Friday, February 8, 2013

Rosalind Franklin

Rosalind Franklin
(1920 - 1958)

By 1952, much was known about DNA, including its exclusive role as genetic material – the sole substance capable of storing practially all the information needed to create a living being. What was not yet known was what the elusive DNA molecule looked like, or how it performed this amazing hereditary function. This would change in the course of a single year. The now familiar double helical structure of DNA, a twisted ladder with base-pairs rungs essential to its hereditary function, was deciphered in 1953. The individuals most commonly associated with this remarkable accomplishment are James Watson and Francis Crick. Maurice Wilkins played a role as well, for which he shared the 1962 Nobel Prize for Physiology and Medicine with Watson and Crick. Yet there was one other person whose truly essential contribution to this discovery could not be recognized by the Nobel Committee in 1962. That person was Rosalind Franklin.
Born in July of 1920, Rosalind Franklin graduated with a Ph.D. from Cambridge University in 1945. In 1951, she went to work as a research associate for John Randall at King's College in London. A chemist by training, Franklin had established herself as a world expert in the structure of graphite and other carbon compounds before she moved to London. In James Watson's account of the discovery of the structure of DNA, entitled The Double Helix, Rosalind Franklin was depicted inaccurately as an underling of Maurice Wilkins at King's College. In fact, Maurice Wilkins and Rosalind Franklin were peers. Franklin had discovered that DNA could crystallize into two different forms, an A form and a B form. John Randall gave Franklin the A form and Wilkins the B form, assigning them each the task of elucidating their molecular structure.
The technique with which Wilkins and Franklin set out to do this is called X-ray crystallography. With this technique a crystal is exposed to x-rays in order to produce a diffraction pattern. If the crystal is pure enough and the diffraction pattern is acquired very carefully, it is possible to reconstruct the positions of the atoms in the molecules that comprise the basic unit of the crystal called the unit cell. By the early 1950s, scientists were just learning how to do this for biological molecules as complex as DNA. Progress in discerning the structure of DNA was blocked because the A and B forms of DNA were mixed together in preparations, yielding impure crystals and "muddy" diffraction patterns that were near impossible to interpret.
After discovering the existence of the A and B forms of DNA, Rosalind Franklin also succeeded in developing an ingenious and laborious method to separate the two forms, providing the first DNA crystals pure enough to yield interpretable diffraction patterns. She then went on to obtain excellent X-ray diffraction patterns of crystalline B-form DNA and, using a combination of crystallographic theory and chemical reasoning, discovered important basic facts about its structure. She discovered that the sugar-phosphate backbone of DNA lies on the outside of the molecule, not the inside as was previously thought. She discovered the helical structure of DNA has two strands, not three as proposed in competing theories. She gave quantitative details about the shape and size of the double helix. The all- important missing piece of the puzzle, that she could not discover from her data, was how the bases paired on the inside of the helix, and thus the secret of heredity itself. That discovery remained for Watson and Crick to make.
After Randall presented Franklin's data and unpublished conclusions at a routine seminar, aspects of her results were informally communicated to Watson and Crick by Maurice Wilkins and Max Perutz, without her or John Randall's knowledge. It was Watson and Crick who put all the pieces of the puzzle together from a variety of sources including Franklin's results, to build their ultimately correct and complete description of DNA's structure. Their model for the structure of DNA appeared in the journal Nature in April, 1953, alongside Franklin's own report.
Rosalind Franklin never knew that Watson and Crick had gotten access to her results. At the time of the Watson and Crick publication and afterwards, Franklin appears not to have been bitter about their accomplishment. In her own publications about DNA structure, she agreed with their essential conclusions but remained skeptical about some details of their model. Franklin moved on to work on an even more challenging problem: the structure of an entire virus, called the Tobacco Mosaic Virus. Her subsequent publications on this topic would include four more papers in the journal Nature. Rosalind Franklin was friendly with both James Watson and Francis Crick, and communicated regularly with them until her life and career were cut short by cancer in April of 1958, at the age of 37. She died with a reputation around the world for her contributions to knowledge about the structure of carbon compounds and of viruses. After her death, Watson and Crick made abundantly clear in public lectures that they could not have discovered the structure of DNA without her work. However, because the Nobel Prize is not awarded posthumously, Rosalind Franklin could not be cited for her essential role in the discovery of the physical basis of genetic heredity.

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