Ahead of the arrival of humans on Mars, which would be the culmination of the evolvable Mars campaign and the horizon goal on which NASA has set its sights, a new body of knowledge needs to be generated to ensure that this activity can be done safely. Not only in the engineering sense, but also in the sense of protecting both the astronauts and Mars from harmful contamination between “biospheres” (should there be a biosphere at Mars). This presentation will discuss the precursor knowledge that is needed to protect the integrity of science data from putative Mars biota during human exploration activities, as well as the information needed to preserve the health of the crew without compromising their effectiveness in exploration, or their return to Earth without threatening the terrestrial biosphere on which we all depend.