Riskgaming

The Science of Survival: Adapting Human Life for Other Planets

Description

Welcome to "Securities," a podcast and newsletter devoted to science, technology, finance, and the human condition. In this episode, Josh Wolfe and Danny Crichton bring science fiction into science fact with our guest, Christopher Mason, a geneticist and computational biologist who has been a principal investigator of 11 NASA missions and projects.

Mason, a professor of genomics, physiology and biophysics at Weill Cornell Medicine, discusses his book, "The Next 500 Years: Engineering Life to Reach New Worlds." The book explores the concept of protecting humanity from inevitable extinction by venturing to other planets. While most focus on the technologies to deliver us to these places, Mason takes a different angle, focusing on the biological adaptations necessary for humans to survive in space.

Mason discusses the need for both physical engineering and biological engineering in space travel. He highlights the importance of understanding and potentially engineering our microbiome for space travel, given its significant role in our health and digestion. He also discusses the potential of gene editing, using the example of the vitamin C gene, which we could potentially reactivate to allow humans to auto-synthesize vitamin C.

The conversation also covers the physical changes experienced by astronaut Scott Kelly during his time on the International Space Station and the implications of these changes for future space travel. Mason discusses the potential of engineering the perfect space specimen, considering factors such as gravity, radiation, and circadian rhythms.

Transcript

This is a human-generated transcript, however, it has not been verified for accuracy.

Danny Crichton:
Hello and welcome to Securities, a podcast and newsletter devoted to science, technology, finance, and the human condition. I'm your host, Danny Crichton. Today we're going to bring science fiction into science fact. We've had some speculative novelists on the show, but I don't think we've ever had someone who I think is bringing speculative science into the present form. And that is in the form of Chris Mason. Christopher Mason is a geneticist and computational biologist who has been a principal investigator of 11 NASA missions and projects. He is a professor of genomics, physiology, and biophysics at Weill Cornell Medicine here in New York City and is the director of the WorldQuant Initiative for Quantitative Prediction. Chris, welcome to the program.

Christopher Mason:
Thanks for having me. A pleasure to be here.

Danny Crichton:
And also joining us today is Josh Wolfe, here from Lux Capital.

Josh Wolfe:
Far less impressive than Chris, but-

Danny Crichton:
You've only worked on three NASA missions. Unbelievable.

Josh Wolfe:
I have actually worked on a grand total of zero NASA missions. I have read The Martian. I have read Hail Mary, and I have to believe that you are, in some cases, an inspiration for some of the sci-fi writers who are looking at scientists and saying, okay, what's the cutting edge that people are at least speculating and developing?

Christopher Mason:
I hope so. I think it's getting... One guy actually Zoomed me and said, "Hey, Dr. Mason, I read your book. I love it." When we got on Zoom, he had taken the book apart and had it all over his house, like a crazy scene. And I thought... I was either going to... I had kind of a stalker, he was either going to come and kill me, but he said he wanted to make movies out of parts of it. So I was like, "Okay, maybe it'll be all right," but it was still alarming.

Josh Wolfe:
You're like, "No, no, that's not Dr. Mason."

Danny Crichton:
Talking about the book, you have the book in The Next 500 Years: Engineering Life to Reach New Worlds, and the premise of the book is really taking this notion of how do we protect humanity going forward. At some point, extinction is inevitable either by our own actions or from billions of years from now when the sun burns out. And so you want us to go to other planets, and so do other people. And most of them are focused on rockets, the technologies to actually deliver us and vessels to these places. And you have taken a completely different angle on it. Explain a little bit more about your theory there.

Christopher Mason:
Yeah, so the rocket's definitely going to be needed, requisite for the mission. You're going to need to actually obviously get there and stay there and survive. And you also, one thing I'll jump on, you said that extinction is inevitable. Extinction if we do nothing is inevitable. But actually, the premise of the book is that we as humans have a unique capacity for understanding extinction. We're actually the only species that can. And I think that gives us a unique duty and responsibility to look ahead and serve really as shepherds, guardians, quite literally guardians of the galaxy, or at least the life in the galaxy, but really any galaxy, it is unique to us. There's no one else with this capacity, no other entity that we know of in the universe that's doing this. So until we find other aliens doing it or an AI is doing it for us, it's up to us.


So I want to think, how do we get there? How do we actually get to Mars, get to other planets? And, of course, there's all the work on telemetry, all the different engineering, physical chemistry, we really need to make the fuel actually work, but then the bodies are not built for it. Our bodies have evolved on this planet. So I really want to detail in the book each of the ways we could think about in a step-by-step fashion, take evolutionary lessons from all creatures, and then embed human cells with new traits that can help them survive.

Danny Crichton:
And one of the lessons from that? It was from Scott Kelly, who spent an extensive period of time on the International Space Station, and he had a variety of physical changes to him that happened up there. What were those?

Christopher Mason:
Yeah, a lot of it was changes in his body, inflammation, not surprisingly, when he got up there, and also stress in the body; his telomeres actually got a bit longer in space, which was ironic. We actually were counterintuitive because we thought, "If you're in space, you actually should be aging faster," which we see by most other measures. But in the brief time in space, that low dose of radiation and stress in the body actually made his telomeres longer on average, which is a sign of youth actually. So that was... It was surprising. But when he got back, it was a lot more alarming. There were significant changes to his DNA, damaged DNA, and genes that were controlling expression were still perturbed even months and months after the flight. And also, it broke out in a rash everywhere, this severe inflammation. He couldn't even have clothes on his skin. Because it would break out into a rash. And so to avoid it, we'd have to walk around naked just to avoid it, which some people do that recreationally. He was doing it more for medical purposes.

Josh Wolfe:
One of the things that you discover in this obviously is the biological differences between people. As CRISPR and targeted gene therapy and gene editing techniques start to evolve and advance, we will have the ability to edit, for example, people's ability to operate or live with less oxygen perhaps, or the ability to contain more oxygen or process it or engineer red blood cells. One of the things I think is interesting in your book is you talk about genes and pleiotropy. Explain what that is and why it's important, and what it suggests for future directions for biotech.

Christopher Mason:
The pleiotropy is a term in genetics that just means that one gene having multiple functions. It's just really a fact of biology that one cell can help your cells stay structurally sound. It can help shuttle something between different cells. It might actually have a different place in the cell where it does a totally different job. So interestingly, Beadle and Tatum, they won a Nobel Prize in the seventies for one gene, one enzyme. This idea that one gene makes one thing which you'll still hear people say, like "What's the gene for intelligence?" Or the gene for height, which is a misnomer. In many cases, there are dozens or hundreds of genes contributing to any trait. And sometimes, just one gene has many functions. So in both directions, genetics is more complicated.

And that's one of the big concerns I have about doing any editing is that you think you know what you're editing, but it actually may backfire, may have problems. So even though I'm a proponent of editing in general and modifications in the engineering of biology because engineering biology is actually the best way for us to understand, do we know biology? But we can be wrong. But the way to find out is actually to try and see did this gene have two or five functions and in what cells and at what time.

Josh Wolfe:
Now the inverse argument, and I want to get into some of the more biological examples of what we would do if we could genetically engineer or induce the perfect human for what we imagine the conditions in space, Mars.

Christopher Mason:
George Clooney. Yeah, something like that.

Josh Wolfe:
Exactly. The perfect space specimen.
But there's a counterargument, which is what Danny alluded to in the beginning, that many people are working on these engineered systems versus engineering the systems inside of us. If you look at eyesight, we could, on the one hand, try to genetically engineer better vision in someone, or you can invent the optics and the glasses. So talk about the trade-off between that.

Christopher Mason:
I think it's viewed as, in some cases, you do one or the other, but I think we'll have to do both or at least consider both. In many cases, a physical engineered product can actually solve the problem. Glasses do a great job with this. Of course, they're very simple and cheap at this point to manufacture. But if you think about other traits I've mentioned in the book, if you want thermographic vision or low light vision, you can sometimes use technology. But if you are in a faraway place without access to common resources like in this planet, A, you want everything you can to be inside of you that is native to the system, is part of the argument. So resource is one argument as to why to do it. The second one is to have it be complimentary. So I think we can apply both solutions to any problem, but it is the harder one. To engineer the biological system is by far the hardest, but it's the one that's the most innate and adaptive to any new situation. So it's the long-term advantage.

Josh Wolfe:
Okay. So now let's go to if you could engineer that perfect space specimen, we've got conditions like, of course, gravity. You've got conditions like radiation. You've got circadian rhythms, which we evolved here on ,Earth that are going to be very different in space. There are endless examples of things that you would have to engineer somebody to be adaptable to. What are the top three or four?

Christopher Mason:
Some of the simplest ones are I'd want ourselves... I look at the human genome, and it's a marvel. It's fascinating, it's amazing. But it clearly has been stitched together as a patchwork quilt of traits that has not been built to go to another planet or even just to survive on its own on this planet. So, for example, a few things, vitamin C, we get scurvy, but there are dogs and cats don't get scurvy. You don't see them wandering around drinking mojitos, trying to get their vitamin C. Maybe some dogs do, but in general, they don't go get it because they can auto-synthesize their own vitamin C.

And interestingly, we still have the gene inside of us called GULO to make our own vitamin C. It's just inactivated. It's called a pseudogene. It's been mutated too much. But we could repair it and reactivate it may have auto-synthesis of vitamin C.

We have nine amino acids we have to get in our diet, but we didn't 50 years ago know all the biochemical pathways to create all our own amino acids, but we do now. So what if we could make it so you could go somewhere and make all of your own basically nutrients and amino acids to make all your own proteins, so it makes your diet simpler? And then I would also that radiation shielding is a big concern for space. So different ways to correct the DNA damage, detect it, and also just account for and quickly fix all the bombardment on our cells and damage. So

Danny Crichton:
So some of those cases, we already have these genes in our current code, and it could be repaired. In some cases, we can borrow them transgenically from other animals or other plants. What are some of the cases where there is no option available? In some cases, we have the genes inside of us, so this vitamin C gene we could actually turn back on if we were to repair it. In some cases, we could borrow the genes transgenically from plants or animals that already exist on Earth. But then there are other genes where say, radiation. I don't know if there are species that are immune to radiation today on Earth, but presumably, we'd have to invent from scratch. How do you go about doing that in those cases?

Christopher Mason:
So yeah, in some cases, there definitely are genes from existing organisms like tardigrades that are what are called water bears that can survive in the vacuum of space. And they have a gene we've put into cells in my lab where we can actually get them to have an 80% reduction in damage to DNA.

Josh Wolfe:
By the way, if you ever see these things, pictures of them, whether under a microscope or... Everybody ever is like, "Hey, are there aliens? Do you believe in aliens?" It's like they exist, they're in the microscope, they're amazing.

Christopher Mason:
They can survive in the vacuum of space too. They've been put outside the space station, brought back in, they can rehydrate, and they'll start walking around again, and there are [inaudible 00:09:27], they're actually multicellular organisms, they're fairly complicated. That's one trait we've taken from those organisms, put into human cells, but we haven't yet found the gene to survive the vacuum of space. And if anyone could have it, it might be tardigrades. But you'd have to be able to basically shut your entire body down, go into extremely cold conditions with no pressure, and then come back. So that's something we have not solved yet, but we at least have one example where they could.

Josh Wolfe:
And when I think about these microorganisms, we, of course, here on earth, are increasingly aware of how interdependent and symbiotic we are with "Microbiome," bacteria, and viruses that sometimes confer protective variants for us. If you're in space, you have less exposure to bacteria and viruses. And so you would have to really understand our microbiome to understand how we're helping to digest food, process, excrete because you would have these conditions just like people like develop asthma because maybe they're missing something or they get cured of it when they're infected with some other parasite. The entire encyclopedia of our microbiome would have to be well understood so that you could survive up there without-

Christopher Mason:
But you want to engineer... That's not the case. We'd want to at least know who's there on the walls of the space station or the spacecraft, but ideally even engineer them. There's even discussion of doing this on [inaudible 00:10:36] Earth where you say, "Look at the buildings around us and look in the room that you're in right now on the walls, on the ceilings, on the floor, if you're outside, it's everywhere. There are microbes in everything." And they're present, and we've been accidentally engineering ecosystems and buildings for centuries. But maybe it's time we start to do it with volition and actually a design and say, "Okay, if we have this ecosystem anywhere around us, we should engineer that or at least understand it. But also in our body, it's a mini pharmacy in our gut, and it controls a lot of response to food, medications, and general health." And we have to be able to at least monitor it, but ideally, actually have it be probiotics that are nudging it the right way or improving that microbiome.

Josh Wolfe:
In the case of Kelly, just thinking about many of these things is not going to be one-way trips. People are going to be coming and going, presumably back between space, the ISAs, whatever future versions of it there are, and back to Earth; what happened when he returned to Earth?

Christopher Mason:
When he got back, the day that he landed, it was extremely painful basically. So, of course, he was glad to be back. We were all elated that he didn't die in the reentry. He brought a lot of samples back with him, but there was a mixture of cognitive changes. So some of the reaction time was lower, his body broke out in rashes and really pain for the first four, eight hours, it was really just impossible to even wear clothes.

Josh Wolfe:
Was the pain a result of an immune response to the absence of bacteria? Was it bone, gravity, cartilage?

Christopher Mason:
So we looked at a lot of changes inside of his blood work. Something's called cytokines, where you can see the signaling molecules in the blood and see what's active. Almost all of them look like muscle regeneration pathways. So you can see his body essentially reactivating the "Holy crap, I need to use my muscles signature." And then we think a lot of the inflammation response, it looks like when you're sick basically, the other parts of those cytokines spiking. IL6, for example, is one that you see in COVID-19 patients. It spikes up really high. And so actually coming back to earth after a year in space is like getting COVID-19, you could almost say at least at a molecular level.

It was really painful, but also his body was suddenly awash with these microbes that he hadn't seen in a year. We did do one analysis. He actually started to pick up other microbes from other crew members, and they got more similar to each other in the space station, which is what you'd expect if you spoon with somebody, for example, you're having a transfer. If it's an elevator ride, if it's a really close elevator, you're probably transferring microbes with someone in an elevator.

Josh Wolfe:
I sometimes do that on purpose; I just-

Danny Crichton:
Let me ask you this upfront. You're trying to build the spacefaring human. Is it possible to have both the Earth-faring human and the spacefaring human at the same time, or is this going to be like a one-way street? You're essentially being genetically designed for that mission, and that's the only way you can go.

Christopher Mason:
It may start that way, but if that happened, I would consider it a failure. What I want is cellular liberties. So you can do anything you want with your cells at any time. They're your cells; you can do with them as you, please. The same thing should be true for, I like to say in the book, planetary liberty, the ability to go to any planet you want. Right now, we have no planetary liberty. We can't go anywhere, although Earth is wonderful, of course, but I'd want to be able to go to Mars and come back.

But for other planets, which have much more complicated ecosystems or more radiation or different gravity, you would've to probably more severely engineer the biological system to be able to go back and forth. And the Expanse is a great book series and show where they even torture people because limbs are very long and they can't handle the gravity. You could very much imagine something like that. But I think what that showed didn't get right in the books as well as we could engineer some of these things away, I think. Or you can even have CRISPR systems that turn on genes just for a while and just change the expression of genes. You don't have to completely modify the genome. You can change just the plasticity of specific targets, which are even being used in some clinical trials.

Josh Wolfe:
In the case of genetic engineering people, I have to assume that many of the big breakthroughs also happened because we discovered people naturally on Earth that might've had interesting traits.

Christopher Mason:
Yes.

Josh Wolfe:
And this is a little bit of a controversial question, but we know that there are certain people that can go to depths of the ocean and hold their breath for long periods of time or the heights of the Himalayas, and some of the Tibetan Sherpas do not need oxygen. Are there certain people that genetically, I'm not suggesting ethnically, but just genetically seem like they may already be predisposed to be superior performers as astronauts or in space?

Christopher Mason:
It's a controversial question, but if you take an empirical view at it, the answer's just going to be yes. A simple question are there some people that are better suited to play basketball? Some people are just taller, and they're going to do better in basketball. And so, some people have less risk of complications in flight. It doesn't mean they'd be the best astronaut for every mission, but you could take on average that they might be better. Again, Stephen Curry's not that tall. He can drop three-pointers like it's no one's business, but there are other skills that people have in different missions.

I actually had someone who read my book who was actually blind and had read to him, and he said... Because there's a section that I talked about other things that activate when you lose one sense, you start to get others that really prime. And I talk about it could be an advantage, maybe being blind for certain missions where you need different tactile abilities that we don't know yet. So I think there'll be certain people that are, on average, in general better for most missions, but I think that we always have to keep our eye out for those unique individuals that might be better at certain ones.

Danny Crichton:
Every time you describe one of these individuals, I'm imagining the ensemble cast for one of these sci-fi shows. You've got the blind engineer. See, this is the Star Trek you never saw. Just all the different actors, but then you actually realize they're all going to look differently. They're going to have the limbs and the infrastructure they need.
I want to ask a question, though. You have a plan, a roadmap. Where do you start on that road? What's next to get going on there?

Christopher Mason:
We just finished phase one of the 10-phase plan, which I actually posted on our lab's blog page for a genetically engineered machines competition. It just is like, "Here's what I think we should do for the next 500 years," which everyone's really confused. "I thought we were just doing this for a summer project. What is this?" But I've been thinking about this since I was a kid. It's just that there's... About space and about genetics. I went to space camp when I was a kid; I've been thinking about it for a long time.

But I also read just a lot of philosophy. I'm thinking about the ethics of it. And the big question is, we do a lot with cancer research in my lab, and we're all inventing new diagnostics to find essentially infections. Keeping people alive longer is a laudable pursuit. But the underlying question is always, keep them alive for what? It's great to be alive and have more people have better life expectancy. But to what end? And I just kept thinking more and more that there's always been two kinds of philosophies. There's Kantian ethics, really, and utilitarian ethics, the greatest good for the greatest number, or do you make a principle for everyone?

But they both depend on us just being alive in the first place. So it dawned on me that the first duty we have is just to life itself, and life is fragile. And so I thought, "That's what we have to do first." And so I laid out this plan basically saying, "For the next 500 years, here's what we should do, to make it so we can understand life well enough to go to other planets and survive on them." And after 500 years, basically put people on a ship that would be a generation ship. So multiple generations live and die on the same spacecraft on their way towards stars, which I detailed in the book that we know we could get to and probably survive.

Danny Crichton:
One of the things I think is interesting is you're connecting to this theme of long-term, which has popped up in the last couple of years. Toby Ord's book The Precipice mostly focused on the downsides of a lot of issues. So nuclear catastrophe, a pandemic that wipes out all of humanity, AGI coming in and having machines take over everything. And I think what's interesting is you've spun this into a more positive angle, which is to say, "Actually, we can solve a lot of these sorts of things." You can actually fix many of these problems by having multiple planets, multiple places to go, and you have a trajectory and an architecture to go and do that, which Toby doesn't really get into. He's much more focused on the risks and the existential risk plan.

Josh Wolfe:
This is a debate that Danny and I have had in prior conversations here recorded, which was, do you believe that the ultimate resource is human ingenuity and, given enough time and statistical probability with enough people on the planet or more lives there, that somebody is going to invent the thing that is currently... To prevent the thing that is potentially ailing us? Or statistically, the more people you have, the more ego and the permanency of our human condition will lead to inevitable nuclear disaster and-

Christopher Mason:
Something goes wrong, yeah. Or superbug or someone engineer... Something goes wrong in a lab, or someone's engineering a cell, and it goes wrong, for example, could be us.

Josh Wolfe:
So this idea of the 500 years, and as Danny was saying, you've got other things like the Long Now Foundation and people that are taking very, very long-term views. We always feel as investors, we have time arbitrage, which is if the market is looking or discounting 12 or 18 or 24 months and you're able to take a three plus, four or five 10-year period, then your advantage; you have time arbitrage. You're thinking longer than everybody else's. And so there's scarcer competition. You're thinking out 500 years. And so either your philosophies and the roadmap will have to be adopted and inherited, or you will have to find a way to live a very long time yourself. On that ladder, what are you doing personally? I realize this isn't doctoral advice for anybody else, but are you taking 50 supplements a day like Ray Kurzweil? Are you injecting yourself with young people's blood?

Christopher Mason:
The parabiosis, I've not done that. I just take actually rats from the New York City subway, and they're so delicious and-

Josh Wolfe:
Oh, they last forever.

Christopher Mason:
That's right. So I've been eating-

Josh Wolfe:
[inaudible 00:19:24] roaches that have survived, yeah.

Christopher Mason:
I have a longevity company called Onegevity. It was acquired by Thorne. I do take some various probiotics and supplements that Thorne has, but not crazy. My dad takes more things in the morning when he takes vitamins and fish oil. I just take a few things more occasionally, really. I think it's too early to know what's going to be the most important molecules for us to take. I think we're still in the next five 10 years of measuring all the molecules that change the most as we age, which gives us enough targets. But I think actually there's a lot more discovery on different peptides, small molecules that we can use. But they're still being discovered; they're still generating a lot of them.

And I think I don't plan to live 500 years. In fact, I think there's a great sense of peace of knowing that you'll die but that there's a torch that can be carried on. I actually think it's not fearing that you're going to die if you know that you're going to die and then plan accordingly. It's actually a great way to think about, "What can I do to make the world better while I'm here, and what can I leave behind?"

Josh Wolfe:
I'm definitely in that camp of I'm not afraid of dying; I just don't want to be there when it happens.

Christopher Mason:
That's right.

Josh Wolfe:
I was on this weird text thread with these two billionaires. One of them is a famous biotech investor, one runs a big industrial global thing, and they were talking about what life extension stuff do you have. And one of them takes rapamycin six grams, six milligrams. Again, not advice, whatever. And then the other guy said, "What are the side effects?" He says, "Terrible mouth sores." And he's like, "I don't know, like an extra six months or six years," but you basically have giant herpes.

Christopher Mason:
What I don't know is... But I applaud everyone running clinical trials-

Josh Wolfe:
In themselves.

Christopher Mason:
[inaudible 00:21:02] sharing the data and people... I think we're going to have to explore. We haven't beaten the record for the longest lifespan since the seventies. So I think we're moving the average up a lot. But if you look at the distribution of ages, it's just pushing up towards the average going up, but the maximum hasn't changed in decades. So I think we're exploring, and we're trying a lot of things, but I don't think we could say anything's working quite well yet. But we're running clinical trials with Thorne. We're trying new ideas all the time. Lots of people are. So I think we'll learn a lot in the next five, 10 years for sure.

Danny Crichton:
When you talk about these long scientific projects, you're connecting to a theme that our scientists and residents, Sam [inaudible 00:21:36] likes to talk a lot about, which is the institutions of science. And I'm curious, when you think about your trajectory and roadmap for the next 500 years, how much do the institutions of sciences conducted in the United States globally have to change? Are they sufficient today to be able to conduct this sort of research and move forward? Do they have to be radically altered in order to be able to execute your plan? What needs to happen there?

Christopher Mason:
Good question, [inaudible 00:21:57]. The research world really is changing. So it used to be that the United States had the most papers, the most citations, most sort of scientific output by almost any metric. That changed just this year, where China actually now has the most papers being produced and the most citations. It's actually a really clear space race also to get this. But they want to get to Mars before NASA does. They want to become academic leaders and clinical leaders for every aspect of science. It's a rich history in humanity of competition between nations to try and push the needle and improve progress.

But right now, there's no collaboration really happening between the US and China. They're adversaries, but I think, again, taking the long view, I think that is... It might be good in the short term. For example, no one wanted to collaborate with anyone in Japan in 1942 for obvious reasons. But now I have many great friends and collaborators, and we're closer than ever. So I think if you take a long enough view, a little bit of competition might be good, assuming we don't go to war. But then, eventually, I think a hundred years from now, maybe our closest collaborators will be in Shanghai and Shanghai Jiao.

Danny Crichton:
And when you think about funding, do you need funding projects? The R01 grant, two years, you can get maybe an early career grant from the NSF gives you a little bit more time, but you're talking about 500 years. How do you structure that in a way that a funding agency can actually back over that period of time?

Christopher Mason:
Currently, there are none that do. So it's a great question. I was just on a call this morning, really bemoaning the fact that there's no agency that's built to even give 10-year grants or 20-year grants. Just the idea of even thinking a little bit longer than five years there is almost impossible to find. But a lot of it is through philanthropy. The people that have already made a crap ton of money and said, "Now, what can I do with this that would have some more longevity?" That's where most of it's going to have to come from. And that's actually funding a good part of the work in the lab is more philanthropic donations, partners who come in. Even industry partners are helping. So I think science in my lab and elsewhere, you have to really be creative and think about how do I do industry, academic and philanthropic partners.

Danny Crichton:
One last question on this part. How much of an organizing principle do you think your plan is? Going to Mars, you want to do this over the next 500 years? Does that organize all of biology, chemistry, medicine, and clinical sciences over that period of time as the Manhattan Project that brings everyone together and drives a lot of science forward? Or is it more some subspecialties that really take advantage of that?

Christopher Mason:
I think it actually could nucleate all these different fields together because you'll need them all. The manufacturing, food production, the science diagnostics, all just the building of an entirely really new city on a new planet, will require a broad cross-disciplinary engagement. And I think it's not... Mars, a lot of people think, are you escaping Earth? And I really want to change the narrative and say, "No, it's going there, it's plan A, it's not plan B. We have to go there." And again, if you take a long enough view after a billion years when the oceans start to get boiled off by the sun, no matter how amazing life is here, which it is, it will all go away if we do nothing. And extinction is inevitable unless we go. And so I think this is plan A, not plan B. And hopefully... And we'll need everyone to get there.

Josh Wolfe:
As you guys were both talking about this, something came to mind. Earlier this summer, I visited in Spain, the Sagrada Familia, which started in 1882. So we've been going 150 years with the construction of this giant Spanish cathedral Gaudí and gorgeous. And it required religious institutions. And just the other day, I was looking at a tweet from Balaji Srinivasan, and it said, "When quasi-religious taboos block technological progress, you may need quasi-religious belief to unblock technological progress." So you may end up getting a space religion. [inaudible 00:25:25].

Christopher Mason:
There are small things that drive me bananas. If I'm in an elevator and there's no 13th floor, I just want to lose my mind. It's when superstition triumphed over rationale, and I just can't understand it. Listen, if we had to make elevators that could get us to space, but there's no 13th floor, I'll take it. I'll go for it.

Josh Wolfe:
Actually, okay, on the space elevator idea, going back over a decade, people were talking about using carbon nanotubes, trying to build this giant vertical structure, you descend. I always imagine this thing just flopping in the wind and planes banging into it. And I was like, "This makes no sense. The rockets are just Occam's razor. We're going to propel ourselves up to space." Are there things that you see being developed in space now that you're just like, "That makes absolutely no sense to me; it's just absurd; they're preying on people's gullibility, naivete?"

Christopher Mason:
This is the biggest question for the space economy is what is the killer app? What is something that you can prove you need to create and manufacture in space and that it's better or unique and you can't do it on Earth? And so far, there's frankly nothing. There's tourism. Tourism's a big part of many countries' economies. So it's nothing to shake your fist at. But the only thing I've seen, there's a company called Lambda Vision; I have no relationship with them, but they make artificial retinas and manufacture them in space. And so now I don't know if it has to be made in space. And they've even said it's not guaranteed, but it is something... The idea of manufacturing layers of cells that have to be perfectly arranged, or there was a discussion of maybe growing diamonds in space in the early days, but none of it's quite panned out to be that this is so much better. It doesn't even have to be cheaper. But there's nothing that's really demonstrably and unequivocally better in space yet.

Josh Wolfe:
And, in fact, you probably want the inverse, the fact that everything has gotten low cost per kilogram to get up there; you would want something that's insanely expensive and really valuable to be able to justify bringing it back down.
Manufacturing something else, which again, I'm going to sound somewhat absurdist here, but a human, has a human ever been born in space yet?

Christopher Mason:
No, not yet. And technically, officially, there's never been sex in space. And there are cameras in the space station, and the personal quarters are pretty small. I did ask Scott Kelly, actually, last year; I said, "Officially, there's never been sex and space, but for future crews and missions, what would you recommend, Captain Kelly?" And he said, "Everything in space is generally harder except for two things. Moving heavy objects is easy, and then just orienting your body or doing really easy things." He said, "But for sex, you're definitely going to need a lot of straps and a lot of restraints." And he said, "Not in a creepy way, but you'll need the restraint things on." And he said, "But then I think it would be good." So we'll find out.

Josh Wolfe:
So that strikes me as something really interesting, what's going to be born in space?

Christopher Mason:
There have been mice born in space, so pregnant females have gone up and been born. Drosophila and [inaudible 00:28:05], so different fruit flies and small worms have been born in space. We know it's possible, but human embryogenesis and gastrulation is a complex process that has evolved under gravity. So we don't know yet.

I actually proposed this experiment to a space agency, I won't say which one, and said, "Hey, I've got an idea for an experiment. What if we take some IVF embryos, send them up to space just for 14 days," which is normally when you stop the experiment, "Fix them, bring them down and see how it developed." But [inaudible 00:28:30] too controversial. There's no good way that headline ends. Even if everything's fine, it's crazy scientists are shooting embryos across the stars, or if they're deformed it's space will destroy humanity. So it's interesting. I still think it's a worthwhile experiment just for the sake of knowledge, but I've yet to find anyone who wants to either fly it or find it because it's too much of a risk of PR.

Danny Crichton:
I think that this brings up an interesting question because you would've to do an immense amount of clinical research. There's ethics on what you can do to... Research subjects, obviously. How do you progress on that front in space? You're making these edits to the genome. Someone gets rocketed up, doesn't work, they expire. How does that function? How do you do clinical research in that context?

Christopher Mason:
We have some of the very first clinical trials that we've been doing in space. Actually, we chatted recently about Ursa and [inaudible 00:29:20] some companies that are actually working in the space. So how do we start to do actual clinical trials in flight and get more and more data? I just consented to the Polaris Dawn astronauts, which is Jared Isaacman, and the crew that's going up to actually go and do a spacewalk with the next SpaceX rocket. So in the process of consenting all those crews and doing [inaudible 00:29:38] and deep characterization of all of them, just like we did Scott Kelly, to get ready for... Having baseline data before we start to add more interventions could be a simple thing as a probiotic, but it could also be maybe life extension potential molecules like rapamycin.

We need to have this baseline before we do the trials, but we're starting to go in that direction, and I think you can now fund the trial. So if you have funds, you can do anything you want. Axiom will take quotes; they're going to have a private space station. If you want to have a wedding in space, you could do it. You just have to pay for it. So if you want to go around the moon, you can get SpaceX to give you a quote. There's the dearMoon project, which is doing just that. It's an interesting time in space flight because if you have the funds, you can do whatever you want up there. And I think space flight is an accelerated aging model in general. So I think it will help as a platform. If you think about osteoporosis, thinking about muscle loss, atrophy. Telomeres are only briefly longer, but then they actually come back a little bit lower when you get back, and there's more DNA damage. So I think it will become a platform for studying.

Josh Wolfe:
I'm going to say there's obviously a moral dimension to this, and I want to go back to the technical details of consenting somebody, which presumably is collecting blood samples, getting permission to collect before, what the governing bodies are over that. But the moral case I'm going to make is everybody's bemoaning all the billionaires that are going to space and launching rockets and getting these rides. But maybe it's the billionaires who, in risking themselves out of their own vanity or desire to live longer, end up advancing the science that the rest of us get to benefit from.

Christopher Mason:
Actually, and so far do and have. For example, Jared Isaacman who's funding the Polaris Dawn missions and the Inspiration4 mission, he's just buying rockets to take out. But there'll be a press release soon. So there's going to be 40 experiments flown on that one five-day mission, and it's going to go to the highest elevation ever except for going to the moon. And so they're packing as much science as possible. So we work with the SpaceX operations team to talk to them very closely on the medical ops to say, "What can we do in this short interval and get as much science done as best possible?" And they're funding it.

So the consent, though is it's like any clinical trial. You say, "There are risks." My favorite moment was when I went to the Cornell IRB; I said, "I need to get this set up even for the twin study." And they said, "Does this prevent greater than minimal risk?" And I said, "They're going to space." But then the person in the IRB office said, "It's just a blood draw, so that's not that high risk." I said, "Yeah, but it's in space." I said, "Listen, it's your IRB, I'll tell you what I think, but I just need to tell patients to sign or the crew to sign it. So the first IRB I ever had for the twin study said, "This is considered minimal risk," going to space for a year, which was laughable, but now says greater than minimal. But we're also doing skin biopsies and a bunch of other work on them.

But you can send them; you tell them the risks. You tell them also the genetic data and genetic risk factors. So I can send all the crews for all these factors. And at the end of the day, it's their choice. They can decide whether or not they share their data. At any point, they can unenroll from a clinical trial they can say, "I changed my mind." And you have to really, like with any clinical trial, empower the patients, empower the people, say, "It's your data, it's your choice. Anytime you have any... And you don't even have to have a reason; you can say, 'I'm just out,' that is fine." And then you have to really make them feel like they have a sense of agency over their decision and their data. I embed as much of that as I can to every crew I consent. And it's been good so far. They know they could die. They know they could [inaudible 00:32:41] could explode. They know it could happen.

But for future crews, when we're doing clinical trials in space and trying new therapies in space. That's going to be different because it's going to be trying a new drug in a new place where things could go wrong, and things probably will go wrong sometimes. And I think even if you think... The best analogy I can think of is when ships would come to cross the Atlantic to come to this continent, not to find it for the first time, but just to come here. It was obviously found before, but many ships were lost. Many people died. I think 95% of people died in the first winter, and more people just came the next year. Now, of course, no one could send them a text and say, "Oh, by the way, there's no food here, and everyone's dead." So maybe it was a benefit. But I think humanity has always pushed the borders and been really undeterred, even from obvious mortality.

Danny Crichton:
On clinical recruitment. I'm curious, typically in clinical sciences, people have a disease, say, if Alzheimer's a potential treatment, they go into a clinical trial, they try the treatment, it works, doesn't work, and they're there because they're looking for that sort of help. In your case, you're creating new capabilities, things we don't even know about before. What's it like to recruit people? Are people super excited and are banging at the door to sign up? Or is it something that you actually have to stress people out over?

Christopher Mason:
Yeah, actually definitely, people excited. They want to join the trials, especially if they're astronauts. All the ones I've consented to date, dozens of people have all... They see the value, they're excited, they want to contribute. They also know there's only, at this point been, 670 human beings ever past the Kármán lines, a hundred kilometers. We don't have that much information. So when I explain just the value of getting any data, they all really immediately say, "I want to contribute. What can I do to help?" Because it can help them live longer or just live better or help future crews or just help humanity in general understand physiology better. Everybody wins.

Yeah, they've been really excited. The weirdest thing is some of them have said, "I want to do more. I want to do... Can you CRISPR me up in space, or can you take a bone marrow biopsy?" Or even, one question I got from actually from Mark Kelly, now Senator Mark Kelly, is I sent them a report on all the mutations that they have. "Okay, here's what you had before the launch and after. And, of course, we're monitoring them every year. So we get blood through the Secret Service now, but I just do like an annual report on how's your DNA looking?" And then he said, "Can you know CRISPR it back? If I have these mutations, can you just get rid of them?" And I said, "Great question, not yet. We can do it in mice, I think, comfortably." But I'm not going to do a somatic CRISPR therapy quite yet to a sitting senator. But we can consider it down the line.

Josh Wolfe:
Are there any experiments, whether it's on the upcoming Isaacman stuff that you want to do that the IRB said no and you're going to have to wait on?

Christopher Mason:
No, not yet. Actually ,we have been doing skin biopsies. We've been doing it's hair, it's blood, it's tears, literally. Blood, sweat, and tears collecting. But we haven't pushed the envelope. I haven't said yet we want to do a bone marrow biopsy, which is a bit more invasive. But actually, in the upcoming mission, there'll be some announcements about doing, even looking at lumbar punctures or even looking at cerebrospinal fluid. The engagements with different space agencies, we're getting a bit more creative and, I think, invasive, but in a good way. We want to understand at a very fine-grain level what happens to the body. And there's a lot of pressure that builds up in the brain and can lead to what's called SANS, which is space flight-associated neuro-ocular syndrome where you just can't see that well when you come back because the pressure on the eyes and the damage and we want to figure out what's causing it. But lumbar punctures are a bit invasive, but that's recently been approved. So it's getting more invasive.

Josh Wolfe:
I have to imagine a world that whether it's some decades from now, in the same way, people do medical tourism and may go to a different country that's renowned for something, whether it's plastic surgery or something like that, we will find that there is an advantage to being in low gravity or zero gravity and actually performing some type of surgery. I have no idea. I can't imagine what that is today. But it feels probable.

Christopher Mason:
That something would be better. Or even just to go for a short term, like hormesis, just stressing the body, and it could be low doses of radiation might be good. So it could be a burst of zero-G for... Or really microgravity; I should say a zero-G is no such thing. Every place in the universe has gravity, so no one should say zero gravity.

Josh Wolfe:
And I know it's not physiologically true, but it would be comforting for somebody like me who does not like needles, which is, as the old quote from the 1979 Alien movie goes, in space, no one can hear you scream.

Christopher Mason:
Actually, we did... It just released, actually got FDA approval, and also it's now released in Japan as a drawbridge device. So you can actually do a blood draw really quickly from your arm. And actually, we're flying that in the next mission that's going up into space. So for the first time, instead of doing full phlebotomy, which is annoying in space, the tube is flying around, and you have negative pressure in the Vacutainer and positive pressure in your body. So it works. But we're going to have these smaller contraptions called drawbridge; it'll actually pull up.

Danny Crichton:
I was actually going to follow up on that. Sample collection, obviously in space, is harder and more difficult. How much do you have to reinvent the collection techniques and the tools versus inventing something new for the space environment?

Christopher Mason:
It's hard. Because everything is mass dependent. It has to be small and light as possible. But we've flown a small nanopore sequencer that's only the size of your phone to do sequencing in space. So we can begin to do diagnostics, and we're flying that again for the next mission, which fortunate is that it's only that... It's that small form factor, so we can actually fly it in space. Most other hardware is too big, though, to fly in space, or it doesn't work in microgravity. The fluidics don't work. So I think almost everything has to either be reconsidered or completely reinvented. And there there's even the guy... Even just the treadmill that astronauts use in the space station. At one of the conferences, I met the guy who engineered; he's like, "I built this really amazing treadmill, but there's only... It's not a big market; there's only one of them in the whole literal universe." But it's essential. You need to have these very custom bespoke products that will actually function. It at the very least [inaudible 00:38:07] review, often re-engineering or complete redesign.

Josh Wolfe:
I am definitely confident that the work that you're doing on the biological front, and you look at the history of what's been invented out of necessity to go to space, wireless headsets that some of us are using now, rubber, better tires, solar cells, shock absorbers, LASIK, dust busters, space ice cream. Favorite. Scratch-resistant lenses, artificial limbs. All these things came out of the space program. So even if we don't have the imagination now to imagine biologically what's going to come from this as you do, it's very inspiring.

Christopher Mason:
Oh, thanks. I think we'll get there and get there together.

Danny Crichton:
Chris, thanks so much for joining us.

Christopher Mason:
A pleasure. Thanks so much.

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