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Apr 1, 2013 (Vol. 33, No. 7)

The Genesis of a Discovery: First Steps

  • Seeds of Conflict

    Unfortunately Franklin thought that she was a senior post-doctoral fellow and completely independent. Wilkins assumed that she would freely interact with him, as did most other people in the lab. The seeds of conflict were sown, which caused a great deal of angst. In retrospect I should have realized this and tried to prevent this conflict.

    Early in 1951, Wilkins met James Watson at a conference where he had presented our work. Watson asked Wilkins if he could join the group at King’s but was rebuffed. Consequently, he went to Bragg’s unit at Cambridge. There he met Francis Crick who knew all about our work, as he was a close friend of Wilkins.

    Franklin joined the DNA group in early 1951. Her first directive to me was to make up a series of saturated salt solutions that would give a constant humidity to the hydrogen we bubbled through to displace the air in our camera. So we were then able to take the same specimen through stages of water content from dry (disorientated pattern) to 92% humidity and to do this with a single fiber.

    This painstaking experimentation I later realized was the hallmark of her science. She was able to show that NaDNA could exist in two stable forms, which we named A and B. We realized that all the published fiber diagrams up to now had been mixtures of these two forms. That I had produced a pure form of A with Maurice’s multifiber specimens was serendipitous.

    A result of just the right rate of flow of dry hydrogen through water was to give a steady 75% humidity. My only concern at that time was not to blow myself up by filling the lab with hydrogen and getting a spark from 50,000 volts on the rather old x-ray tube.

    As to the structure, it was obvious from the B pattern—the best we ever got was Photo 51—that at high humidity and therefore presumably in vivo, the molecule was helical. From Stoke’s theoretical math we found that the diameter was 20Å and the repeat distance was 34 Å containing 10 nucleotides per turn of the helix with a slope of 40°.

    However, Franklin was more excited by the crystallized gene structure shown in “A.” Her view was that although “B” was helical it did not necessarily follow that “A” was.

  • Direct Structural Information

    Franklin and I convinced ourselves that we had so much direct structural information in the intensity and position of the diffracted beams, nearly a 100, that we should calculate a Patterson Function from the data. This would show helical or asymmetric chains without the need to build models.

    At this time we were summoned to Cambridge to see a proposed structural model that Watson and Crick had built. This showed the Na/P ionic atoms forming a central core and the sugar rings coming out to the bases on the outside. Franklin demolished this suggestion with gusto! Mainly because we knew the Na/P complex must be on the outside of the structure because the water went in and out so easily. As Crick remarked later, it was the only time he had seen Watson at a loss for words!

    With hindsight it is easy to see that the structure they had built was so rigid that it must be wrong. It is know that there are 3 billion base pairs in the human genome. At 34Å thick, this would mean a length of 102 cm, thus requiring great flexibility to allow folding of the structure to fit into the cell nucleus.

    So we returned to Kings and started with renewed vigor on our intensity measurements, correction factors, and Patterson function calculations. For us, model building was out. Bragg forbade Watson and Crick from any further model building. The DNA problem, it was agreed, belonged to Kings!

    However some months later, on learning that Pauling was actively thinking of DNA structure, Bragg lifted his ban on model building, and Watson and Crick began building models again, this time using our data as to helical radius 10Å, and to the number of nucleotides along the fiber axis per repeat interval, 10 in 34Å, and the space group of structure A, Monoclinic C2. This permitted Crick to rightly postulate two chains per lattice point related by a diad axis, i.e., one going up and one going down.

    When they added to this data, the specific pairing of the bases all fell into place. We were summoned once more to Cambridge. This time we were convinced. It was so elegant, it must be right. On our return to London Franklin and I examined our Patterson data and everywhere we looked we could see indications of a double helix.

    I think it is very sad that Franklin was never able to see the exponential mushrooming of molecular biology resulting from her work. I would love to have heard her opinion of the current controversy on the cloning of stem cells.

    The laws of the physical universe will always apply, and it is only our interpretation and use of the data that may be wrong. However, when experimenting with living material, even the protocol of the experiment may be questioned.

    I believe Franklin would have advocated a global approach to the regulation of such work. We are now facing direct manipulation of the evolution of our species and the creation of new transgenic life forms. A problem probably more important than global warming.

    Do you think Rosalind Franklin has gotten enough credit for her role in discovering the double-helix structure of DNA?

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