The first experimental evidence for the structure of the Holliday junction came from electron microscopy studies in the late 1970s, where the four-arm structure was clearly visible in images of plasmid and bacteriophage DNA. Later in the 1980s, enzymes responsible for initiating the formation of, and binding to, Holliday junctions were identified, although as of 2004 the identification of mammalian Holliday junction resolvases remained elusive (however, see section "Resolution of Holliday junctions," above for more recent information). In 1983, artificial Holliday junction molecules were first constructed from synthetic oligonucleotides by Nadrian Seeman, allowing for more direct study of their physical properties. Much of the early analysis of Holliday junction structure was inferred from gel electrophoresis, FRET, and hydroxyl radical and nuclease footprinting studies. In the 1990s, crystallography and nucleic acid NMR methods became available, as well as computational molecular modelling tools.