On DNA’s Anniversary: How Rosalind Franklin Missed the Helix

By George Johnson | April 25, 2013 12:13 am

Less than a year before Watson and Crick’s paper, “A Structure for Deoxyribose Nucleic Acid,” was published in Nature, 60 years ago today, Rosalind Franklin sent around a hand-lettered obituary:

It is with great regret that we have to announce the death, on Friday 18th July 1952 of D.N.A. Helix (crystalline) Death followed a protracted illness which an intensive course of besselised injections had failed to relieve. A memorial service will be held next Monday or Tuesday. It is hoped that Dr. M.H.F. Wilkins will speak in memory of the late helix R.E. Franklin R Gosling

Obituary for the helix. Wellcome Library.

Led astray by her own evidence, she had missed, just barely, making the greatest discovery in the history of biology: the coiled, interlaced structure that explained with such clarity the working of the gene. “The secret of life,” Crick called it.

Gosling, the other signatory, was Franklin’s assistant at King’s College in London, and Wilkins was her boss and bête noire. “Besselised” refers to Bessel functions, a mathematical tool used to analyze the photographic images she so expertly produced of DNA. But the most significant word in her mocking postcard was the one in parentheses: crystalline.

Several months earlier, having mastered better than anyone a technique called x-ray crystallography, she had taken the clearest pictures yet of the molecule. It came in two forms, depending on whether it was crystallized (shape A) or dissolved in water (shape B). It was the longer, stretched-out wet form, her Photo 51, that went on to become legendary. Horace Freeland Judson describes it in The Eighth Day of Creation:

The overall pattern was a huge blurry diamond. The top and bottom points of the diamond were capped by heavily exposed, dark arcs. From the bull’s-eye, a striking arrangement of short, horizontal smears stepped out along the diagonals in the shape of an X or a maltese cross. The pattern shouted helix.

The question that has dogged historians ever since is why Franklin didn’t shout out the same. Instead she put image B aside, concentrating instead on the far less certain pattern in image A. No matter how hard she looked, she couldn’t see a helix there.

Franklin’s Photo 51. Wellcome Library.

She bristled when Crick, working with Watson at the Cavendish Laboratory in Cambridge, told her she was allowing herself to be misled by ambiguous markings and that both forms must be helical. But she couldn’t be persuaded. Cautious by nature, she believed in holding back on interpretation and grand theories until all the data were gathered and understood, the seeming contradictions resolved. Her style was to work from the bottom up, meticulously trying to piece together the big picture.

She thought it was rash and premature that Crick and Watson, with their top-down approach, were enthusiastically building models — castles in the air — before they had laid the foundation. As they put together their sheet-metal and wire sculpture, the details, they believed, could be filled in along the way.

By now Crick was already puzzling over what he saw as the next key issue: How are the nucleotide bases (what we now think of as the DNA letters) zipped together in pairs? He assumed it would be a matter of like with like — that adenine would stick to adenine, thymine to thymine, cytosine to cytosine, guanine to guanine. Then a mathematician told him that his calculations showed the pairing was complementary: A-T, C-G. Crick also finally saw the significance of Chargaff ratios. In his analysis of nucleic acid, Erwin Chargaff at Columbia had shown that A and T and C and G exist in roughly the same proportions. Suddenly it all made sense: two interlocking helical templates forming a molecule that could carry information, and that could replicate.

Over a span of about 40 pages, Judson explains the reasoning with a satisfying verve and turns the realizations and false leads into an absorbing drama. At first Watson had the helix inside out. Then he tried to cram together, like mismatched puzzle pieces, the wrong forms for the bases. In the final weeks before the discovery, another contender, Linus Pauling in Pasadena, had convinced himself that DNA was a triple helix. (Watson and Crick had been up that cul-de-sac before.) Meanwhile Franklin had become intent on proving that DNA — the crystal, at least (it’s not entirely clear what she was thinking) — was shaped like a figure 8. All the while her image B remained on a shelf, in a filing cabinet — wherever it was kept — ignored month after month until Wilkins showed it to Watson, resulting in his famous epiphany. A few weeks later he and Crick had the structure.

After negotiations between both labs, papers by Wilkins and by Franklin and Gosling appeared in the same issue of Nature along with the one by Watson and Crick. (They can all be found on a website at Nature, and an annotated version of the Watson-Crick paper is at the Exploratorium’s site.) Toward the end of their paper, they flatly state that “We were not aware of the details of the results presented [by the King's scientists] when we devised our structure, which rests mainly though not entirely on published experimental data and stereochemical arguments.” Yet they go on to write in an acknowledgment, three paragraphs later: “We have also been stimulated by a knowledge of the general nature of the unpublished experimental results and ideas of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King’s College, London.”

The sentences seem to contradict each other, and in any case Watson made a point, in his book The Double Helix, to describe the pivotal moment when he saw Photo 51.

So the controversy continues. Was it ethical for Wilkins to show Watson his colleague’s work without asking her first? Should she have been invited to be a coauthor on the historic paper? Watson hardly helped his case with his belittling comments about Franklin in The Double Helix.

In Brenda Maddox’s biography, Rosalind Franklin: The Dark Lady of DNA (it was Wilkins who called her that) she makes a strong argument that her subject knew all along that the B form of DNA was helical. But she didn’t advertise the fact or begin to see the significance until shortly before Watson and Crick made their breakthrough. With a little more time she might have gotten the structure first. Or maybe Wilkins would have done so if Franklin hadn’t left him with the impression that a helical structure had been ruled out. After the discovery was made, she figured out how the crystalline A form was just a foreshortened version of the B. Like so many things it was clear in retrospect.

During the last week or so I’ve reread Judson’s account of that year before the discovery and then the relevant pages in Maddox’s biography and Robert Olby’s detailed history, The Path to the Double Helix. There are many other wrinkles to the story — the “gentlemen’s agreement” by the Cavendish not to tread on King’s turf, the role of Max Perutz as another conduit between the two laboratories. All of this was hashed out during the 50th anniversary in 2003 and it will be rehashed again for the 70th. That is how fascinating a story it is, revealing how human curiosity vies with human competitiveness in the unfolding of great science.

Related posts: My Letter from Francis Crick

The Best Science Book Ever Written

CATEGORIZED UNDER: DNA, select, top-posts
  • juniper97

    Glad to see Judson being read and talked about again. Regarding credit and authorship, though, I think that such discussion is incomplete without Maxine’s comments (which are, I think, at the end of the book). Maxine points out two things: one, that Franklin was not only a woman but refused to play the gender-politics game (still of value if you’re a woman trying to get along in a male field), and two, that Franklin was Jewish.

    We underestimate — or ignore completely — from here and now the virulence of English anti-semitism. It’s still there, but a hundred years ago it was simply breathtaking in its openness and brutality. Read Keynes’ remarks sometime; they’re not unusual.

    Perutz was Jewish too, of course, but not really, not like one of those; he’d been brought up in a Catholic-converted, happily mitteleuropeen family, and only the Nazis made him a Jew. And besides he was the boss, and a hail-fellow man. Franklin, by all accounts I’ve read, was instantly recognizable as the sort of small, dark, sharp-tongued, very bright, non-ground-giving, highly capable woman found in Jewish communities everywhere. Would this have mattered, yes.

    I do not think there’s anything especially mysterious in her refusal to, as she saw it, jump the gun. There was a great deal of gun-jumping going on in biochemistry at the time, and why not? Gold in them thar hills. Publish now, repent later. She wasn’t into it, and she hadn’t, it seems, the same need to hurry, to make a name. That’s a male obsession, is it not? It seems to me she simply wanted to do her work and do it well, to her own satisfaction. And so she did afterwards on TMV, until her death. What she did do was stand in the way of some young men who were willing to be far less careful in order to score a win, or try to score a win, and she wasn’t SA-friendly about it, so after they ripped her off they treated her badly and refused her credit. She was also part of a minority long held in low esteem, and her institution failed to protect her. I see nothing unusual in this story, unfortunately.

    Amy C.

  • JonFrum

    Franklin deserved credit for the discovery of the structure of DNA to the degree that a lab tech deserves authorship on a paper. She did essential work that produced the breakthrough. Having said that, she did not make the intellectual breakthrough, and she did not take part in making the intellectual breakthrough. Anyone saying that she deserves to be treated on the same basis as Crick and Watson is doing so for non-scientific reasons – transparently non-scientific reasons. Franklin did excellent lab work. She failed to understand the product of that work. Crick and Watson did. She-would-have, she-could-have hypotheticals are good for novels, but for history, not so much.

  • Count Iblis

    Interesting! I wonder if more of the properties could have been discovered theoretically. Von Neumann had discovered the most basic of the properties:
    http://en.wikipedia.org/wiki/Von_Neumann_universal_constructor

    Von Neumann’s crucial insight is that part of the replicator has a double use; being both an active component of the construction mechanism, and being the target of a passive copying process. This part is played by the tape of instructions in Von Neumann’s combination of universal constructor plus instruction tape.
    The combination of a universal constructor and a tape of instructions would i) allow self-replication, and also ii) guarantee that the open-ended complexity growth observed in biological organisms was possible.[3] The image below illustrates this possibility.
    This insight is all the more remarkable because it preceded the discovery of the structure of the DNA molecule by Watson and Crick, though it followed the Avery-MacLeod-McCarty experiment which identified DNA as the molecular carrier of genetic information in living organisms.[5] The DNA molecule is processed by separate mechanisms that carry out its instructions and copy the DNA for insertion for the newly constructed cell. The ability to achieve open-ended evolution lies in the fact that, just as in nature, errors (mutations) in the copying of the genetic tape can lead to viable variants of the automaton, which can then evolve via natural selection.”

  • Roger Schlafly

    The reason for crediting Franklin is that she made original breakthroughs on DNA, and that they were essential to Watson-Crick’s work. See the Wikipedia article on her for details. She had the double helix, the backbones on the outside, the water content, and the crucial experiment. The famous Watson-Crick paper had no great original intellectual breakthrough, and its fame was largely dependent on how it misrepresented its sources.

    • Euler

      That wikipedia article is somewhat misleading. The double helix hypothesis did not originate with Franklin. The idea that DNA might have a helical structure had been around for a while, and many people had opinions on its likelihood, including Franklin, but also including people before her.

      She did not assert that DNA had a helical structure. She, like most people in the field, did not rule out the possibility, but she disfavored it based on the A form data until Watson and Crick put out their model.

      To say that the Watson-Crick paper had no great original intellectual breakthrough and that its fame was largely dependent on how it misrepresented its sources is totally false. Franklin herself acknowledged that the model was Watson and Crick’s. You can read her paper in Nature where she explains how her X-ray results are consistent with Watson and Crick’s model:

      http://www.nature.com/nature/dna50/franklingosling.pdf

      “Thus our general ideas are not inconsistent with the model proposed by Watson and Crick in the preceding communication”

      Watson and Crick’s model was much more specific than the general idea of two helices with the sugars in the middle. There were two antiparrallel strands with precise dimensions for the diameter, the major and minor groove distances and the pitch.

      Howver, the major breakthrough of the structure of Watson and Crick was not the shape, but the arrangement of the base pairs. The reason it is so much more remarkable than Linus Pauling’s structure for the alpha-helix in proteins is that not only does it give geometric information, but it also strongly suggested a solution for the problem of the molecular basis of heredity.

      Since only complimentary bases could pair, this suggested that the DNA polymer could copy itself with high fidelity, since one strand could act as a template for a new strand if they were separated. With this copying mechanism, specific DNA sequences could be passed between generations, suggesting that “genes”, which where at that point only hypothetical constructs, where actual molecular sequences. It would resolve the controversy over whether there was ‘blending inheritance’ where the offspring got averaged traits from their parents, as Darwin thought, or if there were discreet units of inheritance, as others such as Ronald Fisher thought.

      Watson, Crick and Wilkins did not win the nobel prize specifically for that structure, though. It was awarded 10 years later after the three (Franklin had died of cancer already) spent the intervening time providing solid evidence for these conjectures as well. So they really put in place much of the modern understanding of genetics, and did not just guess a shape.

      • Roger Schlafly

        The Wikipedia article documents what it says. Franklin wrote papers on the DNA helical structure.

        Yes, Franklin recognized that her data was consistent with the Watson-Crick model. She never knew that her data was essential to their work.

        You are right that the structure of DNA turned out to be critical to understanding genetics. It is not so clear that Watson-Crick deserve any more credit than Franklin.

  • http://www.facebook.com/people/Tom-Hennessy/100000148200376 Tom Hennessy

    If everyone shared everything openly then we might ‘run ahead’ as opposed to stumbling ahead and the fact one scientist believed in this method , showed his bosses work to others , means many people were helped during the time it would have taken Franklin to prove , by the scientific method , her beliefs. If she was so sure of her beliefs she should have thrown it out there and cared very little of what anyone ELSE thought or worked at. She got unlucky that Watson was so intelligent. Sht happens for the ‘better good’ sometimes.

NEW ON DISCOVER
OPEN
CITIZEN SCIENCE
ADVERTISEMENT

Discover's Newsletter

Sign up to get the latest science news delivered weekly right to your inbox!

Fire in the Mind

Whether a subtle new pattern shows up in an experiment on the Higgs boson, an epidemiological report about a suspected cancer cluster, or a double-blind trial purporting to demonstrate ESP, it can be maddeningly difficult to distinguish between what we see and what we think we see. "Fire in the Mind" takes a look at the big questions behind today’s science news.

About George Johnson

George Johnson writes about science for the New York Times, National Geographic Magazine, Slate, and other publications. His nine books include The Cancer Chronicles: Unlocking Medicine's Deepest Mystery (August 2013), The Ten Most Beautiful Experiments, A Shortcut Through Time, and Fire in the Mind. He is a winner of the AAAS Science Journalism Award and has twice been a finalist for the Royal Society science book prize. Co-founder and director of the Santa Fe Science Writing Workshop, he can be found on the Web at talaya.net. Twitter @byGeorgeJohnson.

ADVERTISEMENT

See More

ADVERTISEMENT

@byGeorgeJohson onTwitter

Collapse bottom bar
+

Login to your Account

X
E-mail address:
Password:
Remember me
Forgot your password?
No problem. Click here to have it e-mailed to you.

Not Registered Yet?

Register now for FREE. Registration only takes a few minutes to complete. Register now »