Everything You Wanted to Know About Spaceradiation but Were Afraid To

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Everything You Wanted to Know About Space Radiation but Were Afraid to Ask Chancellor, JC1,2,9,*, Nowadly, C3, Williams, JA6, Aunon-Chancellor, SM2,7,8, Chesal, ME1, Looper, J4, and Newhauser, W1,5

1Department of Physics & Astronomy, Louisiana State University, Baton Rouge, LA, USA 2Department of Preventive Medicine & Population Health, University of Texas Medical Branch, Galveston, TX, USA 3Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, TX 4Department of Veterinary Clinical Sciences, LSU School of Veterinary Medicine, Baton Rouge, LA, USA 5Department of Physics, Mary Bird Perkins Cancer Center, Baton Rouge, LA, USA 6Departments of Environmental Medicine & Radiation Oncology, University of Rochester Medical Center, Rochester, USA 7Department of Internal Medicine, LSU Health Science Center, Baton Rouge, LA 8Astronaut Ofﬁce, NASA Johnson Space Center, Houston, TX 9Fellow, Outerspace Institute, University of British Columbia, CA *Author to whom correspondence should be addressed; [email protected]

ABSTRACT

The space radiation environment is a complex combination of fast-moving ions derived from all atomic species found in the periodic table. The energy spectrum of each ion species varies widely but is prominently in the range of 400–600 MeV/n. The large dynamic range in ion energy is difﬁcult to simulate in ground-based radiobiology experiments. Most ground-based irradiations with mono-energetic beams of a single one ion species are delivered at comparatively high dose rates. In some cases, sequences of such beams are delivered with various ion species and energies to crudely approximate the complex space radiation environment. This approximation may cause profound experimental bias in processes such as biologic repair of radiation damage, which are known to have strong temporal dependancies. It is possible that this experimental bias leads to an overprediction of risks of radiation effects that have not been observed in the astronaut cohort. None of the primary health risks presumely attributed to space radiation exposure, such as radiation carciogenesis, cardiovascular disease, cognitive deﬁcits, etc., have been observed in astronaut or cosmonaut crews. This fundamentally and profoundly limits our understanding of the effects of GCR on humans and limits the development of effective radiation countermeasures.

Why do we need yet another review of Passive shields use bulk material ﬁelds , e.g., the vehicle, space radiation research? habitat and or local regolith, to attenuate radiation, whereas proposed magnet shields deﬂect charged- particle radiation Space travelers are exposed to a myriad of environmental away from habituated areas.4–9 The expecteds exposures stressors, including chemicals from equipment,“microbes” can be reduced by shortening the mission, e.g., with higher- from occupants of the space vehicle, and microgravity, to impulse propulsion systems such as ion propulsion drives. name a few. Cosmic radiation exposures are a particularly Other approaches include radiation sensitivity as crew selec- challenging environmental stressor because they vary strongly tion criterion, biologic countermeasures (e.g., radioprotective in magnitude and quality with vehicle trajectory, mission du- drugs), increased medical surveillance of exposed crew, and ration, and solar activity. Rare but potentially-lethal solar even pre-exposure prophylactic surgical removal of the sensi- eruptions of protons and other particles, which could result tive female breast has been proposed. More than a half century in mission failures, have so far proven utterly unpredictable, later, intensive research has not revealed a method to fully mit-

arXiv:2103.17153v1 [physics.bio-ph] 31 Mar 2021 1,2 precluding mission timing as a mitigation strategy. To igate the radiation risk, and our understanding of the physics complicate matters further, the risks to humans vary strongly and biology of these risks remains incomplete. Consequently, with the radiation exposure and the host, e.g., age, sex, and radiation risk prediction and management leads as the major genetic profile of each individual. Risk projections for in- unmet challenge for planning future crewed missions, espe- dividuals astronauts are highly uncertain and controversial. cially as spaceflight missions increase and we travel outside Although some progress has been made toward understanding the earth’s protective magnetic field.2 and mitigating the risks of radiation to astronauts, the overall situation has scarcely improved since the dawn of crewed A promising approach to solving major gaps our the knowl- spaceflight.2,3 edge on radiation effects is to rely on ground based research Several approaches are possible to mitigate space radiation involving those effects in animals. Research efforts have risks. The use of shielding can reduce the radiation exposures. been frustrated by a scarcity of robust biologic and physical surrogates for such experiments. These obstacles have Z=28 (Nickel).2, 13 Ions heavier than nickel are also present, made it difficult to translate radiation risk models from animal but they are rare in occurrence. The fluence (the number of models to humans.10, 11 The health risks to spaceflight ex- incident particles crossing a plane of unit area) of GCR par- plorers because of the space radiation environment, therefore ticles in interplanetary space range fluctuates inversely with remains incomplete, compounded by the disparities between the solar cycle, with dose rates of 50 to 100 mGy/year at solar findings from space-based observations of human astronauts maximum to 150 to 300 mGy/year at solar minimum,14–16 vs. ground-based experiments. Recently, we proposed new During spaceflight transit outside of low-Earth Orbit (LEO), methods and avenues of inquiry that overcome many of the every cell nucleus within an astronaut would be traversed by a obstacles previously encountered.12 Here we will discuss sev- hydrogen ion or energetic electron (e.g., delta ray) every few eral methodological aspects of ground-based experimentation days, and by the heavier GCR ion (e.g., O, Si, and Fe ions) which, if improved, will more faithfully mimic the complex every few months.3 Heavy ions, despite their comparatively radiation environment encountered in a variety of spaceflight lower fluences, contribute a significant amount to the GCR missions. dose that astronauts will incur outside of LEO because of their large ionization power because of their large ionization power. Shown in Fig.2 is the GCR flux, dose, and dose equiv- alent1 up to nickel, Z=28. Light ion species such as hydrogen and helium make up most of the GCR spectrum, but heavier ions such as silicon (Z=14), iron (Z=26), etc., contribute significantly once the biological equivalent dose is factored. The swiftest of the GCR heavy ions are so penetrating that shielding can only partially reduce the intra-vehicular (IVA) doses.17 In theory, more massive shielding could provide some additional protection, but in practice this is limited by the payload lift capabilities of spacecraft launch systems. In fact, studies have shown that aluminum shielding equivalent to 16 times the thickness of the Apollo command module can reduce the GCR exposure by up to 25%. Similarly, the equivalent mass of polyethylene, a better shielding material but an inferior structural material, would only provide a %35 Figure 1. Components of the space radiation environment. reduction in GCR dose.18, 19 Operational space radiation environment is comprised of three sources of ionizing radiation, energetic protons from solar particle Flux events, relativistic heavy ions of the galactic cosmic ray spectrum, Dose 100 Dose Equivalent and trapped electrons and protons in the Van Allen Belts. Image

1 courtesy of ESA. 10−

3 What exactly is the operational space radi- 10− ation environment? Relative Contribution

5 The operational space radiation environment, shown in Fig.1, 10− can be divided into three separate ionizing radiation sources, solar wind consisting of mostly low energy protons and elec- H C Na S Sc Fe trons, heavy-charged particles found in the Galactic Cosmic Charge (Z) Ray (GCR) spectrum, and energetic protons associated with a Solar Particle Event (SPE).2 The background dose rate for Figure 2. Relative abundance of the GCR spectrum, and the solar-wind protons varies with the solar cycle (9-14 year pe- contribution to dose and dose equivalent from hydrogen (Z = 1) riod, average of 11 years). Even at solar maximum, the con- to nickel (Z = 28). Heavier ions such as Z = 26 make up a tribution is much less than that from GCR and therefore is relatively small portion of the spectrum, however, they considered a negligible risk.3 GCR nuclei originate from contribute larger energy doses to the cumulative radiation outside our solar system and possess sufﬁcient energies to exposure than even hydrogen or helium ions. penetrate any shielding used on current mission vehicles. As demonstrated in Fig.2, the GCR spectrum consists of about 1Dose equivalent, H, is a measure of the biological damage to living tissue 87% hydrogen ions (Z=1 or protons) and 12% helium ions as a result of radiation exposure and is calculated as the product of absorbed dose, D, in tissue multiplied by a quality factor, Q, the is dependant on the (Z=2 or alpha particles), with the remaining 1-2% heavier linear energy transfer of the radiation particulate, H = QD. The SI units of nuclei with charges ranging from Z=3 (Lithium) to about dose equivalent is sieverts (Sv).

2/9 SPEs consist of high-energy protons that emanate from effects and diseases.10, 24 These experiments have contributed the Sun in regions of magnetic instability.20 SPE radiation significantly to our understanding of disease mechanisms, but is primarily composed of protons with kinetic energies rang- their relevance to and suitability for predicting outcomes in ing from 10 MeV up to several GeV (Giga electron Volts). humans is controversial, e.g., for non-astronaut patients25, 26 The fluence from and occurrence of SPEs is unpredictable, and astronauts alike.2, 27 A major limitation of current animal but dose-rates as high as 1500 mGy/hour (approximately models is that animals are, in some relevant ways, profoundly 3000mSv/hour)2 have been measured.21 During an SPE, a different from humans in their response to radiation, e.g., at localized magnetic disturbance of the Sun resultss in the re- the cellular, organ, and organism levels. This could be ex- lease of intense bursts of ionizing radiation that follow mag- plained by limitations in current methods in animal studies, netic field lines. Their irregular and unpredictable occurrence leading to systematic bias, flawed data, and and uncertainty is evidenced by the unusual occurrence of four comparably of the validity of qualitative conclusions regarding efficacy large SPEs in a period of 4 months during the 22nd solar of, for example, countermeasures.2, 10 Rodent models may be cycle.7, 22, 23 Computer simulations reveal that the dose dis- less well suited to test outcomes in normal tissue responses to tribution in an astronaut would be highly non-homogeneous, radiation in humans due to their high level of genetic instabil- with a relatively high superficial dose and a lower internal ity. There is evidence that larger mammalian models such as dose. Extravehicular exposures carry higher risks than in- canines provide a better model for radiation research. DNA travehicular exposures because the shielding provided by the repair mechanisms are highly conserved between mammalian space suit is much less than that of the vehicle. Even inside species, and that there is high homology between key DNA the vehicle, an SPEwould still expose astronauts within the damage response genes in humans and dogs.10, 28 Numerous spacecraft to non-negligible levels of radiation. Although studies in dogs have modeled normal tissue radiation response large SPE doses can instigate so-called late-occuring effects and those studies have helped optimize human oncology care, such as radiogenic cancer, ocular cataracts, respiratory and however, no large studies of canine models have been used in digestive diseases, and damage to the microvasculature, these space radiation studies on normal tissue effects. are mostly latent for many months, years, or even decades Limitations in the ability to translate study outcomes into after exposure, and by definition they should not manifest as equivalent health consequences in humans also result from an immediate risk to crew health during the mission.3 critical disparities, usually disease-specific, between the ani- As future missions are planned outside LEO and away from mal models and the human subject in clinical trials and space the protection of the Earth’s magnetic shielding, the range of missions, for example the development of harderian gland possible radiation exposures that astronauts may encounter is tumors which only appear in mice.10, 11, 29 Additionally, be- markedly different from those of LEO. The risks from GCR cause non-human mammals are genetically different from and SPE exposures are increased. As previously mentioned, humans, they may yield results that are difficult to interpret. massive shielding in spacecraft can reduce but not eliminate A growing list of genes is known to affect radiation sensitivity these exposures. In fact, collisions between GCR particles phenotypes for numerous radiation effects, such as molec- and the nuclei of shielding materials can initiate an avalance ular, chromosomal, signal transduction associated growth- (sometimes called a nuclear cascade or shower) of nuclear regulating changes, cell killing, tumor acute and late effects, reactions. Consequently, niaively increasing the shielding and animal carcinogens. To date, however, there is still no mass can actually increase the radiation risk from secondary knowledge that would allow a direct connection to be drawn particles from the avalanches. The optimal mass of shielding between observed changes in gene sequence and a correspond- to attenuate SPE radiation is thought to be 30 to 40 g/cm2.2, 12 ing change in radiosensitivity. Recently, however, promising This amount of radiation shielding is somewhat impractical results from Edmondson et al, demonstrated in a mouse model given lift capabilities in current rockets. that the underlying genetics of susceptibility can be similar for tumorigenesis following exposure to both high- and low- What analogs are used to evaluate the LET radiation. This indicates that epidemiology studies from space radiation risk to human health? human exposures to gamma radiation may be of utility for predicting the cancer risks attributed to GCR, but further work Animal models are used as human surrogates in studies of is needed to validate these findings.30 radiobiology to obtain data that cannot be gained in ethical studies of humans. Many animal models have been developed Exactly how do you estimate radiogenic to explore a wide variety of questions in space radiation protection and medicine, e.g., radiation oncology. Mammalian risk? species and other advanced organisms, especially those that It is believed that the high linear energy tranfer (LET) radia- can reproduce quickly and possess genomes similar to humans, tion in the GCR spectrum can induce cancer, cognitive deficits, have the utility to identify mechanisms for radiation-induced changes associated with premature aging and degenerative effects in many organs. The LET quantifies how much energy 2It should be noted that the nominal dose-rate onbard the International Space Station (ISS) is approximately 0.04 mSv/hour and predicted to be is lost by an ion, on average, per unit pathlength traversed in around 0.13 mS/hour during space travel outside LEO. matter, is typically given in units of kilo electron volts per

3/9 micron (keV/µm), and depends strongly on ion velocity for 1 Human Mini-pig d=30cm quantification of radiobiological damage. Additionally, the d=20cm large ionization density of GCR ions makes them a potentially 0.8 significant contributor to cellular and organ damage,3, 31 and therefore, it is essential to study the potential health risks from 0.6 GCR exposures. There are numerous limitations of current terrestrial analogs used to study and predict the effects of 0.4 space radiation on biologic systems. The mechanisms that Relative Dose Deposition 0.2 cause biological damage from GCR differ from those from traditional terrestrial radiation sources. Terrestrial analogs 0 5 10 15 20 25 30 35 often use radiation that causes indirect ionizing events.2, 32 Depth in Tissue (cm) The biological effect of the radiation dose depends on phys- Figure 3. Bragg peak and depth dose characteristics of space ical and biological factors, e.g., multiple particle and energy- radiation. Shown in the figure are the calculated Bragg peaks and specific factors, dose rate per exposure and the frequency of relative dose deposition for ions at energies commonly used in space multiple exposures. The (physical) absorbed dose is the en- radiation studies. These are compared to the x-ray and gamma ergy absorbed per mass (J/Kg, Gy). For a dose-based system sources used as surrogate radiations for RBE quantification. This of radiation protection and for the determination of occupa- effect is very pronounced for fast moving, charged particles. Shown tional dose limits, it is necessary to attempt summing the are 60 MeV protons (hydrogen, purple), 600 MeV/n 56Fe (iron, total risk of radiation from multiple sources (e.g., SPE pro- light blue), 290 MeV/n 12C (carbon, green), 1 GeV/n 56Fe (iron, 33 tons, GCR, etc.) At a given ion velocity, LET increases dark blue), x-ray (orange dotted line), and 60Co (cobalt, yellow with atomic number. Thus, for ground-based research, it is dotted line). The shaded gray area, representing the average key to have the correct abundances and energy distributions diameter of a mouse, demonstrates that the Bragg peak, and thus the of each ion present in the space radiation environment. As majority of dose deposition, is outside the mouse body for SPE charged particles lose energy successively through material protons (energies 50 MeV/n) and GCR ions. Figure reprinted with interactions, each energy loss event can result in damage to permission from Chancellor et al.2 under the Creative Commons the biological tissue. In addition, as charged particles near license. the end of their track (i.e., as they slow down and are nearly stopped) the LET rises sharply, creating the so-called “Bragg peak”.34 The phenomena of the Bragg peak is exploited in ties are taken into account with radiation weighting factors, cancer therapy in order to concentrate the dose at the target tu- which are informed by RBE values (mostly for the endpoint mor while minimizing impact to the surrounding tissue. This of carcinogenesis). Additional factors may be applied to take is demonstrated in Fig.3 where the relative dose deposition in into account variations in dose, dose rate, and other factors. tissue for various radiation types utilized in space radiobiology Combining the physical absorbed dose and the various bio- studies plotted versus depth in tissue. The gray shaded area logic considerations mentioned, one obtains an “equivalent is the average width of a mouse model. Also shown are the dose” in units of Sieverts (Sv) that ideally is proportional to average diameters of Yucatan mini-pigs and humans. Gamma risk in the subject or population being considered.33, 35 and X-ray radiations deposit most of the energy at or near the In the US, radiation therapy with charged particles is domi- surface, while in contrast, charged particles such as protons, nated by protons. An RBE value for proton beams was recom- carbon, iron, etc., have distinct Bragg peaks. In each example, mended at 1.1 for all endpoints, tissues, doses, LET values, the Bragg peak is located outside the body mass of the mouse, and dose rates. This consensus recommendation was made indicating the difficulty in replicating the relative organ dose mainly to increase consistency in dose prescription and re- distribution of a GCR exposure incurred by humans during porting among proton therapy centers. It also is believed to spaceflight. facilitate pooling of data from observational data from photon The relative biological effectiveness (RBE)3 quantifies how beam treatments. Importantly, to date, there remains insuffi- much energy is required for a test radiation (e.g., 1-GeV pro- cient evidence that the RBE is significantly different from 1.0 tons) compared to a reference radiation (e.g., 140 KeV x-rays). for any human tissue for any endpoint. The ICRU [report 78] RBE depends on ion charge and speed, the cell, organ, or tis- and the 2019 report from the American Association of Physi- sue of interest, amd the endpoint considered, (e.g., lethal cist in Medicine described limitations in RBE data for clinical damage and carcinogenesis). To facilitate the aggregation of purposes. Based on the lack of evidence outlined above, we risk to a human, variations in radiation sensitivities in various can conclude that many of the same gaps in knowledge com- tissues and organs are incorporated in a tissue weighting factor. prise obtacles to reliable risk predictions in both radiation Similarly, variations in radiation sensitivity with ion proper- oncology and crewed spaceflight.34, 36 This suggests the pos- sibility of synergistic research studies of open questions in 3The RBE is defined as the ratio of doses between some test radiation, oncology and space exploration. Dr, and the dose of x-rays, Dxray, required for equal biological effect, RBE = 33 Dxray/Dr.

4/9 What outcomes have been seen in astro- Wait, so astronauts can sign off on being nauts so far? launched into space, but not on an un- Since the onset of crewed spaceflight, it has been presumed proven health risk? that exposure to space radiation increases the risks of astro- For decades there have been concerns about the clinical seque- nauts developing cancer, experiencing central nervous system lae of United States astronauts’ exposure to the complex radi- decrements, exhibiting degenerative tissue effects or develop- 1,3, 14, 18, 20, 21, 27, 37–39 ation environment of spaceflight. The National Council of Ra- ing acute radiation syndrome. The ma- diation Protection and Measurements (NCRP) recommended jority of epidemiologic data results from the astronaut cohort to NASA that a career limit be placed on astronaut radiation are from exposures incurred on missions during the Space exposure which when adjusted for age and sex, would not Shuttle era, where less than 100mSv was accumulated by an increase an astronaut’s risk of death by greater than 3%. This astronaut. Over the past decade, however, the nominal mis- risk of exposure-induced death (REID) was first suggested by sion length for astronauts has increased to at least 6 months NRCP Report 98 and is based on a two-sided 95% confidence in duration with exposures of 1 mSv to 1.5 mSv per day, de- interval for estimates of mortality from malignancy.21 Little pending on the phase of the solar cycle, number of spacewalks justification was given as to why a 3% REID was chosen, performed, and the level of solar activity. Even with increas- relative to a higher or lower threshold. At that time, it was ing mission length and radiation exposures (e.g. Fig.4), it is suggested that a 25 year old male astronaut would be able noteworthy that to date no astronaut has been diagnosed with to accomplish 17 Space Shuttle missions of 90 days dura- a cancer that is attributable to space radiation. Although the tion over a 10 year period prior before violating this REID. sample size is small, followup times for large exposures are This proposed limit represented a reasonable ceiling given limited, and cancer latency periods are years to decades. In the available information as no astronaut in the 1980’s flew at addition, the neurocognitive deficits and vascular endothelial this frequency or duration. However, the United States space dysfunction leading to increased cardiovascular mortality has program has fundamentally changed and astronauts now regu- not been demonstrated compared to analog populations. larly complete 6 to 12 month missions aboard the International The limitations in understanding and data on radiogenic Space Station. Long-duration missions to Mars and the Moon risks to astronauts comprise major obstacles to making mean- are expected during the next two decades and could last 1-3 ingful and reliable , predictions of human clinical outcomes. years. These also hamper efforts to develop and inform risk mitigation strategies before, during, or after exposure. The presumed In clinical practice, medical providers and bioethicists often risk of cancer, cardiovascular diseases and cognitive deficits refer to four principles which guide medical decision making: due to space radiation remains one of NASA’s top limiting autonomy, non-maleficence, beneficence, and justice. The factors as we return to the moon and push forward towards first of these principles, autonomy, requires patients to have independent thought, intention and action when making de- Mars. The limitations in knowledge of radiogenic risks been 41 one of the key factors that can limit an astronaut’s potential cisions regarding their own health. In order to abide by flight assignments as well as active spaceflight-career length. the principle of autonomy, patients must fully understand the risks and benefits of any medical decision, including options Fig.4 demonstrates the amount of data obtained by both which increase personal risk or include non-treatment. Pa- NASA and the Russian Space Agency (RSA) in regards to tients must be empowered to have informed consent about the number of astronauts and dose of radiation obtained over vary- treatment options, or lack thereof, for any medical condition. ing lengths of spaceflight. Recently Zeitlin et al., reported Fortunately, in common clinical medical scenarios such as findings that the LET spectrum measured inside ISS at high chest pain, pediatric fever, or the risk of pulmonary embolism, latitudes was very similar to measurements made both in lu- there are clinical decision rules based on robust, prospective, nar orbit and in interplanetary space during transit to Mars.40 and externally validated clinical trials that stratify the patient’s This demonstrates that we now have an increasing data set of individual risk. human population that has flown in space while exposed to doses that in some instances, exceed the identified thresholds Exploration of space is not without risks. Space agencies for some degenerative and carcinogenic outcomes. Given the have rigorous safety programs and oversight to limit risk dur- decades of ground-based radiobiologic research on radiation ing missions planning, spacecraft design, and throughout the effects in space travel, one can only conclude that animal mod- stages of flight. With regards to space radiation, it is important els and the type of radiation utilized in these experiments are to acknowledge current limitations in the understanding of the not adequate surrogates for the complex physiologic response impacts on human morbidity and mortality. The estimations of the human body to the complex radiation environment in of risk from space radiation are likely not as precise as the space. Mice are profoundly different from humans and it risk of vehicle loss during launch or re-entry. As noted in remains very difficult to clinically translate the effects noted this manuscript, there are no validated clinical decision rules in the murine population to astronauts. that medical providers and flight surgeons can use to precisely assess the clinical risk from space radiation. However, the principle of autonomy requires that medical providers provide

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Dose (mSv) > 500 > 400 > 300 > 200 > 100 0 25 NASA ad elsi rudbsdsaerdainaaos NASA’s analogs. radiation space ground-based realistic wards as distribution contained depth-dose was the target of entire portion plateau the the that within such used, often were h ao urn iiain fsaerdainefcsre- effects radiation space of limitations current major The owa osalo hsmean? this of all does what So osmlto tde yueo ai-eunilmono-electric rapid-sequential exposures. of beam use by improvements some studies provide simulation to to able be may simulator GCR to- progress been has There health human spaceflight. to long-duration risks during the of understanding our facili- in greatly advances would tate efforts research terrestrial through ment rates dose low space. continuous in the found mimic fully not may exposures expo- space actual than sures. higher rates magnitude dose of experimental orders the several such, are as over exposure; animals acute the single to a delivered often is dose mission cumulative 3. Figure in demonstrated range MeV/n 1000 to MeV/n 100 the in ions modeling, and radiation space the in poly-energetic present environment. the species of ion multiple instead of sequence, spectra exposures in single-ion ions multiple acute, or and beams mono-energetic of that physiology. analogs human mammalian represent of fully lack the A is laboratories. limitation major terrestrial second at suitable GCR of of precluded reproduction lack accurate has the a that includes sources radiation This accelerator-producted currently researchers. methods the to in available limitations by inhibited are search 50 h blt obte iuaetesaerdainenviron- radiation space the simulate better to ability The 46 2, vntemr eetyue rlne fractionated prolonged used recently more the Even 42–44 RSA 47 utemr,fres fds specification dose of ease for Furthermore, hr sdbt ntesaerdaincom- radiation space the in debate is There 75 hw r h ubrof number the are Shown 46 45, 2, 3 diinly projected, a Additionally, ec tde aeused have studies Bench 100 6/9 munity with respect to the appropriate order of ion exposures 3. Chancellor, J. C., Scott, G. B. & Sutton, J. P. Space delivered, where the alteration of exposure sequence can af- radiation: the number one risk to astronaut health beyond fect the outcomes of an experiment.2, 27, 48 Sequential beam low earth orbit. Life 4, 491–510 (2014). exposures remain ineffective in modeling complex and simul- 4. Cucinotta, F. A., Kim, M.-H. Y. & Ren, L. Evaluat- 49, 50 taneous exposures of the actual GCR environment. Addi- ing shielding effectiveness for reducing space radiation tionally, Chancellor et al., have demonstrated that a moderator cancer risks. Radiation Measurements 41, 1173–1185 block can be placed in a single-ion-species beam without (2006). any requirement to modify the beamline and related infras- tructure.12 As an iron beam passes through the moderator 5. Guetersloh, S. et al. Polyethylene as a radiation shielding block, nuclear spallation processes create desired fragment standard in simulated cosmic-ray environments. Nuclear spectra, resulting in fluences of charged particles with atomic Instruments and Methods in Physics Research Section B: numbers of 1 ≤ Z ≤ 26 and LETs up to approximately 200 Beam Interactions with Materials and Atoms 252, 319– keV/µm. That is to say, the ion species and their distributions 332 (2006). in energy closely mimic those of GCR. Taken together, the 6. Newhauser, W., Dexheimer, D. & Titt, U. Shielding of limitations of terrestrial GCR-like sources and limitation of proton therapy facilities: A review of recent progress . animal models have been major obstacles to understanding 7. Wilson, J. W. et al. Shielding from solar particle event responses at chronic, low-dose and low-dose- rate radiation exposures in deep space. Radiation measurements 30, conditions. Even partially eliminating one of these limitations 361–382 (1999). may help researchers to explain the frequent disparity between 8. Zeitlin, C., Guetersloh, S., Heilbronn, L. & Miller, J. data from ground-based studies and those from astronauts. Shielding and fragmentation studies. Radiation protection dosimetry 116, 123–124 (2005). Disclosure Statement 9. Slaba, T. C. et al. Optimal shielding thickness for galactic The view(s) expressed herein are those of the authors and do cosmic ray environments. Life Sciences in space research not reflect the official policy or position of Louisiana State 12, 1–15 (2017). University, Brooke Army Medical Center, Mary Bird Perkins 10. Williams, J. P. et al. Animal models for medical counter- Cancer Center, the University of Rochester, Johnson Space measures to radiation exposure. Radiation research 173, Center, the National Aeronautics and Space Administration, 557–578 (2010). the U.S. Army Medical Department, the U.S. Army Office 11. Williams, J. P. et al. Addressing the symptoms or fixing of the Surgeon General, the Department of the Army, the the problem? developing countermeasures against normal Department of the Air Force, or the Department of Defense tissue radiation injury. Radiation research 186, 1–16 or the U.S. Government. (2016). 12. Chancellor, J. C. et al. Targeted nuclear spallation from Acknowledgments moderator block design for a ground-based space radia- JCC acknowledges support by the Translational Re- tion analog. arXiv preprint arXiv:1706.02727 (2017). search Institue for Space Health (TRISH) through NASA 13. Simpson, J. Elemental and isotopic composition of the NNX16AO69A. JCC and MEC acknowledges support from galactic cosmic rays. Annual Review of Nuclear and LaSPACE/NASA Grant Number 80NSSC20M0110. JPW Particle Sciences 33 (1983). acknowledges support from the National Institute of Health 14. Mewaldt, R. 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