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The ethics of using transgenic non-human primates to study what makes us human

Abstract

A flood of comparative genomic data is resulting in the identification of human lineage-specific (HLS) sequences. As apes are our closest evolutionary relatives, transgenic introduction of HLS sequences into these species has the greatest potential to produce 'humanized' phenotypes and also to illuminate the functions of these sequences. We argue that such transgenic apes would also be more likely than other species to experience harm from such research, which renders such studies ethically unacceptable in apes and justifies regulatory barriers between these species and other non-human primates for HLS transgenic research.

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References

  1. 1

    Darwin, C. The Descent of Man, and Selection in Relation to Sex (D. Appleton & Company, New York, 1871).

    Google Scholar 

  2. 2

    Huxley, T. H. Evidence as to Man's Place in Nature (Williams & Norgate, London, 1863).

    Google Scholar 

  3. 3

    Lovejoy, C. O., Suwa, G., Simpson, S. W., Matternes, J. H. & White, T. D. The great divides: Ardipithecus ramidus reveals the postcrania of our last common ancestors with African apes. Science 326, 100–106 (2009).

    CAS  PubMed  Google Scholar 

  4. 4

    Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2007).

  5. 5

    Sikela, J. M. The jewels of our genome: the search for the genomic changes underlying the evolutionarily unique capacities of the human brain. PLoS Genet. 2, e80 (2006).

    Article  Google Scholar 

  6. 6

    Konopka, G. et al. Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature 12, 169–170 (2009).

    Google Scholar 

  7. 7

    Hedlund, M. et al. N-glycolyIneuraminic acid deficiency in mice: implications for human biology and evolution. Mol. Cell. Biol. 27, 4340–4346 (2007).

    CAS  Article  Google Scholar 

  8. 8

    Varki, A. & Altheide, T. K. Comparing the human and chimpanzee genomes: searching for needles in a haystack. Genome Res. 15, 1746–1758 (2005).

    CAS  Article  Google Scholar 

  9. 9

    McConkey, E. H. & Varki, A. Thoughts on the future of great ape research. Science 309, 1499–1501 (2005).

    CAS  Article  Google Scholar 

  10. 10

    Go, Y. & Niimura, Y. Similar numbers but different repertoires of olfactory receptor genes in humans and chimpanzees. Mol. Biol. Evol. 25, 1897–1907 (2008).

    CAS  Article  Google Scholar 

  11. 11

    Wang, X., Thomas, S. D. & Zhang, J. Relaxation of selective constraint and loss of function in the evolution of human bitter taste receptor genes. Hum. Mol. Genet. 13, 2671–2678 (2004).

    CAS  Article  Google Scholar 

  12. 12

    Herrmann, E., Call, J., Hernandez-Lloreda, M. V., Hare, B. & Tomasello, M. Humans have evolved specialized skills of social cognition: the cultural intelligence hypothesis. Science 362, 731–744 (2007).

    Google Scholar 

  13. 13

    Taylor, J. Not a Chimp: The Hunt to Find the Genes That Make Us Human (Oxford Univ. Press, New York, 2009).

    Google Scholar 

  14. 14

    Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 431, 931–945 (2004).

  15. 15

    Rhesus Macaque Genome Sequencing and Analysis Consortium. Evolutionary and biomedical insights from the Rhesus macaque genome. Science 316, 222–234 (2007).

  16. 16

    Greene, R. E. et al. A draft sequence of the Neandertal genome. Science 328, 710–722 (2010).

    Article  Google Scholar 

  17. 17

    Fortna, A. et al. Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol. 2, 937–954 (2004).

    CAS  Article  Google Scholar 

  18. 18

    Popesco, M. C. et al. Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains. Science 313, 1304–1307 (2006).

    CAS  Article  Google Scholar 

  19. 19

    Dumas, L. et al. Gene copy number variation spanning 60 million years of human and primate evolution. Genome Res. 17, 1266–1277 (2007).

    CAS  Article  Google Scholar 

  20. 20

    Pollard, K. S. et al. Forces shaping the fastest evolving regions in the human genome. PLoS Genet. 13, e168 (2006).

    Article  Google Scholar 

  21. 21

    Enard, W. et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872 (2002).

    CAS  Article  Google Scholar 

  22. 22

    Caceres, M. et al. Elevated gene expression levels distinguish human from non-human primate brains. Proc. Natl Acad. Sci. USA 100, 13030–13035 (2003).

    CAS  Article  Google Scholar 

  23. 23

    Dumas, L. & Sikela, J. M. DUF1220 domains, cognitive disease, and human brain evolution. Cold Spring Harb. Symp. Quant. Biol. 74, 375–382 (2009).

    CAS  Article  Google Scholar 

  24. 24

    Tachibana, M. et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature 461, 367–372 (2009).

    CAS  Article  Google Scholar 

  25. 25

    Kuang, H., Wang, P. & Rsien, J. Z. Towards transgenic primates: what can we learn from mouse genetics? Sci. China 52, 506–514 (2009).

    CAS  Article  Google Scholar 

  26. 26

    Chan, A. W. S., Chong, K. Y., Martinovich, C., Simerly, C. & Schatten, G. Transgenic monkeys produced by retroviral gene transfer into mature oocytes. Science 291, 309–312 (2001).

    CAS  Article  Google Scholar 

  27. 27

    Yang, S. H. et al. Towards a transgenic model of Huntington's disease in a non-human primate. Nature 453, 863–864 (2008).

    Google Scholar 

  28. 28

    Kurt, S., Groszer, M., Fisher, S. E. & Ehret, G. Modified sound-evoked brainstem potentials in Foxp2 mutant mice. Brain Res. 1289, 30–36 (2009).

    CAS  Article  Google Scholar 

  29. 29

    Koyanagi, Y., Tanaka, Y., Ito, M. & Yamamoto, N. Humanized mice for human retrovirus infection. Curr. Top. Microbiol. Immunol. 324, 133–148 (2008).

    CAS  PubMed  Google Scholar 

  30. 30

    Mangalam, A., Rajagopalan, G., Taneja, V. & David, C. S. HLA class II transgenic mice mimic human inflammatory diseases. Adv. Immunol. 97, 65–147 (2008).

    CAS  Article  Google Scholar 

  31. 31

    Blanco-Aparicio, C. et al. Exploring the gain of function contribution of AKT to mammary tumorigenesis in mouse models. PLoS ONE 5, e9305 (2010).

    Article  Google Scholar 

  32. 32

    Enard, W. et al. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice. Cell 137, 800–802 (2009).

    Article  Google Scholar 

  33. 33

    Chan, A. W. S. & Yang, S. H. Generation of transgenic monkeys with human inherited genetic disease. Methods 49, 78–84 (2009).

    CAS  Article  Google Scholar 

  34. 34

    Romano, G., Marino, I. R., Pentimalli, F., Andamo, V. & Giordano, A. Insertional mutagenesis and development of malignancies induced by integrate gene delivery systems: implications for the design of safer gen-based interventions in patients. Drug News Perspect. 22, 185–196 (2009).

    CAS  Article  Google Scholar 

  35. 35

    Geschwind, D. H. & Levitt, P. Autism spectrum disorders: developmental disconnection syndromes. Curr. Opin. Neurobiol. 17, 103–111 (2007).

    CAS  Article  Google Scholar 

  36. 36

    Seeley, W. W. et al. Early frontotemporal dementia targets neurons unique to apes and humans. Ann. Neurol. 60, 660–667 (2006).

    Article  Google Scholar 

  37. 37

    Fisher, S. E. & Scharff, C. FOXP2 as a molecular window into speech and language. Trends Genet. 25, 166–177 (2009).

    CAS  Article  Google Scholar 

  38. 38

    OIE World Organization for Animal Health. The OIE World Assembly of national delegates adopts a 5th Strategic Plan for pursuing OIE global missions in animal health and welfare, OIE World Organization for Animal Health [online], http://www.oie.int/eng/press/en_100526.htm (2010).

  39. 39

    United States Department of Agriculture. Animal Welfare Act. 7 USC 2131. U.S. Government Printing Office [online].

  40. 40

    National Research Council of the National Academies. Guide for the Care and Use of Laboratory Animals Prepublication Draft (National Academy Press, Washington District of Columbia, 2010).

  41. 41

    United States Code of Federal Regulations. Animal Welfare Regulations: Title 9, sections 2.31 and 2.32. U.S. Government Printing Office [online], (2007).

  42. 42

    Institute of Laboratory Animal Resources Commission on Life Sciences of the National Research Council. Guide for the Care and Use of Laboratory Animals. (National Academy Press, Washington District of Columbia, 1996).

  43. 43

    Kong, Q. & Qin, C. Analysis of current laboratory animal science policies and administration in China. ILAR J. 51, e1–e10 (2010).

    Article  Google Scholar 

  44. 44

    Fenwick, N., Griffin, G. & Gauthier, C. The welfare of animals used in science: how the “Three Rs” ethics guides improvements. Can. Vet. J. 50, 523–530 (2009).

    PubMed  PubMed Central  Google Scholar 

  45. 45

    Weatherall, D. The use of non-human primates in research: a working group report chaired by Sir David Weatherall. The Academy of Medical Sciences [online], (2006).

    Google Scholar 

  46. 46

    Office of Public Sector Information. United Kingdom Animals (Scientific Procedures) Act of 5(5)a and 5(4). Office of Public Sector Information [online], (1986).

  47. 47

    Luy, J. Ethical and legal aspects of animal experiments on non-human primates. Dtsch. Tierarztl. Wochenschr. 114, 81–85 (2007).

    CAS  PubMed  Google Scholar 

  48. 48

    European Commission. Laboratory Animals, European Commission Enviroment [online], (2008).

  49. 49

    Griffin, G. Establishing a Three Rs programme at the Canadian Council on Animal Care. Altern. Lab. Anim. 37, (Suppl. 2) 63–67 (2009).

    CAS  PubMed  Google Scholar 

  50. 50

    Takahashi-Omoe, H. & Omoe, K. Animal experimentation in Japan: regulatory processes and application for microbiological studies. Comp. Immunol. Microbio. Infect. Dis. 30, 225–246 (2007).

    CAS  Article  Google Scholar 

  51. 51

    Omoe, H. Recent trends in animal experimentation in Japan — on the revision and implementation of the law for humane treatment and management of animals. Sci. Tech. Trends Quart. Rev. 21, 13–31 (2006).

    Google Scholar 

  52. 52

    National Center for Replacement, Refinement, and Reduction of Animals in Research. Primate accommodation, care and use. National Center for Replacement, Refinement, and Reduction of Animals in Research [online], (2006).

  53. 53

    Skene, L. et al. Ethics report on interspecies somatic cell nuclear transfer research. Cell Stem Cell 5, 27–30 (2009).

    CAS  Article  Google Scholar 

  54. 54

    Degrazia, D. Human–animal chimeras: human dignity, moral status, and species prejudice. Metaphilosophy 38, 309–329 (2007).

    Article  Google Scholar 

  55. 55

    Greene, M. et al. Moral issues of human–non-human primate neural grafting. Science 309, 385–386 (2005).

    CAS  Article  Google Scholar 

  56. 56

    Karpowicz, P., Cohen, C. B. & van der Kooy, D. Developing human–non-human chimeras in human stem cell research: ethical issues and boundaries. Kennedy Inst. Ethics J. 15, 107–129 (2005).

    Article  Google Scholar 

  57. 57

    Coors, M. & Hunter, L. Evaluation of genetic enhancement: will human wisdom properly acknowledge the value of evolution? Am. J. Bioeth. 5, 21–22 (2005).

    Article  Google Scholar 

  58. 58

    Warren, M. A. Moral Status: Obligations to Persons and Other Living Things (Oxford Univ. Press, New York,1997).

    Google Scholar 

  59. 59

    Nuffield Council on Bioethics. The ethics of research involving animals. Chapter 15. Nuffield Council on Bioethics [online], (2005).

  60. 60

    Banner, M. in Animal Biotechnology and Ethics. (eds Holland, A. & Johnson, A.) 325–339 (Chapman & Hall, London, 1998).

    Book  Google Scholar 

  61. 61

    Robert, J. S. & Baylis, F. Crossing species boundaries. Am. J. Bioeth. 3, 1–13 (2003).

    Article  Google Scholar 

  62. 62

    Juengst, E. T. in Ethics, Genetics and the Future of Sport: Implications of Genetic Modification and Genetic Selection (ed. Murray, T.) (Georgetown Univ. Press, Washington District of Columbia, 2009).

    Google Scholar 

  63. 63

    Brent, L. Life-long well being: applying animal welfare science to nonhuman primates in sanctuaries. J. Appl. Anim. Welf. Sci. 10, 55–61 (2007).

    CAS  Article  Google Scholar 

  64. 64

    Sughrue, M. E. et al. Bioethical considerations in translational research: primate stroke. Am. J. Bioeth. 9, 3–12 (2009).

    Article  Google Scholar 

  65. 65

    de Waal, F. B. A century of getting to know the chimpanzee. Nature 437, 56–59 (2005).

    CAS  Article  Google Scholar 

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Acknowledgements

The authors acknowledge the assistance of C.J. McCormick, M. O'Bleness, L. Dumas, J. Dang, J. Keeney and M. Douse for critical reading and preparation of the manuscript. J.M.S. is supported by National Institutes of Health (NIH) grants R01-MH081203 and RO1-AA11853. M.E.C. is supported by NIH grants 5P60DA011015 and RO1-DA029258. E.T.J. is supported by NIH grant P50-HG03390.

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Correspondence to Marilyn E. Coors.

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Coors, M., Glover, J., Juengst, E. et al. The ethics of using transgenic non-human primates to study what makes us human. Nat Rev Genet 11, 658–662 (2010). https://doi.org/10.1038/nrg2864

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