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Expert Scientific Opinion on the Status of Certain New Techniques of Genetic Modification Under Directive 2001/18/EC

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Expert Scientific Opinion on the Status of Certain New Techniques of Genetic Modification Under Directive 2001/18/EC Centre for Integrated Research in Biosafety Tel: +64 3 364 2500, Fax: + 64 3 364 2590 Email: [email protected] Expert scientific opinion on the status of certain new techniques of genetic modification under Directive 2001/18/EC Professor Jack A. Heinemann, PhD 30 October 2015 This report was commissioned from the University of Canterbury by Greenpeace International. Funding was accepted in accordance with the provisions of the University Research Grants Policy as fulfilling the description of ethical, socially, and culturally responsible research, and the Academic Freedom Policy and Principles. The report was prepared by the author to the agreed scope and is not necessarily the opinion of the University of Canterbury or Greenpeace International. The author thanks Dr David Thaler and Dr Michael Eckerstorfer for their participation in the peer-review process and for their constructive comments of a draft version of this report. All errors remain the responsibility of the author. © the Author i Table of Contents Common Abbreviations ................................................................................................. iii Overview ............................................................................................................................... 1 Mutagenesis or genetic engineering? .................................................................................. 2 Distinguishable and safe? ........................................................................................................ 6 List of conclusions ............................................................................................................. 9 Introduction ..................................................................................................................... 10 Directive 2001/18/EC ................................................................................................... 11 Annex 1 A part 1 ...................................................................................................................... 11 Annex 1 A part 2 ...................................................................................................................... 11 Annex 1 B ................................................................................................................................... 11 Previous work .................................................................................................................. 13 Analysis .............................................................................................................................. 13 OGE is a procedure that creates genetically modified organisms .......................... 14 Inter alia ................................................................................................................................................... 14 Clause 1 terms ........................................................................................................................................ 15 Produced by whatever means outside an organism ......................................................................... 15 Into any virus, bacterial plasmid or other vector system ............................................................... 15 Incorporation into a host organism ......................................................................................................... 16 Capable of continued propagation ............................................................................................................ 16 Clause 2 terms ........................................................................................................................................ 19 Heritable material ............................................................................................................................................ 19 Direct introduction .......................................................................................................................................... 21 Oligonucleotides are unlike traditional chemical and radiation mutagens ....... 22 Safety record ........................................................................................................................................... 23 Spectrum of changes ....................................................................................................................................... 25 Oligonucleotides are chemically and biologically unlike traditional chemical mutagens .................................................................................................................................................. 27 Oligonucleotides are recombinant nucleic acids ......................................................... 30 Summary ........................................................................................................................... 33 References ........................................................................................................................ 35 Appendix One ................................................................................................................... 39 Appendix Two .................................................................................................................. 40 Argument 1 – oligonucleotides can cause DNA sequence changes ......................... 40 Argument 2 – oligonucleotides must be recombinant nucleic acid molecules .. 41 ii Common Abbreviations DNA deoxyribonucleic acid COGEM Netherlands Commission on Genetic Modification GMAG Genetic Manipulation Advisory Group GMO genetically modified organism LMO living (genetically) modified organism NIH National Institutes of Health OGE oligonucleotide-directed genetic engineering ODM/OMM oligonucleotide-direct mutagenesis/ oligonucleotide-mediated mutagenesis rDNA recombinant DNA Recombineering in vivo genetic engineering with short DNA molecules RNA ribonucleic acid iii Heinemann Is OGE a regulated technique of genetic modification? Overview Genetic technologies change. Are new techniques resulting in organisms that should be regulated by member states of the European Union (Podevin et al., 2012)? Organisms considered to be genetically modified cannot be released into the environment before, among other things, a scientific risk assessment has been completed. EU Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms describes in general terms what is and what is not a genetically modified organism (GMO) (Spranger, 2015). Those GMOs in the scope of the Directive are subjected to a mandatory risk assessment as set out in Articles 2(8), 4 and 13. A decision-maker takes the findings of the risk assessment into account, may impose additional risk management requirements, and also takes into account ethical considerations1. The GMO regulations were established in response to the new technologies emerging in the 1970s. These regulations have evolved over time and jurisdiction. Between 1990 and 2001 Directive 90/220/EEC on the deliberate release into the environment of genetically modified organisms was updated to EU Directive 2001/18/EC in part to better capture the scope of coverage. The question here is whether variations of certain techniques, that just in the last few years are beginning to create potential products for release into the environment, are subject to the 2001 Directive. The two general conclusions of the analysis detailed in this report are: 1. application of the techniques discussed creates genetically modified organisms in the sense of Article 2 of Directive 2001/18/EC; and 2. the techniques do not pass at least three tests needed for them to be excluded from the scope of Directive 2001/18/EC. They fail because — a. they are not well established as techniques with a long safety record (in general terms, as opposed to safe/unsafe single products); b. they are not the techniques referred to in Article 3 and listed in Annex 1 B of Directive 2001/18/EC because they are not ‘mutagenesis’ in the same scientific way that the listed excluded techniques are mutagenesis; and c. they are techniques based on the use of recombinant nucleic acid molecules. I have found that the new techniques have substantive scientific continuity with earlier variations of regulated techniques and have no properties that are 1 “Member States may take into consideration ethical aspects when GMOs are deliberately released or placed on the market as or in products” (paragraph 9 of Directive 2001/18/EC). This theme also appears in Regulation (EC) No. 1829/2003 on genetically modified food and feed Article 7(1) with reference to “other legitimate factors” and in Council Conclusions of December 2008 (16882/08): cf. (ii): “under Directive 2001/18/EC, the Commission is to submit a specific report on the implementation of the Directive, including an assessment, inter alia, of socio- economic implications of deliberate releases and placing on the market of GMO.” 1 Heinemann Is OGE a regulated technique of genetic modification? outside of defining features of regulated techniques at the time that Directive 2001/18/EC was written. Many of the new techniques involve small polymers of nucleic acids called oligonucleotides.2 These nucleic acid molecules are introduced into cells3 where they interact with, among other things, a target nucleic acid of (partial to completely) complementary sequence. That interaction results in changes to the target sequence and, consequently, the
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