Happy anniversary: fifty years after Watson and Crick's insight, scientists continue to take a close look at DNA's double helix.

On April 25, 1953, a brief research paper appeared in the British scientific journal Nature. Fifty years later, it's one of the most famous publications of all time and often considered the start of the molecular biology and genetics revolution that continues today. In that report, two young scientists at Cavendish Laboratory in Cambridge, England, proposed what they called a "radically different" structure for DNA, the material that scientists of the time had recently concluded stored an organism's genetic information. The pair argued that the DNA molecule resembles a spiral staircase. In the proposed arrangement, two strands are twisted together and connected at each step by a pair of so-called chemical bases, one jutting off each strand.

Such a structure hinted at the solution to another major riddle of biology: how a dividing cell copies its DNA so each daughter cell gets identical genetic information. The two strands could simply unwind, separate, and each make a new opposing strand according to the string of chemical bases it carries.

"It has not escaped our attention that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material," noted James D. Watson and Francis H.C. Crick.

On the eve of the 50th anniversary of the double helix's grand debut, Science News presents a gallery of images depicting the DNA molecule and, in one case, the genetic information it encodes.

FIRST LOOK (above, inset) The historic X-ray image of DNA taken by Rosalind Franklin of King's College in London in 1952. Though supplied to Watson and Crick without Franklin's knowledge, the image was an important clue to DNA's molecular arrangement as a double helix. The 1953 photograph (above) shows Watson (left) and Crick posing with one of their original models of DNA.

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SURFACE TRACE (left) In the late 1980s, researchers began to study DNA with a scanning tunneling microscope (STM). In this method, a sharp tip establishes an electric current between it and a target below that depends on the distance between them. By moving to maintain a steady current, the STM's tip can map an object's surface. In this false-color image, the DNA double helix is evident as the diagonal ridge of orange mounds. Scientists had hoped that STM imaging could distinguish among DNA's four bases so it could give a direct reading of the sequence of bases on a DNA strand, but the technique's resolution wasn't good enough.

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SPECIAL SITES (below) The fine metallic point of an atomic force microscope (AFM) directly traces the surfaces of microscopic objects. This 1997 picture, taken by researchers at Oak Ridge (Tenn.) National Laboratory, shows the outline created by a loop of DNA (dark blue) placed on an ultrasmooth surface. The six peaks (red) are sites where a protein known as a restriction enzyme is bound to the DNA. The AFM image therefore locates the specific sequence to which the enzyme attaches.

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CRYSTAL POWER (above and right) Some viewers may think that these striking photomicrographs of crystallized DNA are works of art. In fact, posters of them are available at http://micro.magnet.fsu.edu/dna/index.html. Yet there's a serious scientific side to the pictures. "We're looking at how DNA packages itself very tightly," says Michael Davidson of Florida State University in Tallahassee.

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Organisms need to stuff all their DNA into a small space. For example, the DNA in a single human cell would stretch out to about 6 feet. People solve this packing problem by tightly wrapping their DNA around proteins called histones. Viruses, bacteria, and other one-celled organisms don't have histones, however. In those cases, DNA bunches so densely that it achieves a liquid crystalline state, says Davidson.

He and his colleagues duplicate those DNA densities in the laboratory. Although scientists typically study an organism's DNA in a watery solution, Davidson's team reduces the amount of water until the genetic material forms liquid crystalline phases called lyotropic phase transitions. The dramatic differences in the images stem from the crystalline phases being photographed and varying lighting conditions.

COLOR CUES (right) Investigators are struggling to analyze the flood of DNA-base-sequence information that has accumulated in the past few years. The human genome sequence alone comprises some 3 billion base pairs. Some researchers are seeking ways to visualize this information. In work that will be reported in an upcoming IEEE Transactions on Visualization and Computer Graphics, Pak Chung Wong of Pacific Northwest National Laboratory in Richland, Wash., and his colleagues started with the known DNA-base sequences of two strains of the bacterium Chlamydia trachomatics. The researchers assigned each position in the sequence to a point on an image. They then gave each type of base a different color. After applying image-processing software to this information, the researchers created pictures in which genetic differences between the two bacterial strains are evident as color-pattern variations. Wong and his colleagues suggest that with this type of genome visualization, geneticists can more quickly identify subtle DNA differences between two similar organisms.

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