Sep

27

2022

Lessons Learned from Space

Featuring Helen Osborne and Guy Trudel

Guy Trudel, MD MSc FRCPC is Professor of Medicine, Surgery and Biochemistry at the University of Ottawa, Director, Bone and Joint Research Laboratory at the Ottawa Hospital Research Institute, and Physiatrist at The Ottawa Hospital Rehabilitation Centre. Dr. Trudel’s clinical practice involves the rehabilitation of people after polytrauma, after ICU for complex medical and surgical complications and after burns. He leads a multidisciplinary clinical and laboratory-based research group on musculoskeletal complications of immobility, which has led to innovative projects on bone marrow and space anemia. His team has published over 100 original research papers, including seminal findings on the mechanisms of space anemia in Nat Med. 2022 Jan;28(1):59-62.

In this podcast, Dr. Guy Trudel talks with Helen Osborne about:

  • The challenges of undertaking blood research in space
  • Similarities between space and earthly bed rest models
  • Mechanisms of anemia in space
  • The importance of questioning established dogma

Music by Skilsel from Pixabay.

Producer and audio editor: James Aird

Transcript:

HELEN: Welcome to Talking about Blood. I’m Helen Osborne, host of this podcast series and a member of the Advisory Board for The Blood Project. I also produce and host my own podcast series: Health Literacy Out Loud. Talking about Blood podcasts are interviews with experts about many aspects of blood. Today I’m talking with Dr. Guy Trudel about research that he and his team are doing about astronauts and anemia. Dr. Trudel is Professor of Medicine at the University of Ottawa and Director of the Bone and Joint Research Laboratory at the Ottawa Hospital Research Institute. 

His clinical practice involves the rehabilitation of people after polytrauma, including those with burns or who have been in the intensive care unit for extensive periods of time. Working with a multidisciplinary team, Dr. Trudel’s research looks at complications of immobility. Their findings led to innovative projects on bone marrow and space anemia. Their subjects include astronauts during missions to the International Space Station.

Welcome to Talking about Blood. 

GUY: Thank you Helen. Thanks for having me on your program.

HELEN: What a treat. As I said, I love to talk about all aspects of blood including people doing really amazing, innovative, work. And yours certainly is – about astronauts and anemia. Now you started your work from treating immobilized patients, and now you’re doing research with astronauts. Please fill in some of those dots there. How did these two areas connect?

GUY: So my training is in rehabilitation medicine. I am treating people who have been, as you said in the Introduction, in bed for weeks. And these patients are very deconditioned when they come to our rehab center, in our rehab unit. So that has been the focus of my research, how to prevent the deconditioning, or when it happens how to reverse it as quickly as possible. So we have a basic research lab where we look at the effects of immobility and deconditioning. And there are many of them. The bones are weaker, and the muscles are weaker and atrophied. And we were studying this especially in the bone marrow and that’s where the connection with the blood will come. As you know, all of our blood cells originate from the bone marrow. When we were doing our research and looking at bones that were immobilized for long periods of time, we noticed very significant changes in the bone marrow and there came our hypothesis, that maybe the anemia that these patients have could originate at least in part from the bone marrow.

HELEN: I’m trying to just envision this, so you’ve got patients who are so sick, in bed, not moving, have been there a long time. And you have this important medical question you want to answer. But how did you make that leap to “well let’s study astronauts about that?” They’re the opposite of being immobile, aren’t they? 

GUY: So we were doing research in the lab because it’s very difficult to do this research on patients. They are so heterogeneous. No two are alike. And then we heard of this model that people in space research are doing. This human model where people are in bed for extended periods of time and then they study the effects of microgravity, some treatments on this earthly model. For them, bed rest is a very good model of space. But for us, bed rest was a very good model of bed rest, and we tried to apply some of our measures to people in bed and then to astronauts. When I started reading a little bit more about this, I found out that an astronaut returning from space comes with a similar set of issues than a patient coming back from ICU. Meaning that they will have vestibular issues. They will have muscle mass loss. They will have osteopenia. And they also have anemia just like my patients do. So we wondered if the cause of anemia that we were looking at immobile models would also apply to the very well-known problem of space anemia which has been known since the very first humans have been going to space. 

HELEN: Fascinating. So are you talking about someone who is just going up and down, just very quickly going into space, or someone who’s been there a while. Do all these physiologic changes happen right away? Or for a while? 

GUY: In the mid-1990s were seminal works and very innovative works with the techniques of the day. These found out that the anemia might have been caused by destruction of red blood cells that would happen during the first few days in space as an adaptation to other changes happening in space, namely significant fluid shifts happening in the body which makes us having too much fluid and then ejecting that fluid from our blood vessels and then concentrating our red blood cells. So that was the main hypothesis when we started looking at this. 

HELEN: I’m just fascinated by that. I want to hear about two main parts of it. How did you get ready to research astronauts? That doesn’t sound like a very easy population to access. And then of course I want to hear about the applicability to people who are immobile and in bed. So let’s start with the astronauts. How did you go about doing that work? What made the connection, as in here there might be some similar issues? How did you go about actually doing this?

GUY: So the key here was to develop methods that would precisely measure hemolysis, which is the destruction of red blood cells, on the space station in astronauts. So we planned a protocol for that. We submitted it to the space agencies and long and behold, after years and years of study, we were allowed to recruit astronauts, like 6 years later, when we adapted all of our earthly methods so that the function on the space station and all the supplies we needed had to be sent separately on cargo ships heading to the space station, and regularly resupply, and the astronauts had to include in their schedules the blood work and the air samples that they would harvest for this study. 

HELEN: I wanted to just ask you before it goes on too long, you talked about your earthly methods. Can you tell us a story or give us an example about what you mean by that? 

GUY: Yeah, for example if you want to draw blood and filter it, you can do that easily on earth. But in space you cannot do that because there would be a risk of blood being spread in the space station which would be a health hazard. Similarly, if you want to make a measure on the space station, you need specialized machines. The weight and the volume of these machines make it unfeasible for earth in order to achieve the precision we want. In order to collect air samples, for example, breathing air samples, we have to devise a collection method that would trap the air in a metal canister. And then these air samples would be sent back to earth and all the way to our lab in order to analyze a specific component of air which is the carbon monoxide and to us, this was a key change in the methods that allowed us to advance the field of space anemia. Because it would allow to measure directly the hemolysis happening in space as opposed to indirect methods that were used in the past. 

HELEN: Wow, thank you. It makes it more vivid in my mind when I see the blood going everywhere that you have to work around that. That’s what took the years and the preparation to get ready to do this research?

GUY: Yes, this and all of the other supplies we were sending had to go through approval at many levels to make sure that they are safe. For example, in terms of outgassing of various gasses on the space station. In terms of flammabilities. So all these details had to be worked out before you could implement your protocol up in the space station.

HELEN: You certainly are persistent, as well as inquisitive. You and team. What did you learn from this work?

GUY: We made actually a nice discovery that was in some ways unexpected. We did find that the control of our red blood cells in space is very different than on earth for a reason that is still unknown. Our red blood cells cannot live as long in space as on earth. We are destroying many more red blood cells. In fact, we measured over 50% more red blood cells are being degraded at any time. Now this could have been predicted as was measured before in the first few days in space, but the surprise came when we measured the same increased red blood cell destruction later in the flight, at 60 days and then even before landing at 150 days in space. That increased red cell destruction was still proceeding unabated and so the conclusion is that the hemolysis in space is most likely the cause of space anemia and it is a direct effect of being in space because the minute the astronauts landed, then this effect would markedly decrease. So it was a really an on-off phenomenon. In space you increase your red blood cell destruction. You land and it’s almost back to normal upon landing. 

So all of the previous explanations that we had for short adjustments do not hold any longer. We need to orient the research towards the mechanisms of hemolysis in new directions.

HELEN: And what’s the applicability to people who are immobilized? 

GUY: I was pointing to similarities between people who are in bed for a long time and astronauts returning from space. And the one commonality is the anemia. Therefore, the findings that we are making in space may well apply as well to the same populations, in fact the rehabilitation patients who are paralyzed, who are less mobile, who are spending more time in bed, or sitting, and these categories of patients, these groups of patients have long been identified to have anemia but the cause was unknown. They were always classified as “unknown anemia”. An unknown origin. So the measures we developed may well explain part of the anemia in those patients. 

From there it sets a clear direction to try new interventions in order to mitigate the anemia. 

HELEN: I just keep coming up with that word “fascinating”. I don’t think I can come up with another word. Can you tell us another story of something else that you learned from the astronauts in space? You said this was an unexpected discovery. What is something else that you learned in your research? 

GUY: One aspect that in fact we were afraid and working for years in preparing this… we wondered if all of the countermeasures that the astronauts used to prevent or decrease the effects of microgravity – for example, all of the strength testing, all of the aerobic testing, the running on the treadmill in space – if that would overcome the space anemia because recently before our work there was a measure of blood in astronauts that showed that while in space, the astronauts had no anemia. The anemia was really present when landing from space. So we wondered if all these countermeasures that have been refined over the years and that the astronauts are doing in space would actually correct the anemia. In fact, this was not the case. The astronauts came back with a significant red blood cell deficit. So we know that all of the research and all of the protocols developed to mitigate the effects of microgravity do not work on blood. Again, we will have to find specific counter measures in order to prepare for that. The astronauts we studied, the 14 astronauts were in for 6-month missions. But now we are preparing for a much longer manned missions to mars. That raises many more questions about red blood cell destruction. At one point will it become a health hazard? Or when returning from such a long time in space, if there will be difficulties readapting to earth.

HELEN: When someone goes to mars, how long does that take?

GUY: We’re talking 2-3 years for the travel – the mission- there and back. Also in the astronauts we measured how they recover from anemia. We want to know how they recover. We took measures for up to a year after landing and we found out the control of red blood cells was still not back to normal a year after landing. There was still a slightly increased red blood cell destruction compared to pre-flight. And slightly higher levels of red blood cells as well. So it may be that some of the changes that happened and lasted for 6 months on the space station have made structural changes to the organs involved in red blood cell control. And this is where our next research will go, to look at the various organs controlling our red blood cell numbers, mainly the bone marrow, the spleen, and the lungs and see if we would find the cause there for the changes. 

HELEN: It sounds like your work is not over by any means there, both for people in outer space and people in bed here on earth.

GUY: That’s the problem. Discovery is bringing new knowledge but is raising many more questions. We’ll have certainly more work for us and for generations that follow us. 

HELEN: That’s probably a good time to ask you the questions that I often ask guests on Talking about Blood. Our listeners are seasoned professionals and physicians, perhaps hematologists, who have been doing this work for a long time. We also have listeners who are newer in their careers, perhaps in their residency, in medical school or just thinking about entering the health professions. And we also have people like me, who are just curious about blood. Based on your work and experience, what recommendations or tips do you have for any of us?

GUY: I think related to this work Helen, what comes to mind is to be careful at dogmas. The pathophysiology for space anemia had been worked out and for the past 25 years it was thought to be mechanism A. And then we wanted to test this further and there were road blocks. People said, “Why do you want to research this? We’ve known this forever, and this is the mechanism for the disease”. And some aspects of it told us that no I don’t think this has been worked out very well. And then we developed these studies with new hypotheses in mind. In fact, what we found is kind of a rewriting the pathophysiology of this problem which is space anemia. So be careful of dogmas, of ideas that have been accepted for a long time, but is not based on enough science or enough evidence. So don’t be afraid of retesting older hypotheses or older knowledge if there is a need for it. And be persistent over it because in this case it led to discovering a kind of treasure here and reorient the research that can have multiple applications that were not suspected initially. 

HELEN: I’m hearing that actually form a lot people doing innovative work about break the mold, ask those questions, whether you have been doing this work a long time, you’re at a starting phase, there’s so much to learn. You are exemplifying that in how you put those very disparate populations together to be giving us such new knowledge. So I would think that would apply to those doing this work for a long time and those beginning that work with all that inquisitiveness. What would you want those of us who just find this so interesting to take away? What would be that core message about astronauts and anemia? 

GUY: Astronauts have a lot of changes in their bodies and we are adapting very well. Astronauts can come back and recover fairly quickly. But now we’re exploring the next frontier. The really long travel. Being in space for a year, or two years. I believe we don’t know all about that so I think we should verify that our knowledge for short term flight will really apply to long term flights in order to bring the astronauts back safely. And that is specifically true for the problems with space anemia. We know up to 6 months but after that we don’t. We should prepare experiments to test for those as well. 

HELEN: I want to keep talking with you and learning from you. I know you’re well published. I’m hungry to keep learning more about this great topic. But let’s put a pause in this for now. Thank you so much for sharing these stories, especially for doing your research and for talking with us on Talking about Blood. 

GUY: Thank you for your interest on the topic and on our work Helen.

HELEN: As we just heard from Dr. Guy Trudel, it’s important to come up with new hypotheses. New ways of looking at the world, and at space to learn about blood. To learn more about The Blood Project and explore its many resources for professionals, trainees, and patients, go to https://www.thebloodproject.com. I invite you to also listen to my other podcast series and that’s about health communication at http://www.healthliteracyoutloud.com. Please help spread the word about this podcast series and The Blood Project. Thank you for listening. Until next time, I’m Helen Osborne.