Life's Greatest Secret (66 page)

50

.  Jacob and Monod (1961a), p. 334.

51

.  Jacob and Monod (1961a), p. 344. They had first used the term operon in the previous year, in a French publication (Jacob

1960). The precise functioning of the

operon would not be fully understood for some years. See Müller-Hill (1996) for a detailed insider’s account. For an overview of the operon and its legacy, see Morange (2005a).

52

.  Jacob and Monod (1961a), p. 354.

53

.  Jacob and Monod (1961a), p. 354. Jacob could not recall any conscious reference to Schrödinger (Morange, 1998, p. 295, note 36).

54

.  Monod and Jacob (1961), p. 401.

55

.  Jacob (2011).

56

.  Ptashne (2013), p. 1181.

57

.  Brenner (1961); Monod and Jacob (1961), p. 393.

1

.  Crick (1959).

2

.  Belozersky and Spirin (1958), Sueoka

(1959).

3

.  Golomb (1962a), p. 100.

4

.  Rheinberger (1997), p. 213.

5

.  There is a large amount of material covering Nirenberg’s career in the Modern Manuscripts Collection, History of Medicine Division, National Library of Medicine at Bethesda. This includes over 40 volumes of diaries and notebooks – a future researcher’s goldmine. The diary covering this period is D9 IXA, 1960 Sep–[1961] May, to be found in Box 22, Folder 44, Marshall W. Nirenberg Papers, 1937–2003. The Nirenberg diary entries quoted here are all taken from Kay (2000). A tiny proportion of the papers can be found online at

http://profiles.nlm.nih.gov/JJ/

.

6

.  Kay (2000), p. 240.

7

.  Hoagland

(1957, 1958). For a thorough exploration of Zamecnik’s work and its conceptual implications, see Rheinberger (1997).

8

.  Grunberg-Manago

(1955). Ochoa shared the 1959 Nobel Prize with his ex-student Arthur Kornberg, who in 1956 had isolated the enzyme that enables DNA molecules to copy themselves. There was no prize for the co-discoverer of polynucleotide phosphorylase, the French biochemist Marianne Grunberg-Manago.

9

.  Singer (2003).

10

.  Kay (2000), p. 241.

11

.  Nirenberg (1960).

12

.  Lamborg and Zamecnik (1960); Rheinberger (1997), pp. 208–21.

13

.  Kay (2000), p. 246.

14

.  Tissières

(1960).

15

.  Kay (2000), p. 246.

16

.  Nirenberg (1963), p. 84.

17

.  Kay (2000), p. 247.

18

.  Rheinberger (1997), p. 213.

19

.  Crick

(1957), p. 420.

20

.  Crick (1958), p. 160.

21

.  Kay (2000), p. 248.

22

.  Matthaei and Nirenberg (1960).

23

.  Matthaei and Nirenberg (1961a).

24

.  Matthaei and Nirenberg (1961a), pp. 405–6.

25

.  Matthaei and Nirenberg (1961a), p. 407.

26

.  Kay (2000), p. 249.

27

.  Judson (1996), pp. 458–9.

28

.  Judson (1996), p. 460.

29

.  Judson (1996), p. 462.

30

.  Dr Jerry Hurwitz, e-mail to the author, 9 April 2014.

31

.  Lengyel (2012).

32

.  Hargittai (2002), p. 140.

33

.  Matthaei and Nirenberg (1961b), p. 1587. One of the controls later caused much confusion: to show that acidity was not involved in the DNase effect, they added several compounds, including polyadenylic acid, none of which affected protein synthesis. Polyadenylic acid is better known as poly(A); this ‘negative control’ later led some competitors to unfairly cast doubt on whether they had intended to get an effect with poly(U). See Kay (2000), pp. 249–50; Rheinberger (1997), p. 210.

34

.  Nirenberg and Matthaei (1961), p. 1601.

35

.  When interviewed by Judson in the 1970s, Nirenberg seemed unaware of these key papers (Judson, 1996, p. 462).

36

.  Anonymous (1961).

37

.  Anonymous (1961), Morgan (1961), Slater (2003). See also the informal photos of the Congress in the collections of Watson and Brenner, held at Cold Spring Harbor:

http://libgallery.cshl.edu/items/show/51693

and

http://libgallery.cshl.edu/items/show/52212

.

38

.  The manuscript version of this talk, with Nirenberg’s handwritten edits, can be found at

http://profiles.nlm.nih.gov/ps/access/JJBBKB.pdf

. For the published version see Nirenberg and Matthaei (1963).

39

.  Nirenberg (2004) recalled the size of the audience as ‘~35’ (p. 49).

40

.  Hargittai (2002), p. 137.

41

.  Judson (1996), pp. 463–4.

42

.  Watson (2001), p. 265.

43

.  Watson and Berry (2003), p. 76; Crick

(1961), p. 1232; Nirenberg (2004), p. 49.

44

.  Judson (1996), p. 464.

45

.  Interview with Nirenberg by Ruth Harris, 1995–1996.

http://history.nih.gov/archives/downloads/Nirenberg%200ral%20history%20Chap%203a-%20%20Recognition%20Moscow,%20MIT.pdf

46

.  Judson (1996), p. 464.

47

.  Dr Jerry Hurwitz, e-mail to the author, 9 April 2014.

48

.  Varmus (2009), p. 24.

49

.  Letter from Lengyel to Ochoa, 19 August 1961, in Supplemental Material, Lengyel (2012).

50

.  Hurwitz recalled, ‘I was impressed with the data presented by Nirenberg in Moscow but puzzled by the properties of the product (which were due to my own lack of information)’ (e-mail to the author, 9 April 2014).

51

.  Judson (1996), p. 464.

52

.  Lipmann to Crick, 27 November 1961.

http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/SCBBBV

.

53

.  Kay (2000), p. 255.

54

.  Judson (1996), p. 465.

55

.  Judson (1996), pp. 464–5.

56

.  Stent (1971) described the experiment as follows: ‘One day, Nirenberg added artificially synthesised polyuridylic acid to this reaction mixture instead of natural mRNA and obtained a most surprising result’ (p. 528). See also Brenner (2001), p. 99.

57

.  Woese (1967), p. 53, note 1; Nirenberg (2004), p. 50. According to Woese, Beljanski’s results were ‘uninterpretable’. Nirenberg claims that Tissière had also tried and failed to get poly(A) to work, but Tissière said that although poly(A) was sitting in a freezer in the lab next door, he never thought to use it. He described his lack of initiative as ‘idiotic’ (Judson, 1996, p. 465).

58

.  Zamecnik (2005).

59

.  Nirenberg (2004), p. 50.

60

.  Nirenberg (2004), p. 49.

61

.  Judson (1996), p. 465.

62

.  Ochoa (1980), p. 20. Lengyel (2012), p. 32, uses very similar words.

63

.  Judson (1996), p. 469.

64

.  Nirenberg (2004), p. 49.

65

.  Martin (1984), p. 293.

66

.  Nirenberg (2004), p. 50.

67

.  Transcript of BBC talk ‘Cracking the genetic code’ by Crick, 22 January 1962.

http://profiles.nlm.nih.gov/ps/access/SCBBFX.pdf

.

68

.  Crick

(1961), p. 1229. For an appreciation of this paper, see Yanofsky (2007).

69

.  Judson (1996), p. 467.

70

.  Crick

(1961), p. 1227.

71

.  Crick

(1961), p. 1231.

72

.  Crick

(1961), p. 1232.

73

.  Anonymous (1962), p. 19.

74

.  Transcript of BBC talk ‘Cracking the genetic code’ by Crick, 22 January 1962.

http://profiles.nlm.nih.gov/ps/access/SCBBFX.pdf

.

75

.  Crick (1962), p. 16.

1

.  In chronological order: Lengyel

(1961, 1962), Basilio

(1962), Gardner

(1962), Speyer

(1962a, b), Wahba

(1962, 1963a, 1963b).

2

.  Letter from Tomkins to Nirenberg, 25 October 1961.

http://profiles.nlm.nih.gov/ps/access/JJBCBB.pdf

.

3

.  Lengyel

(1961), p. 1941.

4

.  Martin

(1961).

5

.  Lengyel (2012), p. 35.

6

.

31 December 1961. According to the paper, Crick was ‘leader of the Cambridge team which discovered code’, while Ochoa’s colleague Speyer was ‘a British biologist’.

7

.  ‘I have stressed that it is your discovery which was the real breakthrough.’ Crick to Nirenberg, 4 January 1962.

http://profiles.nlm.nih.gov/ps/access/JJBBFL.pdf

.

8

.  Nirenberg to Crick, 15 January 1962.

http://profiles.nlm.nih.gov/ps/access/JJBBFJ.pdf

.

9

.  Speyer

(1962a, b).

10

.  When each batch of these synthetic RNAs was created, the nucleotides were assembled in a different, random way, producing slightly different molecular sequences, and making it difficult to compare studies that claimed to be looking at the same nucleotide ratios (Matthaei

1962, p. 671).

11

.  Martin

(1961), Speyer

(1962a, b).

12

.  Crick to Ochoa, 21 September 1962.

http://profiles.nlm.nih.gov/ps/access/SCBBSY.pdf

.

13

.  Speyer

(1962b), p. 443.

14

.  Speyer

(1962b), p. 445.

15

.  Matthaei

(1962), p. 674.

16

.  Matthaei

(1962). See also Crick to Nirenberg, 29 January 1962.

http://profiles.nlm.nih.gov/ps/access/JJBBGN.pdf

.

17

.  Crick (1966a), p. 6.

18

.  Eck (1961). See also Jukes (1962, 1963), Lanni (1962), Wall (1962) and Woese (1962).

19

.  Tsugita (1962).

20

.  Crick (1963a), p. 170.

21

.  Ageno (1962).

22

.  Woese (1962).

23

.  Roberts (1962).

24

.  Eck (1963).

25

.  Zubay and Quastler (1962).

26

.  Golomb (1962b).

27

.  Bretscher and Grunberg-Manago (1962), Gardner

(1962).

28

.  Gardner

(1962).

29

.  Chantrenne (1963), p. 30.

30

.  Couffignal (1965), p. 182.

31

.  Couffignal (1965), p. 78.

32

.  Chantrenne (1963), p. 27. The term was also used at the meeting by André Lwoff (Couffignal, 1965, p. 176).

33

.  Ochoa (1964), pp. 4, 3.

34

.  Tatum (1963), p. 175.

35

.  Vogel

(1963), p. 517.

36

.  Nirenberg and Jones (1963), p. 461.

37

.  Vogel

(1963), p. 503.

38

.  Vogel

(1963), pp. 517–18.

39

.  Crick (1963a), pp. 177, 180.

40

.  Crick (1963a), p. 182.

41

.  Crick (1963a), p. 212. The original draft of the article contains some even sharper formulations (

http://libgallery.cshl.edu/items/show/52223

). Crick wrote to Ochoa apologising for criticising his work ‘in certain ways’ (Crick to Ochoa, 21 September 1962;

http://profiles.nlm.nih.gov/ps/access/SCBBSY.pdf

). A few months later Crick published a less combative version of these arguments in

but repeated his crushing statement that the experimental evidence for establishing a codon ‘falls short of proof in almost all cases’ (Crick, 1963b, p. 463).