Elucidating the DNA double helix marked the beginning of the molecular biology era, and it became possible to study molecular mechanisms that underpinned observable phenotypes. DNA sequencing methods improved, leading to whole-genome sequencing at the end of the 1990s. Methods for mathematical cell modeling were developed during the 1980s and 1990s, and computer simulations of metabolic networks (also known as genome-scale models of metabolism, or GEMs) could be reconstructed. A defining moment took place in 2008 (red), with the creation of the first artificial genome that mimicked the genetic information of M. genitalium, the free-living, non-synthetic organism with the smallest genome. Thanks to developments in next-generation sequencing methods, this was paired with the rise of large-scale genome sequencing ventures, such as the human microbiome and the 1000 genomes projects. Advances in whole-genome synthesis, assembly, and transplantation helped create the first cell living with an entirely synthetic genome shortly after. Taken together, these achievements marked the coming of age for synthetic biology.