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Maurice Hugh Frederick Wilkins was born in Wellington, New Zealand on December 15, 1916. His father had moved there from Dublin in 1913 to practice medicine and the family did not return until 1923 thereby missing the horrors of World War I and the coincidental troubles in Ireland during and after the war. |
Maurice died on October 5, 2004 at Blackheath, London where he had resided for the last half of his long life. In between there was a good education at King Edward's School in Birmingham and at St John's College, Cambridge where he did not get a good enough degree to be invited to stay on and do research in Physics as he might have wished.
The personal and professional consequences were profound. Exploiting his St John's network he got a place at Birmingham where his old tutor, Mark Oliphant, had recently (1937) become Professor and J. T. Randall, newly arrived with his Warren Research Fellowship of the Royal Society, was looking for recruits to do research on the luminescence of solids. The Oliphant connection led to Maurice's wartime participation in the Manhattan Project (1944-5) and his brief first marriage. The Randall connection provided lifelong scientific patronage on a munificent scale as Sir John moved on from his co-invention at Birmingham of the radar-stabilising cavity magnetron to the Chair of Natural Philosophy at St Andrews, then the Wheatstone Chair of Physics at King's College London and the simultaneous Directorship of the MRC Biophysics Unit there. Randall, the abrasive impresario, had to build and develop two new departments (Biophysics as well as Physics) during his time at King's and throughout used Maurice as an emollient deputy, a congenial and important role that he resented only occasionally as he progressed from assistant to deputy director of the MRC Unit, the Chair of Molecular Biology, and eventually succession to the directorship on Randall's retirement (1970).
Along the way something far more exciting happened: Maurice encountered DNA, played a key role in unveiling and establishing its double helical structures and the related ones of some RNAs. For these achievements he was elected to the Royal Society (1959), received the 1960 Albert Lasker award (made to Wilkins, Crick and Watson in that order), and finally in 1962 shared (also with Watson and Crick) the Nobel Prize for Physiology and Medicine. By this time Maurice had re-married and with his new and growing family might have lived happily ever after had not Jim Watson published a provocative, best-seller about the provenance of the DNA double helix. This spawned other hopeful literary monsters in which Maurice, the unassertive third man of the double helix, became a convenient vaudeville villain for those seeking posthumous recognition of another King's physical scientist, R.E.Franklin, who also had contributed to X-ray diffraction studies of DNA.
It has to be understood that the MRC Biophysics Unit at King's was not intended to study macromolecular structures. Its chosen tools would be physical (optical and electron microscopy and spectroscopy), but the targets of its investigations would be supra-molecular (chromosomes, cells and tissues, and motile elements like cilia and flagella). Consequently there was no early investment in X-ray diffraction equipment or personnel. The Wheatstone Laboratory's diffraction expert, A.R. Stokes, was very much a physicist and not a chemical crystallographer. In fact it is not unfair to say that there was a pervasive suspicion of crystals. These were tombs for dead molecules but physicists who had become biophysicists preferred to be seen to be studying more vital systems. It says a great deal for Maurice Wilkins' insight that he was not only one of the first to accept that DNA was indeed the genetic material but on discovering that its gels could be ordered at the molecular level he at once decided to abandon his optical microscopes for the higher resolution probe of X-ray diffraction.
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Fig.1. A-DNA diffraction with the fiber tipped into the X-ray beam to record the 0,0,11 reflexion dignostic of the 11-fold screw symmetry of the molecules. |
In retrospect it is difficult to imagine a committed and well-trained crystallographer looking at space group no.5 in International Tables and not concluding that the A-DNA unit cell would contain 4 quasi-identical polynucleotide chains, diadically paired and packed like a bundle of cylinders of 22A diameter. Of course the bundled chains could not be cylinders exactly but spirals with 11-fold screw symmetry as indicated by the absence of meridional X-ray reflexions until the appearance of the diagnostic 0,0,11 reflexion that is so prominent at the top of Fig.1. As every crystallographer would know: an 11-fold screw axis could not be a crystal symmetry and therefore it would have to be a molecular property !
If DNA were indeed the genetic material then the information it contained would have to be complex at some level of resolution but here again classical crystallographers should not have been dismayed by the apparent simplicity of the A-DNA crystal structure. Crystalline minerals excited much attention both before and after the discovery of X-ray diffraction . The bewildering complexity of their chemical compositions was a challenge until it could be shown by X-ray crystallography that a relatively few three-dimensional structural motifs of alumina and silica could accommodate a wide variety of chemical variation. DNA presented an analogous challenge: how might the constituents of chemically diverse polynucleotides form isomorphous components that might vicariously replace one another in a simple regular structure like a helix. This was the problem addressed directly by the biologist J.D.Watson and solved by his discovery of base-pairing after some crucial advice about tautomerism from the chemical crystallographer Jerry Donahue. Of course a demonstration model had to be built to show that Watson's base-pairs could be accommodated in a double helical cage with the correct overall dimensions but it is fair to say that such niceties would be of little interest to molecular biologists for whom the duplex nature of DNA and the complementary base pairing would be the key revelations.
All this happened at Cambridge while the London DNA effort was taken on a bizarre detour into the desert of crystallographic orthodoxy by recruitment of R.E. Franklin, a physical chemist with just enough X-ray diffraction education obtained while studying coal and coke to be full of wise saws and modern instances concerning X-ray structure determination in general. Pre-war methods were out. Too often these had used heuristic methods to produce preliminary models of unit cell contents from which were obtained a preliminary set of X-ray phases that were slowly improved by a succession of Fourier syntheses of electron density and sometimes the introduction of yet more chemical insights. By 1950 X-ray crystallography was on the threshold of its robotic, triumphalist stage: with better computational methods and more sophisticated diffraction theorems, number-crunching of the intensities alone would solve the phase problem and produce structures needing no further authentication because no chemical prejudices had tainted their genesis. More experienced experimentalists might prefer to retain a choice of horses for courses and and give priority to getting the right answer rather than to the use of currently correct methods. This kind of thinking was now anathema at King's.
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Fig.2. B-DNA diffraction indicating 10-fold screw symmetry and an overall structure very different in detail from that of A-DNA. |
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Fig.3. Diffraction from a fiber containing 12-fold RNA helices with conformations similar to A-DNA. |
Only when RNA duplexes were
discovered to have A-like conformations (Fig.3) was A-DNA rehabilitated as a
canonical structure.
The Watson and Crick eureka at Cambridge must have disappointed Maurice at
the time but no one who knew him well would have expected him to be other
than pleased with the outcome . He certainly was more committed to getting
the right answer than to following fashionable procedures. It was ironic
therefore that his next role in the DNA saga was the problem of
authenticating the Watson-Crick hypothesis, and doubly ironic that a subtle
property of A-DNA was the ghost in the machine. The stereochemically
reasonable model that Crick and Watson built to reinforce the plausibility
of their conjecture was designed to be a model of B-DNA. Such was their
attention to precise detail that the 5-membered deoxyribose rings in their
model not only had accurate bond lengths and angles but they also were
puckered and not planar as observed in Furberg's pioneering crystal
structure of the nucleoside cytidine at Birkbeck. There are essentially two
ways in which deoxyribose rings can be puckered, C3'-endo and C2'-endo. Both
are observed in polynucleotide duplexes; the former in A-like structures,
the latter in B-like structures. The macroscopic consequences of these local
conformational differences are quite profound. A-type structures have their
base-pairs about 4A nearer the surface of their double helices than B-type
structures and therefore have a deep groove and a shallow groove in contrast
to B-DNA's more similar grooves. None of this was fully and explicitly
understood until many years later so it was especially unfortunate that
Furberg's cytidine had the C3'-endo-puckered rings appropriate for A-DNA but
not for B!
 Fig.4.(a) The electron density distribution in the plane of an (average) Watson-Crick base-pair obtained with diffraction amplitudes for B-DNA and phase angles calculated from the original Crick-Watson demonstration model. The image shows not only the (expected) low resolution but also a poor fit with the model. (b) The corresponding difference map (with positive density in blue and negative density in red) reveals the major geometrical flaw in the model is the position of the base-pairs relative to the helix axis. (c) A model with the correct deoxyribose conformations and other refinements shows a better fit with the new electron density map. |
Thus in 1953, Franklin having left King's for Birkbeck, Maurice Wilkins was once again in sole possession of the DNA diffraction problem but with a new and agonizing twist. There now existed a stereochemically entirely plausible structure for B-DNA that rationalized a great many biochemical observations and clearly suggested how nucleic acids might function biologically, yet this attractive structure provide X-ray intensities profoundly at odds with those observed. The R = 90% discrepancy was nearly twice as bad as that which textbook theory predicted for a completely wrong structure. Such a discordance was too provocative to be ignored but it was to take nearly a decade of improvements in computation, in preparing well-oriented and polycrystalline specimens, in perfecting X-ray cameras for the special needs of fiber diffraction, and in developing new methods of structure refinement before the structures of DNA were fully refined and brought into concordance with all the diffraction data. There was however an additional dividend from Maurice's investment: there could now be rapid analyses not only of fibrous DNAs but also of RNAs and many other spiral structures found with peptide and carbohydrate polymers that did not form single crystals but were of biological or industrial importance.
Maurice Wilkins' early acceptance of DNA as the genetic material and his recognition that it had structures that could and should be tackled by X-ray diffraction analyses, not necessarily under his exclusive control, was important in ensuring that the essence of DNA's structure was discovered as early as it was. His success in resolving patiently and effectively all the technical problems, great and small, that arose unpredictably in the course of his own work on DNA and RNA was substantial. His pacific acceptance of the slings and arrows that unjustly assail those involved in momentous enterprises was typical and showed a life that had a certain style as well as much substance.
Struther Arnott
Note from the webeditor: