MELiSSA (Micro-Ecological Life Support System Alternative) is a long-term technology program of the European Space Agency. Its aim is to construct autonomous habitats in deep space, supplying astronauts with fresh air, water and food through continuous microbial recycling of human wastes. This article considers how anticipated futures of space travel and environmental survival are materialized in the project to engineer the minimal biosphere capable of reliably sustaining human life: a human/microbe association with the fewest possible species. We locate MELiSSA within a history of bio-infrastructures associated with colonisation projects: refugia in which organisms dislocated from their originary habitats are preserved. Analysis of MELiSSA’s sewage-composting technology suggests that the disordering complexity of human waste presents a formidable “bottle-neck” for the construction of the minimal biosphere, in turn suggesting our dependence on microbial communities (soil, the human gut) of potentially irreducible biocomplexity. MELiSSA researchers think of themselves as pragmatic enablers of space exploration, yet a wider family of space colonisation projects are now imagined in terms of the prospect that the Earth might cease to function as the minimal biosphere capable of supporting civilisation. MELiSSA’s politics of anticipation are paradoxical, promising technologies with which to escape from the Earth and through which it may be sustained.