- Email: [email protected]
The forgotten man of DNA
Studies in History and Philosophy of Biological and Biomedical Sciences 51 (2015) 67e69
Contents lists available at ScienceDirect
Studies in History and Philosophy of Biological and Biomedical Sciences journal homepage: www.elsevier.com/locate/shpsc
Essay review
The forgotten man of DNA Matthew Cobb Michael Smith Building, Faculty of Life Sciences, University of Manchester, M13 9PT, UK
When citing this paper, please use the full journal title Studies in History and Philosophy of Biological and Biomedical Sciences
The Man in the Monkeynut Coat: William Astbury and the Forgotten Road to the Double-Helix, Kersten T. Hall. Oxford University Press, Oxford (2014). 256 pp. Price £18.99, hardback, ISBN: 978-0-19-870459-1
William ‘Bill’ Astbury (1898e1961), a physicist who worked at Leeds University in the north of England from 1928, was a key figure in the history of molecular biology. He carried out pioneering work on the X-ray crystallography; he published the first X-ray images of DNA fibres, and he developed the first molecular models of the structure of the molecule. Both these models were wrong, but he correctly suggested that nucleotides were regularly spaced, perpendicular to the phosphate-sugar backbone, thereby setting the scene for the research of Maurice Wilkins and Rosalind Franklin and the discovery of the double helix structure of DNA by James Watson and Francis Crick in 1953. Astbury’s work formed a key part of Robert Olby’s The Path to the Double Helix (Olby, 1994), which described the background to Watson and Crick’s discovery primarily in terms of the techniques that lay beneath it, principally X-ray crystallography. Kersten Hall, a visiting fellow in the School of Philosophy, Religion and History of Science at the University of Leeds has now published an intellectual biography of Astbury, written through the prism of the discovery of the structure of DNA. As well as shedding light on a crucial period in the history of biology, Hall explores the scientific politics of the timedAstbury’s perpetual struggle for recognition and funding will resonate with many of today’s researchers. Hall’s biography covers a vast territory, from Headingley (the Leeds cricket ground, near Astbury’s laboratory) to Asilomar (the Californian seaside town that was the site of an important conference on genetic engineering), with an eye for the striking detail and unexpected historical linksdthe modernist poet T. S. Eliot, the 19th century co-author of the Communist Manifesto Friedrich Engels and the 1980s English cricket legend Ian Botham all pop up in these pages.
E-mail address: [email protected]. http://dx.doi.org/10.1016/j.shpsc.2015.03.004 1369-8486/Ó 2015 Elsevier Ltd. All rights reserved.
Hall has scoured the archives in Leeds, and has made a number of intriguing discoveries linking Astbury with the key moments in the study of the structure and function of DNA. Some of these nuggets have been published in the pages of this journal (Hall, 2011), others are to be found in the pages of the book, some lurking in the footnotes. Hall has also set up a valuable website, ‘X-Ray Marks the Spot: William Astbury and the Birth of Molecular Biology at Leeds’, based on a temporary exhibition of the same name, which includes pictures of a number of artifacts, pieces of equipment and letters. It is highly recommended for those looking for further information about Astbury, or resources for teaching or research: http://www.leeds.ac.uk/heritage/Astbury/ Astbury took a degree in physics at Cambridge, and having survived the horrors of World War 1, learned X-ray crystallography with the elder of the father-son pioneers of the technique, Sir William Bragg, first at University College London, then at the Royal Institution. After failing to get a lectureship at Cambridge in 1927, he was more or less forced by Bragg to accept a lectureship in Textile Physics at Leeds. Astbury was not particularly happy at this apparent promotiondhe described it in a letter to J. D. Bernal as ‘sad news’ because he initially assumed he would have to give up crystallography because of lack of equipment. But with ingenuity and some funding, Astbury was able to develop an effective but extremely dangerous system for taking X-ray diffraction images. As Hall’s subtitle indicates, to modern eyes the high points of Astbury’s career were linked with DNA. At the time, DNA was thought to be an inert and structurally invariant component of chromosomes, while genes were assumed to be made of proteins. Intriguingly, Hall has discovered that in 1937 Astbury was on a tour of the US and visited the Rockefeller Institute where he had a brief meeting with Oswald Avery, who was working at the time on the transformation of bacteria from one type to another, and using chemical means to identify the nature of what he called the ‘transforming principle’dthe white substance that seemed to enable bacteria to change their nature in a heritable fashion. Hall quotes a brief diary entry by Astbury, in which he described his discussions with Avery and his group and concluded ‘Most exciting!’ (p. 216).
68
M. Cobb / Studies in History and Philosophy of Biological and Biomedical Sciences 51 (2015) 67e69
One of the apparent enigmas of the post-war history of biology is why Avery’s 1943 discovery of the importance of DNA in bacterial transformation was not immediately recognized by the scientific community. According to the version of history that is still taught in many biology textbooks, the significance of Avery’s discovery was not recognized because he published in an obscure medical journal, because he was too diffident, because he was working on a bacterial system that most geneticists did not understand, because people were worried that there were protein contaminants in his samples of DNA, or simply because, as the pioneer molecular geneticist Gunter Stent later put it, the discovery was ‘premature’ (Stent, 1972; for a summary of these arguments see Cobb, 2014). The real breakthrough came in 1952, textbooks tell us, when the Hershey-Chase experiment showed that viruses transferred DNA, not protein, into their bacterial hosts (Hershey & Chase, 1952; Wyatt, 1974). This version of history is simply not true. As Hall’s colleague from Leeds, Vivien Wyatt, showed over 40 years ago, the Hershey and Chase experiment did not prove that DNA was the genetic material, and in fact Hershey and Chase did not make any such claim (Wyatt, 1974). Amazingly, in 1953, after the discovery of the double helix structure of DNA, Al Hershey was still arguing that ‘DNA will not prove to be a unique determiner of genetic specificity’ (Hershey, 1953) (for a summary of this period, see Cobb, 2014, 2015). As is now widely accepted and as Hall explains, in reality Avery was not ignored by everyone in the scientific community. During the period 1944e1948, a large number of individuals, journals and learned societies recognized the significance of Avery’s discovery. One of the first to acclaim the importance of this breakthrough was Astbury. In October 1944 he told a friend in a letter that he was ‘terribly thrilled’ that Avery had identified the transforming substance as DNA and that he considered this to be ‘one of the most remarkable discoveries of our time’. Astbury concluded his letter with these prophetic words: ‘I wish I had a thousand hands and labs with which to get down to the problem of proteins and nucleic acids. Jointly those hold the physicochemical secret of life, and quite apart from the war, we are living in a heroic age, if only more people could see it’ (p. 117). In January 1945, Astbury wrote to Avery congratulating him on the identification of the transforming principled‘I have recently been extremely thrilled by your identification’, he wrotedand reminding the American that the two had met in 1937. It is not known if Avery replied to this letter, or even if he received it (the Avery archives at Rockefeller drew a blank when I consulted them). Whatever the case, no DNA sample was ever sent from New York to Leeds. Astbury was enthused by Avery’s work, and does not seem to have given much credence to the criticisms from those scientists such as Avery’s Rockefeller colleague Alfred Mirsky, who argued that infinitesimal protein contaminants might explain the apparent genetic role of DNA in Avery’s experiments. In 1947 Astbury spoke at a meeting on nucleic acids held in Cambridge by the Society for Experimental Biology, at which a number of dissenting voices were heard, so he was clearly aware of the criticisms. At that meeting, Astbury presented his own model of DNA structure. His images indicated very clearly that DNA contains repeated elements, but he was unable draw any conclusion about the arrangement of those elements because the images were not precise enough. That did not stop him speculating, and putting forward a relatively uniform column as his first guess. Astbury also explained that his mode of thinking applied to all molecules, not just nucleic acids: ‘A test that cannot long be dispensed with in any enquiry into the structure of a complex molecule is that of trying to build an accurate atomic model on the
basis of known sizes and inter-bond angles. Chemical formulae are no more than a convenient shorthand, and it is always revealing, and often startling, to see what a molecule looks like in space.’ (Astbury, 1947). Astbury had none of the monomaniacal focus on DNA shown by Jim Watsondhis molecular interests were wide-ranging although the common thread was the relation between form and function. His approach to molecular structureda mixture of precise physicochemical measures and a real feel for the significance of threedimensional structuredcomes over repeatedly in the pages of Hall’s account. Hall explains in simple terms how x-ray crystallography works, and also transmits Astbury’s excitement at realizing that a number of apparently distinct substancesdhair, wool, horndall contain the same fundamental substance, keratin. Supported by funding from the Rockefeller Foundation and from the wool industry in Leeds, in the shape of the Worshipful Company of Clothworkers, Astbury and his colleagues made a decisive breakthrough when they realized that there were two forms of keratin, which altered as the humidity of the sample changed, and which corresponded to different forms, both of which he assumed to be helical. Although Astbury had the initial insight into the structure of keratin, because of lack of funding and focus he did not pursue its description to the end; that goal became the subject of an intense competition between the US chemist Linus Pauling and Lawrence Bragg, the son of Astbury’s PhD supervisor and mentor. As is well known, Pauling won that race in 1950e51, much to Bragg’s fury. When Pauling began to turn his attention to the molecular structure of DNA, heralded by a profoundly mistaken triple-helix structure submitted to the PNAS at the beginning of 1953 and based on Astbury’s 1938 image of DNA, Bragg revoked an agreement he had struck with his rival John Randall of King’s College London, a year earlier. Bragg now allowed his Cambridge group, which included Watson and Crick, to return to the study of DNA. Astbury was well known to all of the major players in the world of molecular biology. In the summer of 1952, Pauling visited Leeds and stayed with Astbury (an event that escaped Thomas Hager’s biography of Pauling, Force of Nature (Hager, 1995)). This is a particularly tantalizing moment, as Pauling was just beginning to turn his focus onto DNA, and was frustrated by the lack of clear images (he had cheekily asked Randall for some photos, but had been given the brush-off). Shortly before Pauling’s visit, Astbury had got his PhD student and technician, Elwyn Beighton, to make some images of a DNA fibre. These pictures were just as clear as those produced by Franklin, and yet Astbury did not publish them. Astbury cannot have shown them to Pauling that evening, or we would surely know. It is quite possible that the two did not discuss DNA at all. Hall gives this non-event weight because of the apparent significance of another DNA X-ray diffraction image, which was also made in May 1952, by Rosalind Franklin and her student, Raymond Gosling, now known as ‘photo 51’, and which was eventually published in their joint Nature paper that accompanied Watson and Crick’s description of the double helix (Franklin & Gosling, 1953). According to Watson’s account in The Double Helix (Watson, 1968), he was shown the photo by Maurice Wilkins at the end of January 1953, at the point when Bragg had just changed his mind about Cambridge’s involvement in the race to discover the structure of DNA. There was nothing underhand about thisdFranklin was preparing to leave King’s for Birkbeck, Gosling was once again Wilkins’ PhD student, and this unstudied photo formed part of the young man’s research. Watson writes that when he saw the photodwhich with its distinctive ‘X’ shape was far clearer than any other he had seend‘my mouth fell open and my pulse began to race.’
M. Cobb / Studies in History and Philosophy of Biological and Biomedical Sciences 51 (2015) 67e69
Hall seems to accept this dramatic version of the decisive importance of photo 51dindeed, his book opens with the immediate aftermath, as Watson scribbled ideas on a newspaper during the train journey from London to Cambridge. In fact, although this account makes for an exciting tale, and highlights the apparent enigma of Astbury’s failure to recognize the significance of a similar shape in Beighton’s photos, there are reasons not to take Watson’s word for it. For one, despite the power of Watson’s account in The Double Helix, photo 51 did not furnish Watson or Crick with any decisive evidence. It simply confirmed Watson’s prejudice, born partly of his obsession with Pauling’s work on the keratin alphahelix, that DNA had the form of a helix. This in itself was no great insightdby this stage everyone in King’s College accepted it, even Franklin, who at one stage had been dubious (Cobb, 2015). The photo neither proved that the molecule was a double helix, nor provided the kind of precise numerical evidence that Crick needed to create the famous model. Crick himself dismissed the suggestion that the photo played any important role (Crick, 1988). What was arguably the decisive insight came in another form, which Hall mentions only in passing (p. 13), and which was unwittingly provided by Franklin herself. In December 1952 the King’s Biophysics laboratory had produced a brief informal report for the Medical Research Council, which funded most of the research in Randall’s lab, containing summaries of the research that the various groups had been carrying out, such as data from Franklin’s work on the structure of DNA. Those numbers, which included the relative distances of the repetitive elements in the A and B forms of DNA, and the dimensions of the monoclinic unit cell (this indicated that the molecule was in two matching parts, running in opposite directions), were much more significant than a glance at photo 51. One of the MRC worthies who was given a copy of the reportdwhich was not confidential, no matter how Watson later described it in The Double Helixdwas Max Perutz of Cambridge University. In February 1953, as Bragg gave Watson and Crick the green light to return to the problem of DNA, Perutz gave Bragg his copy of the King’s report. Crick now had the material he needed to do his calculations, and once he and Watson realized that the versions of the bases they were initially working with were upside down, history was made. This version of events is nowhere near as dramatic or as cinematic as Watson stealing a glimpse at photo 51 and realizing that DNA had a double helix structure, but it explains why Astbury did not recognize the significance of a similar shape when he saw it in Beighton’s x-ray images in the summer of 1952. In fact, the shape alone was not that significantdat best it simply suggested a helix. Two other things were neededdprecise numbers, which Franklin and Gosling had obtained by studying dozens of such images, and above all a mathematical tool for turning those numbers into a 3dimensional shape. The person who had the greatest ability in this field was Francis Crickdhis PhD work was on analyzing the diffraction pattern of a helical molecule, and he published two papers on this topic in 1952. As Hall points out, that also explains why neither Astbury nor Pauling were able to correctly interpret Astbury’s 1938 image, and why Beighton’s images remained unpublished. Neither Astbury nor Pauling had the necessary mathematical tools to come up with the double helix structure. Crick did. The irony of this story is that the data provided by Franklin to the MRC were virtually identical to those she presented at a small seminar in King’s in autumn 1951, when Jim Watson was in the audience. Had Watson bothered to take notes during her talk, instead of idly musing about her dress sense and her looks, as he
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candidly admits he was doing in The Double Helix, he would have provided Crick with some vital numerical evidence 15 months before the breakthrough finally came. Although Hall repeatedly returns to the moments at which Astbury brushed the shoulder of DNA destiny, there are plenty of other, more prosaic aspects to Astbury’s life that are described here. Of particular interest is Astbury’s attempt to pursue cutting-edge science in a relatively under-funded provincial university in the post-war context. In 1952, his failure to secure funding from the MRC at about the same time as he and Beighton made their diffraction images of DNA, may have played an important role in Astbury turning his attention away from nucleic acids and on to the structure of bacterial flagella. Why the MRC did not fund Astbury’s proposal for a new laboratory is not cleardthe archives provide no answer, says Hall, although Astbury may have been maladroit during in his presentation to the panel. Instead it was Randall’s group at King’s that began to soak up the money. Today’s UK funding ‘golden triangle’ of Oxford-Cambridge-London began to appear in the post-war world. Finally, the origin of the book’s enigmatic title is revealed in the last chapter, in which Hall boldly claims that Astbury’s interest in synthetic fibres heralded the later development of biotechnologydin a memorable turn of phrase, Astbury proposed growing vast quantities of viruses and harvesting their products, enabling humanity to ‘spin clothes from disease’. In the end, it was not viruses that Astbury was involved with, but nuts. After the war, the UK government was involved in various schemes to produce large quantities of monkeynuts (also known as peanuts or groundnuts) in its African colonies. Although the primary focus of these projectsdmost of which came to nothingdwas the production of protein for food, Astbury had developed a technique for denaturing globular proteins which the British chemical company ICI applied to monkeynuts to produce a wool-like fibre, called Ardil. The fibre was mass-produced, and Astbury even had a suit made up out of it (his children also had to wear various garments made of the stuff), but the fabric did not prove a success and it eventually went out of production in 1957. Astbury reported that he soon found that his suit became threadbare ‘in the seat’ (p. 187). References Astbury, W. T. (1947). X-ray studies of nucleic acids. Symposia of the Society for Experimental Biology, 1, 66e76. Cobb, M. (2014). Oswald Avery, DNA, and the transformation of biology. Current Biology, 24, R55eR60. Cobb, M. (2015). Life’s greatest secret: The race to crack the genetic code. London: Profile. Crick, F. (1988). What mad pursuit: A personal view of scientific discovery. New York: Perseus. Franklin, R. E., & Gosling, R. G. (1953). Molecular configuration in sodium thymonucleate. Nature, 171, 740e741. Hager, T. (1995). Force of nature: The life of Linus Pauling. New York: Simon & Schuster. Hall, K. (2011). William Astbury and the biological significance of nucleic acids, 1938e1951. Studies in the History and Philosophy of Biological and Biomedical Sciences, 42, 119e128. Hershey, A. D. (1953). Functional differentiation within particles of bacteriophage T2. Cold Spring Harbor Symposia on Quantitative Biology, 18, 135e140. Hershey, A. D., & Chase, M. (1952). Independent functions of viral protein and nucleic acid in growth of bacteriophage. Journal of General Physiology, 36, 39e 56. Olby, R. (1994). The Path to the Double Helix: The Discovery of DNA. New York: Dover. Stent, G. S. (1972). Prematurity and uniqueness scientific discovery. Scientific American, 227(6), 84e93. Watson, J. D. (1968). The double Helix: A personal account of the discovery of the structure of DNA. London: Weidenfeld & Nicolson. Wyatt, H. V. (1974). How history has blended. Nature, 249, 803e805.
Contents lists available at ScienceDirect
Studies in History and Philosophy of Biological and Biomedical Sciences journal homepage: www.elsevier.com/locate/shpsc
Essay review
The forgotten man of DNA Matthew Cobb Michael Smith Building, Faculty of Life Sciences, University of Manchester, M13 9PT, UK
When citing this paper, please use the full journal title Studies in History and Philosophy of Biological and Biomedical Sciences
The Man in the Monkeynut Coat: William Astbury and the Forgotten Road to the Double-Helix, Kersten T. Hall. Oxford University Press, Oxford (2014). 256 pp. Price £18.99, hardback, ISBN: 978-0-19-870459-1
William ‘Bill’ Astbury (1898e1961), a physicist who worked at Leeds University in the north of England from 1928, was a key figure in the history of molecular biology. He carried out pioneering work on the X-ray crystallography; he published the first X-ray images of DNA fibres, and he developed the first molecular models of the structure of the molecule. Both these models were wrong, but he correctly suggested that nucleotides were regularly spaced, perpendicular to the phosphate-sugar backbone, thereby setting the scene for the research of Maurice Wilkins and Rosalind Franklin and the discovery of the double helix structure of DNA by James Watson and Francis Crick in 1953. Astbury’s work formed a key part of Robert Olby’s The Path to the Double Helix (Olby, 1994), which described the background to Watson and Crick’s discovery primarily in terms of the techniques that lay beneath it, principally X-ray crystallography. Kersten Hall, a visiting fellow in the School of Philosophy, Religion and History of Science at the University of Leeds has now published an intellectual biography of Astbury, written through the prism of the discovery of the structure of DNA. As well as shedding light on a crucial period in the history of biology, Hall explores the scientific politics of the timedAstbury’s perpetual struggle for recognition and funding will resonate with many of today’s researchers. Hall’s biography covers a vast territory, from Headingley (the Leeds cricket ground, near Astbury’s laboratory) to Asilomar (the Californian seaside town that was the site of an important conference on genetic engineering), with an eye for the striking detail and unexpected historical linksdthe modernist poet T. S. Eliot, the 19th century co-author of the Communist Manifesto Friedrich Engels and the 1980s English cricket legend Ian Botham all pop up in these pages.
E-mail address: [email protected]. http://dx.doi.org/10.1016/j.shpsc.2015.03.004 1369-8486/Ó 2015 Elsevier Ltd. All rights reserved.
Hall has scoured the archives in Leeds, and has made a number of intriguing discoveries linking Astbury with the key moments in the study of the structure and function of DNA. Some of these nuggets have been published in the pages of this journal (Hall, 2011), others are to be found in the pages of the book, some lurking in the footnotes. Hall has also set up a valuable website, ‘X-Ray Marks the Spot: William Astbury and the Birth of Molecular Biology at Leeds’, based on a temporary exhibition of the same name, which includes pictures of a number of artifacts, pieces of equipment and letters. It is highly recommended for those looking for further information about Astbury, or resources for teaching or research: http://www.leeds.ac.uk/heritage/Astbury/ Astbury took a degree in physics at Cambridge, and having survived the horrors of World War 1, learned X-ray crystallography with the elder of the father-son pioneers of the technique, Sir William Bragg, first at University College London, then at the Royal Institution. After failing to get a lectureship at Cambridge in 1927, he was more or less forced by Bragg to accept a lectureship in Textile Physics at Leeds. Astbury was not particularly happy at this apparent promotiondhe described it in a letter to J. D. Bernal as ‘sad news’ because he initially assumed he would have to give up crystallography because of lack of equipment. But with ingenuity and some funding, Astbury was able to develop an effective but extremely dangerous system for taking X-ray diffraction images. As Hall’s subtitle indicates, to modern eyes the high points of Astbury’s career were linked with DNA. At the time, DNA was thought to be an inert and structurally invariant component of chromosomes, while genes were assumed to be made of proteins. Intriguingly, Hall has discovered that in 1937 Astbury was on a tour of the US and visited the Rockefeller Institute where he had a brief meeting with Oswald Avery, who was working at the time on the transformation of bacteria from one type to another, and using chemical means to identify the nature of what he called the ‘transforming principle’dthe white substance that seemed to enable bacteria to change their nature in a heritable fashion. Hall quotes a brief diary entry by Astbury, in which he described his discussions with Avery and his group and concluded ‘Most exciting!’ (p. 216).
68
M. Cobb / Studies in History and Philosophy of Biological and Biomedical Sciences 51 (2015) 67e69
One of the apparent enigmas of the post-war history of biology is why Avery’s 1943 discovery of the importance of DNA in bacterial transformation was not immediately recognized by the scientific community. According to the version of history that is still taught in many biology textbooks, the significance of Avery’s discovery was not recognized because he published in an obscure medical journal, because he was too diffident, because he was working on a bacterial system that most geneticists did not understand, because people were worried that there were protein contaminants in his samples of DNA, or simply because, as the pioneer molecular geneticist Gunter Stent later put it, the discovery was ‘premature’ (Stent, 1972; for a summary of these arguments see Cobb, 2014). The real breakthrough came in 1952, textbooks tell us, when the Hershey-Chase experiment showed that viruses transferred DNA, not protein, into their bacterial hosts (Hershey & Chase, 1952; Wyatt, 1974). This version of history is simply not true. As Hall’s colleague from Leeds, Vivien Wyatt, showed over 40 years ago, the Hershey and Chase experiment did not prove that DNA was the genetic material, and in fact Hershey and Chase did not make any such claim (Wyatt, 1974). Amazingly, in 1953, after the discovery of the double helix structure of DNA, Al Hershey was still arguing that ‘DNA will not prove to be a unique determiner of genetic specificity’ (Hershey, 1953) (for a summary of this period, see Cobb, 2014, 2015). As is now widely accepted and as Hall explains, in reality Avery was not ignored by everyone in the scientific community. During the period 1944e1948, a large number of individuals, journals and learned societies recognized the significance of Avery’s discovery. One of the first to acclaim the importance of this breakthrough was Astbury. In October 1944 he told a friend in a letter that he was ‘terribly thrilled’ that Avery had identified the transforming substance as DNA and that he considered this to be ‘one of the most remarkable discoveries of our time’. Astbury concluded his letter with these prophetic words: ‘I wish I had a thousand hands and labs with which to get down to the problem of proteins and nucleic acids. Jointly those hold the physicochemical secret of life, and quite apart from the war, we are living in a heroic age, if only more people could see it’ (p. 117). In January 1945, Astbury wrote to Avery congratulating him on the identification of the transforming principled‘I have recently been extremely thrilled by your identification’, he wrotedand reminding the American that the two had met in 1937. It is not known if Avery replied to this letter, or even if he received it (the Avery archives at Rockefeller drew a blank when I consulted them). Whatever the case, no DNA sample was ever sent from New York to Leeds. Astbury was enthused by Avery’s work, and does not seem to have given much credence to the criticisms from those scientists such as Avery’s Rockefeller colleague Alfred Mirsky, who argued that infinitesimal protein contaminants might explain the apparent genetic role of DNA in Avery’s experiments. In 1947 Astbury spoke at a meeting on nucleic acids held in Cambridge by the Society for Experimental Biology, at which a number of dissenting voices were heard, so he was clearly aware of the criticisms. At that meeting, Astbury presented his own model of DNA structure. His images indicated very clearly that DNA contains repeated elements, but he was unable draw any conclusion about the arrangement of those elements because the images were not precise enough. That did not stop him speculating, and putting forward a relatively uniform column as his first guess. Astbury also explained that his mode of thinking applied to all molecules, not just nucleic acids: ‘A test that cannot long be dispensed with in any enquiry into the structure of a complex molecule is that of trying to build an accurate atomic model on the
basis of known sizes and inter-bond angles. Chemical formulae are no more than a convenient shorthand, and it is always revealing, and often startling, to see what a molecule looks like in space.’ (Astbury, 1947). Astbury had none of the monomaniacal focus on DNA shown by Jim Watsondhis molecular interests were wide-ranging although the common thread was the relation between form and function. His approach to molecular structureda mixture of precise physicochemical measures and a real feel for the significance of threedimensional structuredcomes over repeatedly in the pages of Hall’s account. Hall explains in simple terms how x-ray crystallography works, and also transmits Astbury’s excitement at realizing that a number of apparently distinct substancesdhair, wool, horndall contain the same fundamental substance, keratin. Supported by funding from the Rockefeller Foundation and from the wool industry in Leeds, in the shape of the Worshipful Company of Clothworkers, Astbury and his colleagues made a decisive breakthrough when they realized that there were two forms of keratin, which altered as the humidity of the sample changed, and which corresponded to different forms, both of which he assumed to be helical. Although Astbury had the initial insight into the structure of keratin, because of lack of funding and focus he did not pursue its description to the end; that goal became the subject of an intense competition between the US chemist Linus Pauling and Lawrence Bragg, the son of Astbury’s PhD supervisor and mentor. As is well known, Pauling won that race in 1950e51, much to Bragg’s fury. When Pauling began to turn his attention to the molecular structure of DNA, heralded by a profoundly mistaken triple-helix structure submitted to the PNAS at the beginning of 1953 and based on Astbury’s 1938 image of DNA, Bragg revoked an agreement he had struck with his rival John Randall of King’s College London, a year earlier. Bragg now allowed his Cambridge group, which included Watson and Crick, to return to the study of DNA. Astbury was well known to all of the major players in the world of molecular biology. In the summer of 1952, Pauling visited Leeds and stayed with Astbury (an event that escaped Thomas Hager’s biography of Pauling, Force of Nature (Hager, 1995)). This is a particularly tantalizing moment, as Pauling was just beginning to turn his focus onto DNA, and was frustrated by the lack of clear images (he had cheekily asked Randall for some photos, but had been given the brush-off). Shortly before Pauling’s visit, Astbury had got his PhD student and technician, Elwyn Beighton, to make some images of a DNA fibre. These pictures were just as clear as those produced by Franklin, and yet Astbury did not publish them. Astbury cannot have shown them to Pauling that evening, or we would surely know. It is quite possible that the two did not discuss DNA at all. Hall gives this non-event weight because of the apparent significance of another DNA X-ray diffraction image, which was also made in May 1952, by Rosalind Franklin and her student, Raymond Gosling, now known as ‘photo 51’, and which was eventually published in their joint Nature paper that accompanied Watson and Crick’s description of the double helix (Franklin & Gosling, 1953). According to Watson’s account in The Double Helix (Watson, 1968), he was shown the photo by Maurice Wilkins at the end of January 1953, at the point when Bragg had just changed his mind about Cambridge’s involvement in the race to discover the structure of DNA. There was nothing underhand about thisdFranklin was preparing to leave King’s for Birkbeck, Gosling was once again Wilkins’ PhD student, and this unstudied photo formed part of the young man’s research. Watson writes that when he saw the photodwhich with its distinctive ‘X’ shape was far clearer than any other he had seend‘my mouth fell open and my pulse began to race.’
M. Cobb / Studies in History and Philosophy of Biological and Biomedical Sciences 51 (2015) 67e69
Hall seems to accept this dramatic version of the decisive importance of photo 51dindeed, his book opens with the immediate aftermath, as Watson scribbled ideas on a newspaper during the train journey from London to Cambridge. In fact, although this account makes for an exciting tale, and highlights the apparent enigma of Astbury’s failure to recognize the significance of a similar shape in Beighton’s photos, there are reasons not to take Watson’s word for it. For one, despite the power of Watson’s account in The Double Helix, photo 51 did not furnish Watson or Crick with any decisive evidence. It simply confirmed Watson’s prejudice, born partly of his obsession with Pauling’s work on the keratin alphahelix, that DNA had the form of a helix. This in itself was no great insightdby this stage everyone in King’s College accepted it, even Franklin, who at one stage had been dubious (Cobb, 2015). The photo neither proved that the molecule was a double helix, nor provided the kind of precise numerical evidence that Crick needed to create the famous model. Crick himself dismissed the suggestion that the photo played any important role (Crick, 1988). What was arguably the decisive insight came in another form, which Hall mentions only in passing (p. 13), and which was unwittingly provided by Franklin herself. In December 1952 the King’s Biophysics laboratory had produced a brief informal report for the Medical Research Council, which funded most of the research in Randall’s lab, containing summaries of the research that the various groups had been carrying out, such as data from Franklin’s work on the structure of DNA. Those numbers, which included the relative distances of the repetitive elements in the A and B forms of DNA, and the dimensions of the monoclinic unit cell (this indicated that the molecule was in two matching parts, running in opposite directions), were much more significant than a glance at photo 51. One of the MRC worthies who was given a copy of the reportdwhich was not confidential, no matter how Watson later described it in The Double Helixdwas Max Perutz of Cambridge University. In February 1953, as Bragg gave Watson and Crick the green light to return to the problem of DNA, Perutz gave Bragg his copy of the King’s report. Crick now had the material he needed to do his calculations, and once he and Watson realized that the versions of the bases they were initially working with were upside down, history was made. This version of events is nowhere near as dramatic or as cinematic as Watson stealing a glimpse at photo 51 and realizing that DNA had a double helix structure, but it explains why Astbury did not recognize the significance of a similar shape when he saw it in Beighton’s x-ray images in the summer of 1952. In fact, the shape alone was not that significantdat best it simply suggested a helix. Two other things were neededdprecise numbers, which Franklin and Gosling had obtained by studying dozens of such images, and above all a mathematical tool for turning those numbers into a 3dimensional shape. The person who had the greatest ability in this field was Francis Crickdhis PhD work was on analyzing the diffraction pattern of a helical molecule, and he published two papers on this topic in 1952. As Hall points out, that also explains why neither Astbury nor Pauling were able to correctly interpret Astbury’s 1938 image, and why Beighton’s images remained unpublished. Neither Astbury nor Pauling had the necessary mathematical tools to come up with the double helix structure. Crick did. The irony of this story is that the data provided by Franklin to the MRC were virtually identical to those she presented at a small seminar in King’s in autumn 1951, when Jim Watson was in the audience. Had Watson bothered to take notes during her talk, instead of idly musing about her dress sense and her looks, as he
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candidly admits he was doing in The Double Helix, he would have provided Crick with some vital numerical evidence 15 months before the breakthrough finally came. Although Hall repeatedly returns to the moments at which Astbury brushed the shoulder of DNA destiny, there are plenty of other, more prosaic aspects to Astbury’s life that are described here. Of particular interest is Astbury’s attempt to pursue cutting-edge science in a relatively under-funded provincial university in the post-war context. In 1952, his failure to secure funding from the MRC at about the same time as he and Beighton made their diffraction images of DNA, may have played an important role in Astbury turning his attention away from nucleic acids and on to the structure of bacterial flagella. Why the MRC did not fund Astbury’s proposal for a new laboratory is not cleardthe archives provide no answer, says Hall, although Astbury may have been maladroit during in his presentation to the panel. Instead it was Randall’s group at King’s that began to soak up the money. Today’s UK funding ‘golden triangle’ of Oxford-Cambridge-London began to appear in the post-war world. Finally, the origin of the book’s enigmatic title is revealed in the last chapter, in which Hall boldly claims that Astbury’s interest in synthetic fibres heralded the later development of biotechnologydin a memorable turn of phrase, Astbury proposed growing vast quantities of viruses and harvesting their products, enabling humanity to ‘spin clothes from disease’. In the end, it was not viruses that Astbury was involved with, but nuts. After the war, the UK government was involved in various schemes to produce large quantities of monkeynuts (also known as peanuts or groundnuts) in its African colonies. Although the primary focus of these projectsdmost of which came to nothingdwas the production of protein for food, Astbury had developed a technique for denaturing globular proteins which the British chemical company ICI applied to monkeynuts to produce a wool-like fibre, called Ardil. The fibre was mass-produced, and Astbury even had a suit made up out of it (his children also had to wear various garments made of the stuff), but the fabric did not prove a success and it eventually went out of production in 1957. Astbury reported that he soon found that his suit became threadbare ‘in the seat’ (p. 187). References Astbury, W. T. (1947). X-ray studies of nucleic acids. Symposia of the Society for Experimental Biology, 1, 66e76. Cobb, M. (2014). Oswald Avery, DNA, and the transformation of biology. Current Biology, 24, R55eR60. Cobb, M. (2015). Life’s greatest secret: The race to crack the genetic code. London: Profile. Crick, F. (1988). What mad pursuit: A personal view of scientific discovery. New York: Perseus. Franklin, R. E., & Gosling, R. G. (1953). Molecular configuration in sodium thymonucleate. Nature, 171, 740e741. Hager, T. (1995). Force of nature: The life of Linus Pauling. New York: Simon & Schuster. Hall, K. (2011). William Astbury and the biological significance of nucleic acids, 1938e1951. Studies in the History and Philosophy of Biological and Biomedical Sciences, 42, 119e128. Hershey, A. D. (1953). Functional differentiation within particles of bacteriophage T2. Cold Spring Harbor Symposia on Quantitative Biology, 18, 135e140. Hershey, A. D., & Chase, M. (1952). Independent functions of viral protein and nucleic acid in growth of bacteriophage. Journal of General Physiology, 36, 39e 56. Olby, R. (1994). The Path to the Double Helix: The Discovery of DNA. New York: Dover. Stent, G. S. (1972). Prematurity and uniqueness scientific discovery. Scientific American, 227(6), 84e93. Watson, J. D. (1968). The double Helix: A personal account of the discovery of the structure of DNA. London: Weidenfeld & Nicolson. Wyatt, H. V. (1974). How history has blended. Nature, 249, 803e805.