Over the last several hundred years of scientific progress, we have arrived at a deep understanding of the non-living world. We have not yet achieved an analogous, deep understanding of the living world. The origins of life is our best chance at discovering scientific laws governing life, because it marks the point of departure from the predictable physical and chemical world to the novel, history-dependent living world. This theme issue aims to explore ways to build a deeper understanding of the nature of biology, by modelling the origins of life on a sufficiently abstract level, starting from prebiotic conditions on Earth and possibly on other planets and bridging quantitative frameworks approaching universal aspects of life. The aim of the editors is to stimulate new directions for solving the origins of life. The present introduction represents the point of view of the editors on some of the most promising future directions.This article is part of the themed issue 'Reconceptualizing the origins of life'.