THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE
Dear Friends and Colleagues
New GM Plants Must be Subject to Case-specific Premarket Risk Assessment
A broad range of new genetic modification techniques (nGMs) including genome editing is currently available and rapidly being developed. They are used to develop nGM plants with different traits and characteristics, which will carry different levels of risk. The lack of robust biosafety information for nGM plants is a significant issue in the ongoing discussion concerning the regulation of nGM applications by existing biosafety frameworks.
A literature survey was conducted to identify plants developed by nGMs which are relevant for future agricultural use. With respect to intended traits, three categories were distinguished: (i) nGM plants with traits and usage known from conventional approaches and without adverse effects; (ii) nGM plants with traits known from established GM plants, e.g., herbicide resistance or disease resistance, and associated with comparable risk issues; and (iii) nGM plants with traits which have not yet been established and thus need to be considered as novel.
The researchers stress that characteristics of some genome editing applications, e.g., the small extent of genomic sequence change and their higher targeting efficiency, i.e., precision, cannot be considered an indication of safety per se, especially in relation to novel traits created by such modifications. All nGMs considered in the analysis can result in unintended changes of different types and frequencies. Furthermore, the rapid development of nGM plants can compromise the detection and elimination of unintended effects.
The researchers argue that a general framework for biosafety oversight should be implemented for nGM plants, based on a case-specific risk assessment that takes into account (i) the nature of the developed trait; (ii) unintended consequences of the modification introduced; (iii) the available experience with comparable products; and (iv) relevant protection goals specified by the respective countries. They further recommend appropriate molecular characterization to identify unintended changes and/or confirm the absence of unwanted transgenic sequences.
These will require that the existing EU guidance for risk assessment of GMOs be reviewed as to whether it is suitable, sufficient and appropriate for specific types of nGM applications. Specific guidance needs be developed which enables risk assessors to focus their attention and resources on issues of concern specific for the different applications and to use established and emerging tools for their assessment.
With best wishes,
Third World Network
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AN EU PERSPECTIVE ON BIOSAFETY CONSIDERATIONS FOR PLANTS DEVELOPED BY GENOME EDITING AND OTHER NEW GENETIC MODIFICATION TECHNIQUES (nGMS)
Michael F. Eckerstorfer, Andreas Heissenberger, Wolfram Reichenbecher, Ricarda A. Steinbrecher and Friedrich Waßmann
Front. Bioeng. Biotechnol.
5 March 2019
https://doi.org/10.3389/fbioe.2019.00031
https://www.frontiersin.org/articles/10.3389/fbioe.2019.00031/full
Abstract
The question whether new genetic modification techniques (nGM) in plant development might result in non-negligible negative effects for the environment and/or health is significant for the discussion concerning their regulation. However, current knowledge to address this issue is limited for most nGMs, particularly for recently developed nGMs, like genome editing, and their newly emerging variations, e.g., base editing. This leads to uncertainties regarding the risk/safety-status of plants which are developed with a broad range of different nGMs, especially genome editing, and other nGMs such as cisgenesis, transgrafting, haploid induction or reverse breeding. A literature survey was conducted to identify plants developed by nGMs which are relevant for future agricultural use. Such nGM plants were analyzed for hazards associated either (i) with their developed traits and their use or (ii) with unintended changes resulting from the nGMs or other methods applied during breeding. Several traits are likely to become particularly relevant in the future for nGM plants, namely herbicide resistance (HR), resistance to different plant pathogens as well as modified composition, morphology, fitness (e.g., increased resistance to cold/frost, drought, or salinity) or modified reproductive characteristics. Some traits such as resistance to certain herbicides are already known from existing GM crops and their previous assessments identified issues of concern and/or risks, such as the development of herbicide resistant weeds. Other traits in nGM plants are novel; meaning they are not present in agricultural plants currently cultivated with a history of safe use, and their underlying physiological mechanisms are not yet sufficiently elucidated. Characteristics of some genome editing applications, e.g., the small extent of genomic sequence change and their higher targeting efficiency, i.e., precision, cannot be considered an indication of safety per se, especially in relation to novel traits created by such modifications. All nGMs considered here can result in unintended changes of different types and frequencies. However, the rapid development of nGM plants can compromise the detection and elimination of unintended effects. Thus, a case-specific premarket risk assessment should be conducted for nGM plants, including an appropriate molecular characterization to identify unintended changes and/or confirm the absence of unwanted transgenic sequences.
Conclusion
A broad range of nGMs including genome editing is currently available and further methods allowing complex modification of plants are rapidly being developed. They are used to develop nGM plants with different traits and characteristics, which will be associated with different levels of risk. With respect to intended traits three categories of nGM plants can be distinguished (apart from further considerations regarding e.g., crop type, purpose of application, and use, etc., that have to be taken into account additionally):
(1) nGM plants with traits and usage known from conventional approaches and without adverse effects
(2) nGM plants with traits known from established GM plants, e.g., herbicide resistance or disease resistance, and associated with comparable risk issues
(3) nGM plants with traits which have not yet been established and thus need to be considered as novel.
Our study shows that nGM applications may be found for all three categories; the same applies for all sub-classes of genome editing (SDN-1, SDN-2, and SDN-3). Therefore, regulation and risk assessment has to acknowledge that all nGM groups will be comprised of a mix of applications with lower as well as higher uncertainty regarding their level of risk/safety. In addition nGM applications are fairly new and only a few plants developed with these methods have been risk assessed for cultivation purposes so far. Against this background of insufficient knowledge and experience for a variety of applications, we argue that a general framework for biosafety oversight is further implemented for nGM plants, based on a case-specific risk assessment incorporating the following elements:
- Case-specific risk assessment requirements taking into account (i) the nature of the developed trait, (ii) unintended consequences of the modification introduced, (iii) the available experience with comparable products, and (iv) relevant protection goals specified by the respective countries.
- Appropriate molecular characterization to assess among other things (i) the unintentional presence of any transgenic inserts in the final product, and (ii) the presence of off-target modifications and other unintended genetic changes, which might result in adverse phenotypic effects.
- Phenotypic characterization to specifically test parameters related to plausible risk issues associated with a particular nGM plant.
This will require that the existing guidance for risk assessment of GMOs as established in the EU by EFSA be reviewed as to whether it is suitable, sufficient and appropriate for specific types of nGM applications. Specific guidance needs be developed which enables risk assessors to focus their attention and resources on issues of concern specific for the different applications and to use established and emerging tools for their assessment.
With a view to the development of ever faster and ever more complex and sophisticated breeding approaches this will not be an easy task. However, in our opinion the efforts will be worthwhile from a safety perspective and a better alternative to exempting nGM applications from biosafety assessments altogether.