One of the most important advances in genetics, was the discovery of the three-dimensional structure of DNA by James Watson and Francis Crick in 1953. Watson, studying bacteriophages for his Ph.D., had come to understand the importance of DNA for genetics. After receiving his Ph.D., he went to Cavendish laboratory at Cambridge University in England.

At Cavendish laboratory, a number of researchers were studying the three-dimensional structure of large molecules. Among them was Francis Crick, who was working on his Ph.D. there. The two met and became friends and colleagues.

Basic Chemistry and X-Ray Diffraction

Already some knowledge about the basic chemical structure of DNA existed, due to the work of Miescher, Kossel, Levene, Chargaff and others. They had established that DNA was made up out of nucleotides, and that these nucleotides contained a sugar, a base and a phosphate group. It was, however, still unclear how the nucleotides fit together into a three-dimensional structure.

In 1947, a man called William Ashbury began to study the 3D structure of DNA with the help of a technique known as X-ray diffraction. Another groups studying the 3D structure of DNA, at King’s College in London, was led by Maurice Wilkins and Rosalind Franklin. They obtained better pictures than Ashbury, but were unable to finish the project due to some personal issues.

Constructing Models

Watson and Crick were not trying to determine the 3D structure of DNA by collecting new data, but rather by combining all the existing data about the chemistry of the molecule and constructing molecular models based on this. Through the application of the laws of structural chemistry (What binds with what? How does it bind? What type of bond is formed?), they were able to limit the number of possible structures that DNA could form.

Subsequently, they tested these models by building them with metal plates and wire. Assisted by these models, they were able to see whether a certain model was compatible with the chemical principles and the X-ray images.

The Key: Base Pairs

The final step to their discovery was taken when Watson realized that adenine could bind with thymine, and guanine with cytosine, as these pairings were consistent with the base ratios found earlier by Chargaff. The model that arose from this idea showed that DNA consisted of two strand of nucleotides wound around each other, forming a right-handed helix, with the sugars and phosphate on the outside and the bases on the inside.

They published their model in Nature in 1953. At the same time, Wilkins and Franklin published their X-ray data, which provided experimental evidence for the theoretical model. This led to a Nobel Prize for Watson, Crick, and Wilkins in 1962. (Rosalind Franklin died five years earlier).