1932

Abstract

Human gene editing, particularly using the new CRISPR/Cas9 technology, will greatly increase the capability to make precise changes to human genomes. Human gene editing can be broken into four major categories: somatic therapy, heritable gene editing, genetic enhancement, and basic and applied research. Somatic therapy is generally well governed by national regulatory systems, so the need for global governance is less urgent. All nations are in agreement that heritable gene editing should not proceed at this time, but there is likely to be divergence if and when such procedures are shown to be safe and effective. Gene editing for enhancement purposes is not feasible today but is more controversial with the public, and many nations do not have well-developed regulatory systems for addressing genetic enhancement. Finally, different nations treat research with human embryos very differently based on deeply embedded social, cultural, ethical, and legal traditions. Several international governance mechanisms are currently in operation for human gene editing, and several other governance mechanisms have been proposed. It is unlikely that any single mechanism will alone be effective for governing human gene editing; rather, a polycentric or ecosystem approach that includes several overlapping and interacting components is likely to be necessary.

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2021-08-31
2024-04-20
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Literature Cited

  1. 1. 
    Abbott KW, Marchant GE, Sylvester DS. 2006. A framework convention for nanotechnology?. Environ. Law Rep. 36:10931–42
    [Google Scholar]
  2. 2. 
    Adashi EY, Cohen IG. 2015. Editing the genome of the human germline: May cool heads prevail. Am. J. Bioethics 15:40–42
    [Google Scholar]
  3. 3. 
    Adashi EY, Cohen IG. 2019. Heritable genome editing: Is a moratorium needed?. JAMA 322:104–5
    [Google Scholar]
  4. 4. 
    Allyse M, Bombard Y, Isasi R, Michie M, Musunuru K et al. 2019. What do we do now? Responding to claims of germline gene editing in humans. Genet. Med. 21:2181–83
    [Google Scholar]
  5. 5. 
    Araki M, Ishii T. 2014. International regulatory landscape and integration of corrective genome editing into in vitro fertilization. Reprod. Biol. Endocrinol. 12:108
    [Google Scholar]
  6. 6. 
    Asch A. 2003. Disability equality and prenatal testing: contradictory or compatible?. Fla. State Univ. Law Rev. 30:315–42
    [Google Scholar]
  7. 7. 
    Ates H, Rathbone T, Stuart C, Bridges PH, Cottle RN. 2020. Delivery approaches for therapeutic genome editing and challenges. Genes 11:1113
    [Google Scholar]
  8. 8. 
    Baltimore D, Berg P, Botchan M, Carroll D, Charro RA et al. 2015. A prudent path forward for genomic engineering and germline gene modification. Science 348:36–38
    [Google Scholar]
  9. 9. 
    Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P et al. 2007. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315:1709–12
    [Google Scholar]
  10. 10. 
    Baylis F. 2017. Human germline genome editing and broad societal consensus. Nat. Hum. Behav. 1:0103
    [Google Scholar]
  11. 11. 
    Baylis F, Darnovsky M, Hasson K, Krahn TM. 2020. Human germline and heritable editing: the global policy landscape. CRISPR J 3:365–77
    [Google Scholar]
  12. 12. 
    Blendon RJ, Gorski MT, Benson JM. 2016. The public and the gene-editing revolution. N. Engl. J. Med. 374:1406–11
    [Google Scholar]
  13. 13. 
    Botkin JR. 2020. The case for banning heritable genome editing. Genet. Med. 22:487–89
    [Google Scholar]
  14. 14. 
    Brokowski C. 2018. Do CRISPR germline ethics statements cut it?. CRISPR J 1:115–25
    [Google Scholar]
  15. 15. 
    Burrall S. 2018. Rethink public engagement for gene editing. Nature 555:438–39
    [Google Scholar]
  16. 16. 
    Cameron NMDS, Henderson AV. 2008. Brave new world at the General Assembly: the United Nations declaration on human cloning. Minn. J. Law Sci. Technol. 9:145–238
    [Google Scholar]
  17. 17. 
    Caplan A. 2019. Getting serious about the challenge of regulating germline gene therapy. PLOS Biol 17:e3000223
    [Google Scholar]
  18. 18. 
    Carroll D, Charo RA. 2015. The societal opportunities and challenges of genome editing. Genome Biol 16:242
    [Google Scholar]
  19. 19. 
    Charo RA. 2016. On the road (to a cure?)—stem-cell tourism and lessons for gene editing. New Engl. J. Med. 374:901–3
    [Google Scholar]
  20. 20. 
    Charo RA. 2019. Rogues and regulation of germline editing. N. Engl. J. Med. 380:976–80
    [Google Scholar]
  21. 21. 
    Cohen IG. 2016. The FDA is prohibited from going germline. Science 353:545–46
    [Google Scholar]
  22. 22. 
    Cohen IG, Adashi EY, Gerke S, Palacios-González C, Ravitsky V. 2020. The regulation of mitochondrial replacement techniques around the world. Annu. Rev. Genom. Hum. Genet. 21:565–86
    [Google Scholar]
  23. 23. 
    Cohen J. 2019. Inside the circle of trust. Science 365:430–37
    [Google Scholar]
  24. 24. 
    Cohen J. 2019. Moratorium for germline editing splits biologists. Science 363:1130–31
    [Google Scholar]
  25. 25. 
    Cohen J. 2020. A cut above: pair that developed CRISPR earns historic award. Science 370:271–72
    [Google Scholar]
  26. [Google Scholar]
  27. 27. 
    Coller BS. 2019. Ethics of human genome editing. Annu. Rev. Med. 70:289–305
    [Google Scholar]
  28. 28. 
    Collins FS. 2015. Statement on NIH funding of research using gene-editing technologies in human embryos. The NIH Director Apr. 28. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-nih-funding-research-using-gene-editing-technologies-human-embryos
    [Google Scholar]
  29. 29. 
    Com. Consult. Natl. Éthique Sci. Vie Santé, Dtsch. Ethikrat, Nuffield Counc. Bioethics 2020. Joint statement on the ethics of heritable human genome editing Jt. Statement, Mar. 3. https://www.nuffieldbioethics.org/assets/pdfs/Joint-statement.pdf
  30. 30. 
    Comm. Sci. Technol. Law 2016. International Summit on Human Gene Editing: a global discussion Meet. Rep., Natl. Acad. Sci. Eng. Med Washington, DC: https://www.ncbi.nlm.nih.gov/books/NBK343651
  31. 31. 
    Counc. Eur 1997. Convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine: convention on human rights and biomedicine Eur. Treaty Ser. 164 Counc. Eur Strasbourg, Fr: https://rm.coe.int/168007cf98
  32. 32. 
    Counc. Eur 1999. Chart of signatures and ratifications of: the Convention on Human Rights and Biomedicine, the Protocol on the Prohibition of Cloning Human Beings, the Protocol Concerning Transplantation of Organs, Tissues of Human Origin, the Protocol Concerning Biomedical Research, the Protocol Concerning Genetic Testing for Health Purposes DH-BIO/INF (2019) 2 Counc. Eur Strasbourg, Fr: https://rm.coe.int/inf-2019-2-etat-sign-ratif-reserves-bil-002-/16809979a8
  33. 33. 
    Cyranoski D, Ledford H. 2018. International outcry over genome-edited baby claim. Nature 563:607–8
    [Google Scholar]
  34. 34. 
    Daley GQ, Lovell-Badge R, Steffann J. 2019. After the storm—a responsible path for genome editing. New Engl. J. Med. 380:897–99
    [Google Scholar]
  35. 35. 
    Daniels N. 2000. Normal functioning and the treatment-enhancement distinction. Camb. Q. Healthc. Ethics 9:302–22
    [Google Scholar]
  36. 36. 
    Davies K. 2020. Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing New York: Pegasus
  37. 37. 
    Davus BD. 1970. Prospects for genetic intervention in man. Science 170:1279–83
    [Google Scholar]
  38. 38. 
    Desine S, Hollister BM, Abdallah KE, Persaud A, Hull SC et al. 2020. The meaning of informed consent: genome editing clinical trials for sickle cell disease. AJOB Empir. Bioethics 11:195–207
    [Google Scholar]
  39. 39. 
    Doudna JA. 2019. CRISPR's unwanted anniversary. Science 366:777
    [Google Scholar]
  40. 40. 
    Doudna JA. 2020. The promise and challenge of therapeutic genome editing. Nature 578:229–36
    [Google Scholar]
  41. 41. 
    Doudna JA, Charpentier E. 2014. The new frontier of genome engineering with CRISPR-Cas9. Science 346:1258096
    [Google Scholar]
  42. 42. 
    Dryzek JS, Nicol D, Niemeyer S, Pemberton S, Curato N et al. 2020. Global citizen deliberation on genome editing. Science 369:1435–37
    [Google Scholar]
  43. 43. 
    Fogarty NME, McCarthy A, Snijders KE, Powell BE, Kubikova N et al. 2017. Genome editing reveals a role for OCT4 in human embryogenesis. Nature 550:67–73
    [Google Scholar]
  44. 44. 
    Frankel MS, Chapman AR. 2000. Human Inheritable Genetic Modifications: Assessing Scientific, Ethical, Religious, and Policy Issues Washington, DC: Am. Assoc. Adv. Sci.
    [Google Scholar]
  45. 45. 
    Friedman T, Jonlin EC, King NMP, Torbett BE, Wivel NA et al. 2015. ASGCT and JSGT joint position statement on human genomic editing. Mol. Ther. 23:1282
    [Google Scholar]
  46. 46. 
    Garden H, Winickoff D. 2018. Gene editing for advanced therapies: governance, policy and society OECD Sci. Technol. Ind. Work. Pap. 2018/12 Organ. Econ. Co-op. Dev Paris: https://doi.org/10.1787/8d39d84e-en
    [Crossref]
  47. 47. 
    Gardner W. 1995. Can human genetic enhancement be prohibited?. J. Med. Philos. 20:65–84
    [Google Scholar]
  48. 48. 
    Ger. Ethics Counc 2019. Intervening in the human germline Rep., Ger. Ethics Counc Berlin: https://www.ethikrat.org/fileadmin/Publikationen/Stellungnahmen/englisch/opinion-intervening-in-the-human-germline-summary.pdf
  49. 49. 
    Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR. 2018. Gene therapy clinical trials worldwide to 2017: an update. J. Gene Med. 20:e3015
    [Google Scholar]
  50. 50. 
    Greely HT. 2019. CRISPR'd babies: human germline genome editing in the ‘He Jiankui affair.’. J. Law Biosci. 6:111–83
    [Google Scholar]
  51. 51. 
    Gregorowius D, Biller-Andorno N, Deplazes-Zemp A. 2017. The role of scientific self-regulation for the control of genome editing in the human germline. EMBO Rep 18:355–58
    [Google Scholar]
  52. 52. 
    Harris J. 2016. Germline modification and the burden of human existence. Camb. Q. Healthc. Ethics 25:6–18
    [Google Scholar]
  53. 53. 
    Hawthorne WJ, Cowan PJ, Bühler LH, Yi S, Bottino R et al. 2019. Third WHO global consultation on regulatory requirements for xenotransplantation clinical trials, Changsha, Hunan, China December 12–14, 2018. Xenotransplantation 26:e12513
    [Google Scholar]
  54. 54. 
    Hinxton Group 2015. Statement on genome editing technologies and human germline genetic modification Rep., Hinxton Group http://www.hinxtongroup.org/hinxton2015_statement.pdf
  55. 55. 
    Hyun I, Wilkerson A, Johnston J. 2016. Revisit the 14-day rule. Nature 533:169–71
    [Google Scholar]
  56. 56. 
    Int. Comm. Clin. Use Hum. Germline Genome Ed 2020. Heritable Human Genome Editing Washington, DC: Natl. Acad. Press
  57. 57. 
    Int. Soc. Stem Cell Res 2015. The ISSCR statement on human germline genome modification. International Society for Stem Cell Research https://www.isscr.org/news-publicationsss/isscr-news-articles/article-listing/2015/03/19/statement-on-human-germline-genome-modification
    [Google Scholar]
  58. 58. 
    Int. Soc. Stem Cell Res 2016. Guidelines for stem cell research and clinical translation Guidel. Doc., Int. Soc. Stem Cell Res. Skokie, IL: https://www.isscr.org/docs/default-source/all-isscr-guidelines/guidelines-2016/isscr-guidelines-for-stem-cell-research-and-clinical-translationd67119731dff6ddbb37cff0000940c19.pdf
  59. 59. 
    Int. Soc. Stem Cell Res 2019. ISSCR support the development of international guidelines on human embryo genome modification. Policy Doc., Int. Soc. Stem Cell Res Skokie, IL: https://www.isscr.org/docs/default-source/policy-documents/isscr-statement-re-human-embryo-genome-modification-january-2019.pdf
  60. 60. 
    Isasi R, Kleiderman E, Knoppers BM. 2016. Editing policy to fit the genome?. Science 351:337–39
    [Google Scholar]
  61. 61. 
    Jasanoff S, Hurlbut JB. 2018. A global observatory for gene editing. Nature 555:435–37
    [Google Scholar]
  62. 62. 
    Kaiser J. 2019. Update: House spending panel restores U.S. ban on gene-edited babies. Science June 4. https://www.sciencemag.org/news/2019/06/update-house-spending-panel-restores-us-ban-gene-edited-babies
    [Google Scholar]
  63. 63. 
    Kang X, He W, Huang Y, Yu Q, Chen Y et al. 2016. Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing. J. Assist. Reprod. Genet. 33:581–88
    [Google Scholar]
  64. 64. 
    König H. 2017. The illusion of control in germline-engineering policy. Nat. Biotechnol. 35:502–6
    [Google Scholar]
  65. 65. 
    Krimsky S. 2019. Ten ways in which He Jiankui violated ethics. Nat. Biotechnol. 37:19–20
    [Google Scholar]
  66. 66. 
    Lander E, Baylis F, Zhang F, Charpentier E, Berg P et al. 2019. Adopt a moratorium on heritable genome editing. Nature 567:165–68
    [Google Scholar]
  67. 67. 
    Lanphier E, Urnov F, Haecker SE, Werner M, Smolenski J 2015. Don't edit the human germ line. Nature 519:410–11
    [Google Scholar]
  68. 68. 
    Larigauderie A, Mooney HA. 2010. The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services: moving a step closer to an IPCC-like mechanism for biodiversity. Curr. Opin. Environ. Sustain. 2:9–14
    [Google Scholar]
  69. 69. 
    Ledford H. 2015. The landscape of human genome editing. Nature 526:310–11
    [Google Scholar]
  70. 70. 
    Ledford H. 2019. CRISPR babies: When will the world be ready?. Nature 570:293–96
    [Google Scholar]
  71. 71. 
    Liang P, Xu Y, Zhang X, Ding C, Huang R et al. 2015. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6:363–72
    [Google Scholar]
  72. 72. 
    Linvall O, Hyun I 2009. Medical innovation versus stem cell tourism. Science 324:166465
    [Google Scholar]
  73. 73. 
    Ma H, Marti-Gutierrez N, Park SW, Wu J, Lee Y et al. 2017. Correction of a pathogenic gene mutation in human embryos. Nature 548:413–19
    [Google Scholar]
  74. 74. 
    Macer D. 2012. Ethical consequences of the positive views of enhancement in Asia. Health Care Anal 20:385–97
    [Google Scholar]
  75. 75. 
    Marchant GE, Allenby B. 2017. Soft law: new tools for governing emerging technologies. Bull. At. Sci. 73:108–14
    [Google Scholar]
  76. 76. 
    Marchant GE, Wallace W. 2015. Coordinating technology governance. Issues Sci. Technol. 31:443–50
    [Google Scholar]
  77. 77. 
    Matthews DJH, Lovell-Badge R, Chan S, Donovan PJ, Douglas T et al. 2015. A path through the thicket. Nature 527:159–61
    [Google Scholar]
  78. 78. 
    McCaughney T, Budden DM, Sanfilippo PG, Gooden GEC, Fan L et al. 2019. A need for better understanding is the major determinant for public perceptions of human gene editing. Hum. Gene Ther. 30:36–43
    [Google Scholar]
  79. 79. 
    McGee A. 2018. Using the therapy and enhancement distinction in law and policy. Bioethics 34:7–80
    [Google Scholar]
  80. 80. 
    Mehlman MJ. 2003. Wondergenes: Genetic Enhancement and the Future of Society Bloomington: Ind. Univ. Press
  81. 81. 
    Montoliu L, Merchant J, Hirsch F, Abecassis M, Jouannet P et al. 2018. ARRIGE arrives: toward the responsible use of genome editing. CRISPR J 1:128–30
    [Google Scholar]
  82. 82. 
    Natl. Acad. Sci. Eng. Med 2017. Human Genome Editing: Science, Ethics, and Governance Washington, DC: Natl. Acad. Press
    [Google Scholar]
  83. 83. 
    Natl. Acad. Sci. Eng. Med 2019. Second International Summit on Human Genome Editing: continuing the global discussion Meet. Rep., Natl. Acad. Sci. Eng. Med. Washington, DC: https://www.nap.edu/catalog/25343/second-international-summit-on-human-genome-editing-continuing-the-global-discussion
  84. 84. 
    Nature Eds 2018. Human embryo and stem-cell research. Nature 557:6
    [Google Scholar]
  85. 85. 
    Nature Eds 2019. Set rules for germline gene editing. Nature 567:145
    [Google Scholar]
  86. 86. 
    Normile D. 2019. Chinese scientist who produced genetically altered babies sentenced to three years in jail. Science Dec. 30. https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail
    [Google Scholar]
  87. 87. 
    Nuffield Counc. Bioethics 2016. Genome editing: an ethical review Rep., Nuffield Counc. Bioethics London: https://www.nuffieldbioethics.org/wp-content/uploads/Genome-editing-an-ethical-review.pdf
  88. 88. 
    Nuffield Counc. Bioethics 2018. Genome editing and human reproduction: social and ethical issues Rep., Nuffield Counc. Bioethics London: https://www.nuffieldbioethics.org/publications/genome-editing-and-human-reproduction
  89. 89. 
    Ormond KE, Mortlock DP, Scholes DT, Bombard Y, Brody LC et al. 2107. Human germline genome editing. Am. J. Hum. Genet. 101:167–76
    [Google Scholar]
  90. 90. 
    Osborne H. 2020. China confirms three gene edited babies were born through He Jiankui's experiments. Newsweek Jan. 2. https://www.newsweek.com/china-third-gene-edited-baby-1480020
    [Google Scholar]
  91. 91. 
    Pei D, Beier DW, Levy-Lahad E, Marchant G, Rossant J et al. 2017. Human embryo editing: opportunities and importance of transnational cooperation. Cell Stem Cell 21:423–26
    [Google Scholar]
  92. 92. 
    Plomin R, DeFries JC, Knopik VS, Neiderhiser JM. 2016. Top 10 replicated findings from behavioral genetics. Perspect. Psychol. Sci. 11:3–23
    [Google Scholar]
  93. 93. 
    Polez S, Lewis A. 2018. Regulating genetic advantage. Harv. J. Law Technol. 32:26597
    [Google Scholar]
  94. 94. 
    Porteus MH. 2015. Towards a new era in medicine: therapeutic genome editing. Genome Biol 16:286
    [Google Scholar]
  95. 95. 
    Regalado A. 2019. The next trick for CRISPR is gene-editing pain away. MIT Technology Review Aug. 22. https://www.technologyreview.com/2019/08/22/133291/the-next-trick-for-crispr-is-gene-editing-pain-away
    [Google Scholar]
  96. 96. 
    Scheufele D, Xenos MA, Howell EL, Rose KM, Brossard D et al. 2017. U.S. attitudes on human genome editing. Nature 357:553–54
    [Google Scholar]
  97. 97. 
    Shukla-Jones A, Friedrichs S, Winickoff D. 2018. Gene editing in an international context: scientific, economic and social issues across sectors OECD Sci. Technol. Ind. Work. Pap. 2018/04 Organ. Econ. Co-op. Dev Paris: https://doi.org/10.1787/38a54acb-en
    [Crossref]
  98. 98. 
    Soc. Dev. Biol 2015. Position statement from the Society for Developmental Biology on genomic editing in human embryos Pos. Statement, Soc. Dev. Biol. Bethesda, MD: https://www.sdbonline.org/uploads/files/SDBgenomeeditposstmt.pdf
  99. 99. 
    Taylor AL, Bettcher DW. 2000. WHO Framework Convention on Tobacco Control: a global good for public health. Bull. World Health Organ. 78:920–29
    [Google Scholar]
  100. 100. 
    Tonn B. 2007. The Intergovernmental Panel on Climate Change: a global scale transformative initiative. Futures 39:614–18
    [Google Scholar]
  101. 101. 
    Tournas L, Johnson W, Maynard A, Bowman D. 2017. Germline doping for heightened performance in sport. Aust. N. Z. Sports Law J. 12:1–24
    [Google Scholar]
  102. 102. 
    UN Educ. Sci. Cult. Organ 1997. Universal declaration on the human genome and human rights Decl., UN Educ. Sci. Cult. Organ. Paris: http://portal.unesco.org/en/ev.php-URL_ID=13177&URL_DO=DO_TOPIC&URL_SECTION=201.html
  103. 103. 
    UN Educ. Sci. Cult. Organ 2015. Report of the IBC on updating its reflection on the human genome and human rights Rep. SHS/YES/IBC-22/15/2 REV.2 UN Educ. Sci. Cult. Organ. Paris:
  104. 104. 
    Venkataraman B. 2015. Should we engineer future humans?. New America Dec. 17. https://www.newamerica.org/weekly/should-we-engineer-future-humans
    [Google Scholar]
  105. 105. 
    World Anti-Doping Agency 2020. Gene and cell doping. 2020 List of Prohibited Substances: Gene and Cell Doping Montreal: World Anti-Doping Agency https://www.wada-ama.org/en/content/what-is-prohibited/prohibited-at-all-times/gene-and-cell-doping
    [Google Scholar]
  106. 106. 
    World Health Organ 2019. Human genome editing: as we explore options for global governance, caution must be our watchword Policy Statement, World Health Organ Geneva: https://www.who.int/ethics/topics/human-genome-editing/ethics-explore-options-for-global-governance.pdf
  107. 107. 
    World Health Organ 2019. WHO expert panel paves way for strong international governance on human genome editing News Release, Mar. 19 World Health Organ Geneva: https://www.who.int/news/item/19-03-2019-who-expert-panel-paves-way-for-strong-international-governance-on-human-genome-editing
  108. 108. 
    World Health Organ 2020. Human Genome Editing (HGE) Registry. World Health Organization https://www.who.int/health-topics/ethics-and-health/human-genome-editing-registry
    [Google Scholar]
  109. 109. 
    World Med. Assoc 2013. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J. Am. Med. Assoc. 310:2191–94
    [Google Scholar]
  110. 110. 
    Zuccaro MV, Xu J, Mitchell C, Marin D, Zimmerman R et al. 2020. Allele-specific chromosome removal after Cas9 cleavage in human embryos. Cell 183:1650–64.e15
    [Google Scholar]
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