Editing the Genome: Prospects, Progress, Implications, and Cautions
Purpose of Review
Clinicians, clinical researchers, and the general public all need to consider the implications of rapid advances in gene editing technology, which have given rise not only to new hope for the development of corrective interventions for genetic defects and many other diseases and conditions but also to many ethical, social, and policy concerns.
Gene editing tools are potentially both more precise and more accurate than current gene transfer interventions; in addition, the discovery and development of the CRISPR/Cas9 system has made gene editing research considerably easier, faster, and cheaper. As a result, long-standing debates about the safety, efficacy, affordability, ethical and social acceptability, oversight, and control of efforts to pursue human germline alteration and enhancement have been rekindled. Added to these debates are controversies about newly discovered capacities to use gene editing to reshape the environment by altering or eliminating non-human species (insects in particular) that pose threats to humans.
This review examines the science of the new gene editing boom in its social and historical context and discusses both past and current policy debates and future prospects for ethical consensus on whether, where, when, and how to move forward with clinical research and medical applications.
KeywordsCRISPR CRISPR/Cas9 ELSI Gene editing Germline gene editing Genetic enhancement
Compliance with Ethical Standards
Conflict of Interest
Nancy M. P. King, Pat C. Lord, and Douglas E. Lemley declare no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.• Hampton T. Ethical and societal questions loom large as gene editing moves closer to the clinic. JAMA. 2016;315(6):546–8. A brief overview of historical and recent scientific developments and ethical and policy debates about genetic intervention research in general and gene editing in particular.CrossRefPubMedGoogle Scholar
- 3.Weiss R, Nelson D. Methods faulted in gene test death, teen too ill for therapy, probe finds. Washington Post. 1999;8:A1.Google Scholar
- 4.Gelsinger P. Jesse’s intent. Guinea pig zero: a journal for human research subjects. 2000. Issue #8. http://www.guineapigzero.com/jesses-intent.html. Accessed 12 Oct 2016.
- 6.Moran N. First gene therapy glybera (finally) gets EMA approval. BioWorld, Thompson Reuters. 2012. http://www.bioworld.com/content/first-gene-therapy-glybera-finally-gets-ema-approval-1. Accessed 12 Oct 2016.
- 7.Ward A. GSK to allow staggered payments for EMA-approved gene therapy. The financial times. 2016. http://www.msn.com/en-gb/news/other/gsk-to-allow-staggered-payments-for-ema-approved-gene-therapy/ar-BBrdZid. Accessed 12 Oct 2016.
- 8.Pollack A. Eye treatment closes in on being first gene therapy approved in U.S. New York Times. 2015. p. B3. http://www.nytimes.com/2015/10/05/science/eye-treatment-closes-in-on-being-first-gene-therapy-approved-in-us.html. Accessed 12 Oct 2016.
- 12.GeMCRIS website. https://www.gemcris.od.nih.gov/Contents/GC_HOME.asp. Accessed 12 Oct 2016.
- 13.Pollack A. A cell therapy untested in humans saves a baby with cancer. New York Times. 2015;6:B3.Google Scholar
- 15.Keener AB. Gene editing: from roots to riches. Scientist. 2016. http://www.the-scientist.com/?articles.view/articleNo/47156/title/Gene-Editing--From-Roots-to-Riches/. Accessed 12 Oct 2016.
- 16.Comfort N. Can we cure genetic diseases without slipping into eugenics? The nation. 2015. http://www.thenation.com/article/can-we-cure-genetic-diseases-without-slipping-into-eugenics/?print=1. Accessed 12 Oct 2016.
- 17.Specter M. The gene hackers. New Yorker. 2015;16:52–61.Google Scholar
- 18.Park A. Life: the remix. Time. 2016;4:43–8.Google Scholar
- 19.Center for Genomics and Society. About human germline gene editing. http://www.geneticsandsociety.org/article.php?id=8711. Accessed 12 Oct 2016.
- 20.Office of Science Policy, NIH. Next steps on research using animal embryos containing human cells, Under the Poliscope. 2016. http://osp.od.nih.gov/under-the-poliscope/2016/08/next-steps-research-using-animal-embryos-containing-human-cells. Accessed 12 Oct 2016.
- 21.Regalado A. Top US intelligence official calls gene editing a WMD threat. MIT Technology Rev. 2016. https://www.technologyreview.com/s/600774/top-us-intelligence-official-calls-gene-editing-a-wmd-threat/. Accessed 12 Oct 2016.
- 22.Marchant GE, Wallach W. Coordinating technology governance. Issues Sci Technol. 2015;31(4). http://issues.org/31-4/coordinating-technology-governance/. Accessed 12 Oct 2016.
- 24.Pinker S. The moral imperative for bioethics. Boston Globe. 2015. https://www.bostonglobe.com/opinion/2015/07/31/the-moral-imperative-for-bioethics/JmEkoyzlTAu9oQV76JrK9N/story.html. Accessed 12 Oct 2016.
- 26.Regalado A. Engineering the perfect baby. MIT Technol Rev. 2015;118(3):27–33.Google Scholar
- 27.Rogers M. The Pandora’s box Congress, Rolling Stone. 1975.Google Scholar
- 31.Regalado A. Patients favor changing the genes of the next generation with CRISPR, MIT Technol Rev. 2015. https://www.technologyreview.com/s/544141/patients-favor-changing-the-genes-of-the-next-generation-with-crispr/. Accessed 12 Oct 2016.
- 32.National Academies of Sciences, Engineering, and Medicine. International summit on human gene editing: a global discussion–commissioned papers, 2015. www.nationalacademies.org/cs/groups/pgasite/documents/webpage/pga_170455.pdf. Accessed 12 Oct 2016.
- 39.• Maeder ML, Gersbach CA. Genome-editing technologies for gene and cell therapy. Mol Biol. 2016;24:430–46. Definitive scientific overview.Google Scholar
- 44.Jo YI, Suresh B, Kim H, et al. CRISPR/Cas9 system as an innovative genetic engineering tool: enhancements in sequence specificity and delivery methods. Biochim Biophys Acta. 1856;2015:234–43.Google Scholar
- 47.International Society for Stem Cell Research. The ISSCR statement on human germline genome modification. 2015. http://www.isscr.org/docs/default-source/guidelines/isscr-statement-on-human-germline-genome-modification.pdf?sfvrsn=2. Accessed 12 Oct 2016.
- 50.National Institutes of Health. Statement on NIH funding of research using gene-editing technologies in human embryos. 2015. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-nih-funding-research-using-gene-editing-technologies-human-embryos. Accessed 12 Oct 2016.
- 52.Hinxton Group. Statement on genome editing technologies and human germline genetic modification. 2015. www.hinxtongroup.org/Hinxton2015_Statement.pdf. Accessed 12 Oct 2016.
- 53.International Bioethics Committee. Report of the IBC on updating its reflection on the human genome and human rights. (Paris: UNESCO). 2015. http://unesdoc.unesco.org/images/0023/002332/233258E.pdf. Accessed 12 Oct 2016.
- 54.National Institutes of Health. Notice Number NOT-OD-15-158, NIH research involving introduction of human pluripotent cells into non-human vertebrate animal pre-gastrulation embryos. 2015. http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-158.html. Accessed 12 Oct 2016.
- 55.Maynard A. What do you think about scientists creating human-nonhuman hybrids? The National Institutes of Health wants to know. Slate/Future Tense. 2016. http://www.slate.com/articles/technology/future_tense/2016/08/nih_asks_for_public_input_on_chimeras_human_nonhuman_hybrids.html. Accessed 12 Oct 2016.
- 56.National Academies of Sciences, Engineering, and Medicine. On human gene editing: International Summit statement. 2015. www.nationalacademies.org/opinews/newsitem.aspx?RecordID=12032015a. Accessed 12 Oct 2016.
- 59.National Academies of Sciences, Engineering, and Medicine. Human gene-editing initiative consensus study. Human gene editing: scientific, medical, and ethical considerations. http://www.nationalacademies.org/gene-editing/consensus-study/index.htm. Accessed 12 Oct 2016.
- 60.Garde D. The cure for ‘bubble boy’ disease will cost $665,000. STAT News. 2016. https://www.statnews.com/2016/08/03/gene-therapy-price-gsk/. Accessed 12 Oct 2016.
- 63.Begley S. They’re going to CRISPR people. What could possibly go wrong? STAT. 2016. https://www.statnews.com/2016/06/23/crispr-humans-penn-clinical-trial/. Accessed 12 Oct 2016.
- 64.Belkin L. The made-to-order savior: producing a perfect baby sibling. New York Times Magazine. 2001. http://www.nytimes.com/2001/07/01/magazine/the-made-to-order-savior.html?_r=0. Accessed 12 Oct 2016.
- 67.Stein R. Breaking taboo, Swedish scientist seeks to edit DNA of healthy human embryos, Shots Health News from NPR. 2016. http://www.npr.org/sections/health-shots/2016/09/22/494591738/breaking-taboo-swedish-scientist-seeks-to-edit-dna-of-healthy-human-embryos. Accessed 12 Oct 2016.
- 68.Flotte R. Therapeutic germ line alteration: has CRISPR/Cas9 technology forced the question? Mol Ther. 2015;26:1–2.Google Scholar
- 76.Gallagher J. Embryo engineering a moral duty, says top scientist. BBC News. 2015. www.bbc.com/news/uk-politics-32633510. Accessed 12 Oct 2016.
- 77.• Chapman AR, Frankel MS. Human inheritable genetic modification: assessing scientific, ethical, religious, and policy issues. Washington DC: American Association for the Advancement of Science; 2000 .https://www.aaas.org/sites/default/files/migrate/uploads/germline.pdf. Accessed 12 Oct 2016. Definitive examination.Google Scholar
- 78.Walters L, Palmer JG. The ethics of human gene therapy. New York: Oxford University Press; 1997.Google Scholar
- 80.• Juengst ET, Moseley D. Human enhancement. In: Stanford encyclopedia of philosophy. http://plato.stanford.edu/entries/enhancement/ ). Accessed 12 Oct 2016. Clear and detailed examination .
- 82.Walsh F. US bid to grow human organs for transplant inside pigs. BBC News. 2016. www.bbc.com/news/health-36437428. Accessed 12 Oct 2016.
- 83.• National Academies of Sciences, Engineering, and Medicine. Gene drives on the horizon. 2016. http://nas-sites.org/gene-drives/. Accessed 12 Oct 2016. Comprehensive report on the science and the policy implications of gene drives .
- 84.Begley S. Monsanto licenses CRISPR technology to modify crops—with key restrictions. STAT/Scientific American. 2016. https://www.statnews.com/2016/09/22/monsanto-licenses-crispr/. Accessed 12 Oct 2016.
- 85.Goldman J. Harnessing the power of gene drives to save wildlife. Sci Am. 2016. http://www.scientificamerican.com/article/harnessing-the-power-of-gene-drives-to-save-wildlife/. Accessed 12 Oct 2016.
- 86.Swetlitz I. ‘Gene drive’ organisms should be tested in field trials, not widely released, experts say. STAT. 2016. https://www.statnews.com/2016/06/08/gene-drive-field-trials/. Accessed 12 Oct 2016.