Unknown unknowns: essential genes in quest for function

The experimental design of a minimal synthetic genome revealed the presence of a large number of genes without ascribed function, in part because the abstract laws of life must be implemented within ad hoc material contraptions. Creating a function needs recruitment of some pre‐existing structure and this reveals kludges in their set‐up and history. Here, we show that looking for functions as an engineer would help in discovery of a significant number of those, proposed together with conceptual handles allowing investigators to pursue this endeavour in other contexts.