Conceiving the double helix, the canonical structure of DNA, was first and foremost a remarkable achievement in structural biology. Based on the pioneering X-ray diffraction work of Franklin and Wilkins employing relatively crude DNA fibers, Watson and Crick used their chemical know-how to build a compelling helical model for DNA. Not only did their bold approach yield substantially correct results that have stood the test of time, but it paved the way for the more demanding structural analyses of proteins and nucleic acids which have taken place in succeeding decades. Today, determining the structure of biological macromolecules may seem almost routine to judge from the large body of structural work published each month. But ongoing technological evolution means that structural biology is generating (and for the foreseeable future will continue to generate) fundamental new understanding into the workings of diverse biological molecules and assemblies with ever increasing precision.
In a broader sense, the discovery of the structure of DNA was perhaps one of the defining scientific moments of the 20th century. The role of DNA as the main agent of genetic inheritance was already apparent in 1953, but putting things into a three-dimensional context provided swift, prescient insight into how DNA might function and initiated a revolution in research now developed into the vibrant field of molecular biology which continues to this day. Things have, of course, gotten steadily more complicated in the last 50 years. Inside our cells, DNA is packaged with proteins into chromatin, for example, in which multiple layers of compaction contrive to exert exquisite control over the genes encoded within. While the structure of the basic fundamental unit of chromatin, the nucleosome, is known, a precise understanding of structure and function at higher levels of chromatin organization is lacking. Progress has also been slow in studying the organization of specialized chromosomal regions such as telomeres and centromeres. Gradually, however, structural biologists are piecing together an understanding of complex and inaccessible molecular systems by focusing on manageable components.
The sequencing of the human genome promises to bring great benefits in science and medicine and owes a direct debt to the double helix and to its chief protagonists. Soon all human genes will be recognizable in terms of their DNA sequence, and with efficient techniques available to study their expression and function, the fearsome task of understanding mammalian development, physiology and pathology in terms of the underlying genetic and proteomic information should proceed apace in the next 50 years.
The double helix has great cultural significance too. At a superficial level helices might seem simple and attractive, yet in the context of DNA they become serious and profound. To some a double helix may have sinister connotations derived from concerns about the ethical and practical hazards of tinkering with genes, but in academia and the biotechnology industry the same image becomes transformed into an icon of aspiration and progress. Those twin human icons Watson and Crick well deserve their scientific and public stature won albeit not without occasional hubris over the last half-century.
