Authors: Paul A. Offit
This book is based on a series of interviews conducted with Dr. Maurice R. Hilleman on November 12, 19, and 30, 2004; December 3, 10, 15, and 17, 2004; January 6, and 7, 2005; February 17, 2005; and March 11, 2005.
Prologue
The history of vaccine development is contained in Plotkin and Orenstein,
Vaccines,
and Plotkin and Fantini,
Vaccinia.
The Time Capsule
National Millennium Time Capsule: T. Stephens, "UCSC Researchers Produce Human Genome CD for the National Millennium Time Capsule,"
UC Santa Cruz Currents Online,
January 22, 2001, www.ucsc.edu/currents; Press Release, National Archives and Records Administration, "National Millennium Time Capsule Exhibition to Open at the National Archives," Press release, December 4, 2000, www.archives.gov/mediadesk/pressreleases/ nr01â20.html; CNN.com: "Nation's Time Capsule: Dog Tags, a Cell Phone and Dreams," December 6, 2000, http://archives.cnn.com/2000/US/12/06/ timecapsule.ap; and "Clintons Busy with Duties before Dawn of 2000," December 31, 1999, http://archives.cnn.com/1999/ALLPOLITICS/stories.12/31. kickoff; White House Millennium Council: "National Millennium Time Capsule," http://clinton3.nara.gov/Initiatives/Millennium/capsule.html, and http://clinton4.nara.gov/Initiatives/Millennium/capsule/ theme_medalist. html; "Take This Capsule, Call in 100 Years,"
New York Times
, January 2, 2000.
Vaccine impact: J. P. Bunker, H. S. Frazier, and F. Mosteller, "Improving Health: Measuring Effects of Medical Care,"
Milbank Quarterly
72 (1994):225â58.
"My God: This Is the Pandemic. It's Here!"
The best single description of the origin of bird flu in Southeast Asia is contained in Kolata,
Flu
.
Bird flu: E. Check, "WHO Calls for Vaccine Boost to Prepare for Flu Pandemic,"
Nature
432 (2004): 261; T. T. Hien, M. de Jong, and J. Farrar, "Avian Influenza: A Challenge to Global Health Care Structures,"
New England Journal of Medicine
351 (2004): 2363â65; K. Stöhr, and M. Esveld, "Will Vaccines Be Available for the Next Influenza Pandemic?"
Science
306 (2004): 2195â96; R. S. Nolan, "Future Pandemic Most Likely Will Be Caused by Bird Flu,"
AAP News
, January 2005; M. T. Osterholm, "Preparing for the Next Pandemic,"
New England Journal of Medicine
352 (2005): 1839â42; K. Ungchusak, P. Auewarakul, S. Dowell, et al., "Probable Person-to-Person Transmission of Avian Influenza A (H5N1),"
New England Journal of Medicine
352 (2005): 333â40; A. S. Monto, "The Threat of Avian Influenza Pandemic,"
New England Journal of Medicine
352 (2005): 323â25; H. Chen, G. J. D. Smith, and S. Y. Zhang, "H5N1 Virus Outbreak in Migratory Waterfowl,"
Nature
436 (2005):191; J. Liu, H. Xiao, F. Lei, et al., "Highly Pathogenic H5N1 Influenza Virus Infection in Migratory Birds,"
Science
309 (2005): 1206; T. R. Maines, X. H. Lu, S. M. Erb, et al., "Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals,"
Journal of Virology
79 (2005): 11788â800; "The Next Killer Flu: Can We Stop It?
National Geographic
, October 2005; "Avian Flu: Ready for a Pandemic?
Nature
, May 26, 2005; D. Normile: "Outbreak in Northern Vietnam Baffles Experts,"
Science
308 (2005): 477, and "Genetic Analyses Suggest Bird Flu Virus Is Evolving,"
Science
308 (2005): 1234â35; D. Cyranoski, "Flu in Wild Birds Sparks Fears of Mutating Virus,"
Nature
435 (2005): 542â43; D. Butler: "Bird Flu: Crossing Borders,"
Nature
436 (2005): 310â11; "Flu Officials Pull Back from Raising Global Alert Level,"
Nature
436 (2005): 6â7; "Alarms Ring over Bird Flu Mutations,"
Nature
439 (2006): 248â49; "Doubts over Source of Bird Flu Spread,"
Nature
439 (2006): 772; "Yes, But Will It Jump?"
Nature
439 (2006): 124â25; M. Enserink, "New Study Casts Doubt on Plans for Pandemic Containment,"
Science
311 (2006): 1084.
1918 influenza pandemic: Barry,
Great Influenza
; Kolata,
Flu
; R. B. Belshe, "The Origins of Pandemic Influenza: Lessons from the 1918 Virus,"
New England Journal of Medicine
353 (2005): 2209â11; J. S. Oxford, "Influenza A Pandemics of the 20th Century with Special Reference to 1918: Virology, Pathology and Epidemiology,"
Reviews in Medical Virology
10 (2000): 110â33.
AIDS pandemic: "The Global HIV/AIDS Pandemic,"
Morbidity and Mortality Weekly Report
, April 11, 2006.
Jeryl Hilleman quote: "The Vaccine Hunter," BBC Radio 4, producer Pauline Moffatt, June 21, 2006.
Ricketts: H. T. Ricketts, "The Transmission of Rocky Mountain Spotted Fever by the Bite of the Wood-Tick (
Dermacentor occidentalis
),"
Journal of the American Medical Association
47 (1906): 358.
Lorraine Hilleman quote: "The Vaccine Hunter," BBC Radio 4, producer Pauline Moffatt, June 21, 2006.
Infection and wars: McNeill,
Plagues
.
New York Times
article: "Hong Kong Battling Influenza Epidemic,"
New York Times
, April 17, 1957.
1957 pandemic: S. F. Dowell, B. A. Kupronis, E. R. Zell, and D. K. Shay "Mortality from Pneumonia in Children in the United States, 1939 through 1996,"
New England Journal of Medicine
342 (2000): 1399â1407; J. R. Schäfer, Y. Kawaoka, W. J. Bean, et al., "Origin of the Pandemic 1957 H2 Influenza A Virus and the Persistence of Its Possible Progenitors in the Avian Reservoir,
Virology
194 (1993): 781â88; N. J. Cox, and K. Subbarao, "Global Epidemiology of Influenza: Past and Present,"
Annual Reviews of Medicine
51 (2000): 407â21; Y. Karaoka, S. Krauss, and R. G. Webster, "Avian-to-Human Transmission of the PB1 Gene of Influenza A Viruses in the 1957 and 1968 Pandemics,"
Journal of Virology
63 (1989): 4603â8; L. Simonsen, M. J. Clarke, L. B. Schonberger, et al., "Pandemic versus Epidemic Influenza Mortality: A Pattern of Changing Age Distribution,"
Journal of Infectious Diseases
178 (1998): 53â60; D. F. Hoft, and R. B. Belshe, "The Genetic Archaeology of Influenza,"
New England Journal of Medicine
351 (2004): 2550â51.
Hilleman influenza studies: M. R. Hilleman, R. P. Mason, and N. G. Rogers, "Laboratory Studies on the 1950 Outbreak of Influenza,"
Public Health Reports
65 (1950): 771â77; M. R. Hilleman, R. P. Mason, and E. L. Buesher, "Antigenic Pattern of Strains of Influenza A and B,"
Proceedings of the Society for Experimental Biology and Medicine
75 (1950): 829â35; M. R. Hilleman, E. L. Buescher, and J. E. Smadel, "Preparation of Dried Antigen and Antiserum for the Agglutination-Inhibition Test for Influenza Virus,"
Public Health Reports
66 (1951): 1195â1203; M.R. Hilleman, "System for Measuring and Designating Antigenic Components of Influenza Viruses with Analyses of Recently Isolated Strains,"
Proceedings of the Society for Experimental Medicine and Biology
78 (1951): 208â15; M. R. Hilleman, "A Pattern of Antigen Variation,"
Federation Proceedings
11 (1952): 798â803; M. R. Hilleman, and F. L. Horsfall, "Comparison of the Antigenic Patterns of Influenza A Virus Strains Determined by in ovo Neutralization and Hemagglutination-Inhibition,"
Journal of Immunology
69 (1952): 343â56; M. R. Hilleman, and J. H. Werner, "Influence of Non-Specific Inhibitor of the Diagnostic Hemagglutination-Inhibition Test for Influenza,"
Journal of Immunology
71 (1953): 110â17; M. R. Hilleman, J. H. Werner, and R. L. Gauld, "Influenza Antibodies in the Population in the USA,"
Bulletin of the World Health Organization
8 (1953): 613â31; M. R. Hilleman, "Antigenic Variation of Influenza Viruses,"
Annual Review of Microbiology
8 (1954): 311â32; H. M. Meyer, M. R. Hilleman, M. L. Miesse, et al., "New Antigenic Variant in Far East Influenza Epidemic, 1957,"
Proceedings of the Society for Experimental Medicine and Biology
95 (1957): 609â16; M. R. Hilleman, "Asian Influenza: Initial Identification of Asiatic Virus and Antibody Response in Volunteers to Vaccination,"
Proceedings of a Special Conference on Influenza
, U.S. Department of Health, Education, and Welfare, August 27â28 1957; M. R. Hilleman, F. J. Flatley, S. A. Anderson, et al., "Antibody Response in Volunteers to Asian Influenza Vaccine,"
Journal of the American Medical Association
166 (1958): 1134â40; M. R. Hilleman, F. J. Flatley, S. A. Anderson, et al., "Distribution and Significance of Asian and Other Influenza Antibodies in the Human Population,"
New England Journal of Medicine
258 (1958): 969â74; C. C. Mascoli, M. B. Leagus, and M. R. Hilleman, "Influenza B in the Spring of 1965,"
Proceedings of the Society for Experimental Biology and Medicine
123 (1966): 952â60; M. R. Hilleman, "The Roles of Early Alert and of Adjuvant in the Control of Hong Kong Influenza by Vaccines,"
Bulletin of the World Health Organization
41 (1969): 623â28.
Hilleman prediction about bird flu: M. R. Hilleman, "Realities and Enigmas of Human Viral Influenza: Pathogenesis, Epidemiology and Control,"
Vaccine
20 (2002): 3068â87.
Jeryl Lynn
Robert Weibel, Art Caplan, and Jeryl Lynn Hilleman were interviewed on January 6, 2005; March 10, 2005; and March 11, 2005, respectively.
Mumps disease: Plotkin and Orenstein,
Vaccines
.
Hilleman mumps vaccine studies: E. B. Buynak, and M. R. Hilleman, "Live Attenuated Mumps-Virus Vaccine, I: Vaccine Development,"
Proceedings of the Society for Experimental Biology and Medicine
123 (1966): 768â75; J. Stokes Jr., R. E. Weibel, E. B. Buynak, and M. R. Hilleman, "Live Attenuated Mumps-Virus Vaccine. II: Early Clinical Studies,"
New England Journal of Medicine
39 (1967): 363â71; R. W. Weibel, J. Stokes Jr., E. B. Buynak, J. E. Whitman, and M. R. Hilleman, "Live, Attenuated Mumps-Virus Vaccine; 3: Clinical and Serological Aspects in a Field Evaluation,"
New England Journal of Medicine
276 (1967): 245â51; M. R. Hilleman, R. W. Weibel, E. B. Buynak, J. Stokes Jr., J. E. Whitman, "Live, Attenuated Mumps-Virus Vaccine; 4: Protective Efficacy as Measured in a Field Evaluation,"
New England Journal of Medicine
276 (1967): 252â58; R. W. Weibel, E. B. Buynak, J. Stokes Jr., J. E. Whitman, and M. R. Hilleman, "Evaluation of Live Attenuated Mumps Virus Vaccine, Strain Jeryl Lynn," Pan American Health Organization,
Scientific Publication No. 147
, May 1967, 430â37; R. W. Weibel, J. Stokes Jr., E. B. Buynak, M. B. Leagus, and M. R. Hilleman, "Jeryl Lynn Strain Live Attenuated Mumps Virus Vaccine: Duration of Immunity Following Administration,"
Journal of the American Medical Association
203 (1968): 14â18; R. W. Weibel, E. B. Buynak, J. E. Whitman, M. B. Leagus, J. Stokes Jr., and M. R. Hilleman, "Jeryl Lynn Strain Live Attenuated Mumps Virus Vaccine: Duration of Immunity for Three Years Following Vaccination,"
Journal of the American Medical Association
207 (1969): 1667â70; R. W. Weibel, E. B. Buynak, J Stokes Jr., and M. R. Hilleman, "Persistence of Immunity Four Years Following Jeryl Lynn Strain of Live Mumps Virus Vaccine,"
Pediatrics
45 (1970): 821â26.
Polio vaccine studies: Carter,
Breakthrough
; J. Smith,
Patenting the Sun
; Oshinsky,
Polio
; interview with Donna Salk, February 10, 1999; J. A. Kolmer, G. F. Klugh, and A. M. Rule, "A Successful Method for Vaccination against Acute Anterior Poliomyelitis,"
Journal of the American Medical Association
104 (1935): 456â60; J. A. Kolmer, "Susceptibility and Immunity in Relation to Vaccination with Acute Anterior Poliomyelitis,"
Journal of the American Medical Association
105 (1935): 1956â62.
Willowbrook studies: Rothman and Rothman,
Willowbrook
; G. Rivera,
Willowbrook: A Report on How It Is and Why It Doesn't Have to Be That Way
(New York: Vintage Books, 1972); S. Krugman, and R. Ward, "Clinical and Experimental Studies of Infectious Hepatitis,"
Pediatrics
22 (1958): 1016â22; S. Krugman, "The Willowbrook Hepatitis Studies Revisited: Ethical Aspects,"
Reviews of Infectious Diseases
8 (1986): 157â62.
Fernald studies: N. Fost, "America's Gulag Archipelago,"
New England Journal of Medicine
351 (2004): 2369â70.
Impact of mumps vaccine: Plotkin and Orenstein,
Vaccines
.
Mumps versus Jeryl Lynn: A. Dove, "Maurice Hilleman,"
Nature Medicine Supplement
11 (2005): 52.
Eight Doors
An excellent summary of the history of vaccine development and of the historic events that influenced Hilleman's work can be found in the following: Plotkin and Fantini,
Vaccinia
; M. R. Hilleman: "Vaccines and the Vaccine Enterprise: Historic and Contemporary View of a Scientific Initiative of Complex Dimensions,"
The Jordan Report
(2002); "Personal Reflections on Twentieth Century Vaccinology,"
Southeast Asian Journal of Tropical Medicine and Public Health
34 (2003): 244â48; and "Overview of Vaccinology in Historic and Future Perspective: The Whence and Whither of a Dynamic Science with Complex Dimensions," in
DNA Vaccines
, ed. H. C. J. Ertl (Plenum Publishers, London, 2003). 31 Jenner and the smallpox vaccine: Tucker,
Scourge
; Radetsky,
Invaders
; Williams,
Virus Hunters
; B. Moss, "Vaccinia Virus: A Tool for Research and Vaccine Development,"
Science
252 (1991): 1662â67; M. Radetsky, "Smallpox: A History of Its Rise and Fall,
Pediatric Infectious Disease Journal
18 (1999): 85â93.