Is CRISPR a Security Threat?

  • Sonia Ben Ouagrham-GormleyEmail author
  • Shannon R. Fye-Marnien


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.


CRISPR Gene editing Bioweapon Biosecurity 


  1. 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.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Nakata A, et al. Unusual nucleotide arrangements with repeated sequences in the Escherichia coli K-12 chromosome. J Bacteriol. 1989;171:3553–6.PubMedPubMedCentralGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 6.
    Hoe N, et al. Rapid molecular genetic subtyping of serotype M1 group a Streptococcus strain. Emerg Inf Dis. 1999;5:254–63.Google Scholar
  7. 7.
    Barrangou R, Horvath P. A decade of discovery: CRISPR functions and applications. Nat Microbiol. 2017;2(1709):1–9.Google Scholar
  8. 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.PubMedGoogle Scholar
  9. 9.
    Jansen R, et al. Identification of genes that are associated with DNW repeats in prokaryotes. Mol Microbiol. 2002;43(6):1565–75.PubMedGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 11.
    Marx J. New bacterial defense against phage invaders identified. Science. 2007;315:1650–1.PubMedGoogle Scholar
  12. 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.Google Scholar
  13. 13.
    Bolotin A, et al. Clustered regularly interspaced short palindromic repeats (CRISPR) have spacers of extrachromosomal origin. Microbiology. 2005;151:2551–61.PubMedGoogle Scholar
  14. 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.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Barangou R, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315:1709–12.Google Scholar
  16. 16.
    Morange M. What history tells us XXXVII. CRISPR-Cas: the discovery of an immune system. J Biosci. 2015;40(2):221–3.PubMedGoogle Scholar
  17. 17.
    Brouns S, et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science. 2008;321:960–3.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1–9.Google Scholar
  19. 19.
    Ledford H. Five big mysteries about CRISPR’s origins. Nature. 2017;541:280–2.PubMedGoogle Scholar
  20. 20.
    Jinek M, et al. A programmable dual-RNA-guided DNA endonuclease in adaptative bacterial immunity. Science. 2012;337(6096):816–21.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Jinek M, et al. RNA-programmed genome editing in human cells. Elife. 2013.
  22. 22.
    Cong L, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–22.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Begley S. 6 takeaway from the CRISPR patent decision. STAT. 2017, February 16.
  24. 24.
    Cross R. Broad prevails over Berkely in CRISPR patent dispute. C&En, September 10, 2018. Available at:
  25. 25.
    Babcock B. The continuing CRISPR patent battle: The Broad Institute loses a key European patent. MedCityNews. 2018, January 23.Google Scholar
  26. 26.
    Buhr S. China sides with Emanuelle Charpentier and Jennifer Doudna in CRISPR patent war. TechCrunch. 2017.
  27. 27.
    Cohen J. Europe says University of California deserves patent for CRISPR. Science. 2017.
  28. 28.
  29. 29.
    LePage M. Boom in human gene editing as 20 CRISPR trials gear up. New Scientist. 2017. Accessed 29 Sept 2017.
  30. 30.
    LePage M. Why has a UK team genetically edited human embryos? New Scientist. 2017. Accessed 29 Sept 2017.
  31. 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. 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.Google Scholar
  33. 33.
    Krisch JA. First CRISPR clinical trial commences. Scientist. 2016, November 15. Accessed 28 Sep 2017.
  34. 34.
    Clinical Trials Database. PD-1 knockout engineered t cells for metastatic non-small cell lung cancer, Bethesda. 2017. Accessed 29 Sept 2017.
  35. 35.
    Clinical Trials Database. PD-1 and CRISPR. 2017. Accessed 29 Sept 2017.
  36. 36.
    Clinical Trials Database. A safety and efficacy study of TALEN and CRISPR/Cas9 in the treatment of HPV-related Cervical Intraepithelial Neoplasia. 2017. Accessed 29 Sept 2017.
  37. 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.PubMedGoogle Scholar
  38. 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.PubMedGoogle Scholar
  39. 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. 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. 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.PubMedGoogle Scholar
  42. 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.PubMedPubMedCentralGoogle Scholar
  43. 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.PubMedPubMedCentralGoogle Scholar
  44. 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.PubMedPubMedCentralGoogle Scholar
  45. 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).
  46. 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.PubMedGoogle Scholar
  47. 47.
    Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating, and targeting genomes. Nat Biotechnol. 2014;32(4):347–55.PubMedPubMedCentralGoogle Scholar
  48. 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.PubMedGoogle Scholar
  49. 49.
    Shin SE, Lim JM, Koh HG. CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii. Sci Rep. 2016;6:27810. Scholar
  50. 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.PubMedGoogle Scholar
  51. 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.Google Scholar
  52. 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.PubMedGoogle Scholar
  53. 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.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157(6):1262–78.PubMedPubMedCentralGoogle Scholar
  55. 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.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Baltimore D, et al. A prudent path forward for genomic engineering and germline gene modification. Science. 2015;348(6230):36–8.PubMedPubMedCentralGoogle Scholar
  57. 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.PubMedPubMedCentralGoogle Scholar
  58. 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.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Callaway E. Second Chinese team reports gene editing in human embryos. Nature News. 2016. Accessed 29 Sept 17.
  60. 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.Google Scholar
  61. 61.
    LePage M. Mosaic problem stands in the way of gene editing embryos. New Scientist. 2015. Accessed 29 Sept 2017.
  62. 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.PubMedGoogle Scholar
  63. 63.
    Ledford H. CRISPR fixes disease gene in viable human embryos. Nat News. 2017;548:13–4.Google Scholar
  64. 64.
    Servick K. Skepticism surfaces over CRISPR human embryo editing claims. Science Magazine. 2017.
  65. 65.
    Begley S. Federal panel approves first use of CRISPR in humans. STAT. 2016, June 21.Google Scholar
  66. 66.
    LaMotta L. Editas delays CRISPR move to human trials. BioPharmaDive. 2017, May 16.Google Scholar
  67. 67.
    CRISPR Therapeutics. News Release. 2017, March 31.
  68. 68.
    National Academies of Sciences, Engineering, and Medicine. Human genome editing: science, ethics and governance. 2017.Google Scholar
  69. 69.
    Harmon A. Human gene editing receives science panel’s support. NY Times. 2017, February 14.Google Scholar
  70. 70.
    He Jiankui defends ‘World’s first gene-edited babies’. BBC News, November 28, 2018.
  71. 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. 72.
    Begley S. They’re going to CRISPR people: what could possibly go wrong? STAT. 2016, June 23.Google Scholar
  73. 73.
    Araki M, Ishii T. International regulatory landscape and integration of corrective genome editing into in vitro fertilization. Reprod Biol Endocrinol. 2014;12:108. Scholar
  74. 74.
    Konig H. The illusion of control in germ-line engineering policy. Nat Biotechnol. 2017;35:502–6.PubMedGoogle Scholar
  75. 75.
    Vogel G. Embryo engineering alarm. Science. 2015;347(6228):1301.PubMedGoogle Scholar
  76. 76.
    Allen & Overy LLP. Regulating CRISPR genome editing in humans: where do we go from there? JDSupra. 2017, August 14.
  77. 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.
  78. 78.
    Cyranoski D. CRISPR tweak may help gene-edited crops to bypass biosafety regulations. Nature. 2015.
  79. 79.
    FDA (Food and Drug Administration). FDA releases final environmental assessment for genetically engineered mosquito. 2016, August 5.
  80. 80.
    Ledford H. Biohackers gear up for genome editing. Nature. 2015;524:398–9.PubMedGoogle Scholar
  81. 81.
    Esvelt KM. Daisy drive systems. Sculpting Evolution.
  82. 82.
    Ledford H. Safety upgrade found for gene-editing technique. Nature. 2015.
  83. 83.
    Acharya A, Acharya A. Cyberterrorism and biotechnology: when ISIS meets CRISPR. Foreign Affairs. 2017, June 1.Google Scholar
  84. 84.
    Hern A. There are things worse than death: can a cancer cure lead to brutal bioweapons? Guardian. 2017, July 31.Google Scholar
  85. 85.
    Begley S. Gene drive gives scientists power to highjack evolution. STAT. 2015, November 17.Google Scholar
  86. 86.
    Begley S. Why the FBI and pentagon are afraid of this new genetic technology. STAT. 2015, November 12.Google Scholar
  87. 87.
    Ledford H. CRISPR the disruptor. Nature. 2015;522(7554):20–4.
  88. 88.
    Shaw J. Editing an end to malaria. Harvard Magazine. 2016, May–June.
  89. 89.
    Swetlitz I. College students try to hack a gene drive and set a science fair abuzz. STAT. 2016, December 14.Google Scholar
  90. 90.
    Clapper J. Worldwide threat assessment of the US Intelligence Community. Senate Select Committee on Intelligence. 2016, February 9.Google Scholar
  91. 91.
    Mullin E. Obama advisors urge action against CRISPR bioterror threat. MIT Technol Rev. 2016, November 17.Google Scholar
  92. 92.
    Mackby J. Dispute mire BWC review conference. Arms Control Today. 2017, January 11.Google Scholar
  93. 93.
    Brown K. The UN just gave scientists the green light to mess with natural selection. GIZMODO. 2016, December 22.
  94. 94.
    International Bioethics Committee (IBC). Report of the IBC on updating its reflection on the human genome and human rights UNESCO. 2015.
  95. 95.
    Xiong S. Is international CRISPR regulation a pipe dream? Transcripts. 2017, July 24.Google Scholar
  96. 96.
    Doudna JA, Sternberg S. A crack in creation. Boston: Houghton Mifflin Harcourt; 2017.Google Scholar
  97. 97.
    Ledford H. Alternative CRISPR system could improve gene editing. Nature. 2015;526:17.PubMedGoogle Scholar
  98. 98.
    Peng R, et al. Potential pitfalls of CRISPR/Cas9-mediated genome editing. FEBS. 2016;283:1218–31.Google Scholar
  99. 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.PubMedGoogle Scholar
  100. 100.
    Saey T. Gene drives spread their wings. Sci News. 2015;18:16.Google Scholar
  101. 101.
    Ben Ouagrham-Gormley S. Barriers to bioweapons: the challenge of expertise and organization for weapons. Ithaca: Cornell University Press; 2014.Google Scholar
  102. 102.
    Leitenberg M, Zilinskas R, Khun J. The soviet biological weapons program: a history. Cambridge: Harvard University Press; 2012.Google Scholar
  103. 103.
    Vogel K. Phantom menace or looming danger. Baltimore: Johns Hopkins University Press; 2013.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sonia Ben Ouagrham-Gormley
    • 1
    Email author
  • Shannon R. Fye-Marnien
    • 2
  1. 1.Schar School of Government and PolicyGeorge Mason UniversityArlingtonUSA
  2. 2.The Tauri GroupAlexandriaUSA

Personalised recommendations