Sickle Cell Anemia: Reexamining the First "Molecular Disease"

Bulletin of the History of Medicine

Volumn 71, Issue 4, 1997, Pages 623-650

  Feldman, Simon D ^a   Tauber, Alfred I ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; HISTORY; HUMAN; RESEARCH; SICKLE CELL ANEMIA; UNITED STATES;

ANEMIA, SICKLE CELL; HISTORY, 20TH CENTURY; HUMANS; RESEARCH; UNITED STATES;

EID: 0031297832     PISSN: 00075140     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (126)

1. Linus Pauling, Harvey A. Itano, S. J. Singer, and Ibert C. Wells, "Sickle Cell Anemia, a Molecular Disease," Science, 1949, 110: 543-48.
2. Vernon Ingram, "A Specific Chemical Difference between the Globins of Normal Human and Sickle-Cell Anaemia Haemoglobin," Nature, 1956, 178: 792-94.
3. The term molecular disease was apparently coined by Pauling in the title of his 1949 paper, "Sickle Cell Anemia, a Molecular Disease" (n. 1).
4. Horace Judson, The Eighth Day of Creation: Makers of the Revolution in Biology (New York: Simon and Schuster, 1979); C. Lockard Conley, "Sickle-Cell Anemia - The First Molecular Disease," in Blood, Pure and Eloquent: A Story of Discovery, of People, and of Ideas, ed. Maxwell Wintrobe (New York: McGraw Hill, 1980), pp. 319-71; Maxwell Wintrobe, Hematology: The Blossoming of a Science: A Story of Inspiration and Effort (Philadelphia: Lea and Febiger, 1985); Alan N. Schechter and Griffin P. Rodgers, "Sickle Cell Anemia - Basic Research Reaches the Clinic," New England J. Med., May 1995, 332: 1372-74.
5. Horace Judson, The Eighth Day of Creation: Makers of the Revolution in Biology (New York: Simon and Schuster, 1979); C. Lockard Conley, "Sickle-Cell Anemia - The First Molecular Disease," in Blood, Pure and Eloquent: A Story of Discovery, of People, and of Ideas, ed. Maxwell Wintrobe (New York: McGraw Hill, 1980), pp. 319-71; Maxwell Wintrobe, Hematology: The Blossoming of a Science: A Story of Inspiration and Effort (Philadelphia: Lea and Febiger, 1985); Alan N. Schechter and Griffin P. Rodgers, "Sickle Cell Anemia - Basic Research Reaches the Clinic," New England J. Med., May 1995, 332: 1372-74.
6. Horace Judson, The Eighth Day of Creation: Makers of the Revolution in Biology (New York: Simon and Schuster, 1979); C. Lockard Conley, "Sickle-Cell Anemia - The First Molecular Disease," in Blood, Pure and Eloquent: A Story of Discovery, of People, and of Ideas, ed. Maxwell Wintrobe (New York: McGraw Hill, 1980), pp. 319-71; Maxwell Wintrobe, Hematology: The Blossoming of a Science: A Story of Inspiration and Effort (Philadelphia: Lea and Febiger, 1985); Alan N. Schechter and Griffin P. Rodgers, "Sickle Cell Anemia - Basic Research Reaches the Clinic," New England J. Med., May 1995, 332: 1372-74.
7. Horace Judson, The Eighth Day of Creation: Makers of the Revolution in Biology (New York: Simon and Schuster, 1979); C. Lockard Conley, "Sickle-Cell Anemia - The First Molecular Disease," in Blood, Pure and Eloquent: A Story of Discovery, of People, and of Ideas, ed. Maxwell Wintrobe (New York: McGraw Hill, 1980), pp. 319-71; Maxwell Wintrobe, Hematology: The Blossoming of a Science: A Story of Inspiration and Effort (Philadelphia: Lea and Febiger, 1985); Alan N. Schechter and Griffin P. Rodgers, "Sickle Cell Anemia - Basic Research Reaches the Clinic," New England J. Med., May 1995, 332: 1372-74.
8. Conley, "Sickle-Cell Anemia" (n. 4), p. 339. This is a well-known account. For instance, a recent article in the New England Journal of Medicine begins with this representative assertion: "Fifty years ago this spring, a conversation between an eminent clinical investigator and an extraordinarily imaginative physical chemist led to the insight that introduced the era of molecular medicine" (Griffin and Rodgers, "Sickle Cell Anemia" [n. 4]).
9. Conley, "Sickle-Cell Anemia" (n. 4), p. 339. This is a well-known account. For instance, a recent article in the New England Journal of Medicine begins with this representative assertion: "Fifty years ago this spring, a conversation between an eminent clinical investigator and an extraordinarily imaginative physical chemist led to the insight that introduced the era of molecular medicine" (Griffin and Rodgers, "Sickle Cell Anemia" [n. 4]).
10. Wintrobe, Hematology (n. 4), p. 354.
11. Judson, Eighth Day of Creation (n. 4), p. 301.
12. Conley, "Sickle-Cell Anemia" (n. 4), p. 339.
13. Quoted by Judson, Eighth Day of Creation (n. 4), pp. 301-2 (our emphasis).
14. E. Vernon Hahn and Elizabeth B. Gillespie, "Sickle Cell Anemia: Report of a Case Greatly Improved by Splenectomy. Experimental Study of Sickle Cell Formation," Arch. Intern. Med., 1927, 39: 233-54.
15. H. Horlein and G. Weber, "Über chronische familiäre Methämoglobinämie und eine neue Modifikation des Methämoglobins," Deutsche medizinische Wochenschrift., 1948, 73: 476-78.
16. Marie A. Andersch, Donald A. Wilson, and Maud L. Menten, "Sedimentation Constants and Electrophoretic Mobilities of Adult and Fetal Carbonylhemoglobin," J. Biol. Chem., 1944, 153: 301-5.
17. Wintrobe, Hematology (n. 4), p. 355.
18. James B. Herrick, "Peculiar Elongated Sickle-shaped Red Blood Corpuscles in a Case of Severe Anemia," Arch. Intern. Med., 1910, 6: 517-21, quotation on p. 518.
19. Ibid., p. 519.
20. Ibid., p. 521.
21. Ibid.
22. Conley, "Sickle-Cell Anemia" (n. 4), p. 321.
23. See Keith Wailoo, "'A Disease Sui Generis': The Origins of Sickle Cell Anemia and the Emergence of Modern Clinical Research, 1904-1924," Bull. Hist. Med., 1991, 65: 185-208 (quotation on pp. 186-87), where he notes that "Herrick's clinical style gave primacy to the doctor-patient encounter rather than to the encounter between doctor and laboratory." Wailoo argues that Herrick viewed the function of the research laboratory as fundamentally instrumental and subservient to the proven clinical diagnostic process.
24. Ibid., pp. 192-94.
25. Herrick later studied physical and organic chemistry at the University of Chicago and worked in Emil Fischer's laboratory, which was extremely influential in the study of protein chemistry.
26. B. E. Washburn, "Peculiar Elongated and Sickle-shaped Red Blood Corpuscles in a Case of Severe Anemia," Virginia Med. Semi-Monthly, 1911, 15: 490-93.
27. Jerome E. Cook and Jerome Meyer, "Severe Anemia with Remarkable Elongated and Sickle-shaped Red Blood Cells and Chronic Leg Ulcer," Arch. Intern. Med., 1915, 16: 644-51.
28. Ibid.
29. Ibid., p. 648.
30. Victor E. Emmel, "A Study of the Erythrocytes in a Case of Severe Anemia with Elongated and Sickle-shaped Red Blood Corpuscles," Arch. Intern. Med., 1917, 20: 586-98, quotation on pp. 586-87.
31. Ibid., p. 591.
32. Ibid., p. 593.
33. Ibid., p. 587.
34. Ibid., p. 594.
35. Ibid., p. 595.
36. Ibid., p. 598.
37. Wailoo, "'A Disease Sui Generis'" (n. 19), p. 203.
38. Verne R. Mason, "Sickle Cell Anemia," JAMA, 1922, 79: 1318-20, quotation on p. 1320.
39. Ibid.
40. John G. Huck, "Sickle Cell Anaemia," Johns Hopkins Hosp. Bull., 1923, 34: 335-44.
41. Ibid., p. 338.
42. Ibid., p. 339.
43. Ibid., p. 338.
44. Huck also injected a suspension of washed red blood cells from a patient with severe anemia into four rabbits, but he was unable to produce any symptoms in the animals: ibid., p. 339.
45. Ibid.
46. Virgil P. Sydenstricker, "Sickle Cell Anemia," Southern Med. J., 1924, 17: 177-83.
47. Ibid.
48. Ibid.
49. Laurence Snyder, Medical Genetics (Durham, N.C.: Duke University Press, 1941), p. 96.
50. Hahn and Gillespie, "Sickle Cell Anemia" (n. 10), p. 233.
51. Ibid., p. 253.
52. Ibid., p. 251.
53. George S. Graham and Sarah H. McCarty, "Notes on Sickle Cell Anemia," J. Lab. Clin. Med., 1927, 12: 536-47, quotation on p. 543.
54. Ibid.
55. Ibid.
56. Bernhard Steinberg, "Sickle Cell Anemia," Arch. Path., 1930, 9: 876-97, quotation on p. 885.
57. Lemuel W. Diggs, C. F. Ahmann, and Juanita Bibb, "The Incidence and Significance of the Sickle Cell Trait," Ann. Intern. Med., 1933, 7: 769-78.
58. Ibid.
59. James S. Beck and Charles S. Hertz, "Standardizing Sickle Cell Method and Evidence of Sickle Cell Trait," Amer. J. Clin. Path., 1935, 5: 325-32.
60. Hahn and Gillespie, "Sickle Cell Anemia" (n. 10). p. 242.
61. Ibid., p. 245.
62. Jessie B. Scriver and T. R. Waugh, "Studies on a Case of Sickle-Cell Anaemia," Can. Med. Assoc. J., 1930, 23: 375-80.
63. Ibid., p. 380.
64. E. C. Smith, "Postmortem Report on a Case of Sickle-Cell Anaemia," Trans. Roy. Soc. Trop. Med. Hygiene, 1934, 28: 209-14.
65. Lemuel W. Diggs and R. E. Ching, "Pathology of Sickle Cell Anemia," Southern Med. J., 1934, 27: 839-45, quotation on p. 840.
66. Ibid.
67. I. J. Sherman, "The Sickling Phenomenon, with Special Reference to the Differentiation of Sickle Cell Anemia from Sickle Cell Trait," Bull. Johns Hopkins Hosp., 1940, 67: 309-24, quotations on p. 322.
68. Ibid., p. 322.
69. T. Hale Ham and William B. Castle, "Relation of Increased Hypotonic Fragility and of Erythrostasis to the Mechanism of Hemolysis in Certain Anemias," Trans. Assoc. Amer. Physicians, 1940, 55: 127-32, quotation on p. 131.
70. Hahn and Gillespie, "Sickle Cell Anemia" (n. 10).
71. J. Barcroft and A. V. Hill, "The Nature of Oxyhaemoglobin, with a Note on Its Molecular Weight," J. Physiol., 1910, 39: 411-28, quotation on p. 411.
72. James V. Neel, "The Clinical Detection of the Genetic Carriers of Inherited Disease," Medicine, 1947, 26: 115-53.
73. James V. Neel, "The Inheritance of Sickle Cell Anemia," Science, 1949, 110: 64-66; Pauling et al., "Sickle Cell Anemia" (n. 1).
74. James V. Neel, "The Inheritance of Sickle Cell Anemia," Science, 1949, 110: 64-66; Pauling et al., "Sickle Cell Anemia" (n. 1).
75. Neel, "Inheritance of Sickle Cell Anemia" (n. 69), p. 64.
76. Conley, "Sickle-Cell Anemia" (n. 4), p. 326.
77. Jan Sapp, Where the Truth Lies: Franz Moewus and the Origins of Molecular Biology (New York: Cambridge University Press, 1990), p. 41.
78. Joseph Fruton, Molecules and Life: Historical Essays on the Interplay of Chemistry and Biology (New York: Wiley, 1972), pp. 239-46; Sapp, Where the Truth Lies (n. 72), p. 43.
79. Joseph Fruton, Molecules and Life: Historical Essays on the Interplay of Chemistry and Biology (New York: Wiley, 1972), pp. 239-46; Sapp, Where the Truth Lies (n. 72), p. 43.
80. See Robert Olby, The Path to the Double Helix (Seattle: University of Washington Press, 1974), esp. chap. 9, "The Enzyme Theory of Life," and chap. 10, "The Chemistry of Virus- Genes."
81. See Robert Olby, The Path to the Double Helix (Seattle: University of Washington Press, 1974), esp. chap. 9, "The Enzyme Theory of Life," and chap. 10, "The Chemistry of Virus- Genes."
82. See Robert Olby, The Path to the Double Helix (Seattle: University of Washington Press, 1974), esp. chap. 9, "The Enzyme Theory of Life," and chap. 10, "The Chemistry of Virus-Genes."
83. Lily Kay, The Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the New Biology (New York: Oxford University Press, 1993), p. 109. See also Fruton, Molecules and Life (n. 73), p. 240.
84. Lily Kay, The Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the New Biology (New York: Oxford University Press, 1993), p. 109. See also Fruton, Molecules and Life (n. 73), p. 240.
85. German biologist Richard Goldschmidt, taken with the autocatalytic theory, drew the most extreme conclusion, arguing specifically that if genes had material stibstance, they were enzymes. In 1917 the Harvard biologist Leonard T. Troland developed this notion into an ambitious (if not wholly substantiated) theory. In the tradition of Jacques Loeb, these scientists shared a materialist, reductive philosophy that sought to explain reproduction in physicochemical terms. The beauty of autocatalytic theory was that it offered the promise of just such a solution.
86. It was later demonstrated that Stanley's crystals were not "pure" but contained traces of nucleic acid. For a full contextualization of Stanley's celebrated viral work at the Rockefeller Institute, see Lily Kay, "W. M. Stanley's Crystallization of the Tobacco Mosaic Virus, 1930-1940," Isis, 1986, 77: 450-72.
87. Kay, Molecular Vision of Life (n. 75), p. 111.
88. The crystallization of proteins proved vital to the progress of peptide theory in these years. Crystallization became an invaluable tool for the assessment of the molecular weight of proteins and the identification of molecular structure. Although the crystallization of hemoglobin had been observed as early as 1830 (K. H. Baumgaertner, Beobachtungen uber die Nerven und das Blut in ihren gesunden und Krankhaften Zustande, Freiburg, 1830), proteins were not considered crystallizable until about 1900. Indeed, one characteristic of proteins - in contrast to colloids - was that they did not exhibit this property. Thus, work with protein crystals was noteworthy in the progress of protein research - and hemoglobin was the subject of many of these early studies. By 1925, improved techniques allowed Gilbert Adair to report an essentially accurate molecular weight of 67,000 for hemoglobin: Gilbert S. Adair, "The Osmotic Pressure of Haemoglobin in the Absence of Salts," Proc. Roy. Soc. London, ser. A, 1925, 109: 293.
89. The crystallization of proteins proved vital to the progress of peptide theory in these years. Crystallization became an invaluable tool for the assessment of the molecular weight of proteins and the identification of molecular structure. Although the crystallization of hemoglobin had been observed as early as 1830 (K. H. Baumgaertner, Beobachtungen uber die Nerven und das Blut in ihren gesunden und Krankhaften Zustande, Freiburg, 1830), proteins were not considered crystallizable until about 1900. Indeed, one characteristic of proteins - in contrast to colloids - was that they did not exhibit this property. Thus, work with protein crystals was noteworthy in the progress of protein research - and hemoglobin was the subject of many of these early studies. By 1925, improved techniques allowed Gilbert Adair to report an essentially accurate molecular weight of 67,000 for hemoglobin: Gilbert S. Adair, "The Osmotic Pressure of Haemoglobin in the Absence of Salts," Proc. Roy. Soc. London, ser. A, 1925, 109: 293.
90. See Kay, Molecular Vision of Life (n. 75), p. 199; Sapp, Where the Truth Lies (n. 72), p. 49; Fruton, Molecules and Life (n. 73), pp. 245-55.
91. See Kay, Molecular Vision of Life (n. 75), p. 199; Sapp, Where the Truth Lies (n. 72), p. 49; Fruton, Molecules and Life (n. 73), pp. 245-55.
92. See Kay, Molecular Vision of Life (n. 75), p. 199; Sapp, Where the Truth Lies (n. 72), p. 49; Fruton, Molecules and Life (n. 73), pp. 245-55.
93. Coined by Norman Horowitz, a member of Beadle's research group at Caltech, in 1948. It is important to note that there were many objections to claims concerning the gene-enzvme link from such reputed scientists as Max Delbrück, who criticized the methodology of the Neurospora model. Other objections to the one-gene/one-enzyme theory maintained that "limiting the influence of hereditary determinants to merely regulating intermediate chemical reactions along a pathway was tantamount to dethroning the gene(Kay, Molecular Vision of Life [n. 75], p. 209). Claims of one-to-one correspondence seemed to ignore the apparent pleiotropy of the gene, thereby reducing its range of control and violating certain strongly held convictions as to the nature of gene function.
94. "The chromosome theory of Mendelian heredity explained Mendelian segregation, independent assortment, and linkage in terms of the behavior of chromosomes. It did not solve the problem of gene action or the physical nature of a gene that could reproduce, mutate, and control the production of characters. These problems required a new level of organization, whose existence was only suspected before 1930 - the level of the macromolecule" (Lindley Darden, Theory Change in Science: Strategies from Mendelian Genetics [New York: Oxford University Press, 1991], p. 212). See also Robert Olby, "The Significance of the Macromolecules in the Historiography of Molecular Biology," Hist. Philos. Life Sci., 1979, 1: pp. 185-98.
95. "The chromosome theory of Mendelian heredity explained Mendelian segregation, independent assortment, and linkage in terms of the behavior of chromosomes. It did not solve the problem of gene action or the physical nature of a gene that could reproduce, mutate, and control the production of characters. These problems required a new level of organization, whose existence was only suspected before 1930 - the level of the macromolecule" (Lindley Darden, Theory Change in Science: Strategies from Mendelian Genetics [New York: Oxford University Press, 1991], p. 212). See also Robert Olby, "The Significance of the Macromolecules in the Historiography of Molecular Biology," Hist. Philos. Life Sci., 1979, 1: pp. 185-98.
96. Sapp, Where the Truth Lies (n. 72), p. 49.
97. A preeminent early peptide theorist was Emil Fischer, who coined the term polypeptide in 1906. In the years 1901 and 1902 alone he was able to identify and isolate three amino acids from protein hydrolysates - an extraordinary feat for the time. He also devised a general synthesis of amino acids and developed a means of synthesizing oligopeptides, laying the foundation for protein synthesis: Emil Fischer, "Synthese von Polypeptiden," Berichte der deutschen chemischen Gesellschaft, 1907, 40: 1754-67. Despite these contributions, Pierre Laszlo is careful to qualify the significance of Fischer's work by pointing out that Fischer himself rejected the possibility of organic molecules with molecular weights exceeding 5,000 and thought it likely that the peptide bond was not the only link in the protein molecule: Pierre Laszlo, Molecular Correlates of Biological Concepts (New York: Elsevier, 1986). Fischer had no evidence for the homogeneous structure of protein molecules, so when faced with high calculations of the molecular weight of proteins he presumed that this was due to their complex and variable composition. Indeed, until the 1950s, particularly with the work of Frederick Sanger, the polypeptide theory remained strongly contested.
98. A preeminent early peptide theorist was Emil Fischer, who coined the term polypeptide in 1906. In the years 1901 and 1902 alone he was able to identify and isolate three amino acids from protein hydrolysates - an extraordinary feat for the time. He also devised a general synthesis of amino acids and developed a means of synthesizing oligopeptides, laying the foundation for protein synthesis: Emil Fischer, "Synthese von Polypeptiden," Berichte der deutschen chemischen Gesellschaft, 1907, 40: 1754-67. Despite these contributions, Pierre Laszlo is careful to qualify the significance of Fischer's work by pointing out that Fischer himself rejected the possibility of organic molecules with molecular weights exceeding 5,000 and thought it likely that the peptide bond was not the only link in the protein molecule: Pierre Laszlo, Molecular Correlates of Biological Concepts (New York: Elsevier, 1986). Fischer had no evidence for the homogeneous structure of protein molecules, so when faced with high calculations of the molecular weight of proteins he presumed that this was due to their complex and variable composition. Indeed, until the 1950s, particularly with the work of Frederick Sanger, the polypeptide theory remained strongly contested.
99. The distinction between colloids and crystalloids was proposed in 1861 by Thomas Graham, who noted that some substances when separated from an aqueous solution crystallized, whereas others formed amorphous or gelatinous masses. Even in solution, certain colloids formed aggregates, whereas crystalloids were fully soluble. Furthermore, crystalloids were found to diffuse readily through organic membranes (e.g., bladder, parchment), whereas colloids did not - again indicating significant differences in their size, and what Graham understood as reflecting distinctions in their "intimate molecular constitution" (Laszlo, Molecular Correlates [n. 84], p. 137). Proteins were thus considered colloids with chemical properties distinct from those ascertained for salts and other crystalloid substances. Laszlo maintains that colloid theory in fact embodied vitalistic notions that were in conflict with the reduction of protein chemistry to elemental chemistry (Laszlo, Molecular Correlates [n. 84]).
100. The distinction between colloids and crystalloids was proposed in 1861 by Thomas Graham, who noted that some substances when separated from an aqueous solution crystallized, whereas others formed amorphous or gelatinous masses. Even in solution, certain colloids formed aggregates, whereas crystalloids were fully soluble. Furthermore, crystalloids were found to diffuse readily through organic membranes (e.g., bladder, parchment), whereas colloids did not - again indicating significant differences in their size, and what Graham understood as reflecting distinctions in their "intimate molecular constitution" (Laszlo, Molecular Correlates [n. 84], p. 137). Proteins were thus considered colloids with chemical properties distinct from those ascertained for salts and other crystalloid substances. Laszlo maintains that colloid theory in fact embodied vitalistic notions that were in conflict with the reduction of protein chemistry to elemental chemistry (Laszlo, Molecular Correlates [n. 84]).
101. Hermann Staudinger, "Über Polymerisation," Berichte der deutschen chemischen Gesellschaft, 1920, 53: 1073.
102. Hermann Staudinger and J. Fritschi, "Über die Hydrierung des Kautschuks und über seine Konstitution," Helvetica Chimica Acta, 1922, 5: 785-806.
103. Jacques Loeb was able to manipulate proteins to form various salts. This finding suggested that protein solutions might behave as crystalloids in the sense of exhibiting quantitative chemical behavior (as opposed to "globs" of amorphous material), and as such were subject to the same chemical forces demonstrated for crystalloids. This linkage of proteins and salts was an important step toward being able to characterize the molecular forces of proteins, but, as the following statement makes clear, Loeb remained influenced by colloid chemistry and lacked the notion of the macromolecule: "[I]t is incorrect to distinguish between colloids and crystalloids - at least as far as the proteins are concerned - but we must distinguish instead between colloidal and crystalloidal properties. Proteins are crystalloids, but on account of their large size" they cannot readily diffuse through membranes as do smaller and more readily soluble crystalloids. See Jacques Loeb, "Crystalloidal and Colloidal Behavior of Proteins," in The Theory and Application of Colloidal Behavior, ed. R. H. Bogue (New York: McGraw Hill, 1924), pp. 23-69.
104. Theodor Svedberg and Robin Fåhraeus, "A New Method for the Determination of the Molecular Weight of the Proteins," J. Amer. Chem. Soc., 1926, 48: 430-38.
105. Bioenergetics and Thermodynamics: Model Systems, ed. A. Braibanti (Dordrecht: Reidel, 1980); Laszlo, Molecular Correlates (n. 84), p. 181.
106. Bioenergetics and Thermodynamics: Model Systems, ed. A. Braibanti (Dordrecht: Reidel, 1980); Laszlo, Molecular Correlates (n. 84), p. 181.
107. Laszlo, Molecular Correlates (n. 84), p. 183.
108. John D. Bernal and Dorothy Crowfoot, "X-ray Photographs of Crystalline Pepsin," Nature, 1934, 133: 794-95.
109. E.g., Linus Pauling and Carl Niemann, "The Structure of Proteins," J. Amer. Chem. Soc., 1939, 61: 1860-67.
110. Andersch, Wilson, and Menten, "Sedimentation Constants" (n. 12), p. 301.
111. Ibid., pp. 305-4.
112. Kay, Molecular Vision of Life (n. 75), p. 139. See also Lily Kay, "Laboratory Technology and Biological Knowledge: The Tiselius Electrophoresis Apparatus, 1930-1945," Hist. Philos. Life Sci., 1988, 10: 51-72.
113. Kay, Molecular Vision of Life (n. 75), p. 139. See also Lily Kay, "Laboratory Technology and Biological Knowledge: The Tiselius Electrophoresis Apparatus, 1930-1945," Hist. Philos. Life Sci., 1988, 10: 51-72.
114. Conley, "Sickle-Cell Anemia" (n. 4), p. 340.
115. The first peptide sequence (for insulin) was published by Frederick Sanger in 1955. Only then was Fischer's hypothesis - that proteins are composed of chains of amino acids -finally accepted.
116. By situating Pauling's work on sickle cell anemia in the context of his unsuccessful effort to build a program of medical research at Caltech, Lily Kay provides an interesting demonstration of the complex intersections of protein research, genetics, and medicine at this time: Kay, Molecular Vision of Life (n. 75), pp. 259-61.
117. Maxwell Wintrobe, Clinical Hematology, 2d ed. (Philadelphia: Lea and Febiger, 1946), p. 502.
118. Ibid.
119. James V. Neel, Physician to the Gene Pool: Genetic Lessons and Other Stories (New York: Wiley, 1994), p. 41.
120. Neel, "Clinical Detection" (n. 68).
121. M. Susan Lindee, Suffering Made Real: American Science and the Survivors at Hiroshima (Chicago: University of Chicago Press, 1994), pp. 67-70.
122. Wendell Rosse, letter to Alfred I. Tauber, undated [June 1996].
123. Richard Strohman argues against the "strong case" of genetic reductionism, in that most diseases are "multigenic and that single genes interact strongly with other genes and with the environment in producing, or not producing, a particular phenotype. . . . In other words, the living system is mostly an epigenetic, rather than a genetic, system. Thus, evidence from molecular, cell, and developmental biology all tend to undermine the major paradigm of biomedicine that declares genetic determinism the most significant focus of our health care system" (Richard Strohman, "Ancient Genomes, Wise Bodies, Unhealthy People: Limits of a Genetic Paradigm in Biology and Medicine," Perspect. Biol. Med., 1993, 37: 112-45, quotation on p. 138). Our views on the general question of reductionism in biology have been developed in Alfred I. Tauber, The Immune Self, Theory or Metaphor? (Cambridge: Cambridge University Press, 1994) ; Alfred I. Tauber and Sahotra Sarkar, "The Human Genome Project: Has Blind Reductionism Gone too Far?" Perspect. Biol. Med., 1992, 35: 220-35; idem, "The Ideological Basis of the Human Genome Project," J. Roy. Soc. Med., 1993, 86: 537-40.
124. Richard Strohman argues against the "strong case" of genetic reductionism, in that most diseases are "multigenic and that single genes interact strongly with other genes and with the environment in producing, or not producing, a particular phenotype. . . . In other words, the living system is mostly an epigenetic, rather than a genetic, system. Thus, evidence from molecular, cell, and developmental biology all tend to undermine the major paradigm of biomedicine that declares genetic determinism the most significant focus of our health care system" (Richard Strohman, "Ancient Genomes, Wise Bodies, Unhealthy People: Limits of a Genetic Paradigm in Biology and Medicine," Perspect. Biol. Med., 1993, 37: 112-45, quotation on p. 138). Our views on the general question of reductionism in biology have been developed in Alfred I. Tauber, The Immune Self, Theory or Metaphor? (Cambridge: Cambridge University Press, 1994) ; Alfred I. Tauber and Sahotra Sarkar, "The Human Genome Project: Has Blind Reductionism Gone too Far?" Perspect. Biol. Med., 1992, 35: 220-35; idem, "The Ideological Basis of the Human Genome Project," J. Roy. Soc. Med., 1993, 86: 537-40.
125. Richard Strohman argues against the "strong case" of genetic reductionism, in that most diseases are "multigenic and that single genes interact strongly with other genes and with the environment in producing, or not producing, a particular phenotype. . . . In other words, the living system is mostly an epigenetic, rather than a genetic, system. Thus, evidence from molecular, cell, and developmental biology all tend to undermine the major paradigm of biomedicine that declares genetic determinism the most significant focus of our health care system" (Richard Strohman, "Ancient Genomes, Wise Bodies, Unhealthy People: Limits of a Genetic Paradigm in Biology and Medicine," Perspect. Biol. Med., 1993, 37: 112-45, quotation on p. 138). Our views on the general question of reductionism in biology have been developed in Alfred I. Tauber, The Immune Self, Theory or Metaphor? (Cambridge: Cambridge University Press, 1994) ; Alfred I. Tauber and Sahotra Sarkar, "The Human Genome Project: Has Blind Reductionism Gone too Far?" Perspect. Biol. Med., 1992, 35: 220-35; idem, "The Ideological Basis of the Human Genome Project," J. Roy. Soc. Med., 1993, 86: 537-40.
126. Richard Strohman argues against the "strong case" of genetic reductionism, in that most diseases are "multigenic and that single genes interact strongly with other genes and with the environment in producing, or not producing, a particular phenotype. . . . In other words, the living system is mostly an epigenetic, rather than a genetic, system. Thus, evidence from molecular, cell, and developmental biology all tend to undermine the major paradigm of biomedicine that declares genetic determinism the most significant focus of our health care system" (Richard Strohman, "Ancient Genomes, Wise Bodies, Unhealthy People: Limits of a Genetic Paradigm in Biology and Medicine," Perspect. Biol. Med., 1993, 37: 112-45, quotation on p. 138). Our views on the general question of reductionism in biology have been developed in Alfred I. Tauber, The Immune Self, Theory or Metaphor? (Cambridge: Cambridge University Press, 1994) ; Alfred I. Tauber and Sahotra Sarkar, "The Human Genome Project: Has Blind Reductionism Gone too Far?" Perspect. Biol. Med., 1992, 35: 220-35; idem, "The Ideological Basis of the Human Genome Project," J. Roy. Soc. Med., 1993, 86: 537-40.