After decades of searching, scientists have still found no evidence of extraterrestrial civilizations, or indeed of any life beyond Earth. So are we looking for the wrong thing in the wrong place? Is the transition from non-life to life easy and widespread, or a chemical fluke? Might there be new physics lurking in living matter? The answers to these questions affect where we might look for a second genesis. Rather than pinning our hopes on a message from ET, we need to broaden the search for general ‘biosignatures’ and ‘technosignatures’ in the solar system and beyond.