irradiation.21 In nearly all the cases studied so far, these radiation-induced deficits occur with no gross histopathological evidence of disease.22-24

Given that (1) the dose, dose rate, and composition of a radiation field can drastically alter the biological outcome of exposure,25-28 (2) the results of short-term exposures do not predict the results of long-term exposures,29-32 (3) the biological effects of mixed-field radiation are generally worse than the sum of the biological effects of the individual types of radiation,33-35 and (4) microgravity and other environmental factors in the space vehicle are likely to have some influence on the final biological response, it would appear that experiments to assess the risk of prolonged exposure to space radiation can only be performed in the ISS or on the Moon. This would require both restoration of the capacity to perform long-term rodent experiments on the ISS or on the Moon and initiation of preflight and long-term postflight testing of humans for kidney, lung, heart, and brain function.

Importantly, the low linear energy transfer (LET) radiation damage to the kidney and the brain, including cognitive impairment, appears to be modifiable in both humans and rodents using pharmacological interventions.36,37 Although there are no data on mitigating the late effects in liver, kidney, lung, and brain produced by high-LET radiation or mixed radiation fields, there are suitable pharmacological agents that could be tested on the ISS or on the Moon now.38,39


Finding: There is insufficient information about the mixed-beam radiation effects on biological systems to confidently derive risk estimates for a Mars mission. Based on current knowledge, it is dangerous to assume that carcinogenesis is the only long-term risk of extended-duration spaceflight.


Recommendation: A high priority should be given to assessing the noncarcinogenic late effects of exposure to space radiation on the ISS or the Moon and to testing pharmacological interventions for ameliorating these late effects, because the results are critical for designing a Mars mission.

BONE AND MUSCLE

Existing countermeasures have failed to prevent deterioration of bone and muscle in astronauts during spaceflight. Current data based on 4- to 6-month spaceflights indicate that there is impressive bone loss at both the spine and hip.40 Observed losses at the spine and hip average 0.9 percent and 1.5 percent per month, respectively. Quantitative computer tomography studies indicate that loss of trabecular bone at the femoral neck (a frequent hip fracture site) is 2.7 percent per month.41 Although there is a wide spectrum of individual variation, linear extrapolation of these data suggests that approximately two-thirds (64 percent) of astronauts would experience more than a 25 percent loss of bone mineral at the hip during a 30-month Mars outpost-class mission. A 21 percent decline in peak force of slow muscle fibers has been observed after a 17-day spaceflight, and a 20 to 48 percent reduction in maximal voluntary contraction of the plantar flexors has been observed after 6 months in space.42 This level of deterioration will compromise motor performance and increase susceptibility to injury, changes unlikely to be acceptable for an outpost-class mission to Mars. Moreover, reversibility of tissue deterioration is unclear for long-duration flights, particularly in an environment of radiation exposure and suboptimal nutrition. The ability of fractional gravity environments (such as the 0.16-g and 0.38-g fields of the Moon and Mars, respectively) to maintain bone and muscle integrity has not been determined, and recent data indicate that bone density does not return to baseline within 12 months of returning to Earth.43,44 Muscle function appears to return to preflight levels within weeks. However, studies of long-term recovery have not been conducted to ascertain whether the deterioration involved nonpathological muscle cell shrinkage and postflight cell enlargement or a process of pathological cell degeneration followed by cell regeneration. Pathology is a concern, because tissue regeneration may be compromised by exposure to radiation in spaceflight.45,46

NASA has some human experiments planned and in progress to address the issue of bone loss. However, space-based clinical trials of antiosteoporotic therapies lag behind terrestrial applications by



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