Null Detection of Life and the Quest for a more Refined Understanding of the True Limits of Habitability

We propose a transformative approach that includes meta-analysis with laboratory and computation experimentation. This study includes 1) A literature search to identify and select a high-value candidate environment or environmentss that are potentially uninhabited. This surprisingly time-consuming work is already underway. Finding examples in the literature where life has not been found in an environment usually entails looking at exotic life detection studies, identifying samples where life is not found and investigating what slight environmental data there is to inform how it differs from the more celebrated life detection. 2) Laboratory metagenomic analyses to identify boundary limits from those sites based on intrinsic genetic expression of the organisms in the environment and their associated community. Samples selected for this activity would be based on previous analyses and characterization and/or potential limitation of organic carbon chemistry. 3) Metagenome-related thermodynamic modeling to clarify the limitation. This approach reversely uses the methods published by Dick and Shock (2011) to calculate the redox state of a macromolecule (protein, DNA, etc.) and its relative (thermo)chemical stability. The output of this model, the Zc number is co-evaluated through selected metagenomic data. Zc reflects the minimum energetic cost of macromolecule synthesis and can be used to indicate when life is simply not energetically possible, constraining those cases where null life detection may be methodological.