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Review of NASA’s Biomedical Research Program 10 Setting Priorities in Research The Strategy report (NRC, 1998) considered the question of overall priorities for NASA-supported research in the next decade, taking into account budgetary realities and the need for clearly focused programs. In the biomedical arena, the report recommended that highest priority be given to research aimed at understanding and ameliorating problems that may limit astronauts’ ability to survive and/or function during prolonged spaceflight. Such studies should include basic and applied research and ground-based investigations as well as flight experiments. It is clear that such problems must be identified and adequately solved or mitigated before long-term human spaceflight can be considered feasible. It was further recommended that NASA programs focus on aspects of research in which NASA has unique capabilities or those that are underemphasized by other agencies. Six issues in biomedical research were identified as the most important for ensuring astronaut health, safety, and performance during and after long-duration spaceflight. The committee recognized that until the research facilities of the ISS are completed and can be fully utilized, NASA-supported research will necessarily be directed largely to ground-based investigations designed to frame critical hypotheses that can later be tested in space. Thus, implementation of recommendations for research that requires long-duration flight experiments is necessarily delayed until such opportunities reopen, although interim availability of a dedicated Shuttle flight could provide significant advances in some of the designated areas. The following sections summarize the degree to which current programs focus on the six areas of research considered of highest priority. Details are presented in the disciplinary chapters. LOSS OF WEIGHT-BEARING BONE AND MUSCLE In the Strategy report, priority was given to five recommendations, of which two were directed primarily to ground-based research:
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Review of NASA’s Biomedical Research Program Studies that provide mechanistic insights into the development of effective countermeasures for preventing bone and muscle deterioration during and after spaceflight; and Use of ground-based model systems, such as hindlimb unloading in rodents, to investigate the mechanisms of changes that reproduce in-flight and postflight effects. Mechanistic studies and exploitation of ground-based animal models are indeed being emphasized by NASA in both disciplines. The growing use of genetically modified mice (knockout and transgenic) is of particular interest and importance, although flight experiments will be required to validate mechanistic hypotheses so obtained. Caging for mice suitable for Shuttle and International Space Station (ISS) flight experiments is now available. A third recommendation of the Strategy report, to investigate the relationship between exercise activity and protein-energy balance in flight, will ultimately require flight experiments. However, preliminary ground-based studies will be important antecedents to flight and have recently been started. Two additional recommendations—to obtain a database on the course of spaceflight-related bone loss and its reversibility in humans, and to establish hormone profiles on humans before, during, and after spaceflight—cannot be addressed until appropriate flight opportunities return. VESTIBULAR FUNCTION, THE VESTIBULO-OCULAR REFLEX, AND SENSORIMOTOR INTEGRATION The three recommendations of the Strategy report for high-priority research in the areas of vestibular function, the vestibulo-ocular reflex, and sensorimotor integration all involved extensive studies in spaceflight. Preliminary investigations were carried out on Neurolab related to the recommendation for in-flight recordings of signal processing following otolith afferent stimulation. However, the highest-priority recommendation, to determine the basis for the compensatory mechanisms on Earth and in space and evaluate whether the mechanisms are the same, has not yet been addressed. Similarly, studies to determine the effects of microgravity on the adaptation of the vestibulo-oculomotor system to sensory perturbations will require spaceflight. In a parallel section defining high priorities for research in fundamental gravitational biology, the Strategy report recommended functional magnetic resonance imaging (fMRI) studies on astronauts pre-and postflight to determine the effects of microgravity on neural space maps. Initiation of such studies must also await the availability of appropriate flight opportunities. ORTHOSTATIC INTOLERANCE UPON RETURN TO EARTH GRAVITY High-priority issues included determination of the mechanisms underlying inadequate total peripheral resistance during postflight orthostatic stress; extension of current knowledge of cardiovascular adjustments to long-duration exposure to microgravity; reevaluation and refinement of existing countermeasures; and development of methods for referencing intrathoracic vascular pressures to systemic pressures in microgravity. These studies also require flight opportunities. Although the ability to conduct experiments on the ISS will ultimately be required, much of the necessary knowledge could be obtained from short-term Shuttle-based flight and postflight studies.
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Review of NASA’s Biomedical Research Program RADIATION HAZARDS Two of the four high-priority recommendations in this area require improved availability of high-energy and high-Z accelerator facilities: Determine the carcinogenic risks following irradiation by protons and high-atomic-number, high-energy (HZE) particles; and Determine if exposure to heavy ions at the level that would occur during deep-space missions of long duration poses a risk to the central nervous system. These issues are being addressed by National Space Biomedical Research Institute (NSBRI) investigators, and new facilities at Loma Linda University for proton studies and at Brookhaven for heavy ions will provide greatly improved access to investigators for relevant studies. Both areas are given priority in the 2000 NASA Research Announcement (NRA) for biomedical research and countermeasures. One recommended area of study, to determine whether combined effects of radiation and stress on the immune system in spaceflight might have additive or synergistic effects on host defenses, has not been implemented, although preliminary ground-based animal studies could give important insights into this question (Todd et al., 1999). The remaining recommendation, to determine how selection and design of the space vehicle affect the radiation environment, goes beyond the boundaries of the biomedical research program and is not considered in the present report. PHYSIOLOGICAL EFFECTS OF STRESS The Strategy report contained a single high-priority recommendation to examine the role that the host response to stressors plays in alterations in host defenses by investigation of the interactions between the neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis and the immune system during spaceflight. Flight opportunities are lacking for the near term, and although the area has attracted attention under the aegis of other agencies, ground-based studies have not previously received significant attention in NASA programs. However, the 2000 NRA called explicitly for proposals to evaluate effects of stressors on physiological function and emphasized studies using integrated approaches. PSYCHOLOGICAL AND SOCIAL ISSUES The Strategy report gave highest priority to a recommendation for interdisciplinary research on the neurobiological and psychosocial mechanisms underlying the effects of environmental stressors on cognitive, affective, and psychophysiological measures of behavior and performance. The majority of current NASA-supported research concerns neurobiological and neurobehavioral aspects of stress-related effects, with an emphasis on perturbing effects of spaceflight on circadian rhythms and sleep patterns. Until recently, less attention has been paid to psychosocial stressors and their effects; however, the 1999 and 2000 NRAs gave explicit emphasis to these issues. Very little of the research to date has had a significant interdisciplinary focus, although the NSBRI programs are beginning to move in this direction. The International Life Sciences Working Group has also recommended a greater emphasis on interdisciplinary approaches. A second high-priority recommendation was for interdisciplinary research to evaluate the efficacy of existing countermeasures, develop more effective replacements for those that are deemed inadequate,
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Review of NASA’s Biomedical Research Program study the use of psychophysiological countermeasure implementation, and determine the effects of the spaceflight environment on the kinetics and efficacy of psychopharmacological medications. With the exception of the circadian and neurovestibular systems, countermeasure evaluation and development received little attention in the past. However, the 2000 NRA, in soliciting research on the development of predictive tools for the assessment and support of psychological well-being, has begun to redress this imbalance. REFERENCES National Research Council (NRC), Space Studies Board. 1998. A Strategy for Research in Space Biology and Medicine in the New Century. Washington, D.C.: National Academy Press. Todd, P., M.J. Pecaut, and M. Fleshner. 1999. Combined effects of space flight factors and radiation on humans. Mutat. Res. 430:211-219.
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