and an early suggestion of clays as the original information and molecule accumulators (Paecht-Horowitz 1974; Nussinov et al. 1997).

WATER IS LIKELY THE SOLVENT THAT COULD ENABLE LIFE ON MARS, IF IT EXISTS

Life, defined as a chemical system capable of Darwinian evolution, requires the ability to control when and how molecules interact and chemical reactions take place. It is difficult to imagine life as a pure solid, where nutrient and waste flows would be impeded, or as a gas, where interactions between molecules are rare. Life as we currently envision it requires a solvent and exists as a multiphase material: solid, liquid, and gas. For life as we know it, that solvent is water. The potential for life in other solvents is unexplored, although it is known that copious organics are produced in the atmosphere of Titan, which is dominated by liquid methane. The limits of chemical complexity in sulfuric acid (e.g., the Venus clouds) is also unknown, but may not be as limited as once thought—recently 19 of 20 amino acids were found to be stable (Seager et al. 2024) and some peptide bonds (Petkowski et al. 2025). For Mars, the dominant solvent is water.

IF WE DETECT LIFE ON MARS, WHAT WILL WE ALREADY KNOW?

If extant or recently dead or preserved life on Mars is detected, a great deal about it may already be known via the means by which it was detected. For example, the Ladder of Life Detection (Neveu et al. 2018) outlines many candidate biosignatures of varying generality and specificity to life as we know it. Defining life in terms of Darwinian evolution implies heritability, which in turn implies informational polymers or some other means of storing information like electrically and morphologically complex mineral surfaces. Thus, one possibility is that life is detected on Mars by targeting its informational polymers. In the case of water-based life, charged linear polymers have been proposed as a universal biosignature (Benner 2017). Perhaps life will be sought by filtering large quantities of water intended for propellant production while also analyzing charged species (Spacek and Benner 2022). Technologies exist for detecting informational polymers similar to life as know it (Jain et al. 2016; Carr et al. 2020) or do not know it (McKaig et al. 2024). Mars polymers might be found to have a different chemical form than life as we know it. Another possibility is that Mars life could use similar (e.g., nucleic acid) informational polymers to Earth life. The basis for Mars cellular machinery might also be known or quickly discovered, whether based on amino acids or alternative building blocks. In addition, the basis for its compartments might be characterized, perhaps made of lipids or variants thereof.

TESTING FOR COMMON ANCESTRY

It has been proposed that life on Mars, if it exists, could be related to life on Earth owing to transfer of life between planets via large impact events (lithopanspermia) (Gladman and Burns, 1996; Mileikowsky et al. 2000; Worth et al. 2013). Large impact events knock material off one planet; while the shock waves can be destructive, they can also constructively interfere, resulting in only minor (<100°C) heating and high ejection velocities (e.g., Melosh 1985; Weiss et al. 2000; Horneck et al. 2008). Over the past 3.5 billion years, around 1 billion tons of rock is estimated to have been transferred between Earth and Mars without reaching sterilizing temperatures (e.g., Mileikowsky et al. 2000; Worth et al. 2013).

Because 99 percent of this material was transferred from Mars to Earth, finding life on Mars would imply that life as we know it may have originated on Mars. In fact, early Mars might have been an ideal place for life to begin (Carr 2022). With significant land area, shallow water, wet–dry cycling, cold temperatures to preserve organics, higher phosphate availability than early Earth, and other characteristics, early Mars may have been an ideal environment for a cyanosulfidic origin of life (Patel et al. 2015; Sutherland 2016; Ozturk and Sasselov 2022). The plausibility of a cyanosulfidic origin of life can be assessed independently from the discovery of ancient or extent life (e.g., Sasselov et al. 2020). However, a clear detection of life would allow common ancestry to be tested by assessing factors such as whether Mars life uses nucleic acids, and, if so, whether it has sequence conservation and can be placed on the tree of life. Putatively related life would be deeply branching, whereas

forward contamination would be closely related to known Earth life (NRC 2002b; Isenbarger et al. 2008). Nucleic acids are vulnerable to destruction by hydrolysis and radioactivity (Mileikowsky et al. 2000; Dalen et al. 2023) but techniques have been developed to extract them successfully from Mars analogs (Mojarro et al. 2017, 2019). Ancient DNA as old as 2 million years has been recovered on Earth (Kjaer et al. 2022), and much older may be feasible on Mars (Horne et al. 2022). Alternatives include identifying whether Mars life uses the same or a similar set of amino acids (Ligterink et al. 2020) and, if so, whether conserved peptide sequences can be identified. Amino acid (peptide) sequences often show much higher levels of conservation than nucleic acid sequences, and peptides are more resistant to degradation.

To rule in or out contamination, repeated tests can be performed with varying amounts of sample to establish a relationship between Mars material input and measured outputs. In addition, nucleic acid or peptide sequences identified on Mars, even if not found in Earth databases, can be hunted in likely zones of contamination to rule in or out contamination. For example, the exquisitely sensitive polymerase chain reaction can be used to hunt for Mars-identified sequences in spacecraft cleanrooms. In addition to the criteria identified in the Ladder of Life Detection (Neveu et al. 2018), additional measures have been developed such as the confidence of life detection scale (Green et al. 2021).

BIOSIGNATURES OF EXTINCT LIFE

Remnants of ancient life on Mars are also of enormous interest. By the nature of paleontology, many tools and data types useful for pursuing extant life are of less or no value. However, with the classical morphological paleontological understanding of Earth’s biosphere as an example, the past several decades have seen great advances in detecting a variety of biomolecules or their derivatives in the rock record, which can greatly enrich the value of any candidate morphological fossil features found on Mars and also stand alone as evidence of life-like processes (Vinnichenko et al. 2020). Although DNA may be fragile over time as pointed out above, lipids (e.g., hopanes and steranes) can be well preserved in rock materials like chert for extremely long periods of time, particularly under anoxic deposition conditions (Bobrovskiy et al. 2018). Additionally, current and growing knowledge of the biological modification of stable isotopes of organism-relevant elements has added a third line of potential evidence for use on Mars (Boschker and Middelburg 2002).