A three-year mission to Mars will have profound effects on bodies—and brains. The recent NASA study of twin astronauts Scott and Mark Kelly provides a new understanding of how life in space can alter cognition, heart health, and even gut bacteria. Dr. Christopher Mason of Weill Cornell Medicine and Dr. Mathias Basner of the University of Pennsylvania School of Medicine reveal their findings about long-term space flight and explain why using a “free-range astronaut” as a control was uniquely helpful to their work.
Dr. Stieg: Now that travel to Mars is reality in the near future. I'm really excited to welcome two leading scientists who are part of NASA's groundbreaking twins study. We're going to learn from them about their pioneering research on the effects of long term exposure to space flight and the potential for human survivability in space. Dr. Christopher Mason, he's an associate professor genomics at Weill Cornell medicine where his lab focuses on the genetics of human disease and physiology. He's been working with NASA to build integrated molecular portraits of the genomes of astronauts to help establish what genetic defenses are required for successful longterm human space flight. Dr. Mathias Basner who worked closely with Dr. Mason on the twin study is an associate professor of psychiatry at the University of Pennsylvania School of Medicine and has been an advisor to the world health organization. Mathias and Chris, thanks for being here and welcome.
Dr. Mason: Thanks.
Dr. Basner: Thanks for having me.
Dr. Stieg: In this day and age where Elon Musk and Branson are talking about space travel. The general person should be thinking, wait a minute, do I need to prepare for this? Astronauts aren't just going up there cold. What do they do to get ready for this long trip in space, Chris?
Dr. Mason: Well, it's really exciting. As part of this study, we got to tour all the NASA training facilities where they have to do both. Just physically for the training. We have a giant mockup of the entire space station underwater is the world's largest pool. So if you're a scuba diver, it's a cool place to visit and they have to learn everything. All the, basically the hardware, basically the common space mechanics, half of their job is really knowing how to fix anything that goes wrong and read it in Russian, you know? So it is a lot of learning they have to do plus very specific mission tasks that they need to do on the space station. So it could be repairing something, installing a new device. They all become mechanics, scientists, astronauts, engineers to get ready for it.
Dr. Stieg: Mathias, what do they do cognitively to get ready for this?
Dr. Basner: Well, cognitively, the most important thing is training, training, training, repeating things, trying to shift a lot of things from your, from conscious behavior into subconscious that these things are working automatically. So this is why astronauts train for such a long period of time. Going through different positions, actually taking roles and mission control as well, so that they see every aspect of the mission from all different angles. And only then are they fully prepared to go into space.
Dr. Stieg: In addition to radiation, what other things are these astronauts exposed to?
Dr. Mason: Yeah, the radiation is one of the key hazards. So NASA has an entire website that just describes everything that could go wrong in space. And also over the next 30 years, how close are we to solving these problems? So...
Dr. Stieg: What is that website?
Dr. Mason: Oh, it's NASA.gov/HRP/gapsandrisks.
Dr. Stieg: For those who are interested.
Dr. Mason: It's interesting, yes it is. But HRP is the human research program. And so this is planetary science. And if it's an animals that's either everything except human. And then the HRP is the human research programs are longitudinal maps of astronauts as kind of the whole division. And those, the radiation is one of the top risks essentially because we know it can damage cells of course. But the other risks are the lack of gravity as you know, that the change your physiology dramatically. Uh, also you have the isolation, uh, earthbound studies of, of analog seem to indicate there's a risk. You know, you can't pretend that it takes six people in an aluminum tube and hope that they're going to be fine for three years. I don't know how much you like, you know, your family members, but you've known them your whole life. And how many of those would you like to spend a year within a tube?
Dr. Basner: Actually the International Space Station is like a four bedroom house right now. So it's very big and it's much, much bigger than what we will ever be able to send to Mars, at least in the next couple of years. And another thing, what was very important are these private crew quarters, just a private space for the astronauts where they can retreat, you know, close the door and you know, nobody will bother them at the time because mass is a big problem. Sending mass to Mars. Every kilogram costs tremendous amounts of money. So the engineers are always trying to push back and say, you know, we needed smaller, smaller, smaller, and then the human research program, which is, you know, concerned about astronauts behavioral health says, no, we need this kind of room minimally. Otherwise the astronauts are just going to disintegrate.
Dr. Mason: But just that isolation of being far away from Earth, there's nowhere else to go is one of the risks. It's a psychological risk. It's one of the key risks identified. The other risks are just also that the hazards of space flight, so other things can go wrong or the basically if something does go wrong, there's no one out there to save you.
Dr. Stieg: Mathias, you were involved in the twins study looking at the effects of space on astronauts. As part of that study, you followed Scott Kelly and Mark Kelly, both of which are astronauts and they're twin brothers. Scott was in space. Mark was living on the planet Earth. Tell us why the twins made a perfect study model.
Dr. Basner: Well, both Chris and I, you know, we're part of a team of 10 investigators who worked on this twin study. So, most of the missions have actually been up to six months so far. And there's only very few people who spent more than six months consecutively in space. In fact, have only been four people all together over our whole Baselight enterprise that have spent more than one year consecutively in space. So NASA was venturing into studies looking into how these longer stays in space affect humans. Well, they pick Scott Kelly because he had a twin brother Mark Kelly was not only his twin, but who is also an astronaut and in fact a test pilot. So they not only share same genetic code, but they also share very similar history and career. So obviously this was the perfect fit for investigating not only Scott before, during, and after his 12 months mission on the International Space Station, but also having a perfect control on the ground where we, the 10 different investigators could basically do the same studies on Mark Kelly on the ground and then compare the results between Scott and Mark.
Dr. Stieg: What do you think would be the difference between being in space for 6 months versus 12 months? Why is this other than that it's interesting. Why are we asking that question? Why are we making a big deal out of it?
Dr. Basner: It is, it is a big deal in the sense that NASA has something that's called a Mars design reference mission. Basically, you know, planning out what that mission will look like. And that is currently 1000 days long. So you know, it's approximately three years. And again, the bulk of the information we have on, on how humans will behave if they're exposed to very specific space flight environment that includes microgravity and higher radiation levels, non 24 hour light-dark cycles and all the psychological stressors that are involved in living in an isolated, confined and extreme environment. We don't know how humans will behave if they're exposed to that environment for such a long time. And this is why it's so important that we go beyond that six months mark and see, you know, have things really stabilized at the six month mark? Are they getting worse? Are they getting much worse or are they even improving? So we need to have that knowledge before we can confidently send humans out on a much longer mission than the six months that we know about.
Dr. Stieg: Chris, specifically from a genetic standpoint, what could happen in six months versus in a year that's irrelevant?
Dr. Mason: When you head towards Mars, you get out of the protection of the Van Allen Belt. So, as Dr. Basner will describe also, there's some evidence in the literature that this might be part of the cognitive sort of effects of space flight as you are. Your whole body is getting radiated. So we know what that does clinically for radiotherapy. That'll be at the doses on earth are much more than you'd see in space, but still as a whole brain radiation is as bad as it sounds. Whole body radiation is also a worry both genetically and cognitively.
Dr. Stieg: In terms of the brain, I understand that there's evidence of increased pressure in your optic nerves. As I understand it, your heart is actually more efficient in the absence of gravity.
Dr. Mason: Yeah, that the left torso, absolutely.
Dr. Stieg: So there's a plumbing, kind of thing.
Dr. Mason: The plumbing, and also the brain. There's something called SANS or a spaceflight associated neuro-ocular syndrome, which is believed to be sort of the change of the choroid folds in your eye and damage to the retina. It doesn't happen to every astronaut, but it happens to most and it seems to be slightly more affecting male versus female astronauts. And so it is, this was a lot of pressure. Most astronauts get what's called noon face, really puffy face. Once they get into space, several days of feeling really puffy because two liters of fluid, just what used to be on their lower bodies suddenly in their upper body. So the body has to adapt very quickly. Most of the vasculature has to readjust, but it does do so pretty, pretty well.
Dr. Stieg: Mathias, specifically in terms of cognitive skills for the astronauts, what kind of changes occur by being up there for a year?
Dr. Basner: I think the most important changes obviously that they are, that you are in this microgravity environment. The organ in your body that senses the gravity is just, there is no gravity anymore. So they have to readapt to that environment. You know, what is, what is up, what is down. Obviously, on a spacecraft you can use all the surfaces, on the ground. We are like stuck to the floor and you know, we're working on a desk and a on a spacecraft you can work on the ceiling, on the sides of the wall. So there's a lot of, you know, the brain really has to adapt to this and there's a lot of plasticity going on in space flight and obviously one important question is you know what then happens when you, when you get back to the ground because then the same has to happen again in the other direction.
Dr. Stieg: I understand that you found in Scott when he came back that he had lost weight, that he urinated less frequently and he was more dehydrated. The one thing that I was most interested in is the change in his microbiome. What happened there?
Dr. Mason: Sure, yeah. I'll jump in on that one. It was really interesting to see that what's called a shotgun sequence of the gut microbiomes. This means you take all the DNA that's present and you break it apart and you can see any species that's changed before or in flight or afterward. And there's a bit of good news is that the diversity of the microbes in the gut actually stayed pretty constant during the study. So diversity is associated with the gut brain access, which I know you've talked about on the podcast before. So it's a very important mediator for your body's health. And it, most of the diversity was there, but the ratio of what's called Fermicutes to bacteria, cities are these two different kinds of bacteria. It shifted in what is normally considered an unhealthy direction, but when it got back to earth that did return back to normal. So he was eating space food. It was a different selection pressure. We tried to get Mark Kelly to eat the exact same food on Earth to which he politely said, um, expletive, no, you know, so he, you know, he wanted to have nachos and his margaritas and hang out on Earth. So that was one component of the study that they didn't eat exactly the same food and that could be a part of it.
Dr. Basner: Somebody at some point referred to Mark as the free range astronaut because he could do anything he wanted.
Dr. Mason: That's right. That's exactly right.
Dr. Stieg: Chris, can you describe what big changes you saw in Scott when he returned?
Dr. Mason: You know, Dr. Basner said this was a real 10 person team. And so we looked at this from all angles, including the genetic changes. We saw some evidence of the RNA levels change, how your genes are activated or repressed, which is called gene expression regulation, was very, uh, adaptive in the early mission and even six times more genes changed their expression levels later in the mission than we saw earlier on. So there's clearly an ongoing adaptation inside the body that we could see in the blood and the immune cells. But we also saw working with Susan Bailey that the telomeres got longer in space.
Dr. Stieg: So explain what telomeres are.
Dr. Mason: Kind of like looking at your shoelaces, they're basically, what keeps those shoelaces together? It's a little plastic at the end and in the human DNA and inside yourselves, the telomeres are kind of the caps at the end of your DNA, at the end of your chromosomes that keeps them together.
Dr. Stieg: And the importance of the telomeres is?
Dr. Mason: Basically, it's an indicator of aging. As they shrink over time, it tracks with as you get older over time. So it keeps the DNA safe, it keeps it stable, it makes it so you can make faithful copies to the next cell, but if they're damaged or if they're shortened, eventually the cells can die. So it's interesting as we, the hypothesis was that you'd go into space and we all thought he'd get more mutations. All the stress, probably shorter telomeres, but we validated some of the work from Susan's lab in our lab. His telomeres got longer in space, which was the opposite of what we thought would happen. And we've since been looking at this in additional astronauts with Susan's, we have some additional followup papers and we've seen, it's not just Scott, we've been able to see this in other astronauts used to be showing up. So there is a really surprising feature if you go to space on some aspects of the genetics, you look a little bit younger. So he, um, once asked by a reporter that said, well, Dr. Mason, this is amazing. He went into space. He lost weight. You know, his telomeres got longer. You know, basically he's younger and he got a little bit taller, younger, taller, you know, sexier, skinnier, younger, all these things. And he'd say, I want to go to space. I said, well, but he was being irradiated, you know, hit all these immunological challenges. You, you know, he did the telomeres did come back to normal. So it did seem to be something specific to space flight. It's not quite the fountain of youth. The real big shift is he wasn't drinking for a year. He went to bed every night and got a good seven, six to seven hours of sleep and when he'd close his eyes he could see cosmic rays shooting through his retina. So that was kind of disturbing. But you get used to that apparently. Uh, you know, he was actually, ironically in some ways, healthier in space.
Dr. Stieg: Mathias, if we're going to go to Mars, we're talking years, not just one year up in space, but worrisome to me is I read that Scott's cognitive or mental performance actually deteriorated. Can you describe what happened and how you're going to avoid it on a longer flight?
Dr. Basner: Yeah, so I mean there's, I think there's good news and bad news. The good news is that we really didn't see a deterioration in his cognitive performance during that second half of the mission, like that part where we really know don't know a lot about, but it was really performing well while he was on the station. The most surprising finding was that once he returned to earth we saw a more major decline in his cognitive performance and not only in a, in a single test like we administer a whole battery of tests that cover a range of cognitive domains and look at different aspects that were very important for mission success in space flight. And importantly it was not a transient change but basically it persisted up until the six months after his return to earth where we were measuring and that is very much in line with what he and his partner reported that it took him much longer after this 12 month mission compared to an earlier six month mission to to get back to normal, to feel normal. He himself said it was about six months. His partner even said it was more eight months.
Dr. Stieg: Do you find other parameters in their cognitive skills like spatial orientation and vision, art appreciation, or are all of those things altered positively or negatively? While in space?
Dr. Basner: The battery we use is very broad. We look at memory, we look at the ability to do abstract reasoning. Oh, actually also add emotion recognition. That is how well, how well are astronauts able to read a fellow astronaut's face for emotions. Because Chris already mentioned on these very long duration missions where you spend a lot of time with very few people in a very confined space. Obviously, you know, social cohesion and just getting along with the other person is very important. So we, we want the astronauts to be able to go read their fellow astronauts emotions and react in a proper way to them.
Dr. Stieg: So as I understand it, the planned trip to Mars is about 2035, but in planning, NASA has changed where they're going to take off from, you're going to start at the moon and then go from there. Why is that?
Dr. Mason: Yeah, eventually, the deep space gateway as it's called, is basically going to be a space station around the moon. A lot of that just has to do with the orbital mechanics of using fuel. And it's much easier to leave, not from on a planet than just around a planet to get to the next planet to get to Mars. So it just requires less fuel and less energy and then leave from there.
Dr. Stieg: Very interested as a neurosurgeon in the effects of radiation on the brain. And what we see in humans with whole brain radiation is they have a drop of four to eight points in their IQ. Did you see that drop in Scott? And if you did, is it recoverable?
Dr. Mason: We could see DNA was damaged at a global level. It was higher when he was in space, but it was interesting. Some of the genetic rearrangements on chromosomes are called inversions kept increasing even when he got back the repair processes. And so we know that means genetically, but, but for the cognitive state, Dr. Basner could comment. And how does that manifest? It depends on the astronaut.
Dr. Basner: Yeah, and again, you know, we didn't really see a major drop in cognitive performance in flight either in the first or the second half of the mission. But the reason for that may simply be because again, the International Space Station is protected from those types of space radiation that astronauts who will travel to Mars will be exposed to. So very likely whatever radiation dose Scott got on his 12 month mission just wasn't high enough to really show up in his cognitive performance.
Dr. Stieg: What was the effect on sleep and then on his cognitive behavior as a result of any abnormality in his sleep cycle?
Dr. Basner: He was actually wearing an actigraph, which is a little device that measures wrist movements and you can infer rest activity cycles from that. But none of the 10 investigations were specifically looking at sleep in Scott. In general though, sleep on the International Space Station is somewhat shorter than on Earth, very likely to simply the high tempo environment that the ISS is. I mean there's just a lot going on. Lots of maintenance, lots of research staff and you know, we researchers often say, "Oh, it'll take you half an hour and then you know something goes wrong, it takes 90 minutes and then they're already like an hour behind." So very much like on Earth, it's a very busy work week for the astronauts and they're not typically not getting enough sleep during that work week and then they're trying to catch up on the weekends because yes, there are weekends on the International Space Station.
Dr. Stieg: I've got to ask, do either one of you have a desire to go up and be in the space station?
Dr. Mason: 100%, I'd go to Mars, even if it was a one way trip. Yeah. I don't know if you, Mathias—
Dr. Stieg: Mathias, do you feel that way?
Dr. Basner: Well, I would love to go up in space, but I don't have a desire to do a one way trip. Sorry!
Dr. Stieg: What is the duration of flight to Mars and back? How many years are we, talking?
Dr. Mason: About three years is the current estimate.
Dr. Stieg: So there and back?
Dr. Mason: It's about six months to get there. Six to seven months and if you did, there's two options. Either you get there and you immediately turn around. So the way of the planets of course revolving around the sun and moving closer and farther from each other. You actually, yes, it turn around and come right back or wait for the planets to get closer to each other again and then come back. So that's why most of the missions are planned for that model because it would actually be more efficient for fuel purposes. One quick side note, if any of you have like an Alexa device at home, they can say like, you know what Alexa, is that how far away is Mars? And she recalculates every day exactly how far away Mars is or other planets. Kind of a fun thing to do if you're getting ready in the morning.
Dr. Stieg: Useful information, I'm sure.
Dr. Stieg: I find it nice when it's closer. I don't know. But it is far. It's hundreds of millions of miles away.
Dr. Basner: That's only what these people ask who want a one way ticket to Mars. Other people don't ask that question!
Dr. Mason: *laughs*
Dr. Basner: In that, in that realm, you know, there's the saying "Propulsion solves everything." Obviously, the problem is, and Chris just mentioned, is that it takes six months to get to Mars and that's why when the planets are aligned perfectly. So if we only had a propulsion system that would get us there in like let's say three days or something, everything would be great. I mean, astronauts wouldn't be exposed to the hostile space environment for such a long period of time. We wouldn't have to think about the radiation, the microgravity effects, et cetera. I mean, Mars has a third of the, of the gravity of earth, so there's still some gravity there, but the problem is we simply don't have those propulsion systems now, so we have to think about much longer ambitions with all the risks associated for astronauts behavioral health.
Dr. Stieg: Chris and Mathias, I can't thank you enough for this conversation. The thing that I'm most excited about is the fact that the technology that's going to be derived from what you're studying. This is amazing material and thank you so much for being with me.
Dr. Mason: It's a pleasure.
Dr. Basner: Thanks for having us.
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