SiNAPSA, ponedeljek, 6. julij 2020

eSiNAPSA

Spletna revija za znanstvenike, strokovnjake
in nevroznanstvene navdušence

Human physiology in space – interview with Tobias Weber, PhD (European Space Agency)

Nastja Tomat

During their career, astronauts encounter various health challenges. Exposure to microgravity*, radiation, confinement and other factors can impact their psychophysical well-being1. Living in space affects all physiological and anatomical systems of humans, including the nervous system. Microgravity is thought to prompt neurologic dysfunctions that occur after exposure to the space environment 2. Changes in gravity have an impact upon the cytoarchitecture of cells 3 which may negatively influence DNA replication, RNA transcription and protein transport2. Prolonged exposure to microgravity may lead to altered brain structure and function4. In addition, adverse effects of ionizing radiation on the brain are known from clinical literature.

It has been observed that cranial radiotherapy had a negative impact on cognitive processes, e.g. attention, memory, processing speed and executive functions5. However, terrestrial forms of radiation differ from space radiation in doses and quality. Such difference makes predicting the effects of space radiation on astronauts’ brain based on the terrestrial clinical practice difficult2. In spite of that, studies on rodent models have shown that simulated space radiation impacts neuronal morphology, causes structural and functional changes in some brain regions and leads to cognitive deficits6, 7, 8. Other studies have suggested that epigenetic factors play a role in neurological changes following exposure to space9. However, many pathophysiological mechanisms of impact of the space environment to neurologic systems are still unknown10.

Changes in neural and other systems are interconnected 10, 11; the well-being of a neural system depends on the well-being of other systems and organs and vice versa. Researchers have extensively investigated the effect of space exposure to different systems in the human body 12, 13 with the aim to establish countermeasures that would ensure homeostasis in the human body during space travel2.

We talked to Tobias Weber, PhD, a Science Operations engineer at the European Space Agency’s (ESA) European Astronaut Center (EAC) in Cologne, Germany. The EAC is the European center for astronaut training, operations, and space medicine. Its activities include astronaut selection and training, maintaining astronauts’ health, fitness, and proficiency, providing medical care and general support to astronauts, and research in the field of future space exploration14. The Space Medicine team, based at EAC, has a key role in establishing astronauts’ health during all stages of the mission1. Dr. Weber’s work focuses on the effects of micro- and partial gravity on human physiology and on the development and validation of in-flight exercise countermeasures and reconditioning tools. In the interview, we talked about his work at EAC, astronaut training, space research, and the effects that life in space has on the human body.

What does the Space Medicine team do at EAC?

One of the main goals for the European Space Agency is to manage a smooth transition from operations on the International Space Station (ISS) to deep space exploration, beginning with a cis-lunar station orbiting the Moon, the gateway. Amongst others, we will consider some medical records we obtained from 13 European astronauts at long-duration missions, which lasted 6 months. We collected medical data before and after the mission in order to identify how successful we were with maintaining cardiovascular physiology, bone mineral destiny, muscular strength, and other important features of human function. Another research field is optimization of in-flight exercise measures. Currently, astronauts exercise approximately 90 minutes per day. Some of them come back in relatively good shape, while others experience bone mineral loss, cardiovascular deconditioning, and muscle weakening and atrophy. For deep space explorations, we aim to at least maintain the same level of efficiency as currently on the ISS, so we try to learn from terrestrial exercise physiology to optimize the program for missions. Exercise during missions is more or less a tool to mimic the effects of gravity. Through evolution, most physiological systems were designed for 1G gravity. Through exercise, we create a lot of mechanic and metabolic stimuli needed to maintain ‘normal’ physiology, which is also why we do sports on Earth.

There are also other ways of maintaining the integrity of physiological systems: nutrition, pharmacology or wearables and suits that for instance compress the body to mimic the effects of gravity loading, such as the skinsuit.** In space the spine elongates which may lead to acute back pain in space and which may also cause problems when astronauts come back to Earth.

In future we may also use virtual reality to see if visualization of certain movements and coordinative tasks can help maintain and improve coordination. Another important field is rehabilitation of astronauts, especially considering the spine. Some studies show that astronauts are more prone to experience herniated discs and long-term problems with the spine upon returning on Earth. Our physiotherapists look for state-of-the-art rehabilitation strategies and search for ways of applying them to astronauts.

Another task is the exploration of medical challenges of deep space vehicles and habitats, especially what are life support requirements, what kind of hardware is needed, and what are differences in comparison to the ISS. How would confinement and isolation affect astronauts’ well-being and what can we do about it? In the past few decades, we have learned a lot about microgravity and how our bodies adapt to it, but this is not the case with hypogravity***. ESA’s and NASA’s next goal is landing people on the Moon, but we have to learn how the human body will adapt to it. If astronauts live in a lunar village, how will they function? Would lunar gravity, which is only one sixth of terrestrial gravity, be sufficient to maintain bone mineral content, muscle mass, and other physiological systems?

Have you collected any data on the influence of lunar gravity on the human body so far? What is the possibility of humans living on the Moon and remain healthy?

One way to study the acute effects of lunar gravity is via so-called offloading systems — a suspension system that unloads the body of a certain proportion of its weight and then you can walk, run or jump like on the Moon. We can study biomechanics, measure forces and estimate if these forces will be enough to maintain the structure of bones and muscles.

Figure 1
Figure 1. Different offloading systems models. Adapted from “Human biomechanical and cardiopulmonary responses to partial gravity — a systematic review” by C. Richter, B. Braunstein, A. Winnard, M. Nasser and T. Weber, 2017, Frontiers in physiology, 8, p. 3. Copyright 2017 by Richter, Braunstein, Winnard, Nasser and Weber. CC BY.

In addition, we did some tests on a vertical treadmill to mimic the effects of lunar gravity. Participants were running ‘on the wall’ while suspended and pulled toward the treadmill. In one study, participants had to jump and we measured the reaction forces. We could show that simple jumping leads to reaction forces similar to walking and running in 1G. Considering that bones and muscles adapt to mechanical distress, it may be enough for astronauts to jump for around 10 minutes per day instead of doing heavy resistive exercise. But more research is needed to evaluate effectiveness and safety of hopping and jumping as a countermeasure in hypogravity.

Figure 2
Figure 2. The vertical treadmill. Adapted from “Hopping in hypogravity — a rationale for a plyometric exercise countermeasure in planetary exploration missions” by T. Weber, D. A. Green, J. Attias, W. Sies, A. Frechette, B. Braunstein and J. Rittweger, 2019, PLoS ONE, 14(2), p. 4. Copyright 2019 by Weber et al. CC BY.

Do you have any predictions on what would happen if somebody lived on the Moon for, say, 10 years and then come back to Earth?

The human body is incredibly adaptable to different conditions and environments. I assume we would adapt to lunar gravity perfectly. Bone mineral density would decrease, muscles and the cardiovascular system would get weaker. If there weren’t any countermeasures, I would assume astronauts would have severe health issues after returning to Earth, but they would probably perfectly function for the duration of their stay on the Moon in hypogravity. Of course, one of the biggest threats for long term deep space exploration missions is radiation. In deep space, astronauts will be outside of the Earth’s magnetosphere and outside of the atmosphere which protect us from harmful radiation here on Earth. Leaving Earth for prolonged periods during deep space explorations would expose astronauts to significantly higher doses of radiation which is still one of the biggest health risks requiring adequate mitigation strategies. That is why we and other space research teams are trying to identify potential candidate countermeasures. The cost of equipment (payload) has to be also taken into consideration. Each kilogram we would bring to the Moon is very expensive which makes jumping an attractive candidate countermeasure since it would not require any additional hardware, thus saving expensive upload mass.

Can you tell more about how studies about space-induced effects on the human body are conducted?

When researching and training for exploration missions, we need to learn from terrestrial analogues. One commonly used physiological analog is a tilted bed. If a person lies in a bed that is tilted head-down at a six-degree angle, they experience many physiological similarities with microgravity. This angle provokes a fluid shift to the upper body and many physiological reactions of the cardiovascular- and musculoskeletal systems are similar to those experienced by astronauts exposed to microgravity.

The Concordia station in Antarctica is very interesting in terms of psychological research. The crew stays there for a full year, including the Arctic winter, and they are well aware that they are completely isolated and autonomous. This is probably the best we can do to mimic psychological effects and group dynamics in a real confinement, similar to what a crew would experience on a long-term deep space exploration mission.

Regarding psychological effects of living in space, there is something called “Earth-out-of-view-effect”.

Yes, I think this comes from the Apollo era when they first flew by the Moon and they could see Earth and cover it with a thumb. I think something happens when you see how big the universe is and how small and fragile Earth is. This is also something that most astronauts report when they come back from the ISS. The key thing that they say is that we should be careful with the planet because it is so fragile, we just don’t get a real grasp on its fragility when we are walking on our planet’s surface. Astronauts have the privilege to see with their own eyes how fragile and small our planet is – an experience which is certainly overwhelming.

Is research in space oriented towards space-exploration (improving the chances of man living in space) or can it have more general applications? Can space science tell us something new about the human body and mind in general?

There are many projects that have a so-called terrestrial spin-off. There are clinical applications, for example intensive care. In some aspects, coma is physiologically similar to the state of the astronauts: muscles do not work, the cardiovascular system is on ‘sleep mode’, and other physiological systems are shut down. There is some potential for transfer of knowledge we gained from bed rest studies to clinical care on Earth.

Another topic is optimization of exercise. Research on making exercise more time efficient is also relevant for the general public on Earth. Knowledge on astronaut rehabilitation can also be applied to people who have been hospitalized for a long time.

Which systems are most compromised when living in space? Are there always only adverse effects?

The human body adapts perfectly to space and microgravity. If we did not have to go back to Earth, our body would probably function in microgravity until the end of life. Microgravity itself is not a problem, but re-exposure to gravity is. All physiological systems and functions are more or less affected — bones, muscles, the cardiovascular system, motor functions, coordination, proprioception, and vestibular functions. The astronauts’ musculoskeletal systems change in the same way than in people who are exposed to prolonged periods of bed rest — muscles weaken and the bone mineral density decreases because the body is saving energy. The heart gets smaller, perfusion of the muscles decreases, fibers in the muscles get thinner. “Use it or lose it” is the main principle. Orthostatic tolerance**** is also heavily affected after being in space for a long time. When astronauts come back to Earth, this is not so problematic because they are rescued from a capsule and there is a medical team present. On the other hand, if you are on a planetary mission, there is no one waiting there for you to rescue you from the capsule, you have to function on your own. A fainting astronaut could then be life and mission threatening.

How long do space-induced effects on the body last?

We do not know everything about that yet. Our goal is to ensure that after 6 months in space astronauts get back to normal. Research has shown that bone is very inert, so it takes a lot of time for us to lose it, but also to regain it. Some bed rest studies have shown that even after 2 years after getting up some bone characteristics are not back to normal. In contrast to that, muscles and the cardiovascular system are much quicker. You can feel this effect when you start running or weight-lifting; after a couple of times you can already feel you are getting better. Fluid shifts go back to normal within a few hours or days.

How is research, partially conducted in space, different in comparison with research on Earth?

The main problem with research in space is the sample size. In big clinical studies on Earth, there are hundreds or thousands of people and it is easier to reach statistical significance and to draw conclusions on the general public. In contrast to that, we only had 13 European long duration missions in the past decade. Every mission and every astronaut are different. There is a high inter-individual variability so it takes a lot of time before we can draw conclusions about the whole population. Furthermore, everything we do in space is very complicated in terms of logistics — it takes a lot of time to prepare an experiment, train the crew, and ensure safety. Nonetheless ESA offers unique access to its platforms and it is possible for all kinds of research laboratories to submit proposals to ESA Life science if scientists want to conduct space research. ESA will evaluate and select proposals based on ‘best science’, thus ESA offers research platforms for various science disciplines.

Can you give me some examples?

In my field — exercise and physiology — there was a research project focused on strength testing before, during, and after the mission. They performed muscle biopsies and investigated how the muscle adapts after exposure to microgravity. Then there were some coordination experiments where scientists investigated how motor control changes when you are in microgravity. On Earth, you anticipate how much force you have to apply to raise a glass, for example. These anticipations have to be adjusted in microgravity.

What are the effects of space radiation on human body? How to prevent the adverse effects?

When you are exposed to a heavy dose of ionizing radiation, it may destroy your cells which can lead to direct tissue damage and a quick death — this would be considered a primary radiation damage having a deterministic effect. More subtle effects of long-term exposure to radiation can be compared to the events in Chernobyl, e.g. having a higher risk of cancer, through damages at the level of the DNA – this would be considered secondary radiation damage having a stochastic nature. Radiation is probably the most important topic to address when we think about deep space exploration. In that case, we are away from the protective layer of our atmosphere and Earth’s magnetic field and therefore completely exposed to cosmic galactic rays. Our expert groups are investigating the options of shielding from radiation in the vehicle, on the station or with suits.

How do you conduct an experiment in space? Astronauts are not experts in all fields, so I assume you train them to a certain extent so they can collect data and then you analyze it on Earth?

It depends on the nature of the experiment. Astronauts have their own specialization, but they have to conduct experiments in various fields. Before going on a mission, they have very intense training where they learn certain procedures and the whole experiment by heart. If you are a researcher and you want to do research on ISS, you can send a research proposal to ESA. Researchers that are selected are then guided by an astronaut trainer who works at ESA to make the experiment compatible with space-specific constraints.

We talked about terrestrial analogues and simulation studies. Do you use any other methods, e.g. in vitro studies or neurocomputational models?

In the field of space physiology, the most relevant simulations are parabolic flights which are very similar to being in space, but they only last for about 20-25 seconds. There are confinements like Concordia station, bed rest studies and dry immersion studies during which you float in a water tank. Drop towers enable us to experience very short periods of microgravity. On a cellular level, you can imitate the conditions when gravity is gone or it is constantly changing. You rotate cells very gently and study the influence of the rotation and the constantly changing gravity vector. Then there is unilateral limb suspension, which means we unload one leg of its weight and study its adaptation to the conditions when gravity impacts are absent.

Can you tell me more about astronaut selection and training?

The latest 6 astronauts were selected in 2009 and they had to go through a lot of medical and psychological tests. The astronauts have to be healthy, but they do not need to be super fit. The fitness level is slightly above average, but we are not looking for super-athletes. Decision-making and group behavior are very important features.

They have basic training for 2 years where they learn about Soyuz, ISS, they have survival training and they learn Russian. Mission-specific training follows which depends on the program and the experiments they have to conduct on ISS. Every astronaut has to also train for extravehicular activities. The training differs a bit depending on one’s role in the team. There is a lot of training for emergency scenarios.

What are the main challenges and goals in the current and future research in physiology or rehabilitation of astronauts?

How to ensure that astronauts stay healthy during their missions and after they return to Earth. The main challenge of deep space exploration will be how to overcome long-term exposure effects to radiation. If humans really decide to go to Mars, various things will need to be addressed. There will be long time confinement and different, delayed communication with Earth, thus crew autonomy and robust systems will be significantly more important than currently on the ISS.

Glossary
*: “A condition in space in which only minuscule forces are experienced; virtual absence of gravity” 15; a small fraction of 1G gravity. It can be experienced in an orbit, e.g. on ISS, or during parabolic flights16, 17.
**: A tight-fitting suit that clutches the body with a force similar to the one on Earth, designed to reduce back pain18.
***: Reduced gravity. It can be experienced, e.g. on the Moon and Mars12.
****: Orthostatic intolerance is “loss of consciousness, near fainting, or light-headedness occurring when a person stands up from a seated or resting position. It is caused by insufficient blood flow to the brain, typically brought on by inability to raise blood pressure during changes in posture.” 19.

    ___
  1. ESA (n.d.). Space medicine. https://www.esa.int/About_Us/EAC/Space_Medicine

  2. Jandial, R., Hoshide, R., Dawn Waters, J., & Limoli, C. L. (2018). Space–brain: the negative effects of space exposure on the central nervous system. Surgical Neurology International, 16(9), 9. 

  3. Gaboyard, S., Blanchard, M. P, Travo, C., Viso, M., Sans, A., & Lehouelleur, J. (2002). Weightlessness affects cytoskeleton of rat utricular hair cells during maturation in vitro. NeuroReport, 13(16), 2139–2142. 

  4. Roberts, D. R., Brown, T. R., Nietert, P. J., Eckert, M. A., Inglesby, D. C., Bloomberg, J. J., George, M. S., & Asemani, D. (2019). Prolonged microgravity affects human brain structure and function. American Journal of Neuroradiology, 40(11), 1878–1885. 

  5. Makale, M. T., McDonald, C.R., Hattangadi-Gluth J. A., & Kesari, S. (2017). Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours. Nature Reviews Neurology, 13(1), 52–64. 

  6. Haley, G. E., Yeiser, L., Olsen, R. H., Davis, M. J., Johnson, L. A., & Raber, J. (2013). Early effects of whole-body (56)Fe irradiation on hippocampal function in C57BL/6J mice. Radiation Research, 179(5), 590–596. 

  7. Lonart, G., Parris, B., Johnson, A. M., Miles, S., Sanford, L.D., Singletary, S. J., & Britten, R. A. (2012). Executive function in rats is impaired by low (20 cGy) doses of 1 GeV/u (56)Fe particles. Radiation Research, 178(4), 289–294. 

  8. Parihar, V. K., Pasha, J., Tran, K. K., Craver, B. M., Acharya, M. M, & Limoli, C. L. (2015). Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation. Brain Structure and Function, 220(2), 1161–1171. 

  9. Acharya M. M., Baddour, A. A., Kawashita, T., Allen, B. D., Syage, A. R., Nguyen, T. H., Yoon, N., Giedzinski, E., Yu, L., Parihar, V. K., & Baulch, J. E. (2017). Epigenetic determinants of space radiation-induced cognitive dysfunction. Scientific Reports, 7, 42885. 

  10. Wrona, D. (2006). Neural-immune interactions: an integrative view of the bidirectional relationship between the brain and immune systems. Journal of Neuroimmunology, 172(1-2), 38–58. 

  11. Mayer, E. A., Knight, R., Mazmanian, S.K., Cryan, J. F., & Tillisch, K. (2014). Gut microbes and the brain: paradigm shift in neuroscience. The Journal of Neuroscience, 34(46), 15490–15496. 

  12. Lacquaniti, F., Ivanenko, Y. P., Sylos-Labini, F., La Scaleia, V., La Scaleia, B., Willems, P. A., & Zago, M. (2017). Human locomotion in hypogravity: from basic research to clinical applications. Frontiers in Psysiology, 8, 893. 

  13. De Martino, E., Salomoni, S. E., Winnard, A., Mccarty, K., Lindsay, K., Riazati, S., Weber, T., Scott, J., Green, D.A., Hides, J., Debuse, D., Hodges, P. W., Van Dieen, J. H., & Caplan, N. (2020). Hypogravity reduces trunk admittance and lumbar muscle activation in response to external perturbations. Journal of Applied Physiology, 128(4), 1044–1055. 

  14. ESA (n.d.). EAC. http://www.esa.int/About_Us/EAC/About_us 

  15. Microgravity (n.d.). In Merriam-Webster.com dictionary.
    https://www.merriam-webster.com/dictionary/microgravity 

  16. ESA (n.d.). Microgravity and ISS. https://www.esa.int/Education/Orbit_Your_Thesis/Microgravity_and_ISS2 

  17. ESA (n.d.). Falling upwards: how to create microgravity. https://www.esa.int/Science_Exploration/Human_and_Robotic_Exploration/Research/Falling_upwards_how_to_create_microgravity 

  18. ESA (n.d.). Suit up for Skinsuit. https://www.esa.int/Science_Exploration/Human_and_Robotic_Exploration/Astronauts/Suit_up_for_Skinsuit 

  19. Orthostatic intolerance. (n.d.) V Medical Dictionary.
    https://medical-dictionary.thefreedictionary.com/orthostatic+intolerance

Nastja Tomat, mag. psih.
Oddelek za otroško hematologijo in onkologijo
Pediatrična klinika
Univerzitetni klinični center Ljubljana

Prejeto: 29.3.2020
Objavljeno: 27.5.2020