History, Reviews, Science.

The Dark Lady of DNA

Book Book Review, Title Rosalind Franklin: The Dark Lady of DNA, Author Brenda Maddox, Rating 4.5,

Rosalind Franklin: The Dark Lady of DNA

Brenda Maddox

Book Review

Rosalind Franklin was one of the primary actors in the search for the structure of the DNA molecule.

In 1968 James Watson published The Double Helix, his personal account of the elucidation of the structure of DNA, in which he de-emphasized Rosalind Franklin's critical contributions during the period of discovery, while drawing a negative portrait of her.  Franklin did not receive the Nobel Prize for this discovery, but Watson and Crick did. Why not? Rank villainy?

Brenda Maddox does a superb job of sorting out Franklin's complex story.

Franklin took the all-important X-ray crystallographic photo of the B form of DNA, photo 51. Watson and Crick relied on this picture, along with several other lines of evidence and theoretical work, and emulated Linus Pauling by building actual physical models of the molecule of life, finally producing the correct model, which they published in 1953 in the periodical Nature, alongside Franklin’s paper describing her crystallographic evidence. Another colleague from her lab who had done a great deal of crystallographic work on DNA, Maurice Wilkins, also published a paper about the structure of DNA in the same issue of Nature. This method of publishing was intended and received as a direct acknowledgement of contribution to the solution by the various parties. (View the original papers here.)

Franklin, who left her work on DNA to pursue other topics before Watson and Crick published their model, died five years later, still four years before the Nobel prize was awarded for the discovery of DNA. Wilkins was awarded the Nobel prize along with Watson and Crick for the DNA discovery; Nobel prizes are not awarded posthumously, so Franklin was no longer a candidate for the award. It is possible that Franklin would have received the honor instead of Wilkins had she lived, but quite uncertain (the Nobel committee limits the sharing of the Medicine prize to no more than 3 recipients). Beyond the initial simultaneous publications in Nature, Watson, Crick and Wilkins did little to promote the importance of her work in the discovery of the DNA structure while she was alive.

Book Briefly Noted, Title Rosalind Franklin and DNA, Author Anne Sayre, Rating 3.0,

Rosalind Franklin and DNA

Anne Sayre

Briefly Noted

Her first biographer, Anne Sayre, wrote more of a defense of her friend than a balanced history; in her book Rosalind Franklin and DNA, she argued that Franklin was ignored and treated shabbily by the men’s club of British science; certainly Watson’s tone in The Double Helix supported that hypothesis.

Brenda Maddox’s treatment of Franklin’s story is much more nuanced, balanced, and richer. Maddox certainly found much to support the idea that at the time, women in science, few in number, and Franklin in particular, bucked up against a great deal of sexist prejudice and dismissal. But she also noted that Franklin herself had had good opportunities and comfortable working relationships in the labs she worked in before and after her DNA work, performing and getting appropriate credit for first rate work, and suggested that the some of the problems she encountered, some alluded to by the crass Watson, were specific to her situation in that lab. Randall, the head of Franklin’s lab, brought her in to work on DNA, which prior to her arrival at the lab was the sole domain of Maurice Wilkins. Randall deviously pitted the two researchers against each other rather than foster collaboration between them; he told Franklin but not Wilkins that she was responsible for the DNA research. Also, Wilkins, Watson and Franklin rubbed each other the wrong way, and found it difficult to work together for reasons beyond the sexism and heavy-handed leadership. (The ironical Dark Lady of the book’s title is from a phrase used by Wilkins to describe Franklin.)

Franklin was only one part of the controversy over who deserved credit for the discovery of DNA. Many, especially some of those more directly involved in the experimental research, were bitter about Watson’s and Crick’s getting there before they did, chief among them Erwin Chargaff, who had been researching nucleic acids, and had discovered one of the critical facts needed to solve the structure: When analyzing DNA from various species, the four organic bases that were part of the DNA polymer showed the same specific ratios, with the number of adenines equaling the number of thymines, and the number of guanines equaling the number of cytosines.

Another, Jerry Donohue, had determined the most probable conformation of those same bases using theoretical quantum mechanical arguments, another critical factor. Both of these men felt that they had claim to a share of the Nobel Prize that went to Watson and Crick. Even Maurice Wilkins, who did share the prize, was unsettled about the role of Watson and Crick; in England in the 1950’s, it wasn’t considered quite cricket to use someone else’s research to further one’s own, a rather odd and solopsistic view that did not survive the era. All alluded to the idea that Watson and Crick had taken their work and only put it together (a remarkably obtuse viewpoint!), despite the fact that their evidence had been made public. Chargaff and Donohue had published their results, and Franklin had led a colloquium which Watson attended and to which Crick was invited, and some of her results had been published in a Medical Research Council (MRC) report which was designed to share information between labs sponsored by the MRC. In hindsight it was clearly required to take information from several approaches and disciplines in order to solve the structure, an attempt made only by Watson and Crick.

Also complicating this point of view was that Linus Pauling, already a Nobel Prize winner, had made a similar attempt to Watson and Crick, proposing a physical model of DNA from published facts and chemical bonding principles, but his model was seriously flawed. Pauling had recently determined a sub-structure of a large and complex biological macromolecule, the alpha helix found in collagen, using such modeling techniques. Additionally, Crick had independently determined a theoretical model for a helical biomolecule, and Watson had done viable research on the helical structure of the tobacco mosaic virus capsule, so both were actively contributing to the general field of macromolecular structures.

Perhaps surprisingly, Rosalind Franklin did not hold the attitudes of Chargaff or Dononue. Once having left her DNA work before the structure was determined, by most accounts because she was unhappy with her working situation rather than her disinterest in the subject, she made no public nor private argument over the matter, even though her research contributed the most critical experimental information needed to solve the structure. Her crystallographic results, including photo 51, provided clearer evidence of the helical structure (some of Wilkins’ earlier photos suggested a helical structure, but were not definitive), allowed precise measurements of the helical width and repeat, along with more accurate density and humidity measurements (allowing a determination of the number of chains in the molecule, two), provided clearer arguments and evidence that the bases were in the interior rather rather than on the outside of the molecule, and finally identified the correct symmetry group, which allowed Crick to determine that the two chains were going in the opposite direction of each other. (Interestingly, Franklin did not catch this.) She also was the first to determine that there were two structurally distinct forms of DNA, which she labeled A and B. It is the B form that is found predominantly in nature; previous X-ray photos of DNA were usually blurred due in part to their being a mixture of the A and B forms.

-CC BY-SA 2.0, Robin Stott

Photo 51, X-ray diffraction photo of the B-form of DNA. Attrib: Robin Stott, CC BY-SA 2.0.


Franklin did make some of her own attempts to solve the structure using purely crystallographic analytical techniques. The experimental technique used to produce photo 51 involved shining X-rays through the target crystalline DNA molecule (meaning the molecule had been prepared in a way that the conglomeration of target molecules in the sample were in a very regular structure), which then were scattered in a unique way determined by the internal atomic structure of DNA, exposing film in a spot pattern particular to DNA. Franklin’s mathematical analysis of the X-ray patterns was an attempt to work backwards from the spots on the photo and figure out what the structure of the molecule was by the way the light was deflected from the direction of the original source of X-rays, a little bit like a criminologist determining the direction from which a bullet was fired by working backward from the bullet imbedded in a wall. The crystallographic analysis is much more complex than the problem the criminologist has, particularly in the case of DNA, composed of many atoms in a complex arrangement, all of which can affect the scattering of the incoming X-rays. Franklin’s analysis bore fruit, but it did not lead her to a clear description of the structure. Today, with the availability of powerful computers, this is a more accessible technique for large molecules, but was extremely time-consuming and difficult in the 1950’s, made no easier by the fact that it was done manually. (Using similar techniques in the same era, Perutz and Kendrew solved the structure of hemoglobin, another large and even more complex biomolecule; it took them better than twenty years.)

Francis Crick, who collaborated with Franklin occasionally in the years after the DNA discovery, may have said it best, that Rosalind just needed someone to talk things over with, to collaborate with, like he and Watson had fallen into, and then she may well have been able to get past her own mental blocks in finding the structure, to separate the wheat from the chaff, to become knowledgeable of important information and methods outside of the field of crystallography (for example, at the time she had not yet embraced the new method of physical model building central to Watson and Crick’s approach) that were used to help solve the puzzle, and may well have been the one to find the structure of DNA first. (Aaron Klug said something similar, after he had analyzed her notebooks from her DNA research.)

In any event, the Nobel Prize does not generally reflect the collaborative nature of leading edge science. Even large individual contributions to knowledge are made on the shoulders of giants, as the great physicist Isaac Newton pointed out: Among many examples, Newton was led to his Universal Law of Gravitation in part by Kepler’s Laws of Planetary Motion, and his own Laws of Motion were in part built on work done by Galileo and Descartes.

The discovery of the structure of DNA, a seminal event in the field of molecular biology, was indeed a result of many years of research, the most notable perhaps (where to start? who to leave out?): Miescher’s characterization of nucleic acid, organic crystallographic work by the Bragg’s, von Laue and Pauling; Griffith’s pneumococcal transformation by nucleic acid, Avery’s identifying DNA as the transforming agent; Hershey and Chase’s demonstration that DNA was the genetic component of bacteriophage viruses; Chargaff’s careful determination of organic base ratios; Donohue’s identification of organic base conformations; Astbury, Wilkins and particularly Franklin’s crystallographic work on DNA; and finally the puzzle solving Watson and Crick, who put all of these pieces together to describe the correct physical model of DNA. Only some of these people received Nobel prizes for their efforts.

In some ways, Rosalind Franklin’s story is a tragedy, a life quite possibly brought short by cancer induced by her heavy overexposure to X-rays, but is first the tale of a brilliant physical chemist who contributed a great deal to science in her short life, extending scientific understanding of the structure of DNA, of coal, and of the tobacco mosaic virus.

Other books recommended on the subject of the discovery of the structure of DNA:

The Double Helix: A Personal Account Of The Discovery Of The Structure Of Dna (Norton Critical Editions), by James D. Watson, Gunther Stent

The Eighth Day of Creation, by Horace Freeland Judson

The Path to the Double Helix: The Discovery of DNA, by Robert Olby

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