Life's Greatest Secret

by Matthew Cobb

  Yčas, M., The Biological Code, London, North-Holland, 1969.

  Yčas, M. and Vincent, W. S., ‘A ribonucleic acid fraction from yeast related in composition to desoxyribonucleic acid’, Proceedings of the National Academy of Sciences USA, vol. 46, 1960, pp. 804–11.

  Yockey, H. P., ‘Some introductory ideas concerning the application of information theory in biology’, in H. P. Yockey, R. L. Platzman and H. Quastler (eds), Symposium on Information Theory in Biology, London, Pergamon, 1958, pp. 50–9.

  Yockey, H. P., Information Theory and Molecular Biology, Cambridge, Cambridge University Press, 1992.

  Yockey, H. P., Platzman, R. L. and Quastler, H. (eds), Symposium on Information Theory in Biology, London, Pergamon, 1958.

  Yong, E., ‘The unique merger that made you (and ewe, and yew)’, Nautilus, 10, http://nautil.us/issue/10/mergers--acquisitions/the-unique-merger-that-made-you-and-ewe-and-yew, 2014.

  Young, J. Z., ‘Memory, heredity and information’, in J. Huxley, A. C. Hardy and E. B. Ford (eds), Evolution as a Process, London, Allen & Unwin, 1954, pp. 281–99.

  Yoxen, E. J., ‘Where does Schroedinger’s What is Life? belong in the history of molecular biology?’, History of Science, vol. 17, 1979, pp. 17–52.

  Yu, A., Lepère, G., Jay, F. et al., ‘Dynamics and biological relevance of DNA demethylation in Arabidopsis antibacterial defense’, Proceedings of the National Academy of Sciences USA, vol. 110, 2013, pp. 2389–94.

  Zagorski, N., ‘Profile of Alec J. Jeffreys’, Proceedings of the National Academy of Sciences USA, vol. 26, 2006, pp. 8918–20.

  Zamecnik, P., ‘From protein synthesis to genetic insertion’, Annual Review of Biochemistry, vol. 74, 2005, pp. 1–28.

  Zamecnik, P. C. and Keller, E. B., ‘Relation between phosphate energy donors and incorporation of labeled amino acids into proteins’, Journal of Biological Chemistry, vol. 209, 1954, pp. 337–54.

  Zamenhof, S., ‘Properties of the transforming principle’, in W. D. McElroy and B. Glass (eds), A Symposium on the Chemical Basis of Heredity, Baltimore, The Johns Hopkins Press, 1957, pp. 351–72.

  Zubay, G., ‘A possible mechanism for the initial transfer of the genetic code from deoxyribonucleic acid to ribonucleic acid’, Nature, vol. 182, 1958, pp. 112–13.

  Zubay, G. and Quastler, H., ‘An RNA-protein code based on replacement data’, Proceedings of the National Academy of Sciences USA, vol. 48, 1962, pp. 461–71.

  PHOTO INSERT

  1. Erwin Schrödinger (left) with the Irish President Hyde (in wheelchair) and Prime Minister De Valera (far right), at the official opening of the Institute for Advanced Studies, Dublin 1943.

  2. Norbert Wiener in the 1950s, accompanied by some of his fiendish equations.

  3. Oswald Avery at a laboratory party, Christmas 1940.

  4. Claude Shannon with paper tape used for programming computers.

  5. Harriett Ephrussi-Taylor, Boris Ephrussi and Leo Szilárd at the 1951 Cold Spring Harbor Symposium.

  6. Alfred Mirsky (left) and Masson Gulland in conversation at the 1947 Cold Spring Harbor Symposium. Four months later, Gulland was killed in a train crash south of Berwick.

  7. André Boivin (left) discusses with Joshua Lederberg at the 1947 Cold Spring Harbor Symposium.

  8. Salvador Luria (standing) and Max Delbrück at Cold Spring Harbor, 1953.

  9. Leo Szilárd (left) and Al Hershey in the rain at the Cold Spring Harbor Symposium, 1951. They look like characters in a film by the Coen Brothers.

  10. Team photo of Al Hershey’s laboratory at Cold Spring Harbor, 1952. Martha Chase is second from the left, Hershey is standing next to her.

  11. Rosalind Franklin on holiday in Tuscany, 1950.

  12. Maurice Wilkins with an X-ray crystallography apparatus in the 1950s.

  13. Jim Watson describes the double helix structure of DNA in the heat of the June 1953 Cold Spring Harbor Symposium.

  14. Watson and Crick with the double helix, photographed by Antony Barrington Brown, in May 1953 in their office at the Cavendish Laboratory in Cambridge. The photograph was not published at the time.

  15. One of many letters sent by George Gamow. In this letter to Linus Pauling, written in November 1953, Gamow explains his ‘diamond’ model of the genetic code.

  16/17. The RNA Tie Club in the 1950s. Right: George Gamow, wearing his Club tie and tie-pin. Below, left to right: Francis Crick, Alexander Rich, Leslie Orgel and Jim Watson in 1955. Orgel was apparently not playing the game – he was not wearing his RNA Club tie.

  18. Heinrich Matthaei (left) and Marshall Nirenberg, 1961, after they had cracked the genetic code.

  19. Moscow Biochemistry Congress 1961: Commemorative stamp and photo showing Crick (left) and Benzer (to his right), with Jacob (second from right). All five men are wearing Congress badges.

  20. Crick’s annotations to the programme for the Moscow Biochemical Congress session he chaired on 15 August 1961, showing his handwritten inclusion of Nirenberg during the 10:00 Discussion period. This gem was discovered by Bob Goldstein.

  21. François Jacob and his wife, Lise, on the beach at La Tranche-sur-Mer, on the west coast of France, August 1962.

  22. Jacques Monod (left) and Sydney Brenner in the 1960s.

  23. François Jacob (left) and Jacques Monod in the laboratory in the early 1970s. Monod died of leukemia in 1976.

  24. Francis Crick speaking at the 1963 Cold Spring Harbor Symposium. On the blackboard is a diagram of the central dogma.

  25. Francis Crick (lying down with back to camera) hosts a ‘flower party’ at his house in Cambridge, in the mid-1960s. The house was named The Golden Helix. According to Henry Selby-Lowndes, the son of the photographer, Guy Selby-Lowndes, the music included hits by Herman’s Hermits and Herb Alpert.

  26. Jacques Monod (left) and Leo Szilárd discuss the operon, Cold Spring Harbor, 1961. Monod described Szilárd as looking ‘like a petty Italian fruit-merchant’.

  27. Francis Crick (left) and Seymour Benzer at a Symposium on Nucleic Acids held in Hyderabad, India, in January 1964.

  28. Exchange of letters between Seymour Benzer and François Jacob, André Lwoff and Jacques Monod, on the occasion of the French trio being awarded the Nobel Prize, in 1965. Benzer was renowned for his sense of humour.

  29. Banner put up in Marshall Nirenberg’s laboratory at the National Institutes of Health in Bethesda, Maryland, when news came through of his 1969 Nobel Prize.

  30. Asilomar conference on recombinant DNA, 1975. Left to right: Maxine Singer, Norton Zinder, Sydney Brenner and Paul Berg. The possibility of using CRISPR to change the human germ line has recently led to calls for a ‘new Asilomar’ to debate the ethical and technical questions involved.

  NOTES

  Chapter 1

  1.Wood and Orel (2001), p. 258; see also Cobb (2006a), Poczai et al. (2014).

  2.López-Beltrán (1994), Müller-Wille and Rheinberger (2007, 2012).

  3.Harvey basically shrugged his shoulders and gave up (Cobb, 2006b).

  4.Cobb (2006a).

  5.For Mendel’s work and its implications, see Bowler (1989), Gayon (1998), Hartl and Orel (1992). For critical accounts of the way in which Mendel’s work has been interpreted and used, see Brannigan (1979) and Wolfe (2012).

  6.There are many historical accounts of twentieth-century genetics, for example Carlson (1966, 1981, 2004), Hunter (2000), Pichot (1999), Schwartz (2008), Sturtevant (1965). For conceptual aspects see the articles in Beurton, Falk and Rheinberger (2000) as well as Falk (2009) and Müller-Wille and Rheinberger (2012). For the changing views of de Vries, see Stamhuis, Meijer and Zevenhuizen (1999).

  7.Sutton (1902), p. 39. See Crow and Crow (2002).

  8.Sutton (1903), p. 236.

  9.Hegreness and Meselson (2007).

  10.Boveri (1904), cited in Crow and Crow (2002).

  11.Pichot (1999), p. 111.

  12.Shine and Wrobel (1976).

  13.Carlson (1981), Kohler (1994), Sturtevant (1965).

  14.Mo
rgan (1933).

  15.All details from Carlson (2004).

  16.Morgan (1919), p. 246.

  17.Morgan (1933), p. 316.

  18.von Schwerin (2010).

  19.For a translation of the Three-Man Paper, and discussions of its significance by historians and philosophers, see Sloan and Fogel (2011).

  20.Sloan and Fogel (2011), p. 257.

  21.Sofyer (2001), Morange (2011). Koltsov’s name can also be transliterated as Koltzoff. For a discussion of Koltsov’s contribution to ideas of messages and codes, see Kogge (2012).

  22.Olby (1994), Sofyer (2001).

  23.Muller (1922), p. 37; Troland (1917).

  24.Quoted in Pollock (1970), p. 13.

  25.Haldane (1945), Morange (2011).

  26.Pringle (2008).

  27.Olby (1994), pp. 73–96.

  28.Caspersson et al. (1935), p. 369.

  29.Stanley (1935).

  30.Muller (1922).

  31.Cairns et al. (1966), Summers (1993).

  32.Kay (1986).

  33.All quotes from Wrinch (1936).

  34.Schultz (1935), p. 30.

  35.Beadle and Tatum (1941).

  36.For example Troland (1917).

  37.Horowitz et al. (2004), p. 4.

  38.Tatum and Beadle (1942), p. 240.

  39.Berg and Singer (2003), pp. 171–86.

  40.Time, 5 April 1943; The Irish Press, 6 February 1943.

  41.The Irish Press, 13 and 16 February 1943.

  42.Moore (1989).

  43.5, 12 and 19 February 1943. Moore (1989), p. 35.

  44.Using different calculations, Schrödinger at one point suggested that a gene was composed of a few million atoms, at another ’1,000 and possibly much less’. Schrödinger (2000), p. 46.

  45.Schrödinger (2000), p. 20.

  46.Schrödinger (2000), p. 21.

  47.Schrödinger (2000), p. 22.

  48.Schrödinger (2000), p. 62.

  49.Olby and Posner (1967).

  50.In 1999, Joshua Lederberg argued that Schrödinger did not really mean that the genetic material was ‘aperiodic’, but rather that it had ‘elements of crystallinity’ or was ‘near-crystal’ (Dromanraju, 1999, p. 1074).

  51.The Irish Press, 6 and 16 February 1943.

  52.The Kerryman, 22 January 1944.

  53.In 1945 Schrödinger had a brief correspondence with the geneticist J. B. S. Haldane over the genetics of hornless cattle (Crow, 1992).

  54.Yoxen (1979), p. 45, note 9; Olby (1971), p. 122.

  55.Pauling (1987), p. 229.

  56.Perutz (1987), p. 243; Waddington (1969), p. 321.

  57.Wilkins (2003), p. 84; Crick (1988), p. 18; Inglis et al. (2003), p. 3.

  58.For example, Morange (1983), Symonds (1986), Kay (2000), Sarkar (2013).

  Chapter 2

  1.Administrative Framework of OSRD (1948).

  2.Conway and Siegelman (2005), p. 199.

  3.Mindell (1995), p. 91. See also Bennett (1994), Masani (1990) and Mindell (2000, 2002).

  4.Mindell (1995), p. 92; Owens (1989). Wiener’s grant was the smallest awarded by D-2.

  5.In 2013, the then occupant of the room, Dr Bjorn Poonen, kindly sent me photos of his office, looking pretty much as it must have done in 1940, with the exception of the floor. The room was due to be completely remodelled in a few months. Dr Poonen is the Claude Shannon Professor of Mathematics at MIT.

  6.Wiener (1956), p. 249.

  7.Rosenblueth et al. (1943).

  8.Mindell (1995), p. 95.

  9.Kay (2000), p. 83.

  10.On Pitts, see Easterling (2001) and Schlatter and Aizawa (2008). Easterling (2001) begins: ‘There are no biographies of Walter Pitts, and any honest discussion of him resists conventional biography.’

  11.Conway and Siegelman (2005), p. 134.

  12.Galison (1994).

  13.It has been argued that there is a direct engineering and conceptual link between this device and the computer mouse (Roch, 1998).

  14.Kay (2000), p. 81.

  15.Wiener (1949), p. 2.

  16.Shannon (1940); Roch (1999), p. 265.

  17.Rogers (1994).

  18.Hodges (2012), p. 251.

  19.Conway and Siegelman (2005), p. 126.

  20.For a comparison of the relatively minor editorial differences between the 1945 original and the two published articles (Shannon 1948a, b), see Roch (1999).

  21.Conway and Siegelman (2005), p. 146.

  22.Macrae (1992), p. 242; Heims (1980), pp. 192–9.

  23.Galison (1994), p. 253; Triclot (2007, 2008).

  24.Conway and Siegelman (2005), p. 155.

  25.Wiener (1948a).

  26.von Neumann (1997).

  27.Carlson (1981), pp. 307 and 310.

  28.http://encyclopedia.gwu.edu/index.php?title=Theoretical_Physics_Conference,_1946. A more sober, and less interesting, summary was provided by Gamow and Abelson (1946).

  Chapter 3

  1.Judson (1996), p. 44.

  2.Burnet (1968), p. 81.

  3.Heidelberger et al. (1971).

  4.Griffith (1928).

  5.Hotchkiss (1965), p. 5.

  6.Dobzhansky (1941), pp. 48–9.

  7.Dobzhansky (1941), pp. 49–50.

  8.Biscoe et al. (1936).

  9.McCarty (1986), p. 104. McCarty’s memoir is the main source for much of the detail of life in the Avery laboratory. Some of Avery’s lab books, along with reports, articles and letters, can be found at http://profiles.nlm.nih.gov/ps/retrieve/Collection/CID/CC.

  10.McCarty (1986), p. 127. Transformation as studied in the Avery lab in fact involved two different types of pneumococcus, the Type II R form and the Type III S form. For the sake of simplicity, I have referred only to the R and S characteristics.

  11.McCarty (2002), p. 25.

  12.Report of the Director of the Hospital to the Corporation of the Rockefeller Institute for Medical Research, 19 April 1941. Rockefeller Archive Center. http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/CCAANJ.

  13.Schultz (1941), p. 56.

  14.Mirsky (1943), p. 19.

  15.Report of the Director of the Hospital to the Corporation of the Rockefeller Institute for Medical Research, 17 April 1943, pp. 151–2. Rockefeller Archive Center. http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/CCAADS.

  16.Letter from Roy Avery to Wendell Stanley, 26 January 1970. University of California, Berkeley. Bancroft Library. Wendell M. Stanley Papers, Box 4, Folder 7. http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/CCAAHG.

  17.The scientific part of the letter is reproduced in Dubos (1976), pp. 216–20. A full transcript and links to a scanned version of the letter can be found at http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/CCBDBF#transcript.

  18.McCarty (1986), p. 168.

  19.Avery et al. (1944), p. 155.

  20.McCarty (1986), p. 168.

  21.McCarty (1986), p. 195.

  22.McCarty and Avery (1946a, b).

  23.McCarty and Avery (1946a), p. 94.

  24.McCarty and Avery (1946a), p. 95.

  25.Morgan (1944), p. 764; Haddow (1944), p. 196.

  26.Anonymous (1944), p. 329.

  27.Bearn (1996), p. 552.

  28.Muller (1947), p. 22.

  29.Mueller (1945), p. 734.

  30.Lederberg diary entry, 20 January 1945. http://profiles.nlm.nih.gov/ps/access/CCAAAB.pdf.

  31.Boivin et al. (1945a), p. 648.

  32.Judson (1996), p. 44. Salvador Luria showed Boivin’s paper to Avery and then lunched with Avery’s group.

  Chapter 4

  1.Chargaff and Vischer (1948).

  2.These and subsequent quotes are from Hall (2011), p. 124.

  3.Astbury (1947), p. 69. The diffraction pattern produced by a helix had yet to be described – this was Francis Crick’s PhD work, which helped give him the insight into the problem of DNA structure (Cochran et al., 1952). See comment 3 at http://paulingblog.wordpress.com/2009/07/09/the-x-ray-crystallography-that-propelled-the-race-for-dn
a-astburys-pictures-vs-franklins-photo-51/.

  4.This and subsequent quotes are from Gulland (1947a), pp. 3–4.

  5.Stacey (1947), p. 96.

  6.Stedman and Stedman (1947), p. 244.

  7.McCarty, Taylor and Avery (1946), p. 177.

  8.Spiegelman (1946), p. 274. This was Cohen’s contribution to the discussion of Spiegelman’s paper.

  9.Mirsky and Pollister (1946), pp. 134–5. For Mirsky’s life and work, see Cohen (1998).

  10.Muller (1947), pp. 22–3.

  11.Cohen (1947) seems to have been the English-language pioneer in this respect. Soon the abbreviation was everywhere, and it has now passed into the English language.

  12.Boivin et al. (1945a, b), Boivin (1947).

  13.Boivin (1947), pp. 12–13. He also thought that changes acquired during the organism’s life might be stored in RNA molecules.

  14.Boivin (1947), p. 16. Mirsky’s comments can be found on the same page.

  15.Chargaff (1947), p. 32.

  16.Gulland (1947b), p. 97.

  17.Gulland (1947b), p. 102. It is not clear whether Gulland would have pursued this work had he lived – he had recently taken up a post in industry. On what Gulland’s role might have been, see Manchester (1995).

  18.Stedman and Stedman (1947), p. 235.

  19.Schultz (1947), p. 221.

  20.Gulland (1944), Thieffry (1997), Thieffry and Burian (1996).

  21.Lederberg (1948), p. 182.

  22.Dubos (1976), p. 159.

  23.Bohlin (2009) conducted interviews with Swedish scientists who were involved with nucleic acids research in the 1950s and explored why Avery was not given the prize. An English translation of Bohlin’s Swedish-language paper would be most welcome. Avery’s contribution was eventually acknowledged when a crater on the Moon was named after him. Mendel, Schrödinger, Szilárd, von Neumann and Wiener have all been similarly honoured.