Mention DNA today and immediately the iconic image of the double helix is conjured up - the familiar spiralling ladder that carries the codes for the vast majority of the earth's huge variety of life forms. It wasn't always this way. This view of DNA only goes back to the inspired home-made model created by Watson and Crick 50 years ago. Determined to solve the puzzle posed by the research evidence at the time, they required new insight - insight that was finally achieved by visualizing the structure through a physical model.

Previously, DNA was a far more esoteric concept, seen only as some form of fibre. Nucleic acids were extracted from cell nuclei in the late nineteenth century and by the early 1900s DNA was known to be a chain made up of four different nucleotides. In the 1940s X-ray diffraction was applied to the problem of DNA's three-dimensional structure. This technique is used to locate individual atoms within a molecule. DNA fibres are prepared and are then bombarded with X-rays. Most of the X-rays go straight through the molecule, passing between the atoms, but when an atom is hit the beam is deflected.

Because DNA has a regular structure, the X-ray waves are diffracted in the same directions at equivalent points along the molecule, reinforcing the signal and creating a regular diffraction pattern. It was this pattern (actually produced by Rosalind Franklin) that helped Watson and Crick to deduce the double helix structure.

The advent of computers and stronger X-ray sources greatly enhanced the way complex molecules such as DNA are studied. Before their arrival X-ray diffraction was time-consuming and required great skill and many complex calculations to arrive at a structure. Nowadays, computers fo the calculations and generate striking three-dimensional images of macromolecules.

Other techniques have also been applied. Neutron diffraction is a similar technique, used to study the position of water molecules around the DNA helix. Neutrons are diffracted by water far better than are X-rays, giving much stronger signals and therefore more accurate results. These two techniques are also being used together to understand how certain sequence-specific drugs bind to the DNA helix. With people's individual DNA profiles now a realistic possibility, the ways that these drugs work will be of huge importance for personalized prescribing.

All these computer-generated images, although derived from actual measurements of real molecules, are generalized models rather than direct images of a physical piece of DNA; for direct images other techniques are required.

DNA can be visualized under a light microscope but only as relatively amorphous chromatin within the nucleus or condensed chromosomes in dividing cells. An electron microscope is needed to see individual DNA fibres, although the images of DNA have never been very detailed. A more recent technique, scanning probe microscopy, on the other hand, is able to reveal surface structure of the double helix. An ultrafine probe moves over the surface of the molecule, producing a three-dimensional image that looks more like a thick twisted rope than the thin thread seen with the electron microscope. The computer colour-codes the height of the DNA molecule above the surface, revealing that the helical structure of a real piece of DNA is actually stretched and kinked - rather less regular than suggested by the classical view.

With the explosion of research in molecular biology and biotechnology and the fruits of the Human Genome Project, new types of DNA images are emerging. DNA sequencing and differential gene expression patterns can generate fascinating visual representations of complex information. The 'rainbow image' is now becoming increasingly familiar as a current vision of DNA.

As research moves increasingly towards understanding how the genome functions in health and disease, new ways of seeing DNA will inevitably develop, adding further to the wealth of imagery available to stimulate our senses, our curiosity and our understanding of this amazing molecule.

See also

• Medical Photographic Library