Science and Engineering Ethics

, Volume 21, Issue 3, pp 595–617 | Cite as

Human–Animal Chimera: A Neuro Driven Discussion? Comparison of Three Leading European Research Countries

  • Laura Yenisa Cabrera Trujillo
  • Sabrina Engel-Glatter
Original Paper


Research with human–animal chimera raises a number of ethical concerns, especially when neural stem cells are transplanted into the brains of non-human primates (NHPs). Besides animal welfare concerns and ethical issues associated with the use of embryonic stem cells, the research is also regarded as controversial from the standpoint of NHPs developing cognitive or behavioural capabilities that are regarded as “unique” to humans. However, scientists are urging to test new therapeutic approaches for neurological diseases in primate models as they better mimic human physiology than all current animal models. As a response, various countries have issued reports on the topic. Our paper summarizes the ethical issues raised by research with human–animal brain chimeras and compares the relevant regulatory instruments and different recommendations issued in national reports from three important European research nations: Germany, Switzerland and the United Kingdom. We assess and discuss the focus and priorities set by the different reports, review various reasons for and perspectives on the importance of the brain in chimera research, and identify critical points in the reports that warrant further specification and debate.


Human–animal chimera Moral status Neuroethics Stem cells 



We would like to thank the Brocher Foundation for supporting the writing of this paper through their visiting fellowship program. We would also like to thank the insightful comments and suggestions of our blind reviewers.


  1. Academy of Medical Sciences (2010). Exploring the Boundaries: Report on a public dialogue into animals containing human material.Google Scholar
  2. Alzheimer’s Disease International (2009). World Alzheimer’s report.Google Scholar
  3. Araki, R., Uda, M., Hoki, Y., Sunayama, M., Nakamura, M., Ando, S., et al. (2013). Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature, 494(7435), 100–104. doi: 10.1038/nature11807.CrossRefGoogle Scholar
  4. Baker, M. (2013). Safety of induced stem cells gets a boost. Nature, 493(7431), 145. doi: 10.1038/493145a.CrossRefGoogle Scholar
  5. Balaban, E., Teillet, M., & Le Douarin, N. (1988). Application of the quail-chick chimera system to the study of brain development and behaviour. Science, 241(4871), 1339–1342. doi: 10.1126/science.3413496.CrossRefGoogle Scholar
  6. Barker, R. A. (2012). Stem cells and neurodegenerative diseases: where is it all going? Regenerative Medicine, 7(6s), 26–31. doi: 10.2217/rme.12.64.CrossRefGoogle Scholar
  7. Baylis, F., & Fenton, A. (2007). Chimera research and stem cell therapies for human neurodegenerative disorders. Cambridge Quarterly of Healthcare Ethics, 16(02), 195–208. doi: 10.1017/S0963180107070211.CrossRefGoogle Scholar
  8. Boland, D. F., & Stacy, M. (2012). The economic and quality of life burden associated with Parkinson’s disease: A focus on symptoms. The American Journal of Managed Care, 18(7 Suppl), S168–S175.Google Scholar
  9. de Melo-Martin, I. (2009). Chimeras and Human dignity. Kennedy Institute of Ethics Journal, 18(4), 331–346.CrossRefGoogle Scholar
  10. Dunnett, S. B., & Rosser, A. E. (2014). Challenges for taking primary and stem cells into clinical neurotransplantation trials for neurodegenerative disease. Neurobiology of Disease, 61, 79–89. doi: 10.1016/j.nbd.2013.05.004.CrossRefGoogle Scholar
  11. Deutsher Ethikrat (2011). Human-animal mixtures in research. [Berlin: German Ethics Council (Opinion)].Google Scholar
  12. Emborg, M. E., Liu, Y., Xi, J., Zhang, X., Yin, Y., Lu, J., et al. (2013). Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain. Cell Reports, 3(3), 646–650. doi: 10.1016/j.celrep.2013.02.016.CrossRefGoogle Scholar
  13. ESTOOLS. (2008). Ethical aspects of research on interspecies embryos and iPS cells. Sweden: Lund.Google Scholar
  14. European Commission (2013). Neurodegenerative Disorders.Google Scholar
  15. Fangerau, H., Fegert, J. M., & Trapp, T. (2011). Implanted minds: The neuroethics of intracerebral stem cell transplantation and deep brain stimulation. Bielefeld: Transcript Verlag.Google Scholar
  16. Greely, H. T., Cho, M. K., Hogle, L. F., & Satz, D. M. (2007). Thinking about the human neuron mouse. The American Journal of Bioethics, 7(5), 27–40.CrossRefGoogle Scholar
  17. Greene, M. (2005). Human to non-human primate neural grafting: is it justified?
  18. Greene, M., Schill, K., Takahashi, S., Bateman-House, A., Beauchamp, T., Bok, H., et al. (2005). Ethics: Moral issues of human-non-human primate neural grafting. Science, 309(5733), 385–386. doi: 10.1126/science.1112207.CrossRefGoogle Scholar
  19. Grunwell, J., Illes, J., & Karkazis, K. (2009). Advancing neuroregenerative medicine: A call for expanded collaboration between scientists and ethicists. Neuroethics, 2(1), 13–20. doi: 10.1007/s12152-008-9025-5.CrossRefGoogle Scholar
  20. Harding, J., Roberts, R. M., & Mirochnitchenko, O. (2013). Large animal models for stem cell therapy. Stem Cell Research & Therapy, 4(2), 23. doi: 10.1186/scrt171.CrossRefGoogle Scholar
  21. Harvey, A., & Salter, B. (2012). Anticipatory governance: Bioethical expertise for human/animal chimeras. Science as Culture, 21(3), 291–313.CrossRefGoogle Scholar
  22. Held, V. (2006). The ethics of care: Personal, political, and global. Oxford; New York: Oxford University Press.Google Scholar
  23. Human Fertilisation and Embriology Authority (2007a). Hybrids and chimeras: a consultation on the ethical and social implications of creating human/animal embryos in research. London, UK.Google Scholar
  24. Human Fertilisation and Embryology Authority (2007b). Hybrids and chimera: A report on the findings of the consultation.Google Scholar
  25. Hunther, C. (2009). Chimeras: The ethics of creating human-animal interspecifics. Munchen: Universitat Munchen, Ludwig-Maximilians-Universitat Munchen.Google Scholar
  26. Hyun, I., Taylor, P., Testa, G., Dickens, B., Jung, K. W., McNab, A., et al. (2007). Ethical standards for human-to-animal chimera experiments in stem cell research. Cell Stem Cell, 1(2), 159–163. doi: 10.1016/j.stem.2007.07.015.CrossRefGoogle Scholar
  27. Karpowicz, P., Cohen, C. B., & Van der Kooy, D. (2005). Developing human-nonhuman chimeras in human stem cell research: Ethical issues and boundaries. Kennedy Institute of Ethics Journal, 15(2), 107–134.CrossRefGoogle Scholar
  28. Kobayashi, N. R. (2003). A scientist crossing a boundary: a step into the bioethical issues surrounding stem cell research. [Comment]. The American Journal of Bioethics, 3(3), W15–W16. doi: 10.1162/15265160360706750.CrossRefGoogle Scholar
  29. Kriks, S., Shim, J. W., Piao, J., Ganat, Y. M., Wakeman, D. R., Xie, Z., et al. (2011). Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature, 480(7378), 547–551. doi: 10.1038/nature10648.Google Scholar
  30. Lindvall, O., Rehncrona, S., Gustavii, B., Brundin, P., Astedt, B., Widner, H., et al. (1988). Fetal dopamine-rich mesencephalic grafts in Parkinson’s disease. Lancet, 2(8626–8627), 1483–1484.CrossRefGoogle Scholar
  31. MacKellar, C. (2013). Differentiating between human and non-human interspecies embryos. Journal of Medical Ethics,. doi: 10.1136/medethics-2013-101363.Google Scholar
  32. Macrì, S., Ceci, C., Altabella, L., Canese, R., & Laviola, G. (2013). The Directive 2010/63/EU on animal experimentation may skew the conclusions of pharmacological and behavioural studies. Science Report 3. doi: 10.1038/srep02380.
  33. Magnani, T. A. (1999). The patentability of human-animal chimeras. Berkeley Tech. L.J., 14, 443–460.Google Scholar
  34. Menache, A. (2010). The replacement of human primates in brain research. Strasbourg: One Voice (Report).Google Scholar
  35. NEK (2006). Research involving human embryos and fetuses. [Bern: National Ethikkommission im Bereich Humanmedizin (NEK) (Opinion no. 11/2006)].Google Scholar
  36. Nuffield Council on Bioethics (2005). The ethics of research involving animals. London, UK.Google Scholar
  37. Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., et al. (2008). Disease-specific induced pluripotent stem cells. Cell, 134(5), 877–886. doi: 10.1016/j.cell.2008.07.041.CrossRefGoogle Scholar
  38. Pluchino, S., Gritti, A., Blezer, E., Amadio, S., Brambilla, E., Borsellino, G., et al. (2009). Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Annals of Neurology, 66(3), 343–354. doi: 10.1002/ana.21745.CrossRefGoogle Scholar
  39. Purves, D., Augustine, G., Fitzpatrick, D., & Al, E. (2001). Development of language: a critical period in humans. In D. Purves, G. Augustine, D. Fitzpatrick, & E. Al (Eds.), Neuroscience (2nd ed.). Sunderland (MA): Sinauer Asscociated.Google Scholar
  40. Redmond, D. E., Bjugstad, K. B., Teng, Y. D., Ourednik, V., Ourednik, J., Wakeman, D. R., et al. (2007). Behavioral improvement in a primate Parkinson’s model is associated with multiple homeostatic effects of human neural stem cells. Proceedings of the National Academy of Sciences, 104(29), 12175–12180. doi: 10.1073/pnas.0704091104.CrossRefGoogle Scholar
  41. Reusser, R., & Schweizer, R. J. (2008). Kommentar zur Art. 119. In B. Ehrenzeller, P. Mastronardi, R. J. Schweizer, & K. A. Vallender (Eds.), Die schweizerische Bundesverfassung- Kommentar, 2. Auflage, dike Verlag und Schulthess Juristische Medien (St Gallen Commentary on the Federal Constitution).Google Scholar
  42. Ricceri, L., & Vitale, A. (2011). The law through the eye of a needle. EMBO Report, 12(7), 637–640.CrossRefGoogle Scholar
  43. Robert, J. S. (2006). The science and ethics of making part-human animals in stem cell biology. The FASEB Journal, 20(7), 838–845. doi: 10.1096/fj.05-4286lsf.CrossRefGoogle Scholar
  44. Robert, J. S., & Baylis, F. (2003). Crossing species boundaries. The American Journal of Bioethics, 3(3), 1–13. doi: 10.1162/15265160360706417.CrossRefGoogle Scholar
  45. Rose, N. (2009). The Politics of Life Itself: Biomedicine, power, and subjectivity in the twenty-first century. Princeton: Princeton University Press.Google Scholar
  46. Russell, W. M. S., & Burch, R. L. (1959). The principles of humane experimental technique. London: Methuen.Google Scholar
  47. Secretary of State for the Home Department (1986). Guidance on the Operation of the Animals (Scientific Procedures) Act 1986. UK.Google Scholar
  48. Streiffer, R. (2005). At the edge of humanity: human stem cells, chimeras, and moral status. Kennedy Institute of Ethics Journal, 15(4), 347–370.CrossRefGoogle Scholar
  49. Streiffer, R. (2010). Chimeras, moral status, and public policy: Implications of the abortion debate for public policy on human/nonhuman chimera research. The Journal of Law, Medicine & Ethics, 38(2), 238–250. doi: 10.1111/j.1748-720X.2010.00484.x.CrossRefGoogle Scholar
  50. Suran, M., & Wolinsky, H. (2009). The end of monkey research? EMBO Report, 10(10), 1080–1082.CrossRefGoogle Scholar
  51. Swiss Academy of Medical Sciences (2009). Interspecies Crosses: Aspects of Animal Protection. [Basel: Ethics Committee for Animal Studies of the Swiss Academy of Medical Sciences and Swiss Academy of Sciences (Position statement)].Google Scholar
  52. Swiss Academies of Arts and Sciences (2010). The dignity of animals and the evaluation of interests in the Swiss Animal Protection Act. [Ethics Committee for Animal Experimentation of the Swiss Academies of Arts and Sciences (Position statement)].Google Scholar
  53. Tamaki, S., Eckert, K., He, D., Sutton, R., Doshe, M., Jain, G., et al. (2002). Engraftment of sorted/expanded human central nervous system stem cells from fetal brain. Journal of Neuroscience Research, 69(6), 976–986. doi: 10.1002/jnr.10412.CrossRefGoogle Scholar
  54. The Academy of Medical Sciences (2011). Animals containing human material.Google Scholar
  55. The Danish Council of Ethics (2008). Man or Mouse? Ethical aspects of chimera research.Google Scholar
  56. The National Academies. (2005). Guidelines for human embryonic stem cell research. Washington: The National Academies Press.Google Scholar
  57. Tomasello, M., & Call, J. (2011). Methodological challenges in the study of primate cognition. Science, 6060, 1227–1228. doi: 10.1126/science.1213443.CrossRefGoogle Scholar
  58. Uchida, N., Buck, D. W., He, D., Reitsma, M. J., Masek, M., Phan, T. V., et al. (2000). Direct isolation of human central nervous system stem cells. Proceedings of the National Academy of Sciences, 97(26), 14720–14725. doi: 10.1073/pnas.97.26.14720.CrossRefGoogle Scholar
  59. Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Sudhof, T. C., & Wernig, M. (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature, 463(7284), 1035–1041. doi: 10.1038/nature08797.CrossRefGoogle Scholar
  60. Walter, S. (2010). Locked-in syndrome, BCI, and a confusion about embodied, embedded, extended, and enacted cognition. Neuroethics, 3(1), 61–72. doi: 10.1007/s12152-009-9050-z.CrossRefGoogle Scholar
  61. World Health Organization (2003). Global Declaration for Parkinson’s Disease.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Laura Yenisa Cabrera Trujillo
    • 1
  • Sabrina Engel-Glatter
    • 1
  1. 1.Institute of Biomedical EthicsUniversity of BaselBaselSwitzerland

Personalised recommendations