The Coming Plague

by Laurie Garrett

  61 H. Ludwig, “B Virus,” in Roizman, ed. (1982), 1: 417–19; and J. E. Kaplan, “Herpesvirus Simiae (B Virus) Infection in Monkey Handlers,” Journal of Infectious Diseases 157 (1988): 1090.

  62 The Mason-Pfizer virus was found in nineteen French blood donors and in some healthy people in Guinea-Bissau. See V. A. Morozov, F. Saal, A. Gessain, et al., “Antibodies to Gag Gene Coded Polypeptides of Type D Retroviruses in Healthy People from Guinea-Bissau,” Intervirology 32 (1991): 253–57.

  A type D virus similar but not identical to Mason-Pfizer was found in the blood of a Texas AIDS patient. See L. A. Donehower, R. C. Bohannon, R. J. Ford, and R. A. Gibbs, “The Use of Primers from Highly Conserved Pol Regions to Identify Uncharacterized Retroviruses by the Polymerase Chain Reaction,” Journal of Virological Methods 28 (1990): 33–46.

  63 Centers for Disease Control, “Primate Zoonoses Surveillance,” Report II, U.S. Department of Health, Education, and Welfare, issued September 1973.

  64 Periodically the CDC would manage to spot faults in the monkey importation system before significant numbers of human beings were infected. For example, between June 1990 and May 1993 a West African export company made 249 monkey shipments to the United States: 7 percent of the animals arrived in the United States carrying tuberculosis, some of them suffering active cases of disease. See Centers for Disease Control, “Tuberculosis in Imported Nonhuman Primates—United States, June 1990-May 1993,” Morbidity and Mortality Weekly Report 42 (1993): 572–75.

  65 The data do not include bone marrow transplants. Data derived from F. H. Cate and S. S. Laudicina, “Transplantation White Paper,” Annenberg Washington Program, Northwestern University, 1991.

  66 C. R. Hitchcock, J. C. Kiser, R. L. Telander, et al., “Baboon Renal Grafts,” Journal of the American Medical Association 189 (1964): 159; and T. E. Starzl, T. L. Marchioro, G. N. Peters, et al., “Renal Heterotransplantation from Baboon to Man: Experience with Six Cases,” Transplantation 2 (1964): 752.

  67 L. L. Bailey, S. L. Nehlsen-Cannarella, W. Concepción, et al., “Baboon-to-Human Cardiac Xenotransplantation in a Neonate,” Journal of the American Medical Association 254 (1985): 3321— 29; A. L. Caplan, “Ethical Issues Raised by Research Involving Xenografts,” Journal of the American Medical Association 254 (1985): 3339–43; taped interview with Bailey conducted by Dr. Norman Swann, Australian Broadcasting Company, 1985; and T. E. Starzl, J. Fung, A. Tzakis. et al., “Baboon-to-Human Liver Transplantation,” Lancet 341 (1993): 65–71.

  68 R. Nowak, “One Baboon Liver, Two Baboon Livers … ,” Journal of NIH Research 5 (1993): 36–37; and R. Nowak, “Hope or Horror? Primate-to-Human Organ Transplants,” Journal of NIH Research 4 (1992): 37–38.

  69 J. D. Meyers, N. Flournoy, and E. D. Thomas, “Risk Factors for Cytomegalovirus Infection After Human Marrow Transplantation,” Journal of Infectious Diseases 153 (1986): 478–88; and E. Dussaix and C. Wood, “Cytomegalovirus Infection in Pediatric Liver Recipients,” Transplantation 48 (1989): 272–74.

  70 O. Chazouilères, D. Mamish, M. Kim, et al., “‘Occult’ Hepatitis B Virus as Source of Infection in Liver Transplant Recipients,” Lancet 343 (1994): 142–46.

  71 A. F. Sheids, R. C. Hackman, K. H. Fife, et al., “Adenovirus Infections in Patients Undergoing Bone-Marrow Transplantations,” New England Journal of Medicine 312 (1985): 529–33; and B. Koneru, R. Jaffe, C. O. Esquivel, et al., “Adenoviral Infections in Pediatric Liver Transplant Recipients,” Journal of the American Medical Association 258 (1987): 489–92.

  72 S. Euvrard, C. P. Noble, J. Kanitakis, et al., “Brief Report: Successive Occurrence of T-Cell and B-Cell Lymphomas After Renal Transplantation in a Patient with Multiple Cutaneous Squamous-Cell Carcinomas,” New England Journal of Medicine 327 (1992): 1924–26; and I. J. Spiro, D. W. Yandell, C. Li, et al., “Brief Report: Lymphoma of Donor Origin Occurring in the Porta Hepatitis of a Transplanted Liver,” New England Journal of Medicine 329 (1993): 27–29.

  73 E. K. Kuhn, “Deadly Fly Finds Home in Africa,” New African, November 1989: 24.

  74 W. C. Reeves, Epidemiology and Control of Mosquito-Borne Arboviruses in California, 1943— 1987 (Sacramento, CA: California Mosquito and Vector Control Association, 1990).

  75 Centers for Disease Control, “Arboviral Infections of the Central Nervous System—United States, 1985,” Morbidity and Mortality Weekly Report 35 (1986): 341–49; and Centers for Disease Control, “Arboviral Infections of the Central Nervous System—United States, 1989,” Morbidity and Mortality Weekly Report 39 (1990): 407–16.

  76 Centers for Disease Control, “Arboviral Surveillance—United States, 1990,” Morbidity and Mortality Weekly Report 39 (1990): 593–98; Centers for Disease Control, “Update: St. Louis Encephalitis—Florida and Texas, 1990,” Morbidity and Mortality Weekly Report 39 (1990): 756–59; and Centers for Disease Control, “Update: Arboviral Surveillance—Florida, 1990,” Morbidity and Mortality Weekly Report 39 (1990): 650–51.

  77 A. James, “Molecular Biology of the Mosquito Salivary Gland,” presentation to the Annual Meeting of the American Society of Tropical Medicine and Hygiene, Seattle, November 16, 1992.

  78 A. E. Hussein, R. F. Ramig, F. R. Holbrook, and B. J. Beaty, “Asynchronous Mixed Infection of Culicoides variipennis with Bluetongue Virus Serotypes 10 and 17,” Journal of General Virology 70 (1989): 3355–62.

  79 B. J. Beaty, D. W. Trent, and J. T. Roehrig, “Virus Variation and Evolution: Mechanisms and Epidemiological Significance,” Chapter 3 in T. Monath, ed., The Arboviruses: Epidemiology and Ecology (Boca Raton, FL: CRC Press, 1988).

  80 P. K. Anderson and F. J. Morales, “The Emergence of New Plant Diseases: The Case of Insect-Transmitted Plant Viruses,” presentation to the Workshop on New Disease, Woods Hole, MA, November 7–10, 1993; and K. Schneider, “Study Finds Risk in Making Plant Viruses Resistant,” New York Times, March 11, 1994: A16.

  81 B. W. Falk and G. Bruening, “Will Transgenic Crops Generate New Viruses and New Diseases?” Science 263 (1994): 1395–96.

  82 A. E. Greene and R. F. Allison, “Recombination Between Viral RNA and Transgenic Plant Transcripts,” Science 263 (1994): 1423–25.

  83 J. Davies, “Inactivation of Antibiotics and the Dissemination of Resistance Genes,” Science 264 (1994): 375–82.

  84 M. A. McClure, M. S. Johnson, D. F. Feng, and R. F. Doolittle, “Sequence Comparisons of Retroviral Proteins: Relative Rates of Change and General Phylogeny,” Proceedings of the National Academy of Sciences 85 (1988): 2469–73.

  85 H. M. Temin, “Is HIV Unique or Merely Different?” Journal of Acquired Immune Deficiency Syndromes 2 (1989): 1–9; and H. M. Temin, “Retrovirus Variation,” Chapter 20 in Morse, ed. (1993), op. cit.

  86 Temin had no doubt that successful recombination events had occurred in the viral world, and he cited as an example REV-T, a lymphatic cancer virus of birds. REV-T arose in 1946, the result of a recombination event between a retrovirus and a bird oncogene (inherent cancer-causing gene in the bird’s DNA).

  87 J. H. Strauss and E. G. Strauss, “Evolution of RNA Viruses,” Annual Review of Microbiology 42 (1988): 657–83.

  88 P. J. Cascone, T. F. Haydar, and A. E. Simon, “Sequences and Structures Required for Recombination Between Virus-Associated RNAs,” Science 260 (1993): 801–5.

  89 Hypervariable regions were also found in human DNA. For example, in 1992–94 scientists working separately in laboratories all over the world made the exciting discovery that human DNA contained stretches of long repetitive sequences of what seemed to b
e garbage. Three nucleotides, such as a CTG, would be repeated over and over, up to fifty or sixty times. For unknown reasons, some people’s cells would suddenly expand those repeats, up to 200 or more CTGs, and diseases would occur. Fragile-X Syndrome (Down’s Syndrome), Huntington’s Disease, Myotonic Dystrophy, and Spinobulbar Muscular Atrophy were all clearly linked to such triple-repeat regions of DNA. There were indications that Alzheimer’s Disease was also a triple-repeat disorder.

  90 This is the work of Ron Montelaro at Louisiana State University, often in collaboration with Jim Mullins, at Stanford University.

  91 M. C. Y. Heny, S. Y. Heng, and S. G. Allen, “Co-Infection and Synergy of Human Immunodeficiency Virus-1 and Herpes Simplex Virus-1,” Lancet 343 (1994): 255–58.

  92 D. Bartels, New Scientist, July 30, 1987: 53–54.

  93 L. Feigenbaum and G. Khoury, “The Role of Enhancer Elements in Viral Host Range and Pathogenicity,” in B. Fields, M. A. Martin, and D. Kamely, eds., Genetically Altered Viruses and the Environment (New York: Cold Spring Harbor Laboratory, 1985).

  94 B. N. Fields, D. M. Knipe, R. M. Chanock, et al., Virology (New York: Raven Press, 1985).

  95 For a sense of the microbial ecology issues Fields felt constituted the mysterious “orchestration,” see M. L. Nibert, D. B. Furlong, and B. N. Fields, “Mechanisms of Viral Pathogenesis,” Journal of Clinical Investigation 88 (1991): 727–34; A. Learmouth, Disease Ecology (New York: Basil Blackwell, 1988); and D. E. Pomeroy and M. W. Service, “The Ecology of Man,” Chapter 8 in Tropical Ecology (Essex, Eng.: Longman Scientific and Technical, 1986).

  96 J. D. Watson, N. H. Hopkins, J. W. Roberts, et al., Molecular Biology of the Gene (4th ed.; Menlo Park, CA: Benjamin/Cummings, 1987).

  97 See, for example, J. W. Ajioka and D. L. Hartl, “Population Dynamics of Transposable Elements,” Chapter 43 in D. E. Berg and M. M. Howe, Mobile DNA (Washington, D.C.: American Society for Microbiology, 1989).

  98 S. E. Luria and M. Delbruck, “Mutations of Bacteria from Virus Sensitivity to Virus Resistance,” Genetics 28 (1943): 491–511; and J. Lederberg and E. M. Lederberg, “Replica Plating and Indirect Selection of Bacterial Mutants,” Journal of Bacteriology 63 (1952): 399–406.

  99 J. Cairns, J. Overbaugh, and S. Miller, “The Origin of Mutants,” Nature 335 (1988): 142–46.

  100 A key counterargument came also from Harvard—the rival Medical School. Researchers showed that E. coli which carried an advantageous mutation could take over an apparently stagnant population of bacteria under stress. In their experiment, stressing a colony of bacteria caused the genetically advantaged to replace those that died without changing the overall size of the population. The researchers argued that Cairns and other supporters of the notion that bacteria could selectively mutate under stress were misinterpreting their results; randomness, they argued, was still at play, simply well disguised. See M. M. Zambrano, D. A. Siegele, M. Almirón, et al., “Microbial Competition: Escherichia coli Mutants That Take Over Stationary Phase Cultures,” Science 259 (1993): 1757–58.

  101 P. L. Foster, “Escherichia coli and Salmonella typhirium, Mutagenesis,” Encyclopedia of Microbiology 3 (1992): 1–8.

  102 R. I. Morimoto, “Cells in Stress: Transcriptional Activation of Heat Shock Genes,” Science 259 (1993): 1409–10.

  103 C. T. Walsh, “Vancomycin Resistance: Decoding the Molecular Logic,” Science 261 (1993): 308–9.

  104 S. P. Cohen, W. Yan, and S. B. Levy, “A Multidrug Resistance Regulation Chromosomal Locus Is Widespread Among Enteric Bacteria,” Journal of Infectious Diseases 168 (1993): 484–88.

  105 J. R. Johnson, I. Orskov, F. Orskov, et al., “0, K, and H Antigens Predict Virulence Factors, Carboxylesterase B Pattern, Antimicrobial Resistance, and Host Compromise Among Escherichia coli Strains Causing Urosepsis,” Journal of Infectious Diseases 169 (1994): 119–26.

  106 J. Travis, “Possible Evolutionary Role Explored for ‘Jumping Genes,’” Science 257 (1992): 884–85.

  107 A. A. Beaudry and G. F. Joyce, “Directed Evolution of an RNA Enzyme,” Science 257 (1992): 635–41.

  108 R. E. Lenski and J. E. Mittler, “The Directed Mutational Controversy and Neo-Darwinism,” Science 259 (1993): 188–93.

  109 D. A. Watson, “Unusual Mutational Mechanisms and Evolution,” Letter, Science 260 (1993): 1958.

  110 L. D. Hurst, “Unusual Mutational Mechanisms and Evolution,” Letter, Science 260 (1993): 1959.

  111 D. W. Hecht, T. J. Jagielo, and M. H. Malamy, “Conjugal Transfer of Antibiotic Resistance Factors in Bacteroides fragilis: The btgA and btgB Genes of Plasmid pBFTM10 Are Required for Its Transfer from Bacteroides fragilis and for Its Mobilization by IncP Beta Plasmid R751 in Escherichia coli,” Journal of Bacteriology 173 (1991): 7471–80.

  112 D. R. Schaberg, “Evolution of Antimicrobial Resistance and Nosocomial Infection: Lessons from the Vanderbilt Experiment,” American Journal of Medicine 70 (1981): 445–49; and C. F. Amabile-Cuevas and M. E. Chicurel, “Bacterial Plasmids and Gene Flux,” Cell 70 (1992): 189–99.

  113 S. Schwarz and S. Grolz–Krug, “The Cloramphenicol-Streptomycin-Resistance Plasmid from a Clinical Strain of Staphylococcus sciuri and Its Structural Relationship to Other Staphylococcal Resistance Plasmids,” FEMS Microbiology Letters 66 (1991): 319–22; and T. J. Coffey, C. G. Dowson, M. Daniels, et al., “Horizontal Transfer of Multiple Penicillin-Binding Protein Genes, and Capsular Biosynthetic Genes, in Natural Populations of Streptococcus pneumoniae,” Molecular Microbiology 5 (1991): 2255–60.

  114 P. Viljanen and J. Boratynski, “The Susceptibility of Conjugative Resistance Transfer in Gram-Negative Bacteria to Physiochemical and Biochemical Agents,” FEMS Microbiology Reviews 8 (1991): 43–54.

  115 D. S. Thaler, “The Evolution of Genetic Intelligence,” Science 264 (1994): 224–25; and R. S. Harris, S. Longerich, and S. M. Rosenberg, “Recombination in Adaptive Mutation,” Science 264 (1994): 258–60.

  116 See, for example, R. Levins, T. Awerbach, U. Brinkmann, et al., “The Emergence of New Diseases,” American Scientist 82 (1994): 52–60; A. Gibbons, “Where Are ‘New Diseases’ Born?” Science 261 (1993): 680–81; K. McAuliffe, “How New Are Today’s New Diseases?” U.S. News & World Report, November 17, 1986: 75–76; and A. S. Moffat, “Theoretical Ecology: Winning Its Spurs in the Real World,” Science 263 (1994): 1090–92.

  117 N. M. Ampel, “Plagues—What’s Past Is Present: Thoughts on the Origin and History of New Infectious Diseases,” Review of Infectious Diseases 13 (1991): 658–65.

  118 P. J. Kanki, K. U. Travers, S. MBoup, et al., “Slower Heterosexual Spread of HIV-2 Than HIV-1,” Lancet 343 (1994): 943–96; and K. M. DeCock, G. Adjarlolo, E. Ekpini, et al., “Epidemiology and Transmission of HIV-2. Why There Is No HIV-2 Pandemic,” Journal of the American Medical Association 270 (1993): 2083–86.

  119 P. W. Ewald, Evolution of Infectious Disease (New York: Oxford University Press, 1993).

  120 In Robert Gallo’s lab at the National Cancer Institute researchers showed in 1990 that mixing different HIV-1 quasispecies and a mouse retrovirus resulted in an expansion of the range of cell types the viruses were able to infect, suggesting that the various viral strains swapped useful genes. See P. Lusso, M. di Veronese, B. Ensoli, et al., “Expanded HIV-1 Cellular Tropism by Phenotypic Mixing with Murine Endogenous Retroviruses,” Science 247 (1990): 848–52.

  121 R. M. Anderson, R. M. May, M. C. Boily, et al., “The Spread of HIV-1 in Africa: Sexual Contact Patterns and the Predicted Demographic Impact of AIDS,” Nature 352 (1991): 581â�
�“89.

  122 P. W. Ewald, “Transmission Modes and the Evolution of Virulence,” Human Nature 2 (1990): 1–30; and P. W. Ewald, “The Evolution of Virulence,” Scientific American (April 1993): 86–93.

  123 R. B. Johnson, “Human Disease and the Evolution of Pathogen Virulence,” Journal of Theoretical Biology 122 (1986): 19–24; G. C. Williams and R. M. Neese, “The Dawn of Darwinian Medicine,” The Quarterly Review of Biology 66 (1991): 1–22; P. W. Ewald, “Pathogen-Induced Cycling of Outbreak Insect Populations,” Chapter 11 in Insect Outbreaks (New York: Academic Press, 1987); and P. W. Ewald, “Waterborne Transmission and the Evolution of Virulence Among Gastrointestinal Bacteria,” Epidemiology of Infection 106 (1991): 83–119.