ENSSER Statement: New genetic modification techniques and their products pose risks that need to be assessed

Australia should reverse deregulation of new GM techniques

As a network of scientists concerned about the health of citizens worldwide as well as our environment and biodiversity, the European Network of Scientists for Social and Environmental Responsibility (ENSSER) is deeply concerned about Australia’s recent decision (October 8) to deregulate a number of the new genetic modification techniques. On November 13, the Australian Senate will vote on a motion which reverses this decision. ENSSER has sent all Senators and Members of Parliament a statement explaining that the current state of the science strongly supports this reversion.


There is no guarantee that the use of these techniques will result in predictable outcomes – or that any resulting products will be safe. The basis of the deregulation decision, the advice from the Australian Office of the Gene Technology Regulator that “SDN-11 organisms present no different risk than organisms carrying naturally occurring genetic changes”, is scientifically untenable.


Apart from this, the consequences of the decision will deeply affect not just Australia but also Europe and the rest of the world, due to our economies being deeply interconnected. In particular, if the decision is upheld, Australia will no longer be able to guarantee that its food products are GM free. Also, its organic products will lose their organic status.

ENSSER strongly encourages the Australian Senators to support, in their vote on November 13, the motion disallowing the amendments to the Gene Technology Regulations which deregulate the techniques concerned, on the basis that the motion accurately reflects the current state of the science behind gene editing and gene silencing. The ENSSER statement contains the arguments, based on the most recent literature. This statement has also been presented to the members of the House of Representatives, in the hope that the Senate vote will not be the last step in this political process.

[1]    SDN1 = Site Directed Nucleases 1


ENSSER Statement:
New genetic modification techniques and their products pose risks that need to be assessed

Gene editing and RNA interference are powerful new genetic engineering techniques with no history of safe use. We believe that when these techniques are applied to living organisms, they should be regulated in the same way as other genetic modification (GM) techniques – including any null segregant products. There is no guarantee that the use of these techniques will result in predictable outcomes – or that any resulting products will be safe. Furthermore, we are deeply concerned that deregulation of some processes will result in the use of these techniques on living organisms in the open environment – a practice without precedent or a history of safe use.1


On 13th November, the Australian Senate will vote on whether to disallow amendments to the Gene Technology Regulations that deregulate a number of gene editing and RNA interference techniques. We strongly encourage Senators to support the disallowance motion, on the basis that it accurately reflects the current state of the science behind gene editing and gene silencing.


On 8th October, amendments to Australia’s Gene Technology Regulations deregulated the creation and release into the environment and our food chain of modified organisms whose genes are altered using ‘Site Directed Nucleases 1’ (SDN-1). GM animals, plants and microbes produced using these techniques will hence no longer be subject to safety assessment or traceability requirements. The decision is based on advice from the Office of the Gene Technology Regulator that “SDN-1 organisms present no different risk than organisms carrying naturally occurring genetic changes.”2 A growing body of new peer-reviewed research now renders this conclusion untenable.


The deregulated technologies can be used to produce genetic changes that could never occur in nature. They can be used to make a series of different alterations to the same genes, or changes to many genes simultaneously or one after the other – either in a laboratory or in the open environment – with unknown ecological consequences. The techniques can also target areas of the genome that are normally highly resistant to mutation.3 Furthermore, recent research has found that gene editing can result in numerous unexpected, unpredictable and undesirable outcomes, even at the intended gene editing site. This includes large deletions and complex rearrangements of DNA,4 and the creation of new proteins.5 It is important to note that these unpredictable and undesirable genetic mutations result after the gene editing tool has completed its task (e.g. of creating a break in the DNA) and will occur regardless of the precision of the initial edit.


The recent discovery that cattle that had been gene-edited to be hornless unexpectedly contained antibiotic resistance genes from bacteria illustrates why all gene editing techniques should be regulated.6 The company which gene-edited the cattle using SDN-3, had claimed “we have all the scientific data that proves that there are no off-target effects.”7 After the discovery by others that genes from bacteria had been inserted into the cattle during the procedure, the company admitted “we did not look for [these bacterial genes]” and acknowledged a more thorough examination of the work “should have been done”.


We cannot leave public and environmental safety to the expectations or assumptions of those who alter the genetics of living things and whatever potential hazards they chose to look for. Instead, we need impartial regulators empowered by strong legislation to protect public health and the environment.


Unexpected integrations of foreign DNA through the gene editing process have been observed in many species including mice, fruit flies, medaka fish, yeast, Aspergillus (a fungus), the nematode C. elegans, the small crustacean Daphnia magna, and various plants. 8 Very recently, studies have shown that gene editing can result in the unintended integration in organisms’ genomes of DNA from common reagents used in the tissue culture media or other contaminants.9 Furthermore, applications of the SDN-1 technique can lead to modifications to genes as different or even more pronounced than introducing genes from other species. This is due to the ability to apply SDN-1 rapidly and repeatedly to the same genes or to simultaneously or serially alter many genes at once.


The regulatory changes will also deregulate the direct application of RNAs to alter gene expression. RNA interference (RNAi) through, for example, the use of “spray on” or other topical products may be hazardous to non-target organisms – including humans. It may also alter the DNA of ecologically critical non-target organisms such as protozoa. It is therefore of paramount importance that these products are thoroughly assessed for safety on a case by case basis.10


Under the regulatory changes, so-called “null segregant” organisms will also be regarded as non-GM if (1) they have gone through a genetic modification process but “no longer have the genetic modification or any traits that occurred because of gene technology” or (2) have not inherited a transgenic gene from a parent.11 Both these examples assume that the genetic modification process has caused no unintended or unexpected changes or effects. Such organisms should not be deregulated until thorough checking standards are established.


Current genetic modification techniques – including gene editing and gene silencing – are not sufficiently specific to introduce only the intended molecular changes. Unexpected molecular changes could result in the production of novel toxins and allergens or unpredictable impacts on other organisms and ecosystems. Even intended molecular changes can result in unexpected effects, due to the incomplete understanding of the role (often multiple roles) of the gene sequences or gene product(s) in regulatory or metabolic processes12. For these reasons, it is vital that a case-specific risk assessment be conducted for all organisms modified by gene editing or RNAi. 13


Regulation does not prevent responsible industries from bringing forward safe products that are sought by the public. However, it is essential to provide a series of checks and balances to stop potentially dangerous products from being released into our environment and food chain.


Professor Jack Heinemann, Geneticist, University of Canterbury, New Zealand

Dr Michael Antoniou, head of the Gene Expression and Therapy Group, King’s College, London School of Medicine, UK

Dr Judy Carman BSc (Hons) PhD MPH MPHAA, Epidemiologist and Biochemist, Director Institute of Health and Environmental Research, Australia

Dr Jonathan Latham, Geneticist and Director of the Bioscience Resource Project, USA

Dr Ulrich Loening, Retired Molecular Biologist and Human Ecologist, formerly University of Edinburgh, Scotland, UK

Professor Giuseppe Longo, Mathematician and Theoretical Biologist, formerly Research Director of CNRS, Ecole Normale Supérieure, Paris, France, and School of Medicine, Tufts University, Boston, USA

Dr Brigitta Kurenbach, Geneticist, University of Canterbury, New Zealand

Dr Ricarda A. Steinbrecher, Geneticist and Biologist, Board Member of ENSSER, Oxford, UK

Dr Christian Vélot, Molecular Geneticist, University Paris-Sud and CRIIGEN, France

Dr François Briens, Socio-ecological Economist, independent, France

Dr Andrea Beste, Leader of the Institute for Soil Conservation and Sustainable Agriculture, Mainz, Germany

Dr Joël Spiroux de Vendômois, University of Caen and President of CRIIGEN (Committee for Research and Independent Information on Genetic Engineering), France

Dr Ernst von Weizsäcker, Professor emeritus of Biology, Essen University, Germany

Dr Arnaud Apoteker, Board Member of ENSSER, General Delegate, Justice Pesticides, France

David Gee, Visiting Fellow, Institute of Environment, Health and Societies, Brunel University, London, UK

Dr Polyxeni Nicolopoulou-Stamati MD PhD, Chair of ENSSER, Professor of Environmental Pathology, Medical School of National and Kapodistrian University of Athens, Greece

Dr Nicolas Defarge, Biologist, Vice Chair of ENSSER, Switzerland

Dr Janet Cotter, Biogeochemist, Logos Environmental Consultancy, UK

Alja Hoeksema MA, Ethicist, independent, Netherlands

Dr Angelika Hilbeck, Board Member of ENSSER, Institute of Integrative Biology, Swiss Federal Institute of Technology (ETH), Switzerland

Diederick Sprangers MSc, Biochemist, Coordinator of ENSSER, Netherlands

Bernadette Oehen, Botanist, Research Institute for Organic Agriculture, Switzerland

Professor Gilles-Eric Séralini, Molecular Biologist / Endocrinologist, University of Caen, France

Professor George Chrousos MD, MACP, MACE, FRCP, Professor of Pediatrics and Endocrinology Emeritus, University of Athens and Aghia Sophia Children’s Hospital, Greece, Holder UNESCO Chair on Adolescent Health Care, Distinguished Investigator Emeritus, National Institutes of Health, USA

Professor Dr Regine Kollek, Professor of Technology Assessment, Hamburg University, Germany

Dr Ignacio Chapela, Microbial Ecologist, Associate Professor, University of California, Berkeley, USA

Dr Lefkothea Evrenoglou, Environmental Engineer, Associate Professor, University of West Attica, Greece


1      Heinemann, J.A. & Walker, S. Environmentally Applied Nucleic Acids and Proteins for Purposes of Engineering Changes to Genes and Other Genetic Material. Biosafety and Health, in press.

2      OGTR (2019) Questions & Answers on the Technical Review of the Gene Technology Regulations 2001, http://www.ogtr.gov.au/internet/ogtr/publishing.nsf/Content/A0E750E72AC140C4CA2580B10011A68E/$File/Technical%20Review%20QA%20July%202019.pdf

3      Kawall, K. (2019) New Possibilities on the Horizon: Genome Editing Makes the Whole Genome Accessible for Changes, Frontiers in Plant Science, 10:525, doi: 10.3389/fpls.2019.00525

4      Kosicki, M. et al. (2019) Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements, Nat Biotechnol. 36(8): 765–771. https://europepmc.org/articles/pmc6390938

5      Tuladhar R, Yeu Y, Piazza JT, et al. (2019) CRISPR-Cas9-based mutagenesis frequently provokes on-target mRNA misregulation. Nat Commun.10(1):1-10

6      Norris, A. L. et al. (2019) Template plasmid integration in germline genome-edited cattle, 28/7/19, https://www.biorxiv.org/content/10.1101/715482v1

7      Berman, R. (2019) Serious problem found with gene-edited celebrity cows, Big Think, https://bigthink.com/technology-innovation/hornless-dna-problem?rebelltitem=3#rebelltitem3

8         Ono, R. (2015) Double strand break repair by capture of retrotransposon sequences and reverse-transcribed spliced mRNA sequences in mouse zygotes, Scientific Reports, 5: 12281, https://www.nature.com/articles/srep12281; Jacobs, T.B. et al. (2015) Targeted genome modifications in soybean with CRISPR/Cas9, BMC Biotechnology, 5:16, https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-015-0131-2; Zhongsen Li, Zhan-Bin Liu, Aiqiu Xing, Bryan P. Moon, Jessica P. Koellhoffer, Lingxia Huang, R. Timothy Ward, Elizabeth Clifton, S. Carl Falco, A. Mark Cigan (2015) Cas9-Guide RNA Directed Genome Editing in Soybean, Plant Physiology, 169 (2): 960-970; http://www.plantphysiol.org/content/169/2/960; Gutierrez-Triana, J.A. et al. (2018) Efficient single-copy HDR by 5’ modified long dsDNA donors, eLIFE, https://cdn.elifesciences.org/articles/39468/elife-39468-v2.pdf

9      Ono, R. et al. (2019) Exosome-mediated horizontal gene transfer occurs in double-strand break repair during genome editing, Communications Biology, https://www.nature.com/articles/s42003-019-0300-2.pdf?origin=ppub

10    Heinemann, J.A. (2019) Should dsRNA treatments applied in outdoor environments be regulated? Environ Int., 132:104856

11    Gene Technology Amendment (2019 Measures No. 1) Regulations 2019. 4/4/19, https://www.legislation.gov.au/Details/F2019L00573/Download; . Explanatory statement, Select Legislative Instrument 2019 No. XX, Gene Technology Act 2000, Gene Technology Amendment (2019 Measures No. 1) Regulations 2019. https://www.legislation.gov.au/Details/F2019L00573/Download,

12    Baltimore, D. et al. (2015) A prudent path forward for genomic engineering and germline gene modification. Science 348, 36-38

13      Eckerstorfer, M.F. et al. (2019) An EU Perspective on Biosafety Considerations for Plants Developed by Genome Editing and Other New Genetic Modification Techniques (nGMs), Front. Bioeng. Biotechnol., https://doi.org/10.3389/fbioe.2019.00031