As a thought experiment, it's interesting to ponder the Mars One project:
It's interesting how this project is announced after all of the success of the SpaceX Dragon mission last week. My first thoughts are about the "one way" nature of the mission design. I guess that makes concerns about calcium and muscle loss less, if they are never going to face anything but .38 Earth gravity ever again. But imagine if the Apollo project had been one-way to the moon. Ugh.
I wonder if there are historical precedents of explorers setting out knowing that the trip was one way? Adds something to the equation.