Science Friday - Genetics of Depression, Engineering Humans for Space, Tech Ethics. June 4, 2021, Part 2

Episode Date: June 4, 2021

Research Reveals 178 Genes Are Associated With Depression If you have a family member that suffers from depression, chances are you may have more than one. Doctors often say “depression runs in families,” but scientists really had no good idea how—until a major analysis of the genomes of 200,000 military veterans uncovered the 178 genes that influence your risk of major depression.  Science Friday producer Katie Feather talked to Dr. Daniel Levey, assistant professor of psychiatry at Yale University School of Medicine. He explains why there are so many associated genes, and more about the massive database that helped scientists find them. Can Genetic Engineering Help Humans Live In Space? The next ambitious goal for space flight is to send a human to Mars. After decades of sending space probes and rovers, there are now actual plans for human voyages. Elon Musk says the deadline for Space X’s Mars Mission may be as early as 2024.    This raises big questions, both about how to survive the trip, and then inhabit a world hostile to humans. In his new book, The Next 500 Years: Engineering Life to Reach New Worlds, geneticist Christopher Mason says the biggest technical challenges could be met by genetically engineering humans to survive long-term space living.  He is joined by astronaut Scott Kelly, who spent one year in space, to talk about how we might genetically engineer ourselves, and the effects that space flight has on the body.  How Might Technology Shift Our Morality? What is right, and what is wrong? Today’s debates range from the ethics of eating meat, to abortion rights. Conversely, some questions are much less contentious than they once were: we no longer debate whether abducting and enslaving human beings is wrong—it is. And we no longer question technologies like in vitro fertilization.  Author Juan Enriquez says we can thank technological changes for modern shifts in ethical rights and wrongs, from energy technologies that reduce the value of manual labor to social media that boosts the visibility of LGBTQ people. Enriquez writes that technology changes over history have—and will continue to—change the nature of what we consider right and wrong. As he writes in Right/Wrong: How Technology Transforms Ethics, published in 2020, scientific advances in genetic engineering and neuroscience are bound to shift our ethical conversations even further. Think about CRISPR-edited genomes, or the potential privacy violations posed by being able to interpret brain activity. Climate change, and how to combat it, also raises important ethical questions. Enriquez talks to Ira about his work, and what he predicts our future ethical quandaries might look like.  Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Iroflato. If you have a family member who suffers from depression, you may have more than one. Doctors often say depression runs in families. We've all heard that, right? But scientists really had no good idea of how until recently. An analysis of the genomes of 200,000 military veterans uncovered the genes that put one at risk. Science Fighter producer Katie Feather is here to chat more about it. Hey, Katie. Hi, Ira. So scientists have found the gene that influences your risk of depression? Not gene, Ira. Genes, 178 of them. Whoa, there's a lot of genes. Why so many? Yeah, that's exactly what I wanted to know. People often think about this one gene causing this one disorder in someone, but that's not what's happening here. And Dr. Daniel Levy, who is an assistant

professor of psychiatry at Yale University School of Medicine and co-author on this study answered that by explaining that, well, depression is really complicated. Depression ends up being a pretty big basket. So we call it one thing. We say this is major depressive disorder, but probably people that have this diagnosis get it for a wide variety of reasons. And it can come from biologically many different genes could be linked to the increased risk and different environmental exposures and societal factors kind of also influence that. And so it's because it's such a complex trait that so many genes have the potential to influence your risk for it. And did you have an idea of which genes you wanted to

look at ahead of time? No, that's the beauty of this kind of study, because at this point, we really are early on understanding this disorder. And through treatments, there's some effective ones, but we could really do a whole lot better. And so the point is to look at the entire genome, and we're trying to discover new targets for further studies. When did we start to think that depression might be genetically linked? So the research in this goes back a lot of years. It wasn't until very recently the last couple of decades where the technology has been to a place where we can really start investigating it. We know that genetics only makes up a small proportion of your risk for developing depression, but we think it's an important piece.

And how common is major depression among the population? Do we know that? Yeah, I think it's approximately 20% in the population. And it's something we didn't study in this paper, but something that is something we want to look at in the future, as there does seem to be a difference in prevalence between men and women, with women being as much as twice as likely to report being diagnosed. What does genetically linked depression actually mean? Does it mean you inherit it? So there is a portion of heritability that we explain with how we're looking at these genetics. But again, that's not any kind of fate. It just gives you an increased probability and increased risk.

it's only going to give you kind of a small window into your increased risks. So the individual variations we see have small effects individually. But we're finding if we can combine those small effects into a large panel of many, many variants up to like millions of variants, we can explain a lot more. And so that might give an indication of if you're increased risk and maybe there's some preventative measures you can take. But we're still, I think, a few years out on having a good grasp on that. So tell me about this massive data set.

You needed the genetic information of people, and then you needed information about their mental health. So how did you get those two pieces of data? So the big thing we added was from the Department of Veteran Affairs, Million Veteran Program. And that's a project within the Veteran Affairs system where they're trying to recruit more than a million people, veterans. And we have access to, unlike many other systems within the U.S., the VA has excellent medical health records. So we were able to look up people's health codes, ICD codes, just like an insurance record almost, of what they've had claims for disease-wise. And so we would use that to identify people that had depression. And then in this huge cohort, we could look at what genetic variants associated with the diagnosis of depression.

We also work with some other cohorts from the UK Biobank in England, FinGen, which is a Finnish biobank. And also the personal genomics company that many people have heard of, 23 and me, provided a lot of people that we included in a big meta. for depression. So like what is the value there of having this huge data set? So as we were saying earlier, it's part of seeing so many genes, 178 genes. We think that as studies get larger, we're going to see even more, twice that, three times that. Really? Yeah, absolutely. And so it's because the risk is so broadly distributed across your entire genome. And so the individual variations have a small effect size. So we need to look at all of them to get kind of a combinational score for how these genes influence depression. What does it tell you about the biology

of depression versus the biology of something that's really just influenced by one or two genes? Well, there's very few things that are influenced by one or two genes, and it's like some specific kind of trait. So, yeah, it's just, it just really speaks to how complicated brain disorders and psychiatric disorders are. It's the most complicated organ and the things that, that influence are going to be complicated as well. Do you think maybe depression has been too broadly defined? with so many genes influencing it? Absolutely 100% agree with that. I think that as we move forward in psychiatry,

and that's not just the biological or genetic perspective, that's also, you know, noisology, looking at the study of the disease itself. I think that we will over time identify many different subtypes, people with similar symptoms, but different causes, and that might influence how we end up treating it. This brings me to an ethical question. I know these veterans signed up to have their data used in research studies,

but is there any concern about someone, getting identified from their data and then having that get used against them in some way. That's a great question. So I think that there's something that's been in the news a bit lately is there's some of these genetic tests that try to identify risk for, I think it's for different psychiatric traits for babies that are in development. And I think the point is that we're just nowhere near close enough that the things we're studying are not going to single you out is, yes, you're definitely going to have depression or anxiety disorders or any of these other psychiatric disorders, I don't think that we'll get to the point where you can tell just from

somebody's genetics that you have depression. It's more about identifying risk factors, and when we see what genes, and it's going to be a widely distributed number of genes are impacted by depression, we'll have new ideas for how we can treat it. I don't think we're going to get to the point where we can say, yes, you definitely will have this disorder purely based on the genetics. But even someone with a high risk of depression who may never get it because their environmental factors don't lead to that could still be profiled because they have that high risk, either by insurance companies or medical providers or employers and things like that. It's a possibility, but I think it's one of those things where intervention could be highly beneficial. And so if it's looked instead as a way to intervene and provide benefit for people, that could help employers. I mean, essentially, you're going to want to keep, well, I don't know.

That's actually a great question. I think really at this point the concern is maybe a little overhyped, just because I don't think we're going to be able to explain that much data. And then my hope is if we did get to that point, that this is something that could be used in a more beneficial way for the people that have this trait. And that people wouldn't be screening out just based on elevated risk. they'd hopefully be looking for ways that they can help. But of course, we know that the world doesn't always work that way.

But let's talk for a second about the benefits to people experiencing depression. Could the results of this study be used to help them in any way? So I feel like the main benefit from this kind of work will end up coming down the road where we've identified new novel ideas for future investigation for new therapeutics. One thing that could be more influential sooner would be repurposing of drugs. So we were able to identify certain pathways that are involved with other treatments. I believe one of those drugs is realizol, which has previously been used for ALS. I think there have been some trials investigating that drug in treatment for depression.

So we might be able to identify some things that are already approved for other indications that might be beneficial for depression. You've talked about what we're going to know further on as we keep studying this. What would we need in order to learn more about the genetics of depression and other mental illnesses? Would we need more of these types of data sets, more computing power, interest, or funding? I think funding, we need to increase our recruitment. One thing that I often forget to mention, but I think is very important, is that a lot of the recruitment for these kinds of studies happened in America and in England and in Europe, and you're going to end up studying the population that's most prevalent that ends up being people of European ancestry. So we need to

do a better job of recruiting underrepresented ancestries to make sure that what benefits we expect to come down the line is available to everyone. So the MVP, one of the great advantages of that is it's one of the largest collections of non-European ancestries. And so the MVP specifically is doing a good job of starting to address that, but that is an area that is lagging behind looking at understudied ancestries. Were you able to see any differences based on race or ethnicity? So when we looked in an African ancestry sample, we didn't identify anything that was significant, like individual variants. We were able to look at some overlap across the samples, and there did seem to be some positive correlations. They did seem to be what was seen in one

population indicated it might be there in the other population, but there's just concerned that if we might be missing something of value. And this work was primarily funded by the Department of Veterans Affairs. What does the VA have to do with all this? So they're trying to enhance, you know, treatment, future treatment for veterans. And so they're able to access this large data set and really drive this kind of discovery that wouldn't be available through other areas. Very specifically, again, looking at non-European ancestries because America is much more diverse to many other places that are collecting samples currently.

Did you see anything in the data that would confer some type of resistance to major depression? So we had that susceptibility to it, but are there any trends that show you, oh, this person with this type of genetic profile would actually be the least likely to have depression? Yeah, I mean, one way you can look at it. I mean, it's just the inverse of the increased risk. You'll also see on the flip side of the distribution and people will be at reduced risk. And individual variants, sometimes they confer increased risk and sometimes they do confer protection for depression. So nothing specific. But yes, the polygenic risk score at one end of the spectrum is going to be people that are, at increased risk for depression, but also there might be some indication at the other side of the scale of people that are more resilient. When people think about genetics, they might think about

inheritability and maybe natural selection. So why haven't we seen cases of depression decrease over time? I mean, psychiatry as a field is still somewhat new. I think that there are elements within many of the psychiatric disorders that track with, maybe with empathy, with things that we consider to be very positive traits. And also, when we consider how broadly distributed the genetic variations are, there's not going to be a lot of selective pressure against many of them. So that's why I think that it's persisted. Dr. Dan Levy is an assistant professor in the Department of Psychiatry at the Yale University School of Medicine. Thanks so much for joining us. Well, thank you very much for having me. For Science Friday, I'm Katie Feather. Thank you, Katie. When we come back,

I'll look at the engineering it'll take for humans to live on Mars and beyond. And I'm not talking about rockets. How might we genetically engineer ourselves for a long-term spaceflight? Stay with us. This is Science Friday. I'm Ira Flato. The next ambitious goal for spaceflight is to send a human to Mars. Now, of course, you know that yearning from Mars is nothing new. We've been talking about inhabiting Mars ever since astronomers thought they saw canals on the red planet. But something has materially changed. After decades of sending space space probes and rovers, there are actual plans to put people on Mars. But there's one small detail that needs to be worked out if we aren't to land and even colonize that real estate. How to first

survive the trip and then inhabit a world hostile to humans. As for worlds beyond Mars, well, it could take years or even generations to get there. How do we accomplish that? My next guest says the biggest technical challenges could be met by engineering humans ourselves to survive long-term space living. And he's come up with an extensive plan for that in his new book called the next 500 years engineering life to reach new worlds. Christopher Mason is here to fill us in on that plan. He's also a professor of physiology and biophysics at Wild Cornell Medicine in New York.

Welcome to Science Friday. It's a pleasure to be here. Thanks for having me. So nice to have you. You say that humans have a responsibility to present. reserve life. In other words, a duty to engineer. What do you mean by this? Why do we have a duty to do that? So I just published this book because I really wanted to give a concrete plan as well as a sense of a reason as to why we should go. A lot of times people think of exploring space or going to other

faraway islands just because, because it's there, because it's hard, all of which are good reasons and humans have always been extraordinary explorers. But I make the case here, really, it's a moral argument, which if you say, if you're at a party and you say, I want to talk to you about duty, most people immediately would go get a drink and talk to somebody else. But in this case, I make the strong argument because we're the only species with awareness of extinction. And I think, therefore, we have an actual duty to prevent it, not only our own, of course, but also to serve as guardians and shepherds, really, for all the life forms we see on Earth. So we have this unique capacity and therefore this unique duty that I think extends out to the stars. And in your book, you outline a five

year plan for re-engineering. How do you approach this from the very start? So I put this together first as a series of bullet points on a bar napkin, which is where a lot of good ideas start. But it's, again, it's another human, very specific trait that we can make plans that are intergenerational, that we can look far ahead and posted this on the lab's website in 2011 and started to realize that we really need to have a better understanding of genetics and also thinking about how it changes in the most stressful of environments. And that was actually I first started writing the first grant proposal I wrote for the lab was one to NASA to say we should start to look at this for astronauts. And at the time, there had never been something quite

like this study until we did something with the Kelly brothers and the twin study. So I wanted to lay out a 10-phase plan to better understand the human genome in the most stressful of environments. And then also to think about what you can be modified at the DNA, the RNA level, even microbes. Think about what are things that could be slightly tweaked to give us better odds for the long missions ahead. Slightly tweaked and stressful environments. I mean, there's no better place to start than radiation, because it's one of the biggest risks to the human body

in terms of long-term spaceflight. Tell us, what could we do genetically to protect ourselves from the effects of radiation? Do we have a number of things that are already done both physically and pharmacologically just to keep everyone safe? And this is done not just in space, but also in the clinic, thinking about when you have radiotherapy, how do you actually keep all the cells safe that aren't the ones being targeted?

So think about this when you get x-rays at the dentist. We do the same thing that's just simple protection. But we know there's actually microbes that can make small molecules that can keep intestinal lining safe. One molecule is called the rachidonic acid, and we can actually think about what do we give that could actually help be protective, or we've even looked at things from other species that can keep us safe. One little organism is called a water bear or a tardigrade that can survive the vacuum of space. And in our own lab, we've had human cells that can survive really high amounts of radiation, but still be fine.

But we're basically borrowing the evolutionary tools and tricks of a different species to keep ourselves in our own cells safe, at least in, at least in culture. We're not doing this in astronauts yet. That's probably several decades away. But the concepts and the molecules and the tools we're beginning to develop now, and we can see them work extraordinarily well in my laboratory today. You know, you're familiar with the physicist Freeman Dyson, the late Freeman Dyson. He had some far-fetched sounding ideas that they used to call Dysonian because they were so far-fetched.

Do we have Masonic things now that we'll have to rebrand? I mean, your ideas are far-fetched, but they're really based in real science. And I'm talking in specifics about using chloroplasts to create chloro-humans. I think humans with green skin that photosynthesize. Yeah, so I have a whole section of the book that describes, what could happen if you're really far from a sun? Every photon is a little bit of energy you'd want to capture. And everything that's written in the book is projected.

It's prospective. But it's all based on experiments we have working in the lab today or that molecules we've already found. And there are other creatures that sometimes eat chloroplasts and can survive with them for a little while. So I talked a bit about that in the book. But I also did a fun calculation to say, if you really did have green skin and wanted to be a chloro-human, you know, how much skin would you need? And you wanted to lay out in the sun, say, today, on Earth. It turns out if you do the math and you make some assumptions and the formulas in the book,

you just need about two tennis courts worth of skin, which is kind of a fun idea to think about. Some people think it's totally disgusting. I think it depends on your view of skin. But at least we have some of the math in terms of what we need for shuttling photons to capture them, you know, in terms of laying inside of a human cell, which again sounds a little bit kooky until you realize that mitochondria, which are the powerhouse of our own cells, are themselves probably captured bacteria from many, many millions of years ago. So we already kind of have some visitors in our human cells that have been with us for a long time.

Do you think that we have to genetically engineer astronauts for specific planets? Let's say if you're going to go to Saturn or Saturn's Moon Titan, you have to have different kinds of genetic modifications for going to Mars? It's possible. And it really, I really want to think carefully about any time you modify someone, there's two kinds of modifications. And a lot of people have talked about this with the CRISPR revolution, that's happened recently is that you can modify someone somatically, meaning just their current

cells or germline engineering, where germline means you're actually changing multiple generations and you're constantly changing the human genome really forever. Now, the first one is actually widely deployed. There's already hundreds of millions of dollars that the NIH is funding clinical trials today for sickle cell anemia, beta thalcemia, other diseases. And the success stories are astounding. We actually can already see really great evidence of curing disease by doing gene editing today in humans that's really successful, but none of them are doing germline engineering where you do it basically as a way to change the next generation because it's still too early. We just don't know quite well enough how well CRISPR works to make sure there's no off-target

effects or at least an acceptably low number. So that's why I say some of these ideas would be decades away. However, if you think of really harsh planets, sometimes the changes would make it so you could only survive on one planet if they're too significant. But I think that would be a failure. I described in the concept of a book of something called planetary liberty is how many planets can you live on if you've done your engineering correctly? So would you be able to go to Mars with 38% gravity and come back and still be fine? Today that's hard to do.

And Captain Kelly could describe it quite clearly when he came back to Earth after a year in zero gravity. It was hard. But what if you did 38% gravity for one or two years and come back? Would that be one third is hard or half as hard or two? twice as hard. You know, we just, we just don't know yet, but I would want to endeavor to give the greatest degree of planetary and cellular liberty to anybody. Well, speaking of Captain Kelly, he's sitting right by, standing by to come on the program. Scott Kelly is joining us. He's a former NASA astronaut who spent an entire year up in space. He's author of many books, including

Endurance, a Year in Space, a Lifetime of Discovery. Welcome to Science Friday. Thank you for having me, Ira. Do you think that there are enough astronauts who would love to take on this kind of challenge? Well, if you're talking about going to Mars, I think most of them probably would do it. You know, the way I feel about it is I would go in a second as long as I had some kind of reasonable possibility of coming home. I'm not a fan of the idea of just moving to Mars with no hope of ever returning, you know, having lived in a confined environment for a long period of time and, you know,

essentially something that would be similar to a Martian habitat. but, you know, flying around the Earth and low Earth orbit, I would not, you know, want to spend the rest of my life like that. But I would certainly go if I had the opportunity. So if NASA is listening, you know where to find. Well, let me see if I can make a meeting, a mind meld here. Scott, would you be willing to get genetically tweaked if it meant increasing your odds of surviving a trip to Mars? Absolutely. I was all about like, you know, stretching the limits of the science.

I mean, I even offered up to put a pressure sensor in my skull to better understand this, you know, the issue we have with vision in astronauts and, you know, swelling of the optic nerve that they think is probably caused by fluid shift to the brain in the absence of, you know, living in microgravity. So, you know, I consider it part of my job. and I was basically all in on the science program, even if it involved some stuff that was kind of out there, you know, cutting edge, new ways to prevent the nasty things that happened to us when we're flying in space. Christopher, let's say that Scott volunteers to be part of the astronaut core that will accept genetic engineering.

How do you get that past an ethics panel about what you'd like to do? Yeah, I actually think it's relatively easy in the sense that we, like with any medical therapy, with any medical treatment, we define what we know to be the risks and make sure that, you know, the risk we're proposing aren't worse than what an alternative would be. And then it also has to be necessary. It's something that's not just whimsical. We're not just wantonly editing humans because we're curious, although we do that with human cells in a dish.

But, you know, it would have to be clear that this is a benefit and that we can track outcomes and ensure it's safe and efficacious. And we would start small. It's like, you know, like most clinical trials, like recently of vaccine trials, we've all seen. You do phase one, two, and three, you start small. You get bigger and test safety and efficacy. But the problem with astronauts, there's only, I think to date, only 590 or so ever. And so, you know, we can't run 10,000 person clinical trials like these.

But what we can do is take lessons from other therapies that are already ongoing, that are using somatic methods to repair disease genes, to modify, to even turn genes back on that were once turned off, like what's called fetal hemoglobin. You can actually, you know, we all had a different version of hemoglobin, which carries oxygen in our blood that was active in your fetus. And for some therapies, they're just turning it back on. And it's actually being deployed right now in clinical trials. So I think we would, for the astronauts, we'd learn from them as well as every other variation of a genome modification therapy. Christopher, you looked at the genetic changes happening in Scott during his trip.

There were some pronounced ones. One example is that his teeth. telomeres change? There are some claims that he got a little bit younger in space by multiple measures, actually. His telomeres got longer. I think last time on the show, we also were Dr. Bailey talking about that. And really, you know, other measures, even some of the mutations he saw that were in him before he went in space got better even. So there were some aspects of flight that were good. He lost weight. He got taller and got a little bit younger in some ways by telomeres, which sounds like the best diet plan ever, really, get taller, younger, and, you know, lose weight. So a lot of it did go back to normal when he got back to Earth. And so I can I can confirm

here once and for all that Scott has a very great genome. It's really, it's a solid piece of DNA. This is Science Friday from WNYC Studios. And for you, Scott, getting back to Earth once you got here was not, well, how should I put this? A terribly pleasant experience. Yeah, it was a little rough initially. And, you know, I think everyone deals with returning to Earth or even going to space differently. Some people get sick when they get there. Others don't. Some people have issues when they return. My flights were progressively longer. I flew in space four times. My first flight was a week, my second, two weeks, my third, 159 days. And the fourth flight being nearly a year at 340 days. And it seems to me that the longer I spent in space, my symptoms were progressively worse. If you actually, if you actually,

we, you know, graphed that, you know, time in space over my four flights. It's a second order polynomial. So if I was going to fly in space for a fifth flight, it would have to be like, you know, to match that curve, it'd be like 500 and something days. So over five years, I'm sorry. It would be like five years in space. So, you know, that's why my next flight has to be to Mars, because that's where the curve projected it to be.

So, but yeah, every time I flew, the symptoms were. progressively harder on me. And I would say, you know, the first few days back were pretty tough, as I explained in my, in the beginning of my book when I returned and wrote that. So the other thing that Chris did not mention, though, is that not only was I taller, thinner, better telomeres, but according to Einstein's general relativity, I was actually three milliseconds more younger than I used to be from my twin brother, Mark, because I went so fast for so long. Oh, there goes those birthdays. Wow.

Everything in space travel or in large planning has an order. You have a plan. Let's say that you get enough funding. You know, I'll give you the Science Friday blank check. Right here in my back pocket, too bad. We're not in this. I can't. Not going to Venmo it either because it's not there.

What would you do? I mean, what would steps do you take to create the reality that you see, Christopher? Some of what we're doing already, which is more health monitoring for astronauts, and NASA is doing a lot of this already, is longitude and a whole lifetime monitoring of astronauts to make sure we keep them safe and see if there's any changes we missed during the missions. But what's really exciting, I think, is we're now looking at other commercial spaceflight providers. A lot of them are planning to go to the moon, going farther. And so I think that's happening.

A lot of the work in the lab is building these genetic circuits and these constructs to actually make sure that they work in human cells and can be really protective. So, you know, some of this is already happening. But I think the other thing is to really think also just about activating, you know, let's like I talked about some of the genes that are inactive or adding in components that we can make ourselves more self-reliant. You know, the essential amino acids that we all have to eat because we can't make them, I feel like we should add. them back in. So a lot of this is experiments we're just starting now. But then also some of the CRISPR therapies being tried in humans today, some of the genome editing. It's happening today. So I think we need to do more of it and scale it up, actually. I don't think we have to. What's great is we don't

have to invent some entire new kind of science. We just have to do more of it and do it faster. And last question to you, Captain Kelly. Let's say you could go any place. Think about it. Where would you like to go? I would go to the nearest Earth-like planet, which is, really, really far away. I mean, not in our solar system. Just Scott's point, Mars actually, as far as a planet to go to, it's one of the crappier planets, it's nice because it's close, but if you're looking for one, planets that we know of that have a good size and have likely liquid water and are, you know, probably the right temperature, there's a lot better candidates that are all really

close by, relatively close by in galactic terms. Unfortunately, we are out of time. I would like to thank my guests, former astronaut Scott Kelly, out with a new book, Good Night Astronaut, and Christopher Mason, Professor Physiology and Biophysics at Wild Cornell Medicine, and his new book is The Next 500 Years, Engineering Life to Reach New Worlds. Thanks so much. It's a pleasure. Yeah, thanks, Sarah. And if you want to hear more about Scott Kelly's time and space and read an excerpt of Christopher's book,

go to our website. It's up there at Science Friday.com slash new worlds. After the break, as you've been hearing, technology changes over time, and so do our concepts of what's right and wrong. Are they connected? My next guest says yes. Stay with us. This is Science Friday. I'm Ira Plato. Think of a hot button political issue right now, and there's probably an ethical question at the heart of it. For example, the Supreme Court in its fall session has agreed to rule on Roe v. Wade and might limit abortion rights. How about is it right to allow people to buy and carry assault weapons in public spaces? There are other questions much less contentious than they once were. For example, we no longer debate whether abducting and

enslaving human beings is wrong. We no longer question technologies like in vitro fertilization. My next guest says that technology changes over history have and will change the nature of what we consider right and wrong. And as he writes in a new book, as science advances, is in genetic engineering and neuroscience, the things we are technologically capable of are bound to shift our ethical conversations further. Think about CRISPR edited genomes or the potential privacy violations that can come with being able to interpret brain activity. Juan Enriquez is an academic and managing director of Excel Venture Management, a venture capital firm that invests in synthetic biology and brain research. His latest book is called Right, Wrong,

How Technology Transforms Our Ethics. Welcome to Science Friday, One. Well, thank you so much, Ira. Let's go right to that title. How does technology change ethic? So in this very polarized time, everybody's certain they're right, and anybody who disagrees of them is wrong. The thing that people don't understand is how often what we consider ethical flips 180 degrees.

So take the example of CRISPR babies. there's been justified outrage over how those babies were edited in China, the lack of transparency on it. But you could easily see a conversation with our kids or grandkids saying, you know, my parents were so primitive back then that they didn't edit out the KRAZ P53 Brachyans and I now have cancer. And you could see how editing babies becomes not only acceptable but mainstream. And you think that's where we're headed. I think a whole lot of technologies have flipped the logic 180 degrees. When you talk about one of the hottest botan issues of the time, which is oppressing other human beings, enslaving them, putting them in surf them,

the question is, why did this happen for tens of thousands of years in every civilization? It happened in China, in Greece, in India, the Incas, the Mayans, the Africans. And so why did people tolerate it for so long? And just as important, over a few short decades, most countries did away with it in legal terms. I understand slavery still happens today, but in legal terms, most countries said enough. And it may not be a complete coincidence that that happened just as he started using oil and energy. because a single barrel of oil contains five to ten years of a human beings labor. And when you tie that to thousands of horsepower,

then all of a sudden you have the equivalent of 320,000 of those rowers that used to sit in the Viking ships rowing while the guy drummed in the front. Well, that's basically what's powering you across the nation on two jet engines when you go from New York to California. Are we really saying then that technology is the cause of being more humane and not just a natural evolution of our ethical frameworks? So people often think of technology in Terminator terms and, you know, this awful technology is going to do X, Y, or Z. But on the whole, I think technology allows us to be more ethical. There used to be long periods of time when we couldn't generate enough food.

for the planet and you had massive starvation. We now have more than enough calories to feed everybody, in fact to overfeed everybody. And the issue of capitalism and the economy being the allocation of scarcity is no longer the fig leaf you can use to justify why you keep too much. Now you have more than enough to feed everybody. And then it's an issue of distribution, it's not an issue of availability. And that changes the ethical debate. And talking about the ethics of new sex, as you refer to it in your book, what we now take for granted, you say, would seem like witchcraft to earlier generations.

Please explain what that means. So you remember that wonderful time machine in Back to the Future? Imagine you use that time machine, you bring back dear old grandpa and grandma, you're sitting at the table, you're talking about the birds and the bees. but if you told them you can consistently have sex and not have a child, that separates the act from the consequence. And yes, they did have early birth control, but it wasn't terribly effective. And now it is.

And then you talk about IVF, and you explain to your dear old grandparents, oh, by the way, two people never have to physically touch each other. They don't have to be in the same room. They don't have to be in the same city or even the same country to conceive a child. And they would look at you like you were crazy because they used to call that kind of miracle the immaculate conception. And then you talk to them about freezing embryos. And imagine freezing two twins, having a surrogate mother and having embryos born decades apart. So just take these three things that we now take for granted.

You've separated the act from the consequence. you've separated the act from physical contact, and you've separated conception from time. And if you'd ask them, do you think these things are ethical? They would have said, absolutely not. Now try the experiment going forward. Now imagine your grandkids bringing you back. Do you think sex is going to look anything like what it looks like today in 20 years, 30 years?

Well, tell me what you think looking forward. What are the new technology? that are really likely to shift our ethics even further? What will I consider to be a grandpa about? You know, there were a couple of articles in Nature magazine about bringing calves to term or mice to term in the equivalent of Ziploc bags. So you've created an artificial uterus.

You can work from conception through birth without the animal ever being inside a mother's blanket. Lecente. But you could easily see a debate in 20 or 30 years of Grandma was so primitive that she used to carry the baby around when she went mountain biking. She used to carry the baby around when she was exposed to diseases. She used to carry the baby around even though it was enormously polluted. So the notion of exposing a baby instead of laying a baby in a nice protected environment and the notion of not editing the genes in that baby to take out the cancer-causing genes. All of that stuff will seem really backward. And by the way, this also fundamentally

changes debates about issues like abortion and viability. You may see flip-flops of 180 degrees on these topics as time goes over. But will something remain constant? And that is the inequality, the people who can afford to have an artificial womb or transfer their baby to that womb and people who can't afford it. So that issue you're pointing out, Ira, of who has and who hasn't, is I think one of the absolutely fundamental ethical issues

of our time. Because you used to be able to say there wasn't enough for everybody. And you could justify having more than somebody else because there just wasn't enough to go around. But when there is more, enough to go around. When we have more than enough bicycles and computers and phones and medicines and everything else, it becomes harder and harder to justify why you keep it all and you don't

give others a minimum. And that's especially important because technology is displacing jobs at an incredibly rapid rate. And it's also concentrating wealth. It's giving us the ability to generate these unicorn companies with 30 kids. So on the one hand, that gives us degrees of freedom to give others and to provide a universal basic income. On the other hand, as you point out, it enormously generates wealth and power very quickly in a few spots. Let's move on to something that I find absolutely interesting, and I know you know a lot about, and that's neuroscience and our eventual ability to manipulate the brain. A lot of ethical questions. who's there? It's really interesting. If you think of timelines, the brain is about where genetics

was in the 1990s. So you don't have the rapid mapping machines for the brain. You don't have the first map of a full human brain, much less thousands of human brains. But you're getting there, and you're going to have those maps, and they're going to be standard, and they're going to be measurable across time. And then you're also beginning to generate instruments that allow us to grow little tiny brains and dishes, to study how people get Alzheimer's, how you stop it, how people come down with Parkinson's, how you stop it. You're beginning to get an idea of which parts of the brain

fire when you come down with PTSD. And if you put some electricity in a targeted way or some light in a targeted way, can you stop those memories? Can you erase those memories? And boy, does that have a few ethical implications, right? Because as soon as you begin mapping memories, maybe you can share them, maybe you can alter them, maybe you can insert them, maybe you can delete them. And that is, that's going to be a period that's going to be fraught with opportunities and perils. And that's why discussing and putting an ethical context into science at this point is so incredibly important.

your questions are all about should we do this? Should we, you know, change the genetic makeup of people? Should we, is it ethical to make people better people before they're born? Or what is the actual measurement of what better means? And yet on the other hand, you turn it around and I think in an interesting way, looking forward to our next generations again asking backwards, why didn't you take that opportunity to relieve suffering and pain when you could have? Exactly that context you're putting in their IRA is just so important because the rules are going to continue to change, the things we take for granted, the things we do, those may be seen as 180 degrees wrong in the future. Let me give you one example. This 4th of July,

a lot of us are going to be very happy out there grilling and having a gathering with people. we haven't seen for a long time. And that could be really, really controversial in 20 years because a synthetic hamburger cost about $320,000 in 2013 and $30 in 2015 and $7 last week. And in the measure that synthetic meats are faster, better, cheaper, the notion that we systematically slaughtered over 6 billion animals a year is going to look very different.

Walking into the fanciest, steakhouse in town and seeing these racks of rotting meat, which we called aged steaks. That may be a photograph that looks very different in 20 years. And that's interesting that you bring that up because in your book you call climate change, quote, the ultimate ethical existential challenge. And you note that many, many people have not changed their habits around flying or energy consumption, also part of an ethical decision that people are making. You always have these early adopters that are incredibly brave and ahead of the rest of us.

But what's going to happen, I think, on climate change is the cost curves, the price of energy from wind, from solar is dropping so fast that it's already crossed the price of coal. And it's going to cross the price of oil. In fact, there's a report out by the International Energy Council this week that's talking about how it doesn't make sense to develop. any other oil fuels ever because these price curves are coming down so quickly. Once you have faster, better, cheaper, once you have an alternative, once you can power your house and your car without having to burn hydrocarbons, then you can become very judgmental about what people did in the past. How dare they have warmed the planet? How dare they have burned this stuff? But you're doing so from a position of, I have faster, better, cheaper energy, and it becomes a lot easier to judge

and to act in a different way. That doesn't justify what we did, but it puts a context on what we did that is a context we don't often recognize today. This is Science Friday from WNYC Studios. In case you're just joining us, we're talking with Juan Enriquez, author of Right, Wrong,

how technology transforms our ethics. Do corporations have ethics? We can see from statistics about corporations responsible for over 70% of global carbon emissions? Can we look at corporations or institutional ethics with the same lens that we do individual ethics? So I think one of the most damaging recent rulings by the Supreme Court was where they started saying that corporations have similar rights to those of people. There was a wonderful meme out there by some smart character who said, all believe that corporations are human the day Texas executes a corporation.

You can't mix these two things. Human beings have rights in and of themselves as human rights. And they shouldn't have the same rights that a human being has. It's confusing corporate law and human rights law. And those few things should not be conflated. You work at a venture, capital firm that invests in synthetic biology and brain research. Do businesses that you invest in take ethics into account when they develop or use these new technologies to create products or services? So I've been on this journey for a few decades of discovering genomics in the early 1990s and then moving from academia into investment and still writing and trying to teach some about this world that I find so fascinating.

And the more I learned about it, the more I thought, hmm, I should really start thinking carefully about the uses and abuses and ethics of some of the instruments we're creating because they fundamentally change life, they fundamentally change humanity, they fundamentally change thoughts. And I better be clear on what I'm going to do.

This is not a book that ends with a chapter that says, if only you follow these 10 ethical precepts, you'll be fine. This is a book that says, the rules keep changing, keep questioning yourself, listen to people who disagree with you, understand how it changes over time, and be a little bit more humble, a little bit more forgiving in your judgments. I want to thank you for taking time to be with us today, and thank you for the book.

It really gives you something to think about. Well, it's been a great pleasure. Thank you so much. Juan Enriquez is managing director of Excel Venture Management, a venture capital firm that invests in synthetic biology and brain research. His latest book is called Right, Wrong, How Technology Transforms Our Ethics. One thing before we go, it's almost the most wonderful time of the year. I'm talking about Cephalopod Week.

It's back and better than ever for our eighth annual celebration of squid, octopuses, and older kin. So join us from June 18th to the 25th for a themed trivia night, interviewing octopus experts, and you could help crown one lucky creature with our Cephalopot of the Year award by joining our sea of support. How nice is that? Find out all about this year's festivities at ScienceFriday.com slash squid. That's science friday.com slash squid. Have a great weekend. We'll see you next week.

I'm Ira Plato.