Taking Stock of the Environmental Risk Assessment of Genetically Modified Plants and Gene Therapy

Taking stock of the environmental risk assessment of genetically modified plants and gene therapy 30 December 2015 Study performed for the National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu) Project 4410001148 Patrick L.J. RÜDELSHEIM & Greet SMETS PERSEUS BVBA Advisory Committee The authors gratefully acknowledge the members of the advisory committee for the valuable discussions and patience. Prof. dr. G.A.P. Hospers Universitair Medisch Centrum Groningen Dr. W.J. de Kogel Wageningen University & Research Centre Dr. I. de Kort Ministerie van Infrastructuur en Milieu (Ministry of Infrastructure and Dr. J.E.E. Ng-A-Tham Environment) Dr. D.C.M. Glandorf, Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Dr. H.C.M. van den Akker Public Health and the Environment) Dr. ir. M.M.C. Gielkens Dr. D.A. Bleijs Dr. ir. P.A.M. Hogervorst H. de Wijs Disclaimer This report was commissioned by the RIVM. The contents of this publication are the sole responsibility of the authors and may in no way be taken to represent the views of the RIVM or members of the advisory committee. 2 | 170 Summary Based on the precautionary principle, legislation addressing environmental aspects of research on, development and marketing of genetically modified organisms (GMOs) was established in the early nineties. At that moment, limited knowledge on environmental effects of GMOs was available. Since then a vast amount of data has been generated. Both applicants and research institutes in Europe and elsewhere studied a diversity of aspects relating to environmental safety. In Europe and in the Netherlands in particular many field trials and clinical trials have been conducted. Much experience is gained on genetically modified (GM) crops that have been commercialised in several parts of the world. However, some topics may still lack sufficient high quality data. The National Institute for Public Health and the Environment (RIVM) commissioned PERSEUS bvba to inventory the areas of concern in environmental risk assessments (ERA) for development and market introduction, to evaluate the type of information necessary to perform ERAs both in the field of GM plants and gene therapy for humans, to identify areas in which our understanding has evolved to a level that provides confidence for conclusions in the ERA, to point out remaining areas of uncertainty and to recommend topics for further studies and initiatives. A comparison of European legislation and legislation in other jurisdictions provides a basis for identifying the areas of concern in ERA. There are differences in the trigger to conduct an ERA mainly depending on the scope of organisms covered by the legislation and whether activities are considered contained use or not. Irrespective these differences, the methodology as well as the areas of concern are very comparable to what has been established in the EU: likelihood of the GMO to become more persistent and/or invasive than the recipient or parental organism; any selective advantage or disadvantage conferred to the GMO and the likelihood of this becoming realised; potential for gene transfer to other species and any selective advantage or disadvantage conferred to those species; potential immediate and/or delayed environmental impact of the direct and indirect interactions between the GMO and target organisms (if applicable); potential immediate and/or delayed environmental impact of the direct and indirect interactions between the GMO with non-target organisms, including impact on population levels of competitors, prey, hosts, symbionts, predators, parasites and pathogens; possible immediate and/or delayed effects on human health resulting from potential direct and indirect interactions of the GMO and persons working with, coming into contact with or in the vicinity of the GMO release(s); possible immediate and/or delayed effects on animal health and consequences for the feed/food chain; possible immediate and/or delayed effects on biogeochemical processes; possible immediate and/or delayed, direct and indirect environmental impacts of the specific techniques used for the management of the GMO where these are different from those used for non-GMOs. This convergence of methodology can be linked to the fact that most national and international regulations build on the criteria and principles set out in the Organisation for Economic Cooperation and Development (OECD) Blue Book on "Recombinant DNA Safety Considerations", published in 1986. For GM plants all concerns are investigated. For gene therapy trials and products, the focus is predominantly on human health including that of the patient as well as staff and family members. Other environmental concerns are less addressed. Depending on the vector type some are deemed less relevant in gene therapy applications (e.g. effects on animals and consequences for the feed/food chain for human pathogen derived vectors, effects on biogeochemical processes for viral vectors as opposed to bacterial vectors, and effect of change in management techniques). 3 | 170 Some concerns voiced by stakeholders and the public at large may reflect important policy options, but they may not fit in the framework of an ERA. On the other hand, ERA could be further improved by agreement on protection goals and translating them in measurable assessment endpoints. This report then presents an overview of available information that may serve to evaluate the different elements of the ERA for respectively GM plants and gene therapy: documents issued by governmental bodies (authorities, advisory committees); research commissioned by a governmental body; government funded research projects; consortium sponsored research; information from applicants; and scientific reports and publications, including monographs, reviews, meta-analyses, conferences and activities from societies. This overview indicates that there is far more information relevant for ERA of GM plants than for the ERA on gene therapy. Possible factors influencing this bias include: prominent environmental exposure of GM plants; legal regime (focus on containment for gene therapy instead of environmental exposure); more advanced GM crop projects and products; global scale of GM crop products; responsive scientific community; and heightened critical public attention for GM plant applications. With this “body of evidence”, an attempt was made to identify elements for which ERA can be conducted with acceptable confidence and no additional information may be required as well as identifying areas in which research can be conducted to serve future ERA. For GM higher plants: The comparative assessment acknowledges that the ERA of most activities with GMOs can build on what is already known for the non-modified host/parental organism. It recognises that the engineered modifications only change specific aspects of the organism. When the host organism has a history of safe use (or rather a use for which the impact is accepted), the ERA can focus on the potential impact resulting from the modification. It is questioned whether genes and gene constructs that were independently and repetitively assessed leading to the authorisation of different transformation events, should be subjected to a full assessment when deployed in new events. Similarly, experience obtained with stacked events should allow limiting the review to those cases where the stack is potentially leading to an interaction between the inserted traits. Major field crops are well documented and provide a model for other plant species. While the comparative method has been well established for field crops, it may proof to be difficult to apply for other plants (e.g. trees). Traits like specific herbicide tolerances and insect resistance have been elaborated and can serve as model for other traits. Looking ahead, modifications addressing essential aspects of the life cycle of the GM plant (e.g. modification of the reproductive biology) will potentially require adapted paradigms for evaluating invasiveness and/or persistence. Mechanism such as spread in the environment (seeds, pollen) and transfer to other organisms (pollen flow) have been documented in detail and further accumulation of information is unlikely to provide new insights for the risk assessment. The hypothetical concern for horizontal gene transfer can be neglected unless the trait would indicate a special safety issue. The interaction with other organisms, i.e. non-target organisms (NTO), has been studied in great detail for Bt proteins and more specifically Cry1Ab delta-endotoxin. Additional scientific research as well as experience from large scale release continues to broaden the range of NTOs exposed to these proteins and increases the level of confidence, but unless an unexpected counter- indication would be identified, there is no justification to expand the requirements for pre- authorisation NTO testing. Finally, given the diversity of existing agronomic practices, evaluating changes in management is largely influenced by the choice of the reference management regime. 4 | 170 For gene therapy: Only in specific gene therapy cases the parental organism has a history of safe use. Rather, in most applications, the non-modified parental organism is related to a pathogen, which can be strongly attenuated and/or to which the population may have built up immunity. The comparative approach must therefore identify the new intended modification; while at the same time

Load more