Discovery of the Structure of DNA.

Discovery of the Structure of DNA

Most biological experiments are done with samples of living matter- cells, tissues, whole organisms or extracts of these materials. Only a few experiments are done with mathematical or physical models of biological components. Occasionally, however, a model experiment gives an insight that would be difficult to obtain in any other way. This was true of the discovery of the structure of DNA. A crucial experiment was done by James Watson in 1952 using nothing more complicated than chemical models cut out of cardboard.

What Was Known About the Structure of DNA in Late 1952

By 1952 conventional laboratory experiments had shown the following:

DNA was the molecule of heredity: it had been shown that transferring DNA into bacteria could change them genetically. This made the solving of the DNA structure one of the top priorities in biology
DNA was known to be composed of phosphate, the 5 carbon sugar deoxyribose and 4 nucleotide bases: adenine, cytosine, guanine and thymine
Chemical structures of all of the components (phosphate, sugar & bases) were known
The sugar (S) and phosphate (P) were known to be connected together to form a backbone. The bases (B) were known to be stuck out to the side, attached to the sugar of the backbone by one of their N atoms:
Rosalind Franklin had pointed out that phosphate has negative charges at cellular PHs. Since these charges would repel each other she insisted that the sugar-phosphate backbone was on the outside of the molecule
Hydrogen bonds had been shown to be very important in determining the shapes of proteins and it was expected that they would be important in DNA as well
Rosalind Franklin had taken excellent x-ray diffraction pictures of DNA. The pictures had a distinctive pattern that was known from theory (developed by Francis Crick) to be due to a helical structure (2 or more strands spiralling around each other)
Erwin Chargaff had been making accurate measurements of the base composition of DNA from many different species.

Discovery of the Structure of DNA

Almost everything needed to solve the structure of DNA is in this list, but although a number of people had this data no one had come up with a reasonable solution (several "unreasonable" solutions had been suggested and even published).

An Experiment With Cardboard Models

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Discovery of the Structure of DNA

An Experiment With Cardboard Models

In late 1952 several laboratories were actively working on the structure of DNA. Linus Pauling at Cal Tech had published an incorrect structure with 3 DNA chains wound in a helix. Rosalind Franklin and Maurice Wilkins were doing x-ray diffraction experiments at King's College in London. Erwin Chargaff thought that the secret to the structure was in the base composition of DNA and he was doing painstaking chemical analyses at Columbia University. Finally, at Cambridge University Francis Crick and a young American postdoctoral student, James Watson, were very interested in the DNA structure. They were an unlikely pair because they were doing no laboratory experiments of their own. Instead they were talking to all of the other participants and building chemical models. After a number of mistakes they ordered a set of metal models of the 4 bases to be made by the university shop. The models were slow in coming, so one afternoon Watson became impatient and decided to draw the base structures on cardboard and cut them out. He did this and then went out to dinner and the theatre. The next morning he returned to his models and moved them around in pairs to see how they might fit together. He was starting to think that the DNA had 2 chains and he wanted to see if interactions between the bases might hold them together. It was immediately apparent that interactions between the bases would involve hydrogen bonds. Within a few minutes the structure of DNA became apparent and Watson had an explanation for Chargaff's results (A = T and C = G) and even a good idea of how DNA replicated itself!

This is the exact same experiment that Watson performed to discover the structure of DNA.

The objective is to move the models around to see how they might fit together. You must pay special attention to possible hydrogen bonds. Hydrogen bonds occur between 2 groups of atoms:

hydrogen atoms attached to oxygen and nitrogen
hydrogen acceptors: oxygens and nitrogens without attached hydrogens

In the drawings of the A, C, G and T bases below the hydrogen’s available for H bonds are colored red and the hydrogen acceptors are colored green, as shown in this table:

Here are the 4 DNA bases with the correct color-coding:

The DNA model is known as the Watson and Crick model.