The CHAPEA experiment simulates the confinement, resource limitations, and interpersonal dynamics of a Mars mission. It cannot replicate crucial physical factors like one-third gravity or high radiation, making it a study of human psychology and group dynamics under stress rather than a physiological test.

The small, non-representative group of initial colonists will create a genetic bottleneck. Their specific genetic makeup will have an outsized influence on all subsequent generations born on Mars, leading to rapid evolutionary change and reduced overall genetic diversity compared to Earth's population.

Isolated on islands with limited resources, species undergo rapid size changes. While Homo floresiensis ('hobbits') and pygmy elephants shrank, other species like Komodo dragons and tortoises became giants. This evolutionary pressure applies to any isolated population, including future human colonists on Mars.

Natural selection often favors traits that maximize reproductive fitness, even if it pushes them to a dangerous peak where a small step further leads to catastrophic failure. This "cliff edge" model helps explain disorders like schizophrenia or childbirth complications, where genes beneficial in moderation can be disastrous in excess.

Living in a sterile Martian habitat, colonists would only be exposed to a tiny fraction of Earth's microbes. Their immune systems would be unprepared for Earth's vast microbial diversity, making a return journey potentially fatal. This creates a permanent biological quarantine that would accelerate human speciation.

A human born and raised in Mars's one-third gravity would likely not develop the bone density and muscular strength required to withstand Earth's gravity. The physical stress would be painful and potentially debilitating, effectively trapping them on their home planet for life.

Despite decades of spaceflight, there is almost no research on conception, pregnancy, childbirth, and child development in a low-gravity environment. Our assumption that humans can successfully reproduce off-world is a massive, unverified leap of faith and the single biggest unknown for establishing a permanent settlement.

To shield against radiation and meteorites, Martian habitats will likely be built underground, not in glass domes. A society that lives its entire existence underground, reliant on artificial light and disconnected from an open sky, would develop a psychology profoundly different from Earth's.

Since Mars cooled and had water before Earth, Avi Loeb argues life likely started there first. This primordial life could have been transported to Earth inside rocks ejected by asteroid impacts. This makes humans descendants of Martian microbes and Elon Musk's mission a 'return to our childhood home'.