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An Initial Review of Microgravity Research in Support of Human Exploration and Development of Space 2 The Current Microgravity Research Program and HEDS Goals HEDS GOAL 1: INCREASE KNOWLEDGE OF NATURE USING THE SPACE ENVIRONMENT As described above, the first of the HEDS goals adopted by NASA mandates the scientific study of nature and its processes in microgravity for the purpose of increasing human knowledge. Some of these studies use microgravity as an experimental variable, and others use microgravity to enable the study of phenomena obscured by gravity. (While microgravity is technically defined as 10- 6 of Earth's gravity, the actual spaceflight environment in which experiments are performed ranges from 10-3 to 10-6 g). Microgravity can also permit an experimental protocol or measurement that cannot be performed on Earth. The current MRD science program is already closely aligned to the objectives of HEDS Goal 1 and has been so almost from its inception. The science programs of each of the five current MRD disciplines, described in greater detail in a previous report of this committee,1 are briefly presented below. Fluid Physics The greater part of the current MRD program deals with heat and mass transport processes in reduced gravity or microgravity that are associated with density, temperature, and concentration gradients in gaseous, liquid, and particulate matter, especially when changes of phase take place. Studies of nucleation and boiling in reduced gravity are under way, as are studies of the dynamic behaviors of droplets, bubbles, and foams and of suspensions of particulate materials as they are transported in fluid media. A variety of interfacial problems, for example in multilayer convection and jet impingement, arise in many of the current studies.

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Electrohydrodynamic forces and effects, including electrophoresis, appear in a number of these microgravity studies, in addition to capillary, thermocapillary, and diffusional effects. Theoretical studies have been initiated in which investigators have begun to examine the influence of reduced gravity (e.g., on the Moon or Mars) rather than microgravity, and some studies consider the consequences of "g-jitter" on gravity-sensitive flows. The present program shows a strong emphasis on experimental research. Experiments in flow physics requiring access to a long-duration, low-gravity environment have been carried out successfully in the Space Shuttle program. For experiments that can be conducted in shorter periods, continuing use has been made of aircraft flight tests and of a number of drop-tower facilities for flow physics research. While this experimental research is strongly fundamental in character, the current MRD fluid physics program does not greatly emphasize theory or analysis, nor does it emphasize computational fluid-dynamics simulation (which is developed from theory) as much as do fluid mechanics programs in other fields of aerospace research where the boundary conditions are better understood. This is understandable for the present. However, as NASA's interest grows in the application of fundamental scientific insights to specific design conception, then theory, analysis, and computational simulation will assume greater importance in microgravity work. In general terms, issues involving the physics of fluids in low gravity underlie a great many of the scientific and engineering technology problems of space travel, and these are more fully discussed in subsequent sections of this chapter and in Chapter 3. Therefore, elements of the broad current fluid physics program of MRD will doubtless find expression within interdisciplinary studies undertaken by NASA to support the design of general and specific systems needed for future HEDS missions. Materials Science The essential quest of materials science is to understand the relationships among processing, structure, and properties. Within this context, the MRD program in materials science seeks to understand the influences of gravity on those relationships. Hence, a large fraction of the science funded by MRD is focused on understanding the fundamentals of nucleation and growth of solids from liquids. Emphasis is also placed on elucidating the details of the genesis and evolution of microstructure, as well as on the formation of crystal defects and solute segregation. The ultimate goal of this research is understanding how to improve materials properties. Additionally, because the microgravity environment enables measurements of the thermophysical properties of liquids in stable (and even metastable) states that might not be possible to perform in terrestrial gravity, this area has also attracted researchers. Examples of such properties are viscosity, heat capacity, and chemical diffusivity.

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The materials research currently funded by MRD addresses most major classes of materials. At present, a strong emphasis exists on metals and their alloys as well as on electronic and photonic materials; a moderate emphasis is placed on ceramic materials, and less on polymeric materials. The reduced emphasis on viscous polymeric materials is related to the smaller effects of gravity on their structure. Indeed, conventional fluid mechanics show that buoyancy-induced convection occurring in materials processes at terrestrial gravity levels has a much greater influence on process outcomes in the case of liquid metals and semiconductor melts than it has for highly viscous melts associated with high-molecular-weight polymers and network (silica-based) glasses. Within the scope of these investigations, a number of important processes are being examined, such as directional solidification, chemical vapor deposition, containerless processing, polymerization, and co-polymerization. Combustion synthesis and welding and joining are also receiving some attention. As work progresses, additional areas of research of importance to the HEDS enterprise are expected to be identified. Combustion MRD currently supports a rigorous flight- and ground-based effort in combustion science in line with the fundamental science objectives of HEDS Goal 1 through work exploring effects of gravity on flammability limits, smoldering, flame spread, and material flammability, all of which are substantially affected by a reduction in gravity. Related fundamental work includes investigations of the dynamics of flame balls, structures of diffusion flames, and characteristics of droplet and particle combustion (which, at reduced gravity, give rise to a closer approach to spherical flames, new flame instabilities, and modified soot formation processes), and focuses on the importance of radiative transfer in combustion processes. Along with associated theoretical studies, this program is leading to improved understanding of combustion phenomena at altered gravity levels, thereby contributing scientific knowledge needed for the HEDS enterprise. Biotechnology The biotechnology discipline within MRD currently supports three areas of research: protein crystal growth, mammalian cell culture, and bioseparations. Each is a key technology for the production of biology-based products and involves processes that are affected by gravity. Protein crystal growth provides the crystals that are required to determine the unique three-dimensional structures these macromolecules adopt to perform their biological functions. The relationship between structure and function in proteins targeted for drug intervention, for example, has been found to be of

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critical importance to the rapid design of useful therapeutic agents. (The most recent example of this structure-based drug design using protein crystallographic data is the family of new HIV protease inhibitors that are the linchpins of more effective combination therapies against AIDS.2) The process of protein crystal growth is sensitive to gravity because of density-driven convection at growing crystal surfaces and because of sedimentation of crystals from liquid growth media. A first phase of spaceflight experimentation has proved that growth in microgravity can, in some cases, produce crystals exhibiting improved X-ray diffraction performance and more precise structure determination. A second phase of experimentation has just begun that focuses on determining the physicochemical mechanisms of protein crystal growth so that the knowledge can be used to extend the beneficial effects of microgravity to the widest possible array of proteins. Most of the experimentation in mammalian cell culturing supported by MRD has been aimed at the study of the basic functions of three-dimensional cellular aggregates that form in bioreactor devices on Earth. The rotating-wall, perfused-vessel bioreactor was designed to mimic the low-shear-stress environment of microgravity. This cell culturing technology provides a great advance over the use of monolayer or stirred cultures and often permits culturing of differentiated cells and tissues that cannot otherwise be achieved.3 Culturing of mammalian cells is important to provide cells and tissues for potential production of biological products such as insulin, cartilage,4 and cellular proteins. In addition to presenting research opportunities, these tissues would also be available for transplantation and genetic therapies.5,6,7 It is anticipated that the further reductions in shear forces that are possible in space will allow larger and more complex tissue masses to be grown. Biological products are isolated from culture media by a number of techniques. Gel electrophoresis, a widely used method for purification of biological products for both industrial and research purposes, involves separation by size and charge in a water-based gel. Resolution is normally limited by the gravitationally mediated phenomena of density-driven thermal convection and sedimentation. The results of electrophoretic experiments carried out in microgravity demonstrated that buoyancy-driven phenomena are diminished, but new electrohydrodynamic effects have been uncovered that limit the benefits gained by the effects of microgravity on the system.8 Biological separations will also be important for nutrient production and waste recycling in space, which may provide the basis of future critical mission technologies. Low-temperature Microgravity Physics The MRD program in low-temperature microgravity physics has sponsored several flight-approved projects, covering both condensed matter physics (Confined Helium Experiment, Critical Fluid Light Scattering, and Critical Dynamics in Microgravity) and general relativity (Satellite Test of the Equivalence Principle (STEP)). These projects use extended-duration microgravity to probe

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certain extreme physical limits, such as asymptotic approaches (within microkelvins) to certain critical temperatures of classical (xenon liquid-gas) and quantum (helium's lambda point) systems, where the physics of thermodynamic fluctuations near these singularities is revealed much more clearly than on Earth. The Quick STEP mission, which falls within this subdiscipline, is a geodesy science satellite that will establish new limits on the gravitational-to-inertial-mass ratio. The detection of any departure of this mass ratio from unity would present the physics community with a significant challenge to current relativity and gravitational theories; the absence of any systematic departure from unity would, by contrast, establish new limits on the accuracy of current physics theories. These projects in microgravity physics represent unique scientific opportunities for NASA to advance our deepest understanding of how matter and energy interact with gravity. The Importance of Fundamental Research Taken together, the individual discipline-specific science programs within MRD represent an integrated approach to microgravity research that has already contributed important knowledge of processes occurring in space and on extraterrestrial bodies and will continue to do so in the future. Moreover, the MRD program presents a relatively comprehensive response to the scientific opportunities and challenges provided by the microgravity environment. Basic microgravity research in the core disciplines should continue to be supported as the fundamental science component of the MRD program. The fundamental insights provided by the core disciplines can also form the basis for the evolution of technologies required by the other HEDS goals. The current research sponsored by MRD is subject to rigorous peer review and generally is of high quality. A distinguished, broadly based scientific community is involved with the execution of these investigations, and significant new results are emerging from the program.9 This effort, specifically directed at HEDS Goal 1, should be maintained at least at its current level. NEW CHALLENGES: HEDS GOALS 2, 3, AND 4 Although MRD has established itself as an effective basic science program and thus meets the objectives of Goal 1 as described above, it can also play a significant role in NASA's attempt to meet the remaining HEDS goals. Contributing to NASA's HEDS Goal 2, "to explore and settle the solar system," would require the recognition that the output from the MRD science program should also be used to support the HEDS mission technologies. In other words, the results of microgravity research should be used not only for terrestrial applications, but also to improve the feasibility of the eventual exploration and settlement of near-Earth space. The scientific challenges presented by this new

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approach to the use of microgravity research findings also encompass to a large extent those posed by the subsequent HEDS goals, specifically Goal 3, "to achieve routine space travel," and Goal 4, "to enrich life on Earth through people living and working in space." These new goals imply long-term exposure to, and function in, a variety of environments with gravity levels ranging from microgravity to the gravity of Earth. One should note that with the possible exception of lunar base missions, the space missions envisioned by HEDS would still spend a substantial portion of their time under microgravity conditions, affecting not only humans but also the machines, systems, and devices needed for crewed and robotic exploration. As is described further in the next chapter, many of these systems are directly or indirectly affected by the gravity level. A fundamental understanding of the low-gravity behavior of fluids and materials is likely to be critical to the successful development and performance of such systems—both to avoid the expensive alternative of trial-and-error development and to create the knowledge base for the generation of novel designs capable of increasing efficiency and decreasing cost. No list of microgravity phenomena prepared today would be sufficient in scope and depth to describe all the challenges to be encountered in spaceflight missions in the future. However, with the goals now stipulated by HEDS, at least some of the new challenges can be considered to merit near-term microgravity research support, and strategies and programs can be developed to ensure that over time all important challenges will be discovered and addressed. In order to understand the technology needs of HEDS, and the part to be played by microgravity research in addressing those needs, NASA will need to specify target missions for study. Two possible target missions that are often cited are a return to the Moon for an extended period of human habitation and a crewed mission to Mars.10 Such target missions help create a focus on the specifics of the appropriate technical challenges that should drive additional scientific research and technological development. Moreover, target missions, in their accomplishment, also provide unique "laboratories" for performing additional research that could help make settlement and travel to the inner planets at least possible, if not precisely routine, in the future. Definitions of target missions should not be used, however, to constrain the scope of either basic or applied research to conform to near-term purposes, nor should the range of technology interests be limited. Indeed, the technologies in which significant resources are invested should be those that are capable of evolution and extension to meet the long-range HEDS goals of interplanetary travel. It is especially important that MRD research in support of these goals not be limited to specific targets. 1. Space Studies Board, National Research Council. 1995. Microgravity Research Opportunities for the 1990s. National Academy Press, Washington, D.C. 2. Steele, F.R. 1996. Optimism invades HIV conference. Nature Med. 2:257-258. 3. Duray, P.H., Hatfill, S.J., and Pellis, N.R. 1997. Tissue culture in

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microgravity. Science and Medicine 4:46-55. 4. Freed, L.E., and Vunjak-Novakovic, G. 1997. Microgravity tissue engineering. In Vitro Cell Dev. Biol. Anim. 33:381-385. 5. Akins, R.E., Schroedl, N.A., Gonda, S.R., and Hartzell, C.R. 1997. Neonatal rat heart cells cultured in simulated microgravity. In Vitro Cell Dev. Biol. Anim. 33:337-343. 6. Baker, T.L., and Goodwin, T.J. 1997. Three-dimensional culture of bovine chondrocytes in rotating-wall vessels. In Vitro Cell Dev. Biol. Anim. 33:358- 365. 7. Molnar, G., Schroedl, N.A., Gonda, S.R., and Hartzell, C.R. 1997. Skeletal muscle satellite cells cultured in simulated microgravity. In Vitro Cell Dev. Biol. Anim. 33:386-391. 8. Hymer, W.C., Barlow, G.H., Blaisdell, S.J., Cleveland, C., Farrington, M.A., Feldmeier, M., Grindeland, R., Hatfield, J.M., Lanham, J.W., and Lewis, M.L. 1987. Continuous flow electrophoretic separation of proteins and cells from mammalian tissues. Cell Biophys. 10:61-85. 9. National Aeronautics and Space Administration (NASA). 1996. NASA's Microgravity Science and Applications: Program Tasks and Bibliography for FY 1995. NASA-TM-4735, NASA, Washington, D.C. 10. Cohen, A. 1989. Report of the 90-Day Study on Human Exploration of the Moon and Mars. NASA-TM-102999, NASA, Washington, D.C.