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Music.
Chris Powell 00:07
Welcome to Tiny Expeditions, Season Five, Episode Five. Today we're talking GATTACA once again. In the last episode, we talked about GATTACA with our resident bioethicist, Dr. Tom May, and asked the question, ‘If GATTACA were to exist in the world, is it one that we would actually want to live in?’ Today, we're going in a little bit of a different direction. Sarah, where are we headed today?
Sarah Sharman 00:31
Today, we're headed out of the ethical realm into the scientific realm. So, we're really talking about, could GATTACA exist scientifically?
Chris Powell 00:41
So, the spoiler is, can it?
Sarah Sharman 00:43
You'll have to listen and find out, Chris.
Chris Powell 00:47
Okay, I thought I would get some behind-the-scenes information, but we'll just hang with it. For those of you listening, my name is Chris. I'll be your storytelling guide today.
Sarah Sharman 00:54
And I'm Dr Sarah Sharman, here to help you understand the science
Chris Powell 00:58
Before we get to the science of GATTACA, though, I think we kind of need to reset everything. There may be a few people who didn't listen to the previous episode. So, Sarah, can you give us just an overview of GATTACA? We're gonna reference that movie a lot. What happens in the movie?
Sarah Sharman 01:13
For all you slackers, here is a CliffsNotes version of GATTACA. So, GATTACA is set in a future, and in that future, they have a lot of knowledge about genetics, and they're using that to basically make the perfect human.
Chris Powell 01:25
And this movie is an older movie, correct?
Sarah Sharman 01:28
Yeah, it's from the mid-90s, and while they didn't say they were using genetic engineering technology, with our knowledge, we now know that they probably were. And so, we really wanted to dig in on whether or not that's possible in our day today.
Chris Powell 01:42
And so when we talked about ethics, we talked with Tom May, our bioethicist. Today, we have a different guest who's going to talk about the science of it. So, can you introduce us to our guest today?
Sarah Sharman 01:51
Our expert guest today is HudsonAlpha Faculty Investigator Dr. Nick Cochran.
Nick Cochran 01:58
My name is Nick Cochran. I'm a faculty investigator here at HudsonAlpha, and my lab is focused on genetic contributors to Alzheimer's and related dementias, as well as other neurodegenerative diseases.
Sarah Sharman 02:10
One of the main plotlines of GATTACA is that they're basically making designer babies. How do those worlds compare to what we're doing today with genetic technology? Is that just so far-fetched different, or are there aspects of it that are similar to how we're using it right now?
Nick Cochran 02:28
So, I think there are some aspects that are not so far-fetched, and then other pieces that are maybe a little bit outside of what technology could reasonably do right now but are not too far into the future, and it's worth thinking about and considering. So, I am familiar with GATTACA, and, you know, I think GATTACA is pretty well ahead of its time on some of the things that we are dealing with today. So, you know, a lot of the places where maybe there is selection for particular traits, and that's something that ethically lots of people have lots of different opinions about. But from the scientific perspective, as long as the legislation allows for this to happen, one thing that can technically happen very easily is that you can select for some traits. I'm using the word select very carefully. They are not introduced because it is still just a stochastic, random chance.
Nick Cochran 03:25
So, I'll give an example from the neurodegeneration field. There are approaches where you can select against a dominant neurodegeneration mutation. So you may imagine a family that carries Huntington's disease, a devastating neurodegenerative disease, or dominant Alzheimer's disease, or something like this, where perhaps they want to select against that trait. That's a scenario where most people, I think, would agree that you know, maybe is, if you're going to say that any of this is okay, that would be a scenario where it's okay why they're doing that. There's all these cost considerations and considerations with different governments, and then you know, the logistical implications for how difficult that can be of a process. But if you set all that aside, that's something that can be done today. And while you're doing that, maybe they say, hey, you know, do you have a preference for male or female? And that's, again, you know, something where it's 50/50, so it's maybe something that can be selected for fairly easily. Now you can imagine a case where maybe you do it just for male or female, and a lot of folks may have more of an ethical concern about that, because is that really worth everything that you have to go through? Is it worth the ethical implications of the embryos that are exposed? All of these things are things that I think people have to have their own opinion about. Logistically, it's something that we can do. One important aspect, though, is that there are a lot of traits that are not just one thing like that. And so that's something that is really important to consider. Or maybe it's a rare trait where you know it would take finding something. Maybe it's you would have to introduce it using a type of editing technology, and that's something that's a little further away from not only ethical consideration, but even just logistical implementation.
Chris Powell 05:17
Last episode, we spent the whole episode talking about the ethics of these types of questions you mentioned just a moment ago, what is possible through legislation. What are the main guardrails that are put up for you as a scientist? We've talked through what we could or, you know, the options that are available, but as a practicing scientist, what are the primary guardrails that you look to? Is it legislation? Is it funding? Is it just your own inner sense of what is right?
Nick Cochran 05:47
I think what we do as scientists in the lab, we're not doing things that are going to directly affect living people. Now, there are some researchers who are doing things that affect living people. I'm not one of those. But you know, if I put myself in the shoes of someone who's maybe doing research in that area or a clinician working in that area, then your guardrails do become largely legislation, which can vary from state to state and country to country. And then, beyond that, I think that everyone does have their own personal guard rails. And they may say, maybe this is allowed in my state, but I personally don't feel comfortable practicing and implementing this. So that's some of the things that people consider as a scientist in a lab. If we're working in a system that's very reductionist, there's pretty well-defined guidelines in the field.
Nick Cochran 06:43
So, one thing is that, for example, we work a lot with stem cells. That's a hot-button topic, but what most people think about when they think about stem cells and the controversy around stem cells is embryonic stem cells, and that is something that we do not work within my lab. So, what we work with is stem cells that are derived from healthy consenting adults. You can take skin or blood cells from a healthy consenting adult and back convert them to stem cells. In that way, there's a very ethical source of those cells, right? Then, we can use those cells for all sorts of experiments in the lab. We can use them to make cultures of neurons and cultures of immune cells of the brain to do experiments that are relevant to the diseases that we care about. You can even create more complicated symboloids and organoids. These are things that may be a little ball of cells that can all communicate together. But importantly, these cells are not alive. Well, they are alive, but they're not. They don't have sensory organs. In that way, we feel very reasonable at working with that ethically. If you expand beyond this, there are all sorts of ethical considerations with animal work. We don't actually do animal work in my group, so the considerations around stem cells are one of the main things we think about. And then beyond that, you mentioned guardrails of funding. Of course, as a scientist, we're always looking for ways to fund our work, and so that's certainly something that you know is a limitation to what we do and implement.
Sarah Sharman 08:20
So, they didn't say they were doing gene editing in GATTACA. They probably were based on what we know now. Can you kind of explain what gene editing technology is? Maybe hit on CRISPR, which I think people hear about often. Basically like, what are we talking about when we're talking about gene editing technology?
Nick Cochran 08:39
This concept is you can make some sort of targeted change, right? And maybe it's a small, single change for a single thing, or maybe it's a broader change, like the concept in Jurassic Park of getting back to a dinosaur eventually by starting with a modern lizard and then making all the all the changes along the way. So, I'll talk about the big changes first and then get to CRISPR. So, the big changes, there actually is some Jurassic Park-esque type of work going on in efforts to bring back the Wooly Mammoth. And so this is something where because Wooly Mammoths are not that old, and some have been preserved well in frozen areas, there's good genetic material. We know what the genetic sequence looks like. So logistically, to bring back a Wooly Mammoth, you could imagine putting big pieces into an elephant genome slowly over time, and eventually you get to a genome that's all Wooly Mammoth, and you've brought it back. That's something that logistically may actually be possible. Now, you know, is it worth the effort? I don't know. That's a question for somebody else. I think it's scientifically kind of an interesting thing to do. You know, again, should we do it? A dangerous dinosaur is a little different from a Wooly mammoth, which probably, maybe, hopefully, wouldn't pose such a danger. So, you know maybe that's okay as a demonstration of that kind of approach.
Nick Cochran 10:09
Now, gene editing of single particular things is the concept we've talked about with could you use this for designer babies? And I think that currently, the technology is close to that. So, you could, in theory, do CRISPR of embryos, and then make sure that there's not off target effects with rigorous sequencing, and then reintroduce it back in. That's something that I think is a little more controversial. Something that may be a little less controversial is using CRISPR for therapeutic applications in a way that does not affect the germline. And there are some examples of some things that have that have happened with that. One of the main logistical challenges of CRISPR is delivery. But some places where you can deliver easily are the eye. So there have been some successes in that area, also with stem cells. So, stem cells, and now we’re talking about stem cells in the blood, what you can do is get stem cells out of someone's blood. You can make an edit, for example, in sickle cell disease, this is something that's happened, or radiate any remaining stem cells and then transplant the edited stem cells back in. And now the difficulty with that is that you end up with the possibility of off target effects. So again, that's, that's something with CRISPR that can happen, and you have to be careful about it because off-target edits could end up leading to something like cancer or something like that. Then you've kind of traded one disease for another. That's not such a good thing. So those are some of the logistical considerations. But gene editing is in the clinic. It's something that is being implemented and probably will be more so now. Then, the question is, where do you draw the line on that? If someone wants to pursue gene editing just for some trait that they view as beneficial, can you do that? Should you do that? The ‘can you do that’ is probably a big limitation right now for most things. So, for example, in diseases of the brain, which is where I work, this is all still really far away. And the reason for that is that delivery is a big problem. The brain is classically really hard to get to even with small molecule drugs. And even if you do, you've got to be really careful, because once you make an edit, that's it, it's done. You want to be really sure about those off-target effects and that sort of thing because you can't turn it off once it's done with something like a gene editing technology.
Chris Powell 12:40
So, we're talking about CRISPR, but AI is massively in our consciousness right now. Right? I know it's being used to help find targets that could be targeted. Is that also being used to help predict these unintended consequences?
Nick Cochran 13:02
This is such a new field, and there are all sorts of possibilities. And with any new technology, there's always a huge amount of enthusiasm at first, right? And that's, I think, the place that we're at with AI. We're thinking about all sorts of ways that we can implement and leverage AI. One important thing is that people say AI, and it can mean a lot of things; primarily, the furthest along applications are these large language models, which are really good at interpreting and processing text information. There are good applications for that in the lab, and we use this with things like coding. So we may say, I need a Python script to do this thing. And instead of a person having to sit there for several hours considering how they would do this thing, AI is good at interpreting that text and then very quickly converting it to the syntax used in code. So we use that all the time already to facilitate more efficient coding.
Nick Cochran 14:14
Another application of AI, and this is not large language model, but something with image recognition.
So, folks may have heard about radiologists using AI, and that's something that is being implemented another place in science is with microscopy. So really being able to look at complicated microscopy information and deconvolute some sort of signal out of it is something that AI is already pretty good at. So, there are these initial applications in science that are really important. As far as using AI to predict unintended consequences, I think that that's potentially something that could be done. It's a little outside of my area, but I could imagine AI incorporating lots of literature from ethicists on considerations of different things like this, and then predicting some of the consequences. Even looking at historical text and incidents like some of the things that we've talked about today and considering and thinking about how those might translate if you were to do something similar with the new technology, right? So this is one of those occasions where, you know, history doesn't always repeat itself, but a lot of times it rhymes. And you know, maybe AI can help us identify some of those patterns and how we can project out what some of the consequences could be.
Sarah Sharman 15:32
So, we've talked a lot about how you are using genetic engineering right now and how the field is using it. Where do you see that going in the next decade or so, or where would you like to see it going?
Nick Cochran 15:43
So, one thing that I've been saying for a long time specific to the field that I work in is coming is good biomarkers for Alzheimer's disease, so that one day you're going to be able to go to your primary care doctor and say, I want to know about my risk for Alzheimer's. I've heard that there are brain changes that happen really early. I want to see if that's happening, and we're there now. So there's really good biomarkers. There's lots of different companies that offer it, where you can go and say, Okay, I'm going to get this really predictive marker, phosphotau 217. That's a $200 test, and now I know that I'm at high risk and need to pursue some treatment options in the future. And that's something that it's like a switch flipped where it was in development for a long time. There were lots of trials; there was a lot of research. It was which of these different markers is going to be the best? And then, finally, one emerges. It gets implemented in clinical practice and it's really just like this year that that's really happened, and it's happened very quickly. So, you see this acceleration towards the end and implementation. So that's something I see that we could see this kind of technology going as well. So currently, we're in those earlier phases. There are trials in rare populations, and there are edge cases where it's being implemented for really devastating diseases. But as that technology evolves, and as the delivery gets better and we're able to hit more tissues, you're going to start to see that transition, and then it'll be a rapid implementation, more broadly for these kinds of technologies. And so I think that it is the appropriate time now to be thinking about the implications before there's that switch that flips of really being able to roll these things out broadly and clinical practice.
Sarah Sharman 17:43
And I think another thing that plays into that, adjacent to the science side and the ethics of that, is the public opinion. And I know that there's been fear and confusion around gene editing for decades, probably, and I think some of that is fed by the media, but they're also an uptick of these storylines in movies and TV shows. How important is correct representation of gene editing? How important is science communication in this?
Nick Cochran 18:11
Yeah, so I think it is really important. And you know, I think that there's always going to be this tendency for media to portray things that we know maybe could be in practice in 10 or 20 years, but maybe aren't quite there yet, but to portray them as if they are in practice currently. So I think of you know the crime shows where they have a grainy picture, and they say, enhance, enhance, and you know that's not really something, that’s not really a thing. It's similar with genetic technologies; they're always going to be talking about things that maybe they get a scientist to say, Yeah, in theory that could be possible in the future. And then now they're showing it now. And there's gonna be this perception then by the population that maybe we are there now, or even if they recognize that maybe it's a little futuristic, it's still an unconscious bias that we're further along than we really are with some of these technologies. So I do think it's important to communicate where we really are practical with this.
Nick Cochran 19:20
And the other thing about that is that I think that in the media, the other thing is that you're trying to tell a story, right? And you're trying to make an impactful point. So, it often may be used as a mechanism to talk about some of the cautionary tales of some of the things that could go wrong with these technologies, right? So maybe it's huge dinosaurs that escape from their enclosures, right? And I think that we need to do a better job in the media and in communication of talking about some of the things that are going right, some of the things that are clear wins for this technology. For gene editing, these clear wins of treating sickle cell disease. These clear wins of gene therapy of treating these devastating childhood neurologic diseases like SMA. These are the things that I'd love to see a movie or a show covering some of those things. But maybe it's not as flashy as some of the other things that you can do with cautionary tales like dinosaurs, right? So, I think it is important to communicate not only the cautionary tales but the real advantages that these things can have, both in advances in the lab and also for clinical implementation,
Chris Powell 20:36
As we were planning for the season of the podcast, it was almost overwhelming to look through the vast catalog of films and TV shows to see what we could discuss. There's a lot of TV shows, a lot of films out there. Just look at your Netflix queue, right? You can be overwhelmed very easily. And as a producer of media, and also a consumer of media, after working on this season, I found myself kind of vacillating between thinking that I should be a more discerning consumer of media based on the science that's portrayed, and alternatively, just not worrying about it and allowing even these fantastical portrayals of science to, if you will, ignite a curiosity that then causes me to dive deeper into the realities of the science.
Sarah Sharman 21:17
And as a scientist, I know that I'm probably supposed to be like, yes, science should be represented accurately in everything that we're consuming. But I mean, what if you just want to watch something for entertainment purposes? What is the harm if you know that we aren't actively cloning dinosaurs right now, that you get to watch a film like Jurassic Park, and it gets to entertain you for an hour and a half to two hours. So I think you're right, Chris, there is a line, but I think we also have to think about it as what is the purpose of the thing we're consuming, and if it is entertainment, is there harm in the science being a little inflated or superfluous?
Chris Powell 21:55
Some of the topics that we've covered over this season are quite controversial, and that's honestly why they make for good movies is because you can talk about them in story form, and you can really wrestle with the consequences of, well, do I want to live in this world or not with genetic engineering? That's one of those hot button controversial topics. And if you didn't listen to it, go back and listen to the previous episode. We sat down with bioethicist Tom May, and we talked through the ethics of genetic engineering and what a world like GATTACA may look like.
Sarah Sharman 22:26
Thank you for exploring the possibilities and limitations of genetic engineering with us.
Chris Powell 22:31
In our next episode, we'll continue exploring the representations of genetics and pop culture, and maybe your favorite show or movie make an appearance.
Sarah Sharman 22:39
Tiny Expeditions is a podcast about genetics, DNA, and inheritance from the Hudson Alpha Institute for Biotechnology. We're a nonprofit research institution in Huntsville, Alabama, with a unique mission.
Chris Powell 22:51
We bring together scientists and companies to develop and apply genomic advances to make a better world. That's everything from cancer research to agriculture for a changing climate.
Sarah Sharman 23:00
If you enjoyed this episode, swing by your favorite podcast app and hit that subscribe button while you're there, consider leaving us a review. It really helps us spread the knowledge.
Sarah Sharman 23:11
Season Five of Tiny Expeditions is made possible in part by our sponsor, EBSCO Information Services. They are the leading provider of online research, content, search technologies and workflow tools serving public libraries, schools, academic institutions, corporations and medical institutions around the world, proudly delivering information access for Researchers at all levels, online@ebsco.com
Chris Powell 23:38
Thanks for joining us.
