makes a lot of sense.

H: That’s why you should listen to our podcast. [laughter].

GENE IMPROVEMENT? [36:15-42:34]

A: Yahoo Questions is always a good place to find what people are thinking. [laughter, crosstalk]. But one of them I found says, is it possible to edit human DNA for advantageous purposes such as enhanced strength, since gene therapy is being used for replacing bad genes could  replace it normal ones with better ones, and it be no side effects like with steroids?  

S: In theory, yes.  If we knew enough about a specific gene, and we knew what a perfect replacement would be, yeah, we we would be able to go in, delete out the “bad gene”, or the normal gene, and then replace it with the awesome gene.

A: But if this was an adult and they wanted enhanced strength, they’d have to be… You’re not just hitting one cell, you’d have to be able to get CRISPR into…

S: And there are ways of doing that. You can use viruses…

A: It would be an expensive…

S: It would be an expensive process. The other problem is, and I’ve seen this in other places, in pop-science conversations, but if you wanted to have….  take muscles from a tiger, I don’t know, some other ridiculous animal, and then swap out your own muscles with his own muscles… [H & A: Yeeees] … the problem with that is, just because you give a cell a set of instructions doesn’t mean that it’s necessarily gonna know what to make or that it’s gonna make it correctly, especially if you’re taking instructions from a tiger and sticking them into a human.

H: Are you saying our bodies don’t speak tiger?

S: That is… That is what I’m saying.

H: You are shattering my dreams right now.

S: I know… I know… Animorphs lied to you.

H: Dammit.

A: They made it look so easy on those photos too. It was like a holographic cover that gradually changes.

S: It’s so classy.

H: Oh, so it’s not as easy as an animorphs cover

S: Not as easy as animorphs. That’s the take away of this episode. And there are risks to any sort of modification, you could accidentally change the wrong part of our genome, or the gene that you give, it could not work. So saying that there would be no side effects like steroids… it  probably wouldn’t be the same side-effect as steroids, but I wouldn’t say that it was safe, or recommended.

A: And we did mention, the whole human genome has been sequenced but… that’s not true for all animals, is that…?

S: There are a lot of animals we have not sequenced, I am actually not sure…

A: Okay. Have we done a tiger? I don’t know…

H: We need to get on that tiger sequencing [crosstalk]

S: Someone need to go sequence that tiger.

A: But also, we don’t know…  just ’cause we have the sequence we don’t know what it means, necessarily.

H: Right

S: Yes, absolutely. There are whole sequence stretches of the genome where we don’t know what it means, and there’s whole regions of the genome that for a long time people have called “junk DNA”, that they thought didn’t do anything important, and was basically just like, useless stuff left over from millennia of evolution, except it turns out that it does a lot of really important regulatory stuff, so you don’t wanna go and chop into things that you don’t know what they are doing because you might.. break yourself.

H: An advice that could be applied to many things.

S: Don’t cut your own hair kids.

H: You are too late Sasha, I’ve tried that. It was very bad [laughter] So kind of along the same lines of super strength, someone else was asking, can the process of gene splicing grant supernatural abilities such as… some of the most unlikely powers like electricity, like electric eels in the ocean is the example they give. Can we create abilities from scratch?

S:  I’m gonna go with no… not really… not in this, like… “I wanna have the ability to zap people right now” like… I know actually a fair amount  about the way that electric eels produce current, which is totally a useful thing to know. And there’s just a whole… It’s not just like, it’s like one gene that you add and you can do it, there’s like a whole… it’s a whole organ we don’t have, as people, that you’d have to grow all of the constituent parts of that organ and then get it all working together and then get it so that it was happy with being human temperature and in a human, and so…

A: This CRISPR is sounding more and more disappointing [laughter]. You said CRISPR was revolutionary.

S: It is revolutionary when it works.

A: Ah, okay.

H: When it works.

S: When it works. Like, it won’t turn you into an electric eel.

H: You say it doesn’t work the way we want it to work.

S: No.. It’s a really powerful tool, it’s really fast, you can do it all in your own lab, but there’s still limitations. I’ve been working on making a specific fish with a specific mutation in two receptors and I’ve been at it for seven or eight months.Just trying to make sure that when the CRISPR or goes in and it makes these deletions, you don’t always necessarily have a lot of control over exactly what the deletion is gonna be. And so sometimes it’s, it doesn’t make the changes you want, or  it has taken out too much of the genome. And so there’s a fair amount of control but at the same time, like don’t turn yourself into an electric eel.

H: It’s not there yet

S: It’s not there yet… I mean…

H: We are getting there

S: It’s too complex. If you wanted to do something like take one part of your hand and express green fluorescent protein in it like… that’s doable…  ’cause that’s one protein that you need to express in one body part, but to develop electric eel powers… there’s a lot of steps.

H: So all I heard there is we’re one step closer to becoming green lantern. So there’s hope.

S: Yes. So there’s always hope [laughter, crosstalk about grad school and coffee]

DEFECTIVE GENES [42:34-44:02]

H: We’ve talked a little bit about what can happen if you have a mutation with a base pair for example, but someone was asking in Yahoo, generally, what is a condition caused by defective genes? And we can expand that… What are a couple of examples of diseases that are caused by mutations…?

S:  So one of the most common neurological diseases that people talk about having a specific genetic cause is Huntington’s disease, and they can actually go in and do a genetic screen and tell you you have a certain likelihood of developing Huntington’s later in life.

H: So what is Huntington´s?

S: Huntington’s is a neurodegenerative disease, and it’s a really unpleasant disease to have.  it’s fatal, and basically in the gene huntingtin  there’s a segment of base pairs that repeats a bunch of times when it shouldn’t, and so if you have these repeats then you’re more likely to have the disease.

H: So does it repeat in multiple places of the genome or is it just in one spot?

S:  Just in one spot. So in theory, you could go in, especially let’s say you’re a parent who realizes that you have Huntington’s, but you wanna have kids, and you don’t wanna pass on the disease.  In theory, they could do in vitro fertilization and then take one of the embryos  and chop out that segment, although more likely they would just try to find an embryo that didn’t have the mutation to begin.

GATTACA: SCIENCE OR FICTION? [44:02-45:19]

H: Is the GATTACA movie more science or fiction?

S: Fiction. 100% fiction.  [laughter]. Bare minimum, the rate at which they can sequence a genome, in the amount of paper they think it fits on…

H: And that photography? Come on, the photography is so bad!  

S: I mean, it is a gorgeous – – with the exception of the photography and the IDs- it is a gorgeous movie, it’s got a really beautiful aesthetic, very fun 1950s retro… but it’s fiction. Nobody’s iPhone can sequence an entire genome. 100% fiction.

A: But like we sort of said earlier, it wouldn’t really make for a good movie if it was 100% science. No one would watch it [crosstalk].

S: I mean the the fear that people have about designer babies is definitely ….this movie plays into that fear really well because everybody’s fear isn’t…”oh I’m gonna have this awesome designer baby”, it’s gonna be “I’m gonna have the shitty normal baby that can’t compete.” And that’s in there. And sort of the economic disparity is in there, so if you have more money you can pay for in vitro fertilization…

A: It’s already happening.

S: It’s already happening.

A: Better access to medicine…..

ETHAN HAWKE OR DETECTIVE BROTHER? [45:19-

H; Would you rather be Ethan Hawke or Jude Law?

S: Ethan Hawke or HIS brother? [crosstalk]

H: Oh yeah! His brother, who will remain nameless.

S: Detective brother.

H: Detective brother! [laughs]

S: Okay so, Ethan Hawke’s character is  Vincent Anton.

H: Yeah… Oh Anton is the dad’s name! When he was born the doctor was like, “Oh your kid’s got a hard problem” and the dad was like, “I know I was gonna name him Anton but now he can be Vincent Anton”. And then when his brother was born, his dad was like “Name that one Anton”. He didn’t even just change it to Vincent, it was like, Vincent Anton. It’s like, “you could have been my favorite… but you are not”

A: Gotta save it from the next one! [crosstalk, laugh]

S: Save it for the better child

A: Oh my God

S: So yeah, would you… what’s the question?

H: Would you rather your parents love you, or not? [laughter] Sounds like the question!

S: Listen, the unloved child went to space. That’s all I’m saying.

H: Also the unloved child was able to swim farther than the loved child. We didn’t talk about that.

S: ‘Cause swimming was a big metaphor. [crosstalk, laughter]. Swim and have feelings in the ocean. [crosstalk, laughter]. Like, the point of going to the beach is to drink wine and relax! [crosstalk]

A:  I didn’t see the movie, but based off of your guys’s very good summary,  I’d rather be the the son that was loved by the parents, [laughter], the one that have special abilities his whole life, so he’s always gonna have special abilities, he’s always had them, his parents clearly like him more,  I’m scared of space, so that’s not really a very good selling point.

I would not go to space regardless of my skill set, so…

H: I guess we didn’t really learn much about detective brother, did we? He was the most boring character.

A: Oh… So I choose the boring one then.

S: He is just like, a cardboard cut out.

A: But he doesn’t go to space. I choose whoever doesn’t go to space is really my true answer. What about you Heidi?

H: Hmm.. So I feel like my data collection is very biased from the fact that I saw everything from the Invalid’s point of view, but… I mean, considering the society… I guess I would also like to be the loved brother! [laughs]

A: Privilege, like, helps people out.

H: I don’t wanna have to work hard!

S: I know… You really want to be like, “I identify with the underdog!”  I wanna be the invalid brother, but also it’s kind of been my life’s dream to be about 4 inches taller than I am, so I wanna go with the genetic modification.

A: So you are doing it for the height.

S: Absolutely!

A: Allrighty.. Well.. it sounds like we are in agreement. [laughter]

S: Like, sorry Ethan Hawke!

H: Sorry Ethan Hawke. You were great but … [crosstalk]. Well he did get Uma Thurman in the end.

S: Well but then he went to space and maybe died so…

A: He has the heart murmur, and she has those eyebrows…

S: Yeah, I don’t think I can marry a woman with eyebrows like that.

A: Like, Uma Thurman is probably super attractive, but if you put eyebrows like that…

S: I am desperately trying to remember what my eyebrows looked like at my wedding, in hopes that I’m not being a complete ass right now [laughter]

A: I’m saying knowing that I had terrible eyebrows.

H: Yeah, high school was a rough year.

[mumbles about the terrible years of high school]

S: I love to how you invited me to your podcast and all we’ve talked about are eyebrows and murder.

A: That’s usually the subject matter we get back to. Regardless of what we intend.

H: Even Kyle talked about eyebrows and murder.

S: Yeah, I can tell. Definitely.

A: All grad students just talk about this.

[laughter]

H: On that note…

Thank you Sasha, for being on our episode! What are some ways that our listeners can contact you if they have any questions?

S: So you can follow me on Twitter @SashaJessica or on Instagram, my handle on that is SashaLuks-Morgan. Fair warning, it’s 20% science 60% politics, and then 20% cute animals at that dose.

H: That sounds like a great instagram.

A: It’s a great mix.

S: Babies, voting, dogs…  

H: What more do you need?

S:  In life? Not much.

H: All right well, thank you again!

H: If  you’d like to learn more about our guest’s research, or the  topics that were covered in today’s episode, check out our website  at cinemasciencepodcast.com. You can find us collectively on Twitter @CinemaSciCast and you can find Heidi at @PandaBumHah. Anne  doesn’t have a Twitter, but her dog Hubble sure does, you can find him at @HubbleGibson. Our intro and outro music was composed by Kagan Breitenbach. You  can find more information about him at our website but also check out his personal website at kaganbreitenbach.com . The first season in Cinema Science is graciously funded by the University of Utah’s Neuroscience Initiative. Thank you for tuning in to today’s episode. Byeee!