Sandeep Burma, Professor of Neurosurgery and Biochemistry and Structural Biology at The University of Texas Health Science Center at San Antonio talks about how space radiation affects the cancer risk of astronauts.
Interview conducted by Ivanhoe Broadcast News in 2022.
So, you are looking at radiation in space?
BURMA: Space, exactly. We’ve been sort of funded by NASA for about 15 years or so to investigate the detrimental effects of space radiation, and especially given sort of my background as a radiation biologist and my current cancer focus being glioblastomas, especially the risk of brain cancers from space radiation exposure on long duration missions to Mars, for example.
Is there a higher risk for astronauts?
BURMA: I think based upon epidemiological studies, it’s perhaps not clear cut yet from studies of astronauts themselves. Unlike, let’s say, survivors of atomic bomb explosions, Hiroshima and Nagasaki, where there’s a very clear risk of radiation induced cancers, the numbers of astronauts are sort of very small for us to get a very clear cut picture of radiation risks from space radiation. Well, therefore, we start to do mouse models and other modeling to understand the sort of risks that space radiation poses to astronauts. The fact of the matter is that we know that gamma rays or x rays, which is sort of terrestrial radiation, is carcinogenic based upon A-bomb survival data. What we do not know is how much more carcinogenic space radiation is, given that space radiation is a completely different beast compared to x-rays and gamma rays in terms of the DNA damage they induce, in terms of what they constitute, in terms of how penetrating they are and how prevalent they are.
Do you have that information yet? Like, oh, it’s 100 times more than if you’re in the ISIS space station than having an x-ray or?
BURMA: Right, exactly. So, we have a pretty good idea about that from our cell-based studies and mouse-based studies. So, gamma rays or x-rays, they’re just waste of energy. Right? They kind of induce this sort of diffuse DNA damage in the cells, and that sort of damage is repairable. All the gamma rays and x rays, mind you, is also very carcinogenic, but that sort of damage is quite repairable. On the other hand, space radiation consists of accelerated ions accelerated by supernova explosion. So, these are essentially the nuclei of atoms, heavier atoms especially are dangerous, that are essentially moving at nearly the speed of light. They are highly penetrating. They can go through novel shielding materials and all that, and they leave in their wake a very dense track of DNA damage is what we have found based upon our in vivo and in vitro cell based studies. This sort of damage is not repaired by the cell. It’s sort of if gamma rays were birdshot, for example, then space radiation would be like a rifle bullet that is kind of spinning through your body. That’s the difference perhaps greater. So, the question that arose next is what the carcinogenic risks from space radiation are compared to the known risks from x-rays or gamma rays, which different NASA researchers have gone at this question using different models of different cancers. We have sort of pursued this question using mouse models of brain cancer that we have developed. We find that compared to x-rays or gamma ray space radiation, even very small doses of space radiation can be very, very carcinogenic or in this case, glioma genic. The higher in atomic number you go, like the bigger and bigger the particle is, like if you go from, let’s say, carbon to silicon to iron, these radiation components become more and more carcinogenic. So, there’s a very real risk is what we gather.
Well, what I was talking to Rocky about this in the car before, and he said, well, that’s why they wear the space suits. That’s why it can’t get in. Can it get in?
BURMA: Yes. That’s the thing because these ions are very penetrating. They can easily go through space suits or even normal sort of shielding, which would be aluminum on the spacecraft. In fact, if you had each astronaut’s helmets, you would see entry and exit, sort of etchings of these space radiation components that have gone through. In fact, astronauts, sort of report seeing flashes of light. Those flashes of light are caused by these ions hitting the brain cells of the neurons. So very, very penetrating is the problem, cannot be shielded using sort of conventional shields.
So, is it different? So, we’re sending people up into space now. It’s just I have a feeling. I don’t know but it’s just that line that is here is not space. Here is space and they’re going for space vacations now. Once you get out into space, is it all the same or is Mars more radioactive than the Elon Musk space station or whatever?
BURMA: So, as I was sort of mentioning when we were conversing before the interview that we on Earth are largely protected by these sorts of the magnetic sort of feel of the earth. Then as you go off to the space station, you have more exposure to these sorts of accelerated ions, and of course, as you sort of go into deeper space, then the exposure increases. Also, the time increases, so for example, if you just went up to space on a single shot, and came back, it’s a very short exposure. If you were to go to Moon and to the Mars and back, that’s by some estimates, I’m not an expert, but I’m just speaking almost from a layman’s point of view, that’s a three-year exposure to space radiation. Again, the difference, the qualitative difference, is what counts, maybe not the total dose, but the fact that even a small dose of these accelerated ions is a very different beast compared to a similar dose of x rays or gamma rays.
So, if there’s no protection, and it seems like it’s not doable, I mean, it’s just survival?
BURMA: So, the question, of course, is on an exposure on a trip to Mars, right? I mean, is it a lethal dose or is it a dose that can increase the risk of cancers or neurodegeneration? So, while it may not be a lethal dose, you do have a sort of increased risk of cancers or neurodegeneration. So, the thinking, from my understanding right now, is that if you really cannot shield completely from sort of these elements, then we must start thinking about countermeasures and which then tells us that we need to understand how these space radiation elements cause cancer or neurodegeneration, which again, kind of brings me back to my research on senolytics. A part of that sort of cancer risk could arise from the generation of senescent age cells in the normal sort of tissue which could promote cancer development. Again, senolytics which would remove these prematurely age cells, prematurely aged by space radiation exposure, senolytics could perhaps counter both, at least in the context of brain tumors, both GB development as well as neurodegeneration.
Well, it’s funny now that you are all talking about this that the guy that went to space for the longest amount of time, that twin hasn’t his body aged, is that part of the study that’s come out of that quicker than his twin?
BURMA: Yeah, but I cannot speak to that very accurately. They had multiple sessions and I couldn’t attend those sessions because my session was going on. I was speaking, so I missed all of that.
It’s the aging cells.
BURMA: The astronauts go off, but they do come back, with increased sort of chromosomal aberrations and so on, so forth. So certainly, there are differences which presumably arise from zero gravity and radiation exposure.
All right. Let’s go back to this one. One of the ways that you might fight this would be CDDO? Is that a drug that you can give before?
BURMA: So, these are antioxidants, right?
OK
BURMA: So certainly, I mean, these are certainly other approaches being pursued by other laboratories, though not by our laboratory now. Certain there are other approaches. I mean, we are kind of keen on understanding what the senolytics can serve as countermeasures, but other antioxidants can also do the trick.
So, what would your preventative measures be then?
BURMA: Given the absence of shielding right? Preventive measures could be from the standpoint of our research, senolytics may be given intermittently after radiation exposure, which would be obviously after a space mission is underway, and the advantage of senolytics is that it’s not something that has to be given continuously because the senescent cells kind of, develop over time. So you could then, after a certain period of time, come in with a single or a let’s say two doses of the senolytics therapy to remove the senescent cells that have accumulated. Then you could wait for a certain period of time and then give another round of senolytics again, which can reduce the risk of cancer or neurodegeneration. So that could be, of course, one approach. But there are other labs, other scientists working on other approaches to mitigate cancer risks, including CDDO.
Where does your study stand right now?
BURMA: So, at this point of time, we have with support from NASA been able to develop mouse models, two complementary mouse models that do not develop spontaneous gliomas, but they do develop high grade gliomas once you hit them with either high doses of x-rays or gamma rays or very low doses of space radiation components. Using these mouse models, we have tried to understand the basic sort of genetic changes that trigger brain tumor development. We have also been able to kind of draw a correlation between different space radiation components and brain tumor risk. In other words, we find that as you go up to bigger and bigger ions, as I mentioned before, from carbon to silicon to ion, you have an increased risk of brain tumor development in these mouse models. Given now that we know that senescence in the sort of tumor microenvironment caused by radiation also promotes tumor growth, our goal right now is to use these mouse models, if possible, to study countermeasures, of which, of course, we would test senolytics, but we could also test other countermeasures in these mouse models. So, the idea would be to obviously irradiate these mice with either x-rays or with space radiation components and then come in with countermeasures depending upon the type of countermeasure we’re using. So that’s where we stand now with these models.
Did you ever dream when you started neurology that you’d be dealing with space exploration?
BURMA: No, not really. I mean, one thing leads to another. I’m not trained as a neurologist, but I happen to be neurosurgery now.
So, the question could be that did you have a dream when you started working in radiation biology and thinking about people going to Mars?
BURMA: No, it’s how things happen in life. Right? One thing kind of leads to another. It was possibly at the time when I was working, I was trained as a radiation biologist at the Los Alamos National Lab, where the A-bomb was developed, and from the Los Alamos National Lab, I was a scientist at the Brookhaven National Lab in Berkeley, and I was trained as a radiation biologist. I was working on basic radiation biology effects on the DNA and how damage DNA damage is repaired and signaled by the cell, but it was at that time when I was in Berkeley, another senior scientist kind of got me interested in the shielding aspects of space radiation. Berkeley had several scientists who were kind of interested in space radiation, and some of them are funded by NASA. So, a senior scientist there who sort of acted as my mentor, he kind of got me intrigued, and then I realized that we have these accelerated ions, the so-called Z particles, which are very different from x rays or gamma rays, which I’d been studying for a few years, and that they induce a very different kind of damage and that the signaling is different. So that’s what got me interested. From then on, fortunately, I was supported by NASA funding for many years. So yes, I really didn’t know that I would be sort of doing sort of space radiation and NASA related work, which I find very cool.
Well, and I think what’s amazing is that you think about going to Mars and you think about how are we going to get there? How are we going to stay there for long periods of time? You don’t realize that all the health risks that are also from brain tumors to everything. There’s a lot more playing into it.
BURMA: Right. That’s sort of the human spirit, right? I mean, we keep pushing boundaries and we keep exploring, right? So that’s what makes us human. A better understanding of the risks and more importantly, the biological mechanisms underlying this risk can help us mitigate this risk so that we continue to be human, but in a more sort of well informed and more cautious way, perhaps.
END OF INTERVIEW
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