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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 29 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. 2 Critical Research Requirements The cardinal consideration in any discussion of prolonged human exploration is the safety and well-being of the crew. This led CHEX to define a set of critical research requirements related to conditions known to be life threatening or seriously debilitating: they are the potential "showstoppers" of human exploration. All previous experience from Mercury to the Space Shuttle and from Vostok to Mir is helpful in indicating possible problems. This experience is, however, insufficient to provide all the answers about the long- term effects of spaceflight on humans, since that experience is limited to less than three months for U.S. astronauts (almost 20 years ago) and just over one year for a small number of cosmonauts. In addition to the limited time, many of the effects were inadequately studied from a research protocol point of view. In contemplating round-trip voyages to Mars of two years or more, we enter a new arena of human experience. Factors such as radiation, the effects of prolonged exposure to microgravity on physiologic functions, the psychosocial phenomenon of sequestration of a small crew in a confined area, with a closed environmental system and without any prospect of escape in the event of catastrophe, are all without precedent.1 Ground-based research characterizing the effects of psychosocial and radiation phenomena should be continued and enhanced. Space biology and medicine are in such a primitive state of development that knowledgeable researchers cannot state with any degree of assurance that human crews will be able to operate their spacecraft or function Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 30 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. usefully on Mars after their voyage. Even if nuclear- or solar-thermal (or nuclear- or solar-electric) propulsion systems can be realized, trip time will still be nearly six months each way. Even this is well beyond U.S. experience, and the former-Soviet Union's program offers very limited solid biomedical data for missions of this duration. Once astronauts reach their destinations, they may face additional problems. We have no information at all about the physiological effects of long- duration (more than one year in some scenarios) exposure to the fractional-g lunar or martian environments. One recent report asserts that "it is expected that while crews are on the martian surface, the three-eighths Earth's gravity will help maintain their physiological health."2 There is absolutely no scientific evidence to support this expectation. Some space planners are optimistic that essential information can be obtained and necessary measures taken to ensure reasonable safety for crew members. In the view of CHEX this is far from a certainty. Thus life-sciences research must be the dominant factor in any consideration of prolonged human spacefaring. All other aspects of a Moon/Mars program fade into secondary importance until the relevant life-sciences research has been conducted and preventive or ameliorative measures investigated. It is critical that planners recognize that current knowledge about human performance in space is predicated on relatively short-term experiences. CHEX predicts that human problems that we cannot anticipate today will be discovered during long-term missions. It has been suggested that some of the enabling biomedical data can be gained in operations conducted on the Moon.3 Such operations will not, however, be sufficient to yield the biological and physiological information required for a comprehensive understanding of the effects of microgravity. There can be no assurance that countermeasures derived in an ad hoc manner will be effective for all crew members in all situations. CHEX recommends that those implementing a Moon/Mars program commit to and lead a comprehensive program of basic and applied life-sciences research on the effects on human physiology of the microgravity, reduced- gravity, and space-radiation environment prior to finalizing spacecraft designs or undertaking long-duration flights. For this purpose, a long-term research program in adaptation to microgravity and reduced gravity, properly conducted in a suitably equipped space station in low Earth orbit, will be required. Such a research program may require 5 to 10 years because of the necessarily long- duration of individual experimental protocols. Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 31 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. RADIATION Bombardment by energetic particles is a major hazard facing space travellers.4 Indeed, NASA has recognized that the cumulative radiation dose "will probably be the ultimate limiting factor for human exploration."5 Humans conducting extended space voyages face two different radiation hazards: a protracted exposure to galactic cosmic rays at a low dose rate and some probability of exposure to considerably higher doses of solar energetic particles. Depending on the total exposure suffered, these twin effects will increase the probability of stochastic effects (such as cancer and genetic damage) and may also increase the incidence of deterministic effects (physical damage to tissues). The effects of acute irradiation during solar particle events are of particular concern. The high-dose-rate exposures they could inflict on astronauts could cause acute damage to the skin, gut, bone marrow, and germinative tissues and, at a later date, cause cataracts. Estimating the probability of very large solar flares and predicting the resultant exposure of astronauts to radiation are among the principal concerns that need to be addressed before we can safely design new space vehicles and plan voyages of human exploration. Radiation Levels The health hazard posed by energetic particles depends, in part, on the energy deposited as the particles pass through tissue or come to rest in vital organs. This is traditionally characterized by the "dose equivalent," which reflects the biological effect of exposure to radiation. The dose equivalent is equal to the absorbed dose multiplied by the "quality factor" (Q), which varies from ~1 for minimally ionizing particles such as gamma rays to ~20 for neutrons and heavy ions such as iron nuclei. The International Commission on Radiological Protection has recently recommended that the term "quality factor" be replaced by "radiation weighting factor" (WR). The values of WR for specific types and energies of radiation have been selected to be representative of the relative biological effectiveness (RBE) of radiation in inducing stochastic effects at low dose.6 There are, however, no recommendations for values of WR for causing either early or late deterministic effects such as acute tissue damage and cataracts, respectively. However, the RBE for cell killing by radiation with high linear-energy-transfer rates (e.g., heavy ions and neutrons) is considerably lower (by factors of about two to five) than that for the induction of cancer. NASA currently has no limits for exposure to radiation during deep-space missions conducted beyond the protective shield of the geomagnetic field because little is known about the physiological effects of the heavy ions found in cosmic rays. In terms of the traditional dose-equivalent for Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 32 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. mulation, NASA's current limits for exposure of astronauts in low Earth orbit are 0.25 sievert (Sv)7 per month, 0.5 Sv per year, and 1 to 4 Sv for a lifetime exposure (depending on age and sex). (For comparison, the typical dose used to sterilize food and drugs is 20,000 Sv.) NASA's current limits correspond to a 3% excess risk of eventual death due to cancer and are about 10 times that allowed for terrestrial radiation workers and about 100 times that allowed for the general population. Sources of Hazardous Radiation As mentioned above, two types of radiation are hazardous to astronauts— galactic cosmic rays and solar energetic particles. The risk posed by galactic cosmic rays is principally due to protons (with a broad range of energies) and heavy ions (in particular, energetic iron nuclei). The principal danger from solar energetic particles is posed by sporadic, large fluxes of energetic protons. Galactic Cosmic Radiation Galactic cosmic rays consist of ions of all atomic numbers from 1 to 92, with energies ranging up to 1020 electron volts (eV). Those combining high (H) atomic number (Z) and high energy (E) are collectively called HZE particles. Of these, the iron-group ions are the most hazardous because they combine relatively high abundance, a high rate of energy deposition (proportional to the square of their electric charge), and a high Q-factor. To a lesser extent, ions with atomic numbers between those of oxygen and silicon are also important. Many questions concerning HZE particles are unanswered. How effective are they, for example, in inducing cancers? Can the late deterministic effects of HZE particles be predicted from our present understanding of the long-term effects of radiations with low linear-energy-transfer rates such as x rays and gamma rays? Two other areas where more data are needed are of particular relevance to human exploration. The first is the 10 to 30% range of uncertainty in the measured fluxes of heavy ions in the critical energy range from 50 to 5000 MeV per nucleon (which includes more than 90% of the cosmic-ray flux). Second, the Sun's 11-year activity cycle modulates the cosmic-ray flux such that the flux at energies below 5000 MeV per nucleon is greater during years of solar- activity minimum than during solar maximum. As alluded to previously, a better understanding of the biological effects, both acute and long-term, of energetic radiation must also be achieved. The materials that form the spacecraft or the layers of a spacesuit shield astronauts from radiation to some extent. In addition, the human body Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 33 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. provides ~5 cm of additional shielding for some critical organs, which is equivalent to about 4 cm (or 10 gm/cm2) of aluminum. Figure 1 illustrates the estimated dose equivalent at 5-cm tissue depth for aluminum shielding of different thicknesses for galactic cosmic rays during the cosmic-ray maximum (solar-activity minimum) in 1977.8 As can be seen, only the first 5 cm of shielding is very effective; disproportionately thicker shields are required for greater protection. For comparison, one third of the solid angle inside the space shuttle has a shielding of less than 8 cm of aluminum, while 11% of the solid angle has a shielding equivalent to less than 0.8 cm of aluminum.9 In addition to attenuating the flux, the thickness and type of shielding determine how cosmic rays fragment into secondary particles. The nature and abundance of these secondaries, which account for the flattening of the dose-versus-shielding curve, are a major determinant of the radiation dose astronauts will receive. Figure 1 Estimates (solid curve) of the radiation dose equivalent received from galactic cosmic rays at a depth of 5 cm in body tissue (representative of, for example, bone marrow) versus aluminum shielding thickness during the 1977 solar- activity minimum. The dashed curve is an upper bound on the dose equivalent at the 90% confidence level. From Adams et al., 1991 (see reference 8). The great penetrating power of cosmic rays combined with their high RBE suggests it may be impractical to shield against them in deep space. Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 34 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. Therefore, if background cosmic rays were the only radiation hazard, the safest time for a mission to Mars might be when the Sun's activity is near maximum and the flux of galactic cosmic rays might be 10 to 30% lower due to the modulation effect. Unfortunately this time corresponds to the period of the highest probability of solar-flare occurrence. Thus, a voyage to Mars during solar maximum should be conducted only if timely forecasts of solar energetic particle events will exist to allow adequate defensive measures to be taken. Before any final conclusions on mission timing are drawn, the probability of solar-flare occurrence must be considered along with the uncertainties in cosmic-ray fluxes, their modulation, attenuation, and fragmentation in shielding, and biological effects. Solar Energetic Particles The intensity, spectra, and composition of energetic particles from solar flares are much more variable than those of galactic cosmic rays. The flare- produced energetic-particle population can also be dramatically enhanced by strong shocks in the solar wind associated with coronal mass ejection. An unprotected astronaut caught in a very large flare event could be exposed to a very high or even a lethal dose in a few hours to a day. The most dangerous events are those that include solar protons with energies above a few tens of MeV. The alpha particles, electrons, and heavier nuclei accompanying the protons pose comparatively slight additional hazards. Shielding can provide some degree of protection against solar energetic particles. Figure 2 shows the effectiveness of aluminum shielding for the large flare of August 1972 and a hypothetical "worst case" combining the very-high- energy particles observed in the February 1956 event with the very high flux levels attained in the August 1972 event.10 As can be seen, a worst-case event would place astronauts at considerable risk because of their prolonged exposure to energetic protons at relatively high dose rates even if they were shielded by 16 cm of aluminum. It must be noted that detailed measurements of solar flares have been available for only a few decades, and so events with characteristics even more extreme than this "worst case" cannot be excluded with any confidence. A lunar or martian base could be partially buried so that its inhabitants would be protected from radiation when inside. They would, however, still be at risk in transit between Earth, the Moon, and Mars and when on the lunar and martian surfaces. Thus space travellers will likely need some type of early warning system to alert them to dangerous solar events. In addition, mission rules would need to take into account the time needed to seek shelter. Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 35 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. Figure 2 The radiation dose equivalent received at a depth of 5 cm in body tissue (representative of, for example, bone marrow) versus aluminum shielding thickness for the August 1972 solar flare (solid squares) and a composite, worst-case solar energetic particle event (open squares). Reprinted with permission from J.R. Letaw, R. Silberberg, and C.H. Tsao, "Galactic Cosmic Radiation Doses to Astronauts Outside the Magnetosphere," in Terrestrial Space Radiation and Its Biological Effects, P.D. McCormack, C.E. Swenberg, and H. Bucker (eds.), Plenum Press, New York, 1988. Copyright 1988 by Plenum Publishing Corp. In addition to hazardous energetic particles, solar flares produce energetic neutrons and enhanced electromagnetic emissions at all wavelengths. Although the increased radio, optical, ultraviolet, and x rays do not constitute a hazard, they do signal the onset of proton acceleration in the Sun. This electromagnetic radiation travels at the speed of light and takes only eight minutes to reach the Earth-Moon system in contrast to energetic solar-flare protons, which may take from 15 minutes to 60 hours to travel the same distance.11 Thus, a flare- radiation detection system could give adequate warning for crews working near a lunar base. For astronauts engaged in surface traverses on the Moon or Mars, emergency procedures must be developed to provide temporary shielding rapidly. Orbital transfer vehicles will need storm shelters where crew members can take refuge during an event. The need for emergency procedures will tend to be minimized if dangerous flare conditions can eventually be predicted a day or more in advance. Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 36 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. Relevant Measurements and Research There are several possible approaches for making significant progress in reducing some of the current uncertainties in the flux of heavy ions in galactic cosmic rays. These include the following: • The fluxes of cosmic-ray nuclei (especially oxygen through iron) should be measured throughout the 22-year magnetic solar cycle using a new generation of instruments with large geometric factors, such as NASA's planned Advanced Composition Explorer; • Measurements of the intensities of the electron and positron components of galactic cosmic rays over most of a 22-year cycle would separate charge-sign-dependent effects from other cosmic-ray propagation effects, thereby leading to better understanding of the modulation process; • Measurement of the galactic cosmic-ray intensities beyond the boundary of the heliosphere would establish an upper limit to the radiation intensity independent of its modulation by the solar wind and magnetic field. Continued tracking of the Voyager spacecraft is clearly cost-effective in this respect; and • Theoretical studies of the solar- and plasma-physical processes that modulate the intensity of galactic cosmic rays are required to better understand and predict their variability. Improved measurements of cross-sections and better modeling of heavy- ion interactions, particularly for the yield and spectra of neutrons and other secondary particles generated in the shielding material, are also required. NASA currently helps support the Bevalac heavy-ion accelerator and some cross- section studies. However, the Bevalac has been threatened with closure, thus endangering some of the enabling research on both cross-section measurements and the long-term biological effects of ionizing radiation.12 Research conducted during the International Geophysical Year in the late 1950s helped lay the groundwork for the basic theoretical understanding of the triggering of solar flares: fast magnetic reconnection in a magnetically dominated plasma. Since then, progress in understanding the details of the solar- flare mechanism has been slow. Moreover, in the absence of human spaceflights beyond low Earth orbit, flare prediction has not been the focus of solar-flare researchers for the last 15 years. There is, however, reason to believe that significant progress can be made if the objectives are compelling. Two types of research programs should be considered: first, those that help us understand the process of particle acceleration and release and that might eventually lead to improved forecasting of energetic-particle events, and second, those that provide warning that a potentially dangerous event has occurred. Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 37 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. In the first category, the following programs would lead to significant progress in understanding flares: • A meter-class space telescope to observe the Sun continuously with 100- km resolution. This facility should advance our fundamental understanding of flare-production mechanisms by spotting such precursor events as the emergence of magnetic flux through the photosphere and the buildup of magnetic shear; • A global network of some 6 to 10 small Earth-based solar telescopes to measure magnetic fields and optical radiation over the full solar disk with approximately 700-km resolution. By monitoring active regions and logging flare precursors, these instruments should lead to better flare forecasting on time scales of hours to days; • An x-ray and gamma-ray imaging telescope in space to provide information on the acceleration and propagation of energetic electrons and ions in the flare plasmas, and hence on the nature of the flare process. When coupled with direct and proxy measurements of the evolution of the magnetic-field structure in the flaring regions, this could substantially increase our ability to predict the acceleration and release of energetic flare particles; and • Theoretical studies and computer simulations of flare-related magnetohydrodynamic processes to interpret the required measurements and direct future observations. Whether or not we are ever able to forecast flares with high confidence, the following space-based measurements could be used as part of an advance- warning system for energetic particles once a flare has occurred. 1. A solar-observing spacecraft stationed 1 astronomical unit from the Sun in solar orbit 60 to 90 degrees ahead of Earth. Its payload would consist of an extreme-ultraviolet/x-ray telescope, a white-light coronagraph, and a small telescope designed to detect the onset of flares. 2. A network of satellites spaced at 90-degree intervals in a solar orbit with a radius of 0.3 to 0.5 astronomical unit. These satellites would carry energetic-particle detectors to provide reliable early warnings of energetic flare particles. A solar-observing spacecraft is an important component of a short-term (a few minutes to a few hours) warning system because it would allow modeling and predictions of the paths taken by energetic particles as they are channeled from flare sites into interplanetary space. The coronagraph would allow coronal mass ejections (CMEs) to be observed and their initial speeds to be determined. Such observations provide 1- to 3-day advance warning of the arrival of the CME-driven shocks Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 38 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. that can dramatically enhance the population of flare-produced energetic particles. A single spacecraft is sufficient to cover the Earth-Moon system, but a network of three or four spacecraft (with 90- to 120-degree spacing) is required to cover Mars exploration, because Earth and Mars have different orbital periods and solar longitudes. BONE DEGENERATION AND MUSCLE ATROPHY Microgravity has major, potentially dangerous effects on human physiology. Extensive research is required to understand the responses of humans to microgravity and to assess their implications for long-duration spaceflight. Because a small number of astronauts and cosmonauts have survived long-duration missions in low Earth orbit, there is a false perception that there is no need to be concerned about health-related issues when contemplating interplanetary voyages. According to the Committee on Space Biology and Medicine, ''Based on what we know today, this assumption of continued success cannot be rigorously defended.''13 The committee continued, "If this country is committed to a future of humans in space, particularly for long periods of time, it is essential that the vast number of uncertainties about the effects of microgravity on humans and other living organisms be recognized and vigorously addressed. Not to do so would be imprudent at best—quite possibly, irresponsible."14 The bone degradation (osteopenia) and muscle atrophy that occur in a microgravity environment are severe hurdles to an extended human presence in space.15 The primary risk is to the functioning of the musculoskeletal system upon reexposure to planetary gravity. At present, our understanding of the causes of space-induced osteopenia and muscle atrophy is inadequate to devise effective countermeasures to be taken on long-duration space missions. Also lacking are data on the temporal sequence of bone remodeling and muscle atrophy in prolonged exposure to microgravity and the ways in which these processes may depend on other risk factors such as age, gender, race, or nutrition. Without such data, we cannot be confident that a prolonged microgravity mission such as a Mars flight would not lead to irreparable musculoskeletal damage. Such damage could both impair the effectiveness of crew members during their stay on Mars and pose serious problems upon their return to Earth. There is also the possibility that some bone demineralization will occur during prolonged flight in spite of countermeasures. If so, astronauts en route to Mars might be at risk for bone fracture with mild trauma and for the formation of kidney stones. There is great depth and breadth to current research on osteopenia, muscle atrophy, and their underlying causes, thanks to sponsorship by the National Institutes of Health. These studies have concentrated on the problems of bone metabolism in relation to aging, menopause, endocrine disor Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 39 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. ders, poor nutrition, immobilization, and extended bed rest. A major effort is now needed to develop parallel studies to acquire basic knowledge about these problems as they occur in microgravity and to begin devising appropriate countermeasures. A critical factor in such studies must be the use of appropriate animal models and the development of computational and experimental methodologies to test and validate mechanisms of bone remodeling and muscle conditioning. In addition, the development of suitable in vitro systems using bone and muscle tissue cultures should be undertaken. One approach to counteracting the physiological effects of microgravity is to subject organisms in space to artificial gravity. Although such an environment could correct bone degeneration, muscle atrophy, and other changes due to microgravity, it could also exacerbate other effects not now perceived to be major problems. Head movements made in a spinning environment or Coriolis effects can lead to disturbing vestibular sensations and motion sickness. Changes in gravity experienced when moving to different parts of a spinning spacecraft or when changing the spin rate might induce symptoms of disequilibrium. A comprehensive program is required to (1) determine the gravity threshold required to reverse or prevent the deleterious effects of microgravity and (2) evaluate the effects of centrifugation on behavior and/or sensorimotor function. Part of the required research could be accomplished by using human surrogates, including nonhuman primates, on a dedicated centrifuge in low Earth orbit. Studies of human responses to spinning will require a centrifuge of sufficient dimension to accommodate humans. An alternative strategy would be to investigate the use of rotating tethered spacecraft16 to provide artificial gravity. It is possible that the detrimental vestibular effects of spinning can be eliminated if the tethers are sufficiently long. Even assuming an optimistic schedule for lunar operations or space station activation, the relevant life-sciences knowledge developed from them will probably not be available before the beginning of the second decade of the 21st century. This implies a substantial technical risk in any program of Mars exploration that relies on a comprehensive solution to problems of human adaptation to microgravity. The prudent alternative is to carry forward, during conceptual design phases, alternatives providing for artificial gravity (as recommended in a National Research Council report17) during the cruise flight phase, and possibly in Mars orbit as well. If satisfactory countermeasures are confidently identified during a vigorous and rigorous program of orbital life- sciences research, this alternative design path can be abandoned. Conversely, if an effective artificial-gravity system is developed, research on countermeasures will become less urgent. The design, construction, and operation of rotating spacecraft may pose formidable technical challenges. Nonetheless, all investments in the program will otherwise be hostage to a favorable outcome in the human adap Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 40 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. tation issue. In the view of CHEX, the Synthesis Group's report erred ab initio in discarding consideration of artificial-gravity scenarios in its four architectures. Indeed, the provision of artificial gravity may well prove to be an architectural variable of more fundamental importance than the thematic differences between alternative mission emphases presented in the report of the Synthesis Group. CARDIOVASCULAR AND PULMONARY FUNCTION The redistribution of intravascular fluid toward the head is one consequence of exposure to a microgravity environment.18 This shift has not impaired astronauts' cardiovascular and cardiopulmonary function during the relatively short periods of exposure to microgravity experienced thus far. It has, however, caused clinically significant dysfunction following return to Earth. This dysfunction manifests itself as an orthostatic intolerance and decreased capacity for exercise. Full recovery appears to occur rapidly (within 2 to 5 days) following short flights but can take as long as 30 days following long flights. The potential exists for permanent impairment following prolonged adaptation to microgravity. Both acute and longer-term problems could occur upon landing on Mars, since its gravity is only about three-eighths that of Earth's. With limited health support available, reduced cardiovascular function could threaten the success of crew activities on Mars. Microgravity leads to a reduction in plasma volume that also contributes to orthostatic and exercise intolerance upon return to Earth. When the blood volume in the chest and head increases, the kidneys excrete more fluid. Another factor contributing somewhat to orthostatic hypotension and reduction in exercise performance is a decrease in total red blood cell mass. When exposures to microgravity are brief, both of these effects are reversible. Atrial and ventricular rhythm disturbances have occurred with significant frequency in both astronauts and cosmonauts and thus require attention. Particular examples include the following: 1. One cosmonaut was prematurely returned from Mir because of a refractory atrial rhythm disturbance. 2. Apollo 15's lunar module pilot sustained premature ventricular contractions (PVCs) with some episodes of bigeminy; 60 hours later he also had premature atrial contractions (PACs). Apollo 15's commander also sustained a run of PVCs. 3. The crew of Skylab 3 showed occasional PVCs and ectopic supraventricular contractions. 4. Atrioventricular block of brief duration has been observed in several crew members upon release of lower-body negative pressure before reentry. Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 41 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. 5. PACs have been observed in several astronauts during extra-vehicular activity. The mechanisms for these effects remain unknown but could be related to shifts in intravascular volume and ensuing perturbations of regulatory hormones. The significance of these effects is also unknown but could be a prelude to more severe problems. Further studies of the response of humans and animals to changes in gravitational force are essential to complete our understanding of the mechanisms responsible for cardiovascular and pulmonary deconditioning in space. Questions about the reversibility of deconditioning can be answered only by careful studies of animals and eventually humans, during and after prolonged exposure to microgravity. Adequate experimental controls require a centrifuge designed to accommodate primates. Specific high-priority areas of cardiovascular investigation include: 1. The role of exercise and physical fitness before, during, and after flight; 2. Countermeasures against cardiovascular dysfunction during flights and rehabilitation after long flights; 3. Validation of ground-based models of microgravity for short-term and long-term studies; and 4. Characterization of drug pharmacodynamics in microgravity. It is necessary to study the effects of long-term spaceflight on: 1. Cardiodynamics (e.g., cardiac output, chamber pressures and dimensions, and performance); 2. Cardiac rhythm (as shown by electrocardiograms taken at rest and during maximum exercise); 3. Hormone release and metabolism (e.g., of antidiuretic hormone, atrial antidiuretic peptide, and aldosterone); 4. Baroreceptor function (neural regulation of blood pressure); 5. Peripheral resistance (resistance offered to blood flow through the circulatory system); and 6. Pressures, degree of tone, and capacitance of the venous system. Ventilation and blood flow to the different regions of the lung are affected by gravity and so will obviously be affected by microgravity. To quantify these effects, studies of the rate and depth of respiration, the component lung volumes, air flow, gas exchange, and pulmonary pressures at 1 g and at different levels of microgravity are necessary. Another topic needing attention is potential effects of the space environment on cardiovascular and pulmonary physiology when modified by disease processes or pharmacological agents. Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 42 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. BEHAVIOR, PERFORMANCE, AND HUMAN FACTORS Empirical evidence suggests that the performance of crews composed of competent, highly trained individuals is critically determined by psychological and social factors.19 Moreover, psychosocial considerations necessarily assume greater importance when people are confined in isolated and inescapable environments. Reports from both cosmonauts and astronauts confirm the importance of psychological factors during long-duration missions. Despite awareness of the importance of these issues, systematic research into the determinants of human performance and adaptation under these conditions has received only minimal support. Only limited progress has been made since publication in 1987 of the Committee on Space Biology and Medicine research strategy, which included a chapter on human behavior. Because of the limited number and duration of American spaceflights, systematic research in this field could be conducted in analog environments such as polar stations, undersea habitats, and aviation settings. However, generalizing the results of research in such analogs has its limitations. Nevertheless, available data strongly indicate that focused research on small groups in confined quarters may result in practical knowledge that could reduce the incidence of interpersonal conflict and psychological problems. The utility of such data should be even greater when groups work for prolonged periods in isolation and when experimental interventions can be conducted under controlled conditions. The psychological factors relevant to the success of a mission can be organized into three domains: individual, group, and environmental. More basic research is urgently needed in each area. In addition to investigations in analog environments on Earth, the psychological determinants of current space operations, even short-duration shuttle missions, need more intensive study. Any single investigation, however, will lack features of a Mars mission such as the microgravity environment, exposure to radiation, mission duration, and lack of escape capability. Nevertheless, the aggregate findings from many such studies should provide important guidelines for the planning and conduct of very long missions. Individual Factors Just as technical competence is a prerequisite for task fulfillment, so also will the personality and motivation of each crew member critically influence the success of long-duration space missions. Efforts must be directed toward determining psychological profiles associated with performance and adjustment under conditions of prolonged isolation. Psychological selection strategies must be refined to focus not on screening out those Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 43 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. candidates showing evidence of psychopathology but rather on selecting those candidates with optimal attributes. Disruption of normal circadian (i.e., 24-hour) rhythms is another important factor to consider when planning long spaceflights. If unchecked, such disruption can lead to serious perturbations in human performance and productivity, with both psychological and physical consequences. Problems arising during exploration missions may be particularly severe since these rhythms appear to be disrupted by microgravity and/or high stress. Studies are needed to determine the optimal environmental conditions necessary to create the sense of normal circadian rhythms within the body during long-duration space missions. Group Factors Even the most technically competent and highly motivated individuals do not necessarily perform effectively and harmoniously when sequestered for prolonged periods in a confined environment. Moreover, the effects of seclusion can be exacerbated if escape is impossible. Improved methods are necessary for selecting and training teams so that they can sustain high levels of motivation, work quality, and interpersonal relationships. Training techniques developed to improve leadership, crew coordination, decision making, and conflict resolution in civil- and military-aviation settings need to be refined and validated in the space environment. Environmental Factors On long spaceflights, the crew's psychological environment is no less important than its physical environment. Additional research in operational, analog settings is required to determine the best social organization for human exploration missions. Issues central to crew effectiveness include: 1. How to organize daily activities to maximize performance and satisfaction (e.g., by providing meaningful, intellectually challenging work and enjoyable leisure activities) and to avoid boredom; 2. How to establish levels of automation that will balance efficient operations against operator control and satisfaction; and 3. How to establish an optimal division of responsibility between ground and space components to provide appropriate mission control while maintaining an efficient, cooperative relationship. Since crew safety is of paramount importance, the spacecraft commander must be vested with the final authority in all questions relating to the crew's health and welfare. The design of the physical environment for long-duration missions should be based on research into requirements for privacy, habitability, and social Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 44 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. interaction. A balance is necessary between engineering constraints and the requirements for harmonious group living over extended periods. In addition, the characteristics of the physical environment and the scheduling of work, leisure, and sleep cycles should minimize disruption of normal circadian functions. Many of these environmental and organizational issues could be profitably investigated in polar research stations and undersea habitats. BIOLOGICAL ISSUES The biological aspects of missions to Mars fall into two categories: those related to human well-being and those related only to exobiology. These overlap if a crew member is infected by a putative martian microorganism or if such organisms are returned to Earth. Although the chance is small that organisms, pathogenic or otherwise, exist on Mars today, public and legal concerns dictate close attention to this issue. The protocols for the preparation of Mars-bound craft or the handling of martian samples returned to Earth will depend both on the relevant planetary protection regulations promulgated by the Committee on Space Research (COSPAR) and on public perception of the risks. The latter arises now much more stridently than it did in the past when the issues of forward and back contamination were first raised. Existing COSPAR regulations (currently under review) may require that landers be sterilized to prevent the introduction of terrestrial organisms to the martian environment.20 The Viking spacecraft, for example, were decontaminated by a combination of presterilizing components and dry-heating the assembled landers prior to launch. Although these procedures were time consuming and extremely expensive, it may be required that they be applied to future robotic missions. Similarly, there is no question that rigorous procedures will be required for handling samples returned to Earth by robotic missions. A recent study21 has concluded that the question of forward contamination by robotic missions is an issue only for those that include life- detection experiments, where the concern is contamination of the experiment. It would, however, be virtually impossible to avoid forward contamination of Mars or back contamination of Earth from human exploration. Using the return flight as an incubation period and the crew as guinea pigs (as has been suggested22) is not a solution to back contamination on human missions. Would the whole mission be risked if an unanticipated contamination occurred? How would the cause of an infection be known with enough certainty to justify destroying the returning spacecraft before it entered Earth's atmosphere? The whole spacecraft, not only the astronauts, would be contaminated. In addition, infection might not be the only risk. A returning organism could possibly cause some long-term changes in our Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 45 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. environment, perhaps remaining undetected for a while. Although such an event may be judged to have a very low probability, a convincing case that prudence has been exercised will have to be made to the public. The scientific requirements relating to planetary protection and the assessment of the possibility of health-threatening microorganisms include: 1. How to detect the presence of indigenous microorganisms (potential pathogens) and their activities in samples returned to Earth prior to a human visit to Mars. A corollary is how to certify the biological safety of samples returned to Earth and of potential sites for human habitation. Simple culture experiments are insufficient because some organisms (e.g., the cholera-causing pathogen Vibrio cholerae) are not culturable using standard microbiological techniques. In fact, there is no unbiased assay to enable detection of even terrestrial microorganisms present at low concentrations. 2. How to detect potential pathogens during residence on Mars. The need for such detection may arise as novel habitats are encountered or as humans make use of martian resources such as water. 3. How to treat and handle an explorer in the highly unlikely event of infection by a martian life form. 4. How to monitor the fate and impact of terrestrial microorganisms unavoidably transported to Mars by vehicles or humans. Addressing these issues will involve investigations of Mars-like environments on Earth as well as laboratory studies to develop the necessary tests, procedures, and protocols. NOTES AND REFERENCES 1. Space Science Board, Space Science in the Twenty-First Century: Imperatives for the Decades 1995 to 2015: Overview, National Academy Press, Washington, D.C., 1988, pp. 67– 68. Also see Advisory Committee on the Future of the U.S. Space Program, Report of the Advisory Committee on the Future of the U.S. Space Program (the "Augustine report"), U.S. Government Printing Office, Washington, D.C., 1990, p. 6. 2. Synthesis Group, America at the Threshold, Report of the Synthesis Group on America's Space Exploration Initiative, U.S. Government Printing Office, Washington, D.C., 1991, p. 24. 3. See Ref. 2, p. 27. 4. NASA, Report of the 90-Day Study on Human Exploration of the Moon and Mars, NASA, Washington, D.C., November 1989, p. 6–2. 5. See Ref. 4, p. 6–3. 6. International Commission on Radiological Protection, Recommendations of the International Commission on Radiological Protection, ICRP Publication 60, Annals of the ICRP 21(1–3):1– 201, 1991. The equivalent dose in tissue, HT, is given by the summation: HT = ΣR WR ·DT, R Copyright © National Academy of Sciences. All rights reserved.

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The Human Exploration of Space http://www.nap.edu/catalog/6058.html CRITICAL RESEARCH REQUIREMENTS 46 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. where DT, R is the absorbed dose averaged over the tissue or organ T due to radiation R. The weighting factor, WR, is selected for the type and energy of the radiation incident on the body. Its value is based on the relative biological effectiveness (RBE) for the radiation in inducing stochastic effects (that is, cancer and genetic damage) at low doses. It is vitally important to remember that these effects of long-term exposure to relatively low doses of radiation are in addition to any deterministic effects (the physical damage to tissues) likely to result from large doses of ionizing radiation. 7. The sievert is the unit of dose equivalent and is equal to the absorbed dose (in grays) multiplied by the quality factor. One gray is an absorbed dose of 1 joule per kilogram. One sievert = 100 rem. One gray = 100 rad. 8. J.H. Adams, Jr., G.D. Badhwar, R.A. Mewaldt, B. Mitra, P.M. O'Neill, J.F. Ormes, P.W. Stemwedel, and R.E. Streitmatter, "The Absolute Spectra of Galactic Cosmic Rays at Solar Minimum and Their Implications for Manned Space Flight," Galactic Cosmic Radiation Constraints on Space Exploration, NRL Publication 209–4154, Naval Research Laboratory, Washington, D.C., November 1991. 9. J.R. Letaw, R. Silberberg, C.H. Tsao, and E.V. Benton, Advances in Space Research, Vol. 9, No. 10, p. 257, 1989. 10. J.H. Adams, Jr., and A. Gelman, "The Effects of Solar Flares on Single Event Upset Rates," IEEE Transactions on Nuclear Science, NS-31, pp. 1212–1216, 1984. 11. National Council on Radiation Protection and Measurements, Guidance on Radiation Received in Space Activities, NCRP Report No. 98, National Council on Radiation Protection and Measurements, Bethesda, Maryland, 1989, p. 25. 12. Space Studies Board, Letter to James D. Watkins and Daniel J. Goldin, August 20, 1992, Washington, D.C., 1992. 13. Space Science Board, A Strategy for Space Biology and Medical Sciences for the 1980s and 1990s, National Academy Press, Washington, D.C., 1987, p. xiii. 14. See Ref. 13, p. ix. 15. See Ref. 13, Chapter 5. 16. L.G. Lemke, "An Artificial Gravity Research Facility for Life Sciences," Proceedings of the 18th Intersociety Conference on Environmental Systems, American Institute of Aeronautics and Astronautics, 1988. For more information on tethers, see P.A. Penzo and P.W. Ammann (eds.), Tethers in Space Handbook, Second Edition, NASA, Washington, D.C., 1989. 17. Committee on Human Exploration of Space, Human Exploration of Space: A Review of NASA's 90-Day Study and Alternatives, National Academy Press, Washington, D.C., 1990, p. xi. 18. See Ref. 13, Chapter 6. 19. See Ref. 13, Chapter 11. 20. Space Science Board, Recommendations on Quarantine Policy for Mars, Jupiter, Saturn, Uranus, Neptune, and Titan, National Academy of Sciences, Washington, D.C., 1978. See also Space Studies Board, Biological Contamination of Mars: Issues and Recommendations, Task Group on Planetary Protection, National Academy Press, Washington, D.C., 1992. 21. Space Studies Board, Biological Contamination of Mars: Issues and Recommendations, National Academy Press, Washington, D.C., 1992. 22. See Ref. 2, p. 77. Copyright © National Academy of Sciences. All rights reserved.