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Components of Cells
The Macromolecules
The Double Helix
A most important discovery

James Watson
The three dimensional structure of the complete DNA molecule was officially discovered by James D. Watson and Francis Crick in 1953. But, as with so much in science, many other scientists and researchers contributed important details and information which Watson and Crick then correctly put together into the "big" picture.

All molecules, especially very large, macro-molecules have a three dimensional shape, but their size is so small, smaller than the wave lengths of all visible light, that they cannot be seen using traditional microscopic techniques. How then were scientists supposed to "see" the shape of these molecules?

Part of the answer was to use a form of radiation with much shorter wavelengths - X-rays.

X-rays were discovered in 1895 by Wilhelm Roentgen, but it was Max von Laue who suggested in 1912 that it might be possible to irradiate crystals with X-rays and then deduce the shape of the molecules in the crystal from the pattern of the rays leaving the crystal.

The Double Helix
the structure of DNA
as determined by the work of many
and credited to Watson and Crick
The father and son team of William Henry Bragg and Lawrence Bragg exploited this new idea to analyze the shape of several crystal structures, and were soon world leaders in this new technology. The Braggs were awarded the Nobel Prize in 1915 for this work, and it looked as if the shape of molecules could now be visualized, if not directly, then by irradiating crystals and using mathematical formulae to analyze the results.

Willam Thomas Astbury, forced by scarcity of funds to use wool fibers from his own clothes, used X-ray diffraction to look at the structure of a biological molecule; keratin protein fibers. He found regular repeating patterns that were characteristic of two different forms of the molecule, a compact, folded form and an expanded, unfolded form. He could, therefore, use this technique to analyze a biological molecule for its form and its function!

However, fibers were natural "crystals" and were already in a form that could be looked at by X-ray diffraction, what about other macro-molecules such as globular proteins that did not automatically form crystals, and the new molecule of great interest - DNA?

A skiing holiday in Normay provided the answer. John Philpot left a solution of pepsin (a globular digestive enzyme protein) in a refrigerator while he went on a skiing vacation, and was astounded to find crystals of the protein in the tube when he returned. With these crystals, it was now possible to look into the structure of large, complex protein shapes - and perhaps DNA.

The final needed breakthrough was provided by Linus Pauling, who, in the 1930's, determined that polypeptides folded into the alpha-helix configuration. This was an important part of the secondary structure of almost all globular proteins. It also showed that a helix could be an important structural configuration in other biological molecules - including the constituents of chromosomes.

Wilkins and DNA
Maurice Wilkins
In 1950 Maurice Wilkins slowly pulled a long thread of DNA from solution, and keeping it moist, subjected it to irradiation with X-rays. To his delight and surprise the rays leaving the moist DNA created a definite pattern of spots that Alex Stokes could mathematically explain as the diffraction pattern of a helix. DNA had a three dimensional shape that spiraled round and round like a spring or coil. But how?

The story of how James Watson and Francis Crick met in Cambridge and their joint decision to work on DNA structure is by now quite famous in the history of science. At that time, DNA structural analysis was almost the personal property of Maurice Wilkins and Rosalind Franklin, and Watson actually misinterpreted Franklin's findings and built a three stranded model of DNA! This mistake cooled their ardor for a time, but the role of DNA in genes and the obvious importance of its molecular structure keep them thinking.

The final piece of the puzzle
Francis Crick
Watson has said that the idea of building a two chain model of DNA came to him while taking a train ride from London to Cambridge. He built accurate scale models of the sugars, bases and phosphate, and finally grasped the significance of a statement by Franklin that the phosphates were on the outside of the molecule.

The final piece of the puzzle was put in place by Jerry Donohue who pointed out to Watson that he was using the wrong molecular configuration (shape) of the nitrogenous bases, and when he had put them right, it was clear that adenine could be paired up with thymine, and guanine with cytosine. When an excited Watson cut these revised base structures out of stiff cardboard, on Saturday, February 21, he was able to clear his desk and see how all the parts could come together.

When Francis Crick showed up a bit later he claims he did not get more than halfway through the door before he was bombarded by Watson that "everything was in our hands".

A proper, accurate scale model of the DNA molecule convinced Bragg and other important people in the X-ray diffraction field, so a manuscript was immediately prepared for submission to the science journal Nature. In this article Watson and Crick "suggest" a structure for the DNA molecule that has some "Novel features". How right they were!

Figure legend: Xray diffraction allowed scientists to "look inside" molecules and determine their 3D structure. It was not easy and needed a lot of math.
Xrays, when passed through crystals, scatter in regular patterns that can be detected using a piece of photographic film. Working backwards from the regularity of the "dots" on the film it is possible to work out the arrangement of the molecules in the crystal, hence the structure of the molecule.

© 2001, Professor John Blamire