Despite years of research, understanding of the space radiation environment and 
the risk it poses to long-duration astronauts remains limited. There is a 
disparity between research results and observed empirical effects seen in human 
astronaut crews, likely due to the numerous factors that limit terrestrial 
simulation of the complex space environment and extrapolation of human clinical 
consequences from varied animal models. Given the intended future of human 
spaceflight, with efforts now to rapidly expand capabilities for human missions 
to the moon and Mars, there is a pressing need to improve upon the understanding 
of the space radiation risk, predict likely clinical outcomes of interplanetary 
radiation exposure, and develop appropriate and effective mitigation strategies 
for future missions. To achieve this goal, the space radiation and aerospace 
community must recognize the historical limitations of radiation research and 
how such limitations could be addressed in future research endeavors. We have 
sought to highlight the numerous factors that limit understanding of the risk of 
space radiation for human crews and to identify ways in which these limitations 
could be addressed for improved understanding and appropriate risk posture 
regarding future human spaceflight.