Emile Zuckerkandl, Linus Pauling, and the Molecular Evolutionary Clock, 1959-1965

Journal of the History of Biology

Volumn 31, Issue 2, 1998, Pages 155-178

  Morgan, Gregory J ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; EUROPE; EVOLUTION; HISTORY; MOLECULAR BIOLOGY; UNITED STATES;

EUROPE; EVOLUTION; HISTORY, 20TH CENTURY; MOLECULAR BIOLOGY; UNITED STATES;

EID: 0032084980     PISSN: 00225010     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1004394418084     Document Type: Article

References (152)

1. Emile Zuckerkandl and Linus Pauling, "Evolutionary Divergence and Convergence in Proteins," in Vernon Bryson and Henry Vogel, eds., Evolving Genes and Proteins (New York: Academic Press, 1965), pp. 97-166. The molecular evolutionary clock is not a "metronomic" clock; rather, it "ticks" are stochastic events.
2. A. Wilson, S. Carlson, and T. White, "Biochemical Evolution," Ann. Rev. Biochem. 46 (1977), 573-639.
3. Roger Lewin, Patterns in Evolution: The New Molecular View (New York: Freeman, 1997), p. 107.
4. Francis Crick, "The Impact of Linus Pauling on Molecular Biology," in The Pauling Symposium: A Discourse in the Art of Biography, ed. Ramesh Krishnamurthy (Corvallis: Special Collections, Oregon State University, 1996), p. 17.
5. Simon Easteal, Chris Collet, and David Betty, The Mammalian Molecular Clock (Austin: R. G. Lands, 1995), p. 1.
6. Michael R. Dietrich, "The Origins of the Neutral Theory of Molecular Evolution," J. Hist. Biol., 20 (1994), 21-59; Edna Suárez and Ana Barahona, "The Experimental Roots of the Neutral Theory of Molecular Evolution," Hist. Phil. Life Sci., 18 (1996), 55-81. See also Motoo Kimura, The Neutral Theory of Molecular Evolution (Cambridge: Cambridge University Press, 1983), p. 23; Motoo Kimura, "The Rate of Molecular Evolution Considered from the Standpoint of Population Genetics," Proc. Nat. Acad. Sci., 63 (1969), 1181-1188; and Motoo Kimura, "The Molecular Evolutionary Clock and the Neutral Theory," J. Mol. Evol., 26 (1987), 24-33.
7. Michael R. Dietrich, "The Origins of the Neutral Theory of Molecular Evolution," J. Hist. Biol., 20 (1994), 21-59; Edna Suárez and Ana Barahona, "The Experimental Roots of the Neutral Theory of Molecular Evolution," Hist. Phil. Life Sci., 18 (1996), 55-81. See also Motoo Kimura, The Neutral Theory of Molecular Evolution (Cambridge: Cambridge University Press, 1983), p. 23; Motoo Kimura, "The Rate of Molecular Evolution Considered from the Standpoint of Population Genetics," Proc. Nat. Acad. Sci., 63 (1969), 1181-1188; and Motoo Kimura, "The Molecular Evolutionary Clock and the Neutral Theory," J. Mol. Evol., 26 (1987), 24-33.
8. Michael R. Dietrich, "The Origins of the Neutral Theory of Molecular Evolution," J. Hist. Biol., 20 (1994), 21-59; Edna Suárez and Ana Barahona, "The Experimental Roots of the Neutral Theory of Molecular Evolution," Hist. Phil. Life Sci., 18 (1996), 55-81. See also Motoo Kimura, The Neutral Theory of Molecular Evolution (Cambridge: Cambridge University Press, 1983), p. 23; Motoo Kimura, "The Rate of Molecular Evolution Considered from the Standpoint of Population Genetics," Proc. Nat. Acad. Sci., 63 (1969), 1181-1188; and Motoo Kimura, "The Molecular Evolutionary Clock and the Neutral Theory," J. Mol. Evol., 26 (1987), 24-33.
9. Michael R. Dietrich, "The Origins of the Neutral Theory of Molecular Evolution," J. Hist. Biol., 20 (1994), 21-59; Edna Suárez and Ana Barahona, "The Experimental Roots of the Neutral Theory of Molecular Evolution," Hist. Phil. Life Sci., 18 (1996), 55-81. See also Motoo Kimura, The Neutral Theory of Molecular Evolution (Cambridge: Cambridge University Press, 1983), p. 23; Motoo Kimura, "The Rate of Molecular Evolution Considered from the Standpoint of Population Genetics," Proc. Nat. Acad. Sci., 63 (1969), 1181-1188; and Motoo Kimura, "The Molecular Evolutionary Clock and the Neutral Theory," J. Mol. Evol., 26 (1987), 24-33.
10. Michael R. Dietrich, "The Origins of the Neutral Theory of Molecular Evolution," J. Hist. Biol., 20 (1994), 21-59; Edna Suárez and Ana Barahona, "The Experimental Roots of the Neutral Theory of Molecular Evolution," Hist. Phil. Life Sci., 18 (1996), 55-81. See also Motoo Kimura, The Neutral Theory of Molecular Evolution (Cambridge: Cambridge University Press, 1983), p. 23; Motoo Kimura, "The Rate of Molecular Evolution Considered from the Standpoint of Population Genetics," Proc. Nat. Acad. Sci., 63 (1969), 1181-1188; and Motoo Kimura, "The Molecular Evolutionary Clock and the Neutral Theory," J. Mol. Evol., 26 (1987), 24-33.
11. According to the bibliographic search engine Medline more than fifty articles over the past four years discuss the evolutionary molecular clock. See also John Gillespie, The Causes of Molecular Evolution (Oxford: Oxford University Press, 1991).
12. Emile Zuckerkandl, "Around the Molecular Clock: Aspects of Molecular Evolution" (ca. 1986, unpublished), p. 2; Easteal et al., The Mammalian Molecular Clock (above, n. 5) devotes a chapter to the relationship between the clock and the neutral theory.
13. Emile Zuckerkandl, "Around the Molecular Clock: Aspects of Molecular Evolution" (ca. 1986, unpublished), p. 2; Easteal et al., The Mammalian Molecular Clock (above, n. 5) devotes a chapter to the relationship between the clock and the neutral theory.
14. This point is made in Hager's biography but not developed at any length. Thomas Hager, Force of Nature: The Life of Linus Pauling (New York: Simon & Schuster, 1995), p. 541.
15. See Ave Helen and Linus Pauling Papers, Oregon State University (hereinafter OSU), box 160, folder 1, for Pauling's travel plans.
16. Lily Kay, The Molecular Vision of Life: Cal Tech, the Rockefeller Foundation and the Rise of the New Biology (New York: Oxford University Press, 1993).
17. See Linus Pauling and D. Coryell, "The Magnetic Properties Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin," Proc. Nat. Acad. Sci. USA, 22 (1936), 159-163; and Linus Pauling, "The Magnetic Properties and Structure of Hemoglobin and Related Substances," Science, 83 (1936), 488. For their motivation, see Robert Olby, "'The Mad Pursuit': X-Ray Crystallographers' Search for the Structure of Haemoglobin," Hist. Phil. Life Sci., 7 (1985), 171-193, especially p. 181.
18. See Linus Pauling and D. Coryell, "The Magnetic Properties Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin," Proc. Nat. Acad. Sci. USA, 22 (1936), 159-163; and Linus Pauling, "The Magnetic Properties and Structure of Hemoglobin and Related Substances," Science, 83 (1936), 488. For their motivation, see Robert Olby, "'The Mad Pursuit': X-Ray Crystallographers' Search for the Structure of Haemoglobin," Hist. Phil. Life Sci., 7 (1985), 171-193, especially p. 181.
19. See Linus Pauling and D. Coryell, "The Magnetic Properties Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin," Proc. Nat. Acad. Sci. USA, 22 (1936), 159-163; and Linus Pauling, "The Magnetic Properties and Structure of Hemoglobin and Related Substances," Science, 83 (1936), 488. For their motivation, see Robert Olby, "'The Mad Pursuit': X-Ray Crystallographers' Search for the Structure of Haemoglobin," Hist. Phil. Life Sci., 7 (1985), 171-193, especially p. 181.
20. Linus Pauling et al., "Sickle Cell Anemia, a Molecular Disease," Science, 109 (1949), 443. But see also Linus Pauling et al., "Sickle Cell Anemia Hemoglobin," Science, 111 (1950), 459. To Pauling's knowledge, the 1949 paper was the first use of the term "molecular disease." Letter from Linus Pauling to Richard Sasuly, 16 October 1961, OSU, box 128, folder 1.
21. Linus Pauling et al., "Sickle Cell Anemia, a Molecular Disease," Science, 109 (1949), 443. But see also Linus Pauling et al., "Sickle Cell Anemia Hemoglobin," Science, 111 (1950), 459. To Pauling's knowledge, the 1949 paper was the first use of the term "molecular disease." Letter from Linus Pauling to Richard Sasuly, 16 October 1961, OSU, box 128, folder 1.
22. See Pauling's Research Book 17, OSU, pp. 110-111.
23. H. Rhinesmith, Walter Schroeder, and Linus Pauling, "A Quantitative Study of the Hydrolysis of Human Dinitrophenyl (DNP) Globin: The Number and Kind of Polypeptide Chains in Normal Adult Hemoglobin," J. Amer. Chem. Soc. 79 (1957), 4682-4686.
24. Hager, Force of Nature (above, n. 9), p. 236; Pauling, "Fifty Years of Progress in Structural Chemistry and Molecular Biology," Daedalus, 99 (1970), 998-1014, on p. 1005. I thank Tom Hager for pointing this out to me. Pauling's personal copy of the first edition of The Specificity of Serological Reactions contains many margin notes throughout the book.
25. Hager, Force of Nature (above, n. 9), p. 236; Pauling, "Fifty Years of Progress in Structural Chemistry and Molecular Biology," Daedalus, 99 (1970), 998-1014, on p. 1005. I thank Tom Hager for pointing this out to me. Pauling's personal copy of the first edition of The Specificity of Serological Reactions contains many margin notes throughout the book.
26. Linus Pauling, "The Harrison Howe Lecture: Analogies between Antibodies and Simpler Chemical Substances," Chem. Eng. News, 24 (1964), p. 1064, quoted in R. J. Paradowski, "The Structural Chemistry of Linus Pauling" Ph. D. diss., University of Wisconsin, 1972, p. 87.
27. Linus Pauling, "The Harrison Howe Lecture: Analogies between Antibodies and Simpler Chemical Substances," Chem. Eng. News, 24 (1964), p. 1064, quoted in R. J. Paradowski, "The Structural Chemistry of Linus Pauling" Ph. D. diss., University of Wisconsin, 1972, p. 87.
28. K. Landsteiner, The Specificity of Serological Reactions Springfield, Illinois: (Charles Thomas, 1936). E. T. Reichert and A. P. Brown, "The Differentiation and Specificity of Corresponding Proteins and other Vital Substances in Relation to Biological Classification and Organic Evolution" Carnegie Institute Washington (1909), 116. Incidentally, the revised edition of Landsteiner's book included an introductory chapter by Pauling.
29. K. Landsteiner, The Specificity of Serological Reactions Springfield, Illinois: (Charles Thomas, 1936). E. T. Reichert and A. P. Brown, "The Differentiation and Specificity of Corresponding Proteins and other Vital Substances in Relation to Biological Classification and Organic Evolution" Carnegie Institute Washington (1909), 116. Incidentally, the revised edition of Landsteiner's book included an introductory chapter by Pauling.
30. Hager interview. This was contrasted with the more typical utilitarian formulation of maximization of human happiness. Happiness, Pauling thought, was too subjective and difficult to measure, unlike suffering, which, it was hoped could be given a scientific basis.
31. Paradowski, "The Structural Chemistry of Linus Pauling" (above, n. 17), p. 107.
32. I am expanding upon a point made by Hager, Force of Nature (above, n. 9), p. 541.
33. Ibid., p. 461.
34. Letter from Linus Pauling to Willard Libby, 30 March 1955, OSU, box 64, folder 1. See also Alfred Sturtevant, "Social Implications of the Genetics of Man," Science, 120 (1954), 52-53.
35. Robert Divine, Blowing in the Wind: The Nuclear Test Ban Debate, 1954-1960 (New York: Oxford University Press, 1978), p. 182.
36. Edward Teller; transcript of KQED debate, p. 14, OSU, box 1958a, folder 4. A similar statement made in 1962 is quoted by S. Blumberg and G. Owens, Energy and Conflict: The Life and Times of Edward Teller (New York: G.P. Putnam's Sons, 1976), p. 411.
37. Linus Pauling, No More War! (New York: Dodd, Mead, 1958), p. 53; See also Linus Pauling, "Genetic and Somatic Effects of Carbon-14," Science, 128 (1958), 1183-1186.
38. Linus Pauling, No More War! (New York: Dodd, Mead, 1958), p. 53; See also Linus Pauling, "Genetic and Somatic Effects of Carbon-14," Science, 128 (1958), 1183-1186.
39. Letter from Linus Pauling to Willard Libby, 5 March 1958, OSU, box 64, folder 1; Hager, Force of Nature (above, n. 9), pp. 485-486.
40. Hager, personal communication, July 1996.
41. Pauling's small black notebook, undated, OSU safe; Interoffice memo from Bea to Joan, OSU, box 186, folder 5.
42. Letter from Linus Pauling to Willam Libby, 10 May 1957; Letter from William Libby to Linus Pauling, 17 May 1957; Comments on book, from E. B. Lewis to Linus Pauling, undated, OSU, box 411, folder 15.
43. It is perhaps significant that Pauling ordered George Gaylord Simpson's The Meaning of Evolution and his Behavior and Evolution, as well as Charles Darwin's On the Origin of Species in February 1959. Book Orders, OSU, box 187, folder 11. It is also significant that when asked to write an article for Scientific American on the role of mutation in evolution, Pauling replied that Dobzhansky, L. C. Dunn, or J. B. S. Haldane would be better because he was not a "competent geneticist." Letter from R. H. Kent to Linus Pauling, 7 February 1959, OSU box 59, folder 3; Letter from Linus Pauling to R. H. Kent, 11 February 1959, OSU, box 59, folder 3.
44. Memo from Linus Pauling to Prof. Swift, 2 March 1959, OSU, box 153, folder 5.
45. Interview with Emile Zuckerkandl, July 24, 1996 (hereafter Zuckerkandl interview).
46. Vernon M. Ingram, "Abnormal Human Haemoglobins: The Comparison of Normal Human and Sickle Cell Haemoglobins by Finger Printing," Biochim. et Biophys. Acta, 28 (1958), 539.
47. Interview with Richard T. Jones, July 26, 1996, (hereafter Jones interview); Chemistry and Chemical Engineering Division, "Chemical Structure Studies of Animal Hemoglobins," Chemistry and Chemical Engineering Divisional Report (Pasadena: California Institute of Technology, 1959-1960), p. 82, stored at the Cal Tech Archives.
48. Jones interview.
49. Recommendation for Richard Jones, 3 January 1958, OSU, box 56, folder 23.
50. Biochemists now believe that the minor components are glycosylated forms of hemoglobin.
51. Jones interview.
52. Zuckerkandl interview.
53. Emile Zuckerkandl, Richard T. Hones, and Linus Pauling, "A Comparison Animal Hemoglobins by Tryptic Peptide Pattern Analysis," Proc. Nat. Acad. Sci. 46 (1960), 1349-1360. Italics mine.
54. Jones interview. Incidentally, Pauling had a "high opinion" of Braunitzer's work, although he met him only once. Letter from Linus Pauling to W. Grassman, 26 November 1963, OSU, box 42, folder 7.
55. Zuckerkandl, "On the Molecular Evolutionary Clock," J. Mol. Evol, 26 (1987), 34-46, see p. 35. This homology was independently hypothesized first by Itano in 1957 and later by Ingram in 1961: Harvey A. Itano, "The Human Hemoglobins: Their Properties and Genetic Control," Adv. Protein Chem., 12 (1957), 215-268; Vernon Ingram, "Gene Evolution and the Haemoglobins," Nature 139 (1961), 704-708.
56. Zuckerkandl, "On the Molecular Evolutionary Clock," J. Mol. Evol, 26 (1987), 34-46, see p. 35. This homology was independently hypothesized first by Itano in 1957 and later by Ingram in 1961: Harvey A. Itano, "The Human Hemoglobins: Their Properties and Genetic Control," Adv. Protein Chem., 12 (1957), 215-268; Vernon Ingram, "Gene Evolution and the Haemoglobins," Nature 139 (1961), 704-708.
57. Zuckerkandl, "On the Molecular Evolutionary Clock," J. Mol. Evol, 26 (1987), 34-46, see p. 35. This homology was independently hypothesized first by Itano in 1957 and later by Ingram in 1961: Harvey A. Itano, "The Human Hemoglobins: Their Properties and Genetic Control," Adv. Protein Chem., 12 (1957), 215-268; Vernon Ingram, "Gene Evolution and the Haemoglobins," Nature 139 (1961), 704-708.
58. Emile Zuckerkandl, personal communication, 30 October 1996.
59. Chemistry and Chemical Engineering Division, "Investigation of the Amino Acid Sequences of Gorilla Hemoglobin," Chemistry and Chemical Engineering Divisional Report (Pasadena: California Institute of Technology, 1961-1962), p. 94, stored at the Cal Tech Archives.
60. Interoffice memo from Linus Pauling to Dr. Walter Schroeder, 20 January 1961, OSU, box 153, folder 3.
61. Emile Zuckerkandl and Walter A. Schroeder, "Amino-Acid Composition of the Polypeptide Chains of Gorilla Hemoglobin," Nature, 192 (1961), 984-985, see p. 985. It was later found that the gorilla and human α-chain actually differed by only one residue.
62. Letter from Linus Pauling to Dr. Bernard Pullman, 22 November 1960. OSU, box 1962a, folder 2. Szent-Györgyi was an active promoter of Pauling for the Nobel Prize in Chemistry in 1953. See the correspondence beginning with the letter from Szent-Györgyi to Linus Pauling, 8 November 1952, OSU, box 118, folder 1.
63. Letter from Linus Pauling to Dr. Bernard Pullman, 22 June 1961. OSU, box 1962a, folder 2.
64. Zuckerkandl interview.
65. Letter from Linus Pauling to Dr. Herbert York, 15 September 1962: ". . . I enclose a paper by [Zuckerkandl] and me - mainly written by him; Zuckerkandl interview: "I essentially wrote it ["Molecular Disease, Evolution, and Genic Heterogeneity"]." Note also that Zuckerkandl has first authorship.
66. Zuckerkandl interview. I pursue this further below.
67. Interoffice memo from Pauling to Zuckerkandl, 24 October 1961, OSU box 153, folder 3; letter, Pauling to Academic Publishers, 1 November 1961, OSU box, 1962a, folder 2.
68. Zuckerkandl interview.
69. Emile Zuckerkandl and Linus Pauling, "Molecular Disease, Evolution and Genic Heterogeneity," in Horizons in Biochemistry: Albert Szent-Györgyi Dedicatory Volume ed. Michael Kasha and Bernard Pullman (New York: Academic Press, 1962), pp. 189-225, see p. 198.
70. Ibid., p. 201.
71. Ibid. Note that when the correction value of one substitution difference between gorilla enchain and human α-chain is taken into account, the divergence time from the common ancestor of gorilla-α and human-α is 7.3 million years.
72. Ibid.
73. Ibid., p. 202. Eleven million years as an estimate of the human-gorilla divergence is on the lower side of the range estimated by anthropologists at the time.
74. Zuckerkandl and Pauling deal with the problems of accounting for back mutations, "minor" components of hemoglobin, change from an aquatic to a terrestrial environment, and changing population sizes. They conclude that their estimates are probably underestimates. Zuckerkandl and Pauling, "Molecular Disease, Evolution and Genic Heterogeneity" (above, n. 55), pp. 203-204.
75. Easteal et al., The Mammalian Molecular Clock (above, n. 5), p. 9.
76. As Lindley Darden pointed out to me, Easteal et al., The Mammalian Molecular Clock (above, n. 5), appear to conflate discovery and justification.
77. Linus Pauling, "Fifty Years of Progress" (above, n. 16), p. 1014. More specifically, regarding the paternity of the molecular clock Pauling writes, "I think it was my idea, but I am not sure. We were just collaborating on these studies. Perhaps it was Emile's idea." Linus Pauling, "An Extraordinary Life: An Autobiographical Ramble." in Creativity: Paradoxes and Reflections. ed. Harry A. Wilmer (Wilmette, Ill: Chiron Publications, 1991), pp. 69-85, p. 74.
78. Linus Pauling, "Fifty Years of Progress" (above, n. 16), p. 1014. More specifically, regarding the paternity of the molecular clock Pauling writes, "I think it was my idea, but I am not sure. We were just collaborating on these studies. Perhaps it was Emile's idea." Linus Pauling, "An Extraordinary Life: An Autobiographical Ramble." in Creativity: Paradoxes and Reflections. ed. Harry A. Wilmer (Wilmette, Ill: Chiron Publications, 1991), pp. 69-85, p. 74.
79. Zuckerkandl and Pauling, "Molecular Disease, Evolution and Genic Heterogeneity" (above, n. 55), p. 203.
80. Ibid., p. 204, italics mine.
81. Ibid., p. 209. Other than the first application of the clock concept, the paper is novel in introducing the notion of a dormant gene, the conceptual precursor to what are now called pseudogenes.
82. Zuckerkandl interview.
83. Ibid.
84. Ibid.
85. Linus Pauling, "The Molecular Basis of Genetic Defects" (typescript, 1962), p. 14, OSU, box 1962a, folder 1. This speech was published in International Medical Congress, First Inter-American Conference on Congenital Defects (Philadelphia: Lippincott, 1963), pp. 15-21. For Pauling's correspondence regarding this conference, see OSU, box 164, folder 3.
86. Linus Pauling, "The Molecular Basis of Genetic Defects" (typescript, 1962), p. 14, OSU, box 1962a, folder 1. This speech was published in International Medical Congress, First Inter-American Conference on Congenital Defects (Philadelphia: Lippincott, 1963), pp. 15-21. For Pauling's correspondence regarding this conference, see OSU, box 164, folder 3.
87. Date book 1962, OSU.
88. Itineraries: July 1961-July 1963, OSU, box 164, folder 1. Incidentally, these lectures were performed under "rather tense" conditions partly due to Pauling's disapproval of Kennedy's actions during "the Cuban Situation." Letter from William White to Linus Pauling, 7 November 1962; letter from A. B Garrett to Linus Pauling, 8 November 1962, OSU, box 164, folder 12.
89. Itineraries: July 1961-July 1963, OSU, box 164, folder 1; letter from William Grum to Linus Pauling, 12 March 1963, box 78, folder 5.
90. Date book entry for 6 June 1963, OSU. Pauling notes that there were fifty people picketing against him outside. See also OSU, box 164, folder 1.
91. Date book 1963, OSU.
92. OSU, box 164, folder 16. Pauling literally takes the speech "Molecular Disease and Evolution," makes some minor stylistic changes, and retitles it "Abnormal Hemoglobin and Molecular Disease." This "new" speech was given at Congreso del Centenario de la Academia Nacional de Medicina, in Mexico on May 3, 1964. See also letter from Edward Pols to Linus Pauling 15 October 1963, OSU, computer search.
93. Letter from Linus Pauling to Tanya Menci, 29 November 1966, OSU, computer search.
94. Letter from Linus Pauling to R. S. Ramakrishna; letter, Linus Pauling to V. K. Gokak, OSU, box 164, folder 18.
95. OSU, box 1962s; this speech was printed as Linus Pauling, "Molecular Disease and Evolution," Proc. Rudolf Med. Soc. N.Y., 21 (1963), 131-140. It was reprinted in Karger Gazette, Basel/New York 7/8, 3-4, and Bulletin N. Y. Acad. Med., 40 (1964) 334-342.
96. OSU, box 1962s; this speech was printed as Linus Pauling, "Molecular Disease and Evolution," Proc. Rudolf Med. Soc. N.Y., 21 (1963), 131-140. It was reprinted in Karger Gazette, Basel/New York 7/8, 3-4, and Bulletin N. Y. Acad. Med., 40 (1964) 334-342.
97. OSU, box 1962s; this speech was printed as Linus Pauling, "Molecular Disease and Evolution," Proc. Rudolf Med. Soc. N.Y., 21 (1963), 131-140. It was reprinted in Karger Gazette, Basel/New York 7/8, 3-4, and Bulletin N. Y. Acad. Med., 40 (1964) 334-342.
98. Letter from Vernon Ingram to Linus Pauling, 16 February 1962. OSU, box 164, folder 12; Pauling's date book entry for 6 November 1962: "to Arden House (50 mins out) V. Ingram, I participate - opening address Hb conf." The proceedings of this conference were not published.
99. Alexander Rich, quoted in Hager, Force of Nature (above, n. 9), p. 541; Tom Hager, personal communication, July 1996.
100. Alexander Rich, quoted in Hager, Force of Nature (above, n. 9), p. 541; Tom Hager, personal communication, July 1996.
101. Zuckerkandl interview.
102. Ibid.
103. Linus Pauling and Emile Zuckerkandl, "Chemical Paleogenetics Molecular 'Restoration Studies' of Extinct Forms of Life," Acta Chem. Scand., 17 (1963), S9-S16.
104. With current synthesizing technology, researchers are beginning to synthesize postualed ancestral sequences to determine their biochemical properties. This possibility was first suggested by Pauling and Zuckerkandl in this article (p. S15).
105. Letter from Emile Zuckerkandl to Linus Pauling, 25 March 1963, OSU, box 1963a, folder 1; Pauling and Zuckerkandl, "Chemical Paleogenetics" (above, n. 84), p. S16; Zuckerkandl interview.
106. Letter from Linus Pauling to W. L. Kretovich, OSU, box 1963a, folder 3.
107. Interoffice memo from Linus Pauling to Emile Zuckerkandl, OSU, box 1963a, folder 3.
108. The article was published in English as Emile Zuckerkandl and Linus Pauling, "Molecules as Documents of Evolutionary History," J. Theoret. Biol., 8 (1965), 357-366.
109. The article is a very explicit use of the "metaphor" that semantides contain information and hence have some form of meaning.
110. Zuckerkandl interview. The original reason for Lederberg's inviting Zuckerkandl to Stanford was to discuss possible potential forms of life on Mars. For the particular genetic code Zuckerkandl considered, see R. V. Eck, "Genetic Code: Emergence of a Symmetrical Pattern," Science, 140 (1963), 477-481. Joshua Lederberg does not recall the details of their discussions (Lederberg, personal communication, April 1997).
111. Zuckerkandl interview. The original reason for Lederberg's inviting Zuckerkandl to Stanford was to discuss possible potential forms of life on Mars. For the particular genetic code Zuckerkandl considered, see R. V. Eck, "Genetic Code: Emergence of a Symmetrical Pattern," Science, 140 (1963), 477-481. Joshua Lederberg does not recall the details of their discussions (Lederberg, personal communication, April 1997).
112. Thomas Jukes, "Some Recent Advances in Studies of the Transcription of the Genetic Message," Adv. Biol. Med. Phys., 9 (1963), 1-42; see also Thomas Jukes "Relations between Mutations and Base Sequences in the Amino Acid Code," Proc. Nat. Acad. Sci., 48 (1962), 1809-1815; letter from Emile Zuckerkandl to Linus Pauling, 21 July 1963, OSU, box 153, folder 5; letter from Linus Pauling to Emile Zuckerkandl, 29 July 1963, OSU, box 153, folder 5; letter from Thomas Jukes to Linus Pauling, 13 June 1963, OSU, box 56, folder 28; letter from Zuckerkandl to Linus Pauling, 26 October 1963, OSU, box 153, folder 5.
113. Thomas Jukes, "Some Recent Advances in Studies of the Transcription of the Genetic Message," Adv. Biol. Med. Phys., 9 (1963), 1-42; see also Thomas Jukes "Relations between Mutations and Base Sequences in the Amino Acid Code," Proc. Nat. Acad. Sci., 48 (1962), 1809-1815; letter from Emile Zuckerkandl to Linus Pauling, 21 July 1963, OSU, box 153, folder 5; letter from Linus Pauling to Emile Zuckerkandl, 29 July 1963, OSU, box 153, folder 5; letter from Thomas Jukes to Linus Pauling, 13 June 1963, OSU, box 56, folder 28; letter from Zuckerkandl to Linus Pauling, 26 October 1963, OSU, box 153, folder 5.
114. Hager, Force of Nature (above, n. 9), p. 549.
115. Pauling oversaw this trip. Interoffice memo from Linus Pauling to Emile and Jane Zuckerkandl, 10 September 1963, OSU, box 153, folder 5; letter from Richard Jones to Linus Pauling, 26 November 1962, OSU, box 54, folder 10; Jones interview; for a review of automatic peptide chromatography, see Richard T. Jones, "Automatic Peptide Chromatography," Methods Biochem. Analysis, 18 (1970), 206-251.
116. Emile and Jane Zuckerkandl, Zuckerkandl interview.
117. Emanual Margoliash, "Primary Structure and Evolution of Cytochrome c," Proc. Nat. Acad. Sci., 50 (1963), 672-679.
118. Manuscript, "The Chemical Paleogenetics of Hemoglobin," dated April 64, box 153, folder 5, p. 8.
119. The difference is in part due to a difference in perspective: if one considers the actual number of substitution events, then the function is linear; if one considers the number of observed substitutions, then the function is asymptotic. Although the terminology is a little loose, the 1962 paper implicitly assumes the latter as an estimate of the former.
120. If one focuses on observable substitutions, then this number will always be equal to or less than the number of actual changes.
121. Emile Zuckerkandl, "Further Principles of Chemical Paleogenetics as Applied to the Evolution of Hemoglobin," in Protides of the Biological Fluids, ed. Hubert Peeters (Amsterdam: Elsevier, 1964), pp. 102-109. See also the earlier manuscript in OSU, box 153, folder 5. The paper is also significant in that it is Zuckerkandl's first use of the "parsimony principle" to construct the topology of a phylogenetic tree.
122. Manuscript, "The Chemical Paleogenetics of Hemoglobin" (above, n. 97). The table on slide #2 was not included in the published paper.
123. Emile Zuckerkandl, personal communication, 20 July 1996. He, however, saw "living fossils" as a test of the molecular clock hypothesis.
124. The full proceedings were published; see Bryson and Vogel, Evolving Genes and Proteins (above, n. 1). A short summary by Bryson and Vogel was published in Science, 147 (1965), 68-72.
125. The full proceedings were published; see Bryson and Vogel, Evolving Genes and Proteins (above, n. 1). A short summary by Bryson and Vogel was published in Science, 147 (1965), 68-72.
126. Robert Paradowski, "Chronology," in Linus Pauling: A Man of Intellect and Action, ed. Fumikazu Miyazaki (Tokyo, Japan: Cosmos Japan International, 1991), pp. 186-211, see p. 206.
127. It is common for people to mistakenly cite this paper as the origin of the molecular clock concept. For example, Wen-Hsiung Li, "So, What about the Molecular Clock Hypothesis," Curr. Opin. Genet. Devel., 3 (1993), 896-901; Naoyuki Takahata, "Molecular Clock," in Population Genetics, Molecular Evolution and the Neutral Theory: Selected Papers of Motoo Kimura, ed. Naoyuki Takahata (Chicago: University of Chicago Press, 1994), pp. 535-536.
128. It is common for people to mistakenly cite this paper as the origin of the molecular clock concept. For example, Wen-Hsiung Li, "So, What about the Molecular Clock Hypothesis," Curr. Opin. Genet. Devel., 3 (1993), 896-901; Naoyuki Takahata, "Molecular Clock," in Population Genetics, Molecular Evolution and the Neutral Theory: Selected Papers of Motoo Kimura, ed. Naoyuki Takahata (Chicago: University of Chicago Press, 1994), pp. 535-536.
129. I discuss this further in the next section.
130. Manuscript dated September 12, OSU, unsorted; letter from Zuckerkandl to Pauling, 3 [sic] September 1964. The date of this letter is obviously incorrect - the letter reports on the meeting that occurred on September 17 and 18. A similar equation was used by Margoliash and Smith at the conference. Emanual Margoliash and Emil Smith, in Evolving Genes and Proteins (above, n. 103), p. 233.
131. Zuckerkandl interview.
132. Zuckerkandl, personal communication, October 30, 1996.
133. Zuckerkandl and Pauling, "Evolutionary Divergence" (above, n. 1), p. 149.
134. Letter from Zuckerkandl to Pauling, 3 [sic] September 1964 (above, n. 107).
135. Zuckerkandl interview.
136. Emile Zuckerkandl, "Perspectives in Molecular Anthropology," in Classification and Evolution ed. Sherwood Washburn (Chicago: Aldine, 1963), pp. 243-272, see p. 254.
137. Zuckerkandl interview. Incidentally, Goodman sent Pauling some papers on his work in 1961. Letter from Morris Goodman to Linus Pauling, 12 May 1961, OSU. box 42, folder 5.
138. Zuckerkandl, "Perspectives in Molecular Anthropology" (above, n. 113), p. 259.
139. Ibid., p. 268.
140. George Gaylord Simpson, "The Meaning of Taxonomic Statements," in Classification and Evolution, ed. Sherwood Washburn (Chicago: Aldine, 1963), pp. 1-31, see p. 25, italics in original.
141. George Gaylord Simpson, Concession to the Improbable: An Unconventional Autobiography (New Haven: Yale University Press, 1978), p. 217.
142. George Gaylord Simpson, "Organisms and Molecules in Evolution," in Protides of the Biological Fluids, ed. Hubert Peeters (Amsterdam: Elsevier, 1965), pp. 29-35, see p. 31.
143. E. Mayr. "The Taxonomic Evaluation of Early Hominids," Classification and Evolution, ed. Sherwood Washburn (Chicago: Aldine, 1963), pp. 332-346, see p. 344. However, in his book Animal Species and Evolution, Mayr acknowledges the evolutionary work done by Goodman and Pauling; Ernst Mayr, Animal Species and Evolution (Cambridge, Mass.: Harvard University Press, Belknap Press, 1963), p. 628. Pauling annotates this in his copy of the book.
144. E. Mayr. "The Taxonomic Evaluation of Early Hominids," Classification and Evolution, ed. Sherwood Washburn (Chicago: Aldine, 1963), pp. 332-346, see p. 344. However, in his book Animal Species and Evolution, Mayr acknowledges the evolutionary work done by Goodman and Pauling; Ernst Mayr, Animal Species and Evolution (Cambridge, Mass.: Harvard University Press, Belknap Press, 1963), p. 628. Pauling annotates this in his copy of the book.
145. Bryson and Vogel, summary (above, n. 103), p. 68.
146. Ibid.
147. Letter from Zuckerkandl to Pauling, September 3 [sic], 1964 (see above, n. 107).
148. E. Mayr, in "Discussion of Part III," in Evolving Genes and Proteins (above, n. 1), p. 198.
149. Morris Goodman, "On the Emergence of Intraspecific Differences of the Protein Antigens of Human Beings," Amer. Nat., 94 (1960), 77-92; C. A. Williams and C. T. Wemyss, "Experimental and Evolutionary Significance of Similarities among Serum Protein Antigens of Man and the Lower Primates," Ann. N. Y. Acad. Sci., 94 (1961), 77-92.
150. Morris Goodman, "On the Emergence of Intraspecific Differences of the Protein Antigens of Human Beings," Amer. Nat., 94 (1960), 77-92; C. A. Williams and C. T. Wemyss, "Experimental and Evolutionary Significance of Similarities among Serum Protein Antigens of Man and the Lower Primates," Ann. N. Y. Acad. Sci., 94 (1961), 77-92.
151. Letter from Linus Pauling to Robert Gould, 19 October 1959, OSU, box, 1959a, folder 2.
152. See above, n. 6.