CRISPR and the Genetic Astronaut

That's right. This Uh the panel that I ended up attending. This was one of their salons at World Science Festival, Evolution Beyond Earth. It was. It was one of the highlights for me because it basically revolved around a discussion of genetically modifying humans for space exploration. And this is a great topic because it touches on some stuff that we've covered before. The idea of augmenting humans for space, uh is an idea that goes back decades, and we'll

get into that. And it also touches upon just genetically modifying organisms in general and the crisper technology, something that we've been we've wanted to talk about on the show for years, and I feel like this gives us a proper science fiction flavored excuse to discuss it within uh,

you know, a particular set of parameters. Okay, So today we are going to be doing our best to try to give a simple, straightforward explanation what the Crisper gene editing process is and what it does, but also to uh explore a little bit of what they talk about in this panel about genetically modifying astronauts and ask should we do it? Should we make our spacemen and space women of tomorrow creatures of the gene scalpel? Well, if you phrase it like that, um, I mean, really it

seems like a reasonable proper position, doesn't it. I mean, when you consider I want you could consider the options. Okay, you could potentially terraform another world. You could you could strain to bring a particular human environment into space. You know, basically, can a canned version of Earth throw it into space and let people live in that? Or perhaps you can

just change what people are. You can make you can either adapt people to existing environments beyond Earth or tweak them in such a way that you're not having to bend over backwards to create an environment for them beyond Earth. And this is this is an idea that is resonated in science fiction for some time. A few different examples come to my mind. I don't I don't know if if any of these, uh, we're knocking around your head as well, or if you have your own examples to

to discuss. No, let's hit yours man, all right? Well? Um. The first is a novel by a Clifford D. Simic, who is a kind of a legend and science fiction circles. He was very prolific. He is probably best known for a collection of short stories, but he wrote titled City. One of the tales I think involves um speaking dogs, like a race of intelligence talking dogs that wait. Telepathic dogs are just like saying words out loud with their

dog mouths. I think they're they're speaking, but I'm not certainly, because there's not one that I've read. One book of his that I have read though, is N sevens The Werewolf Principle. And this is this is a great book in a number of ways because essentially, I I don't know the origin of it, but it feels like someone said, hey, Clifford, can you write a space werewolf book for us. I think that's something people would like to read, and who wouldn't.

But he does a fantastic spin on it that is just so thoroughly, so thoroughly late sixties, early seventies, you know, science fiction. Uh So, it's a wonderfully weird novel in which a human space traveler is augmented to rapidly adapt to alien worlds. He's sort of an android designed to scan and mimic alien species for research purposes. He's one of only two constructed, and he's sent out to alien worlds,

uh two hundred years ago. He visits a number of these planets and then he returns to Earth and begins to experience transformations into these into certain certain monstrous forms. He's having an identity crisis. And in the background to all this, the the the the earth setting that all of this has taken place on Invote includes flying houses because humans have these, you know, these space age houses. Why I stay in one spot when you can have your house moved from spot to spot. And also the

woods are teeming with brownies or maybe not teaming. Teeming is not the right word. But we've reached the point as a human species to realize. Oh yeah, most of the mythical creatures that we taught, we spoke about and sing songs about, they weren't real. Up for brownies, brownies were real. Are brownies like fairies? Yeah, they're just like a race of fairies and they live in the Pope Woods.

And I don't I don't recall to what extent they actually play a part in the plot of the werewolf principle, but just that they're there because the world its own unique stent. You know. I'm glad to hear that there's a space werewolf novel because that's something that there could stand to be plenty of. I'm waiting for the Space Mummy novel. When does that happen? Well, there was that film. I forget the title of it or the titles, but

it was. It was featured on Mystery Sentence. Theater three thousand had an ancient astronauts money is like, was it the Frankenstein and the Aztec Mummy? No, but maybe that was also space Mummy. But this one was like visitor from another world or something to that effect. No, I don't know what that is. Well, anyway, I will agree that it is an under utilized sub genre, the space mummy. That's what we should be going back to. Ye, So if you're in the middle of writing a space vampire novel,

give it up, just put it on hold. Give us space mummies first. Yeah, and then the sequel can be space mummies versus space werewolves. Now, another sci fi property that comes to mind is a two thousand nine film that I know some people did not enjoy, but I actually really enjoyed this one to two thousand nine Pandorum like some things about it. Yeah, I I embraced the mixed review. I embraced all of it. This is the

one that had Dennis Quaid in it. It did. It's yeah, I will say it's not one of Dennis Quaids finer performances. It's no enemy mine. But the plot, the look at the film I thought was great and the plot was kind of cool. They so they're a colonists aboard and interstellar arc named the Elysium, and the colonists are augmented to rapidly adapt to the environment of their destination exoplanet,

which is a world called Tennis. But of course, something goes horribly wrong and a portion of the crew wakes up early, they go a little crazy, and their descendants rapidly adapt to the environment of the spaceship and they become the essentially become a race of cannibal mutant trog lafuna. It's kind of like the descent in a spaceship instead of a cave. Yes, yeah, I think that's a that's a fair assessment, and it also reminds me a bit of a movie that came out of along the same time, uh,

known as eden Log. Did you happen to see this? No? I don't think so. Eden Log is is hauntingly familiar. It's like a more artistic French reflection of the same film. So I would say, if if anyone out there enjoyed Pandoram, go see eden Log, or if you enjoyed parts of Pandorum, go watch eden Log. You probably won't understand what's happening. But when has that ever gotten in the in the way of a good good time in a science fiction movie.

I should also point out that in Dan Simon's Hyperion novels, you have the the Alsters, humans who have adapted to life in space, granted suited and within ships, but still uh that they've been able to adapt due to extensive genetic self manipulation. And then the Expanse series based on the books by James S. A. Corey. You see belters who are who have adapted to to life on ships on the sort of the the outer limits of human

habitation in the Solar System. Yeah, this is probably the example I would have mentioned if I was going to bring up genetic adaptation to space conditions, because obviously living in lower gravity environments, this would be problematic for humans who have been tailored by billions of years of evolution to survive on a Earth gravity world. If you're out in a small gravity world, you just probably need a

different body, right, And so these differently adapted creatures. There's this one scene I remember in the Expanse of gravity torture Belters being brought back to Earth and tortured with Earth gravity. Yeah, just the the the the act of of living on a higher gravity world is torment to them.

And that kind of underlines the reverse challenges of taking your You're taking a creature and expecting it to live in an environment that is tortured to them, that they that they just simply have not evolved to cope with. So the panel that I that I attended. It was moderated by neuroscientist Stuart fire Stain, and the panelists were geneticist Chris Mason geneticist Ting Wu who as a sort

of trivia on Teing Woo. She is the wife of noted geneticist Georgia m. Church and also astrobiologist Caleb Sharf. So we we don't even have to consider the challenges of an alien planet to consider the the benefits or the potential benefits of of altering humans for space travel.

In fact, you might say space travel itself is the harshest possible environment, maybe even more so than another plan And I guess depending on what the planet is like, because on another planet you'd at least expect to have some gravity, right, or you can only assume there will be like some level of robust radiation shielding, either in the form of a of a naturally occurring magnetosphere or

like hopefully a substantial underground base or whatever. Your your off world colonies gonna consist of an atmosphere and an atmosphere which is also gonna entail a certain amount of radiation shielding. But your your your tin can, your your generation ship sailing across the space. Sailing across interstellar space, even that's going to be a different proposition. Unless you're going to a comet or small asteroid. The ship is probably a harsher environment and and uh and probably a

long journey. Oh. An important point that that that the moderator Stewart Finstein made in this is that humans have proven incredibly adaptable here on Earth. And I think this leads into this idea that we should be able to survive anywhere. Right we live all over the world. We can,

we can sustain ourselves in pretty harsh conditions. And yet, um, even though we've become a global species, even though we're considering this leap uh into becoming an interplanetary species species, we entertain quote a migration to a place that has never impacted our evolution in any way. That's a really good point. I mean, yeah, there's there's just been zero input whatsoever of for example, zero you know, microgravity conditions on on the evolution of any life form on Earth,

no precedent whatsoever. So on the other hand, so on one hand, you can say that place is not for us, the space is horrible, why would you want to go there? But there are plenty that argue that, hey, we need to figure it out, that that life beyond Earth is vital to the long term survival of the human race. That if we're going to continue to exist long term, we have to exist places other than this world. Right.

We can debate what the number is, but the natural ecology of Earth, or even the augmented ecology of Earth, does have some kind of natural carrying capacity. There's some maximum number of humans that it can sustain in terms of giving them clean air to breathe, freshwater, food space to live, all those kinds of things. At some point, we we will run out of that if we keep multiplying, and of course there are there there are hard stops for just the habitability of Earth in the long term

future as well. Yeah, at some point the sun will sort of increase in size. That's not so great for

the surface dwellers of the Earth. Yeah, and uh, And then there's there's another argument to be made here, and this is the one that that the astrobiologist Caleb sharfmin and the talk he said, he said a human exploration remains the best option for exploration, that robots can only get us so far, and that there's and the this you kind of get into a more I guess, philosophical argument for exploration when you're saying that, yeah, you can send robots, that you can send probes out. Uh, we can.

We can move a joystick and then move a robotic arm in another world with some degree of lag time. But are we losing something? Is there something? Is there something lost in not having actual human exploration. Sure you can make that argument. I mean, I think I'm of the opinion that robotic exploration can get us a lot of what we need. We can get some good research results, we can reduce the risk of human death and injury, and reduce the risk of cross contamination of environments and

and all that kind of stuff. You can do a lot with robots. But there are some things that humans are sort of unique providers of. One is on site ingenuity. Robots at this point do not have the kind of intelligence and ingenuity and creativity that a human astronaut would have. If you were trying to trying to not just say, do a few specific tests on the surface of Mars, but to create a robust research environment on a faraway

planet that makes sense. But then also on top of that, humans have inspiration potential for the rest of humanity in a way that robots don't. Not to say it's not inspiring to see the Curiosity rover, for example, moving around on the surface of Mars. But you can't deny there will be a very different kind of effect when there are human feet on the soil of Marsh, no doubt. And so we end up and then asking the question, well, how is this going to happen? How are we going

to pull it off? And indeed, what changes might we want or need to make to the human body to enable those feet uh, those footsteps to actually take place on Mars. Well, I know one answer is we gotta got to replace these hands with crab claws. When are we finally going to get our clause? Robert, Well, I mean maybe there's an our baby steps though, right, Because if our knowledge of GMOs has thought us anything thus far, is that people are are going to be resistant to

the idea of like rapid change. Right, They're not gonna go for crab clouds right off the bat, but maybe more subtle changes at any rate. Genesis Chris Mason says that we need to consider a five hundred year lab plan. So a multi stage plan to advance our understanding of the human genome, figure out exactly what we can tweak where we need to tweak it to adapt humans to better Uh. For instance, a thrive on a trip to Mars and then the subsequent stay on Mars, a subsequent

colonization of Mars. So five dred years that's a pretty slow ascent, and I can see some benefits to that. Number one, that gives the technology plenty of time to get there. But number two, it's what you were talking about with baby steps and acclimatizing people. Yeah, it would give people in general a chance to say, okay, this is fine, you know, because each generation the changes would be small. Yeah, so hopefully by the time crab class

came along, everyone would be cool with it. And it's but it's also it's easy to say, well this that this sucks is an option because five years we're not going to be around to to see the fruits of that labor. But it also really plays to humanity strengths because no matter granted, we we often suffer for our ability to not um not calculate things long term, but yet at the at the same time, we do have

a unique ability to plan beyond our own lifespan. So it's it's kind of a it's a special magic that that other organisms do not have. Even if it's a one that we are, we're not completely competent with ourselves. Yet, even if we're not great at it, we can at least do it. And as they say in the in the Space Program, doing a bad job is better than not doing it at all. They don't say that, do they.

I'm not sure that that might have been included on the voyager plates and not not positive all right, So before we consider the present solutions, before we consider genetically modifying humans for space, I think it's a it's a good opportunity to look back and see what two individuals, Nathan Klein and Manfred Klein's said in their their Cyborg paper back in nineteen sixty. Sure, because hey, if you want to modify human beings to explore space, you don't

have to go straight to their genes. You could instead basically give them a few mods right now. Yeah, And that's that's basically what what these authors were arguing back in nineteen sixty. They presented a grocery list of ways that technology and medical science could retrofit the human body for the star hopping lifestyle. And this is where the concept of the cyborg came from, was this paper in nineteen sixty by the client, by the clients, by client

and clients. Yes, one with a C, one with a K, one one with an ass on the end, one without it. So it always trips me up as well. But yeah, they made this argument early on to say, hey, you want to put people in space, you need to be willing to change people. And we were not willing to change people. Or we can look at it two different ways. Either we were not willing to do it, or we did not really have the the the scientific advances to make those changes, at least not the more radical changes

that are proposed in this paper. This is a very if you if you go read this paper, the tone of it is incredibly gung ho, you know what I mean. It's just so like, well, let's get her done, come on, changing humans for space. Yeah, yeah, it is very gung ho. Uh. I'm gonna read a quick quote from it here to

give you a taste. Solving the many technical problems involved in man's space flight by adapting man to his environment rather than vice versa will not only make a significant step forward in man's scientific progress, but may well for vide a new and larger dimension for man's spirit as well. So they're like, let's not just change ourselves for space,

let's change ourselves for the principle of it. Yeah, it's kind of It kind of gets back to the idea that if you change the body, you change the soul. When they're saying, hey, we're gonna in big in the body, We're gonna in big in that human soul. Uh, you're gonna it's a perfectly cromulent idea. So their recommendations were all very much in the vein of retrofits. So we're gonna get more into the idea of of sort of

you know, front end changes via genetic modification. But they were all about taking the creature that is evolved for this world and adapting it to survive in the other or you know, in the space between worlds. Uh. That they made a point of not altering the heredity of the human being. Interesting, So here's another quote. In the past, evolution brought about the altering of bodily functions to suit

different environments. Starting as of now, it will be possible to achieve this to some degree without alteration of heredity by suitable biochemical, physiological, and electronic modification modifications of man's existing modus vivindi. Okay, so the way of getting along in life previously we would make an adaptation to our genes in a way that could be transferred from adult

to child. So it's a it's an indirect modification. It's not the Slamarckian idea of like, well, I had to reach up to a tree, so my arms got longer and my kids had longer arms. It's no, you're born with longer arms by accident you can reach the tree better unless your kids get that as well. That's, you know,

the the accepted version of heredity. Now, of course, epigenetics and lots of weird things have sort of modified that slightly over the years, but still we basically are operating on a germline heredity model for for where our body traits come from. And they're saying, no, we don't have to do that anymore. We can change people who were alive right now. They don't have to get these changes from their their ancestors, and the changes are rather fascinating.

The ones that they proposed. So they make suggestions in including the use of hypothermic hibernation for extended space travel, lowering body temperature, and administering various drugs through an automatic osmotic pump of course to alter enzyme levels, low gravity tolerance, etcetera. There's also the the idea that you could use a solar or nuclear powered inverse fuel cell in place of a lung. Isn't that just beautiful? A nuclear powered fuel

cell for respiration. And then this is probably my favorite passage from the paper, fluid intake and output fluid balance in the astronaut could be largely maintained via a shunt from the uritors to the venous circulation after removal or conversion of noxious substances. Sterilization of the gastro intestinal tract plus intravenous or direct intra gastric feeding could reduce fecal elimination to a minimum. And even this might be reutilized.

This is ambition, This ambition if I've ever seen it, Yeah, this is the basic cybernetic replumbing of the human body. Yeah, they're looking at what the human body does. They're saying, like, look,

pooping and peaking so much waste here. We gotta find a way to reclaim all of this waste from poop and p This enthusiasm reminds me of passage in Mary Roach's excellent book Packing from Mars, But she talks about the clash of culture between the NASA scientists and the astronauts themselves, especially early on when the astronauts themselves tended to be essentially cowboys. They were they were the they were the test pilots. They were that they were very

man only men of the of of the sixties. Well, I think actually the astronauts may have better embodied this, uh, this client inclined, gung ho attitude of like, yeah, let's do whatever, get her done. Well to a point, because, as Roach points out, you have scientists who would say, all right, uh to and to enable this kind of space journey, that needs to be a certain amount of like repurposing fecal matter, We need to we need to figure out how to make the interior of the spaceship

out of consumable products, that sort of thing. And and she said that there there would there would come a point where the at the astronauts that they caught wind of this idea, they would say Yeah, well we're not doing that. That's just that's too far. So how's that, how's that spaceship ready Salisbury stake meal coming? Well, it's it's still a work in progress. But well, I guess it does come down to the oh, just the the

scope of what you're trying to do. Just this just this impossible dream of of of of taking terrestrial organisms and allowing them to to journey and even thrive beyond our world. You've got to You've got to enter into that with a very gung home change everything attitude. Otherwise how are you going to get there? Well? Yeah, there there are different ways you could approach this. So if you're talking about modifying astronauts for space travel, one way you could think about it is how do we get

them through the mission? Right? How do we modify astronauts so that they can complete their mission objectives and survive the whole time and come back, versus thinking about modifying astronauts to be the kind of organism where this is the environment they thrive in. We're going to space is natural to them, and it's not just to get them through it without them dying or suffering debilitating illness, but to make them at home in these new environments like

space and other planets. Does that make sense? So in order to carry all this up, why should we depend on crude aftermarket fixes like replumbing the human body and installing nuclear lungs? Why do that when we could achieve the ideal or you know, quote unquote ideal space faring human via modern and near future gene editing technology. And that is not as far fetched as it might sound. And when we come back from this break, are you ready for a break, Robert, I'm ready for a break.

All right, we'll take a quick break, and when we come back, we're going to talk about the Crisper gene editing method. Alright, we're back, so again, gene editing Crisper. This is a topic that we've wanted to discuss for some time. I know we've had listeners who've reached out and said, he said, hey, do an episode on Crisper.

And I don't know about you, but and I know you've you've covered Crisper, I think on other shows before, but I always found it a bit huh intimidating because there's there's too to look at Crisper and then draw in sort of the the more everyday examples of how it might be utilized in the fighting of diseases and whatnot, and then drawing in a lot of the continued controversy

over GMO in general. It it becomes a bit intimidating, and I like I like the idea of discussing it here because it lines up nicely with a specific science fiction flavored UM use for its products. Sure, for the purposes of today's conversation, you can think of it as the tiny micro molecular structure that makes better astronauts. Okay, So CRISPER has been in the news for several years now, and if you're one of those people who've heard about it but you've been afraid to ask what it is,

you're not alone. We we get this question popping up all the time. A lot of people, I think I've heard of it, and they know it's a genetic technique. They know genetesists are going crazy about its potential, both for good and for ill, but they're not quite clear what exactly is it. So I'm going to try to give the easy version to explain what it is UM without getting overly complicated. So CRISPER is the most common shorthand for this new form of genetic technology that's revolutionizing

our ability to edit the genomes of living organisms. The ability to edit a genome has already existed, so it's not that we can edit genomes whereas we could not before. That's existed at least since the nineteen nineties. But the CRISPER tool kit is making the process easier, more efficient, more precise, and cheaper. Now, when I say that it's a tool or a technology, this can be a little bit misleading because CRISPER is not something that was invented

in a lab. Rather, it was identified in living microbes and then harnessed and modified for human scientific use. So CRISPER is part of the natural immune system. It's the immune function of single, single celled organisms like bacteria and archaea, and it allows them to protect themselves against viruses. But you still might be asking, wait a minute, but what is it? What's the thing? So I'll try to explain

that as clearly as I can. CRISPER stands for clustered regularly inner spaced short palindromic repeats, and in a direct sense, these are just segments of DNA. So you've got the genome of a prokariotic organism, for example, of bacterium of E. Coli, and it's got its DNA, and along that DNA of this E. Coal I, you'll find places where there are these clusters of DNA that read the same forwards as they read backwards their palindromic, just like palindromes in words. Robert,

do you have a favorite palindrome? I've got the I love Rats Live on No Evil Star. Oh, man, that that one is great. I don't think I've ever heard that one before. But that's impossible to follow. I think I saw that on the internet at some point. I assume someone has a book with that title. That would that's a great book title, Rats Live on No Evil Star. It implies like rats may live on a good star.

It it feels like it should have there should be some wisdom in their right plasma rats like where someone's like, man, I just I haven't really down about the state of the world today. Well you know what what they say, Rats live on no Evil Star? Right on? Yeah, it has that fortune cookie vibe. But anyway, so there are these segments of DNA that read the same forwards as backwards and in between them. So that's where the term

inner space comes in the eye and crisper. In between these palindromic repeats are segments of DNA that exactly match the DNA of viruses that are bacteria killing viruses like bacteria phages. So in a similar way to how your body makes antibodies, so your immune system can harget and destroy germs that have already infected you in the past, a bacterium makes copies of viral DNA and its genome, so it can recognize that viral DNA in the future and destroy it. But how does this happen? Well I

mentioned that crisper is shorthand. It's sort of a shorthand for a tool kit of genes and proteins associated with crisper in the wild, and one of these systems is the Crisper CAST nine system. This is one of the main ones that's actually being talked about when people talk about crisper. So CAST genes are genes, they're Crisper associated genes, which is where CAST comes from. And like all genes, they're also made of DNA and they're part of the genome.

So DNA of course creates proteins, and proteins can do work inside a cell. So CAST DNA makes DNA editing proteins. If you think about your DNA has this part that generate proteins that can make edits to your DNA. For example, these would be enzymes called nucleases that are able to snip DNA at certain points like scissors. So let's try to imagine you are a prokaryotic cell. So you are a cell of the bacterium Streptococcus pyogenes. Robert, can you

put yourself in that frame of mind? How hard is it? Well? So it's it's it's more of a challenge than imagining myself as a hoppit or a dwarf. But yeah, I think I can do it. Okay, So you're this Streptococcus bacterium and your CAST genes in your genome create this big blob of proteins called CAST nine for Crisper associated protein nine. And this CAST nine is is this protein

structure that's equipped with nucleases. Remember those are the enzymes that can snip DNA, and it's also equipped with strands of RNA matching all of the viral DNA that you've stored up in your genome over the generations. So this CAST nine object floats around inside you, inside this cell, and if a virus comes along and squirt some of its DNA into you, the CAST nine system can latch onto that viral DNA with its matching set of crisper

RNA and then bust up that viral DNA with its nucleases. Right, So it's got the profile of the viral DNA it wants to catch, and it's got these proteins, these nucleases that can destroy that viral DNA. Now, if it comes across viral DNA that's not already stored in your genome, it can also make a copy of that viral DNA, snip a hole in the crisper part of your genome, and insert it so that you were protected in the future. So this gets incorporated into future generations of your germline.

Now that's some amazing molecular technology. But the way it comes in to the scientific research is what if we could harness that for our own purposes, And that's what scientists within the past few years have been doing. So the Crisper CAST nine technology is a modified version of this biological system, and what it does is it allows scientists to insert whatever DNA they want as the model

for the Crisper RNA in the cast nine system. So this Crisper cast nine tool can be given a target segment of DNA and then it can go in with precision and snip that and only that section out of your genome. You. Now, this can be useful if you want to, for example, knockout a gene that's causing some unwanted effect. Or it can even be used to insert a specific string of DNA code at a targeted location, and that's really interesting. So it can punch a hole in a gene that you want knocked out, or it

can go in and make an edit. It can cut open a hole, insert what you want, and move back out. And what this all amounts to is that we can edit our DNA and the DNA of other organisms with much greater precision, much easier than ever before. And obviously this is a big deal. This technology is going to be incredibly powerful. It's not just a future thing. It's already being used in the lab today as a research tool. But there is this really strong, robust argument among scientists

and bioethicists about how it should be used. Right, But most people are okay with the idea of trying to develop uses that would, for example, heal a cancer causing mutation in an adult human, or cure some other disease. But other things are a lot more controversial when you consider ideas like editing the germline DNA, and that's the DNA that's not just part of your somatic cells, not just part of your body now, but the DNA that

would get passed on from one generation to another. Because if you make edits to that, you're essentially editing all of the children and grandchildren and future to sentence that a person would have without the consent of those future descendants. You are modifying the human being. And in doing that you were I mean that that encompasses all the potential positives and negatives of that that godlike act. Yeah, and and there are tons of other things to consider it.

I think it's a very interesting debate about what should be done with this technology, if anything at all. I mean, I think it's hard to argue that we shouldn't use it for anything, because it's clearly a powerful research tool, not just for editing people as they exist, but just for for for example, identifying certain types of genes that do certain things. It's powerful in the lab to find things out about the human genome um, but there are tons of questions about what it should be used for.

For example, we found this one really interesting article just from I think, published just a few days ago in June in the New York Times by Moises of Alaska's man Off called and it was an argument quote in favor of bad genes. Yeah, this is a great read. He so he points in the article, he points to UH,

specifically to the case of sickle cell. So the gene itself is usually found in people of Sub Saharan Africa, the Middle East, in India, and having one copy of the gene can prevent the worst symptoms of malaria and UH. Whereas if you have if you have to, then you get into the that that's where the problems arise. Right. So yeah, so it's a it's a gene that if you have two copies of this can cause a terrible disease that leads to a lot of suffering. But if you just have one copy of it, it can be

incredibly beneficial in the environment. So it's not it's not just like a defect. It arose for a reason, it provides a survival advantage. Right, it's just when it when you end up having more than one, or when it becomes out of balance. It's kind of it's kind of the reality of life in general. Right. There are plenty things in our life, in our life that in moderation are very helpful, but it's when they become unbalanced. You know, having having one pet dog in your house is cool.

Having twenty eighth is is an unbalanced reality. Yeah. Uh. And and there are lots of cases of genes like this, Genes that may appear that that do in fact cause negative effects, but also do confer some strong advantage in certain environments. Yeah. For instance, a gene variants that cause

lung disease cystic fibrosis. It's hypothesized that having just one copy of the gene protects against TB tuberculosis, also known as the White Plague of Europe of Esca's men Off points out, uh in one and people from Northwest Europe or Northwest European descent have it. So you're probably wondering at this point, why do we need to worry about established diseases? Why do we need to worry about ailments for which we already have uh uh, you know, more

robust means of combating them. Well, the problem is that new pathogens for which we don't have cures continue to emerge, and some of these bad gene might be needed one day. So I was thinking about this in terms of Batman. It's like, if you have a situation where a Gotham city, you've managed to to rid yourself of all of these criminals, they're no more super villains running amuck. Let's kill Batman. Let's get rid of Batman. Why don't we have a Batman.

He's just a distraction, right, He's probably a drain on the local economy. It's a lot of traffic pile ups. Yeah, yeah, and is and and is himself you know, an illegal entity by the way. But then the Joker shows up after you've gotten rid of Batman, yeah, or some new super villain that we can't even envision yet, And then are we going to have the basic vigilante tools to combat him and in the case of of our own genome, or we're gonna have the basic genomic tools in our

body for our body to combat this threat. And I think this is a very interesting argument that I mean, part of it is that we just don't understand everything about our genome, and genes that do appear to cause some kind of negative effect may also be doing something important for us that we don't realize. That's right, And as Vasco's men Off points out, environment is also a key to here. So some of the gene variants now linked with disease probably don't cause as many problems in

other environments, depending perhaps on microbes in their home environment. Uh, he'd be pointsed, for instance, uh, the biome of a less hygienic past. Uh, because you have to think about the fact that, uh, you know, it's it's basically the

same scenario we have with space travel. The humans evolved within a very firm set of parameters, and even within our world they are there, they evolved in certain portions of of our environment, geologically isolated for long periods of time, and so you have to factor that into their into their genes, into the expression of those genes, and into

the microbiome that become is uh pretty much standard for them. Yeah, But I mean the broader application to space travel is just that you don't know exactly what some of your genes that appear to be uh, useless or harmful in space might do for you once you're up there, right, Yeah, there's there's actually a wonderful quote from this New York Times article that I think sums up a lot of

what we're talking about here. He says, quote, we evolved in environments that are radically different from today's, and some of our genes may work better in those environments. This complicates the idea of trying to perfect the human genome with technology. Given how much the world has changed in just the past one hundred and fifty years and how much it's likely to change again in the next one hundred and fifty the question is what environment will we

optimize our genes for? Yeah, now, what if here's another thing. So imagine you've got people on an interstellar arc ship, you know, it's an intergenerational or multigenerational starship taking you to another planet, and you optimize their genes for survival on that spaceship on the journey so that they can survive and thrive in this spaceship environment. What if the way you've optimized them for the spaceship undercuts their ability

to survive once they arrive at the target colonization planet. Yeah, and then you run into a situation where you're having to first adapt the crew members, and then there's a different adaptation process that has to kick in for the intended colonists. Anyway, I mean, I think this is not necessarily an argument that we should never use crisper to

modify the human genome. But I think it is a good word of caution to say, like, if there are areas where we're not sure we understand everything a gene does, and we're not we don't have a very clear picture of the full range of effects of a certain gene and what our life would be like without it, we

should be careful about being being too cavalier to change things. Yeah, I mean, just we don't understand all of the ramifications necessarily for some of these changes, But that that's kind of baked into the challenge though, right is determining what tweaks we can make that are going to potentially benefit a human space traveler without creating any you know, additional constraints, creating additional problems or or situation that could be problematic

later on. Yeah, And of course, all of the cautionary questions and ethical dilemmas about Crisper don't in there. There's a ton of stuff to consider, and um, that's probably a realm for future episodes where we can talk more about all of the controversies with Crisper. I know, just in the past few months, I think there have been there's been some back and forth with letters about the ethics and and the wisdom of using Crisper in the

journal Nature. Yeah, and then on top of that, of course they're just uh, you know, the public's response to it. So as as King Wu pointed out in this panel, there they are many ethnic groups in particular that have not been well served by genetics and especially by eugenics and the task which was it's worth the pointing out both immoral science and bad science. So a failure on two fronts. Um, So you know, to some to some degree, it's it's unfair to to loop them together. But there's

undeniably a connection between eugenics and and genetics. Yeah, I mean, you can see people's understandable fear about the idea of making better humans. Like, Okay, so if somebody out there is trying to engineer humans to be better humans, do they have a specific idea about what better humans are and is that not just like uh, having fewer diseases,

but do they also have aesthetic ideas? Yeah, and these are all questions we need to ask as we potentially enter into an age where where this kind of technology is utilized or more you know, we consider its use. But while a lot of groups take issue with gene atit, Woo points out that the most people, when when questioned about it, they're cooler with the idea of the technology

being used to better protect astronauts in space. Yeah. So I think people are generally cooler with the more specific applications. Feeling cancer patients, Okay, Yeah, I'm good with that. Modifying astronauts for space sounds great. Yeah, tear them up, do what you gotta do. But when it just comes to this general, free form, open ended should we change human beings,

that starts to get a little squeaky. Yeah, I mean, I mean, I guess it's it's kind of always the case, right Like if you if you if you make the question broad enough, if you, for instance, were to say, should humans live in the sky, No, that sounds preposterous. Humans should not live in the sky. Humans were were you know, evolved or were created? If you want to go that route to to live here on the ground. We should absolutely not live in the sky. If we

went in the sky, we'd fall down and die. But if you were to say, oh, well, should we create planes that we can we can fly around in some sort of vehicle that allow us to go from point A to point B. Could we create a luxury hotel on an airship and then if you if you're interested in it, and you have enough of money to flip the bill, you can go out there and spend the night in the air. Yes, that sounds much more reasonable.

It's also kind of like if you ask people, would you be okay with scientists experimenting on ways to resuscitate people who have encountered twenty minutes of brain death, it might be like, well, sure, but if you say, should we be working on experiments to revive the dead? Yeah, then you're gonna get some pushback. Alright, we're gonna take another quick breaking. When we come back, we will continue

our discussion about the genetically modified astronaut. Alright, we're back, so we should we should definitely drive home something that we've we've discussed in length and past episodes, the icularly Your Life as a Mars colonist, and that is that the traveling in space or and certainly traveling to other world it's gonna open you up to a number of unhealthy scenarios. I guess youho'ld say, yeah, I got. We also touched on this in five Reasons Never to Take

your Space Helmet Off. So the big one, the one, that one that we spent a lot of time in that episode with, is of course radiation. Exactly. Now, there are in fact organisms that are naturally radio resistant organisms. I would tend to think, just intuitively if I had never read anything about this, the radiation is one of those things kind of like a fire or something that just kind of kills everything. But there are in fact vastly different levels of susceptibility to radiation in the animal

kingdom and in organisms generally. And it's not just that there are some extreme aphile micro organisms that can survive radiation. I mean, we know about tartar grades and things like that, but there you know, even if you just look at animals like it looks like turtles have more radio resistance than dogs probably, so there is some room within large mammals like us to modify our bodies to be more

resistant to radiation. Alright, So, so one potential there is if we can and again there are a lot of gifts and and and and butts and and all of this, But if we can figure out ways to alter the human genome to encourage a greater resistance to radiation, greater protection from radiation, that would be an area of opportunity. Yeah, and I mean there are lots of ways you can think that you might be able to do this. One would be the body already has natural DNA repair properties, right.

If there's DNA damage, the genome will try to put itself back together, and of course, if it puts itself back together wrong, this can lead to a mutation that can have bad effects and maybe cause cancer or something like that. But you could try to genetically modify the human body so as to have stronger DNA repair precision

and stronger DNA repair resilience. Or here's another possibility, Robert, remember when we did the episode about the eater of rads, the radiation resistant fungi that that supposedly, if these results are correct, and not only survive in the presence of, for example, gamma radiation, but can apparently gain some kind of usable bio energy from it. And this was done

by absorbing the radiation through melaninrich cells. Now, I wonder if you could try to do something similar to take some inspiration from that and try to modify human somatic cells so that they have similar properties of of you know, internal chemicals and molecules that are absorbent of radiation and dissipating the radiation instead of allowing it to penetrate the

DNA in your cells. Yes, so, so we're looking at ways to further protect the body against radiation and make it less susceptible to damage from radiation and UH and then potentially better repair itself. Okay, Now on top of that, one one UH issue that was brought up in this World Science Festival discussion is a cancer treatment in the reduction of cancer risk totally. Some of that falls in

line with the radiation here for sure. But you know, at first this might seem like more of a terrestrial concern, right, But what if you're talking about a ten year trip and then you realize you've developed cancer three years in five years in so you can't take a risk. You can't risk an astro not coming down with cancer developing cancer uh during the trip, because they might not have time to make it back to Earth for treatment, or it might not even be in the cards for a

return trip at all. Sure, I mean, if this is a colonization, or if it's a trip to Mars, this is going to be a multi year kind of thing. Yeah. I mean, even if it's one of these, uh, these one way trips that we've in a lot of discussion about. The plan is probably not for you to get to Mars and then die immediately. I mean, that may happen.

That's thus are the risks of such a venture, but you it would be it would be even more of a tragedy if it were to occur due to uh to the effects of cancer, um, you know, within the first year of landing on Mars totally. Now, what about the effects of micro gravity? This is obviously going to be one of the biggest challenges that biological systems encounter

in space. We are adapted to an environment with Earth gravity with one G. You go to a place without one G, or at least without consistent one G, you're going to encounter some biological disturbances. Yeah, this is this is the area where and I think we've covered some of the science on this show before, Like this is an area that there's been a lot of study, Uh, not necessary, a lot of great answers other than lots of exercise and uh and in certain vitamin supplements. Get

on that treadmill. Uh yeah, and and tread use of to the treadmills. The use of exercise devices seems to be one of the key ways to make up for it because we don't have artificial gravity. Even though we have these these wonderful sci fi visions of of an artificial gravity created via centrifugal force via like a spinning space station, like a tourist or like the space station we see in two thousand one of Space Odyssey, we

these ideas are largely unproven. Um and it I mean, we we do know you could create a force towards the floor if you did that. Yes, yeah, we we know we know that. Yeah, we know we could create the force, but we don't know exactly what it would be like to try and then function as an astronaut in such an environment, but for a really long period of time especially Yeah, and then think about if you get to maybe so if you're going to another planet.

Once you get to the planet, you're not really going to have that option there the planet, You're just gonna be dealing with whatever the natural gravity of that planet is. Yeah, it was brought up in the talk by A. Caleb sharf h that we might have to if we were on one of these spinning artificial environment uh constructions, we might have to deal with the of course, the coreolis effects. What would happen if I threw an apple to you on board one of these space stations. I don't know.

I've never tried to throw an apple in a spinning drum. What would happen? I don't know. But it's one of those those new realities you would have to get used to just the way objects behave in the space, because you would be replicating gravity, but it would be it would be artificial gravity in in a in a in a very real sense. I mean, there are just so many ways that space messes with you in a systemic way.

In some cases, I think it's not even totally clear when say, astronauts on the International Space Station exhibit symptoms, what in what ways the symptoms are informed by the different conditions of space. So you've got micro gravity, But it's not just the micrograp You've also got a different microbial environment, and you've got you know, you've got a million different things going on at once. Some of it's

probably just stress and things like that. So we don't even know at this point for sure exactly what parts of space travel do what to you. In some cases we have a good idea, in other cases were not as sure. Yeah, and the talk, Mason also pointed out that when you when you get into space, thousands of genes become perturbed. So we have a short list of risk genes for space and an example of this would

be stress response genes, DNA damage and repair genes. Yeah, and a lot of this was to be expected because gene expression changes all the time. It happens, it happens here on Earth every time you eat. It kind of goes back to our discussion about the the role that your local environment, your local microbiome, would have on the expression of your genes to and that could that gets into another fact of life in space pointed out by Mason and this, and that's that that microbes become more

active in space. So salmonella, for instance, becomes more deadly for mice that have been studied in orbital environments. Yeah. I think we mentioned that in the Reasons Not to Take Your Space Helmet Off episode. So, yeah, once you get into space, it appears that space conditions, for whatever reason, increase the virulence of pathogens, which is just great. Who decided that would happen? Um. Yeah, it increases the virulence of pathogens and depresses your immune function, right, it leads

to these immune problems. Like we we talked in in that other episode about all the ways that space messes with your immune system, including creating these sort of almost allergic like effects. And so maybe that is one fruitful place to start looking about modification of humans. If you want to modify astronauts to survive in space, you might need to make changes to how the immune system is expressed and regulated by the genome. Yeah, I mean it

sounds like just across the board. You know, in the same way that an astronaut is does not it is probably not going to be your average physical specimen, you know. They they need to be Yeah, they need to be in shape, they need to they need to be able to survive the rigors of space. So in order to to tweak the genome you need to essentially tweak for

just a really healthy person. So ignore you know, don't worry about crab clause just yet, Like, focus on creating a really healthy astronaut that's going to be able to withstand these changes that's gonna you know, for instance, not suffer as much bone and muscle loss due to the effects of micro gravity. You know. It's it's also worth noting in all of this that that some of these negatives that we're talking about, you know, or but are actually examples of the body adapting in real time. Uh,

you know, not evolving, but adapting. Uh So, so all that bone and muscle mass uh that is lost unless you know, vigorous exercises kept up to sort of keep it in check. But that's essentially the body acclimatizing to this low gravity environment. It's being smart, it's using its resources wisely. Yeah, thing, I don't need to be strong.

And then there are other changes that are happening as well, Like it was pointed out that you will end up with callouses on the tops of your feet as well, because it's not just the bottom so your feet that are coming in contact with the surfaces in your environment. You're becoming You're not this just top down gravity organism anymore. You're weird. Ye. And then there's the example of clothing.

So Mason uh Or he talked a bit about in this about his work with the NASA astronaut twins Mark and Scott Kelly, because he did a number of of of of experiments who was essentially you know, looking at the at the genetic differences between the two after one of them returned from space and uh And he pointed out that that after Scott Kelly returned, like he could not wear clothing for a couple of days because just the feeling of clothing held down by gravity on his

skin made him experience quote unquote pain. Yeah. So it's just that you become that unaccustomed to even just minor aspects of of gravity. It's hard to imagine your shirt hurts. Yeah, And and that's just and that's one of the small things. It's not even getting into you know, you know, potential you know, radiation or or or major bone and muscle

mass loss. Oh. And then of course there's there's the fact that your circadian rhythm is screwed up and is you're trying to sleep unless you have your hands trapped down, they're gonna be floating in your face, you know, phantom hands coming at you. And this is something I hadn't thought about that Mason pointed out, is that you're you're

setting there, you're laying there, floating there. However you want to look at it, strapped down, trying to sleep, and you're already up, like puffed up and snotty, just from just hey fever kind of condition, yeah, hey fever kind of condition. Just but by virtue of being in space and sharing everybody's micro biome. But you're also liable to wind up sweeping in a bubble of c O two what yeah, what he refers to as uh in your own respiratory excrement um, just by virtue of breathing into

this this uh, this this microgravity environment. So like the gases don't disperse is easily, I guess. Yeah, I've never heard that before. I had not either, but it makes sense now. In a rare reversal of everything we've been talking about, of all these dire consequences of venturing into space, Mason points out that our telomeres actually get longer in space. Oh, the telomeres now are these um, these are things having to do supposedly with the natural length of cell division

and reproduction in the human body. Yes, so yeah, you get into the like the whole science of telomeres, and we won't get into it here. There's a there's there's an article on how stuff works dot com that I wrote years ago about it. But the short version is that the telomere length is directly related to uh to lifespan. So if timomeres are longer than than than life is longer.

That's kind of the very brief explanation of it. So you could make an argument that if you were in that life and space lasts longer, that you could live longer in space, of course, if you were ignoring many of these other debilitating effects. So why did roy Baby come back to Earth? If he wants more life, maybe

he should have stayed in space. Well, but I mean that's kind of the thing, right, that the telomeres were artificially shortened on replicance, I guess yeah, Or maybe it's because he came back because this is I don't know if if there's been much treatment on this, but the replicants in Blade Runner, where they made for use and off world scenarios for use in space. Yeah, I think so.

You know, it seems like you could probably create a replicant then that would live longer in space, and if a return to a higher gravity world, it would have a genetic effect on it that would kill it. I mean, this is almost a perfect example of one of the dangers of you say you want to create crisper modified astronauts thrive in space. What if their mission changed and they wanted to come back to Earth. A thing optimized

for space would no longer be optimized for Earth. And there are many cases where if you want a genetic advantage in one environment, it's not just like a it's it's not just like a win with no drawback. You know, if you were to come back to Earth, it would actually hurt you. There's a there's a win loss, there's a trade off. Yeah. I guess part of it comes down to, like, how how far into the future are

you gazing? You know, are you creating creating and maybe a too heavier turn, but are you augmitting augmenting people too to remain within this next phase? Are you essentially creating an an interplanetary humanoid species or subspecies? Are you are you creating subspecies then that are acclimatized to various soft world environments or are you are you saying, all right, these people are gonna come back to and then and then like, how does that affect their rights as a citizen? Uh,

as a member of the human species. How much would you have to modify astronauts before they began to lose their sense of kinship with earth dwelling humans and earth dwelling humans lost their sense of kinship for the astronauts. I mean, we are incredibly genetically similar to chimpanzees and sometimes show a remarkable callousness despite how similar we are. How much would you have how many genes would you have to change before we no longer recognize the astronaut

just the same animal as us. Well, and think of just spatial distance here on Earth And granted this kind of a clunky analogy, but uh, think of the callousness that one group of people can show for another on the other side of the Earth. And then imagine us sending people even greater distances, like distances between people that have not been possible until until the advent of interplanetary travel. In other words, the spatial distance between people will be

greater than it has ever been in human history. Yeah, what will be the ramifications of that? Yeah, that's a tough thing to consider. Um, and then when you start factoring in the the increased time it takes to transmit information as interconnected as we are on on Earth, now, like that is not necessarily going to carry over to

an interplanetary scenario. I'm thinking kind of you know, far future here, But can you imagine, you know, how out of the loop you feel when you come in fourteen minutes after the beginning of a public discussion on Twitter about from public event that just happened. Now, people on Mars are going to be like that constantly, where Mars will have to have its own Twitter. I guess it's the thing of Martian Twitter and Earth Twitter. Uh, that's the only way to do it from Mars Twitter. Now,

I think it would be great. It would just be one person. Would you need a genetic modification in order to be able to keep up with the jokes on Mars Twitter? Yeah, I mean either red red humor gene maybe. I mean you do get into so many different when you when you start thinking you know, far future. Uh, there's so many a cultural changes that can occur, so many changes in value on top of various microbial changes

that have taken place. Now, a lot of the changes we've talked about so far, the potential genetic changes have been to survive in a space environment, you know, just to get along with all of the natural hardships you'd face. But there are also things that you could imagine changing about people just to make them like more efficient in space. I mean, one of the things I can imagine would

be like better eyesight for low light conditions. He wanted to have that in space to conserve power or all kinds of power conserving things like could you make people that had slower metabolisms and space so they needed to consume fewer resources. Would you make people who's I don't know, genetic engineering so their kidneys are more efficient so they don't don't need to drink as much water to stay

healthy or something. Yeah, And I wonder, I mean, I can't help it draw in I guess kind of kind of clunky comparisons to other natural world organisms and say, well, if we had if we had this feature, would that make us a little uh, you know, a little better in a microgravity environment? For instance, I'm thinking like a cat's whiskers, Like if humans had cat whiskers, would they be better at floating around through various tubes and whatnot because they have a very ready read on the space

or is the size of their body. Now, maybe humans instead of crab claws need spider spinnerets in space so that they can like shoot webs out and pull themselves from place to place in a microgravity environment. Huh. I wonder how would we spend I guess maybe we would like milk it from our nipples. That would be because because I don't know how, I like a spider man

web shooter uh scenario would work. But I'm thinking back on the the goat we discussed that had been genetically augmented to produce spider silk from its uh it's utters the spider goat. Yeah, so if we could create our own spider nipple scenario, I can imagine like a shirtless astronaut. He's floating around in the cabin and he needs to move across the room, so he reaches down to his nipple, pulls out some some silk, and like throws a drag

line across the room and then navigates on that. I commend you, Robert, but I think we've reached the end of this conversation probably so uh, anytime the spider goat is invoked, you've you've kind of reached the limits of human understanding. I guess, well, hey, you out there, what do you think would be one of the most useful or interesting genetic modifications for future astronauts and space colonists?

Or do you think that we shouldn't dabble in trying to modify trying to modify humans except for maybe life threatening or survival needs. And to what extent should we focus on changing individuals into what extent should we focus on changing the species? Like, are you just changing an individual astronaut or a group of astronauts for a journey for a mission, or are you altering the human species entirely and creating a subspecies that's going to thrive in

a particular environment. Yeah, I don't know. It's a really interesting question. So, yeah, you out there, let us know what you think. Yeah, hit us with those other science fiction examples. I'm sure there are tons of them. As always, you can find us all the normal places where on Facebook, Twitter, Instagram, Tumbler all those websites. We also have the mother show up stuff to bow your Mind dot com. That's where we'll find all the podcast episodes dating back to the

very beginning. You'll find videos, blog posts, et cetera, and to email us directly. As always, you can hit us up at blow the Mind at how stuff works dot com for more on this and thousands of other topics. Is it how stuff works dot com