De Kruif's Boast: Vaccine trials and the construction of a virus

Bulletin of the History of Medicine

Volumn 80, Issue 3, 2006, Pages 409-438

  Eyler, John M ^a,b  

^a Department of History of Medicine ^*  (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Christopher Andrewes; Field trial; Frank Horsfall; Influenza; Joseph Stokes; Thomas Francis, Jr.; Vaccine; Virus

Indexed keywords

EID: 33749670267     PISSN: 00075140     EISSN: None     Source Type: Journal    
DOI: 10.1353/bhm.2006.0092     Document Type: Review

References (158)

1. Paul de Kruif, "The Flu-Trappers," Country Gentleman, January 1936, pp. 5-7, 54-55;
2. de Kruif, "The Flu-Trappers," Reader's Digest, February 1936, pp. 15-18.
3. Subsequent citation will be to the version in Country Gentleman.
4. (De Kruif did not provide references for his readers. I cite here and below the most important articles presenting this research.) Richard E. Shope, "Swine Influenza. III. Filtration Experiments and Etiology," J. Exper. Med., 1931, 54: 373-85.
5. Wilson Smith, C. H. Andrewes, and P. P. Laidlaw, "A Virus Obtained from Influenza Patients," Lancet, 1933, 1: 66-68.
6. Thomas Francis, Jr., "Transmission of Influenza by a Filterable Virus," Science, 1934, 80: 457-59.
7. C. H. Andrewes, P. P. Laidlaw, and Wilson Smith, "The Susceptibility of Mice to the Viruses of Human and Swine Influenza," Lancet, 1934, 2: 859-62, on p. 861;
8. Wilson Smith, C. H. Andrewes, and P. P. Laidlaw, "Influenza: Experiments on the Immunization of Ferrets and Mice," Brit. J. Exp. Path., 1935, 16: 291-302;
9. Thomas Francis, Jr., "Immunological Studies with the Virus of Influenza," J. Exp. Med., 1935, 62: 505-15;
10. Thomas Francis, Jr., "Vaccination of Human Subjects with the Virus of Human Influenza," Proc. Soc. Exp. Biol. &Med., 1936, 33: 604-16, on pp. 604-6.
11. De Kruif, "Flu-Trappers" (n. 1), p. 55.
12. I am preparing an article on the controversies about the testing of influenza vaccines during this pandemic.
13. Harry Lee Barnes, "The Prophylactic Value of Leary's Vaccine," JAMA, 1918, 71:1899;
14. William A. Hinton and Edna Sypher Kane, "Use of Influenza Vaccine as a Prophylactic - An Experimental Study Conducted by the Massachusetts State Department of Health," J. Tennessee State Med. Assoc., 1918-19, 11:442-46;
15. Augustus B. Wadsworth, "The Results of Preventive Vaccination with Suspensions of the Influenza Bacillus," Pub. Health J. (Toronto), 1919,10: 309-14;
16. John B. Hawes II, "Experience of Massachusetts State Sanatoria for Tuberculosis during the Recent Influenza Epidemic," Boston Med&Surg. J., 1919, 180: 35-37.
17. "A Working Program against Influenza," Amer. J. Pub. Health, 1919, 9:1-13. This document was also circulated as a pamphlet.
18. Joseph Stokes to Ellen C. Potter, 16 November 1935, Joseph Stokes Papers, Influenza Studies #6a, American Philosophical Society, Philadelphia, Pa. (hereafter cited as SP/IS).
19. See Lawrence B. Berk, "Polio Vaccine Trials of 1935," Trans. Coll. Physicians Philadelphia, ser. 5, 1989, 11:321-36;
20. Sydney A. Halpern, Lesser Harms: The Morality of Risk in Medical Research (Chicago: University of Chicago Press, 2004), pp. 48-65;
21. John R. Paul, A History of Poliomyelitis (New Haven: Yale University Press, 1971), pp. 252-62.
22. Potter to Stokes, 18 November 1935, SP/IS #6a.
23. Stokes to Potter, 20 November 1935; Stokes to Potter, 22 November 1935, ibid.
24. Potter to Stokes, 23 November 1935; Stokes to Potter, 6 December 1935, ibid.
25. See, e.g., Potter to Stokes, 20 October 1937, SP/IS #1; Ralph G. Gladen (Resident Physician, New Jersey State Colony, New Lisbon) to Stokes, 21 January 1936, SP/IS #8; C. T. Jones (Superintendent, New Jersey State Colony, New Lisbon) to Stokes, 30 March 1936, ibid.
26. Christopher Howard Andrewes, "Adventures among Viruses, II. Epidemic Influenza," New England J. Med., 1950, 242:197-203, on p. 197;
27. C. H. Andrewes, "Influenza: Theme and Variations," California Med., 1956, 84: 375-80, on p. 375.
28. The literature on the historical use of the construction metaphor is vast. For short discussions, see Michael Worboys, Spreading Germs: Disease Theories and Medical Practice in Britain, 1865-1900 (Cambridge: Cambridge University Press, 2000), pp. 10-13;
29. Ludmilla Jordanova, "The Social Construction of Medical Knowledge," Soc. Hist. Med., 1995, 8: 361-81.
30. This episode is a favorite in popular histories of the influenza. See, e.g., Gina Kolata, Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It (New York: Simon & Schuster, 2001), p. 74.
31. It is less well known that a similar accident resulted in the infection of an assistant in Francis's laboratory in 1934: Francis, "Transmission of Influenza" (n. 4), p. 458.
32. Andrewes, Laidlaw, and Smith, "Susceptibility of Mice" (n. 5), pp. 859-60;
33. Francis, "Transmission of Influenza" (n. 4), pp. 458-59.
34. Frank L. Horsfall, Jr., Edwin H. Lennette, and Elsmere R. Rickard, "A Complex Vaccine against Influenza A Virus: Quantitative Analysis of the Antibody Response Produced in Man," J. Exp. Med., 1941, 73: 335-55, on p. 336.
35. For a description of how the neutralization test was conducted in the late 1930s, see Thomas Francis, Jr., T. R Magill, E. R. Rickard, and M. Dorothy Beck, "Etiological and Serological Studies in Epidemic Influenza," Amer. J. Pub. Health, 1937, 27: 1141-60, on pp. 1142-43;
36. or Morris Siegel, Ralph S. Muckenfuss, Morris Schaeffer, Harriet Leslie Wilcox, and Ann G. Leider, "A Study in Active Immunization against Epidemic Influenza and Pneumococcus Pneumonia at Letchworth Village. III. The Results of Active Immunization against Epidemic Influenza from 1937 to 1940," Amer. J. Hygiene, 1942, 35: 55-96, on pp. 59-60.
37. Frank L. Horsfall, Jr., "Present Status of Knowledge Concerning Influenza," Amer. J. Pub. Health, 1940, 30: 1302-10, on p. 1304.
38. Joseph Stokes, Jr., Aims C. McGuinnes, Paul H. Langner, Jr., and Dorothy R. Shaw, "Vaccination against Epidemic Influenza with Active Virus of Human Influenza," Amer. J. Med. Sci., n.s., 1937, 194: 157-68, on p. 759.
39. F. L. Horsfall, Jr., E. H. Lennette, E. R. Rickard, C. H. Andrewes, Wilson Smith, and C. H. Stuart-Harris, "The Nomenclature of Influenza," Lancet, 1940, 2: 413-14.
40. See also Horsfall, "Present Status" (n. 22), pp. 1302-3;
41. E. R. Rickard, Edwin H. Lennette, and Frank L. Horsfall, Jr., "A Comprehensive Study of Influenza in a Rural Community," Pub. Health Rep., 1940, 55'. 2146-67, on pp. 2146-47.
42. Thomas Francis, Jr., "A New Type of Virus from Epidemic Influenza," Science, 1940, 92: 405-8.
43. For descriptions of the projects and budgets, see "Influenza Study," SP/IS#3; Stokes to John A. Ferrell (Rockefeller Foundation), 21 April 1937, SP/IS #24;
44. "Reporten Influenza Studies 1936-37," Influenza Study,ibid.;
45. "Proposed Budget from July 1,1937 to July 1, 1938," Influenza Study, ibid.
46. Also "Influenza. Progress Report-May 15,1936," SP/IS #28; Stokes to J. R. Mohler (Chief, Bureau of Animal Industry, USDA), 24 March 1938, SP/IS #8.
47. For the report of this trial, see Joseph Stokes, Jr., Alice D. Chenoweth, Arthur D. Waltz, Ralph G. Gladen, and Dorothy Shaw, "Results of Immunization by Means of Active Virus of Human Influenza," J. Clin. Invest., 1937, 16: 237-43.
48. Stokes et al., "Vaccination against Epidemic Influenza" (n. 23).
49. Morris Siegel and Ralph S. Muckenfuss, "A Study in Active Immunization against Epidemic Influenza and Pneumococcus Pneumonia at Letchworth Village. I. The Plan of the Study," Amer. J. Hygiene, 1941, 34 (Sect. A): 39-65;
50. Siegel et al., "Study in Active Immunization, III" (n. 21);
51. Morris Siegel, Ralph S. Muckenfuss, Morris Schaeffer, Harriet Leslie Wilcox, and Ann G. Leider, "A Study in Active Immunization against Epidemic Influenza and Pneumococcus Pneumonia at Letchworth Village. IV. Results in an Epidemic of Influenza Q in 1940-41," Amer. J. Hygiene, 1942, 35:186-230.
52. See also Morris Siegel and Ralph S. Muckenfuss, "Serological Response and Problems in Evaluation of Prophylactic Value following Human Inoculation with Influenza Vaccine," J. Barter., 1940, 39: 51-52.
53. John W. Brown, Monroe D. Eaton, Gordon Meiklejohn, John B. Lagen, and W. J. Kerr, "An Epidemic of Influenza. Results of Prophylactic Inoculation of a Complex Influenza A-Distemper Vaccine," J. Clin. Invest., 1941, 20: 663-69.
54. Walter P. Martin and Monroe D. Eaton, "Experiments on Immunization of Human Beings against Influenza A," Proc. Soc. Exp. Biol. & Med., 1941, 47: 405-9.
55. Gilbert Dalldorf, Elinor Whitney, and Arthur Ruskin, "A Controlled Clinical Test of Influenza A Vaccine," JAMA, 1941, 116: 2574-77.
56. E L. Horsfall, Jr., E. H. Lennette, E. R. Rickard, and G. K. Hirst, "Studies of the Efficacy of a Complex Vaccine against Influenza A," Pub. Health Rep., 1941, 56: 1863-75.
57. For example, Thomas Francis, America's leading influenza researcher, told Stokes that his manuscript lacked clarity and gave the appearance of carelessness: Francis to Stokes, 8 January 1937, Francis Papers, box 2, Joseph Stokes Jr. folder, University of Michigan, Ann Arbor, Mich. See also the literature review in Siegel et al., "Study in Active Immunization, III" (n. 21), p. 55.
58. See Siegel and Muckenfuss, "Study in Active Immunization, I" (n. 29), pp. 48-49, 51-56;
59. Siegel et al., "Study in Active Immunization, III" (n. 21), pp. 84-88.
60. For their conclusions about their own trial, see Siegel et al., "Study in Active Immunization, IV (n. 29), pp. 224-26.
61. For their review of other trials, see Siegel et al., "Study in Active Immunization, III" (n. 21), pp. 55-58;
62. Siegel et al., "Study in Active Immunization, IV" (n. 29), pp. 186-87. For the disappointment at the International Health Division, see J. H. Bauer to W. A. Sawyer, 7 February 1941, RG 1, ser. 100, box 54, folder 537, Rockefeller Archives, New York, N.Y. (hereafter RA); Frank L. Horsfall, Jr., to R. M. Taylor, 20 March 1941, ibid. Horsfall and his colleagues soon concluded that the favorable laboratory results he had obtained with his complex vaccine were due to random sampling errors:
63. G. K. Hirst, E. R. Rickard, Loring Whitman, and F. L. Horsfall, "Antibody Response of Human Beings following Vaccination with Influenza Viruses," J. Exp. Med., 1942, 75: 495-511, on pp. 501-2.
64. E. H. Lennette, E. R. Richard, G. K. Hirst, and F. L. Horsfall, "The Diverse Etiology of Epidemic Influenza," Pub. HealthRep., 1941, 56: 1777-88, on pp. 1781-82. See also the correspondence between Horsfall, P.J. Crawford, andj. H. Bauer in August 1940, RA, RG 1, ser. 100, box 54, folder 535; Horsfall to C. H. Andrewes, 14 September 1940, ibid., folder 536.
65. Horsfall et al., "Studies of the Efficacy" (n. 33), p. 1869;
66. Horsfall to R. M. Taylor, 20 March 1941, RA, RG 1, ser. 100, box 54, folder 537.
67. Wilson Smith, "The Complement-Fixation Reaction in Influenza," Lancet, 1936, 2: 1256-59;
68. R. W. Fairbrother and L. Hoyle, "Observations on the Aetiology of Influenza," J. Path. &Bacter., 1937, 44: 213-33.
69. Siegel et al., "Study in Active Immunization, III" (n. 21), p. 59.
70. Horsfall et al., "Studies of the Efficacy" (n. 33), pp. 1865, 1870.
71. George K. Hirst, "The Quantitative Determination of Influenza Virus and Antibodies by Means of Red Cell Agglutination," J. Exp. Med., 1942, 75: 49-64;
72. Jonas E. Salk, "A Simplified Procedure for Titrating Hemagglutinating Capacity of Influenza-Virus and the Corresponding Antibody," J. Immunol., 1944, 49:87-98.
73. For a description of the use of Hirst's test, see Hirst et al., "Antibody Response of Human Beings" (n. 36), pp. 497-98.
74. Siegel et al., "Study in Active Immunization, III" (n. 21), pp. 59-78, 88-90;
75. Siegel et al., "Study in Active Immunization, IV" (n. 29), pp. 205-6.
76. Siegel et al., "Study in Active Immunization, III" (n. 21), pp. 57-58, 65-78;
77. Siegel et al., "Study in Active Immunization, IV" (n. 29), pp. 205-6.
78. Compare these results to those in Thomas Francis, Jr., T. P. Magill, M. Dorothy Beck, and E. R. Rickard, "Studies with Human Influenza Virus during the Influenza Epidemic of 1936-37," JAMA, 1937, 109: 566-69;
79. Francis et al., "Etiological and Serological Studies" (n. 21);
80. Rickard, Lennette, and Horsfall, "Comprehensive Study of Influenza" (n. 24).
81. Stokes et al., "Results of Immunization" (n. 27), p. 238;
82. Stokes et al., "Vaccination against Epidemic Influenza" (n. 23), p. 759.
83. Stokes et al., "Vaccination against Epidemic Influenza" (n. 23), pp. 758-59;
84. Siegel and Muckenfuss, "Study in Active Immunization, I" (n. 29), pp. 47-48;
85. Siegel et al., "Study in Active Immunization, III" (n. 21), pp. 58-59.
86. F. M. Burnet, "Influenza Virus Infections of the Chick Embryo Lung," Brit. J. Exp. Path., 1940, 21: 147-53;
87. Burnet, "Influenza Virus Infections of the Chick Embryo by the Amniotic Route. 1. General Character of the Infections," Austral. J. Exp. Biol. & Med. Sci., 1940, 18: 353-60.
88. For a sense of the contemporary importance attached to this form of cultivation, see C. H. Stuart-Harris, "The Study of Epidemic Influenza," J. Roy. Inst. Pub. Health & Hygiene, 1947, 10: 222-34, on pp. 224-25.
89. Stokes et al., "Results of Immunization" (n. 27), pp. 239-40;
90. Stokes et al., "Vaccination against Epidemic Influenza" (n. 23), pp. 763-65.
91. Frank L. Horsfall, Jr., and Edwin H. Lennette, "A Complex Vaccine Effective against Different Strains of Influenza Virus," Science, 1940, 91: 492-94;
92. "A Vaccination against Influenza [an excerpt from the Trustees Confidential Bulletin]," RA, RG 1, ser. 100, box 54, folder 535.
93. Frank L. Horsfall, Jr., and Edwin H. Lennette, "The Synergism of Human Influenza and Canine Distemper Viruses in Ferrets," J. Exp. Med., 1940, 72: 247-59;
94. Horsfall, Lennette, and Rickard, "Complex Vaccine" (n. 20).
95. F. M. Acree, "A Vaccine for Epidemic Influenza: Preliminary Report," J. Arkansas Med. Soc., 1941, 38: 61-63, on pp. 62-63.
96. Mona Gardner, "Fighting the Flu," Atlantic Monthly, February 1941, pp. 160-65, on pp. 164-65. See also Horsfall to Andrewes, 14 September 1940, RA, RG 1, ser. 100, box 54, folder 536; J. H. Bauer to R. D. Defries, 27 December 1940, ibid.
97. J. D. Ratcliff, "They've Got the Flu!" Collier's, 18 January 1941, pp. 18, 48;
98. Gardner, "Fighting the Flu" (n. 53), pp. 160-65.
99. Ratcliff, "They've Got the Flu!" (n. 54), p. 18.
100. Thomas Francis, Jr., "Vaccination against Influenza," in Influenza: A Review of Current Research (Geneva: WHO, 1952), pp. 125-40, on pp. 127-29;
101. Francis G. Blake, "An Evaluation of Vaccination against Epidemic Influenza in Man," Bull. New York Acad. Med., 1948, 24; 308-28, on p. 315.
102. S. Bayne-Jones, "Board for the Investigation and Control of Influenza and Other Epidemic Diseases in the Army," Army Med. Bull., 1942, 64:1-22.
103. See also Thomas Francis, Jr., "History of the Commission on Influenza of the Board for the Investigation and Control of Influenza and Other Epidemic Diseases in the Army, February 1941-December 1945," Francis Papers, box 32, University of Michigan, Bentley Library, Ann Arbor, Mich.
104. Thomas Francis, Jr., "Development of the 1943 Vaccine Study of the Commission on Influenza," Amer. J. Hygiene, 1945, 42:1-11, on pp. 2-5.
105. See the special issue on the trial, which includes evaluations of the results at each study unit, in Amer. J. Hygiene, 1945, 42: 1-105.
106. Thomas Francis, Jr., "A Clinical Evaluation of Vaccination against Influenza," JAMA, 1944, 124: 982-85, on p. 984;
107. Monroe D. Eaton and Gordon Meiklejohn, "Vaccination against Influenza: A Study in California during the Epidemic of 1943-44," Amer. J. Hygiene, 1945, 42: 28-44, on pp. 41-43.
108. Study Committee on Vaccination against Influenza of the Subcommittee on Evaluation of Administrative Practices, Committee on Administrative Practice, American Public Health Association, "The Present Status of Vaccination against Influenza," Amer. J. Pub. Health, 1947, 37: 1109-12, on p. 1109.
109. Thomas Francis, Jr., to J. H. Bauer, 7 March 1944, RA, RG 5, ser. 4, box 12, folder 122.
110. Arie C. Van Ravenswaay, "Prophylactic Use of Influenza Virus Vaccine: An Instance of Inadequate Protection against Influenza A," JAMA, 1948, 136: 435-37;
111. M. M. Sigel, F. W. Shaffer, M. Wiener Kirber, A. B. Light, and W. Henle, "Influenza in a Vaccinated Population," JAMA, ibid., pp. 437-41;
112. Clayton G. Loosli, James Schoenberger, and Gwendolyn Barnett, "Results of Vaccination against Influenza during the Epidemic of 1947,"J. Lab. & Clin. Med., 1948, 33: 789-98;
113. Helen Mellanby, C. H. Andrewes, J. A. Dudgeon, and D. G. MacKay, "Vaccination against Influenza A," Lancet, 1948, 1: 978-82.
114. For a recent reevaluation of the vaccine failure and the role of antigen change, see Edwin D. Kilbourne et al., The Total Influenza Vaccine Failure of 1947 Revisited: Major Intrasubtypic Antigenie Change Can Explain Failure of Vaccine in a Post-World War II Epidemic," Proc. Nat. Acad. Sci., 2002, 99: 10748-52.
115. R. W. Fairbrother and L. Hoyle, "Observations on the Aetiology of Influenza," J. Path. & Barter., 1937, 44: 213-33, on p. 213;
116. Richard E. Shope, "The Incidence of Neutralizing Antibodies for Swine Influenza Virus in the Sera of Human Beings of Different Ages," J. Exp. Path., 1936, 63: 669-84, on p. 680.
117. Thomas Francis, Jr., "Immunological Relationships of Strains of Filtrable Virus Recovered from Cases of Human Influenza," Proc. Soc. Exp. Biol. & Mid., 1935, 32: 1172-75;
118. Fairbrother and Hoyle, "Observations" (n. 39), pp. 213, 217, 219.
119. T. P. Magill and Thomas Francis, Jr., "Antigenic Differences in Strains of Epidemic Influenza Virus: I. Cross-Neutralization Tests in Mice," Brit. J. Exp. Path., 1938, 19: 273-84;
120. Thomas Francis, Jr., and T. P. Magill, "Antigenic Differences in Strains of Epidemic Influenza Virus: II. Cross-Immunization Tests in Mice," Brit. J. Exp. Path., ibid., pp. 284-93.
121. See also Thomas Francis, Jr., "Epidemiology of Influenza," JAMA, 1943, 122: 4-7, on p. 6.
122. Francis and Magill, "Antigenic Differences II" (n. 67), pp. 291, 292.
123. Horsfall, "Present Status" (n. 22), p. 1307.
124. George K. Hirst, "Studies of the Mechanism of Adaptation of Influenza Virus to Mice," J. Exp. Mod., 1947, 86: 357-66.
125. George K. Hirst, J. Exp. Mod., Ibid., p. 362.
126. R. M. Taylor, "Studies on Survival of Influenza Virus between Epidemics and Antigenic Variants of the Virus," Amer. J. Pub. Health, 1949, 39: 171-78.
127. Italo Archetti and Frank L. Horsfall, Jr., "Persistent Antigenic Variation of Influenza A Viruses after Incomplete Neutralization in Ovo with Heterologous Immune Serum," J. Exp. Med., 1950, 92: 441-62.
128. C. H. Andrewes, "Epidemiology of Influenza," in Influenza: A Review of Current Research (Geneva: WHO, 1954), pp. 9-24, on p. 15.
129. Ttylor, "Studies on Survival" (n. 72), pp. 177-78.
130. Frank MacFarlane Burnet, "Some Biological Implications of Studies on Influenza Viruses," Bull Johns Hopkins Hasp., 1951, 88:119-80, on pp. 170-71.
131. C. H. Stuart-Harris, "The Present Status of Prophylactic Immunization against Influenza," Brit. Med. J., 1957, 2: 777-79, on p. 777.
132. Francis, "Vaccination against Influenza" (n. 56), pp. 134-35.
133. Jonas E. Salk, "Principles of Immunization as Applied to Poliomyelitis and Influenza," Amer.J. Pub. Health, 1953, 43:1384-88, on p. 1386.
134. Jonas E. Salk, "An Interpretation of the Significance of Influenza Virus Variation for the Development of an Effective Vaccine," Bull. New York Acad. Med., 1952, 28: 748-65.
135. Thomas Francis, Jr., "The Current Status of the Control of Influenza," Ann. Internal Med., 1955, 43: 534-38, on pp. 535-36.
136. See also Francis, "Vaccination against Influenza" (n. 56), pp. 137-38.
137. James T. Culbertson, "Plans for United States Cooperation with the World Health Organization in International Influenza Study Program," Amer. J. Pub. Health, 1949, 39: 57-42;
138. C. H. Andrewes, "The Work of the World Influenza Centre," J. Roy. Inst. Pub. Health of Hygiene, 1952, 15: 308-18, on pp. 314-15;
139. Dorland J. Davis, "Influenza Study Program in the United States," Pub. Health Rep., 1952, 67:1185-90, on pp. 1185-87, 1189-90;
140. A. M.-M. Payne, "The Influenza Programme of WHO," in Influenza (n. 74), pp. 153-68.
141. Andrewes, "Work of the World Influenza Centre" (n. 82), pp. 315-17;
142. Davis, "Influenza Study Program" (n. 82), pp. 1187-89:
143. Payne, "Influenza Programme" (n. 82), p. 160.
144. Roslyn Q. Robinson, "Strain Characteristics of Asian Influenza Virus," International Conference on Asian Influenza (February 17-19, 1960), in Amer. Rev. Resp. Dis., 1961, 83 (2): 105-8, on p. 105.
145. For a brief summary of the current understanding of antigen change in influenza, see Raphael Dolin, "Influenza," in Harrison's Principles of Internal Medicine, 16th ed. (New York: McGraw-Hill, 2005), 1:1066-67;
146. JohnJ. Treanor, "Influenza Virus," in Mandell, Douglas, and Bennttt's Principles and Practice of Infectious Diseases, 6th ed. (Philadelphia: Elsevier, Churchill, Livingstone, 2000), 2: 2064-65.
147. Fred M. Davenport, "Inactivated Influenza Virus Vaccines," in International Conference on Asian Influenza (n. 84), pp. 146-50, on p. 148.
148. Joseph E. Smadel, "Influenza Vaccine," Pub. Health Rep., 1958, 73: 129-32, on p. 131.
149. Davenport, "Inactivated Influenza" (n. 86), pp. 148-49.
150. C. H. Andrewes, in General Discussion, International Conference on Asian Influenza (n. 84), p. 188.
151. James H. Steele, "Animal Influenza," General Discussion, International Conference on Asian Influenza, ibid., pp. 41-46;
152. E. R. Doll, "Influenza of Horses," General Discussion, International Conference on Asian Influenza, ibid., pp. 48-50;
153. General Discussion, General Discussion, International Conference on Asian Influenza, ibid., pp. 50-53.
154. Shope, "Incidence of Neutralizing Antibodies" (n. 65), pp. 680-83;
155. Steele, "Animal Influenza" (n, 90), p. 42.
156. This suggestion was made earlier, but with less experimental evidence, in P. P. Laidlaw, "Epidemic Influenza: A Virus Disease," Lancet, 1935, 1: 1118-24, on p. 1123.
157. Worboys, Spreading Germs (n. 17),p.l3.
158. The point is made more forcefully in Charles E. Rosenberg, "Framing Disease: Illness, Society, and History," in Framing Disease: Studies in Cultural History, ed. Charles E, Rosenberg and Janet Golden (New Brunswick, N.J.: Rutgers University Press, 1992), pp. xiii-xxvi, on pp. xiii-xv, xx-xxi.