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Without the protection of the Earth's atmosphere, astronauts are exposed to higher levels of radiation from a steady flux of cosmic rays. The station's crews are exposed to about 1 millisievert of radiation each day, which is about the same as someone would get from natural sources on Earth in a year. This results in a higher risk of astronauts' developing cancer. High levels of radiation can cause damage to the chromosomes of lymphocytes. These cells are central to the immune system and so any damage to them could contribute to the lowered immunity experienced by astronauts. Over time lowered immunity results in the spread of infection between crew members, especially in such confined areas. Radiation has also been linked to a higher incidence of cataracts in astronauts. Protective shielding and protective drugs may lower the risks to an acceptable level, but data is scarce and longer-term exposure will result in greater risks.

Despite efforts to improve radiation shielding on the ISS compared to previous stations such as Mir, radiation levels within the station have not been vastly reduced, and it is thought that further technological advancement will be required to make long-duration human spaceflight further into the Solar System a possibility.