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 dependencies. It is possible that this experimental bias leads to an over-prediction of risks of radiation effects that have not been observed in the astronaut cohort. None of the primary health risks presumably attributed to space radiation exposure, such as radiation carcinogenesis, 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.

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.