The discovery of a genome editing system in bacteria and its use for editing genomes of many organisms is transforming the way biotechnology is done. Likewise, the use of the gene drives (a form of stimulating biased inheritance of particular genes to alter entire populations) opens up new applications for the control of pests and invertebrate vectors or hosts, whenever they have a short life cycle. But the knowledge of the two techniques is far from being widespread and sufficient, even among geneticists.
In parallel with the rapid development of genome editing and gene drives, regulatory issues arise questioning the applicability of risk assessment procedures, as originally established for GMOs, and legal issues, such as the inclusion of this or that product in the regulatory framework of each country, regulatory asynchrony, the ethical issues involved, etc.
Any meaningful discussion of these issues must be grounded in updated and quality information. We therefore collected and offer the reader a set of selected references that may be helpful in understanding both new technologies and in establishing the applicability and eventual limits of present risk assessment rules of new genome-edited or gene drive products.
We split a little arbitrarily texts in three subsets, the first devoted to the issue of genome editing by the CRISPR/Cas9 system, the second to gene drives and the third for risk assessments available for the GM Aedes aegypti previously evaluated by CTNBio in Brazil and considered safe for commercial use in 2014. The latter references also include general considerations on GM mosquitoes and emphasize the importance of new tools in vector control, particularly in mosquito-borne diseases.
The texts whose links follow below can be of various kinds: scientific articles, technical reports, reviews written by scientists, reviews written by activists, conference presentations, etc. Many are available to the general public. Texts marked with a square are suitable for a first approach to the subject. The search for texts was not exhaustive and therefore we know that there may be relevant texts that are not listed below. So over the next few months, other texts may be added, appropriately highlighted as new.
Finally, we remind the reader that national regulatory frameworks should not regulate a technology, but their products. In fact, each product carries its risks and benefits, even if produced by the same technology. The serious mistake many countries committed regulating the technology, rather than the product, should not be repeated again. We also recall that the risk assessment conceptual basis, as established for GMOs, probably will suffice for a careful and responsible risk assessment of products arising from any other technology, especially the CRISPR system / Cas9.
A. Selected texts on genome editing issues
A1. Texts describing the technology and general issues
Bhaya D, Davison M, Barrangou R, 2011. CRISPR-Cas Systems in Bacteria and Archaea: Versatile small RNAs for adaptive defense and regulation. Annu. Rev. Genet. 45:273–97. http://www.ncbi.nlm.nih.gov/pubmed/22060043
Anonymous, 2016. CRISPR/Cas9 Guide. https://www.addgene.org/crispr/guide/
Medina-Aparicio L, Rebollar-Flores JE, Gallego-Hernández AL, Vázquez A, Olvera L, Gutiérrez-Ríos RM, Calva E, Hernández-Lucas I, 2011. The CRISPR/Cas Immune System Is an Operon Regulated by LeuO, H-NS, and Leucine-Responsive Regulatory Protein in Salmonella enterica Serovar Typhi. J. Bacteriol. 193(10): 2396-2407. http://jb.asm.org/content/193/10/2396.full
Ran FA, Hsu PD, JWright J, Agarwala V, Scott DA, Zhang F, 2013. Genome engineering using the CRISPR-Cas9 system. Nature Protocols 8(11): 2281-2308 doi:10.1038/nprot.2013.143.
A2. Texts on regulatory and ethical issues (risk assessment, risk analysis, legal framework, etc.)
Jasanoff S, Hurlbut JB, Saha K, 2015. "CRISPR Democracy: Gene Editing and the Need for Inclusive Deliberation." Issues in Science and Technology 32, no. 1 (Fall 2015). http://issues.org/32-1/crispr-democracy-gene-editing-and-the-need-for-inclusive-deliberation/
Hoffman S, 2016. CRISPR: The GMO technology that needs no regulation, says USDA. Organic Consumers Association. https://www.organicconsumers.org/news/crisprgmotechnologyneedsnoregulationsaysusda
Entine J, 2015. Ethical and regulatory reflections on CRISPR gene editing revolution. Genetic Literacy Project, https://www.geneticliteracyproject.org/2015/06/25/ethical-and-regulatory-reflections-on-crispr-gene-editing-revolution/
Magnus D, Martinez N, 2016. In Embryo research we need laws first, then science. http://time.com/4204059/crisprregulation/
Caplan AL, Parent B, Shen M, Plunkett C, 2015. No time to waste—the ethical challenges created by CRISPR. EMBO reports 16(11): 1421-1426. http://embor.embopress.org/content/16/11/1421.long
The Third World Network, 2016. Gene Editing: In Urgent Need of Regulation. http://www.biosafetyinfo.net/article.php?aid=1216
B. Selected texts on gene drive issues
B1. Texts describing the technology and general issues
Anonymous, 2016. A review of the safety & efficacy of genetically engineered mosquitoes. Effective Altruism Forum. http://effective-altruism.com/ea/tp/a_review_of_the_safety_efficacy_of_genetically/
Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, Gribble M, Baker D, Marois E, Russell S, Burt A, Windbichler N, Crisanti A, Nolan T, 2016. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 34(1):78-83. http://www.ncbi.nlm.nih.gov/pubmed/26641531
Esvelt KM, Smidler AL, Catterucci F, Church GM, 2014. Concerning RNA-guided gene drives for the alteration of wild populations. eLife 2014;3:e03401. https://elifesciences.org/content/3/e03401v3
Sinkins SP, Gould F, 2006. Gene drive systems for insect disease vectors. NATURE REVIEWS, GENETICS, 7: 427-435. http://www.nature.com/nrg/journal/v7/n6/full/nrg1870.html
Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA, 2015. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc Natl Acad Sci U S A. 112(49):E6736-43. http://www.ncbi.nlm.nih.gov/pubmed/26598698
Akbari OS, Matzen KD, John M. Marshal JM, Huang H, Ward CM, Hay BA, 2013. A synthetic gene drive system for local, reversible modification and suppression of insect populations. Current Biology 23: 671–677. http://dx.doi.org/10.1016/j.cub.2013.02.059
Marshall JM, Hay BA, 2014. Medusa: A Novel Gene Drive System for Confined Suppression of Insect Populations. PLoS One. 9(7): e102694. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108329/
Marshall JM, Akbari OS, 2016. Gene Drive Strategies for Population Replacement, Chap. 9. http://jmarshall.berkeley.edu/Chapter9GeneticControlOfDengueAndMalaria.pdf
Champer, J., Buchman, A., Akbari, O. S., 2016 Cheating evolution: engineering gene drives to manipulate the fate of wild populations. Nat Rev Genet 17: 146-159doi: 10.1038/nrg.2015.34. http://www.nature.com/nrg/journal/v17/n3/full/nrg.2015.34.html
Esvelt K, Church G, Lunshof J, 2014. "Gene Drives" and CRISPR could revolutionize ecosystem management. Scientific American Blog Network. http://blogs.scientificamerican.com/guestblog/genedrivesandcrisprcouldrevolutionizeecosystemanagement/?print=true
B2. Texts on regulatory and ethical issues (risk assessment, risk analysis, legal framework, etc.)
Westra J, van der Vlugt CJB, Roesink CH, Hogervorst PAM, Glandorf DCM. 2016. Gene drives. Policy report. RIVM Letter report 2016-0023 (National Institute for Public Health and the Environment, The Netherlands) - http://rivm.nl/en/Documents_and_publications/Scientific/Reports/2016/februari/Gene_drives_Policy_report
Anonymous, 2015. Engineering the Future: How Can the Risks and Rewards of Emerging Technologies Be Balanced? Report. World Economic Forum. http://reports.weforum.org/global-risks-2015/part-2-risks-in-focus/2-4-engineering-the-future-how-can-the-risks-and-rewards-of-emerging-technologies-be-balanced/
Oye KA, Esvelt K,Appleton E, Catteruccia F, Church G, Kuiken T, Lightfoot SB-Y, McNamara J, Smidler A, Collins JP, 2014. Regulating gene drives. http://science.sciencemag.org/content/345/6197/626 / 17 July 2014 / Page 1 / 10.1126/science.1254287
Benedict M, D'Abbs P, Dobson S, Gottlieb M, Harrington L, Higgs S, James A, James S, Knols B, Lavery J, O'Neill S, Scott T, Takken W, Toure Y, 2008. Guidance for Contained Field Trials of Vector Mosquitoes Engineered to Contain a Gene Drive System: Recommendations of a Scientific Working Group. VECTOR-BORNE AND ZOONOTIC DISEASE, 8 (2): 127-66. http://www.ncbi.nlm.nih.gov/pubmed/18452399
Cobb M, 2016. Gene drives need global policing. The Guardian, 9 February 2016. https://www.theguardian.com/science/2016/feb/09/genedrivesneedglobalpolicing
Spradling A, 2015. Gene Drive: More research, not more regulations. Genes to Genomes blog. https://genestogenomes.org/gene-drive-more-research-not-more-regulations/
Carter SR, 2015. Gene Drives and the U.S. Biotechnology Regulatory System. Presentation. J. Craig Venter Inst. http://nas-sites.org/gene-drives/files/2015/11/2-Carter-NAS-Gene-Drive-webinar.pdf
Pennisi E, 2015. Gene drive workshop shows technology’s promise, or peril, remains far off. http://www.sciencemag.org/news/2015/10/gene-drive-workshop-shows-technology-s-promise-or-peril-remains-far
C. Selected texts on OX513A Aedes aegypti risk assessment and general issues on GM insects
Beech CJ, Koukidou M, Morrison NI, Alphey L. 2012. Genetically Modified Insects: Science, Use, Status and Regulation. International Centre for Genetic Engineering and Biotechnology (ICGEB). Collection of Biosafety Reviews Vol. 6 (2012): 66-124. http://www.icgeb.org/biosafety/publications/collections.html
Beech CJ, Nagaraju J, Vasan SS, Rose RI, Othman RY, Pillai V, Saraswathy TS, 2009. Risk analysis of a hypothetical open field release of a self-limiting transgenic Aedes aegypti mosquito strain to combat dengue. AsPac J. Mol. Biol. Biotechnol. 17 (3): 99-111 https://www.researchgate.net/profile/Camilla_Beech/publication/268060205_Risk_analysis_of_a_hypothetical_open_field_release_of_a_self-limiting_transgenic_Aedes_aegypti_mosquito_strain_to_combat_dengue/links/547599db0cf245eb4370e0fa.pdf .
FDA, 2016. Preliminary finding of no significant impact (FONSI) in support of an investigational field trial of OX513A Aedes aegypti mosquitoes. 6pp. http://www.fda.gov/downloads/AnimalVeterinary/DevelopmentApprovalProcess/GeneticEngineering/GeneticallyEngineeredAnimals/UCM487379.pdf
Brazil, 2014. Technical Opinion no. 3964/2014. Request for Opinion on Commercial Release of Genetically Modified Mosquito. http://bch.cbd.int/database/attachment/?id=14514
Mumford JD, 2012. Science, Regulation, and Precedent for Genetically Modified Insects. Plos Neglected Trop. Dis. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001504
Anonymous, 2010. Report of the genetic modification advisory committee (GMAC) for an application to conduct a limited mark-release-recapture of Aedes aegypti (l.) wild type and OX513A strains. bch.cbd.int/database/attachment/?id=10793
Anonymous, 2014. The Guidance Framework for testing genetically modified mosquitoes. http://www.who.int/tdr/publications/year/2014/guide-fmrk-gm-mosquit/en/