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International roadmap for artificial gravity research

International roadmap for artificial gravity research www.nature.com/npjmgrav REVIEW ARTICLE OPEN International roadmap for artificial gravity research Gilles Clément In this paper, we summarize the current and future research activities that will determine the requirements for implementing artificial gravity (AG) to mitigate the effects of long duration exposure to microgravity on board exploration class space vehicles. NASA and its international partners have developed an AG roadmap that contains a common set of goals, objectives, and milestones. This roadmap includes both ground-based and space-based projects, and involves human subjects as well as animal and cell models. It provides a framework that facilitates opportunities for collaboration using the full range of AG facilities that are available worldwide, and a forum for space physiologists, crew surgeons, astronauts, vehicle designers, and mission planners to review, evaluate, and discuss the issues of incorporating AG technologies into the vehicle design. npj Microgravity (2017) 3:29 ; doi:10.1038/s41526-017-0034-8 INTRODUCTION held at NASA Ames Research Center in February 2014. Roadmaps effectively translate abstract needs and concepts into concrete In the past, countermeasures to mitigate the physiological effects research activities that specify deliverables and the resources of deconditioning due to microgravity were delivered in a piece- necessary to make progress in a timely fashion. A coordinated AG meal fashion, e.g., fluid loading to counteract effects on the roadmap will provide information for the space vehicle designers, cardiovascular system, and exercise to mitigate muscle and bone mission planners, and managers regarding AG requirements for a loss. Although these countermeasures have greatly reduced manned mission to Mars. It will also provide a framework that health risks due to physiological deconditioning, they involve facilitates collaboration using the full range of available AG extensive crew time and a great deal of equipment. Since artificial facilities worldwide. To this end, NASA organized a workshop in gravity (AG) can reproduce Earth-like gravity, it could be used to February 2016 in Galveston, Texas, and invited representatives simultaneously mitigate the effects of microgravity on all the from NASA and from space agencies of France, Germany, Europe physiological systems. AG can be generated by continuously and Japan, as well as scientists who were actively involved in AG rotating the entire spacecraft, or part of the spacecraft, or by research. This paper is a review of the roadmap that was discussed means of an onboard short-radius centrifuge that the crewmem- during this workshop (Fig. 1). bers can use intermittently. The parameters that are most effective for mitigating physiological deconditioning in microgravity (rota- tion rate, radius of the centrifuge, and duration and frequency of ORGANIZATION OF THIS REVIEW AG exposure) need to be determined early in the exploration mission planning process to inform optimal decisions on the The overarching goal of AG research is to inform managers and vehicle capabilities. In addition, potential side effects of mission designers of specific requirements and the costs and intermittent or continuous rotation need to be understood and benefits of AG for any given mission scenario. AG can be adjusted addressed. These side effects, which include motion sickness, by varying the rotation rate of the spacecraft or centrifuge or disorientation, and falls, are caused by the Coriolis and cross- varying the distance of the habitat or crewmember relative to the coupled angular accelerations generated by head and body axis of rotation. These AG parameters impact vehicle design and motion in a rotating environment. Apathy, fatigue, and impair- operations. The questions that need answers are (a) what ment in cognitive performance have also been observed in evidence is there to support the requirement for AG during a 2,3 volunteers living in slowly rotating rooms; therefore, AG long-duration mission; (b) what design parameters should be research requires an integrative approach that includes physiolo- levied on the engineers; and (c) what prescriptions (gravity level, gical, behavioral, and human factor aspects. duration, frequency) should be recommended to the crewmem- Humans have had limited exposure to AG (see review in ref. 4) bers? In addition, recommendations must also be provided and no AG capability exists for humans on board the International regarding additional, complementary countermeasures that will Space Station (ISS). A complete research program is warranted to ensure the health and performance of crewmembers who determine both the requirements and constraints of intermittent participate in long-duration missions. These questions must be and continuous rotation of humans in space before deciding answered and recommendations must be provided before the whether AG should be implemented during a Mars mission. Until design of the spacecraft and mission is completed. recently, however, no coordinated research plan existed. The The international roadmap for AG research uses the same development of an international roadmap for AG research was management architecture as other projects in NASA’s Human recommended during a workshop on “Research and Operational Research Program. The architecture is based on (a) evidence that Considerations for Artificial Gravity Countermeasures” what was forms the basis of the existence of a risk to the human health, (b) KBRwyle, 2400 NASA Parkway, Houston, TX 77030, USA Correspondence: Gilles Clément (gilles.r.clement@nasa.gov) Received: 10 July 2017 Revised: 2 November 2017 Accepted: 3 November 2017 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA Artificial gravity research G Clément Fig. 1 International AG roadmap. The international AG roadmap lists the research activities (tasks) that address each of the five identified knowledge gaps. Research projects are ground-based (Earth, Analogs) or space-based (ISS, DSH, HTV-X). Projects are planned on board the ISS up to 2024 and other vehicles/habitats thereafter. CCA cross-coupled angular accelerations, EMCS European Multi Cultivation System, HUT head up tilt, HDT head down tilt, ICP intracranial pressure, LRC large radius centrifuge, MHU Mouse Habitat Unit, RCF Rodent Centrifuge Facility, SRC short-radius centrifuge, SRR slow rotating room, RPM random positioning machine, VIIP visual Impairment due to Intracranial Pressure gaps in current knowledge on how to characterize or mitigate the gravity levels, including fractional gravity such as on the Moon risk, and (c) tasks that produce the deliverables needed to close and Mars, and hypergravity. the gaps and reduce the risk. AG is considered a countermeasure that might include some intrinsic risk. Five gaps in our knowledge Studies in cell and animal models of how to implement AG in a space vehicle were identified: the Several investigators have proposed using the random positioning minimum AG level (Gap 1) and duration (Gap 2) required to machine (RPM) to study the effects of a range of gravity levels on mitigate the effects of microgravity; the potential effects of Mars 8–12 cell cultures. A RPM rotates biological samples along two gravity (Gap 3); the health consequences of Coriolis, cross-coupled independent axes; this changes the orientation and eliminates the acceleration, and gravity gradient (Gap 4); and whether the AG effect of gravity on the samples. Theoretically, two methods can prescription determined during ground-based studies in humans be used to simulate a range of partial gravity levels using the RPM: will be effective, acceptable, and safe for the crew in space (Gap rotating for longer or faster in one specific direction than for other 5). directions, or stopping the rotation for short periods when the gravity vector is pointing downwards. However, each of these methods seems to give different results. Also, it is not possible to GAP 1—AG LEVEL use the RPM in space. Without a direct comparison between We must understand how gravity affects fundamental physiolo- ground and space data, it is difficult to conclude whether gical processes before we can understand physiological adapta- biological reactions and organismic responses are caused by the tion during spaceflight and develop the most efficient conditions of simulated partial gravity or by any of the possible countermeasures. The first step is to define the relationship 13 side effects of the simulation technique. between gravitational dose and physiological response by The results of hypergravity studies on Earth can potentially shed assessing gravity levels ranging from 0 to 1 g. The second step some light on the effects of partial gravity in space because data is to identify the range of gravity level in which physiological demonstrate a remarkable continuum of response across the 14,15 response is the closest to normal, i.e., response to Earth gravity. hypogravity and hypergravity environments. For example, This analysis will determine the operating range of AG levels that centrifugation on Earth can be used to study the re-adaptation is most likely to be effective as a countermeasure. Although thresholds for the level and duration of centrifugal force (Fig. 2). In gravitational dose–response curves have been obtained for some these protocols, samples are exposed to hypergravity (e.g., 2 g) for biochemical systems in animals, these dose–responses are several weeks; centrifugation is stopped, and after various unknown for most human physiological systems. durations it is re-instated at different gravity levels. The minimum It is important to note that, in addition to the aims outlined duration and level of centrifugal force required to prevent re- above, these studies will document and improve our under- adaptation of various physiological responses to 1 g can be standing of the mechanisms of adaptation to chronically altered extrapolated to partial gravity using this method. npj Microgravity (2017) 29 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA 1234567890 Artificial gravity research G Clément Research using mice will also provide information indicating whether the partial gravity of the Moon or Mars sufficiently protects against the physiological changes that occur in 0 g, or whether astronauts will require additional countermeasures while on these planets. Studies in humans The AG roadmap outlines several approaches for studying gravity in human subjects. Parabolic flight will be used to characterize the relationship between gravitational dose and acute responses of the cardiovascular, cerebrovascular, ocular, muscular, and sensor- imotor systems. Previous parabolic flight studies were performed in the U.S., Canada, and Europe during short, repeated exposures to 0.16 and 0.38 g. ESA and its partners from the International Life Science Working Group are coordinating a partial gravity parabolic flight campaign in spring 2018. During this campaign an integrated study of a single test subject during several flights and using several experimental protocols will measure the responses of multiple systems at 0.25, 0.5, and 0.75 g. The effect of graded head-out water immersion will be Fig. 2 Design of ground-based experiments for investigating the investigated using subjects seated in an upright posture while threshold in centrifugation force level and duration. Animals are they are immersed up to the hip, heart, or neck. The hydrostatic exposed to continuous rotation at 2 g for several weeks (Adapta- water pressure on the body counteracts the intravascular tion). Centrifugation stops and re-adaptation of the physiological hydrostatic pressure gradients, simulating what is expected to responses to Earth gravity is then compared for various intermittent 23,24 occur in Martian gravity, lunar gravity, or microgravity. periods (1 h daily, 0.5 h daily) or intervals. Once the minimum Partial gravity will be simulated by placing subjects supine with duration of centrifugation force preventing re-adaptation to 1 g has their heads tilted upward 11.5° to 30° from horizontal at been identified, other animals are submitted to various levels of increments of ~6°, thus simulating gravity at increments of 0.1 g centrifugation force (1.8–1.2 g) to determine the minimum level that from 0.2 g–0.5 g along Gz axis the subject’s body. Subjects will prevents re-adaptation to 1 g. Red curves show no retention of adaptation; blue curves show retention of adaptation. (Adapted sleep in the horizontal position. Five days of bed rest in a head from ref. 16) down tilt induces orthostatic intolerance, endocrine response changes, and changes in muscle and bone markers, similar to 25–27 Centrifuges that are available on the ISS for studying the effects those in actual spaceflight. Bed rest of more than 5 days will of partial gravity on biological processes in plants, cells, and be studied to determine effects on sensorimotor function. animals include European Space Agency's (ESA) European Suspension techniques can be used to simulate partial gravity Modular Cultivation System (EMCS), Kubik, and Biolab, and JAXA’s on subjects while they perform locomotion studies and training Mouse Habitat Unit. EMCS is dedicated to experiments on plants, exercises. Overhead suspension systems typically use cables, including studies of gravity threshold on early development and springs, and air bearing rails to partially or fully unload the growth, and can provide AG levels as low as 0.001 g. The first subject’s weight. NASA’s partial gravity simulator, also known as studies on the effects of fractional gravity on board the ISS were POGO, is used to train astronauts and evaluate their ability to performed on plants, and the results showed that gravity sensing perform tasks in simulated partial gravity and microgravity. 17,18 was saturated between 0.1 g and 0.3 g. Kubik is a small Massachusetts Institute of Technology’s partial gravity simulator, incubator in which small containers of biological samples can be known as Moonwalker, also uses a spring-offset system to study exposed to AG levels from 0.2 g to 2 g in 0.1 g increments. Biolab body movements in simulated partial gravity as low as 0.05 g. The supports biological research on small plants, small invertebrates, body can be suspended for as long as necessary using these microorganisms, animal cells, and tissue cultures. It includes an systems, but the subject’s degree of freedom is limited. incubator equipped with centrifuges that can generate AG levels Lower body positive pressure treadmills can be used to study from 0.01 to 2 g. muscle activation and gait patterns during body weight unload- Animal models of simulated microgravity, such as tail suspen- ing. An inflated air chamber around the lower body lifts the sion in rats, have yielded important information on how the subject upwards at the hips, effectively reducing gravitational cardiovascular, neuromuscular, and neuroendocrine systems forces at the feet, and reducing the apparent weight of the body adapt to microgravity. The rat is preferred for rodent studies up to 80%. because rats have a larger mass than mice, making them more Ballasted partial gravity systems have been used to study sensitive to the effects of partial gravity. However, the rodent human operational activities in an underwater environment. The centrifuge on the ISS can only accommodate mice. The centrifuge subject wears a body harness with attached weights that can be in the JAXA Mouse Habitat Unit can spin six cages, each adjusted to provide the correct buoyancy. This type of simulation containing an individual mouse, at a distance of 15 cm from the is best suited for quasi-stationary studies (such as load lifting, axis of rotation, generating AG levels ranging from 0.1 to 4 g for ingress/egress) that minimize the effect of water drag on the up to 6 months. Studies have shown that the mouse is a subject’s movement. However, recent studies using a ballasting valuable model for studying musculoskeletal and cardiovascular system and an underwater treadmill have provided valuable 21 31 changes during microgravity. Also, because the mouse genome information on the dynamics of human gaits in partial gravity. has been extensively studied, physiological mechanisms can be Computational models can predict how physiological response examined on a gene-specific basis. In-flight centrifugation of mice might adapt to different gravity levels and will provide data that will provide valuable data on how mammalian health and are unavailable from experimental-based analog studies. Compu- behavior is affected by partial gravity. Research will focus on tational modeling can also simulate the effect of long duration bone loss, muscle atrophy, changes in intracranial pressure, exposures to partial gravity that might be impossible or too costly vascular flow, aerobic capacity, immunity, and inner ear function. to investigate in analogs. Additionally, models will be used for Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2017) 29 Artificial gravity research G Clément hypothesis testing and parametric studies to help refine the activity, exercise capacity, and postural stability after bed rest. experimental protocols for ground or flight studies. The NASA However, centrifugation did not prevent immune system defi- Digital Astronaut Project is currently working with bone specialists ciency, and the effects on bone loss were inconclusive, to establish models of bone loss due to skeletal unloading, models presumably because of the limited duration of bed rest. In of renal stone formation, and changes in heart shape and stress addition, with the exception of two very short-duration (4–5 days) distribution in microgravity. Once validated using spaceflight studies, the effects of multiple daily centrifugation sessions vs. a and bed rest data, these models will be used for predicting single bout of centrifugation have not been systematically studied changes in these physiological systems during partial gravity. in bed rest subjects. These studies suggest that repetitive, short- duration centrifugation sessions are more effective in mitigating 25 37 orthostatic intolerance, neurovestibular symptoms, and neu- GAP 2—MARS GRAVITY LEVEL roendocrine alterations than longer sessions. The studies outlined in gap 2 of the AG roadmap will quantify the In an upcoming study, 24 subjects will participate in a 60-day effects of Martian gravity (0.38 g) using centrifugation of cell bed rest study at the:envihab facility in Germany. Subjects will be cultures and animals on board the ISS. Recent studies of mice divided into three groups: one group of subjects will be exposed what were exposed to partial weight-bearing suspension for to bed rest alone; a second group will be exposed to 1 Gz at the 21 days have shown that Martian gravity, as simulated on Earth, is center of mass (about 2 Gz at the feet) for a continuous period of not sufficient to protect against the bone loss observed in 30 min per day (i.e., half of the current duration of physical 33,34 microgravity, but it does mitigate reduction in soleus mass. exercise on board the ISS); a third group will be exposed to six The JAXA ISS mice centrifuge will be used to investigate if the bouts a day of the same centrifugation level for five minutes each same effects are seen during simulated Martian gravity in orbit, session. Musculoskeletal deterioration, cerebral and cardiovascular and these studies will help determine whether astronauts will changes, neurocognitive performance, and brain plasticity will be require countermeasures to mitigate muscle and bone loss while compared across these three groups of subjects before, during, they are on the Martian surface. and after the bed rest. The effects of Martian gravity on the human sensorimotor, Dry immersion causes the same physiological changes as head- cardiovascular, musculoskeletal, and immune systems, as well as down bed rest, but changes occur after a relatively shorter effects on behavior, general health and performance, are duration of exposure. The effectiveness of intermittent Gz unknown. The only data available have been obtained during centrifugation using a short-radius centrifuge has been previously short periods in parabolic flight. The plan is to use suspension investigated in volunteers during dry immersion studies lasting 38,39 systems (body inclination, suspension with springs or counter- 3–28 days. The duration of centrifugation ranged from 40–90 weight, lower body positive pressure) to assess how simulated min per day, but only for a limited number of days. Russian short-duration (e.g., minutes) exposure to Martian gravity affects investigators are currently performing dry immersion studies functional performance. combined with daily intermittent centrifugation sessions. After they return from 6 months in space, ISS crewmembers will It can be argued that the ‘ideal’ AG level for humans might not be exposed to head-up tilt (HUT) to investigate physiological be continuous 1 g, but gravity levels that are contingent on the adaption from 0 g to Martian gravity. Immediately after landing duration and the amount of acceleration generated during and a few days later, ISS crewmembers will be placed in a sitting walking in 1 g; therefore, a combination of both centrifugation or standing 22.3° HUT position. In this HUT position, the and exercise might be a preferable countermeasure for the effects gravitational acceleration component along the long axis of the of microgravity. Studies are planned to address the biomechanics body is 0.38 g, which is equivalent to Martian gravity. We need to and constraints of performing acute exercise during rotation on a 40,41 know whether crewmembers’ sensorimotor and cardiovascular short-radius centrifuge. When adequate training protocols are systems will function adequately in the early post-landing phase established, bed rest studies will determine the effectiveness of on Mars and how long will it take for them to gain full AG exercises to counteract immobilization-induced decondition- functionality. Standard protocols currently used for assessing the ing. ESA is planning two more bed rest studies to compare the recovery of physiological functions after spaceflight will be mitigation effects of exercise regimes that will be performed performed and the results will be compared with the database outside the centrifuge and during centrifugation. ESA’s long-term of responses to these protocols during normal recovery. plan also includes bed rest studies using intermittent lunar and Martian gravity (subjects in HUT at 9.5° or 22.3°, respectively) for a duration that is similar to the duration of planned planetary GAP 3—AG DURATION surface activities (HDT at −6° the rest of the time). Another issue Because NASA is considering AG to counteract the effects of that must be addressed is the optimal time of day when microgravity in humans, and this includes potentially rotating intermittent centrifugation is applied because animal studies either the entire spacecraft or a device within a spacecraft, we have shown that exposure to altered gravity levels changed must determine early in the vehicle design process what homeostatic parameters and circadian rhythms. centrifugation force levels and rotation rates humans can adapt to. It is particularly important to determine as soon as possible GAP 4—HEALTH EFFECTS OF AG whether there are any obvious showstoppers. Studies in the 1960s using slowly rotating rooms and large-radius centrifuges have In previous centrifugation studies, the subjects’ heads were provided theoretical limits for the rotation rates and radii to which immobilized and the effects of cross-coupled angular and Coriolis humans can adapt. These limits are generally assumed to be accelerations during head and limb movements were not correct, but they must be validated by experimental evidence. investigated. In addition, limited data are available on how gravity Recent work suggests that a human’s ability to adapt to rotating gradient during short-radius centrifugation affects physiological environments might be less limited than these earlier studies had functions, and the exact etiology of anatomical ocular changes anticipated. and visual functional changes observed during and after space- Short-radius centrifugation has been used during 5–28 day bed flight is unknown at present. Short-radius centrifugation that rest studies to generate 1–2 g at the heart along the subjects’ generates Gz centrifugal force from head to foot might potentially longitudinal body axis (Gz) for periods ranging from 1–2 h per day. mitigate this spaceflight associated neuro-ocular syndrome (SANS) Intermittent centrifugation has been shown to attenuate ortho- by counteracting the headward fluid shift, reducing vascular and static intolerance, and reduce alterations in parasympathetic lymphatic congestion, and allowing outflow of cerebrospinal fluid. npj Microgravity (2017) 29 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA Artificial gravity research G Clément A greater number of behavioral and physiological responses than those measured in the earlier slow rotating room studies need to be investigated. These responses include but are not limited to the evaluation of changes in the sensorimotor, cardiovascular, and musculoskeletal system; behavior, health and performance assessment; and eye and vision changes. In addition, we need to evaluate the consequences of long-duration exposure to rotating environment on cognition, functional performance, exercise, material handling, interaction with other devices and control interfaces, simulated extra-vehicular activity, and selected operational task performance. GAP 5—VALIDATION STUDIES We do not know whether the AG prescription determined during ground-based studies will be effective, acceptable, and safe for Fig. 3 Design of an experiment using a large radius centrifuge to the crew in space. Although ground-based studies have the investigate the effects of gravity gradient. Top panel: centrifuge potential for determining a sound AG prescription (including AG drawing (courtesy of NASA). Middle and lower panels: comparison level and exposure duration/frequency), validation can only be between the amplitude of the +Gz centrifugal forces generated at performed in space. Given the time constraints of this project, it is the inner ear, center of mass, and feet in a supine subject placed most likely that a full validation using an ISS-based human rated close (r = 2.9 m) and far (r = 8.8 m) from the axis of rotation. ω: centrifuge won’t be feasible. rotation rate. The formula for calculating the gravity gradient across Adaptation to a rotating environment is different on Earth than the subject’s long body axis is shown for both conditions in space because gravity is perpendicular to the plane of rotation of the slow rotating room on Earth, whereas the centripetal Objects in a rotating environment have a different ‘weight’, acceleration vector is in the plane of rotation in space. In depending on their distance from the center of rotation. This microgravity, the cross-coupled effect of a particular head gravity gradient makes it difficult to move limbs and change body movement with respect to the body is different for each direction positions in a rotating room. The gravity gradient is also the person faces. This effect could confound adaptation to the responsible for different AG levels at the head, heart, and feet in rotating environment in space and re-adaption to normal supine subjects who are on a short-radius centrifuge. These effects conditions after return from space. A large, very slow 1 g will be assessed by comparing the physiological responses and centrifuge where a subject can walk 45° relative to the plane of the effects of handling objects as the radius of centrifugation is rotation will approximate the in-plane condition in space and help increased. In a long-radius centrifuge the subject can be placed at determine if adaptation is different. Alternatively, an aircraft that various distances from the axis of rotation as shown in Fig. 3. produces sustained coordinated 1 g level bank and turn can be This ground-based effort is required to evaluate the effects of used to simulate in-plane conditions. Two or three-hour exposure AG levels on ocular anatomy and function, head and neck vascular to these conditions may be sufficient to evaluate adaptation and subsequent recovery problems. parameters, and intracranial pressure. A long-radius centrifuge is required in which subjects are exposed to Gz with a small gravity The rodent centrifugation studies on board the ISS mentioned gradient. Human tolerance to + Gz is about 60 min at 4 g. This above will provide opportunities to compare the effectiveness of project will determine level of the gravity at the head that is the AG prescription in the ground-based and space conditions. sufficient to cause caudal drainage. The proposed project can also The rodents will be exposed to centrifugation for 90 days to potentially study the effects of centrifugation on terrestrial investigate the long-term effects of AG. Tests will be repeated populations with elevated intracranial pressure and vision issues during several times to fine-tune the AG prescription in orbit and of unknown etiology e.g., idiopathic intracranial hypertension or evaluate inter-individual differences. pseudo tumor cerebri, which share some of the signs and For humans, a simple, lightweight onboard centrifuge could be symptoms of SANS. used to assess impacts of vibration level, motion sickness, or crew Slowly rotating rooms have been designed to study human time during centrifugation inside a space vehicle. JAXA is behavioral and physiological responses to rotating environments, considering implementing a lightweight, human-powered short- and studies focus on the effects of rotation rate and the resulting radius centrifuge inside its HTV-X transfer vehicle to be used as a spatial disorientation generated by Coriolis and cross-coupled test bed when the vehicle is docked with the ISS. The objectives of accelerations during head or body movements. A series of this engineering demonstration will be to assess the acceleration 2,3 investigations were performed in Pensacola in the 1960s. After loads, g jitters, and the airflow, and to identify potential hazard 12 days at 10 rpm, most subjects had not adapted completely and and safety issues. experienced apathy, slower reaction times, and lack of motivation. The Engineering Division at NASA Johnson Space Center is Progressively increasing the speed of rotation helped the subjects currently working on concepts for a 5-m radius human centrifuge to adapt quicker. The various rotation rates (both incremental inside the Deep Space Habitat (DSH) that will be compatible with and discrete), and training techniques for adapting to the rotating NASA’s new Space Launch System. The first steps will be to environment must be tested, and must include more physiological perform studies using a ground model of the DSH centrifuge endpoints than in the earlier studies. Precise measures of the (based on the requirements defined above to validate the AG subjects’ body movements were not obtained during the earlier prescription: AG level, duration, frequency, etc.) as recommended slow rotating room studies. In fact, most subjects did not perform by the outcomes of Gaps 1, 2, 3, and 4. The ground-based AG the prescribed tasks (presumably to avoid motion sickness) and prescription would then be validated using the DSH centrifuge in remained inactive. Therefore, it is important to study how space. The main objective is to get a quick feedback on whether subjects walk, move, manipulate objects, and how they interact the AG dose determined from ground-based studies (and fine- with other devices and control interfaces in slowly rotating rooms tuned based on the results of the comparison between animals —tasks that are required to efficiently work in a rotating ground-based and flight studies) is effective. This flight project will environment. also investigate a number of factors associated with crew Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2017) 29 Artificial gravity research G Clément compliance, crew safety, and operational issues during cis-lunar 3. Graybiel, A. et al. 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Hyper- gravity facilities in the ESA ground-based facility program—current research anticipate the effort needed to implement AG in manned space activities and future tasks. Microgravity Sci. Technol. 28, 205–214 (2015). mission within budget and on time. 20. Morita, H. et al. Feasibility of a short-arm centrifuge for mouse hypergravity experiments. PLoS One 10, e0133981 (2015). 21. Powers, J. & Bernstein, D. The mouse as a model of cardiovascular adaptations to ACKNOWLEDGEMENTS microgravity. J. Appl. Physiol. 97, 1686–1692 (2004). The author is grateful to Mark Shelhamer, Peter Norsk, Yael Barr, and Kerry George for 22. Pletser, V. et al. The first joint European partial-g parabolic flight campaign at their inputs, and Marilyn Sylvester and Stephanne Ploeger for their logistic support. Moon and Mars gravity Levels for science and exploration. Microgravity Sci. This review is a product of the International Roadmap for Artificial Gravity Research Technol. 24, 383–395 (2012). Workshop, which was supported by NASA’s Human Research Program. 23. Navasiolava, N. M. et al. Long-term dry immersion: review and prospects. Eur. J. Appl. Physiol. 11, 1235–1260 (2011). 24. Norsk, P. Blood pressure regulation IV: adaptive responses to weightlessness. Eur. AUTHOR CONTRIBUTIONS J. Appl. Physiol. 114, 481–497 (2014). The author participated in the acquisition, analysis and interpretation of the data, and 25. Linnarsson, D. et al. Effects of an artificial gravity countermeasure on orthostatic wrote the manuscript. tolerance, blood pressure and aerobic power after short-term bed rest (BR-AG1). J. Appl. Physiol. 118,29–35 (2015). 26. Choukèr, A. et al. Psychoneuroendocrine alterations during 5 days of head-down ADDITIONAL INFORMATION tilt bed rest and artificial gravity interventions. Eur. J. Appl. Physiol. 113, 2057–2065 (2013). Competing interests: The author declares that he has no competing financial 27. Kos, O. et al. 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State of cardiovascular function after adaptation, distribution and reproduction in any medium or format, as long as you give immersion for three days and prophylactic spinning on a short-radius centrifuge. appropriate credit to the original author(s) and the source, provide a link to the Creative Human Physiol. 6, 150–154 (1980). Commons license, and indicate if changes were made. The images or other third party 39. Vil-Viliams, I. F. & Shulzhenko, E. B. Functional state of the cardiovascular system material in this article are included in the article’s Creative Commons license, unless system during combined exposure to 28-day immersion, rotation in a short indicated otherwise in a credit line to the material. If material is not included in the radius centrifuge, and physical loading on a bicycle ergometer. Kosm. Biol. article’s Creative Commons license and your intended use is not permitted by statutory Aviakosm. Med. 14,42–45 (1980). regulation or exceeds the permitted use, you will need to obtain permission directly 40. Iwase, S. Effectiveness of centrifuge-induced artificial gravity with ergometric from the copyright holder. To view a copy of this license, visit http://creativecommons. exercise as a countermeasure during simulated microgravity exposure in org/licenses/by/4.0/. humans. Acta Astronaut. 57,75–80 (2005). 41. Diaz-Artiles, A., Trigg, C. & Young, L. R. Combining ergometer exercise and arti- © The Author(s) 2017 ficial gravity in a compact-radius centrifuge. Acta Astronaut. 113,80–88 (2015). Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2017) 29 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png npj Microgravity Springer Journals

International roadmap for artificial gravity research

npj Microgravity , Volume 3 (1) – Nov 24, 2017

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Life Sciences; Life Sciences, general; Classical and Continuum Physics; Biotechnology; Immunology; Space Sciences (including Extraterrestrial Physics, Space Exploration and Astronautics) ; Applied Microbiology
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www.nature.com/npjmgrav REVIEW ARTICLE OPEN International roadmap for artificial gravity research Gilles Clément In this paper, we summarize the current and future research activities that will determine the requirements for implementing artificial gravity (AG) to mitigate the effects of long duration exposure to microgravity on board exploration class space vehicles. NASA and its international partners have developed an AG roadmap that contains a common set of goals, objectives, and milestones. This roadmap includes both ground-based and space-based projects, and involves human subjects as well as animal and cell models. It provides a framework that facilitates opportunities for collaboration using the full range of AG facilities that are available worldwide, and a forum for space physiologists, crew surgeons, astronauts, vehicle designers, and mission planners to review, evaluate, and discuss the issues of incorporating AG technologies into the vehicle design. npj Microgravity (2017) 3:29 ; doi:10.1038/s41526-017-0034-8 INTRODUCTION held at NASA Ames Research Center in February 2014. Roadmaps effectively translate abstract needs and concepts into concrete In the past, countermeasures to mitigate the physiological effects research activities that specify deliverables and the resources of deconditioning due to microgravity were delivered in a piece- necessary to make progress in a timely fashion. A coordinated AG meal fashion, e.g., fluid loading to counteract effects on the roadmap will provide information for the space vehicle designers, cardiovascular system, and exercise to mitigate muscle and bone mission planners, and managers regarding AG requirements for a loss. Although these countermeasures have greatly reduced manned mission to Mars. It will also provide a framework that health risks due to physiological deconditioning, they involve facilitates collaboration using the full range of available AG extensive crew time and a great deal of equipment. Since artificial facilities worldwide. To this end, NASA organized a workshop in gravity (AG) can reproduce Earth-like gravity, it could be used to February 2016 in Galveston, Texas, and invited representatives simultaneously mitigate the effects of microgravity on all the from NASA and from space agencies of France, Germany, Europe physiological systems. AG can be generated by continuously and Japan, as well as scientists who were actively involved in AG rotating the entire spacecraft, or part of the spacecraft, or by research. This paper is a review of the roadmap that was discussed means of an onboard short-radius centrifuge that the crewmem- during this workshop (Fig. 1). bers can use intermittently. The parameters that are most effective for mitigating physiological deconditioning in microgravity (rota- tion rate, radius of the centrifuge, and duration and frequency of ORGANIZATION OF THIS REVIEW AG exposure) need to be determined early in the exploration mission planning process to inform optimal decisions on the The overarching goal of AG research is to inform managers and vehicle capabilities. In addition, potential side effects of mission designers of specific requirements and the costs and intermittent or continuous rotation need to be understood and benefits of AG for any given mission scenario. AG can be adjusted addressed. These side effects, which include motion sickness, by varying the rotation rate of the spacecraft or centrifuge or disorientation, and falls, are caused by the Coriolis and cross- varying the distance of the habitat or crewmember relative to the coupled angular accelerations generated by head and body axis of rotation. These AG parameters impact vehicle design and motion in a rotating environment. Apathy, fatigue, and impair- operations. The questions that need answers are (a) what ment in cognitive performance have also been observed in evidence is there to support the requirement for AG during a 2,3 volunteers living in slowly rotating rooms; therefore, AG long-duration mission; (b) what design parameters should be research requires an integrative approach that includes physiolo- levied on the engineers; and (c) what prescriptions (gravity level, gical, behavioral, and human factor aspects. duration, frequency) should be recommended to the crewmem- Humans have had limited exposure to AG (see review in ref. 4) bers? In addition, recommendations must also be provided and no AG capability exists for humans on board the International regarding additional, complementary countermeasures that will Space Station (ISS). A complete research program is warranted to ensure the health and performance of crewmembers who determine both the requirements and constraints of intermittent participate in long-duration missions. These questions must be and continuous rotation of humans in space before deciding answered and recommendations must be provided before the whether AG should be implemented during a Mars mission. Until design of the spacecraft and mission is completed. recently, however, no coordinated research plan existed. The The international roadmap for AG research uses the same development of an international roadmap for AG research was management architecture as other projects in NASA’s Human recommended during a workshop on “Research and Operational Research Program. The architecture is based on (a) evidence that Considerations for Artificial Gravity Countermeasures” what was forms the basis of the existence of a risk to the human health, (b) KBRwyle, 2400 NASA Parkway, Houston, TX 77030, USA Correspondence: Gilles Clément (gilles.r.clement@nasa.gov) Received: 10 July 2017 Revised: 2 November 2017 Accepted: 3 November 2017 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA Artificial gravity research G Clément Fig. 1 International AG roadmap. The international AG roadmap lists the research activities (tasks) that address each of the five identified knowledge gaps. Research projects are ground-based (Earth, Analogs) or space-based (ISS, DSH, HTV-X). Projects are planned on board the ISS up to 2024 and other vehicles/habitats thereafter. CCA cross-coupled angular accelerations, EMCS European Multi Cultivation System, HUT head up tilt, HDT head down tilt, ICP intracranial pressure, LRC large radius centrifuge, MHU Mouse Habitat Unit, RCF Rodent Centrifuge Facility, SRC short-radius centrifuge, SRR slow rotating room, RPM random positioning machine, VIIP visual Impairment due to Intracranial Pressure gaps in current knowledge on how to characterize or mitigate the gravity levels, including fractional gravity such as on the Moon risk, and (c) tasks that produce the deliverables needed to close and Mars, and hypergravity. the gaps and reduce the risk. AG is considered a countermeasure that might include some intrinsic risk. Five gaps in our knowledge Studies in cell and animal models of how to implement AG in a space vehicle were identified: the Several investigators have proposed using the random positioning minimum AG level (Gap 1) and duration (Gap 2) required to machine (RPM) to study the effects of a range of gravity levels on mitigate the effects of microgravity; the potential effects of Mars 8–12 cell cultures. A RPM rotates biological samples along two gravity (Gap 3); the health consequences of Coriolis, cross-coupled independent axes; this changes the orientation and eliminates the acceleration, and gravity gradient (Gap 4); and whether the AG effect of gravity on the samples. Theoretically, two methods can prescription determined during ground-based studies in humans be used to simulate a range of partial gravity levels using the RPM: will be effective, acceptable, and safe for the crew in space (Gap rotating for longer or faster in one specific direction than for other 5). directions, or stopping the rotation for short periods when the gravity vector is pointing downwards. However, each of these methods seems to give different results. Also, it is not possible to GAP 1—AG LEVEL use the RPM in space. Without a direct comparison between We must understand how gravity affects fundamental physiolo- ground and space data, it is difficult to conclude whether gical processes before we can understand physiological adapta- biological reactions and organismic responses are caused by the tion during spaceflight and develop the most efficient conditions of simulated partial gravity or by any of the possible countermeasures. The first step is to define the relationship 13 side effects of the simulation technique. between gravitational dose and physiological response by The results of hypergravity studies on Earth can potentially shed assessing gravity levels ranging from 0 to 1 g. The second step some light on the effects of partial gravity in space because data is to identify the range of gravity level in which physiological demonstrate a remarkable continuum of response across the 14,15 response is the closest to normal, i.e., response to Earth gravity. hypogravity and hypergravity environments. For example, This analysis will determine the operating range of AG levels that centrifugation on Earth can be used to study the re-adaptation is most likely to be effective as a countermeasure. Although thresholds for the level and duration of centrifugal force (Fig. 2). In gravitational dose–response curves have been obtained for some these protocols, samples are exposed to hypergravity (e.g., 2 g) for biochemical systems in animals, these dose–responses are several weeks; centrifugation is stopped, and after various unknown for most human physiological systems. durations it is re-instated at different gravity levels. The minimum It is important to note that, in addition to the aims outlined duration and level of centrifugal force required to prevent re- above, these studies will document and improve our under- adaptation of various physiological responses to 1 g can be standing of the mechanisms of adaptation to chronically altered extrapolated to partial gravity using this method. npj Microgravity (2017) 29 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA 1234567890 Artificial gravity research G Clément Research using mice will also provide information indicating whether the partial gravity of the Moon or Mars sufficiently protects against the physiological changes that occur in 0 g, or whether astronauts will require additional countermeasures while on these planets. Studies in humans The AG roadmap outlines several approaches for studying gravity in human subjects. Parabolic flight will be used to characterize the relationship between gravitational dose and acute responses of the cardiovascular, cerebrovascular, ocular, muscular, and sensor- imotor systems. Previous parabolic flight studies were performed in the U.S., Canada, and Europe during short, repeated exposures to 0.16 and 0.38 g. ESA and its partners from the International Life Science Working Group are coordinating a partial gravity parabolic flight campaign in spring 2018. During this campaign an integrated study of a single test subject during several flights and using several experimental protocols will measure the responses of multiple systems at 0.25, 0.5, and 0.75 g. The effect of graded head-out water immersion will be Fig. 2 Design of ground-based experiments for investigating the investigated using subjects seated in an upright posture while threshold in centrifugation force level and duration. Animals are they are immersed up to the hip, heart, or neck. The hydrostatic exposed to continuous rotation at 2 g for several weeks (Adapta- water pressure on the body counteracts the intravascular tion). Centrifugation stops and re-adaptation of the physiological hydrostatic pressure gradients, simulating what is expected to responses to Earth gravity is then compared for various intermittent 23,24 occur in Martian gravity, lunar gravity, or microgravity. periods (1 h daily, 0.5 h daily) or intervals. Once the minimum Partial gravity will be simulated by placing subjects supine with duration of centrifugation force preventing re-adaptation to 1 g has their heads tilted upward 11.5° to 30° from horizontal at been identified, other animals are submitted to various levels of increments of ~6°, thus simulating gravity at increments of 0.1 g centrifugation force (1.8–1.2 g) to determine the minimum level that from 0.2 g–0.5 g along Gz axis the subject’s body. Subjects will prevents re-adaptation to 1 g. Red curves show no retention of adaptation; blue curves show retention of adaptation. (Adapted sleep in the horizontal position. Five days of bed rest in a head from ref. 16) down tilt induces orthostatic intolerance, endocrine response changes, and changes in muscle and bone markers, similar to 25–27 Centrifuges that are available on the ISS for studying the effects those in actual spaceflight. Bed rest of more than 5 days will of partial gravity on biological processes in plants, cells, and be studied to determine effects on sensorimotor function. animals include European Space Agency's (ESA) European Suspension techniques can be used to simulate partial gravity Modular Cultivation System (EMCS), Kubik, and Biolab, and JAXA’s on subjects while they perform locomotion studies and training Mouse Habitat Unit. EMCS is dedicated to experiments on plants, exercises. Overhead suspension systems typically use cables, including studies of gravity threshold on early development and springs, and air bearing rails to partially or fully unload the growth, and can provide AG levels as low as 0.001 g. The first subject’s weight. NASA’s partial gravity simulator, also known as studies on the effects of fractional gravity on board the ISS were POGO, is used to train astronauts and evaluate their ability to performed on plants, and the results showed that gravity sensing perform tasks in simulated partial gravity and microgravity. 17,18 was saturated between 0.1 g and 0.3 g. Kubik is a small Massachusetts Institute of Technology’s partial gravity simulator, incubator in which small containers of biological samples can be known as Moonwalker, also uses a spring-offset system to study exposed to AG levels from 0.2 g to 2 g in 0.1 g increments. Biolab body movements in simulated partial gravity as low as 0.05 g. The supports biological research on small plants, small invertebrates, body can be suspended for as long as necessary using these microorganisms, animal cells, and tissue cultures. It includes an systems, but the subject’s degree of freedom is limited. incubator equipped with centrifuges that can generate AG levels Lower body positive pressure treadmills can be used to study from 0.01 to 2 g. muscle activation and gait patterns during body weight unload- Animal models of simulated microgravity, such as tail suspen- ing. An inflated air chamber around the lower body lifts the sion in rats, have yielded important information on how the subject upwards at the hips, effectively reducing gravitational cardiovascular, neuromuscular, and neuroendocrine systems forces at the feet, and reducing the apparent weight of the body adapt to microgravity. The rat is preferred for rodent studies up to 80%. because rats have a larger mass than mice, making them more Ballasted partial gravity systems have been used to study sensitive to the effects of partial gravity. However, the rodent human operational activities in an underwater environment. The centrifuge on the ISS can only accommodate mice. The centrifuge subject wears a body harness with attached weights that can be in the JAXA Mouse Habitat Unit can spin six cages, each adjusted to provide the correct buoyancy. This type of simulation containing an individual mouse, at a distance of 15 cm from the is best suited for quasi-stationary studies (such as load lifting, axis of rotation, generating AG levels ranging from 0.1 to 4 g for ingress/egress) that minimize the effect of water drag on the up to 6 months. Studies have shown that the mouse is a subject’s movement. However, recent studies using a ballasting valuable model for studying musculoskeletal and cardiovascular system and an underwater treadmill have provided valuable 21 31 changes during microgravity. Also, because the mouse genome information on the dynamics of human gaits in partial gravity. has been extensively studied, physiological mechanisms can be Computational models can predict how physiological response examined on a gene-specific basis. In-flight centrifugation of mice might adapt to different gravity levels and will provide data that will provide valuable data on how mammalian health and are unavailable from experimental-based analog studies. Compu- behavior is affected by partial gravity. Research will focus on tational modeling can also simulate the effect of long duration bone loss, muscle atrophy, changes in intracranial pressure, exposures to partial gravity that might be impossible or too costly vascular flow, aerobic capacity, immunity, and inner ear function. to investigate in analogs. Additionally, models will be used for Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2017) 29 Artificial gravity research G Clément hypothesis testing and parametric studies to help refine the activity, exercise capacity, and postural stability after bed rest. experimental protocols for ground or flight studies. The NASA However, centrifugation did not prevent immune system defi- Digital Astronaut Project is currently working with bone specialists ciency, and the effects on bone loss were inconclusive, to establish models of bone loss due to skeletal unloading, models presumably because of the limited duration of bed rest. In of renal stone formation, and changes in heart shape and stress addition, with the exception of two very short-duration (4–5 days) distribution in microgravity. Once validated using spaceflight studies, the effects of multiple daily centrifugation sessions vs. a and bed rest data, these models will be used for predicting single bout of centrifugation have not been systematically studied changes in these physiological systems during partial gravity. in bed rest subjects. These studies suggest that repetitive, short- duration centrifugation sessions are more effective in mitigating 25 37 orthostatic intolerance, neurovestibular symptoms, and neu- GAP 2—MARS GRAVITY LEVEL roendocrine alterations than longer sessions. The studies outlined in gap 2 of the AG roadmap will quantify the In an upcoming study, 24 subjects will participate in a 60-day effects of Martian gravity (0.38 g) using centrifugation of cell bed rest study at the:envihab facility in Germany. Subjects will be cultures and animals on board the ISS. Recent studies of mice divided into three groups: one group of subjects will be exposed what were exposed to partial weight-bearing suspension for to bed rest alone; a second group will be exposed to 1 Gz at the 21 days have shown that Martian gravity, as simulated on Earth, is center of mass (about 2 Gz at the feet) for a continuous period of not sufficient to protect against the bone loss observed in 30 min per day (i.e., half of the current duration of physical 33,34 microgravity, but it does mitigate reduction in soleus mass. exercise on board the ISS); a third group will be exposed to six The JAXA ISS mice centrifuge will be used to investigate if the bouts a day of the same centrifugation level for five minutes each same effects are seen during simulated Martian gravity in orbit, session. Musculoskeletal deterioration, cerebral and cardiovascular and these studies will help determine whether astronauts will changes, neurocognitive performance, and brain plasticity will be require countermeasures to mitigate muscle and bone loss while compared across these three groups of subjects before, during, they are on the Martian surface. and after the bed rest. The effects of Martian gravity on the human sensorimotor, Dry immersion causes the same physiological changes as head- cardiovascular, musculoskeletal, and immune systems, as well as down bed rest, but changes occur after a relatively shorter effects on behavior, general health and performance, are duration of exposure. The effectiveness of intermittent Gz unknown. The only data available have been obtained during centrifugation using a short-radius centrifuge has been previously short periods in parabolic flight. The plan is to use suspension investigated in volunteers during dry immersion studies lasting 38,39 systems (body inclination, suspension with springs or counter- 3–28 days. The duration of centrifugation ranged from 40–90 weight, lower body positive pressure) to assess how simulated min per day, but only for a limited number of days. Russian short-duration (e.g., minutes) exposure to Martian gravity affects investigators are currently performing dry immersion studies functional performance. combined with daily intermittent centrifugation sessions. After they return from 6 months in space, ISS crewmembers will It can be argued that the ‘ideal’ AG level for humans might not be exposed to head-up tilt (HUT) to investigate physiological be continuous 1 g, but gravity levels that are contingent on the adaption from 0 g to Martian gravity. Immediately after landing duration and the amount of acceleration generated during and a few days later, ISS crewmembers will be placed in a sitting walking in 1 g; therefore, a combination of both centrifugation or standing 22.3° HUT position. In this HUT position, the and exercise might be a preferable countermeasure for the effects gravitational acceleration component along the long axis of the of microgravity. Studies are planned to address the biomechanics body is 0.38 g, which is equivalent to Martian gravity. We need to and constraints of performing acute exercise during rotation on a 40,41 know whether crewmembers’ sensorimotor and cardiovascular short-radius centrifuge. When adequate training protocols are systems will function adequately in the early post-landing phase established, bed rest studies will determine the effectiveness of on Mars and how long will it take for them to gain full AG exercises to counteract immobilization-induced decondition- functionality. Standard protocols currently used for assessing the ing. ESA is planning two more bed rest studies to compare the recovery of physiological functions after spaceflight will be mitigation effects of exercise regimes that will be performed performed and the results will be compared with the database outside the centrifuge and during centrifugation. ESA’s long-term of responses to these protocols during normal recovery. plan also includes bed rest studies using intermittent lunar and Martian gravity (subjects in HUT at 9.5° or 22.3°, respectively) for a duration that is similar to the duration of planned planetary GAP 3—AG DURATION surface activities (HDT at −6° the rest of the time). Another issue Because NASA is considering AG to counteract the effects of that must be addressed is the optimal time of day when microgravity in humans, and this includes potentially rotating intermittent centrifugation is applied because animal studies either the entire spacecraft or a device within a spacecraft, we have shown that exposure to altered gravity levels changed must determine early in the vehicle design process what homeostatic parameters and circadian rhythms. centrifugation force levels and rotation rates humans can adapt to. It is particularly important to determine as soon as possible GAP 4—HEALTH EFFECTS OF AG whether there are any obvious showstoppers. Studies in the 1960s using slowly rotating rooms and large-radius centrifuges have In previous centrifugation studies, the subjects’ heads were provided theoretical limits for the rotation rates and radii to which immobilized and the effects of cross-coupled angular and Coriolis humans can adapt. These limits are generally assumed to be accelerations during head and limb movements were not correct, but they must be validated by experimental evidence. investigated. In addition, limited data are available on how gravity Recent work suggests that a human’s ability to adapt to rotating gradient during short-radius centrifugation affects physiological environments might be less limited than these earlier studies had functions, and the exact etiology of anatomical ocular changes anticipated. and visual functional changes observed during and after space- Short-radius centrifugation has been used during 5–28 day bed flight is unknown at present. Short-radius centrifugation that rest studies to generate 1–2 g at the heart along the subjects’ generates Gz centrifugal force from head to foot might potentially longitudinal body axis (Gz) for periods ranging from 1–2 h per day. mitigate this spaceflight associated neuro-ocular syndrome (SANS) Intermittent centrifugation has been shown to attenuate ortho- by counteracting the headward fluid shift, reducing vascular and static intolerance, and reduce alterations in parasympathetic lymphatic congestion, and allowing outflow of cerebrospinal fluid. npj Microgravity (2017) 29 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA Artificial gravity research G Clément A greater number of behavioral and physiological responses than those measured in the earlier slow rotating room studies need to be investigated. These responses include but are not limited to the evaluation of changes in the sensorimotor, cardiovascular, and musculoskeletal system; behavior, health and performance assessment; and eye and vision changes. In addition, we need to evaluate the consequences of long-duration exposure to rotating environment on cognition, functional performance, exercise, material handling, interaction with other devices and control interfaces, simulated extra-vehicular activity, and selected operational task performance. GAP 5—VALIDATION STUDIES We do not know whether the AG prescription determined during ground-based studies will be effective, acceptable, and safe for Fig. 3 Design of an experiment using a large radius centrifuge to the crew in space. Although ground-based studies have the investigate the effects of gravity gradient. Top panel: centrifuge potential for determining a sound AG prescription (including AG drawing (courtesy of NASA). Middle and lower panels: comparison level and exposure duration/frequency), validation can only be between the amplitude of the +Gz centrifugal forces generated at performed in space. Given the time constraints of this project, it is the inner ear, center of mass, and feet in a supine subject placed most likely that a full validation using an ISS-based human rated close (r = 2.9 m) and far (r = 8.8 m) from the axis of rotation. ω: centrifuge won’t be feasible. rotation rate. The formula for calculating the gravity gradient across Adaptation to a rotating environment is different on Earth than the subject’s long body axis is shown for both conditions in space because gravity is perpendicular to the plane of rotation of the slow rotating room on Earth, whereas the centripetal Objects in a rotating environment have a different ‘weight’, acceleration vector is in the plane of rotation in space. In depending on their distance from the center of rotation. This microgravity, the cross-coupled effect of a particular head gravity gradient makes it difficult to move limbs and change body movement with respect to the body is different for each direction positions in a rotating room. The gravity gradient is also the person faces. This effect could confound adaptation to the responsible for different AG levels at the head, heart, and feet in rotating environment in space and re-adaption to normal supine subjects who are on a short-radius centrifuge. These effects conditions after return from space. A large, very slow 1 g will be assessed by comparing the physiological responses and centrifuge where a subject can walk 45° relative to the plane of the effects of handling objects as the radius of centrifugation is rotation will approximate the in-plane condition in space and help increased. In a long-radius centrifuge the subject can be placed at determine if adaptation is different. Alternatively, an aircraft that various distances from the axis of rotation as shown in Fig. 3. produces sustained coordinated 1 g level bank and turn can be This ground-based effort is required to evaluate the effects of used to simulate in-plane conditions. Two or three-hour exposure AG levels on ocular anatomy and function, head and neck vascular to these conditions may be sufficient to evaluate adaptation and subsequent recovery problems. parameters, and intracranial pressure. A long-radius centrifuge is required in which subjects are exposed to Gz with a small gravity The rodent centrifugation studies on board the ISS mentioned gradient. Human tolerance to + Gz is about 60 min at 4 g. This above will provide opportunities to compare the effectiveness of project will determine level of the gravity at the head that is the AG prescription in the ground-based and space conditions. sufficient to cause caudal drainage. The proposed project can also The rodents will be exposed to centrifugation for 90 days to potentially study the effects of centrifugation on terrestrial investigate the long-term effects of AG. Tests will be repeated populations with elevated intracranial pressure and vision issues during several times to fine-tune the AG prescription in orbit and of unknown etiology e.g., idiopathic intracranial hypertension or evaluate inter-individual differences. pseudo tumor cerebri, which share some of the signs and For humans, a simple, lightweight onboard centrifuge could be symptoms of SANS. used to assess impacts of vibration level, motion sickness, or crew Slowly rotating rooms have been designed to study human time during centrifugation inside a space vehicle. JAXA is behavioral and physiological responses to rotating environments, considering implementing a lightweight, human-powered short- and studies focus on the effects of rotation rate and the resulting radius centrifuge inside its HTV-X transfer vehicle to be used as a spatial disorientation generated by Coriolis and cross-coupled test bed when the vehicle is docked with the ISS. The objectives of accelerations during head or body movements. A series of this engineering demonstration will be to assess the acceleration 2,3 investigations were performed in Pensacola in the 1960s. After loads, g jitters, and the airflow, and to identify potential hazard 12 days at 10 rpm, most subjects had not adapted completely and and safety issues. experienced apathy, slower reaction times, and lack of motivation. The Engineering Division at NASA Johnson Space Center is Progressively increasing the speed of rotation helped the subjects currently working on concepts for a 5-m radius human centrifuge to adapt quicker. The various rotation rates (both incremental inside the Deep Space Habitat (DSH) that will be compatible with and discrete), and training techniques for adapting to the rotating NASA’s new Space Launch System. The first steps will be to environment must be tested, and must include more physiological perform studies using a ground model of the DSH centrifuge endpoints than in the earlier studies. Precise measures of the (based on the requirements defined above to validate the AG subjects’ body movements were not obtained during the earlier prescription: AG level, duration, frequency, etc.) as recommended slow rotating room studies. In fact, most subjects did not perform by the outcomes of Gaps 1, 2, 3, and 4. The ground-based AG the prescribed tasks (presumably to avoid motion sickness) and prescription would then be validated using the DSH centrifuge in remained inactive. Therefore, it is important to study how space. The main objective is to get a quick feedback on whether subjects walk, move, manipulate objects, and how they interact the AG dose determined from ground-based studies (and fine- with other devices and control interfaces in slowly rotating rooms tuned based on the results of the comparison between animals —tasks that are required to efficiently work in a rotating ground-based and flight studies) is effective. This flight project will environment. also investigate a number of factors associated with crew Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2017) 29 Artificial gravity research G Clément compliance, crew safety, and operational issues during cis-lunar 3. Graybiel, A. et al. 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