Advertisement

The Costs of Animal Experiments

  • Aysha Akhtar
Chapter
  • 479 Downloads
Part of the The Palgrave Macmillan Animal Ethics Series book series (PMAES)

Abstract

Despite our tremendous prevention power, the fact remains that drugs are important tools in the arsenal of modern medical science. To produce new drugs, we need research. This involves applied research, that is, research directly intended to produce a new treatment. Basic, or more exploratory, research is also utilized to help direct applied research. To approve a drug for the market, regulatory requirements usually dictate at least two major stages of safety and efficacy testing. The preclinical stage includes the use of in vitro and/or animal experiments to assess whether a drug is a viable candidate for further clinical investigation based on safety and efficacy evaluations. The clinical stage is broken down into three phases. Phase 1 typically involves a small group of healthy human volunteers to test the safety of a compound. Phases 2 and 3 usually include larger groups of volunteers in controlled clinical trials to test for both safety and efficacy of the potential treatment against the targeted disease or condition. Post-marketing studies are also often required to monitor the safety of a product once in use.

Keywords

Spinal Cord Injury Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome Human Result Human Spinal Cord Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

  1. 1.
    Dorsey ER, de Roulet J, Thompson JP et al. ‘Funding of US biomedical research, 2003–2008’ Journal of the American Medical Association 2010; 303: 137–143;CrossRefGoogle Scholar
  2. Roberts J. ‘Spending on medical research soars. U.S. now spends $95 billion a year on research, study finds’ CBS News September 20, 2005. www.cbsnews.com/stories/2005/09/20/health/main861059. shtml, date accessed December 10, 2010; Moses H. ‘Researchers, funding, and priorities: The razor’s edge’ Journal of the American Medical Association 2009; 302: 1001–1002;CrossRefGoogle Scholar
  3. Philipson L. ‘Medical research activities, funding, and creativity in Europe: Comparison with research in the United States’ Journal of the American Medical Association 2005; 294: 1394–1398.CrossRefGoogle Scholar
  4. 5.
    Hampton T ‘Targeted cancer therapies lagging. Better trial design could boost success rate’ Journal of the American Medical Association 2006; 296: 1951–1952.Google Scholar
  5. 9.
    Persson CCA, Erjefalt JS, Uller L, Andersson M, Greift L. ‘Unbalanced research’ Trends in Pharmacological Sciences 2001; 22: 538–541;CrossRefGoogle Scholar
  6. Horrobin DF. ‘Innovation in the pharmaceutical industry’ Journal of the Royal Society of Medicine 2000; 93: 341–345;Google Scholar
  7. Moses H, Dorsey ER, Matheson DHM, Thier SO. ‘Financial anatomy of biomedical research’ Journal of the American Medical Association 2005; 294: 1333–1342.CrossRefGoogle Scholar
  8. 12.
    Rosenberg RN. ‘Translating biomedical research to the bedside: A national crisis and call to action’ Journal of the American Medical Association 2003; 289: 1305–1306.CrossRefGoogle Scholar
  9. 14.
    Ioannidis JPA. ‘Evolution and translation of research findings: From bench to where?’ PLoS Clinical Trials 2006; 1: e36; O’Connell D, Roblin D. ‘Translational research in the pharmaceutical industry: From bench to bedside’ Drug Discovery Today 2006; 11: 833–838.CrossRefGoogle Scholar
  10. 15.
    Johnston CS. ‘Translation: Case study in failure’ Annals of Neurology 2006; 59: 447–448.CrossRefGoogle Scholar
  11. 16.
    Hurko O, Ryan JL. ‘Translational research in central nervous system drug discovery’ NeuroRx 2005; 2: 671–682.CrossRefGoogle Scholar
  12. 17.
    Johnston, 2006; Wall RJ, Shani M. ‘Are animal models as good as we think?’ Theriogenology 2008; 69: 2–9.CrossRefGoogle Scholar
  13. 20.
    Macleod MR, O’Collins T, Howells DW, Donnan GA. ‘Pooling of animal experimental data reveals influence of study design and publication bias’ Stroke 2004; 35: 1203–1208.CrossRefGoogle Scholar
  14. 24.
    Sinha G. ‘Cell-based tests tackle predicting safety of antibody drugs’ Nature Medicine 2006; 12: 485;CrossRefGoogle Scholar
  15. Allini M, Eisenstein SM, Ito K et al. ‘Are animal models useful for studying human disc disorders/degeneration? European Spine Journal 2008; 17: 2–19;CrossRefGoogle Scholar
  16. Horrobin DF. ‘Modern biomedical research: An internally self-consistent universe with little contact with medical reality?’ Nature Reviews Drug Discovery 2003; 2: 151–154; New Scientist. ‘Brainstorming’ New Scientist October 16, 2004: 2469. www.newscientist.com, date accessed January 14, 2011; Wall and Shani, 2008.CrossRefGoogle Scholar
  17. 25.
    Matthews RJ. ‘Medical progress depends on animal models—Doesn’t it?’ Journal of the Royal Society of Medicine 2008; 101: 95–98.CrossRefGoogle Scholar
  18. 26.
    Archibald K. ‘No need for monkeys’ New Scientist 2006; 191: 26;Google Scholar
  19. Neyt JG, Buckwalter JA, Carroll NC. ‘Use of animal models in musculoskeletal research’ Iowa Orthopedic Journal 1998; 18: 118–123;Google Scholar
  20. Sams-Dodd F. ‘Strategies to optimize the validity of disease models in the drug discovery process’ Drug Discovery Today 2006; 11: 355–363; Allen A. ‘Of mice and men: The problems with animal testing’ Slate June 1, 2006.CrossRefGoogle Scholar
  21. 27.
    Pound P, Ebrahim S. ‘Supportive evidence is lacking on animal studies’ British Medical Journal 2002; 325: 1038.CrossRefGoogle Scholar
  22. 29.
    Pound P, Ebrahim S, Sandercock P et al. ‘Where is the evidence that animal research benefits humans?’ British Medical Journal 2004; 328: 514–517; Matthews, 2008.CrossRefGoogle Scholar
  23. 30.
    Varga OE, Hansen AK, Sandoe P, Olsson IA. ‘Validating animal models for preclinical research: A scientific and ethical discussion’ Alternative to Laboratory Animals 2010; 38: 245–248.Google Scholar
  24. 34.
    Akhtar A, Pippin JJ, Sandusky CB. ‘Animal studies in spinal cord injury: A systematic review of methylprednisolone’ Alternatives to Laboratory Animals 2009; 37: 43–62;Google Scholar
  25. Akhtar A, Pippin JJ, Sandusky CB. ‘Animal models in spinal cord injury: A review’ Reviews in the Neurosciences 2008; 19: 47–60;CrossRefGoogle Scholar
  26. Kwon BJ, Hillyer J, Tetzlaff W. ‘Translational research in spinal cord injury: A survey of opinion from the SCI community’ Journal of Neurotrauma 2010; 27: 21–33.CrossRefGoogle Scholar
  27. 37.
    Baldwin A. Bekoff M. ‘Too stressed to work’ New Scientist 2007; 194: 24.CrossRefGoogle Scholar
  28. 38.
    Yevgenia K, Gross CG, Kopil C et al. ‘Experience induces structural and biochemical changes in the adult primate brain’ Proceedings of the National Academy of Sciences 2005; 102: 17478–17482.CrossRefGoogle Scholar
  29. 39.
    O’ Neil BJ, Kline JA, Burkhart K, Younger J. ‘Research fundamentals: V. The use of laboratory animal models in research’ Academic Emergency Medicine 1999; 6: 75–82;CrossRefGoogle Scholar
  30. Balcombe JP, Barnard ND, Sandusky C. ‘Laboratory routines cause animal stress’ Contemporary Topics in Laboratory Animal Science 2004; 43:42–51.Google Scholar
  31. 40.
    Akhtar et al., 2008; Balcome et al., 2004; Wilson LM, Baldwin AL. ‘Environmental stress causes mast cell degranulation, endothelial and epithelial changes, and edema in rat intestinal mucosa’ Microcirculation 1999; 6: 189–198; Baldwin and Bekoff, 2007.CrossRefGoogle Scholar
  32. 42.
    Kriegsfeld LJ, Eiasson MJ, Demas GE et al. ‘Nocturnal motor coordination deficits in neuronal nitric oxide synthase knock-out mice’ Neuroscience 1999; 89: 311–315.CrossRefGoogle Scholar
  33. 44.
    Chesler EJ, Wilson SG, Lariviere WR, Rodriguez-Zas SL, Mogil JS. ‘Identification and ranking of genetic and laboratory environment factors influencing a behavioral trait, thermal nociception, via computational analysis of a large data archive’ Neuroscience & Biobehavioral Reviews 2002; 26: 907–923.CrossRefGoogle Scholar
  34. 45.
    Gawrylewski A. ‘The trouble with animal models. Why did human trials fail?’ The Scientist 2007; 21: 44.Google Scholar
  35. 47.
    Akhtar et al., 2009; Lonjon N, Prieto M, Haton H et al. ‘Minimum information about animal experiments: Supplier is also important’ Journal of Neuroscience Research 2009; 87: 403–407; O’Neil et al., 1999; MacLeod et al., 2004.CrossRefGoogle Scholar
  36. 49.
    Crabbe JC, Wahlsten D, Dudek BC. ‘Genetics of mouse behavior: Interactions with laboratory environment’ Science 1999; 284: 1670–1672.CrossRefGoogle Scholar
  37. 50.
    Sandercock P, Roberts I. ‘Systematic reviews of animal experiments’ Lancet 2002; 360: 586;CrossRefGoogle Scholar
  38. Macleod M, Sandercock P. ‘Can systematic reviews help animal experiments work?’ RDS News Winter 2005; Roberts I, Kwan I, Evans P, Haig S. ‘Does animal experimentation inform human health care? Observations from a systematic review of international animal experiments on fluid resuscitation’ British Medical Journal 2002; 324: 474–476; CAMARADES, date accessed December 30, 2010; Gawrylewski, 2007.CrossRefGoogle Scholar
  39. 55.
    Curry SH. ‘Why have so many drugs with stellar results in laboratory stroke models failed in clinical trials? A theory based on allometric relationships’ Annals of the New York Academy of Sciences 2003; 993: 69–74;CrossRefGoogle Scholar
  40. Dirnagl U. ‘Bench to bedside: The quest for quality in experimental stroke research’ Journal of Cerebral Blood Flow & Metabolism 2006; 26: 1465–1478.CrossRefGoogle Scholar
  41. 57.
    Dirnagl, 2006; Macleod et al., 2004; Sena E, van der Worp B, Howells D, Macleod M. ‘How can we improve the pre-clinical development of drugs for stroke?’ Trends in Neurosciences 2007; 30: 433–439.CrossRefGoogle Scholar
  42. 58.
    Wiebers DO, Adams HP, Whisnant JP. ‘Animal models of stroke: Are they relevant to human disease?’ Stroke 1990; 21: 1–3.CrossRefGoogle Scholar
  43. 61.
    Fallon L. ‘Drug discovery for neurodegeneration—Inaugural Alzheimer’s drug discovery foundation meeting’ IDrugs 2007; 10: 233–236.Google Scholar
  44. 62.
    McGowan E, Eriksen J, Hutton M. ‘A decade of modeling Alzheimer’s disease in transgenic mice’ TRENDS in Genetics 2006; 22: 281–289;CrossRefGoogle Scholar
  45. Balducci C, Forloni G. ‘APP transgenic mice: Their use and limitations’ Neuromolecular Medicine December 9, 2010 (epub ahead of print); Jay GW, Memattos RB, Weinstein EJ et al. ‘Animal models for neural diseases’ Toxicologic Pathology November 30, 2010 (epub ahead of print); Götz J, Ittner LM. ‘Animal models of Alzheimer’s disease and frontotemporal dementia’ Nature 2008; 9: 532–544; Fallon, 2007.Google Scholar
  46. 68.
    Cabrera O, Berman DM, Kenyon NS et al. ‘The unique cytoarchitecture of human pancreatic islets has implications for islet cell function’ Proceedings of the National Academy of Sciences 2006; 103: 2334–2339;CrossRefGoogle Scholar
  47. Kakulas BA. ‘The applied neuropathology of human spinal cord injury’ Spinal Cord 1999; 37: 79–88; Akhtar et al., 2009.CrossRefGoogle Scholar
  48. 73.
    Mogil JS, Wilson SG, Bon K et al. ‘Heritability of nociception I: Responses of 11 inbred mouse strains on 12 measures of nociception’ Pain 1999; 80: 67–82.CrossRefGoogle Scholar
  49. 75.
    Terszowski G, Muller SM, Bleui CC et al. ‘Evidence for a functional second thymus in mice’ Science 2006; 312: 284–287.CrossRefGoogle Scholar
  50. 78.
    Laboratory News. ‘New guidlines published as mouse models thrown into question’ June, 2008. www.labnews.co.uk, date accessed December 27, 2010; Liao B-Y, Zhang J. ‘Null mutations in humans and mouse orthologs frequently result in different phenotypes’ Proceedings of the National Academy of Sciences 2008; 105: 6987–6992.CrossRefGoogle Scholar
  51. 81.
    Odom DT, Dowell RD, Jacobsen ES et al. ‘Tissue-specific transcriptional regulation has diverged significantly between human and mouse’ Nature Genetics 2007; 39: 730–732.CrossRefGoogle Scholar
  52. 95.
    Attarwala H. ‘TGN1412: From discovery to disaster’ Journal of Young Pharmacists July–September 2010; 2 (3): 332–336;CrossRefGoogle Scholar
  53. Hanke T. ‘Lessons from TGN1412’ Lancet 2006; 368: 1569–1570.CrossRefGoogle Scholar
  54. 97.
    Fraga MF, Ballestar E, Paz MF et al. ‘Epigenetic differences arise during the lifetime of monozygotic twins’ Proceedings of the National Academy of Sciences 2005; 102: 10604–10609.CrossRefGoogle Scholar
  55. 98.
    Ahmed J., Günther S, Möller F, Preissner R. ‘A structural genomics approach to the regulation of apoptosis: Chimp vs. human’ Genome Informatics 2007; 18: 22–34;Google Scholar
  56. Palfreyman et al., 2002; Khaitovich P, Muetzel B, She X et al. ‘Regional patterns of gene expression in human and chimpanzee brains’ Genome Research 2004; 14: 1462–1473;CrossRefGoogle Scholar
  57. Normille D. ‘Gene expression differs in human and chimp brains’ Science 2001; 292: 44–45.CrossRefGoogle Scholar
  58. 100.
    Lane E, Dunnett S. ‘Animal models of Parkinson’s disease and L-dopa induced dyskinesia: How close are we to the clinic?’ Psychopharmacology 2008; 199: 303–312.CrossRefGoogle Scholar
  59. 102.
    Hogan RJ. ‘Are nonhuman primates good models for SARS?’ PLoS Medicine 2006; 3: 1656–1657.CrossRefGoogle Scholar
  60. 104.
    Bettauer RH. ‘Chimpanzees in hepatitis c virus research: 1998–2007’ Journal of Medical Primatology 2010; 39: 9–23;CrossRefGoogle Scholar
  61. Bailey J. ‘An assessment of the use of chimpanzees in hepatitis c research past, present and future: 1. Validity of the chimpanzee model’ ATLA 2010; 38: 387–418.Google Scholar
  62. 105.
    Tonks A. ‘The quest for the AIDs vaccine’ British Medical Journal 2007; 334: 1346–1348.CrossRefGoogle Scholar
  63. 106.
    Archibald, 2006; Bailey J. ‘An assessment of the role of chimpanzee in AIDS vaccine research’ Alternative to Laboratory Animals 2008; 36: 381–428.Google Scholar
  64. 107.
    Ledford H. ‘HIV vaccine may raise risk’ Nature November 15, 2007; 450 (7168): 325.CrossRefGoogle Scholar
  65. 110.
    Bailey J. ‘Non-human primates in medical research and drug development: A critical review’ Biogenic Amines 2005; 19: 235–255.CrossRefGoogle Scholar
  66. 111.
    Schmidt C. ‘Researchers exploring faster alternatives to 2-year test for car-congenicity’ Journal of the National Cancer Institute 2006; 98: 228–230;CrossRefGoogle Scholar
  67. Ward JM. ‘The two-year rodent carcinogenesis bioassay—Will it survive?’ Journal of Toxicologic Pathology 2007; 20: 13–19.CrossRefGoogle Scholar
  68. 112.
    Gori GB. ‘The costly illusion of regulating unknowable risks’ Regulatory Toxicology and Pharmacology 2001; 34: 205–212;CrossRefGoogle Scholar
  69. Ward, 2007; Schmidt, 2006; Ennever FK, Lave LB. ‘Implications of the lack of accuracy of the lifetime rodent bioassay for predicting human carcinogenicity’ Regulatory Toxicology and Pharmacology 2003; 38: 52–57.CrossRefGoogle Scholar
  70. 117.
    Knight A, Bailey J, Balcombe J. ‘Animal carcinogenicity studies: 1. Poor human predictivity’ Alternative to Laboratory Animals 2006; 34: 19–27.Google Scholar
  71. 120.
    Heywood R. ‘Target organ toxicity’ Toxicology Letters 1981; 8: 349–358.CrossRefGoogle Scholar
  72. 123.
    Fletcher AR ‘Drug safety tests and subsequent clinical experience’ Journal of the Royal Society of Medicine 1978; 71: 693–696.Google Scholar
  73. 127.
    Brown LP. ‘Do rats comply with EPA policy on cancer risk assessment for formaldehyde?’ Regulatory Toxicology and Pharmacology 1989; 10: 196–200; Royal Society of Chemistry, Environment, Health and Safety Committee (EHSC). Note on potency of chemical carcinogens October 22, 2004. www.rsc.org, date accessed January 10, 2010.CrossRefGoogle Scholar
  74. 128.
    Corry DB, Irvin CG. ‘Promise and pitfalls in animal-based asthma research: Building a better mousetrap’ Immunology Research 2006; 35: 279–294.CrossRefGoogle Scholar
  75. 129.
    Contopoulis-Ioannadis DC, Ntzani EE, Ioannidis JPA. ‘Translation of highly promising basic science research into clinical applications’ American Journal of Medicine 2003; 114: 477–484.CrossRefGoogle Scholar
  76. 131.
    Harris RBS. ‘Appropriate animal models for clinical studies’ Annals of the New York Academy of Sciences 1997; 819: 155–168;CrossRefGoogle Scholar
  77. Dirnagl, 2006; Heywood, 1981; Heywood R. ‘Animal models: Their use and limitations in long-term safety evaluation of fertility-regulating agents’ Human Reproduction 1986; 1: 397–399;Google Scholar
  78. Tator CH. ‘Review of treatment trials in human spinal cord injury: Issues, difficulties, and recommendations’ Neurosurgery 2006; 59: 957–982;Google Scholar
  79. Heywood R. ‘Target organ toxicity II’ Toxicology Letters 1983; 18: 83–88; Sinha, 2006.CrossRefGoogle Scholar
  80. 132.
    Corpet DE, Pierre E ‘How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men’ European Journal of Cancer 2005; 41: 1911–1922;CrossRefGoogle Scholar
  81. Beyer C, Schett G, Distler O, Distler JHW. ‘Animal models of systemic sclerosis’ Arthritis and Rheumatism 2010; 62: 2831–2844;CrossRefGoogle Scholar
  82. Lazzarini L, Overgaard KA, Conti E, Shirtliff ME. ‘Experimental osteomyelitis: What have we learned from animal studies about the systemic treatment of osteomyelitis?’ Chemotherapy 2000; 18: 451–460;CrossRefGoogle Scholar
  83. Corry and Irvin, 2006; Krug N, Rabe KE ‘Animal models for human asthma: The perspective of a clinician’ Current Drug Targets 2008; 9: 438–442;CrossRefGoogle Scholar
  84. Gerlach M, Riederer P. ‘Animal models of Parkinson’s disease: An empirical comparison with the phenomenology of the disease in man’ Journal of Neural Transmission 1996; 103: 987–1041;CrossRefGoogle Scholar
  85. Codarri L, Fontana A, Becher B. ‘Cytokine networks in multiple sclerosis: Lost in translation’ Current Opinions in Neurology 2010; 23: 205–211;CrossRefGoogle Scholar
  86. Jay et al., 2010; Tabakoff B, Hoffman PL. ‘Animal models in alcohol research’ Alcohol Research and Health 2000; 24: 77–84;Google Scholar
  87. Dyson A, Singer M. ‘Animal models of sepsis: Why does preclinical efficacy fail to translate to the clinical setting?’ Critical Care Medicine 2009; 37 (Suppl.): S30–S37;CrossRefGoogle Scholar
  88. Marshall JC, Deitch E, Moldawer LL et al. ‘Preclinical models of shock and sepsis: What can they tell us?’ Shock 2005; 24 (Suppl. 1): 1–6;CrossRefGoogle Scholar
  89. van der Staay FJ. ‘Animal models of behavioral dysfunctions: Basic concepts and classifications, and an evaluation strategy’ Brain Research Reviews 2006; 52: 131–159; New Scientist, 2004.CrossRefGoogle Scholar
  90. 133.
    Knight A. ‘Systematic reviews of animal experiments demonstrate poor contributions toward human healthcare’ Reviews on Recent Clinical Trials 2008; 3: 89–96;CrossRefGoogle Scholar
  91. Craig W ‘Relevance of animal models for clinical treatment’ European Journal of Clinical Microbiology and Infectious Diseases 1993; 12 (Suppl. 1): S55–S57;CrossRefGoogle Scholar
  92. Knight BA. ‘Animal experiments scrutinised: Systematic review demonstrate poor human clinical and toxicological utility’ ALTEX 2007; 24: 320–325;Google Scholar
  93. Rohra DK, Jawaid A, Tauseef-ur-Rehman, Zaidi AH. ‘Reliability of rodent animal models in biomedical research’ Journal of the College of Physicians and Surgeons Pakistan 2005; 15: 809–812;Google Scholar
  94. Fletcher, 1978; Bailey, 2010; Bailey, 2008; Schein PS. ‘Preclinical toxicology of anticancer agents’ Cancer Research 1977; 37: 1934–1937;Google Scholar
  95. Lindl T, Voelkel M, Kolar R. ‘Animal experiments in biomedical research. An evaluation of the clinical relevance of approved animal experimental projects’ ALTEX 2005; 22: 143–151; Perel P, Roberts I, Sena E et al. ‘Comparison of treatment effects between animal experiments and clinical trials: Systemic review’ British Medical Journal Published online December 15, 2006. doi: 10.1136/bmj.39048.407928.BE.Google Scholar
  96. 134.
    Bracken MB. ‘Why are so many epidemiology associations inflated or wrong? Does poorly conducted animal research suggest implausible hypotheses?’ Annals of Epidemiology 2009; 19: 220–224.CrossRefGoogle Scholar
  97. 136.
    Lemon R, Dunnett SB. ‘Surveying the literature from animal experiments. Critical reviews may be helpful—Not systematic ones’ British Medical Journal 2005; 330: 977–978.CrossRefGoogle Scholar
  98. 142.
    Greek R, Greek J. ‘Animal research and human disease’ Journal of the American Medical Association 2000; 283: 743–744.CrossRefGoogle Scholar
  99. 145.
    Monastersky R. ‘Protesters fail to slow animal research’ Chronicle of Higher Education 2008; 54: 1.Google Scholar
  100. 152.
    Walker RL. ‘Human and animal subjects of research: The moral significance of respect versus welfare’ Theoretical Medicine and Bioethics 2006; 27: 305–331.CrossRefGoogle Scholar
  101. 153.
    Orlans FB. ‘Ethical decision making about animal experiments’ Ethics & Behavior 1997; 7: 163–171;CrossRefGoogle Scholar
  102. Rollin BE. ‘The regulation of animal research and the emergence of animal ethics: A conceptual history’ Theoretical Medicine and Bioethics 2006; 27: 285–304;CrossRefGoogle Scholar
  103. Walker, 2006; Kolar R. ‘Animal experimentation’ Science and Engineering Ethics 2006; 12: 111–122.CrossRefGoogle Scholar
  104. 156.
    Flecknell P. ‘Partnerships for progress’ Veterinary Anaesthesia and Analgesia 2005; 32: 239–240.CrossRefGoogle Scholar
  105. 157.
    Prescott MJ, Morton DB, Anderson D et al. ‘Refining dog husbandry and care—Eighth report of BVAAWF/FRAME/RSPCA/UFAW—Joint Working Group on Refinement’ Laboratory Animals 2004: 38 (Suppl. 1): S1–S94;CrossRefGoogle Scholar
  106. Würbel H, Stauffacher M, von Hoist D. ‘Stereotypies in laboratory mice—Quantitative and qualitative description of the ontogeny of “wire-gnawing” and “jumping” in Zur: ICR and Zur: ICR nu’ Ethology 1996; 102: 371–385;CrossRefGoogle Scholar
  107. Lutz C. ‘Stereotypic and self-injurious behaviour in rhesus macaques: A survey and retrospective analysis of environment and early experience’ American Journal of Primatology 2003; 60: 1–15;CrossRefGoogle Scholar
  108. Novak MA. ‘Self-injurious behaviour in rhesus monkeys: New insights into its etiology, physiology, and treatment’ American Journal of Primatology 2003; 59: 3–19.CrossRefGoogle Scholar
  109. 158.
    Mason GJ, Latham NR. ‘Can’t stop, won’t stop: Is stereotypy a reliable animal welfare indicator?’ Animal Welfare 2004; 13 (Suppl. 1): 57–69 (13).Google Scholar
  110. 159.
    Vertein R, Reinhardt V. ‘Training female rhesus monkeys to cooperate during in-homecage venipuncture’ Laboratory Primate Newsletter 1989; 28: 1–3.Google Scholar
  111. 160.
    Suckow MA, Weisbroth SH, Franklin CL (eds) The Laboratory Rat, 2nd edn. (Burlington, MA: Elselvier Academic Press) 2006, p. 323.Google Scholar
  112. 164.
    Flow BL, Jaques JT. ‘Effect of room arrangement and blood sample collection sequence on serum thyroid hormone and Cortisol concentrations in cynomolgus macaques(Macaca fascicularis)Contemporary Topics in Laboratory Animal Science 1997; 36: 65–68.Google Scholar
  113. 166.
    Nakayama K, Goto S, Kuroaka K, Nakamura K. ‘Decrease in nasal temperature of rhesus monkeys (Macaca mulatto) in negative emotional state’ Physiology & Behavior 2005; 84: 783–790.CrossRefGoogle Scholar
  114. 171.
    Voskoglou-Nomikos T, Pater JL, Seymour L. ‘Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models’ Clinical Cancer Research 2003; 9: 4227–4239.Google Scholar
  115. 172.
    Mayor S. ‘Researchers refine in vitro test that will reduce risk of “first in humans” drug trial’ British Medical Journal 2009; 358: 11.Google Scholar
  116. 174.
    Arnaud CH. ‘Systems biology’s clinical future. Although it now remains a research tool, systems biology is moving toward clinical applications, including personalized medicine’ Chemical and Engineering News July 31, 2006; 84: 17–26.Google Scholar
  117. 181.
    National Research Council of the National Academies. Toxicity Testing in the 21st Century: A Vision and a Strategy (Washington, DC: The National Academies Press) 2007.Google Scholar
  118. 182.
    DeGrazia D, Ashcroft RE, Dawson A, Draper H, McMillan J. (eds) On the Ethics of Animal Research in Principles of Health Care Ethics, 2nd edn. (West Sussex, England: Wiley Publications) 2007, p. 692.Google Scholar
  119. 183.
    Goldberg AM, Hartung T. ‘Protecting more than animals: Reducing animal suffering often has the unexpected benefit of yielding more rigorous safety tests’ Scientific American 2006; 294: 84–91;CrossRefGoogle Scholar
  120. Becker RA, Borgert CJ, Webb S et al. ‘Report of an ISRTP Workshop: Progress and barriers to incorporating alternative toxicological methods in the U.S.’ Regulatory Toxicology and Pharmacology 2006; 46: 18–22.CrossRefGoogle Scholar
  121. 185.
    Hartung T. ‘Food for thought… on animal tests’ ALTEX 2008; 25: 3–9.Google Scholar
  122. 187.
    Gottschall JG, Nichols R. ‘Head pitch affects muscle activity in the decerebrate cat hindlimb during walking’ Experimental Brain Research 2007; 182: 131–135.CrossRefGoogle Scholar
  123. 188.
    Ballard CL, Wood RI. ‘Partner preference in male hamsters: Steroids, sexual experience and chemosensory cues’ Physiology and Behavior 2007; 91: 1–8.CrossRefGoogle Scholar
  124. 189.
    Brenowitz EA, Lent K, Rubel EW. ‘Auditory feedback and song production do not regulate seasonal growth of song control circuits in adult white-crowned sparrows’ Journal of Neuroscience 2007; 27: 6810–6814.CrossRefGoogle Scholar
  125. 190.
    Alekseyenko OV, Waters P, Zhou H, Baum MJ. ‘Bilateral damage to the sexually dimorphic medial preoptic area/anterior hypothalamus of male ferrets causes a female-typical preference for and a hypothalamic Fos response to male body odors’ Physiology and Behavior 2007; 90: 438–449.CrossRefGoogle Scholar
  126. 191.
    de Oca BM, Minor TR, Fanselow MS. ‘Brief flight to a familiar enclosure in response to a conditional stimulus in rats’ Journal of General Psychology 2007; 134: 153–172.CrossRefGoogle Scholar
  127. 192.
    Winger G, Galuska CM, Hursh SR. ‘Modification of ethanol’s reinforcing effectiveness in rhesus monkeys by cocaine, flunitrazepam, or gamma-hydroxybutyrate’ Psychopharmacology 2007; 193: 587–598.CrossRefGoogle Scholar
  128. 193.
    Rollin BE. ‘Animal research: A moral science’ EMBO Reports 2007; 8: 521–525.CrossRefGoogle Scholar
  129. 194.
    Greek R, Greek J. ‘Is the use of sentient animals in basic research justifiable?’ Philosophy, Ethics, and Humanities in Medicine 2010; 5: 14.CrossRefGoogle Scholar

Copyright information

© Aysha Akhtar 2012

Authors and Affiliations

  • Aysha Akhtar
    • 1
    • 2
  1. 1.Oxford Centre for Animal EthicsUK
  2. 2.US Food and Drug AdministrationNorth PotomacUSA

Personalised recommendations