The human expansion component of the Step-by-step strategy requires an extensive database of space life science research. Currently, our knowledge of the long-term physiological and psychological effects of the space environment is very limited. The Space Studies Board of the National Research Council of the USA recommends that research aimed at understanding and ameliorating problems limiting astronaut survival and function during prolonged space flight should be a top NASA priority. The following table summarizes current knowledge regarding the medical consequences of long-duration space flight.

	SPACE FLIGHT EFFECTS	FUTURE DIRECTIONS
Muscular System	- in-flight muscle deterioration - muscle weakness, atrophy, fatigue and muscle/ ligament pain post-flight but these changes reversible - in-flight exercise only partially successful in prevention	- determine cellular and molecular mechanisms of muscular weakness, atrophy and fatigue. - explore role of growth factors and hormones in neuromuscular adaptation
Bone	- bone mineral density reduction exceeding 1%/month in weight-bearing bones even with in-flight exercise - bone loss possibly irreversible - bone mineral mass loss may predispose to fractures	- determine mechanism of bone loss - bone loss countermeasure development including exploration of pharmacological means - establish microgravity related bone loss data base
Neurophysiology	- space motion sickness experienced by 70% of astronauts - symptoms usually subside after 48hrs - mismatch between sensory and visual cues suspected	- evaluate whether neurovestibular adaptation and its mechanism is the same on Earth as in space - space motion sickness countermeasure development
Immunological System	- decrease in numbers and function of T lymphocytes - potential for increased susceptibility to infections	- determine if space flight stress alters immune system by evaluating interaction between HPA axis and immune system in space flight
Cardiovascular System	- fluid shifts headward causing facial fullness+sinus congestion - body interprets shift as volume overload and adapts - 1.5-2L of fluids lost + decrease in red blood cell mass - orthostatic intolerance upon return to gravity despite antiorthostatic measures	- investigate mechanism of inadequate peripheral resistance postflight - re-evaluate effectiveness of current countermeasures - magnitude, time course and mechanism info for cardiovascular changes must be compiled for long duration flights - determine relationship of cardiovascular adjustments during space flight with changes in other physiological systems
Psychological/ Sociological	- after 6 months in space, fatigue results in decreased work efficiency and productivity -analog environments report increased hostility, anxiety, depression resulting in group conflict	- determine efficacy of current crew selection, training and support measures - in-flight neurobiological and psychosocial investigations for space environment specific data - mixed gender crews seem most effective
Radiation Concerns	- current astronaut limit 50 rem/year - ISS concern is trapped protons from South Atlantic Anomaly - Moon and Mars concerns: galactic cosmic radiation and solar particle events - 2 major effects of chronic long-term exposure are neoplasia and lenticular cataracts	- determine carcinogenic effects of GCR exposure and high-energy heavy charged particle exposure -improved characterization of GCR environment and solar cycle variations - further investigations in shielding options chemopreventive strategies. - besides shielding as 1st line of defense, chemoprevention strategies also effective.

Information obtained from "Exploration of Mars: The Human Aspect" (Garshneck, 1997) and A Strategy for Research in Space Biology and Medicine in the New Century (NRC, 1998)

Radiation Concerns for Manned Lunar / Mars Missions

During space flight, human exposure to natural ionizing radiation may induce genetic mutations and have carcinogenic effects. Currently, within the Shuttle program, the astronaut radiation exposure limit is 50 rem/year with a career limit set at 400 rem.

On the ISS, the total dose of radiation is mostly due to trapped protons from the South Atlantic Anomaly and Galactic Cosmic Radiation. On the way to Mars and the Moon, crews will be exposed to the ionizing radiation of Earth's inner and outer radiation belts. Outside the Earth's magnetosphere, Galactic Cosmic Radiation (GCR) and Solar Particle Events (SPE) are of grave concern. However, shielding due to planetary mass cuts the surface radiation levels by half as compared to free space levels. Also, the Martian atmosphere provides additional shielding. Shielding is therefore an important consideration during the transit phase of a mission. The best strategy for minimizing the effects of radiation during long duration missions is to combine the use of shielding devices with new chemopreventive agents such as bioantimutagens and antioxidants (Stanford, 1999)

During the next two decades, additional Spacelab missions and research facilities on the International Space Station will try to tackle some of the issues outlined in the above table. However, currently, most space agencies place a greater emphasis on ground-based studies for protecting astronaut health and safety in space. As we travel from low Earth orbit to Mars and beyond within our strategy, we expect that space access will become more routine thus creating a continuous human presence in space. This will enable us to shift our emphasis from ground-based life science research to in-flight research. Thus we will be able to generate more space specific data.

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