After the double helix Rosalind Franklin's research on tobacco mosaic virus

ISIS

Volumn 99, Issue 2, 2008, Pages 239-272

  Creager, Angela N H ^a   Morgan, Gregory J ^b  

^a PRINCETON UNIVERSITY   (United States)

^b SPRING HILL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

VIRUS DNA;

ART; ARTICLE; CONFORMATION; GENETICS; HISTORY; HUMAN; MEDICAL RESEARCH; MOLECULAR BIOLOGY; TOBACCO MOSAIC VIRUS; UNITED STATES; X RAY CRYSTALLOGRAPHY;

BIOMEDICAL RESEARCH; CRYSTALLOGRAPHY, X-RAY; DNA, VIRAL; HISTORY, 20TH CENTURY; HUMANS; MOLECULAR BIOLOGY; NUCLEIC ACID CONFORMATION; PORTRAITS AS TOPIC; TOBACCO MOSAIC VIRUS; UNITED STATES;

EID: 47849110943     PISSN: 00211753     EISSN: 15456994     Source Type: Journal    
DOI: 10.1086/588626     Document Type: Article

References (294)

1. We have followed current nomenclature in italicizing the full names of virus species.
2. James D. Watson and Francis H. C. Crick, "A Structure for Deoxyribose Nucleic Acid," Nature, 1953, 171 .'737-738.
3. There are many accounts of the relationship of Franklin's diffraction patterns to Watson and Crick's model; for a recent appraisal that cites others see Lynne Osman Elkin, "Rosalind Franklin and the Double Helix," Physics Today, 2003, 56:42-48.
4. James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA, ed. Gunther S. Stent (1968; New York: Norton, 1980)
5. (hereafter cited as Watson, Double Helix).
6. For analysis of the mythic dimensions of the representation of Franklin as a martyr, in which she is cast as the "Sylvia Plath of molecular biology," see Brenda Maddox, "The Double Helix and the 'Wronged Heroine,'" Nature, 2003, 427:407-408.
7. Anne Sayre's book played a crucial role in drawing public attention to the injustices of Watson's portrayal: Anne Sayre, Rosalind Franklin and DNA (New York: Norton, 1975).
8. Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (New York: Harper Collins, 2002)
9. (hereafter cited as Maddox, Rosalind Franklin).
10. A few examples of the media accounts are Tara Pepper, "Genes, Girls, and Gall," Newsweek, 5 Aug. 2002, p. 54;
11. Jim Holt, "Photo Finish: Rosalind Franklin and the Great DNA Race," New Yorker, 28 Oct. 2002, p. 102;
12. Bernadine Healy, "Let's Remember Rosy," U.S. News and World Report, 24 Feb. 2003, p. 47;
13. and Denise Grady, "A Revolution at Fifty: Fifty Years Later, Rosalind Franklin's X-ray Fuels Debate," New York Times, 25 Feb. 2003, p. 2.
14. The PBS program Nova produced a segment on Franklin that was broadcast on 22 Apr. 2003. For an analysis of the commemorations see Pnina G. Abir-Am, "DNA at Fifty: Institutional and Biographical Perspectives," Minerva, 2004, 42:191-213.
15. Franklin's publications on TMV are cited in the course of this essay; for an overview of her contributions see Kenneth C. Holmes, "Rosalind Franklin and the Tobacco Mosaic Virus," in DNA 50: The Secret of Life, ed. Miriam Balaban (London: Faircount, 2003), pp. 200-208.
16. This risk taking stands in contrast to the image of Franklin as such a cautious experimentalist that she resisted structural speculation; see Watson, Double Helix, pp. 45, 95-96.
17. This, too, contradicts the impression - drawn from her work on DNA at King's College and based largely on the portrayal offered in The Double Helix - of Franklin as a solitary investigator, (Even there, she worked closely with, Raymond Gosling, if not with Wilkins.)
18. On the importance of hemoglobin and insulin to biochemistry and biophysics see Soraya de Chadarevian, "Sequences, Conformation, Information: Biochemists and Molecular Biologists in the 1950s," Journal of the History of Biology, 1996, 29:361-386;
19. de Chadarevian, "Following Molecules: Hemoglobin between the Clinic and the Laboratory," in Molecularizing Biology and Medicine: New Practices and Alliances, 1910s-1970s, ed. de Chadarevian and Harmke Kamminga (Amsterdam: Harwood, 1998), pp. 171-201;
20. and de Chadarevian, Designs for Life: Molecular Biology after World War II (Cambridge: Cambridge Univ. Press, 2002) (hereafter cited as de Chadarevinn, Designs for Life). Secondary literature on virus research is cited throughout this essay.
21. For an insightful synoptic account that cites the secondary literature up to the mid-1990s see Michel Morange, A History of Molecular Biology, trans. Matthew Cobb (Cambridge, Mass.: Harvard Univ. Press, 1998).
22. On the coding problem see Lily E. Kay, Who Wrote the Book of Life? A History of the Genetic Code (Stanford, Calif.: Stanford Univ. Press, 2000);
23. and Horace Freeland Judson. The Eighth Day of Creation (New York: Simon & Schuster, 1979), Chs. 5-8, Both Kay and Judson make it clear that researchers employing computational and theoretical methods (largely members of the RNA Tie Club) were not successful in actually cracking the code; this was accomplished by Heinrich Matthei and Marshall Nirenberg using biochemical methods in the early 1960s.
24. The RNA Tie Club was part joke and part scientific network. Watson, George Gamow, and Leslie Orgel launched this clique of scientific correspondents to encourage work to resolve the structure of RNA and to explicate its role in forming proteins, specifically by providing a forum for speculative ideas and untested theories. Other founding members included Crick, Gunther Stent, and Alexander Rich. See Judson, Eighth Day of Creation, pp. 264-265;
25. and de Chadarevian, Designs for life, pp. 186-198.
26. On structural models of protein synthesis (notably the template theory of Linus Pauling) see Bruno Strasser, "A World in One Dimension: Linus Pauling, Francis Crick, and the Central Dogma of Molecular Biology," History and Philosophy of the Life Sciences, 2006, 28:491-512.
27. Pnina G. Abir-Am, "From Multidisciplinary Collaboration to Transnational Objectivity: International Spaces as Constitutive of Molecular Biology, 1930-1970," in Denationalizing Science: The Contexts of International Scientific Practice, ed. Elisabeth Crawford, Terry Shinn, and Sverker Sörlin (Dordrecht: Kluwer, 1992), pp. 153-186;
28. de Chadarevian, Designs for Life;
29. Jean-Paul Gaudillière, Inventer la biomédecine: La France, l'Amérique et la production des savoirs du vivant (1945-1965) (Paris: Découverte, 2002);
30. and Bruno J. Strasser, La fabrique d'une nouvelle science: La biologie moléculaire à l'âge atomique (1945-1964) (Florence: Olschki, 2006).
31. These were transactions, if not monetary ones: scientists exchanged materials and results in return for credit or in the expectation of reciprocity. This understanding of the circulation of scientific information and objects in terms of "gift exchange" draws on economic anthropology and sociology; for an excellent discussion and references see Warwick Anderson, "The Possession of Kuru: Medical Science and Biocolonial Exchange," Comparative Studies in Society and History, 2000, 42:713-744, esp. pp. 714-716.
32. For a nice example of differences in expectations between French and American cultures of molecular biology see Jean-Paul Gaudillière, "Paris-New York Roundtrip: Transatlantic Crossings and the Reconstruction of the Biological Sciences in Post-war France," Studies in History and Philosophy of Biological and Biomedical Sciences, 2002, 33:389-417, esp. pp. 406-408.
33. On this general issue see Soraya de Chadarevian and Bruno Strasser, "Molecular Biology in Postwar Europe: Towards a 'Global' Picture," ibid., pp. 361-365.
34. For an insightful account of how this played out at Cambridge see de Chadarevian, Designs for Life, esp. Ch. 10.
35. On the perception of King's College's prerogative regarding the DNA structure problem see Watson, Double Helix, pp. 13-14.
36. Dmitri Ivanovskii, "Über die Mosaikkrankheit der Tabakspflanze," Bulletin de l'Académie Impériale des Sciences de St. Pétersbourg, Sér. 3, 1892, 35:67-70,
37. trans. James Johnson and rpt. as "Concerning the Mosaic Disease of the Tobacco Plant," Phytopathological Classics, 1942, 7:27-30;
38. and M. W. Beijerinck, "Über ein Contagium vivum fluidum als Ursache der Fleckenkrankheit der Tabaksblätter," Verhandelingen der Koninklijke Akademie van Wetenschappen te Amsterdam Afdeeling Natuurkunde, 1898, 6:3-21,
39. trans. Johnson and rpt. as "Concerning a Contagium vivum fluidum as a Cause of the Spot-Disease of Tobacco Leaves," Phytopatholog. Classics, 1942, 7:33-52.
40. For more on the significance of early research on TMV see Ton van Helvoort, "What Is a Virus? The Case of Tobacco Mosaic Disease," Studies in History and Philosophy of Science, 1991, 22:557-588;
41. Angela N. H. Creager, The Life of a Virus: Tobacco Mosaic Virus as an Experimental Model, 1930-1965 (Chicago: Univ. Chicago Press, 2002)
42. (hereafter cited as Creager, Life of a Virus), Ch. 2;
43. and Karen-Beth G. Scholthof, John G. Shaw, and Milton Zaitlin, eds., Tobacco Mosaic Virus: One Hundred Years of Contributions to Virology (St. Paul, Minn.: American Phytopathological Society Press, 1999).
44. For Stanley's announcement see W. M. Stanley, "Isolation of a Crystalline Protein Possessing the Properties of Tobacco-Mosaic Virus," Science, 1935, 81:644-645.
45. On the reception of Stanley's paper as a scientific sensation see Lily E. Kay, "W. M. Stanley's Crystallization of the Tobacco Mosaic Virus, 1930-1940," Isis, 1986, 77:450-472;
46. and Creager, Life of a Virus, Ch. 3.
47. For the clarification see F. C. Bawden, N. W. Pirie, J. D. Bernal, and I. Fankuchen, "Liquid Crystalline Substances from Virus-Infected Plants," Nature, 1936, 138:1051-1052. These authors illustrated the spontaneous birefringence of TMV, which indicated the presence of highly elongated particles, with a photograph showing the pattern left by a goldfish swimming in a solution of the virus.
48. Bernal and Fankuchen prepared both "wet" and "dry" gels of TMV; the wetter preparations, particularly one in which the long particles were oriented in capillary tubes, gave the clearest diffraction patterns, with hundreds of distinct spots. The analysis of X-ray diagrams from these materials is based not on crystallography proper but on fiber-diffraction methods. See J. D. Bernal and I. Fankuchen, "Structure Types of Protein 'Crystals' from Virus-Infected Plants," Nature, 1937, 139:923-924, on p. 923;
49. and Bernal and Fankuchen, "X-ray and Cristallographie Studies of Plant Virus Preparations, I: Introduction and Preparation of Specimens; II: Modes of Aggregation of the Virus Particles; III," Journal of General Physiology, 1941, 25:111-146 (Pts. I and II), 147-165 (Pt. III).
50. For a discussion of Bernal and Fankuchen's diffraction analysis of TMV see Robert C. Olby, The Path to the Double Helix: The Discovery of DNA (1974; New York: Dover, 1994), pp. 164-165, 259-263.
51. The Svedberg used sedimentation studies to estimate a molecular weight for TMV of 17 million daltons in 1937; by 1940 Stanley had revised this figure to 50 million daltons, on the basis of the assumption that the virus was cylindrical rather than spherical in shape. See Inga-Britta Eriksson-Quensel and Theodor Svedberg, "Sedimentation and Electrophoresis of the Tobacco-Mosaic Virus Protein," Journal of the American Chemical Society, 1936, 58:1863-1867;
52. W. M. Stanley, "The Biochemistry of Viruses," Annual Review of Biochemistry, 1940, 9:545-570;
53. and Creager, Life of a Virus, Ch. 4.
54. See F. C. Bawden and N. W. Pirie, "Contribution to Aggregation of Purified Tobacco Mosaic Virus," Nature, 1938, 142:842-843,
55. On these debates see Creager, Life of a Virus, Ch. 4.
56. The first electron micrographs of TMV were published in O. A. Kausche, E. Pfankuch, and H. Ruska, "Die Sichtbarmachung von pflanzlichen Virus im Übermikroskop," Naturwissenschaften, 1939, 27:292-299.
57. The development of the RCA electron microscope led Stanley to collaborate on micrographs of his TMV preparation; see W. M. Stanley and Thomas F. Anderson, "A Study of Purified Viruses with the Electron Microscope," Journal of Biological Chemistry, 1941, 139:325-338,
58. Measurements from their micrographs led Stanley to assign a length of 2,800 Å and a width of 150 Å. Bawden and Pirie interpreted the long rods visualized in electron micrographs of TMV as artifactual aggregates, believing that the biologically active virus particles were much smaller and possibly even spherical, See F. C. Bawden, "Virus Diseases of Plants," Journal of the Royal Society of Arts, 1946, 94:136-168, esp. p. 166.
59. On electron microscopy see Nicolas Rasmussen, Picture Control: The Electron Microscope and the Transformation of Biology in America, 1940-1960 (Stanford, Calif.: Stanford Univ. Press, 1997),
60. On the decline of the colloidal view of proteins see Joseph Fruton, "From Colloids to Macromolecules," in Molecules and Life: Historical Essays on the Interplay of Chemistry and Biology (New York: Wiley-Interscience, 1972), pp. 131-148.
61. Gerhard Schramm, "Über die Spaltung des Tabakmosaikvirus in niedermolekulare Proteine und die Rückbildung hochmolekularen Proteins aus den Spaltstücken," Naturwissenschaften, 1943, 31:94-96.
62. Schramm's techniques are discussed further below. According to Watson, "There already existed biochemical evidence for protein building blocks. Experiments of the German Gerhard Schramm, first published in 1944, reported that TMV particles in mild alkali fell apart into free RNA and a large number of similar, if not identical, protein molecules. Virtually no one outside Germany, however, thought that Schramm's story was right. This was because of the war. It was inconceivable to most people that the German beasts would have permitted the extensive experiments underlying his claims to be routinely carried out during the last years of a war they were so badly losing. It was all too easy to imagine that the work had direct Nazi support and that his experiments were incorrectly analyzed": Watson, Double Helix, p. 68.
63. On Stanley's skepticism about Schramm's result see Creager, Life of a Virus, pp. 249-253.
64. On the institutionalization of biophysics in the postwar United Kingdom, including Randall's laboratory at King's College, see de Chadarevian, Designs for Life, Ch. 3.
65. Maddox sheds new light on why Franklin's arrival to work on DNA created misunderstandings and friction with Wilkins in Rosalind Franklin, pp. 114-116, 128-129, 149-150.
66. M. H. F. Wilkins, "The Molecular Configuration of Nucleic Acids," in Nobel Lectures in Physiology or Medicine (Amsterdam: Elsevier for the Nobel Foundation, 1964), Vol. 3, pp. 754-782, on p. 755;
67. and Olby, Path to the Double Helix (cit. n. 18), p. 331. Another first-hand account of this collaboration can be found in Gerald Oster to Wendell Stanley, 26 Apr. 1949,
68. Wendell M. Stanley Papers, Bancroft Library, University of California, Berkeley, 78/18c (hereafter cited as Stanley Papers), carton 11, folder Oster.
69. M. H. F. Wilkins, A. R. Stokes, W. E. Seeds, and G. E. Oster, "Tobacco Mosaic Virus Crystals and Three-Dimensional Microscopic Vision," Nature, 1950, 166:127-129, on p. 127.
70. They estimated the length of virus rods at 2,800 Å. In his autobiography, Wilkins credits Oster with inspiring him to pursue the DNA structure using X-ray diffraction; see Maurice Wilkins, The Third Man of the Double Helix (Oxford: Oxford Univ. Press, 2003), p. 116.
71. In addition, Robley Williams at the Berkeley Virus Lab strongly challenged the claim of Wilkins and his collaborators that the pattern of banded striations in polarizing light demonstrated a "zig-zag" orientation of virus particles. See correspondence between Robley Williams and M. H. F. Wilkins, Nov. 1952, Feb. 1953, Robley C. Williams Papers, Bancroft Library, University of California, Berkeley (hereafter cited as Williams Papers), 73/7c, carton 5, folder W. On Stokes's helical interpretation see Wilkins, Third Man of the Double Helix, p. 116.
72. Watson went to Europe on a Merck National Research Council Fellowship, which was cut short in 1952 because of his decision to leave Copenhagen for Cambridge; see Watson, Double Helix, p. 66.
73. Thereafter, Max Delbrück helped arrange a fellowship for Watson through the National Foundation for Infantile Paralysis. See Watson, Double Helix, p. 66;
74. Olby, Path to the Double Helix (cit. n. 18), p. 378;
75. and Victor K. McElheny, Watson and DNA: Making a Scientific Revolution (Cambridge, Mass.: Perseus, 2003), p. 46.
76. On the role of the National Foundation for Infantile Paralysis in supporting basic virus research see Creager, Life of a Virus, Ch. 5.
77. W. Cochran, F. H. C. Crick, and V. Vand, "The Structure of Synthetic Polypeptides, I: The Transform of Atoms on a Helix," Acta Crystallographica, 1952, 5:581-586;
78. Bernal and Fankuchen, "X-ray and Cristallographic Studies of Plant Virus Preparations" (cit. n. 18), p. 148;
79. and Olby, Path to the Double Helix, pp. 260, 311-312, 316 (quotation).
80. For Frank's theory see F. C. Frank, "The Influence of Dislocations on Crystal Growth," Discussions of the Faraday Society, 1949, 5:48-54;
81. and Frank, "Crystal Growth and Dislocations," Advances in Physics, 1952, 1:91-109.
82. Watson, Double Helix, p. 69.
83. Ibid, p. 98.
84. According to Maddox, Watson's visit to King's College, during which Wilkins indiscreetly showed him Franklin's "Photograph 51," took place on 30 Jan. 1953;
85. see Maddox, Rosalind Franklin, pp. 193-197.
86. J. D. Watson, "The Structure of Tobacco Mosaic Virus, I: X-ray Evidence of a Helical Arrangement of Sub-units around the Longitudinal Axis," Biochimica et Biophysica Acta, 1954, 13:10-19.
87. Watson took pictures of both wet and dry TMV preparations, but the table of meridional reflections he used to come up with an n of 10 was based on work with the dry specimen. Regarding the protein subunit number, contemporary - and unexpected - biochemical evidence from proteolytic digests of TMV in the Berkeley Virus Lab gave an estimate closer to three thousand; see J. Ieuan Harris and C. Arthur Knight, "Action of Carboxypeptidase on Tobacco Mosaic Virus," Nature, 1952, 170:613-614.
88. On these developments at Berkeley see Creager, Life of a Virus, pp. 266-270;
89. on the various kinds of evidence for TMV subunits from crystallography, physical chemistry, and biochemistry see Donald D. L. Caspar, "The Radial Structure of Tobacco Mosaic Virus" (Ph.D. diss., Yale Univ., 1955), Introduction.
90. Franklin cites Watson's unpublished paper in Annual Report, 1 Jan. 1953 to 1 Jan. 1954, Anne Sayre Collection of the American Society for Microbiology Archives at the University of Maryland, Baltimore County (hereafter cited as Sayre Collection), box 3, folder 6, p. 3. For the published version see Watson, "Structure of Tobacco Mosaic Virus."
91. Rosalind Franklin, Annual Report, 1 Jan. 1953 to 1 Jan. 1954, Sayre Collection, box 3, folder 6. It seems likely that completing the DNA work occupied most of Franklin's time. One virologist has commented that reading through the relevant sources in the plant virus literature could not have taken her more than a few weeks: Karen-Beth Scholthof, personal communication to Angela N. H. Creager, 21 May 2007.
92. Maddox quotes from Randall's letter asking Franklin not only to cease working on DNA but to stop thinking about it; Franklin found this absurd: Maddox, Rosalind Franklin, pp. 212-213, 221.
93. There were five joint publications: Rosalind E. Franklin and R. G. Gosling, "Molecular Configuration in Sodium Thymonucleate," Nature, 1953, 171:740-741;
94. Franklin and Gosling, "Evidence for Two-Chain Helix in Crystalline Structure of Sodium Desoxyribonucleate," ibid., 1953, 172:156-157;
95. and Franklin and Gosling, "The Structure of Sodium Thymonucleate Fibres, I: The Influence of Water Content; II: The Cylindrically Symmetrical Patterson Function; III: The Three-Dimensional Patterson Function," Acta Crystallog., 1953, 6:673-677, 678-685;
96. 1955, 8:151-156.
97. Commentators have speculated on how long it might have taken Franklin to deduce the double-helical structure of DNA during these months had Watson and Crick not already published their model. Franklin's near recognition of the structure is argued in A. Klug, "Rosalind Franklin and the Double Helix," Nature, 1974, 248:787-788;
98. and Elkin, "Rosalind Franklin and the Double Helix" (cit. n. 2);
99. and is taken into account by Maddox, Rosalind Franklin. A more skeptical assessment is offered by Horace Freeland Judson, "Reflections on the Historiography of Molecular Biology," Minerva. 1980, 18:369-421.
100. "I'm sorry you are not having much luck. I'm enclosing a specimen of TMV-which is very highly aggregated indeed. It is also as clean as or cleaner than the specimen which Watson used": Roy Markham to Rosalind Franklin, 23 Nov. 1953, Papers of Rosalind Franklin, Churchill Archives Centre, Churchill College, Cambridge (hereafter cited as Franklin Papers), FRNK 2/33.
101. Franklin to A. L. Patterson, 1 Dec. [1953], Sayre Collection, box 3, folder 1 (complications of TMV fiber diagrams); and Maddox, Rosalind Franklin, p. 229,
102. citing J. D. Bernal to John Randall, 10 Oct. 1953, and Randall to Bernal, 4 Nov. 1953: Franklin Papers, FRNK 2/31.
103. Regarding both the narrow-mindedness of Bernal's left-wing associates and the virtues of working at Birkbeck see Franklin to Anne and David Sayre, 17 Dec. [1953], Sayre Collection, box 3, folder 1. Dorothy Crowfoot Hodgkin, another preeminent woman crystallographer, had been in Bernal's laboratory ten years earlier; see Georgina Ferry, Dorothy Hodgkin: A Life (London: Granta, 1998).
104. Bernal had done his own crystallographic training with William H. Bragg, who had also been supportive of women, most notably Kathleen Lonsdale. Marcel Mathieu played a similarly welcoming role for women crystallographers in France; see Maureen M. Julian, "Women in Crystallography," in Women of Science: Righting the Record, ed. G. Kass-Simon and Patricia Farnes (Bloomington: Indiana Univ. Press, 1990), pp. 335-383.
105. On the significance of socialism in opening research opportunities in radioactivity to women see the excellent article by Maria Rentetzi, "Gender, Politics, and Radioactivity Research in Interwar Vienna: The Case of the Institute for Radium Research," Isis, 2004, 95:359-393.
106. As in the case of X-ray crystallography, the fact that radioactivity research "involved meticulous, routine, and repetitive work" has been used to explain the relatively high numbers of women in the field (ibid., p. 360). Rentetzi instead encourages a serious consideration of the role of progressive politics, an interpretation that seems equally compelling in accounting for the women in X-ray crystallography, at least in Bernal's laboratory.
107. Interviews, Gregory J. Morgan with Aaron Klug, Cambridge, 2 June 1999, 17 July 2000; and Andrew Brown, J. D. Bernal: The Sage of Science (Oxford: Oxford Univ. Press, 2005), p. 353.
108. As Watson explains in his Nobel lecture, he actually took a few diffraction pictures of RNA in 1952 while he was working on TMV, but these were "very diffuse": James D. Watson, "The Involvement of RNA in the Synthesis of Proteins," in Nobel lectures in Physiology or Medicine (cit. n. 24), Vol. 3, pp. 785-808, on p. 787.
109. Alexander Rich and J. D. Watson, "Some Relations between DNA and RNA," Proceedings of the National Academy of Sciences, USA, 1954, 40:759-764, esp. p. 759.
110. While others (especially Crick) shared Rich and Watson's presumption that DNA was the genetic material and RNA was responsible for protein synthesis, this view was complicated by the fact that in most plant viruses, including TMV, no DNA was present, so the viral RNA was presumed to act as the genetic material - assuming the viral protein was not genetic. Rich and Watson state that in "these viruses the genetic material must be the RNA component or the protein component, or possibly both." They point out that if RNA served as genetic material in some viruses, you might expect the base ratios to be complementary in those cases, but in fact the opposite result was observed: "Plant virus RNA's show great departure from the 1:1 ratio, while RNA's from sources to which we need not necessarily postulate a genetic role (e.g., microsomes, mitochondria) often provide beautiful examples of complementarity. We have no explanation for this finding" (ibid., p. 763).
111. Writing retrospectively of his renewed interest in TMV in 1954, Watson states, "Always troublesome to me was the apparent necessity to postulate both genetic and protein synthesis roles for RNA": Watson, "Early Speculations and Facts about RNA Templates," in A Passion for DNA: Genes, Genomes, and Society (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2000), pp. 23-32, on pp. 27-28.
112. On Watson's research at Caltech see Watson, Genes, Girls, and Gamow: After the Double Helix (New York: Knopf, 2002)
113. (hereafter cited as Watson, Genes, Girls, and Gamow), esp. Chs. 6, 15;
114. and Frederic Lawrence Holmes, Meselson, Stahl, and the Replication of DNA: A History of "The Most Beautiful Experiment in Biology" (New Haven, Conn.: Yale Univ. Press, 2001), Ch. 1.
115. See James D. Watson to Max Delbrück, 25 Mar. 1954, Max Delbrück Papers, California Institute of Technology Archives, Pasadena (hereafter cited as Delbrück Papers), 23.23,
116. on this result and on the "very secret society." On the RNA Tie Club see also Watson, Genes, Girls, and Gamow, pp. 67-68.
117. Rich and Watson's first publication also focuses on changes in the diffraction patterns from raising the relative humidity of the RNA samples: Alexander Rich and J. D. Watson, "Physical Studies on Ribonucleic Acid," Nature, 1954, 173:995-996.
118. Attention to the effects of humidity on fiber length originated with Wilkins before being adapted so successfully by Franklin, who controlled the specimen's water content using saturated salt solutions, enabling her to detect different structural conformations of the DNA. See M. H. C. Wilkins, R. G. Gosling, and W. E. Seeds, "Physical Studies of Nucleic Acid: Nucleic Acid: An Extensible Molecule?" Nature, 1951, 167:759-760;
119. Jeremy Bernstein, "A Sorry and a Pity: Rosalind Franklin and The Double Helix." in Experiencing Science (New York: Basic, 1978), pp. 143-162, esp. p. 153;
120. Wilkins, Third Man of the Double Helix (cit. n. 25), pp. 122-124;
121. and Aaron Klug, "The Discovery of the DNA Double Helix," Journal of Molecular Biology, 2004, 355:3-26.
122. Watson to Delbrück, 25 Mar. 1954, Delbrück Papers, 23.23;
123. Rich and Watson, "Some Relations between DNA and RNA" (cit. n. 40);
124. and Alexander Rich, "The Nucleic Acids: A Backward Glance," Annals of the New York Academy of Sciences, 1995, 758:97-142.
125. Rich and Watson, "Physical Studies on Ribonucleic Acid" (cit. n. 41);
126. and Watson to Delbrück, 1 June 1954, Delbrück Papers, 23.23. One paper resulting from Rich's work at the NIH is Alexander Rich, J. D. Dunitz, and P. Newmark, "Abnormal Protein Associated with Tobacco Mosaic Virus: Structure of Polymerized Tobacco Plant Protein and Tobacco Mosaic Virus," Nature, 1955, 175:1074-1075.
127. Rosalind Franklin, Annual Report, 1 Jan. 1953 to 1 Jan. 1954, Sayre Collection, box 3, folder 6; Markham to Franklin, 23 Nov. 1953, Franklin Papers, FRNK 2/33 (on the virus preparation);
128. and Franklin to Stanley, 7 May 1954, Stanley Papers, carton 8, folder Franklin, Rosalind. See similar information in Franklin to Ernest Pollard (of Yale), 13 Apr. 1954, Franklin Papers, FRNK 2/34, quoted in Maddox, Rosalind Franklin, pp. 234-235.
129. Regarding the invitation and Franklin's efforts to raise sufficient funds for the trip, including an application to the Rockefeller Foundation, see Anne Sayre's notes on "REF 1954 US journey," Sayre Collection, box 3, folder 6. To complicate her efforts, Franklin was initially denied a visa by the American consul in London "owing to a misunderstanding about whether she was to be compensated over and above her expenses" (ibid.).
130. On the effort to schedule lectures see Franklin to Stanley, 7 May 1954, Stanley Papers, carton 8, folder Franklin, Rosalind. According to Judson, Crick helped facilitate contacts for her schedule of talks; see Judson, Eighth Day of Creation (cit. n. 10), p. 268.
131. On the planned visit to the Virus Laboratory see Franklin to Stanley, 6 July 1954, Stanley Papers, carton 8, folder Franklin, Rosalind. For Watson's report see Watson to Francis Crick, 15 Oct. 1954, Francis Crick Papers, posted on National Library of Medicine, Profiles in Science: http://profiles.nlm.nih. gov/SC/B/B/J/Q/_/scbbjq.pdf; this meeting with Watson is also described in Maddox, Rosalind Franklin, pp. 240-241.
132. Franklin to Stanley, 14 Oct. 1954, Stanley Papers, carton 8, folder Franklin, Rosalind.
133. On the formation and early accomplishments of the German group see Hans-Jörg Rheinberger, "Virusforschung an den Kaiser-Wilhelm- Instituten für Biologie und Biochemie, 1937-1945," in Epistemologie des Konkreten: Studien zur Geschichte der modernen Biologie (Frankfurt am Main: Suhrkamp, 2006), pp. 185-218;
134. Christina Brandt, Metapher und Experiment: Von der Virusforschung zum genetischen Code (Göttingen: Wallstein, 2004);
135. and Jeffrey Lewis, "From Virus Research to Molecular Biology: Tobacco Mosaic Virus in Germany, 1936-1956," J. Hist. Biol., 2004, 37:259-301.
136. For an account of the rivalry from the Berkeley side see Creager, Life of a Virus, pp. 251-273. The Max Planck Institute for Virus Research gained independent status in 1954; earlier in the postwar period it was a Division of Virus Research within the Institute for Biochemistry.
137. so when appealing for funding, however, Franklin argued that her group's reliance for material on biochemists in other countries was "a most unsatisfactory situation" and reflected the inadequacies of virus research in England in the mid-1950s;
138. see Rosalind Franklin, "X-ray Diffraction and the Structure of Viruses," 17 Oct. 1955,
139. appended to "Note on the Future of the A.R.C. Research Group in Birkbeck College Crystallography Laboratory," 9 Mar. 1956, Franklin Papers, FRNK 2/36.
140. Rosalind E. Franklin and Barry Commoner, "Abnormal Protein Associated with Tobacco Mosaic Virus: X-ray Diffraction by an Abnormal Protein (B8) Associated with Tobacco Mosaic Virus," Nature, 1955, 175:1077-1082. By "abnormal," the authors meant that the protein was not found in uninfected tobacco leaves but was due to the presence of the virus.
141. Pirie criticized Franklin severely for accepting that the 3,000 Å viral rods were not artifacts and for assuming that there was only one type of protein subunit: N. W. Pirie to Franklin, 6 Dec. 1954, Franklin Papers, FRNK 2/33. On Pirie's influence see Maddox, Rosalind Franklin, pp. 251-253.
142. See Watson to Franklin, 3 Dec. 1954, and Crick to Franklin, 8 Dec. 1954: Franklin Papers, FRNK 2/33;
143. and Rosalind E. Franklin, "Structure of Tobacco Mosaic Virus," Nature, 1955, 175:379-381, on p. 380.
144. In this paper she cited biochemical studies of TMV subunits from both the Berkeley Virus Lab and the Max Planck Institute for Virus Research in Tübingen, as well as work from the laboratories of William N. Takahashi (University of California, Berkeley), Commoner (Washington University, St. Louis), and Raymond Jeener (University of Brussels) on a low-molecular-weight virus-like protein from infected plants that polymerizes into rods. Franklin may have gotten the idea that the subunits were divided into two from Crick: Donald Caspar, personal communication to Morgan, 14 Nov. 2007.
145. Franklin, "Structure of Tobacco Mosaic Virus," p. 381.
146. The helical grooving also helped account for the unusually close packing of TMV in dry gels. As Franklin explained, "there are holes between the particles in the strongly dried material, which is inevitable if the particle contour is helically grooved" (ibid., p. 380).
147. See also Rosalind Franklin and Aaron Klug, "The Nature of the Helical Groove on the Tobacco Mosaic Virus Particle," Biochim. Biophys. Acta, 1956, 19:403-415.
148. Schramm himself used this metaphor of the candlewick; see Gerhard Schramm, "Neuere Untersuchungen über die Struktur des Tabakmosaikvirus und ihre biologische Bedeutung," Zentralblatt für Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene, Sect. 2, 1956, 109:322-324, on p. 322.
149. This was the one aspect of Franklin's structure that Pirie found plausible (on his objections see note 52, above): Pirie to Franklin, 6 Dec. 1954, Franklin Papers, FRNK 2/33.
150. st which is definitely split...). So the dimensions you give for the outermost helix are likely to turn up again in my work, but I'm hoping the measurements over the whole photograph will tell us something about the 'stuffing' of the rod." Franklin to Watson, 4 June [1954], James D. Watson Papers, Cold Spring Harbor Laboratory Archives, Cold Spring Harbor, New York
151. "Experience in the past has shown that it is rash to include a drawing with speculation features. It turns up for years and years, and one's reservations get lost in the process": Crick to Franklin, 8 Dec. 1954, Franklin Papers, FRNK 2/33. His appeal for caution apparently did not deter Franklin.
152. Watson to Franklin, 3 Dec. 1954 (with Franklin's annotations), 28 Feb. 1955, Franklin Papers, FRNK 2/33.
153. Caspar to Franklin, 1 Nov. 1954, Franklin Papers, FRNK 2/33. Regarding Caspar's Ph.D. research and his move to Caltech see Caspar to George Beadle, 16 Dec. 1953;
154. Caspar to Beadle, 10 June 1954; and Caspar to David Powell, 30 July 1954: Biology Division Papers, California Institute of Technology Archives, Pasadena (hereafter cited as Biology Division Papers), 21.23.
155. According to Caspar's letter to Powell, he expected to finish his dissertation by the fall of 1954, although the Ph.D. from Yale would be dated June 1955. In the end, having collected data in 1953 and 1954, Caspar continued working on the dissertation after going to California, and the bibliography included papers from early 1955, including Franklin's paper in Nature, "Structure of Tobacco Mosaic Virus" (cit. n. 53). Caspar's work at Caltech was supported by a U.S. Public Health Service Fellowship.
156. On the development of Perutz's technique see de Chadarevian, Designs for Life, pp. 125-126.
157. It was some time before the X-ray diffraction data was taken as more definitive on the issue of RNA location; in Feb. 1955 Watson wrote Franklin that he had seen electron micrographs from Stanley's Virus Lab (taken by Roger Hart and Robley Williams) that "definitely establish that the RNA forms a central core of diameter somewhere between 30 Å and 50 Å": Watson to Franklin, 28 Feb. 1955, Franklin Papers, FRNK 2/33. This followed up Watson's letter dated 3 Dec. 1954 cited in note 59, above.
158. Both virologists in the 1950s and those working today use acronyms extensively to refer to the viruses, as do we, but in the case of Tomato bushy stunt virus we have departed from the currently accepted TBSV to use BSV, in accordance with the usage of researchers in the 1950s.
159. See Biology Division Annual Report, 1955, Biology Division Papers, 21.23;
160. and Watson to Franklin, 28 Feb. 1955, Franklin Papers, FRNK 2/33.
161. Watson to Franklin, 9 Apr. 1955;
162. and Franklin to Watson, 10 June 1955: Franklin Papers, FRNK 2/33. On use of the Spinco centrifuge see Watson, Genes, Girls, and Gamow, p. 130. A few pages later, Watson describes how he and Caspar visited Stanley's Virus Lab to give a joint talk and to use Robley Williams's RCA electron microscope in an unsuccessful attempt to visualize purified TMV RNA.
163. Caspar to Franklin, 1 Nov. 1954; and Franklin to Caspar, 8 Nov. 1954, 28 June 1955: Franklin Papers, FRNK 2/33. Because Caspar's TMV equatorial diffraction data were centrosymmetric, the phases of the diffracted X-rays change sign in many of the valleys separating the peaks of the intensity curve. His assignment of signs was confirmed by Franklin when she discovered that in the high-resolution, low-angle diffraction data there was a small peak in the data between the first two subsidiary intensity maxima.
164. Caspar to Franklin, 9 Apr. 1955;
165. and Franklin to Caspar, 19 May 1955: Franklin Papers, FRNK 2/33.
166. In contrast to TMV, one could obtain true three-dimensional crystals from spherical plant viruses such as TYMV and analyze their X-ray diffraction patterns using crystallographic methods rather than those of fiber diffraction. Finch switched projects prompted by Caspar's discovery of TYMV crystals in Harry Carlisle's refrigerator (see below). Bernal's role as advisor to Holmes and Finch is noted in Brown, J. D. Bernal (cit. n. 38), p. 356.
167. For more on the history of spherical virus crystallography see Gregory J. Morgan, "Historical Review: Viruses, Crystals, and Geodesic Domes," Trends in Biochemical Sciences, 2003, 28:86-90;
168. Morgan, "Early Theories of Virus Structure," in Conformational, Proteomics of Macromolecular Architecture, ed. R. Holland Cheng and Lena Hammar (Singapore: World Scientific, 2004), pp. 3-40;
169. Morgan, "Virus Design, 1955-1962: Science Meets Art," Phytopathology, 2006, 96:1287-1291;
170. and Morgan, "Why There Was a Useful Plausible Analogy between Geodesic Domes and Spherical Viruses," Hist. Phil. life Sci., 2006, 28:215-236.
171. See Maddox, Rosalind Franklin, pp. 251-252, 256, 263.
172. This was despite the remarkable results Franklin and Klug had obtained together. Especially impressive was their demonstration that the number of subunits per three turns of the helix varied slightly - by hundredths of a subunit - among different strains of the virus. See Rosalind E. Franklin and A. Klug, "The Splitting of Layer Lines in X-ray Fibre Diagrams of Helical Structures: Application to Tobacco Mosaic Virus," Acta Crystallog., 1955, 8:777-780.
173. Aaron Klug manuscript, "Bernal and Virus Research at Birkbeck," p. 6,
174. Franklin Papers, FRNK 2/37; and Rosalind E. Franklin, "Structural Resemblance between Schramm's Repolymerized A-Protein and Tobacco Mosaic Virus," Biochim. Biophys. Acta, 1955, 18:313-314.
175. Schramm's method involved disaggregating the TMV particles in alkali, separating the protein and nucleic acid components with electrophoresis, and then reaggregating the protein component in a mild acid. See Gerhard Schramm, "Über die Spaltung des Tabakmosaikvirus und die Wiedervereinigung der Spaltstücke zu höhermolekularen Proteinen, II: Versuche zur Wiedervereinigung der Spaltstücke," Zeitschrift für Naturforschung, 1947, 2(B):249-257.
176. Crick to Franklin, 3 June 1955, Franklin Papers, FRNK 2/33. Watson expressed an interest in PVX in Watson to Crick, 27 May 1955, Crick Papers, National Library of Medicine, Profiles in Science: http://profiles.nlm.nih.gov/ SC/B/B/J/J/scbbjj.pdf.
177. Franklin to Crick, 6 June 1955, Franklin Papers, FRNK 2/33; Watson, Genes, Girls, and Gamow, p. 180;
178. and Franklin to Paul Kaesberg, 18 July 1955, Franklin Papers, FRNK 2/33.
179. Interview, Morgan with Donald Caspar, Tallahassee, Fla., 4-5 Dec. 1998. Caspar recalls that together they attended the opening performance of the Japanese Azuma Kabuki dancers and musicians in Covent Garden.
180. Watson, Genes, Girls, and Gamow, p. 183 (evidence of five-fold symmetry);
181. and personal communication, Caspar to Morgan, 18 Apr. 2003. As Caspar more recently described the cache in Carlisle's fridge, "Finding the sparkling BSV and TYMV crystals was like finding a hoard of diamonds in a secret cavern." Franklin agreed that Caspar could have the BSV crystals he found at Birkbeck. Personal communication, Caspar to Morgan, 14 Nov. 2007.
182. Watson, Genes, Girls, and Gamow, p. 188;
183. and Watson to Christa Mayr, undated [Nov. 1955] letter circulated with, an advance copy of Watson's Genes, Girls, and Gamow (obtained courtesy of Donald Caspar).
184. Personal communication, Caspar to Morgan, 18 Apr. 2003 (burnt jacket). Caspar expressed his take on the division of labor: "My memory and Aaron Klug's memory is somewhat different from Jim Watson's memory. What we had decided was that Rosalind and Aaron would work on Turnip yellow mosaic virus crystals and I would carry on with work on the BSV crystals." Interview, Morgan with Caspar, 4-5 Dec. 1998. Aaron Klug confirms Caspar's memory: communication with Morgan, 16 Aug. 2007.
185. Several historians of science have elaborated on how moral economies of science function, taking inspiration in various ways from E. P. Thompson's classic usage: "The Moral Economy of the English Crowd in the Eighteenth Century" and "The Moral Economy Reviewed," in E. P. Thompson, Customs in Common (New York: New Press, 1991), pp. 185-258, 259-351.
186. See, e.g., Steven Shapin, A Social History of Truth: Civility and Science in Seventeenth-Century England (Chicago: Univ. Chicago Press, 1994);
187. Lorraine Daston, "The Moral Economy of Science," Osiris, N.S., 1995, 10:3-24;
188. and Robert E. Kohler, "Moral Economy, Material Culture, and Community in Drosophila Genetics," in The Science Studies Reader, ed. Mario Biagioli (New York: Routledge, 1999), pp. 243-257.
189. We draw predominantly on Kohler's model, given our interest in the circulation of materials and allocation of credit. Along these lines see also Anderson, "Possession of Kuru" (cit. n. 13);
190. and Paula Findlen, "The Economy of Scientific Exchange in Early Modern Italy," in Patronage and Institutions: Science, Technology, and Medicine at the European Court, 1500-1750, ed. Bruce T. Moran (Rochester, N.Y.: Boydell, 1991), pp. 5-24.
191. Needless to say, our pointing to a moral economy at work does not imply that all of the participants were virtuous or exemplary; Watson and Crick's failure fully to credit Franklin's experimental data on DNA in their 1953 paper was an abrogation of the usual conventions even at the time and remains a troubling aspect of the history.
192. Caspar had sent Franklin his Ph.D. dissertation in June 1955, before he went to England.
193. Franklin to Pirie, 3 Feb. 1956, Franklin Papers, FRNK 2/33. Information regarding Franklin's initial drafting of Caspar's paper comes from interview, Morgan with Caspar, 4-5 Dec. 1998.
194. See also Franklin to Watson, 10 Feb. 1956, Jeremy Norman Collection (this collection - hereafter cited as Norman Collection - was in San Francisco when Morgan used it but has since been auctioned); Watson quotes her cover letter in full in Genes, Girls, and Gamow, p. 203.
195. The published versions of the papers are Donald L. D. Caspar, "Radial Density Distribution in the Tobacco Mosaic Virus Particle," Nature, 1956, 177:928;
196. and Rosalind. E. Franklin, "Location of the Ribonucleic Acid in the Tobacco Mosaic Virus Particle," ibid., pp. 928-930.
197. Watson, Genes, Girls, and Gamow, pp. 189-190.
198. On Rich's stay in Cambridge and his work there with Crick on the triple-helical structure of collagen see Alexander Rich, "Fifty Years with Double-Stranded RNA," Scientist, 2006, 20:34-39.
199. Watson, Genes, Girls, and Gamow, pp. 202-203.
200. F. H. C. Crick and J. D. Watson, "Structure of Small Viruses," Nature, 1956, 177:473-475, on p. 473;
201. D. L. D. Caspar, "Structure of Bushy Stunt Virus," ibid., pp. 475-476;
202. and Crick, as quoted by Aaron Klug in his historical introduction to "Session I: Particle Structure," at "Symposium on Tobacco Mosaic Virus: Pioneering Research for a Century," sponsored by the Royal Society of Edinburgh in association with the Royal Society of London, 7 Aug. 1998, Edinburgh. Klug dates the remark to the late 1950s: personal communication to Creager, 17 Apr. 2001.
203. Caspar dates Crick's remark to around 1955; see D. L. D. Caspar, "Movement and Self-Control in Protein Assemblies: Quasi-Equivalence Revisited," Biophysical Journal, 1980, 32:103-138.
204. A few familiar objects possess the same kind of symmetry. E.g., a soccer ball constructed from twelve black pentagons and twenty white hexagons has 532 symmetry: five-fold symmetries though the centers of the pentagons, three-fold symmetries through the centers of the hexagons, and two-fold symmetries through the edges between the hexagons. Dorothy Hodgkin had earlier speculated that BSV has cubic symmetry but had not drawn general conclusions; see Dorothy Crowfoot Hodgkin, "X-ray Analysis and Protein Structure," Cold Spring Harbor Symposia on Quantitative Biology, 1950, 14:65-78.
205. For more detail on Caspar's work see Morgan, "Early Theories of Virus Structure" (cit. n. 68).
206. Crick and Watson, "Structure of Small Viruses" (cit. n. 82), p. 474;
207. and Caspar, "Structure of Bushy Stunt Virus" (cit. n. 82), p. 476. These results are not inconsistent if each structural subunit consists of multiple chemical subunits.
208. Franklin, "Note on the Future of the A.R.C. Research Group in Birkbeck College Crystallography Laboratory," 9 Mar. 1956, Franklin Papers, FRNK 2/36.
209. In the letter quoted above concerning the incident of Caspar and the TYMV crystals, Watson stated: "This morning was spent persuading Victor Rothschild that Rosy should be supported in spite of her continued insults to the administrative heads of the Agriculture Research Council. This weekend I must write a long report to be submitted to ARC, otherwise she will hopelessly flounder without adequate financial support." Watson to Mayr, undated [Nov. 1955] letter circulated with an advance copy of Watson's Genes, Girls, and Gamow.
210. In his autobiography, Watson describes how he spoke on behalf of Franklin's needs to Rothschild earlier that summer as well and reprints a letter he wrote to Franklin with advice on how to secure funds for a much-needed upgrade to her crystallography equipment: Watson, Genes, Girls, and Gamow, pp. 154-156.
211. Williams to Crick, 20 Sept. 1957, Williams Papers, carton 4, folder C. On the grant from the Public Health Service see Maddox, Rosalind Franklin, pp. 290-292.
212. Williams provided advice to Franklin on her application. See Franklin to Williams, 19 Oct. 1956;
213. Williams to Franklin, 24 Oct. 1956;
214. and Franklin to Williams, 6 Dec. 1956: Williams Papers, carton 4, folder F. Franklin immediately used the American funds to pay for a research assistant at the Molteno Institute to grow and purify more TYMV for crystals, which were in short supply: Franklin to Kenneth Smith, 17 July 1957, and Smith to Franklin, 16 Oct. 1957, Norman Collection. Franklin had requested a letter from Watson supporting her application to the U.S. Public Health Service; her letter to Watson indicates how instrumental Williams was in helping her apply successfully and how crucial the American grant was to enable her and Klug to continue working together. She also mentioned that, since her return from the United States, "I've spent all my time being ill": Franklin to Watson, 14 Nov. [1956], Watson Papers.
215. Franklin and Holmes looked for the influence of the mercury atom, on the outer parts of the zero layer line and were able to infer that n = 16 was the correct solution to Watson's equation (i.e., 3n + 1 = 49): Kenneth C. Holmes, personal communication to Morgan, 24 Dec. 2006.
216. See Rosalind E. Franklin and Kenneth C. Holmes, "Tobacco Mosaic Virus: Application of the Method of Isomorphous Replacement to the Determination of the Helical Parameters and Radial Density Distribution," Acta Crystallog., 1958, 11:213-220.
217. On the state of knowledge in 1956 see Franklin to Pirie, 3 Feb. 1956, Franklin Papers, FRNK 2/33. One missing piece of information was that the handedness of the TMV helix was not revealed by diffraction data.
218. Watson to Stanley, 27 Jan. 1956, Stanley Papers, carton 13, folder Wa Misc.
219. There are reasons to be cautious about taking this letter at face value, even though we find Watson's assent to Franklin's standing in the field to be notable. Stanley was a major power broker in the field, and Franklin was collaborating closely with members of his lab. At the same time, Watson did not find Stanley's Virus Lab very scientifically stimulating; see Watson to Crick, 11 Dec. 1954,
220. Crick Papers, National Library of Medicine, Profiles in Science: http://profiles.nlm.nih.gov/SC/B/B/J/N/_/scbbjn.pdf. Moreover, he had been recommended for an opening there but failed to receive an offer; see Watson to Gunther S. Stent, 9 Dec. 1954, Gunther S. Stent Papers, Bancroft Library, University of California, Berkeley, 99/149z, box 15, folder Watson, J. D.
221. On the symposium as an effort to revivify virology in England see G. E. W. Wolstenholme to Franklin, 21 June 1955, Franklin Papers, FRNK 2/34;
222. and Frank Macfarlane Burnet to Lady Burnet, 13 Mar. 1956, Frank Macfarlane Burnet Papers, University of Melbourne Archives, 2/18.
223. For Franklin's attempt to include Schramm see Franklin to Wolstenholme, 28 June 1955, Franklin Papers, FRNK 2/34. The Ciba/Novartis scrapbook (held at the Ciba Foundation, London) has a printed list of participants in which Wilkins's name is crossed out and Klug's is written in by hand.
224. "It now begins to appear (Fraenkel-Conrat, 1956) that infection can be obtained from solutions in which essentially no full-length TMV particles, either native or reconstituted, are present. The active solutions are believed to be pure RNA, and are infectious when rubbed upon tobacco plants in sufficiently high concentrations": Robley C. Williams, "Structure and Substructure of Viruses as Seen under the Electron Microscope," in Ciba Foundation Symposium on the Nature of Viruses, ed. G. E. W. Wolstenholme and Elaine C. P. Millar (Boston: Little, Brown, 1957), pp. 19-33, on p. 31.
225. The observation by Heinz Fraenkel-Conrat appeared in "'The Role of the Nucleic Acid in the Reconstitution of Active Tobacco Mosaic Virus," J. Amer. Chem. Soc., 1956, 78:882-883;
226. but Alfred Gierer and Gerhard Schramm made the same discovery independently and gave it greater prominence in "Infectivity of Ribonucleic Acid from Tobacco Mosaic Virus," Nature, 1956, 177:702-703.
227. By the same token, Watson has described a hoax he played on Williams, falsifying a telegram from Stanley conveying the news that the TMV protein was infectious; Watson claims that Williams downplayed his new results with nucleic acid in his Ciba Foundation symposium talk as a result: Watson, Genes, Girls, and Gamow. p. 217.
228. F. C. Bawden, in discussion following Williams, "Structure and Substructure of Viruses as Seen under the Electron Microscope," in Ciba Foundation Symposium on the Nature of Viruses, ed. Wolstenholme and Millar (cit. n. 91); the remark appears on p. 35.
229. Pirie argued in the same discussion that Williams should not restrict his search for TMV particles to those 2,000-3,000 Å long, as he might be missing smaller infective units (ibid., p. 36).
230. Watson, Passion for DNA (cit. n. 40), p. 28.
231. This tenet was codified by Crick as the "Central Dogma." See Judson, Eighth Day of Creation (cit. n. 10), pp. 332-336;
232. and Strasser, "World in One Dimension" (cit. n. 11).
233. Rosalind E. Franklin, A. Klug, and K. C. Holmes, "X-ray Diffraction Studies of the Structure and Morphology of Tobacco Mosaic Virus," in Ciba Foundation Symposium on the Nature of Viruses, ed. Wolstenholme and Millar (cit. n. 91), pp. 39-52.
234. F. H. C. Crick and. J. D. Watson, "Virus Structure: General Principles," in Ciba Foundation Symposium on the Nature of Viruses, ed. Wolstenholme and Millar, pp. 5-13, on p. 12.
235. Watson to Crick, 10 Feb. 1955, Crick Papers, National Library of Medicine, Profiles in Science: http://profiles.nlm.nih.gov/SC/B/B/J/L/scbbjl. pdf.
236. Maddox, Rosalind Franklin, p. 268.
237. See Franklin to Klug, 21 June 1956, Norman Collection; and Maddox, Rosalind Franklin, pp. 277-280. Whereas Franklin's hosts at Caltech had her out for dinner and even took her on a camping trip in the mountains, which she relished, she found her collaborators at the Virus Lab to be less sociable.
238. Franklin to Stanley, 4 July 1956, Stanley Papers, carton 8, folder Franklin, Rosalind. Franklin's thank-you note to Stanley, written on 30 Aug. (and in the same folder of the Stanley Papers), makes it clear that she stayed in Berkeley for three weeks.
239. "The most important thing here is that I've recently seen some electron micrographs of TYM by Steere's freezing-shadowing replica technique which show a magnificently clear surface structure. This only happened today, and seems very exciting, so excuse the muddle. The prominent feature is an array of six knobs on each particle around, a central one.... The inter-knob distance is ∼1/4 inter-particle distance, which is consistent with your 60 Å, but the thing does not look 5 folded. ... If it is not 5-folded, the question arises, was the five foldedness in the RNA. ... Believe it or not, he [Robley Williams] says he had a slide of this with him at Ciba but did not show it in case the effect was due to amm. sulphate!!" Franklin to Klug, 27 July 1956, Norman Collection.
240. Franklin to Klug, 30 July 1956, Norman Collection. A cubeoctahedron has 432 symmetry, not the 532 symmetry of an icosahedron such as BSV. A week later, Franklin was still thinking about Steere's electron micrographs, but now from the point of view that the photographs pertained to the determination of the unit cell of the crystal: Franklin to Klug, 5 Aug. 1956, Norman Collection.
241. Crick to Klug, 14 Dec. 1956, Norman Collection; A. Klug, J. T. Finch, and Rosalind E. Franklin, "Structure of Turnip Yellow Mosaic Virus," Nature, 1957, 179:683-684;
242. and Klug, Finch, and Franklin, "The Structure of Turnip Yellow Mosaic Virus: X-ray Diffraction Studies," Biochim. Biophys. Acta, 1957, 25:242-252.
243. For more on the symmetry of TYMV see A. Klug and J. T. Finch, "The Symmetries of the Protein and Nucleic Acid in Turnip Yellow Mosaic Virus: X-Ray Diffraction Studies," J. Molec. Biol., 1960, 2:201-215.
244. On the history of research on cytoplasmic particles see Nicolas Rasmussen, "Mitochondrial Structure and the Practice of Cell Biology in the 1950s," J. Hist. Biol., 1995, 28:381-429;
245. Hans-Jörg Rheinberger, "Comparing Experimental Systems: Protein Synthesis in Microbes and in Animal Tissue at Cambridge (Ernest F. Gale) and at the Massachusetts General Hospital (Paul C. Zamecnik), 1945-1960," ibid., 1996, 29:387-416;
246. Rheinberger, "Cytoplasmic Particles in Brussels (Jean Brachet, Hubert Chartrenne, Raymond Jeener) and at Rockefeller (Albert Claude), 1935-1955," Hist. Phil. Life Sci., 1997, 19:47-67;
247. and Rheinberger, Toward a History of Epistemic Things: Synthesizing Proteins in the Test Tube (Stanford, Calif.: Stanford Univ. Press, 1997).
248. Watson, "Involvement of RNA in the Synthesis of Proteins" (cit. n. 39), p. 787;
249. Klug to Bernal, 31 May 1956, Norman Collection (emphasis in original); and Franklin to Klug, 17 July 1956, Norman Collection (interest of Caspar, Crick, and Watson).
250. On the analogy between spherical viruses and microsomes see Crick and Watson, "Virus Structure" (cit. n. 96), p. 12.
251. Franklin to Klug, 27 July 1956, Norman Collection (regarding Franklin's California connections for obtaining material); and Rosalind. E. Franklin, A. Klug, J. T. Finch, and K. C. Holmes, "On the Structure of Some Ribonucleoprotein Particles," Discussions Faraday Soc., 1958, 25:197-198.
252. F. L. Schaffer and C. E. Schwerdt, "Crystallization of Purified MEF-1 Poliomyelitis Virus Particles," Proc. Nat. Acad. Sci., USA, 1955, 41:1020-1023.
253. For a discussion of their work see Creager, life of a Virus, Ch. 5. Polio crystals were discussed at the International Poliomyelitis Conference in Geneva in July 1957, where Franklin heard Schwerdt give a talk on the crystals he had grown: Franklin notebook entry, 10 July 1957, Franklin Papers, FRNK 3/14.
254. Interview, Morgan with John Finch, Cambridge, 18 July 2000.
255. For correspondence regarding the attempts to mount polio crystals see Franklin to Caspar, 16 Mar. 1958;
256. Franklin to Bawden, 20 Mar. 1958;
257. and Franklin to R. W. Douglas, 24 Mar. 1958:
258. Franklin Papers, FRNK 2/33. The results were published in J. T. Finch and A. Klug, "Structure of Poliomyelitis Virus," Nature, 1959, 183:1709-1714.
259. W. L. Bragg to Crick, 26 June 1956, William Lawrence Bragg Papers, Royal Institution, London (hereafter cited as Bragg Papers), 83P/1.
260. Bragg was appointed by the president of the Royal Society (Cyril Hinshelwood) to serve as the U.K. representative on the Scientific Committee for the Brussels exhibition: Bragg Papers, 83G/1, 2, 3.
261. Bragg also wrote Frederick Sanger about his interest in including his work on insulin chains and to Perutz about his wish to include X-ray crystallographic work on proteins and Huxley's work on muscle: Bragg Papers, 83P/3, 84A/1.
262. E.g., Crick noted in his response to Bragg's letter: "Miss Franklin will cover viruses and Wilkins will, I think, be responsible for DNA. I should be quite happy to look after collagen, but I think that to collaborate with King's on this would, cause unnecessary friction." Crick to Bragg, 8 Dec. 1956, Bragg Papers, 83P/37.
263. See Bragg to Franklin, 26 June 1956, Bragg Papers, 85B/164;
264. Franklin to Bragg, 23 July 1956, Bragg Papers, 85B/165;
265. and copies of correspondence in the same box between Franklin and D. C. Phillips. This TMV model, whose design and construction were overseen by Klug, ended up at the Cambridge MRC Laboratory.
266. Rosalind E. Franklin, D. L. D. Caspar, and A. Klug, "The Structure of Viruses as Determined by X-ray Diffraction," in Plant Pathology: Problems and Progress, 1908-1958, ed. C. S. Holton et al. (Madison: Univ. Wisconsin Press, 1959), pp. 447 461;
267. and Caspar and Klug, "Physical Principles in the Construction of Regular Viruses," Cold Spring Harbor Symp. Quant. Biol., 1962, 27:1-24.
268. On the development of this theory see Morgan, "Early Theories of Virus Structure" (cit. n. 68).
269. Aaron Klug, "From Macromolecules to Biological Assemblies," in Nobel Lectures: Chemistry, 1981-1990, ed. Tore Frängsmyr and Bo G. Malmström (Singapore: World Scientific, 1992), pp. 77-109, on p. 79;
270. also quoted in Maddox, Rosalind Franklin, p. 325. Klug was the sole recipient of that year's prize in chemistry; he felt Franklin would have been recognized earlier had she lived.
271. As Maddox recounts and others have noted, Franklin went to the Cricks' home in Oct.-Nov. 1956 to recover from a second surgery rather than continuing to stay with her family: Maddox, Rosalind Franklin, p. 289.
272. The characterization of Franklin as so cautious an experimentalist that she distrusted both model building and theoretical intuition has been prominent in the historiography since Watson's Double Helix. Needless to say, the depiction draws on gender stereotypes by portraying a woman scientist as attentive to detail, patient, unoriginal, and intellectually timid. In his account of Franklin, Robert Olby points to J. D. Bernal's influence on her. Bernal criticized Linus Pauling's "deductive" model building, arguing that scientists should rely on inductive methods such as "deriving chain types from Patterson sections": Olby, Path to the Double Helix (cit. n. 18), p. 374.
273. This observation explains Franklin's choice of approach and her alleged antihelical stance in 1952, but it does not seem fully to account for the repeated claims that she lacked or distrusted intuition. At the end of her biography, Maddox offers an astute analysis of how the image of Franklin as meticulous and unimaginative gained traction; this characterization was offered, by Crick as well as by Watson, and the depiction works to excuse both of them for using her data by suggesting that she did not seem to know how to interpret it herself. See Francis Crick, "How to Live with a Golden Helix," Sciences, 1979, 19(7):6-9.
274. Maddox points to Franklin's work on coal and on viruses as evidence to the contrary; we feel the evidence is even stronger for TMV than Maddox suggests. See Maddox, "Epilogue: Life after Death," in Rosalind Franklin, pp. 311-328.
275. Franklin's combination of institutional marginality and scientific achievement is reminiscent of that of her contemporary Barbara McClintock. For the definitive account of the institutional obstacles that women scientists faced in the mid-twentieth century United States see Margaret W. Rossiter, Women Scientists in America: Before Affirmative Action, 1940-1972 (Baltimore: Johns Hopkins Univ. Press, 1995).
276. On McClintock see Evelyn Fox Keller, A Feeling for the Organism: The Life and Work of Barbara McClintock (San Francisco: Freeman, 1983);
277. and Nathaniel C. Comfort, The Tangled Field: Barbara McClintock's Search for the Patterns of Genetic Control (Cambridge, Mass.: Harvard Univ. Press, 2001).
278. Negotiations for this move predated Franklin's death and were motivated by Bernal's impending retirement. In addition to Klug, Finch, Holmes, and Reuben Leberman moved from Birkbeck to Cambridge; see de Chadarevian, Designs for life, p. 252.
279. Holmes, Meselson, Stahl, and the Replication of DNA (cit. n. 40), Ch. 1.
280. On the gradual acceptance of Watson and Crick's model see also de Chadarevian, Designs for Life, esp. Ch. 6; and Robert Olby, "Quiet Debut for the Double Helix," Nature, 2003, 421:402-405.
281. Gierer and Schramm, "Infectivity of Ribonucleic Acid from Tobacco Mosaic Virus" (cit. n. 91). The TMV "reconstitution" experiments in Berkeley provided an elegant demonstration of the hereditary role of the RNA, since hybrids composed of RNA from one strain and protein from another always gave rise, once infected into a host, to the "parent" strain from which the nucleic acid had been derived. See Heinz Fraenkel-Conrat and Beatrice A. Singer, "Virus Reconstitution, II: Combination of Protein and Nucleic Acid from Different Strains," Biochim. Biophys. Acta, 1957, 24:540-548;
282. and Creager, Life of a Virus. Ch. 7.
283. See Francis H. C. Crick, "Nucleic Acids," Scientific American, 1957, 197(3):188-200;
284. Kay, Who Wrote the Book of life? (cit. n. 10), pp. 179-192;
285. and Creager, life of a Virus, Ch. 7.
286. 'Die other promising viral model was bacteriophage; Sydney Brenner and his colleagues at Cambridge used mutagens to introduce changes into the genes of phage T4 and follow their effects. See de Chadarevian, Designs for Life, pp. 195-198.
287. See Watson, "Involvement of RNA in the Synthesis of Proteins" (cit. n. 39).
288. Caspar would seem to be a good example of this, although he cautions against idealizing Franklin. He emphasizes that she was strongly focused on achieving her scientific goals and asserted herself as necessary, whereas his own attitude was less proprietary: Caspar, personal communication to Morgan, 14 Nov. 2007. In the end, we see her single-mindedness as consistent with her ability to make effective use of collaboration.
289. P. Jonathan G. Butler and Aaron Klug, "The Assembly of a Virus," Sci. Amer., 1978, 239(5):62-69;
290. and Morgan, "Early Theories of Virus Structure" (cit. n. 68).
291. See Judson, Eighth Day of Creation (cit. n. 10), Chs. 5-8;
292. and Rheinberger, Toward a History of Epistemic Things (cit. n. 104), esp. Chs. 10, 12. 13.
293. De Chadarevian, Designs for Life, Chs. 6, 8.
294. On the popular uses of the double helix see Dorothy Nelkin and M. Susan Lindee, The DNA Mystique: The Gene as a Cultural Icon (New York: Freeman, 1995).