SCIENCE DIRECT"

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2johnson Space Center, Houston, TX 77058, United States of America. 3Langley .... employer is again that of mutual obligation to minimize risk. Accurate and ...
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Pergamon

SCIENCE~DIRECT"

www.elsevier.corrdlocate/asr

PII: S0273-1177(02)00653-1

RADIATION RISK AND HUMAN SPACE EXPLORATION W. Schimmerling 1, F. A. Cucinotta2, and J. W. Wilson 3

1National Aeronautics and Space Administration, Washington, DC 20546, United States of America 2johnson Space Center, Houston, TX 77058, United States of America 3Langley Research Center, Hampton, VA 23681, United States of America ABSTRACT Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented. Published by Elsevier Science Ltd on behalf of COSPAR.

PROBLEM DEFINITION (NASA, 1998) The components of space radiation that are of concern are high-energy, charged particles, especially the component of galactic cosmic rays (GCR) consisting of high-energy (high-E) nuclei of heavier (high atomic number Z) elements ("HZE particles"). Exposure to this radiation results in two main types of radiation risk: 1. Short-term consequences of relatively high levels of radiation, such as might be caused by a Solar Particle Event (SPE). This type of radiation risk is mainly due to cell depletion of sensitive tissues, such as the bone marrow, intestinal epithelium, skin, etc., and may lead to symptoms affecting the health and performance of crews during a mission. 2. Long-term exposure to expected levels of solar and galactic cosmic radiation results in an enhanced probability of cancer and, possibly, changes in the cells of the brain, reproductive organs or other tissues. Some of these risks may have no impact during a mission, but involve a significant probability of deleterious health effects later in life. Predictions about their nature and magnitude are subject to very large uncertainties. The magnitude of these uncertainties is difficult to estimate and depends on the type of risk and the models used for risk prediction. Prudent use of worst-case scenarios based on large uncertainty leads to excessive engineering margins. Such margins may impose unacceptable constraints on shielding mass for spacecraft or habitats and on the radius and duration of sorties on planetary surfaces. The risks posed by space radiation to humans living and working in spacecraft, planetary surfaces or space stations cannot be eliminated entirely by any known means. The goal of radiation protection in space thus becomes the problem of reducing these risks to levels that can be regarded as relatively safe. To achieve this goal, it is necessary to establish what the risks are; in particular, whether space radiation poses any risks not encountered by exposure to radiation sources common on Earth, i.e., mainly Adv. Space Res. Vol. 31, No. 1, pp. 27-34, 2003 Published by Elsevier Science Ltd on behalf of COSPAR Printed in Great Britain 0273-1177/03 $22.00 + 0.00

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x-rays and similar low linear energy transfer (LET) radiation. Secondly, the magnitude of these risks must be predicted, so that procedures based on quantitative information can be devised. Finally, these predictions need to be accurate to avoid incurring excessive costs by compensatory designs or incurring excessive risks by underestimation. Quantitative risk predictions make it possible to establish radiation limits. In reality, these are risk limitations, based on an attainable minimum accepted risk (NCRP, 1989), Such limits cannot, by themselves, be used as operational levels requiring action to control risk; they are intended as absolute barriers that should be unbreachable under any conceivable normal operating procedure (NCRP, 1993) These definitions will also depend on the countermeasures, if any, that can be developed to mitigate radiation risk° ETHICAL CONSIDERATIONS The decision of what risk levels to accept involves moral and legal issues as well as practical issues (NCRP, 1997) The ethics of risk acceptance are, of necessity, a matter requiting continuous deliberation and vigilance in a moral society. Several criteria can be considered in the process of establishing limits to worker risks. A thoughtful series of talks on these issues can be found in the proceedings of the ThirtySixth Annual Meeting of the National Council on Radiation Protection and Measurements, in the session on "Developing Public Policy in the 21 st Century"° April 5-6, 2000. Among the most salient are utilitarian ethical principles and limitations based on informed consent. Utilitarian ethical principles result from a comparison of costs and benefits. In some cases, e.g., military engaged in the defense of their country or medical workers treating victims of infectious diseases, individuals are expected to assume risks for the good of their community that they would not otherwise assume° In daily life, all industrial occupations involve a measure of risk of injury, or even death. Individuals accepting employment incur contractual rights and obligations, including the acceptance of the risks associated with their workplace. In this case, there exists a largely implicit compact between worker and employer, where both accept to act in ways that minimize such risks. Indeed, risk-based radiation limits are based on the risks associated with industries regarded as safe (NCRP, 1997; ICRP, 1990). In democratic societies based on government by consent of the governed, the paradigm of informed consent is also applicable. The informed individual makes his or her own cost/benefit estimates in order to freely enter into contractual rights and obligations and the compact between the individual and the employer is again that of mutual obligation to minimize risk. Accurate and timely information about the risks incurred is essential to ensure informed consent. However, the maximum risks to which individuals may consent are limited by society, representing the interests of an individual's families and associates, as well as the broader societal interest in the well being of the members of the community. In addition, societal limitations serve to insure that an individual's need to pursue a livelihood does not result in coercion (or the appearance of coercion) to accept an untoward risk. Based on these moral considerations, there generally exists a legal framework within which actions are required of management and of workers. Such action levels provide a series of steps at which risks are examined, permissible operations are defined, and procedures are implemented to ensure that the limiting risks are never incurred. Where appropriate, these steps take into account possible countermeasures, which can generally be classified as avoidance, mitigation, and intervention. In the field of radiation protection, such procedures are grouped under the name of ALARA (As Low As Reasonably Achievable) Principle (NCRP, 1998). In a sense, this name is unfortunate because it seems to imply to the casual observer that there is a degree of arbitrariness in the setting of radiation limits. In reality, of course, the term refers to the flexibility allowed in good radiation protection practice that is required to ensure that radiation limits are not only never broached but that exposures are held to an achievable minimum.

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COUNTER/VIEASURES There are five possible approaches to mitigate risk, but only the first two of these are currently practical and cost-effective. 1. Operational: limit the time of exposure and the duration of exposure by various strategies, such as selecting older crew members, avoiding extravehicular activity (EVA) during impending SPE, using spacecraft transfer trajectories that minimize the duration of interplanetary travel, etc. 2. Shielding: Computational tools have been developed to calculate how incident radiation is modified at any depth in materials; these tools have become the standard engineering method for estimating spacecraft shielding (Wilson et al., 1991). These methods can also be used to optimize the shielding properties of different material arrangements. At the present time, shielding is the most effective single countermeasure available. 3. Screening: it is well known that some individuals have genetic predispositions resulting in a higher cancer risk than normal. Procedures to screen for radiation susceptibility (or, if it can be demonstrated, abnormal radiation resistance) may provide the information required for individual consent. The proper course of action to follow if testing reveals higher cancer susceptibility must be ascertained. Aggressive medical surveillance of such individuals, if they elect to continue working in a space radiation environment, may be warranted. 4. Prevention: while current knowledge of substances useful for radiation protection is limited, pharmaceuticals may be used as radioprotectants for proton radiation exposures, but they have serious side effects and may not be useful for protection against HZE particles. Genetic methods to enhance the organism's ability to repair radiation damage (a "radiation vaccine") may be conceptually possible but are clearly beyond the horizon. 5. Intervention may be required to deal with prompt radiation effects arising, for example, from high radiation levels caused by solar disturbances. Biomolecular intervention after radiation exposure may be possible in the future, perhaps using gene therapy methods to enhance cell repair or inspect damaged cells and induce programmed cell death in them. UNCERTAINTIES Long-term risk prediction is based on an analysis of the surviving population of Hiroshima and Nagasaki (NCRP, 1989). This model derives estimates of cancer mortality using a two-part extrapolation: from high dose and dose rate to low dose and dose rate by means of a "dose and dose-rate effectiveness factor" (DDREF); and, from low LET to high LET (the space radiation environment), by means of an LET-dependent quality factor (Q). Radiobiological data, mainly in the form of a relative biological effectiveness (RBE) are used qualitatively, as a guide in defining short-term effects as well as in the definition of Q. Thus, the contribution to the uncertainty in risk prediction for a given radiation exposure consists of uncertainties in each of: space radiation environment, radiation transport through shielding and tissues, DDREF, and Q. The US National Academy of Sciences (NRC, 1996) has estimated a range for these uncertainties as, respectively, +10% to +15% (space radiation environment), _+50% (radiation transport), _+200% to _+300% (DDREF), and _+300% to _+500% (Q). Models of the galactic cosmic radiation environment are now estimated to be accurate to within _+ 15% (Badhwar and O'Neill, 1996). Measurements of shielding properties of conventional and new materials obtained in a laboratory neon beam have been reported to be within _+30% of calculated values (Schimmerling et al., 1989). As in any prediction of risk, uncertainties are correlated, and the final estimate in Ref. 9 is that risk estimates for space exploration may be a factor of 10-15 too large or a factor of 10-15 too small. Without quantitative justification, we guess that further progress in research has reduced the factor of 10-15 to be approximately a factor of 6.1

NOTE ADDED IN PROOF: since this presentation, a quantitative analysis of uncertainties has been published by Cucinotta et al. (2001).

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CRITICAL QUESTIONS (NASA, 1998) In the United States, the National Aeronautics and Space Administration (NASA) has adopted an end-to-end risk assessment approach. This approach is based on integrating basic scientific knowledge into risk predictions. It is assumed that the uncertainty in these predictions reflects the limitations of current'radiobiology, and that advances linked to research will significantly reduce these uncertainties. Over the past decade, several groups of expert scientists have considered the "Critical Questions" that need to be answered in order to achieve this program. A detailed listing may be found in NASA (1998), and an illustration of this description is shown in Fig. 1, detailing how each level of understanding links with the next. • what is radiation risk (effect and uncertainty) to h u m a n s in space?

- synergies, probability of early/late - stochastic/deterministic effects, radiation limits, countermeasures Immune System ] and Other Effects of Weightlessness

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• what is radiation risk to h u m a n s on Earth?

- extrapolation from animal models, age dependence, latency, protection /

[ Life shortening Late effects

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• what is radiation risk for small m a m m a l s ?

- genomic instability, signal transduction, apoptosis, carcinogenesis

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- DNA repair, apoptosis, genomic instability, cell cycle, transformation, mutation, epigenetic effects

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• what is the interaction of radiation with matter?

- radiation environment, energy deposition, track structure, chemical interactions Fig. 1. Critical questions to predict risk and reduce uncertainty with examples of investigations associated with each level of complexity.

In Fig. 1, the arrows at the right denote the type of investigation that is appropriate for the level of complexity to which each group of critical questions refers. The boxes offer examples of some of the ways in which the information from one level may be extrapolated the next upper level. At the level of humans in space, useful predictions can only be made on the basis of human radiation exposures on Earth; the most frequently used being epidemiological studies of bomb survivors. However, when the results of animal studies are incorporated, studies on life shortening and other late effects in small mammals can be used to estimate quality factors and their LET dependence. Extrapolation of data from cellular biology is required to interpret some of the results of in vivo studies; for example, cell survival studies can be linked

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to acute effects. Together with knowledge of dose rate and mixed field exposure effects, these can be used to derive estimates of the relative weight to be assigned to different organs. As knowledge of molecular biology advances, mechanisms for particular radiation responses in cells can be postulated and tested in transgenic animals. Such knowledge can, in turn, be used to derive estimates of carcinogenesis and of the likely effect of combining radiation insults with physiological conditions thought to accompany weightlessness in space. Finally, models of the interaction of radiation with matter and the subsequent fate of the chemical species produced can be used to integrate the entire chain of reasoning into the ultimate risk predictions in space. GROUND LABORATORY AND SPACE MEASUREMENTS The biological knowledge required to predict risk in space is best developed at ground-based accelerator facilities, where beams of the protons and nuclei that constitute GCR can be accelerated to the energies of particles in the space radiation environment (Schimmerling et al., 1999). However, not all studies can be performed on the ground. The requirements for space-based research have been discussed elsewhere [9 > (Schimmerling, 1995). Predictions using 5" ground laboratory data need to be validated in E -,1 space flight, to take into account the C limitations of particle accelerators in 2 simulating space radiation, and to take into c account aspects associated with living in 0 0 space° e_= Some important problems can only be i, resolved in space. One important example is 0 "10 the characterization of the shielding properties of planetary surfaces. Defining the 10-2 10"1 1 10 102 103 radiation dose and radiation quality on the Energy ( M e V ) surface of Mars, which depends on the Fig. 2. Calculated neutron spectrum on the shielding properties of the Martian surface of Mars (for the February 1956 Solar atmosphere, and demonstrating the accuracy Particle Event) and the direct and surfaceof model calculations, requires an on-site backscattered components (left ordinate). Also measurement. An even more interesting d r a w n are the neutron weighting factors example is related to the neutron fluence on recommended by the ICRP (1990) (right ordinate), the Martian surface. In the energy range from showing that the backscattered neutrons are in the thermal up to 20 MeV and above, highest radiation risk range. backscattered neutrons from Martian soil are the main source. These neutrons are made in the Martian atmosphere, but the atmosphere is too thin to attenuate the neutrons effectively. Figure 2 shows a calculation (made by Wilson) of the direct and backscattered neutron component on the surface of Mars, showing that the backscattered component falls into the most effective energy region. A

m

BASIC AND APPLIED SCIENCE For programmatic purposes, it is convenient to consider basic and applied science separately. In this scheme, basic science is best developed by investigator-initiated research, whereas applied science offers greater opportunities for mission-oriented research and development. Furthermore, while the focus of the present article is on the integrated NASA program, the quality of final risk management also depends on progress in related fields. These range from molecular biology and neurosciences, to solar physics. In

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particular, advances in solar physics and development of solar observation are essential to provide the 1012 hr forecast required for SPE, with a 6-8 hr forecast of the magnitude and spectral slope of the event as it progresses. To be credible, such information will have to be more than 90 percent accurate, with a false alarm rate less than 10 percent (Turner, 1996). The basic science components of the NASA research program (NASA, 1998), according to endpoin t , goals and examples of expected outcomes are outlined in the following paragraphs. The overall program also has a significant component directed toward the International Space Station; a discussion of this component has not been explicitly included. • Acute and Early Effects: Goal: understand possibilities of radiation effects with impact on performance Expected outcome: 1) provide data to determine acute risk within factor of 2 by end of 2002; 2) dose rate and LET-aependence for bone marrow, skin, central nervous system (CNS) and lymphopoetic tissue; 3) SPE reference design environment; 4) understand cumulative effects of protons and HZE for 2-3 year exploration class mission. • Risk of Carcinogenesis - Goal: understand risk of cancer and role of genomic instability - Expected outcome: 1) provide data for carcinogenesis RBE accurate to factor of 2 by 2002 and •+50% by 2009; 2) mechanistic in-vivo/in vitro models of carcinogenesis; 3) new approaches for risk extrapolation from animals to humans; 4) implement breakthroughs in general cancer research, expected in the program time frame, for applications to space radiation protection • Risk of CNS Damage - Goal: understand harmful effects of GCR on CNS - Expected outcome: 1) identify any unique effects of HZE on CNS; 2) understand cumulative effects of protons and HZE for 2-3 year exploration class mission; 3) implement breakthroughs in brain research expected in the program time frame • Synergistic Effects of Spaceflight and Radiation Goal: understand possible synergistic effects from microgravity and other spaceflight factors that may alter biological responses to radiation - Expected outcome: 1) establish whether altered cytokine levels affect carcinogenic, CNS, or acute risks; 2) establish whether bone degradation or altered immune response affect carcinogenic risk; 3) establish effects nf hypogravity on cellular and molecular processes related to radiation response -

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The applied science components, similarly outlined according to end-point, goals and examples of expected outcomes are: • Environmental Definition Goal: understanding of space radiation environment including temporal variations - Expected outcome: 1) Mars robotic measurements for transit and surface environments including neutron albedo; 2) SPE reference design environment; 3 ) G C R composition and temporal variations with accuracy of_+15%; 4) SPE forecasting • Radiation Shielding and Spacecraft Design - Goal: optimize shielding for permanent human presence - Expected outcome: 1) nuclear reaction cross sections and yield data from accelerator measurements; 2) improved transport methods validated to +25% accuracy by 2004; 3) new structural materials with improved shielding characteristics; 4) standard engineering design tools • Dosimetry - Goal: characterize spectra of n, p, HZE for individual tissues -

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Expected outcome: 1) improved physical dosimetry; 2) crew personal equivalent-dose measurements; 3) international calibration, data sharing and intercomparisons; 4) biological dosimetry including ch.romosome aberrations and protein expression as biomarkers Crew Risk Mitigation - Goal: develop biomedical countermeasures including prevention, intervention and emergency care for unscheduled radiation exposures in space - Expected outcome: 1) emergency care procedures; 2) resolve ethical issues related to permissible radiation exposure for permanent human presence in space; 3) understand applicability of genetic screening approaches; 4) apply molecular biology breakthroughs to development of radioprotecting agents

CONCLUSIONS The NASA approach to improvement of risk management has been described. It is science-based and relies heavily on the development of an understanding of radiobiological response mechanisms at all levels of complexity. In addition, the program is poised to take advantage of breakthroughs in related fields that the current pace of scientific discovery makes inevitable. A balance of basic and applied research is necessary to ensure that the results are made available in a timely manner to decision makers, both in the planning stage and in the operational stage. Finally, the exposure of human beings to risk demands the highest level of ethical awareness in order to achieve exploration without compromising the respect due to the humanity of the explorers. REFERENCES Badhwar, G.D. and P. M. O'Neill, Galactic Cosmic Radiation Model and its Applications. Adv. Space Res. 17, 7-17, 1996.

Cucinotta, F.A., W. Schimmerling, J. W. Wilson, L.E. Peterson, G.D. Badhwar, P. B. Saganti, and J. F. Dicello. Space Radiation Cancer Risks and Uncertainties for Mars Missions. Radiat. Res. 156, 682688, 2001. ICRP. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Annals of the ICRP, 21: No. 1-3, Pergamon Press, Oxford. 1990. NASA (National Aeronautics and Space Administration of the United States of America). Space Radiation Health Research Strategic Program Plan. 1998. Available on the Internet at the following URL: spaceresearch.nasa,gov/common/docs/radiation strat_plan1998.pdf, 1998. NCRP (National Council on Radiation Protection and Measurements). Guidance on Radiation Received in Space Activities. NCRP Report 98. Bethesda, MD. 1989~ NCRP (National Council on Radiation Protection and Measurements). Limitation of Exposure to Ionizing Radiation. NCRP Report No. 116. Bethesda, MDo 1993. NCRP (National Council on Radiation Protection and Measurements). Acceptability of Risk from Radiation - Application to Human Space Flight. Symposium Proceedings No. 3. Bethesda, MD 1997. NCRP (National Council on Radiation Protection and Measurements). Operational Radiation Safety Program. NCRP Report No. 127. Bethesda, MDo 1998~

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NRC (National Research Council/National Academy of Sciences of the United States). Task Group on the Biological Effects of Space Radiation. Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies. Washington, DC. Space Studies Board Commission on Physical Sciences, Mathematics and Applications. National Academy Press. 1996. Turner, R., Editor, Foundations of solar particle event risk management strategies: findings of the risk management workshop for solar particle events, ANSER Technical Report, Arlington, Virginia, July 1996. Schimmerling, W. Space and radiation protection: scientific requirements for space research. Radiat. Environ. Biophys. 34, 133-137, 1995. Schimmerling, W., J.W. Wilson, F.A. Cucinotta, and M-H. Kim. Requirements for simulating space radiations with particle accelerators. In: Risk Evaluation o__fCo~mic-Ray Exposure in Long-Term Manned Space Mission (K. Fujitaka, H. Majima, K. Ando, H. Yasuda, and M. Susuki, Eds., Kodansha Scientific Ltd., Tokyo, 1999), pp. 1-16 International Workshop on Responses to Heavy Ions. July 9-10, 1999. Chiba, Japan Schimmerling, W., Jack Miller, Mervyn Wong, Marwin Rapkin, Jerry Howard, Helmut G. Spieler, and Blair V. Jarret. The Fragmentation of 670A MeV Neon-20 as a Function of Depth in Water. I. Experiment. Radiat. Res. 120, 36-71, 1989.

Wilson, J.W., Townsend, L. W., Schimmerling, W., Khandelwal, G.S., Khan, F., Nealy, J. E., Cucinotta, F.A., Simonsen, L.C., Shinn, J.L. And Norbury, J.W., Transport Methods and Interactions fo._.~rSoace Radiations. NASA Reference Publication 1257, National Aeronautics and Space Administration, 616 p.Washington, DC. 1991.