By the time of the lac operon, it was evident that the genetics of complex eukaryotes is different to that of bacteria. Plant and animal genomes were found to be orders of magnitude larger and to contain large amounts of differentially expressed ‘repetitive’ sequences, leading to the suggestion that gene regulatory information might occupy the bulk of the genomic information in complex organisms. The repetitive sequences were found to be derived from transposable elements, some of which were shown to act as ‘controlling elements’ affecting phenotypic characteristics in maize, similar to position-effect variegation in Drosophila, neither of which could be explained in conventional terms. Other equally inexplicable genetic phenomena were also observed, including paramutation (‘rogue’ non-Mendelian patterns of inheritance), imprinting (parental allele-specific expression) and transvection (allelic crosstalk), the first indications of epigenetic inheritance and RNA-mediated gene regulation. Homeotic genes controlling body plan formation were identified in Drosophila, along with adjacent non-protein-coding loci that modulate their expression by interaction with genes encoding repressive and activating epigenetic modifiers, notably Polycomb and Trithorax, which later turned out to be ubiquitous in animals and plants and to encode proteins that modify histones. Brave attempts were made to integrate the observations of heterogeneous nuclear RNAs and repetitive sequences into a network model of gene regulation during development, but such models were considered too speculative and unnecessary, then overrun in the stampede of gene cloning.