One major mystery about life’s origin is how phosphate became an essential building block of genetic and metabolic machinery in cells, given its poor accessibility on early Earth. In a study published on March 9 in the journal Cell, researchers used systems biology approaches to tackle this long-standing conundrum, providing compelling, data-driven evidence that primitive life forms may not have relied on phosphate at all. Instead, a few simple, abundant molecules could have supported the emergence of a sulfur-based, phosphate-free metabolism, which expanded to form a rich network of biochemical reactions capable of supporting the synthesis of a broad category of key biomolecules.