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Is CRISPR a Security Threat?

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Defense Against Biological Attacks

Abstract

Since 2012, the new gene editing technique called CRISPR took the world by storm because theoretically it can be used to edit any organism quickly, precisely, and at low cost. Because of these features, many fear that CRISPR could become a technology of choice for terrorists or states who wish to produce novel threat agents or bioweapons. Others fear that it could be the source of a catastrophic event caused by unsafe laboratory practices by amateur or practicing scientists. In this chapter we review the ethical, safety, and security challenges that the technology raises. We conclude that while safety concerns are founded due to the vague regulatory framework worldwide, the risks of misuse by inexperienced terrorists are limited by the fact that the technology currently has a number of limitations and still presents a number of technical challenges.

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Notes

  1. 1.

    DMD is an inherited disease caused by mutations in the gene that encodes for dystrophin, a protein that is required for muscle fiber integrity.

  2. 2.

    World Health Organization, “10 Facts on Malaria,” http://www.who.int/features/factfiles/malaria/en/

  3. 3.

    For example, see: Josiah Francisco, “DIY CRISPR Kits, Learn Modern Science by Doing,” https://www.indiegogo.com/projects/diycrispr-kits-learn-modern-science-by-doing#/; see also “DYI Bacterial Gene Engineering CRIPSR Kit,” ODIN.com, http://www.the-odin.com

  4. 4.

    See: http://www.darpa.mil/program/safe-genes

References

  1. Ishino Y, et al. Nucleotide sequence of the iap gene, responsible for alkaline phospatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987;169:5429–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nakata A, et al. Unusual nucleotide arrangements with repeated sequences in the Escherichia coli K-12 chromosome. J Bacteriol. 1989;171:3553–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Groenen PM, et al. Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis; application for strain differentiation by a novel typing method. Mol Microbiol. 1993;10:1057–65.

    Article  CAS  PubMed  Google Scholar 

  4. Mojica FJ, et al. Long stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferaz mediterranei and Haloferax volcanii and could be involved in replicon partitioning. Mol Microbiol. 1995;17:85–93.

    Article  CAS  PubMed  Google Scholar 

  5. Masepohl B, Gorlitz K, Bohme H. Long tandemly repeated (LTRR) sequences in the filamentous cyanbacterium Anabaena sp. PCC 7120. Biochim Biophys Acta. 1996;1307:26–30.

    Article  PubMed  Google Scholar 

  6. Hoe N, et al. Rapid molecular genetic subtyping of serotype M1 group a Streptococcus strain. Emerg Inf Dis. 1999;5:254–63.

    Article  CAS  Google Scholar 

  7. Barrangou R, Horvath P. A decade of discovery: CRISPR functions and applications. Nat Microbiol. 2017;2(1709):1–9.

    Google Scholar 

  8. Mojica FJ, et al. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol Microbiol. 2000;36:244–6.

    Article  CAS  PubMed  Google Scholar 

  9. Jansen R, et al. Identification of genes that are associated with DNW repeats in prokaryotes. Mol Microbiol. 2002;43(6):1565–75.

    Article  CAS  PubMed  Google Scholar 

  10. Mojica F, et al. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol. 2005;60(2):174–82.

    Article  CAS  PubMed  Google Scholar 

  11. Marx J. New bacterial defense against phage invaders identified. Science. 2007;315:1650–1.

    Article  CAS  PubMed  Google Scholar 

  12. Poucel C, et al. CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology. 2005;151:653–63.

    Article  CAS  Google Scholar 

  13. Bolotin A, et al. Clustered regularly interspaced short palindromic repeats (CRISPR) have spacers of extrachromosomal origin. Microbiology. 2005;151:2551–61.

    Article  CAS  PubMed  Google Scholar 

  14. Makarova K, et al. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol Direct. 2006;1:7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Barangou R, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315:1709–12.

    Article  CAS  Google Scholar 

  16. Morange M. What history tells us XXXVII. CRISPR-Cas: the discovery of an immune system. J Biosci. 2015;40(2):221–3.

    Article  PubMed  Google Scholar 

  17. Brouns S, et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science. 2008;321:960–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1–9.

    Article  CAS  Google Scholar 

  19. Ledford H. Five big mysteries about CRISPR’s origins. Nature. 2017;541:280–2.

    Article  CAS  PubMed  Google Scholar 

  20. Jinek M, et al. A programmable dual-RNA-guided DNA endonuclease in adaptative bacterial immunity. Science. 2012;337(6096):816–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jinek M, et al. RNA-programmed genome editing in human cells. Elife. 2013. https://doi.org/10.7554/eLife.00471.001

  22. Cong L, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Begley S. 6 takeaway from the CRISPR patent decision. STAT. 2017, February 16. https://www.scientificamerican.com/article/6-takeaways-from-the-crispr-patent-decision/

  24. Cross R. Broad prevails over Berkely in CRISPR patent dispute. C&En, September 10, 2018. Available at: https://cen.acs.org/policy/litigation/Broad-prevails-over-Berkeley-CRISPR/96/web/2018/09

  25. Babcock B. The continuing CRISPR patent battle: The Broad Institute loses a key European patent. MedCityNews. 2018, January 23.

    Google Scholar 

  26. Buhr S. China sides with Emanuelle Charpentier and Jennifer Doudna in CRISPR patent war. TechCrunch. 2017. https://techcrunch.com/2017/06/19/china-sides-with-emmanulle-charpentier-and-jennifer-doudna-in-crispr-patent-war/

  27. Cohen J. Europe says University of California deserves patent for CRISPR. Science. 2017. https://doi.org/10.1126/science.aal0969

  28. Clinical Trials Database. CRISPR. 2017. https://clinicaltrials.gov/ct2/results?term=CRISPR&type=&rslt=&age_v=&gndr=&cond=CRISPR&intr=&titles=&outc=&spons=&lead=&id=&cntry1=&state1=&cntry2=&state2=&cntry3=&state3=&locn=&sfpd_s=&sfpd_e=&lupd_s=&lupd_e=. Accessed 29 Sept 17.

  29. LePage M. Boom in human gene editing as 20 CRISPR trials gear up. New Scientist. 2017. https://www.newscientist.com/article/2133095-boom-in-human-gene-editing-as-20-crispr-trials-gear-up/. Accessed 29 Sept 2017.

  30. LePage M. Why has a UK team genetically edited human embryos? New Scientist. 2017. https://www.newscientist.com/article/2148057-why-has-a-uk-team-genetically-edited-human-embryos/. Accessed 29 Sept 2017.

  31. Zhang Y, Long C, Li H, et al. CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice. Sci Adv. 2017;3(4):1–10.

    Google Scholar 

  32. Dever DP, Bak RO, Reinisch A, et al. CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. Nature. 2016;17(539):384–9.

    Article  CAS  Google Scholar 

  33. Krisch JA. First CRISPR clinical trial commences. Scientist. 2016, November 15. http://www.the-scientist.com/?articles.view/articleNo/47528/title/First-CRISPR-Clinical-Trial-Commences/. Accessed 28 Sep 2017.

  34. Clinical Trials Database. PD-1 knockout engineered t cells for metastatic non-small cell lung cancer, Bethesda. 2017. https://clinicaltrials.gov/ct2/show/results/NCT02793856. Accessed 29 Sept 2017.

  35. Clinical Trials Database. PD-1 and CRISPR. 2017. https://clinicaltrials.gov/ct2/results?cond=PD-1&term=CRISPR&cntry1=&state1=&recrs=. Accessed 29 Sept 2017.

  36. Clinical Trials Database. A safety and efficacy study of TALEN and CRISPR/Cas9 in the treatment of HPV-related Cervical Intraepithelial Neoplasia. 2017. https://clinicaltrials.gov/ct2/show/NCT03057912. Accessed 29 Sept 2017.

  37. Zhen S, Hua L, Takahashi Y, et al. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9. Biochem Biophys Res Commun. 2014;450(4):1422–6.

    Article  CAS  PubMed  Google Scholar 

  38. Dong C, Qu L, Wang H, et al. Targeting hepatitis B virus ccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication. Antivir Res. 2015;118:110–7.

    Article  CAS  PubMed  Google Scholar 

  39. Yuen KS, Wong NHM, Jin D. Suppression of Epstein-Barr virus infection in nasopharyngeal carcinoma cells through CRISPR/Cas9 targeting of EBNA1, OriP and W repeats. Paper presented at the 17th international symposium on Epstein Barr virus and associated diseases (EBV 2016), University of Zurich, Zurich, Switzerland, 8–12 August 2016.

    Google Scholar 

  40. Kaminski R, Chen Y, Fischer T. Elimination of HIV-1 genomes from human T-lymphoid cells by CRISPR/Cas9 gene editing. Sci Rep. 2016;6(22555):1–15.

    Google Scholar 

  41. Chandrasekaran J, Brumin M, Wolf D. Development of broad virus resistance in non-transgenic cucumber using CRISPR/Cas9 technology. Mol Plant Pathol. 2016;17(7):1140–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Xu R, Li H, Qin R, et al. Gene targeting using the agrobacterium tumefaciens-mediated CRISPR-Cas system in rice. Rice. 2014;7(1):5.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gao Y, Wu H, Wang Y, et al. Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects. Genome Biol. 2017;18(1):13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Wang H, Yang H, Shivalla CS, et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell. 2013;153(4):910–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Freedman BS, Brooks CR, Lam AQ, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun. 2015;6(8715). https://doi.org/10.1038/ncomms9715

  46. Schwank G, Koo BK, Sasselli V, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013;13(6):653–8.

    Article  CAS  PubMed  Google Scholar 

  47. Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating, and targeting genomes. Nat Biotechnol. 2014;32(4):347–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ajjawi I, et al. Lipid production in Nannochloropsis gaditana is doubled by decreasing expression of a single transcriptional regulator. Nat Biotechnol. 2017;35:647–52.

    Article  CAS  PubMed  Google Scholar 

  49. Shin SE, Lim JM, Koh HG. CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii. Sci Rep. 2016;6:27810. https://doi.org/10.1038/srep27810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schwartz CM, Hussain MS, Blenner M, Wheeldon I. Synthetic RNA polymerase III promoters facilitate high-efficiency CRISPR-Cas9-mediated genome editing in Yarrowia lipolytica. ACS Synth Biol. 2016;5(4):356–9.

    Article  CAS  PubMed  Google Scholar 

  51. Gants VM, Jasinskiene N, Tatarenkova O, et al. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc Natl Acad Sci. 2015;112(49):E6736–43.

    Article  CAS  Google Scholar 

  52. Fu G, Lees RS, Nimmo D, et al. Female-specific flightless phenotype for mosquito control. Proc Natl Acad Sci. 2010;107(10):4550–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hammond A, Galizi R, Kyrou K, et al. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 2015;34(1):78–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157(6):1262–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Niu D, Wei HJ, Lin L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science. 2017;357(6357):1303–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Baltimore D, et al. A prudent path forward for genomic engineering and germline gene modification. Science. 2015;348(6230):36–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Liang P, Xu Y, Zhang X, Ding C, Huang R, et al. CRISPR/Cas9-mediated gene editing in human trioronuclear zygotes. Protein Cell. 2015;6(5):363–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kang X, He W, Huang Y, Yu Q, Chen Y, et al. Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing. J Assist Reprod Genet. 2016;33(5):581–8.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Callaway E. Second Chinese team reports gene editing in human embryos. Nature News. 2016. http://www.nature.com/news/second-chinese-team-reports-gene-editing-in-human-embryos-1.19718. Accessed 29 Sept 17.

  60. Tang L, Zeng Y, Du H, et al. CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein. Mol Gen Genomics. 2017;292(3):525–33.

    Article  CAS  Google Scholar 

  61. LePage M. Mosaic problem stands in the way of gene editing embryos. New Scientist. 2015. https://www.newscientist.com/article/mg23331174-400-mosaic-problem-stands-in-the-way-of-gene-editing-embryos/. Accessed 29 Sept 2017.

  62. Ma H, Marti-Gutierrez N, Park SW, et al. Correction of a pathogenic gene mutation in human embryos. Nature. 2017;548(7668):413–9.

    Article  CAS  PubMed  Google Scholar 

  63. Ledford H. CRISPR fixes disease gene in viable human embryos. Nat News. 2017;548:13–4.

    Article  CAS  Google Scholar 

  64. Servick K. Skepticism surfaces over CRISPR human embryo editing claims. Science Magazine. 2017. https://doi.org/10.1126/science.aap8382

  65. Begley S. Federal panel approves first use of CRISPR in humans. STAT. 2016, June 21.

    Google Scholar 

  66. LaMotta L. Editas delays CRISPR move to human trials. BioPharmaDive. 2017, May 16.

    Google Scholar 

  67. CRISPR Therapeutics. News Release. 2017, March 31. http://ir.crisprtx.com/phoenix.zhtml?c=254376&p=irol-newsArticle&ID=2272286

  68. National Academies of Sciences, Engineering, and Medicine. Human genome editing: science, ethics and governance. 2017.

    Google Scholar 

  69. Harmon A. Human gene editing receives science panel’s support. NY Times. 2017, February 14.

    Google Scholar 

  70. He Jiankui defends ‘World’s first gene-edited babies’. BBC News, November 28, 2018. https://www.bbc.com/news/world-asia-china-46368731

  71. Begley S. Do CRISPR enthusiasts have their head in the sand about the safety of gene editing? STAT. 2016, July 18.

    Google Scholar 

  72. Begley S. They’re going to CRISPR people: what could possibly go wrong? STAT. 2016, June 23.

    Google Scholar 

  73. Araki M, Ishii T. International regulatory landscape and integration of corrective genome editing into in vitro fertilization. Reprod Biol Endocrinol. 2014;12:108. https://doi.org/10.1186/1477-7827-12-108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Konig H. The illusion of control in germ-line engineering policy. Nat Biotechnol. 2017;35:502–6.

    Article  PubMed  CAS  Google Scholar 

  75. Vogel G. Embryo engineering alarm. Science. 2015;347(6228):1301.

    Article  CAS  PubMed  Google Scholar 

  76. Allen & Overy LLP. Regulating CRISPR genome editing in humans: where do we go from there? JDSupra. 2017, August 14. http://www.jdsupra.com/legalnews/august-2017-regulating-crispr-genome-64475/

  77. Carter S, Friedman R. Policy and regulatory issues for gene drives in insects. Workshop Report, August 2016, J. Craig Venter Institute, La Jolla, California. 2016. http://www.jcvi.org/cms/fileadmin/site/research/projects/gene-drive-workshop/report-complete.pdf

  78. Cyranoski D. CRISPR tweak may help gene-edited crops to bypass biosafety regulations. Nature. 2015. https://doi.org/10.1038/nature.2015.18590

  79. FDA (Food and Drug Administration). FDA releases final environmental assessment for genetically engineered mosquito. 2016, August 5. http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm490246.htm

  80. Ledford H. Biohackers gear up for genome editing. Nature. 2015;524:398–9.

    Article  CAS  PubMed  Google Scholar 

  81. Esvelt KM. Daisy drive systems. Sculpting Evolution. http://www.sculptingevolution.org/daisydrives

  82. Ledford H. Safety upgrade found for gene-editing technique. Nature. 2015. https://doi.org/10.1038/nature.2015.18799

  83. Acharya A, Acharya A. Cyberterrorism and biotechnology: when ISIS meets CRISPR. Foreign Affairs. 2017, June 1.

    Google Scholar 

  84. Hern A. There are things worse than death: can a cancer cure lead to brutal bioweapons? Guardian. 2017, July 31.

    Google Scholar 

  85. Begley S. Gene drive gives scientists power to highjack evolution. STAT. 2015, November 17.

    Google Scholar 

  86. Begley S. Why the FBI and pentagon are afraid of this new genetic technology. STAT. 2015, November 12.

    Google Scholar 

  87. Ledford H. CRISPR the disruptor. Nature. 2015;522(7554):20–4. https://doi.org/10.1038/522020a

  88. Shaw J. Editing an end to malaria. Harvard Magazine. 2016, May–June. http://www.harvardmagazine.com/2016/05/editing-an-end-to-malaria

  89. Swetlitz I. College students try to hack a gene drive and set a science fair abuzz. STAT. 2016, December 14.

    Google Scholar 

  90. Clapper J. Worldwide threat assessment of the US Intelligence Community. Senate Select Committee on Intelligence. 2016, February 9.

    Google Scholar 

  91. Mullin E. Obama advisors urge action against CRISPR bioterror threat. MIT Technol Rev. 2016, November 17.

    Google Scholar 

  92. Mackby J. Dispute mire BWC review conference. Arms Control Today. 2017, January 11.

    Google Scholar 

  93. Brown K. The UN just gave scientists the green light to mess with natural selection. GIZMODO. 2016, December 22. https://gizmodo.com/the-un-just-gave-scientists-the-green-light-to-mess-wit-1790413806

  94. International Bioethics Committee (IBC). Report of the IBC on updating its reflection on the human genome and human rights UNESCO. 2015. http://unesdoc.unesco.org/images/0023/002332/233258E.pdf

  95. Xiong S. Is international CRISPR regulation a pipe dream? Transcripts. 2017, July 24.

    Google Scholar 

  96. Doudna JA, Sternberg S. A crack in creation. Boston: Houghton Mifflin Harcourt; 2017.

    Google Scholar 

  97. Ledford H. Alternative CRISPR system could improve gene editing. Nature. 2015;526:17.

    Article  CAS  PubMed  Google Scholar 

  98. Peng R, et al. Potential pitfalls of CRISPR/Cas9-mediated genome editing. FEBS. 2016;283:1218–31.

    Article  CAS  Google Scholar 

  99. Chuai G-h, Wang Q-L, Liu Q. In silico meets in vivo: towards computational CRISPR-based sgRNA design. Trends Biotechnol. 2017;35(1):12–21.

    Article  CAS  PubMed  Google Scholar 

  100. Saey T. Gene drives spread their wings. Sci News. 2015;18:16.

    Google Scholar 

  101. Ben Ouagrham-Gormley S. Barriers to bioweapons: the challenge of expertise and organization for weapons. Ithaca: Cornell University Press; 2014.

    Book  Google Scholar 

  102. Leitenberg M, Zilinskas R, Khun J. The soviet biological weapons program: a history. Cambridge: Harvard University Press; 2012.

    Book  Google Scholar 

  103. Vogel K. Phantom menace or looming danger. Baltimore: Johns Hopkins University Press; 2013.

    Google Scholar 

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Authors and Affiliations

  1. Schar School of Government and Policy, George Mason University, Arlington, VA, USA

    Sonia Ben Ouagrham-Gormley

  2. The Tauri Group, Alexandria, VA, USA

    Shannon R. Fye-Marnien

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  1. Sonia Ben Ouagrham-Gormley
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Correspondence to Sonia Ben Ouagrham-Gormley .

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Editors and Affiliations

  1. Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    Sunit K. Singh

  2. NIH/NIAID, Division of Clinical Research, Integrated Research Facility at Fort Detrick, Frederick, MD, USA

    Jens H. Kuhn

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Ben Ouagrham-Gormley, S., Fye-Marnien, S.R. (2019). Is CRISPR a Security Threat?. In: Singh, S., Kuhn, J. (eds) Defense Against Biological Attacks. Springer, Cham. https://doi.org/10.1007/978-3-030-03053-7_12

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