1950–2000: five decades of curiosity-driven discovery in alternative DNA structures

1953 was a watershed year in the history of science, indelibly linked to the discovery of DNA's double-helix structure by James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin. However, this landmark achievement has often eclipsed the rapid succession of discoveries that followed in its wake, findings that collectively revealed the remarkable structural plasticity of DNA. These early insights, though initially overshadowed, have since re-emerged as cornerstones in the study of alternative DNA structures, notably G-quadruplexes (G4s), which today are not only studied for understanding the roles they play in cellular processes but also hold promise as targets for therapeutic interventions. By revisiting these foundational discoveries-notably the discovery of the many forms of DNA including A-DNA, B-DNA, G4, i-motif, R-loop, triplex-DNA, Z-DNA, 3WJ, and 4WJ-we not only gain a deeper appreciation of their historical significance but also recognize how, in just a few decades, they laid the groundwork for modern nucleic acid research and its far-reaching applications.