Topic 1: Part A, sections 1 to 3
Mr. Stephane Bilodeau,
Secretariat of the Convention on Biological Diversity#11768
Secretariat of the Convention on Biological Diversity#11768
3 years ago3 years ago
Part A: Risk assessment of living modified organisms containing engineered gene drives (EGD-LMOs)
1. Objective and scope of these additional voluntary guidance materials
2. Introduction
3. Overarching issues in the risk assessment process on EGD-LMOs
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1. Objective and scope of these additional voluntary guidance materials
2. Introduction
3. Overarching issues in the risk assessment process on EGD-LMOs
Participants are requested to follow the forum guidelines:
1. Briefly introduce themselves when posting their first message, including their name, country and institutional affiliation.
2. Keep their messages short, concise and focused.
3. Ensure that the messages are relevant to the topic/question being discussed.
4. Make sure that the text or files attached do not contain viruses, corrupted files or any other similar file deficiencies.
5. Be respectful of others’ points of views.
My name is Christoph Then, I am working for Testbiotech, a science based CSO in Germany (http://www.testbiotech.org).
In terms of regulatory issues, one of the decisive differences between genetically engineered gene drive organisms (EGD-LMO) and other genetically organisms (such as annual LMO crops) is the level of uncertainty caused by potential next (or multi-) generation effects, the complexity of the affected ecological networks and a lack of spatio-temporal control.
These points which are of specific relevance of EGD-LMO, have to be considered and discussed under the point uncertainties (3.3). In case no reliable conclusion can be drawn because there too many ‚unknowns‘ and uncertainties, cut-off criteria will be needed that allow the authority to deny the release of the EGD-LMO. In this context, the precautionary principle has to be strengthened.
In terms of regulatory issues, one of the decisive differences between genetically engineered gene drive organisms (EGD-LMO) and other genetically organisms (such as annual LMO crops) is the level of uncertainty caused by potential next (or multi-) generation effects, the complexity of the affected ecological networks and a lack of spatio-temporal control.
These points which are of specific relevance of EGD-LMO, have to be considered and discussed under the point uncertainties (3.3). In case no reliable conclusion can be drawn because there too many ‚unknowns‘ and uncertainties, cut-off criteria will be needed that allow the authority to deny the release of the EGD-LMO. In this context, the precautionary principle has to be strengthened.
My name is Piet van der Meer. I am trained in environmental microbiology and environmental law, and I have for over 35 years been involved in risk assessments in the context of biosafety regulations. I have participated in the CBD COPs and CPB MOPs since COP1, and I have served on a former AHTEG on risk assessment.
My thanks to the Secretariat for preparing the materials for this on line forum and to Luciana for having volunteered again to moderate this debate.
Hereby my observations on the structure of the draft outline of the Additional voluntary guidance materials, and on Part A, _sections 1 to 3_.
Overall, the document has a logical structure, starting with Part A that addresses general aspects of ERA of EGD-LM, followed by case studies of specific EGD-LMs. It is good that the document stays at many places close to the actual language of the CPB, but there are other places where that should be strengthened.
Finally, I was surprised to see reference to “Application of the Roadmap for risk assessment of living modified organisms” (line 37 with footnote 1), because the draft guidance that contained that roadmap was, after long and extensive debate, not endorsed by COPMOP2016, nor ‘welcomed’, but being ‘taken note of’. I believe that these draft guidance materials are not the appropriate place to renegotiate the conclusions of COPMOP2016.
As regards Part A, sections 1 to 3:
Line 7: Underline that this voluntary guidance material does not aim to be prescriptive. NB: this guidance should not contain references to cases where permits should be approved or denied.
Line 11: see comment above in relation to the roadmap.
Line 13: “issues” has a certain connotation. Better find a more neutral term, such as ‘aspects’.
Line 21: Add the notion of ‘relevant uncertainty ‘ (not every uncertainty is relevant to environmental risk).
My thanks to the Secretariat for preparing the materials for this on line forum and to Luciana for having volunteered again to moderate this debate.
Hereby my observations on the structure of the draft outline of the Additional voluntary guidance materials, and on Part A, _sections 1 to 3_.
Overall, the document has a logical structure, starting with Part A that addresses general aspects of ERA of EGD-LM, followed by case studies of specific EGD-LMs. It is good that the document stays at many places close to the actual language of the CPB, but there are other places where that should be strengthened.
Finally, I was surprised to see reference to “Application of the Roadmap for risk assessment of living modified organisms” (line 37 with footnote 1), because the draft guidance that contained that roadmap was, after long and extensive debate, not endorsed by COPMOP2016, nor ‘welcomed’, but being ‘taken note of’. I believe that these draft guidance materials are not the appropriate place to renegotiate the conclusions of COPMOP2016.
As regards Part A, sections 1 to 3:
Line 7: Underline that this voluntary guidance material does not aim to be prescriptive. NB: this guidance should not contain references to cases where permits should be approved or denied.
Line 11: see comment above in relation to the roadmap.
Line 13: “issues” has a certain connotation. Better find a more neutral term, such as ‘aspects’.
Line 21: Add the notion of ‘relevant uncertainty ‘ (not every uncertainty is relevant to environmental risk).
My name is Anastasia Matthies, I have more than 10 years of experience in Biosafety and Risk Assessment of LMOs as scientific officer at the German Federal Office of Consumer Protection and Food Safety. I follow the discussions on risk assessment of LMOs and Cartagena Protocol activities since 2016. Firstly, I wish to thank for the opportunity to contribute to the discussions in this online forum. Further, I would like to thank Ms. Luciana Pimenta Ambrozevicius for moderating this forum, and all colleagues contributing to the discussion.
Before commenting on individual sections, allow me to make a general remark on the structure of the draft outline. Part A of the outline duplicates on chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1). In my view, similar or identical content in the new additional voluntary guidance material on LMO containing engineered gene-drives should be avoided to prevent duplication. The new additional guidance materials should focus on novelties and updates and on specific aspects for risk assessment regarding engineered gene drive organisms. As already stated by parties (see submissions to ntf-2023-007). Therefore, I suggest to reconsider the structure of the whole draft outline.
I have following remarks on Topic 2:
- Line 12: rename “Further guidance and recommendation documents”
- Topic 3.1, lines 15 and 16: Protection goals, assessment endpoints and measurement endpoints are an integrative part of problem formulation steps. Therefore, it is not suitable to describe it out of context. I recommend to describe the entire principle of this process and move it to topic 4.2.
- Topic 3.3, line 23: I understand, that modelling is considered only here. However, the potential role and methodology of modelling should be also addressed in the main part of the outline (methodological part).
Before commenting on individual sections, allow me to make a general remark on the structure of the draft outline. Part A of the outline duplicates on chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1). In my view, similar or identical content in the new additional voluntary guidance material on LMO containing engineered gene-drives should be avoided to prevent duplication. The new additional guidance materials should focus on novelties and updates and on specific aspects for risk assessment regarding engineered gene drive organisms. As already stated by parties (see submissions to ntf-2023-007). Therefore, I suggest to reconsider the structure of the whole draft outline.
I have following remarks on Topic 2:
- Line 12: rename “Further guidance and recommendation documents”
- Topic 3.1, lines 15 and 16: Protection goals, assessment endpoints and measurement endpoints are an integrative part of problem formulation steps. Therefore, it is not suitable to describe it out of context. I recommend to describe the entire principle of this process and move it to topic 4.2.
- Topic 3.3, line 23: I understand, that modelling is considered only here. However, the potential role and methodology of modelling should be also addressed in the main part of the outline (methodological part).
Thank you very much to the moderators for all the work in organising this forum, and for the opportunity to participate in this very important work on risk assessment of engineered gene drives. My name is Eva Sirinathsinghji and I am a research associate with the Third World Network (TWN), working on biosafety issues of genetic technologies with training in molecular biology. I am a current and previous member of the AHTEG on Risk Assessment and current member of the multidisciplinary AHTEG on synthetic biology.
With regard to sections 1-3, I would like to raise a general comment on the issue of uncertainty. The recommendation of the last AHTEG to develop additional guidance was based on recognition of a number of specific challenges to current risk assessment and management processes. One of these recognised challenges relates to next-generation effects due to the novel conceptual and biological properties of gene drive organisms, that are further designed for release across large spatio-temporal scales over evolutionary time-scales. As noted by the last AHTEG:
- para 34 (a) (ii) Difficulty in predicting all relevant genomic effects that could emerge in the next and subsequent generations, and from interactions with the receiving environments;
- Para 34 (d) (vii) Difficulties in assessing next generation effects of organisms containing engineered gene drives
- Para 34 (a) (iii) Controllability of engineered gene drive systems after release
- Para 34 (a) (v) The potential for the engineered gene drive to evolve after release, including through unexpected genetic drift
The issue of gene drives carrying active genetic engineering machinery designed for spread within wild, genetically diverse populations severely undermines current risk assessment protocols, where assessment of issues like genomic stability of the transgene and host organism prior to release may be compromised by next-generation effects that may be mediated over time, and by further factors such as genetic background and ecological conditions. This could have implications for both biodiversity and human health.
This issue is central to the technology of gene drive organisms but has not been sufficiently captured under section 3.3. In my view, and a view that was shared also by others in the online forum and submissions, mechanisms for dealing with uncertainty should be incorporated. It is vital that a mechanism, such as “cut-off criteria”, as suggested here by Christoph Then, is included to allow for full operationalisation of the Precautionary Principle.
In relation to uncertainty, I would again like to raise the issue of modelling and its limitations in addressing uncertainty. This was another specific challenge raised in the previous AHTEG (para 34 (d) (iv) Difficulties with obtaining data for relevant modelling; and para 34 (d) (v) Difficulties with validation and calibration of modelling data before the occurrence of an environmental release). It is my view that the limitations are not fully captured in this outline, which instead suggests that modelling may be used to deal with uncertainty, as opposed to dealing with the uncertainties that may result from modelling data.
I thus propose an additional bullet point in 3.3 as the following: “uncertainty and the use of cut-off criteria under a precautionary approach”
I also propose that the bullet point referring to modelling in 3.3 be modified to: “uncertainty and the potential use and limitations of modelling”.
Thank you very much.
With regard to sections 1-3, I would like to raise a general comment on the issue of uncertainty. The recommendation of the last AHTEG to develop additional guidance was based on recognition of a number of specific challenges to current risk assessment and management processes. One of these recognised challenges relates to next-generation effects due to the novel conceptual and biological properties of gene drive organisms, that are further designed for release across large spatio-temporal scales over evolutionary time-scales. As noted by the last AHTEG:
- para 34 (a) (ii) Difficulty in predicting all relevant genomic effects that could emerge in the next and subsequent generations, and from interactions with the receiving environments;
- Para 34 (d) (vii) Difficulties in assessing next generation effects of organisms containing engineered gene drives
- Para 34 (a) (iii) Controllability of engineered gene drive systems after release
- Para 34 (a) (v) The potential for the engineered gene drive to evolve after release, including through unexpected genetic drift
The issue of gene drives carrying active genetic engineering machinery designed for spread within wild, genetically diverse populations severely undermines current risk assessment protocols, where assessment of issues like genomic stability of the transgene and host organism prior to release may be compromised by next-generation effects that may be mediated over time, and by further factors such as genetic background and ecological conditions. This could have implications for both biodiversity and human health.
This issue is central to the technology of gene drive organisms but has not been sufficiently captured under section 3.3. In my view, and a view that was shared also by others in the online forum and submissions, mechanisms for dealing with uncertainty should be incorporated. It is vital that a mechanism, such as “cut-off criteria”, as suggested here by Christoph Then, is included to allow for full operationalisation of the Precautionary Principle.
In relation to uncertainty, I would again like to raise the issue of modelling and its limitations in addressing uncertainty. This was another specific challenge raised in the previous AHTEG (para 34 (d) (iv) Difficulties with obtaining data for relevant modelling; and para 34 (d) (v) Difficulties with validation and calibration of modelling data before the occurrence of an environmental release). It is my view that the limitations are not fully captured in this outline, which instead suggests that modelling may be used to deal with uncertainty, as opposed to dealing with the uncertainties that may result from modelling data.
I thus propose an additional bullet point in 3.3 as the following: “uncertainty and the use of cut-off criteria under a precautionary approach”
I also propose that the bullet point referring to modelling in 3.3 be modified to: “uncertainty and the potential use and limitations of modelling”.
Thank you very much.
I am John Connolly, working for Target Malaria at Imperial College London.
Uncertainty is not a concept unique to gene drive, and as for other LMOs, the quality of data will correlate with the level of confidence and reduce uncertainty (Connolly et al 2022). It is important to recognize that the existence of uncertainties does not preclude taking a decision. This view is compatible with a precautionary approach.
Modeling, as noted by EFSA (2020) and others, can play a useful role in reducing uncertainty as sensitivity analysis can help identify which components have an effect on outcomes.
Risk assessments for gene drive need to draw from a variety of sources and are likely to combine both probabilistic (quantitative) and qualitative information, elicited through a variety of methods, from interviews with stakeholders to literature review and laboratory studies.(Connolly et al 2022).
Probabilistic risk assessments use quantitative modeling approaches to represent a probability distribution for a range of potential outcomes for a particular event. Qualitative risk assessments categorize, in a structured and systematic way, the likelihoods and consequences of outcomes into a limited number of ordered classes to give a categorical indication of relative risk, such as 'high', 'moderate', 'low', or 'negligible'. Where feasible, such qualitative terms should preferably be defined as precisely as possible in a quantitative way (Connolly et al 2022). Both types of assessments involve seeking expert opinion to determine the likelihood and possible outcomes of certain events.
In addition, there are methodologies that support assessing and weighing different information that is relevant to risk assessment (“weight of evidence”) (EFSA 2017). For example, WHO and other institutions use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. This is a widely endorsed and used approach to assess evidence and develop recommendations.
There is also experience of discussions of these issues with biological control agents, where the same topics have been considered. Although these are not LMOs, the spatial and temporal dimensions are similar to gene drive and could offer useful points of comparison (WHO 2021).
References:
Connolly, J.B., Mumford, J.D., Glandorf, D.C.M. et al. (2022) Recommendations for environmental risk assessment of gene drive applications for malaria vector control. Malar J 21, 152. https://doi.org/10.1186/s12936-022-04183-w
EFSA (2017). EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ,Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V,Solecki R, Turck D, Benfenati E, Chaudhry QM, Craig P, Frampton G, Greiner M, Hart A, Hogstrand C,Lambre C, Luttik R, Makowski D, Siani A, Wahlstroem H, Aguilera J, Dorne J-L, Fernandez Dumont A,Hempen M, Valtue~na Martınez S, Martino L, Smeraldi C, Terron A, Georgiadis N and Younes M, 2017.Scientific Opinion on the guidance on the use of the weight of evidence approach in scientificassessments. EFSA Journal 2017;15(8):4971. https://doi.org/10.2903/j.efsa.2017.4971
EFSA (2020). Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA Panel on Genetically Modified Organisms (GMO), Naegeli H, Bresson J, et al (2020) https://doi.org/10.2903/j.efsa.2020.6297. Page 53
GRADE working group - https://www.gradeworkinggroup.org/
What is GRADE? BMJ Best Practices – available online: https://bestpractice.bmj.com/info/toolkit/learn-ebm/what-is-grade/
WHO. (2021) Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
Uncertainty is not a concept unique to gene drive, and as for other LMOs, the quality of data will correlate with the level of confidence and reduce uncertainty (Connolly et al 2022). It is important to recognize that the existence of uncertainties does not preclude taking a decision. This view is compatible with a precautionary approach.
Modeling, as noted by EFSA (2020) and others, can play a useful role in reducing uncertainty as sensitivity analysis can help identify which components have an effect on outcomes.
Risk assessments for gene drive need to draw from a variety of sources and are likely to combine both probabilistic (quantitative) and qualitative information, elicited through a variety of methods, from interviews with stakeholders to literature review and laboratory studies.(Connolly et al 2022).
Probabilistic risk assessments use quantitative modeling approaches to represent a probability distribution for a range of potential outcomes for a particular event. Qualitative risk assessments categorize, in a structured and systematic way, the likelihoods and consequences of outcomes into a limited number of ordered classes to give a categorical indication of relative risk, such as 'high', 'moderate', 'low', or 'negligible'. Where feasible, such qualitative terms should preferably be defined as precisely as possible in a quantitative way (Connolly et al 2022). Both types of assessments involve seeking expert opinion to determine the likelihood and possible outcomes of certain events.
In addition, there are methodologies that support assessing and weighing different information that is relevant to risk assessment (“weight of evidence”) (EFSA 2017). For example, WHO and other institutions use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. This is a widely endorsed and used approach to assess evidence and develop recommendations.
There is also experience of discussions of these issues with biological control agents, where the same topics have been considered. Although these are not LMOs, the spatial and temporal dimensions are similar to gene drive and could offer useful points of comparison (WHO 2021).
References:
Connolly, J.B., Mumford, J.D., Glandorf, D.C.M. et al. (2022) Recommendations for environmental risk assessment of gene drive applications for malaria vector control. Malar J 21, 152. https://doi.org/10.1186/s12936-022-04183-w
EFSA (2017). EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ,Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V,Solecki R, Turck D, Benfenati E, Chaudhry QM, Craig P, Frampton G, Greiner M, Hart A, Hogstrand C,Lambre C, Luttik R, Makowski D, Siani A, Wahlstroem H, Aguilera J, Dorne J-L, Fernandez Dumont A,Hempen M, Valtue~na Martınez S, Martino L, Smeraldi C, Terron A, Georgiadis N and Younes M, 2017.Scientific Opinion on the guidance on the use of the weight of evidence approach in scientificassessments. EFSA Journal 2017;15(8):4971. https://doi.org/10.2903/j.efsa.2017.4971
EFSA (2020). Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA Panel on Genetically Modified Organisms (GMO), Naegeli H, Bresson J, et al (2020) https://doi.org/10.2903/j.efsa.2020.6297. Page 53
GRADE working group - https://www.gradeworkinggroup.org/
What is GRADE? BMJ Best Practices – available online: https://bestpractice.bmj.com/info/toolkit/learn-ebm/what-is-grade/
WHO. (2021) Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
I am John Connolly, working with Target Malaria and am based at Imperial College London. Thank you very much to the Moderator and Secretariat for providing us with an opportunity to comment on the draft outline.
The guidance should complement existing guidance & focus on items that are novel for gene drive organisms (compared to other LMOs), noting where it is not necessary to reiterate existing guidance.
The guidance should be science-based and based on the principle of case-by-case assessments. The new guidance should remain in alignment with paragraph 11 of CBD decision 14/19 on the necessary conditions for the experimental release of organisms containing engineered gene drives.
A wealth of experience with LMOs is available to draw upon, as well as from other fields (biocontrol, etc). It is important to reflect these existing resources where possible.
Relevant guidance from WHO and from national authorities should also be taken into account to ensure coherence and compatibility with guidance from the CBD. Examples are included in the references below.
References:
EFSA (2020). Panel on Genetically Modified Organisms (GMO); Naegeli H, Bresson JL, Dalmay T, Dewhurst IC, Epstein MM, Guerche P, Hejatko J, Moreno FJ, Mullins E, Nogué F, Rostoks N, Sánchez Serrano JJ, Savoini G, Veromann E, Veronesi F, Bonsall MB, Mumford J, Wimmer EA, Devos Y, Paraskevopoulos K, Firbank LG. Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA J. 2020 Nov 12;18(11):e06297. doi: 10.2903/j.efsa.2020.6297.
National Institute for Public Health and the Environment. Technical evaluation of a potential release of OX513A Aedes aegypti mosquitoes on the island of Saba. https://www.rivm.nl/bibliotheek/rapporten/2017-0087.pdf
Government of Australia. Office of the Gene Technology Regulator (2019). Regulatory requirements for contained research with GMOs containing engineered gene drives. https://www.ogtr.gov.au/sites/default/files/files/2021-06/guidance_on_gene_drives.pdf
James SL, Quemada H, Benedict MQ, Dass B. Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products. Front Bioeng Biotechnol. 2023 Jun 8;11:1205865. doi: 10.3389/fbioe.2023.1205865.
Murray JV, Jansen CC, De Barro P. Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes into the Environment in an Effort to Control Dengue. Front Public Health. 2016 Mar 22;4:43. doi: 10.3389/fpubh.2016.00043.
WHO (2021). Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
The guidance should complement existing guidance & focus on items that are novel for gene drive organisms (compared to other LMOs), noting where it is not necessary to reiterate existing guidance.
The guidance should be science-based and based on the principle of case-by-case assessments. The new guidance should remain in alignment with paragraph 11 of CBD decision 14/19 on the necessary conditions for the experimental release of organisms containing engineered gene drives.
A wealth of experience with LMOs is available to draw upon, as well as from other fields (biocontrol, etc). It is important to reflect these existing resources where possible.
Relevant guidance from WHO and from national authorities should also be taken into account to ensure coherence and compatibility with guidance from the CBD. Examples are included in the references below.
References:
EFSA (2020). Panel on Genetically Modified Organisms (GMO); Naegeli H, Bresson JL, Dalmay T, Dewhurst IC, Epstein MM, Guerche P, Hejatko J, Moreno FJ, Mullins E, Nogué F, Rostoks N, Sánchez Serrano JJ, Savoini G, Veromann E, Veronesi F, Bonsall MB, Mumford J, Wimmer EA, Devos Y, Paraskevopoulos K, Firbank LG. Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives. EFSA J. 2020 Nov 12;18(11):e06297. doi: 10.2903/j.efsa.2020.6297.
National Institute for Public Health and the Environment. Technical evaluation of a potential release of OX513A Aedes aegypti mosquitoes on the island of Saba. https://www.rivm.nl/bibliotheek/rapporten/2017-0087.pdf
Government of Australia. Office of the Gene Technology Regulator (2019). Regulatory requirements for contained research with GMOs containing engineered gene drives. https://www.ogtr.gov.au/sites/default/files/files/2021-06/guidance_on_gene_drives.pdf
James SL, Quemada H, Benedict MQ, Dass B. Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products. Front Bioeng Biotechnol. 2023 Jun 8;11:1205865. doi: 10.3389/fbioe.2023.1205865.
Murray JV, Jansen CC, De Barro P. Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes into the Environment in an Effort to Control Dengue. Front Public Health. 2016 Mar 22;4:43. doi: 10.3389/fpubh.2016.00043.
WHO (2021). Guidance framework for testing genetically modified mosquitoes, second edition. Geneva:
World Health Organization. https://www.who.int/publications/i/item/9789240025233
I am John Connolly, working for Target Malaria at Imperial College London. I support the comments of Anastasia Matthies. See my comments at post #11793
My name is Samson Simon, I work for the German Federal Agency for Nature Conservation (BfN) as a biosafety expert. Thank you to the organizers and other participants of this online forum for the work done so far.
I would find it useful to have a section on risk assessment methods as well (echoing post #11787). EGD-LMOs will challenge those methods with its novel features when compared to other LMOs. Thus, an analysis of available methods, an assessment of usefulness for ERA of EGD-LMOs, as well as an estimation of the uncertainty produced, could be added to the draft outline. Such a section could read (after 3.2): “Methodology for ERA of EGD-LMOs” with subheadings like: “Available Methods”; “Estimation of usefulness for ERA”; “uncertainties associated with current methods”; “demands for method development”.
Line 15: “3.1. Protection goals, assessment endpoints and measurement endpoints” This section could also include the concept of “limit of concern”, which is highly relevant for ERA to ensure that protection goals can be met.
Line 23: “Uncertainty and the potential use and role of modelling”
Comparable to the limits of concern concept, Limits of uncertainty should be part of the voluntary guidance document. Or in other words, the guidance should address the following question: when is uncertainty so prominent that ERA cannot be completed?
Regarding models and uncertainty I would like to echo message #11789. Models might play an important role in risk assessment of EGD-LMOs. However, the use of models in risk assessment is challenging (c.f. Dolezel et al. 2020 Doi: 10.3897/biorisk.15.49297) and associated with many uncertainties. When drafting the voluntary guidance material, these uncertainties should also be taken into account. I suggest to include it in a separate section on methodology (see above).
I would find it useful to have a section on risk assessment methods as well (echoing post #11787). EGD-LMOs will challenge those methods with its novel features when compared to other LMOs. Thus, an analysis of available methods, an assessment of usefulness for ERA of EGD-LMOs, as well as an estimation of the uncertainty produced, could be added to the draft outline. Such a section could read (after 3.2): “Methodology for ERA of EGD-LMOs” with subheadings like: “Available Methods”; “Estimation of usefulness for ERA”; “uncertainties associated with current methods”; “demands for method development”.
Line 15: “3.1. Protection goals, assessment endpoints and measurement endpoints” This section could also include the concept of “limit of concern”, which is highly relevant for ERA to ensure that protection goals can be met.
Line 23: “Uncertainty and the potential use and role of modelling”
Comparable to the limits of concern concept, Limits of uncertainty should be part of the voluntary guidance document. Or in other words, the guidance should address the following question: when is uncertainty so prominent that ERA cannot be completed?
Regarding models and uncertainty I would like to echo message #11789. Models might play an important role in risk assessment of EGD-LMOs. However, the use of models in risk assessment is challenging (c.f. Dolezel et al. 2020 Doi: 10.3897/biorisk.15.49297) and associated with many uncertainties. When drafting the voluntary guidance material, these uncertainties should also be taken into account. I suggest to include it in a separate section on methodology (see above).
Dear All,
I very much concur with the comment of Anastasia Matthies (#11786) that the additional voluntary guidance materials should avoid duplicating chapters from the draft guidance that the COPMOP took note of in 2016, or from any generic guidance for that matter, and that these guidance materials should focus on novelties and specific aspects for risk assessment regarding organisms with engineered gene drive.
I believe that it will be good to start these additional voluntary guidance materials with a brief recap of the methodology of ERA as laid down in Annex III (a bit as is now in Section 5 of the draft outline), thereby staying - as I said in a previous post – as close as possible to the language of the CPB.
That recap of Annex III should be followed by a section that exercises through the methodology of Annex III and addresses aspects and materials that are specific to GD. In that exercise we should remain mindful that we are not renegotiating Annex III and that we are not developing generic guidance or roadmaps for risk assessment. After the difficult discussion in COPMOP2016 about the draft guidance, the COPMOP very decidedly – and in my view very wisely - referred in its decisions to ‘additional voluntary guidance MATERIALS to support case-by-case risk assessment of LMOs containing engineered gene drives in accordance with Annex III of the Cartagena Protocol.
As regards uncertainty, I concur with the post of John Connolly (#11793). Addressing uncertainty is not unique to gene drives, it is in fact of any scientific paper. Annex III has an adequate mechanism of dealing with uncertainty: “Where there is uncertainty regarding the level of risk, it may be addressed by requesting further information on the specific issues of concern or by implementing appropriate risk management strategies and/or monitoring the living modified organism in the receiving environment”.
Question to the moderator: would there be mileage in extending this on line debate so that more colleagues can join the exchange about the nature of the materials that we are developing?
Regards
Piet van der Meer
I very much concur with the comment of Anastasia Matthies (#11786) that the additional voluntary guidance materials should avoid duplicating chapters from the draft guidance that the COPMOP took note of in 2016, or from any generic guidance for that matter, and that these guidance materials should focus on novelties and specific aspects for risk assessment regarding organisms with engineered gene drive.
I believe that it will be good to start these additional voluntary guidance materials with a brief recap of the methodology of ERA as laid down in Annex III (a bit as is now in Section 5 of the draft outline), thereby staying - as I said in a previous post – as close as possible to the language of the CPB.
That recap of Annex III should be followed by a section that exercises through the methodology of Annex III and addresses aspects and materials that are specific to GD. In that exercise we should remain mindful that we are not renegotiating Annex III and that we are not developing generic guidance or roadmaps for risk assessment. After the difficult discussion in COPMOP2016 about the draft guidance, the COPMOP very decidedly – and in my view very wisely - referred in its decisions to ‘additional voluntary guidance MATERIALS to support case-by-case risk assessment of LMOs containing engineered gene drives in accordance with Annex III of the Cartagena Protocol.
As regards uncertainty, I concur with the post of John Connolly (#11793). Addressing uncertainty is not unique to gene drives, it is in fact of any scientific paper. Annex III has an adequate mechanism of dealing with uncertainty: “Where there is uncertainty regarding the level of risk, it may be addressed by requesting further information on the specific issues of concern or by implementing appropriate risk management strategies and/or monitoring the living modified organism in the receiving environment”.
Question to the moderator: would there be mileage in extending this on line debate so that more colleagues can join the exchange about the nature of the materials that we are developing?
Regards
Piet van der Meer
My name is Marco Gielkens. I have a scientific background as a molecular geneticist and I have over 20 years of experience in biosafety and risk assessment of LMOs. I am a senior risk assessor and policy advisor at the Dutch National Institute for Public Health and the Environment (RIVM) within the department of Biological Safety and Gene Technology. I would like to thank the moderator and the Secretariat for the opportunity to contribute to this discussion.
I concur with the contribution of Anastasia Matthies (#11786) that the additional voluntary guidance material should avoid duplicating chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1).
Furthermore I concur with the contributions of John Connolly (#11793) and Piet van der Meer (#11798) regarding the aspects of uncertainties and I would like to refer to section 1.2.6 of the OECD document mentioned in my contribution #11801: […In practice, some hypotheses may be difficult to evaluate or the evaluation using available information may not produce definitive conclusions regarding the likelihood of a particular step in a pathway. This uncertainty may be addressed through a tier-based testing approach, by consideration of multiple sources of information and lines of evidence (i.e. a weight of evidence approach), or by new studies being undertaken. Nevertheless, in some cases uncertainties may remain that must be addressed by decision makers and risk managers.].
I concur with the contribution of Anastasia Matthies (#11786) that the additional voluntary guidance material should avoid duplicating chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1).
Furthermore I concur with the contributions of John Connolly (#11793) and Piet van der Meer (#11798) regarding the aspects of uncertainties and I would like to refer to section 1.2.6 of the OECD document mentioned in my contribution #11801: […In practice, some hypotheses may be difficult to evaluate or the evaluation using available information may not produce definitive conclusions regarding the likelihood of a particular step in a pathway. This uncertainty may be addressed through a tier-based testing approach, by consideration of multiple sources of information and lines of evidence (i.e. a weight of evidence approach), or by new studies being undertaken. Nevertheless, in some cases uncertainties may remain that must be addressed by decision makers and risk managers.].
Greetings to all, my name is Andrew Roberts and I work for a non-profit scientific organization called the Agriculture & Food Systems Institute. I have been working actively in the field of environmental risk assessment since 2005, and with AFSI I have conducted numerous capacity building and training activities around the world working with scientists, developers and governments as they work to implement regulations for biotechnology. I have been engaged in previous online forums around risk assessment and risk assessment guidance under the CPB. I appreciate the opportunity to participate here and I would like to thank the Secretariat and Luciana for enabling this opportunity.
Our instructions are to be concise, so I will make my general remarks here and shorter remarks in each of the subsequent sections. In general, I support the comments of Piet van der Meer and Anastasia Mathies. The challenge, once again, is that we are approaching the task of developing guidance documents when there are clearly different ideas about what "guidance" is supposed to accomplish. Previous efforts attempted to develop a conceptual and instructional document to provide to risk assessors and, notably, were not welcomed by the Parties. In light of this, I have to echo Piet's comment that it seems odd that new guidance would begin with those previous documents as a starting point. At best, this seems to relegate the work of the current AHTEG to be once again "noted" by the COPMOP. At worst, this can be seen as an attempt to subvert the wishes of the Parties and elevate the status of previous guidance.
It is also clear that some participants are (once again) attempting to steer the guidance document to a litany of reasons why a risk assessment cannot be accomplished for EGD-LMOs. As has been mentioned by others, uncertainty is not new or unique to EGD-LMOs. For this reason, I would like to support John Connolly's and Marco Gielkens's interventions and to support Samson Simon's suggestion that any discussion of uncertainty focus on the identification of relevance, and the limits of uncertainty. Communicating uncertainty is a critical component for all risk assessments, and a good faith consideration of how uncertainties are identified, assessed for relevance, and communicated is always welcome. However, this must not be confused with addressing endless speculations about unknowable things.
I would also like to echo the sentiments in previous online forums that, rather than trying to develop a set of instructions for future risk assessors, that useful guidance should focus on providing links to resources and information that would be useful for conducting future assessments.
Our instructions are to be concise, so I will make my general remarks here and shorter remarks in each of the subsequent sections. In general, I support the comments of Piet van der Meer and Anastasia Mathies. The challenge, once again, is that we are approaching the task of developing guidance documents when there are clearly different ideas about what "guidance" is supposed to accomplish. Previous efforts attempted to develop a conceptual and instructional document to provide to risk assessors and, notably, were not welcomed by the Parties. In light of this, I have to echo Piet's comment that it seems odd that new guidance would begin with those previous documents as a starting point. At best, this seems to relegate the work of the current AHTEG to be once again "noted" by the COPMOP. At worst, this can be seen as an attempt to subvert the wishes of the Parties and elevate the status of previous guidance.
It is also clear that some participants are (once again) attempting to steer the guidance document to a litany of reasons why a risk assessment cannot be accomplished for EGD-LMOs. As has been mentioned by others, uncertainty is not new or unique to EGD-LMOs. For this reason, I would like to support John Connolly's and Marco Gielkens's interventions and to support Samson Simon's suggestion that any discussion of uncertainty focus on the identification of relevance, and the limits of uncertainty. Communicating uncertainty is a critical component for all risk assessments, and a good faith consideration of how uncertainties are identified, assessed for relevance, and communicated is always welcome. However, this must not be confused with addressing endless speculations about unknowable things.
I would also like to echo the sentiments in previous online forums that, rather than trying to develop a set of instructions for future risk assessors, that useful guidance should focus on providing links to resources and information that would be useful for conducting future assessments.
Dear all, I am Barbara Pilz from Save Our Seeds, member of the current multidisciplinary AHTEG on synthetic biology. Thank you for opening this crucial discussion.
The mandate of developing this voluntary guidance comes, among other aspects, from the recognition that there are gaps in existing guidance documents and other resources (CP-9/13, 1.). Accordingly, the objective is to develop additional voluntary guidance materials to support case-by-case risk assessment of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol with a specific focus on mosquitos so that a comprehensive guidance specific to this issue would be available (CP-10/10, 5./ Annex 1 (c)), not a mere index.
It is natural that contents of this guidance might overlap with previous documents related to general risk assessment of LMOs. However, guidance on the specific issue mandated would not be completed should the fundamental aspects of risk assessment not be addressed in the specific context.
The mandate of developing this voluntary guidance comes, among other aspects, from the recognition that there are gaps in existing guidance documents and other resources (CP-9/13, 1.). Accordingly, the objective is to develop additional voluntary guidance materials to support case-by-case risk assessment of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol with a specific focus on mosquitos so that a comprehensive guidance specific to this issue would be available (CP-10/10, 5./ Annex 1 (c)), not a mere index.
It is natural that contents of this guidance might overlap with previous documents related to general risk assessment of LMOs. However, guidance on the specific issue mandated would not be completed should the fundamental aspects of risk assessment not be addressed in the specific context.
My suggestions for Part A 1-3 are as it follows:
Section 2., Lines 9-12: In line with submission [#11780] The introduction should make clear reference to the precautionary principle of the Cartagena Protocol to ensure that it is the backbone of the risk assessment. An additional line/bullet point could be included on “Precautionary principle/approach”
Section 2., Line 10: Important to note that an eventual release of gene drive organisms into the environment would be the first time that LMOs are intended to modify/eradicate wild species and their various present and potential future ecosystems and without the possibility of containment. Annex III of the Cartagena Protocol was not developed with such circumstances in mind. In the case of GDOs, acceptability and management of risks are at a higher stake. Accordingly, it should be mention here that Annex III does not account for such a paradigm shift and therefore a high importance should be put on cut-off criteria. The line could read “Annex III of Cartagena Protocol on Biosafety and the particular circumstances of EGD-LMOs”
Section 3.1, Lines 15-16: The precautionary principle could be included as one of the overarching concepts here. The title would read “Precautionary principle, protection goals, assessment endpoints and measurement endpoints”. A description of the approach would be included under “Descriptions of these relevant concepts”
Section 3.2., Line 18: In line with suggestions of inclusion of a multidisciplinary array of expertise to conduct risk assessment, this point should also include other forms of knowledge of practices analogous to risk assessment, particularly traditional knowledge of IPLCs. The line would read “Criteria for the quality of scientific information and other forms of knowledge”.
Section 3.3, Lines 20-23: In line with submission [#11789] This item seems to over focus on the role of modelling and lacks mention to cut-off criteria in case of overwhelming uncertainties and spatial-temporal considerations (given the self-propagating characteristic of EGD-LMOs).
Line 20: Could read “Identification and consideration of uncertainty and cut-off criteria”
Additional line to be added between Line 22 and Line 23: “Spatial and temporal considerations”
Line 23: Could read “Uncertainty, potential use and limitations of modelling” as suggested in [#11789]
Additional Line to be added after Line 23: “Uncertainty and the use of cut-off criteria under a precautionary approach” as suggested in [#11789]
Section 2., Lines 9-12: In line with submission [#11780] The introduction should make clear reference to the precautionary principle of the Cartagena Protocol to ensure that it is the backbone of the risk assessment. An additional line/bullet point could be included on “Precautionary principle/approach”
Section 2., Line 10: Important to note that an eventual release of gene drive organisms into the environment would be the first time that LMOs are intended to modify/eradicate wild species and their various present and potential future ecosystems and without the possibility of containment. Annex III of the Cartagena Protocol was not developed with such circumstances in mind. In the case of GDOs, acceptability and management of risks are at a higher stake. Accordingly, it should be mention here that Annex III does not account for such a paradigm shift and therefore a high importance should be put on cut-off criteria. The line could read “Annex III of Cartagena Protocol on Biosafety and the particular circumstances of EGD-LMOs”
Section 3.1, Lines 15-16: The precautionary principle could be included as one of the overarching concepts here. The title would read “Precautionary principle, protection goals, assessment endpoints and measurement endpoints”. A description of the approach would be included under “Descriptions of these relevant concepts”
Section 3.2., Line 18: In line with suggestions of inclusion of a multidisciplinary array of expertise to conduct risk assessment, this point should also include other forms of knowledge of practices analogous to risk assessment, particularly traditional knowledge of IPLCs. The line would read “Criteria for the quality of scientific information and other forms of knowledge”.
Section 3.3, Lines 20-23: In line with submission [#11789] This item seems to over focus on the role of modelling and lacks mention to cut-off criteria in case of overwhelming uncertainties and spatial-temporal considerations (given the self-propagating characteristic of EGD-LMOs).
Line 20: Could read “Identification and consideration of uncertainty and cut-off criteria”
Additional line to be added between Line 22 and Line 23: “Spatial and temporal considerations”
Line 23: Could read “Uncertainty, potential use and limitations of modelling” as suggested in [#11789]
Additional Line to be added after Line 23: “Uncertainty and the use of cut-off criteria under a precautionary approach” as suggested in [#11789]
Dear All,
My name is Aaron Roberts. I am an ethics and policy researcher in Canada at McMaster University’s Institute on Ethics & Policy for Innovation. I am trained in philosophy and completed a Ph.D. focusing on questions of ethics and policy for the research, development, and use of synthetic biology – particularly gene drive technology. I have followed and been involved with CBD proceedings and discussions, particularly as they have involved gene drive, as a delegate for McMaster University for the past six years.
My thanks for the opportunity to contribute to this discussion, to the Secretariat for preparing the materials for this online forum, to Luciana for having volunteered again to moderate this debate, and to all colleagues who contribute to this discussion.
Much of what I came here to say has already been stated very well by others.
I agree with the contribution of Anastasia Matthies (#11786) that the additional voluntary guidance material should avoid duplicating chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1).
Echoing Mr. Pieter van der Meer (#11798), I too was surprised to see reference to “Application of the Roadmap for risk assessment of living modified organisms” (line 37 with footnote 1), because the draft guidance that contained that roadmap was not endorsed by COPMOP2016, nor ‘welcomed’, but being ‘taken note of’. I also believe that these draft guidance materials are not the appropriate place to renegotiate the conclusions of COPMOP2016.
I agree with the contributions of John Connolly (#11793), Piet van der Meer (#11798), Marco Gielkens (#11802), and Andrew Roberts (#11804) regarding the fact that uncertainties are not unique to gene drive technology, nor synthetic biology, and not all uncertainties are equally relevant. Uncertainties are an aspect of all risk assessment for policy and decision-making, and there are many existing resources to inform risk assessment for policy and decision-making for EGD-LMOs. The existence of uncertainties does not preclude making a decision. This view is compatible with a precautionary approach. There are also uncertainties associated with non-intervention. Relevant references (pertain to Part A, Section 3.3):
1. Committee, E. S. et al. Guidance on Uncertainty Analysis in Scientific Assessments. EFSA Journal 16, e05123 (2018). https://doi.org/10.2903/j.efsa.2018.5123
2. Frieß, J. L., Lalyer, C. R., Giese, B., Simon, S. & Otto, M. Review of gene drive modelling and implications for risk assessment of gene drive organisms. Ecological Modelling 478, 110285 (2023). https://doi.org/10.1016/j.ecolmodel.2023.110285
3. Dhole, S., Lloyd, A. L. & Gould, F. Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex. Annual Review of Ecology, Evolution, and Systematics 51, 505–531 (2020). https://doi.org/10.1146/annurev-ecolsys-031120-101013
As regards Part A, section 2, I provide some additional available relevant guidance from other processes which has not already been mentioned in the contributions above:
1. WHO (2022). Global guidance framework for the responsible use of the life sciences: mitigating biorisks and governing dual-use research. Geneva: World Health Organization. https://www.who.int/publications-detail-redirect/9789240056107.
As regards Part A, section 3, re: engineered gene drive terminology, types and general characteristics it is important to acknowledge in the guidance when defining what constitutes EGD-LMOs that “gene drive” is an umbrella term that covers a wide array of possible constructs and approaches. This diversity should be acknowledged. This is essential because the specifics of the construct and the target species will have important implications for considerations of risks and benefits. This underscores the need for case-by-case assessments. I provide additional relevant references:
1. Luke et al (2020). Standardizing the definition of gene drive. PNAS. 117 (49) 30864-30867. https://doi.org/10.1073/pnas.2020417117
2. Burt & Crisanti (2018). Gene drives: evolved and synthetic. ACS Chem. Biol. 2018, 13, 2, 343–346. https://doi.org/10.1021/acschembio.7b01031
3. James, S.L., O’Brochta, D.A., Randazzo, F. et al. A gene drive is a gene drive: the debate over lumping or splitting definitions. Nat Commun 14, 1749 (2023). https://doi-org.libaccess.lib.mcmaster.ca/10.1038/s41467-023-37483-z
As regards Part A, section 3.1 re: protection goals, assessment endpoints and measurement endpoints – protection goals are expected to be broadly similar to those usually identified for other LMOs. Relevant reference:
1. Teem, J.L., Ambali, A., Glover, B. et al. Problem formulation for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016–2018. Malar J 18, 347 (2019). https://doi.org/10.1186/s12936-019-2978-5
Kind regards,
Aaron Roberts
My name is Aaron Roberts. I am an ethics and policy researcher in Canada at McMaster University’s Institute on Ethics & Policy for Innovation. I am trained in philosophy and completed a Ph.D. focusing on questions of ethics and policy for the research, development, and use of synthetic biology – particularly gene drive technology. I have followed and been involved with CBD proceedings and discussions, particularly as they have involved gene drive, as a delegate for McMaster University for the past six years.
My thanks for the opportunity to contribute to this discussion, to the Secretariat for preparing the materials for this online forum, to Luciana for having volunteered again to moderate this debate, and to all colleagues who contribute to this discussion.
Much of what I came here to say has already been stated very well by others.
I agree with the contribution of Anastasia Matthies (#11786) that the additional voluntary guidance material should avoid duplicating chapters from the Guidance on risk assessment for living modified organisms (UNEP/CBD/BS/COP-MOP/8/8/Add.1).
Echoing Mr. Pieter van der Meer (#11798), I too was surprised to see reference to “Application of the Roadmap for risk assessment of living modified organisms” (line 37 with footnote 1), because the draft guidance that contained that roadmap was not endorsed by COPMOP2016, nor ‘welcomed’, but being ‘taken note of’. I also believe that these draft guidance materials are not the appropriate place to renegotiate the conclusions of COPMOP2016.
I agree with the contributions of John Connolly (#11793), Piet van der Meer (#11798), Marco Gielkens (#11802), and Andrew Roberts (#11804) regarding the fact that uncertainties are not unique to gene drive technology, nor synthetic biology, and not all uncertainties are equally relevant. Uncertainties are an aspect of all risk assessment for policy and decision-making, and there are many existing resources to inform risk assessment for policy and decision-making for EGD-LMOs. The existence of uncertainties does not preclude making a decision. This view is compatible with a precautionary approach. There are also uncertainties associated with non-intervention. Relevant references (pertain to Part A, Section 3.3):
1. Committee, E. S. et al. Guidance on Uncertainty Analysis in Scientific Assessments. EFSA Journal 16, e05123 (2018). https://doi.org/10.2903/j.efsa.2018.5123
2. Frieß, J. L., Lalyer, C. R., Giese, B., Simon, S. & Otto, M. Review of gene drive modelling and implications for risk assessment of gene drive organisms. Ecological Modelling 478, 110285 (2023). https://doi.org/10.1016/j.ecolmodel.2023.110285
3. Dhole, S., Lloyd, A. L. & Gould, F. Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex. Annual Review of Ecology, Evolution, and Systematics 51, 505–531 (2020). https://doi.org/10.1146/annurev-ecolsys-031120-101013
As regards Part A, section 2, I provide some additional available relevant guidance from other processes which has not already been mentioned in the contributions above:
1. WHO (2022). Global guidance framework for the responsible use of the life sciences: mitigating biorisks and governing dual-use research. Geneva: World Health Organization. https://www.who.int/publications-detail-redirect/9789240056107.
As regards Part A, section 3, re: engineered gene drive terminology, types and general characteristics it is important to acknowledge in the guidance when defining what constitutes EGD-LMOs that “gene drive” is an umbrella term that covers a wide array of possible constructs and approaches. This diversity should be acknowledged. This is essential because the specifics of the construct and the target species will have important implications for considerations of risks and benefits. This underscores the need for case-by-case assessments. I provide additional relevant references:
1. Luke et al (2020). Standardizing the definition of gene drive. PNAS. 117 (49) 30864-30867. https://doi.org/10.1073/pnas.2020417117
2. Burt & Crisanti (2018). Gene drives: evolved and synthetic. ACS Chem. Biol. 2018, 13, 2, 343–346. https://doi.org/10.1021/acschembio.7b01031
3. James, S.L., O’Brochta, D.A., Randazzo, F. et al. A gene drive is a gene drive: the debate over lumping or splitting definitions. Nat Commun 14, 1749 (2023). https://doi-org.libaccess.lib.mcmaster.ca/10.1038/s41467-023-37483-z
As regards Part A, section 3.1 re: protection goals, assessment endpoints and measurement endpoints – protection goals are expected to be broadly similar to those usually identified for other LMOs. Relevant reference:
1. Teem, J.L., Ambali, A., Glover, B. et al. Problem formulation for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016–2018. Malar J 18, 347 (2019). https://doi.org/10.1186/s12936-019-2978-5
Kind regards,
Aaron Roberts
Topic 1: Part A, sections 1-3
Hello everyone. My name is Adam Cornish and I work in the Office of Agricultural Policy at the U.S. Department of State and serve as the U.S. national focal point for the Cartagena Protocol on Biosafety. I am pleased to see the continued discussion on the forum and thank the moderators for their work and the thoughtful comments of the other participants in the forum.
The United States is encouraged by the discussion on the topic of LMOs containing engineered gene drives (EGD-LMOs) and appreciates the chance to provide information and perspective on this topic. We note the importance of appropriately scoping the voluntary guidance materials to support Parties, as described in paragraph 1(c) of Annex I of CBD/CP/MOP/DEC/10/10 – “Develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol. A specific focus of this material should be engineered gene drive mosquitos taking into account the current experience with the organism, the type of gene drive and specific issues of risk assessment[.]” This specific focus should be adequately detailed in either section 1 or section 2 of Part A.
During MOP10, Parties recognized that attempts to develop guidance for any or all EGD-LMOs were unlikely to be successful, hence specifying that this guidance was meant to be developed only for EGD modified mosquitoes. As the guidance is to be developed with a specific focus for EGD mosquitoes, the amount of detail currently described in Part A does not seem to match the directive of the description. We recommend that section 3 be appropriately scoped to enable Parties to focus on the most relevant and generalizable components of risk assessments related to EGD-LMOs. A laundry list of all possible EGD-LMOs and their related components is unlikely to be useful to the Parties and should be discouraged.
Hello everyone. My name is Adam Cornish and I work in the Office of Agricultural Policy at the U.S. Department of State and serve as the U.S. national focal point for the Cartagena Protocol on Biosafety. I am pleased to see the continued discussion on the forum and thank the moderators for their work and the thoughtful comments of the other participants in the forum.
The United States is encouraged by the discussion on the topic of LMOs containing engineered gene drives (EGD-LMOs) and appreciates the chance to provide information and perspective on this topic. We note the importance of appropriately scoping the voluntary guidance materials to support Parties, as described in paragraph 1(c) of Annex I of CBD/CP/MOP/DEC/10/10 – “Develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol. A specific focus of this material should be engineered gene drive mosquitos taking into account the current experience with the organism, the type of gene drive and specific issues of risk assessment[.]” This specific focus should be adequately detailed in either section 1 or section 2 of Part A.
During MOP10, Parties recognized that attempts to develop guidance for any or all EGD-LMOs were unlikely to be successful, hence specifying that this guidance was meant to be developed only for EGD modified mosquitoes. As the guidance is to be developed with a specific focus for EGD mosquitoes, the amount of detail currently described in Part A does not seem to match the directive of the description. We recommend that section 3 be appropriately scoped to enable Parties to focus on the most relevant and generalizable components of risk assessments related to EGD-LMOs. A laundry list of all possible EGD-LMOs and their related components is unlikely to be useful to the Parties and should be discouraged.
I am Brinda Dass, Senior Technical Expert at the Foundation for the National Institutes of Health, Gene Convene Global Collaborative and a member of the past AHTEG on risk assessment. Thank you to the Secretariat for the opportunity to discuss the outline and to Luciana for moderating.
What has not been highlighted so far is that following a phased development approach as recommended by the WHO (Guidance framework for testing of genetically modified mosquitoes, second edition https://www.who.int/publications/i/item/9789240025233 ) would allow risk assessments to be truly iterative and informed by data and information from prior phases. This supports the comment from Dr. Marco Gielkens, Netherlands #11802 regarding section 1.2.6 of the OECD document. It would also be truly in line with Precautionary Principle allowing avoidance of potential underestimation of risk due to information gaps by choosing to tend more towards human health and environment protection (typically the high-level protection goals). This could be addressed by selecting appropriate risk hypothesis for subsequent phases to provide better data sets to query assumptions and uncertainty resulting in more robust conclusions of greater certainty. Each phase would have an appropriate risk assessment allowing for an iterative process as well as temporal and ecological appropriate scoping.
With regard to section 3.1 Protection goals, assessment endpoints and measurement endpoints, I would suggest it be moved to Section 4 as these are all part of the larger Scoping activities at the start of the risk assessment process. Under protection goals, perhaps a consideration would be to describe the logical flow of operationalizing high level goals taken from national legislation such that they are particular to EGDOs (particularly EGD Mosquito) in the national context. In so doing one could also include stakeholder concerns along with legal obligations. Identifying granular operational goals would in turn help define appropriate measurement and assessment endpoints. For a relevant example to EGD mosquitoes and operational goals see Connolly et al. Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa. Malar J 20, 170 (2021). https://doi.org/10.1186/s12936-021-03674-6
What has not been highlighted so far is that following a phased development approach as recommended by the WHO (Guidance framework for testing of genetically modified mosquitoes, second edition https://www.who.int/publications/i/item/9789240025233 ) would allow risk assessments to be truly iterative and informed by data and information from prior phases. This supports the comment from Dr. Marco Gielkens, Netherlands #11802 regarding section 1.2.6 of the OECD document. It would also be truly in line with Precautionary Principle allowing avoidance of potential underestimation of risk due to information gaps by choosing to tend more towards human health and environment protection (typically the high-level protection goals). This could be addressed by selecting appropriate risk hypothesis for subsequent phases to provide better data sets to query assumptions and uncertainty resulting in more robust conclusions of greater certainty. Each phase would have an appropriate risk assessment allowing for an iterative process as well as temporal and ecological appropriate scoping.
With regard to section 3.1 Protection goals, assessment endpoints and measurement endpoints, I would suggest it be moved to Section 4 as these are all part of the larger Scoping activities at the start of the risk assessment process. Under protection goals, perhaps a consideration would be to describe the logical flow of operationalizing high level goals taken from national legislation such that they are particular to EGDOs (particularly EGD Mosquito) in the national context. In so doing one could also include stakeholder concerns along with legal obligations. Identifying granular operational goals would in turn help define appropriate measurement and assessment endpoints. For a relevant example to EGD mosquitoes and operational goals see Connolly et al. Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa. Malar J 20, 170 (2021). https://doi.org/10.1186/s12936-021-03674-6
I am a retired biologist, involved for much of my career with LMO risk assessment methodologies and capacity building, including LMOs containing gene drives. First I would like to register my thanks to the International Centre for Genetic Engineering and Biotechnology (ICGEB) for drafting this outline, which follows established LMO risk assessment approaches and Annex III risk assessment methodology.
I agree with Anastasia Matthies (#11786), John Connolly (#11796), Piet van der Meer (#11798), and others that the additional material should deal primarily with topics not dealt with in previous or other guidance. This will be a more efficient use of AHTEG efforts and prevent the misperception that gene drive risk assessments require de novo methodologies.
Regarding uncertainty: identifying different sources of uncertainty is a necessary part of conducting risk assessments. However, decisions can be made that take uncertainty into account. As has been mentioned already in numerous comments in this forum, uncertainty has been a reality of LMO risk assessment already, yet has not precluded decisions to be made in the past for other LMOs (as mentioned already by Aaron Roberts, #11814). The uncertainties listed by several posters to this forum are in fact not unique to gene drives. Furthermore, decisions in the face of uncertainty are common in other fields as well, such as climate change or financial analysis (both for investments and national economic policy). In those fields, decisions are made, using established methodologies, and based on risk assessments. One resource that describes these methodologies is
Marchau VAWJ, Walker WE, Bloemen PJTM, Popper SW (eds) (2019) Decision Making under Deep Uncertainty: From Theory to Practice. Springer International Publishing (https://doi.org/10.1007/978-3-030-05252-2).
See also https://www.deepuncertainty.org/.
The use of established approaches to decision-making under uncertainty is not incompatible with the precautionary approach. It is important to remember once again the three objectives of the CBD:
- Conservation of biological diversity
- Sustainable use of its components
- Fair and equitable sharing of the benefits arising out of the utilization of genetic resources.
As I have pointed out in previous online fora, two of these three objectives require the deployment of biotechnologies in order to be realized. Thus, the precautionary approach or precautionary principle should be applied in the light of these objectives, and not employed as a verbal talisman to avert the proper research and deployment of technologies that will achieve the intended outcomes of the CBD.
I agree with Anastasia Matthies (#11786), John Connolly (#11796), Piet van der Meer (#11798), and others that the additional material should deal primarily with topics not dealt with in previous or other guidance. This will be a more efficient use of AHTEG efforts and prevent the misperception that gene drive risk assessments require de novo methodologies.
Regarding uncertainty: identifying different sources of uncertainty is a necessary part of conducting risk assessments. However, decisions can be made that take uncertainty into account. As has been mentioned already in numerous comments in this forum, uncertainty has been a reality of LMO risk assessment already, yet has not precluded decisions to be made in the past for other LMOs (as mentioned already by Aaron Roberts, #11814). The uncertainties listed by several posters to this forum are in fact not unique to gene drives. Furthermore, decisions in the face of uncertainty are common in other fields as well, such as climate change or financial analysis (both for investments and national economic policy). In those fields, decisions are made, using established methodologies, and based on risk assessments. One resource that describes these methodologies is
Marchau VAWJ, Walker WE, Bloemen PJTM, Popper SW (eds) (2019) Decision Making under Deep Uncertainty: From Theory to Practice. Springer International Publishing (https://doi.org/10.1007/978-3-030-05252-2).
See also https://www.deepuncertainty.org/.
The use of established approaches to decision-making under uncertainty is not incompatible with the precautionary approach. It is important to remember once again the three objectives of the CBD:
- Conservation of biological diversity
- Sustainable use of its components
- Fair and equitable sharing of the benefits arising out of the utilization of genetic resources.
As I have pointed out in previous online fora, two of these three objectives require the deployment of biotechnologies in order to be realized. Thus, the precautionary approach or precautionary principle should be applied in the light of these objectives, and not employed as a verbal talisman to avert the proper research and deployment of technologies that will achieve the intended outcomes of the CBD.
Hello. My name is Karen Hokanson from the University of Minnesota, US. I have been working in the area of biosafety and regulation of biotechnology, mainly providing capacity building for these in developing countries, for more than 20 years. I was an observer member of the AHTEG on Risk Assessment and Risk Management that produced the draft Guidance on Risk Assessment which the Parties ‘took note of’ at COPMOP2016 [I will refer to this as the 2016 Guidance]. I am attaching a paper I wrote in 2019 reflecting on my experience as a member of that AHTEG.
Thanks very much to the Secretariat for hosting this forum and to Luciana for moderating.
All of my comments go to the outset of the draft outline:
Line 7: ‘Part A 1. Objective and scope of these additional voluntary guidance materials.’
In general, regarding the objective and scope of this guidance, I am concerned to see reference to the draft Guidance on Risk Assessment from COPMOP2016. As in a number of other posts to this forum [#11784, #11785, #11786, #11787, #11789, #11793, #11801, #11804, #11814, #11821], I do not see value in duplicating what is in that guidance as part of the current exercise and even more so in repeating the process used to develop that guidance.
In my mind, there are two critical aspects of the ‘objective and scope’ of the current voluntary guidance on EGD-LMOs that should be decided before the work of the AHTEG begins.
1) What is the purpose of the ‘guidance’.
This was reflected well in the post by Andrew Roberts [#11804]: ‘The challenge, once again, is that we are approaching the task of developing guidance documents when there are clearly different ideas about what "guidance" is supposed to accomplish.’
Is the guidance meant to instruct parties on ‘how to do a risk assessment’ on EGD-LMOs or is it meant to ‘provide information’ that could be useful for a risk assessment of EGD-LMOs, or is it meant to actually assess the risk of an EGD-LMO? The 2016 guidance tried to do all of these things at once. I would strongly encourage the AHTEG to settle on the middle approach, and make the goal to provide information that could be useful for a risk assessment and point out where in the risk assessment it could be used. I would suggest to steer far away from anything resembling a ‘roadmap’.
2) Will this document be a ‘consensus’ document or a ‘compromise’ document or neither of these?
The 2016 guidance was a ‘compromise’ document, and in the end this was unacceptable. It is a major challenge for an AHTEG under the CBD which is by its definition representing individuals from a subset of parties who bring vastly different experiences and expertise to the table to reach ‘consensus’. The different views on ‘uncertainty’ in this current online forum discussion are a good example . (And the same different opinions about uncertainty were discussed at length for the 2016 Guidance without reaching any sort of concensus.)
However, ‘compromise’ when there are vastly different opinions about the information to include will likely produce a document that represents the opinion of neither, in which case nobody is satisfied. The solution here is to decide at the outset, where there are differences of opinion, these will be captured as such in the document. Users of the document can then understand both sides of an issue and choose how to use this information to guide their own risk assessment.
The draft outline should probably be revised after these two important questions have been answered.
I also wish to agree with the comments of Adam Cornish regarding the scoping of this guidance document in his posts [#11816, #11818]. It would be best if this guidance is specifically focused on EGD-LMO mosquitos and the information related to these that could be useful in a risk assessment, and less about EGD-LMO’s in general. A clear focus will likely result in a more useful document.
Thanks for this opportunity to share these suggestions.
Karen
Thanks very much to the Secretariat for hosting this forum and to Luciana for moderating.
All of my comments go to the outset of the draft outline:
Line 7: ‘Part A 1. Objective and scope of these additional voluntary guidance materials.’
In general, regarding the objective and scope of this guidance, I am concerned to see reference to the draft Guidance on Risk Assessment from COPMOP2016. As in a number of other posts to this forum [#11784, #11785, #11786, #11787, #11789, #11793, #11801, #11804, #11814, #11821], I do not see value in duplicating what is in that guidance as part of the current exercise and even more so in repeating the process used to develop that guidance.
In my mind, there are two critical aspects of the ‘objective and scope’ of the current voluntary guidance on EGD-LMOs that should be decided before the work of the AHTEG begins.
1) What is the purpose of the ‘guidance’.
This was reflected well in the post by Andrew Roberts [#11804]: ‘The challenge, once again, is that we are approaching the task of developing guidance documents when there are clearly different ideas about what "guidance" is supposed to accomplish.’
Is the guidance meant to instruct parties on ‘how to do a risk assessment’ on EGD-LMOs or is it meant to ‘provide information’ that could be useful for a risk assessment of EGD-LMOs, or is it meant to actually assess the risk of an EGD-LMO? The 2016 guidance tried to do all of these things at once. I would strongly encourage the AHTEG to settle on the middle approach, and make the goal to provide information that could be useful for a risk assessment and point out where in the risk assessment it could be used. I would suggest to steer far away from anything resembling a ‘roadmap’.
2) Will this document be a ‘consensus’ document or a ‘compromise’ document or neither of these?
The 2016 guidance was a ‘compromise’ document, and in the end this was unacceptable. It is a major challenge for an AHTEG under the CBD which is by its definition representing individuals from a subset of parties who bring vastly different experiences and expertise to the table to reach ‘consensus’. The different views on ‘uncertainty’ in this current online forum discussion are a good example . (And the same different opinions about uncertainty were discussed at length for the 2016 Guidance without reaching any sort of concensus.)
However, ‘compromise’ when there are vastly different opinions about the information to include will likely produce a document that represents the opinion of neither, in which case nobody is satisfied. The solution here is to decide at the outset, where there are differences of opinion, these will be captured as such in the document. Users of the document can then understand both sides of an issue and choose how to use this information to guide their own risk assessment.
The draft outline should probably be revised after these two important questions have been answered.
I also wish to agree with the comments of Adam Cornish regarding the scoping of this guidance document in his posts [#11816, #11818]. It would be best if this guidance is specifically focused on EGD-LMO mosquitos and the information related to these that could be useful in a risk assessment, and less about EGD-LMO’s in general. A clear focus will likely result in a more useful document.
Thanks for this opportunity to share these suggestions.
Karen
Dear Colleagues:
I am Bob Friedman with the J. Craig Venter Institute, a nonprofit genomics and synthetic biology research institute in the United States. I am an ecologist by training who has spent many years doing policy related research and advising on both environmental policy and biotechnology policy.
I would like to thank ICGEB for producing the draft outline for additional voluntary guidance and thank all the participants for their thoughtful reviews of it. However, even at four pages, the individual entries in the draft outline are so sparing that they resemble a Rorschach inkblot test for the divergent views of what would be most helpful. Thus, I would like to thank our moderator, Luciana Ambrozevicius, for her recent posting with some important and pragmatic questions for us to consider.
First, Luciana asks whether the proposed format is useful, with Part A focusing on the steps for RA of EGD-LMOs and Part B presenting a case study. I am among the many participants who believe that “additional” voluntary guidance should not be interpreted as “another” voluntary guidance document, rather as “supplemental” guidance material. This can certainly be organized following the steps listed in Annex III (and as proposed in the draft outline), but to be most helpful, should focus on practical suggestions for what might need to be done differently and best practices for how.
I am not certain what would be included in Part B, i.e., a case study of a risk assessment, given that no EGD mosquito has been proposed for regulatory review or even completely developed. In my view, what would be most helpful is to adopt the wider view included in the WHO Guidance Framework for Testing Genetically Modified Mosquitoes. This document makes clear that best practice for both development and risk assessment of EGD mosquitoes is done in phases: starting in the lab, continuing with confined field testing, etc. A case study of a particular development effort to date (e.g., modified Anopheles for malaria control), again focusing on best practices at each step, could be helpful, however, with the caveat that both the EGD mosquito and the risk assessment protocol is still a work in progress.
Luciana also asks whether there are “any aspects of uncertainty in the case of engineered gene drive LMOs that are different from other LMOs? What is the role of modeling, a tier-based testing approach and other tools to reduce uncertainty?”
In my view, the question should be broadened: are there any aspects of uncertainty that are fundamentally different than those posed by prior introductions of LMOs, prior introductions of traditional biocontrol organisms, Wolbachia-infected mosquitoes, sterile insects (LMO and other), and chemical or biochemical methods of population suppression (i.e., pesticides)? EGD-mosquitoes include one or more functional aspects similar to each of these, but no organism to date has included all together. The complete package may be new and different, but as several others have identified earlier in this forum, risk assessments have been successfully performed for all of these pest-control methods and thus provide useful lessons and examples of analytic methods to help reduce uncertainty. These most certainly include both modeling and tier-based testing.
Karen Hokanson [#11824] offers three options for the “additional” guidance by the AHTEG: 1) instruct parties on ‘how to do a risk assessment’ on EGD-LMOs, 2) ‘provide information’ that could be useful for a risk assessment of EGD-LMOs, or 3) actually assess the risk of an EGD-LMO? Both she and I believe that option 2 is the most useful approach.
During the first online forum, I suggested that for each step of the risk assessment process, the AHTEG could identify one or more examples of best practices for each of the specific elements important for a case-specific risk assessment of a field trial or full deployment of a gene drive organism. No individual existing guidance document is strongest in all areas. But each has its strengths.
Thus, the Risk Assessment AHTEG’s primary task would be to choose examples of current best practices for, e.g., identifying pathways to harm, when and how to employ ecological models, incorporating stakeholder views, evaluating the potential efficacy of the intervention, etc. Many useful references have been proposed by participants during this and the earlier online forums. The additional voluntary guidance would be, in essence, guidance for making best use of the existing guidance. Of course, best practice can always be improved, and suggestions for doing so would also be quite helpful, where appropriate. Examples of best practice would both add value today and could be easily updated as needed as both risk assessment practices and gene drive technologies improve in the future.
Regards to all,
Bob Friedman
I am Bob Friedman with the J. Craig Venter Institute, a nonprofit genomics and synthetic biology research institute in the United States. I am an ecologist by training who has spent many years doing policy related research and advising on both environmental policy and biotechnology policy.
I would like to thank ICGEB for producing the draft outline for additional voluntary guidance and thank all the participants for their thoughtful reviews of it. However, even at four pages, the individual entries in the draft outline are so sparing that they resemble a Rorschach inkblot test for the divergent views of what would be most helpful. Thus, I would like to thank our moderator, Luciana Ambrozevicius, for her recent posting with some important and pragmatic questions for us to consider.
First, Luciana asks whether the proposed format is useful, with Part A focusing on the steps for RA of EGD-LMOs and Part B presenting a case study. I am among the many participants who believe that “additional” voluntary guidance should not be interpreted as “another” voluntary guidance document, rather as “supplemental” guidance material. This can certainly be organized following the steps listed in Annex III (and as proposed in the draft outline), but to be most helpful, should focus on practical suggestions for what might need to be done differently and best practices for how.
I am not certain what would be included in Part B, i.e., a case study of a risk assessment, given that no EGD mosquito has been proposed for regulatory review or even completely developed. In my view, what would be most helpful is to adopt the wider view included in the WHO Guidance Framework for Testing Genetically Modified Mosquitoes. This document makes clear that best practice for both development and risk assessment of EGD mosquitoes is done in phases: starting in the lab, continuing with confined field testing, etc. A case study of a particular development effort to date (e.g., modified Anopheles for malaria control), again focusing on best practices at each step, could be helpful, however, with the caveat that both the EGD mosquito and the risk assessment protocol is still a work in progress.
Luciana also asks whether there are “any aspects of uncertainty in the case of engineered gene drive LMOs that are different from other LMOs? What is the role of modeling, a tier-based testing approach and other tools to reduce uncertainty?”
In my view, the question should be broadened: are there any aspects of uncertainty that are fundamentally different than those posed by prior introductions of LMOs, prior introductions of traditional biocontrol organisms, Wolbachia-infected mosquitoes, sterile insects (LMO and other), and chemical or biochemical methods of population suppression (i.e., pesticides)? EGD-mosquitoes include one or more functional aspects similar to each of these, but no organism to date has included all together. The complete package may be new and different, but as several others have identified earlier in this forum, risk assessments have been successfully performed for all of these pest-control methods and thus provide useful lessons and examples of analytic methods to help reduce uncertainty. These most certainly include both modeling and tier-based testing.
Karen Hokanson [#11824] offers three options for the “additional” guidance by the AHTEG: 1) instruct parties on ‘how to do a risk assessment’ on EGD-LMOs, 2) ‘provide information’ that could be useful for a risk assessment of EGD-LMOs, or 3) actually assess the risk of an EGD-LMO? Both she and I believe that option 2 is the most useful approach.
During the first online forum, I suggested that for each step of the risk assessment process, the AHTEG could identify one or more examples of best practices for each of the specific elements important for a case-specific risk assessment of a field trial or full deployment of a gene drive organism. No individual existing guidance document is strongest in all areas. But each has its strengths.
Thus, the Risk Assessment AHTEG’s primary task would be to choose examples of current best practices for, e.g., identifying pathways to harm, when and how to employ ecological models, incorporating stakeholder views, evaluating the potential efficacy of the intervention, etc. Many useful references have been proposed by participants during this and the earlier online forums. The additional voluntary guidance would be, in essence, guidance for making best use of the existing guidance. Of course, best practice can always be improved, and suggestions for doing so would also be quite helpful, where appropriate. Examples of best practice would both add value today and could be easily updated as needed as both risk assessment practices and gene drive technologies improve in the future.
Regards to all,
Bob Friedman
Dear all,
My name is Eder Toppa, I've been working for the Brazilian Ministry of Agriculture and Livestock for the past decade and I am currently the Head of Biosafety Service as well as I am member of the National Biosafety Commission. I attended the COP / MOP meetings held in Montréal last December and I am following all the discussion about gene drive.
Apologies for only writing now, however I would like to stress some general remarks.
Line 7: "Part A, section 1: Objective and scope of these additional voluntary guidance materials."
I strongly support Mr. Adam Cornish's comments [#11816] [#11818]. Briefly, It's important to claim again the paragraph 1.C of the Terms of Reference for the AHTEG on RA - The Annex of the Decision CP-10/10 -, therefore, the voluntary guidance should be restrained on EGD-LMO mosquitos
Line 11: "Part A, section 2. Previous guidance under the Cartagena Protocol" linked with Line 37 and footnote 1.
Echoing Mr. Pieter van der Meer [#11798] and Dr. Aaron Roberts [#11814], I was really surprised with the reference to the COP-MOP 8 Roadmap for RA of LMO for the same reasons - the document was not endorsed by the Parties and should not be used to build on the current work. I suggest the deletion of the COP-MOP8 guidance reference and anything resembling that RoadMap, or else, as stated by Mr. Andrew Roberts [#11804], this will be an attempt to subvert the wishes of the Parties.
Line 12: "Part A, section 2. Relevant guidance from other processes".
I would like to support Dr. Marco Gielkens [#11801] who has mentioned the OECD Environmental Considerations Consensus Document that can be applied more widely - it presents an important reference for ERA that can be used to develop the current work. Also the WHO Guidance Framework For Testing Genetically Modified Mosquitoes is an important reference as the Decision CP10-10 has the focus on gene drive mosquitoes. The voluntary guidelines should capture the difference between LMO and LMO containing gene drive during the risk assessment procedure according to Cartagena Annex III and in the scope of the three objectives of the Convention.
Line 20: "Part A, Section 3.3. Identification and consideration of uncertainty"
I agree with Mr. Andrew Roberts [#11804] about the importance of how uncertainties are identified, assessed for relevance and communicated and for EGD-LMOs, not only modeling is an important tool, but also the use of information obtained through a tier-based testing approach. From WHO Guidance: "At each phase or logical point in the testing pathway, risk analysis will contribute to determining whether to allow trials to move forward. Risk analysis typically follows a standard multi- stage process that should inform and articulate the concerns on which to focus and the acceptability of risks." Instead of elaborating about limits of concern or limits of uncertainty that will depend on the decision making to accept a technology, the voluntary guidelines should focus on the current experience to treat uncertainty and the lines of evidence and studies being undertaken.
Best regards,
Eder Toppa
My name is Eder Toppa, I've been working for the Brazilian Ministry of Agriculture and Livestock for the past decade and I am currently the Head of Biosafety Service as well as I am member of the National Biosafety Commission. I attended the COP / MOP meetings held in Montréal last December and I am following all the discussion about gene drive.
Apologies for only writing now, however I would like to stress some general remarks.
Line 7: "Part A, section 1: Objective and scope of these additional voluntary guidance materials."
I strongly support Mr. Adam Cornish's comments [#11816] [#11818]. Briefly, It's important to claim again the paragraph 1.C of the Terms of Reference for the AHTEG on RA - The Annex of the Decision CP-10/10 -, therefore, the voluntary guidance should be restrained on EGD-LMO mosquitos
Line 11: "Part A, section 2. Previous guidance under the Cartagena Protocol" linked with Line 37 and footnote 1.
Echoing Mr. Pieter van der Meer [#11798] and Dr. Aaron Roberts [#11814], I was really surprised with the reference to the COP-MOP 8 Roadmap for RA of LMO for the same reasons - the document was not endorsed by the Parties and should not be used to build on the current work. I suggest the deletion of the COP-MOP8 guidance reference and anything resembling that RoadMap, or else, as stated by Mr. Andrew Roberts [#11804], this will be an attempt to subvert the wishes of the Parties.
Line 12: "Part A, section 2. Relevant guidance from other processes".
I would like to support Dr. Marco Gielkens [#11801] who has mentioned the OECD Environmental Considerations Consensus Document that can be applied more widely - it presents an important reference for ERA that can be used to develop the current work. Also the WHO Guidance Framework For Testing Genetically Modified Mosquitoes is an important reference as the Decision CP10-10 has the focus on gene drive mosquitoes. The voluntary guidelines should capture the difference between LMO and LMO containing gene drive during the risk assessment procedure according to Cartagena Annex III and in the scope of the three objectives of the Convention.
Line 20: "Part A, Section 3.3. Identification and consideration of uncertainty"
I agree with Mr. Andrew Roberts [#11804] about the importance of how uncertainties are identified, assessed for relevance and communicated and for EGD-LMOs, not only modeling is an important tool, but also the use of information obtained through a tier-based testing approach. From WHO Guidance: "At each phase or logical point in the testing pathway, risk analysis will contribute to determining whether to allow trials to move forward. Risk analysis typically follows a standard multi- stage process that should inform and articulate the concerns on which to focus and the acceptability of risks." Instead of elaborating about limits of concern or limits of uncertainty that will depend on the decision making to accept a technology, the voluntary guidelines should focus on the current experience to treat uncertainty and the lines of evidence and studies being undertaken.
Best regards,
Eder Toppa
Dear colleagues,
My name is Ricarda Steinbrecher, I am biologist and molecular geneticist, and have worked on biosafety, risks and risk assessment of LMOs since the mid-1990s. I have participated in the processes that led to and then of the Cartagena Protocol from its beginning. I was a member of the AHTEG on Risk Assessment and Monitoring from 2009-2013 and serve presently on both the CP AHTEG on RA&M and the CBD mAHTEG on synthetic biology. I have been nominated by the Federation of German Scientists.
Thank you to the moderator and the secretariat for all their work on this.
I would also like to thank those who produced this outline and I am grateful that it follows clearly Annex III and picks up on the issues brought up in previous guidance materials. This is important as these issues and aspects will need to be revisited and worked on in specific light of and relevance to EGDs. There has been a suggestion that the current outline will give a duplication of previous guidance and that duplication should be avoided and only differences should be put forward [#11784, #11814 & #11798] – I would not support this suggestion, as duplications of headings and structures and issues covered is not duplication of the actual content, but is a useful guidance and helping the process of developing and contextualising specifics. Duplication as such has actually a high ranking within science, as it can (and should) be used to validate.
Apologies that this is a lengthy submission.
A1: Concerning objective and scope (lines 7 & 8): It would be helpful to also put this into context of other decisions under the CBD and its protocols relating to engineered gene drives, also bearing in mind that engineered gene drives are part to the field of synthetic biology. Depending on how the guidance is being filled in, this contextualisation may have an own section point, but should not simply ‘disappear’ in an introduction.
A2: I agree with the inclusion of the three points listed so far (lines 10-12). It is important to see and to place the RARM guidance for EGD-LMOs in the context of the previous work of the AHTEG and the development of the Roadmap and the additional guidance materials, including on genetically modified mosquitoes. These are the result of the hard work of all the experts of previous rounds of the AHTEG, with many working sessions, as well as of reviewing processes. They have been welcomed and used by many parties and are highly relevant to our current work. The fact that COP-MOP made the political decision to ‘take note of’ (mentioned in #11784) is a reflection of different party interests at COP-MOP and is understood as that – especially as there were many parties expressing their wish to ‘welcome’ the combined guidance materials and also given that the materials are widely being used in biosafety trainings. This is also relevant for Line 37, which makes reference to the Roadmap, which is helpful and appropriate, and should be kept.
Additionally to the three points already listed I think we need to include three further points: a) previous COP decisions relevant to engineered gene drives, including the contextualisation of EGDs and gene drive organisms (GDOs) as part of synthetic biology and its related decisions; and b) the point of transboundary movement and transboundary impacts (e.g. unavoidable, unintentional or intentional spread and action of the EGD/GDO, or impacts on migrating animals, such as birds, and thus potentially on countries at far distances of the intended or initial release), which needs to be part of aspects such as protection goals, risk assessment, risk management and risk decision making in an “beyond national”, that is international setting and context. This also relates to the aspect of ‘international oversight’, which has been raised at various stages in the debate and should be a sub-section here. Finally c), another point to add either here or at different appropriate section, is: Where does the issue go beyond the scope and/or capacity and/or Annex III assessment process of the CP, that is what are the limit and limitations of the Protocol with regards to a reliable risk assessment of EGDs or some of its categories/classes.
A3: Overarching issues:
Line 14: It may be important to be aware that the ‘engineered gene drive terminology’ referred to here may not be straight forward and the AHTEG may want to have definitions and descriptions for the purpose of the use in the guidance, but not to seek to have general applicability due to a wider debate (see for example Wells and Steinbrecher 2022). It would be good to look at the whole spectrum of EGDs (including ‘types’) and to look both at ‘general’ as well as ‘specific’ characteristics (for EGDs and EGD types along the spectrum) and thus to avoid to loose depth and clarity due to attempting to stay general.
Line 14bis: as these are ‘overarching’ issues it also should include the step-change that EGDs/GDOs represent, namely the release into the wild in order to modify the wild, mostly by transferring the modification actions into the wild.
A3.1: (Lines 15-16) This is a relevant section under A3, especially as it has new aspects as compared to previous LMO categories (see comment line 16) and is overarching. Please keep it here and elaborate further with an extra bullet point:
Line 16bis: reflection of these points in the international context, i.e. that of transboundary and long distance movements and impacts, and of potentially different regulations and protection goals elsewhere (see above, including issue of oversight).
A3.2: (Lines 17-19): this section has to include the issue of lack of knowledge (including known and “unknown unknowns”) and lack of understanding, which is not the same as ‘quality’ or ‘relevance’ of information, nor is it the same as ‘uncertainty’. Line 19 may want to also include the term ‘knowledge’.
A3.3: (lines 20-23: Uncertainty). This is an important section. It should also include the point of uncertainty assessment, as without assessment only assumptions can be made, which would in the context of the precautionary principle have to err on the side of caution. Line 22 could thus say: Consideration, treatment and assessment of uncertainty. Line 23 eludes to a section on uncertainty in the context of modelling (or vice versa). This section has to include looking at the appropriateness and inappropriateness of the use of modelling in risk assessment, and to which extent it might have a role or not. Thus the heading needs to be either more general or more wordy and inclusive.
There was a suggestion [#11784] to change line 21 to Categories of “relevant” uncertainty. I think it is better to keep it wide and start looking broadly (in the context of EGDs and RA) where uncertainties occur, how to categorise them and then to see how to assess and analyse such uncertainties and how to conclude which ones are of relevance.
The suggestion of using modelling to reduce uncertainty [#11792] has been put forward at times especially when there is no actual scientific experimental field data (due to refraining from experiments due to risks). This will be an important debate, where one will also need to look how modelling may actually bring in its own risks and create its own uncertainties, thus questioning the wider role of modelling in risk assessment. Modelling has clear limits and limitations and this needs to be covered. The term ‘modelling’ only comes up in this one line of the outline. If it is being suggested as a means to ‘reduce uncertainty’ then it needs to be assessed and discussed -together with other methodologies - under a new section of “risk assessment methodologies – their usefulness and limits”.
A3.4 (NEW) (lines 23 bis….) A section is missing on (potential) lack of (appropriate) evidence and data and how to deal with this.
A3.5. (NEW) (lines 23 bis bis). A section is missing on cut-off criteria, meaning when and how to declare that there are insufficient means or data or certainty to provide a reliable risk assessment and thus not to grant a release permit.
I support the suggestion to add a section on Risk Assessment Methodology (#11786 & #11796)
with kind regards,
My name is Ricarda Steinbrecher, I am biologist and molecular geneticist, and have worked on biosafety, risks and risk assessment of LMOs since the mid-1990s. I have participated in the processes that led to and then of the Cartagena Protocol from its beginning. I was a member of the AHTEG on Risk Assessment and Monitoring from 2009-2013 and serve presently on both the CP AHTEG on RA&M and the CBD mAHTEG on synthetic biology. I have been nominated by the Federation of German Scientists.
Thank you to the moderator and the secretariat for all their work on this.
I would also like to thank those who produced this outline and I am grateful that it follows clearly Annex III and picks up on the issues brought up in previous guidance materials. This is important as these issues and aspects will need to be revisited and worked on in specific light of and relevance to EGDs. There has been a suggestion that the current outline will give a duplication of previous guidance and that duplication should be avoided and only differences should be put forward [#11784, #11814 & #11798] – I would not support this suggestion, as duplications of headings and structures and issues covered is not duplication of the actual content, but is a useful guidance and helping the process of developing and contextualising specifics. Duplication as such has actually a high ranking within science, as it can (and should) be used to validate.
Apologies that this is a lengthy submission.
A1: Concerning objective and scope (lines 7 & 8): It would be helpful to also put this into context of other decisions under the CBD and its protocols relating to engineered gene drives, also bearing in mind that engineered gene drives are part to the field of synthetic biology. Depending on how the guidance is being filled in, this contextualisation may have an own section point, but should not simply ‘disappear’ in an introduction.
A2: I agree with the inclusion of the three points listed so far (lines 10-12). It is important to see and to place the RARM guidance for EGD-LMOs in the context of the previous work of the AHTEG and the development of the Roadmap and the additional guidance materials, including on genetically modified mosquitoes. These are the result of the hard work of all the experts of previous rounds of the AHTEG, with many working sessions, as well as of reviewing processes. They have been welcomed and used by many parties and are highly relevant to our current work. The fact that COP-MOP made the political decision to ‘take note of’ (mentioned in #11784) is a reflection of different party interests at COP-MOP and is understood as that – especially as there were many parties expressing their wish to ‘welcome’ the combined guidance materials and also given that the materials are widely being used in biosafety trainings. This is also relevant for Line 37, which makes reference to the Roadmap, which is helpful and appropriate, and should be kept.
Additionally to the three points already listed I think we need to include three further points: a) previous COP decisions relevant to engineered gene drives, including the contextualisation of EGDs and gene drive organisms (GDOs) as part of synthetic biology and its related decisions; and b) the point of transboundary movement and transboundary impacts (e.g. unavoidable, unintentional or intentional spread and action of the EGD/GDO, or impacts on migrating animals, such as birds, and thus potentially on countries at far distances of the intended or initial release), which needs to be part of aspects such as protection goals, risk assessment, risk management and risk decision making in an “beyond national”, that is international setting and context. This also relates to the aspect of ‘international oversight’, which has been raised at various stages in the debate and should be a sub-section here. Finally c), another point to add either here or at different appropriate section, is: Where does the issue go beyond the scope and/or capacity and/or Annex III assessment process of the CP, that is what are the limit and limitations of the Protocol with regards to a reliable risk assessment of EGDs or some of its categories/classes.
A3: Overarching issues:
Line 14: It may be important to be aware that the ‘engineered gene drive terminology’ referred to here may not be straight forward and the AHTEG may want to have definitions and descriptions for the purpose of the use in the guidance, but not to seek to have general applicability due to a wider debate (see for example Wells and Steinbrecher 2022). It would be good to look at the whole spectrum of EGDs (including ‘types’) and to look both at ‘general’ as well as ‘specific’ characteristics (for EGDs and EGD types along the spectrum) and thus to avoid to loose depth and clarity due to attempting to stay general.
Line 14bis: as these are ‘overarching’ issues it also should include the step-change that EGDs/GDOs represent, namely the release into the wild in order to modify the wild, mostly by transferring the modification actions into the wild.
A3.1: (Lines 15-16) This is a relevant section under A3, especially as it has new aspects as compared to previous LMO categories (see comment line 16) and is overarching. Please keep it here and elaborate further with an extra bullet point:
Line 16bis: reflection of these points in the international context, i.e. that of transboundary and long distance movements and impacts, and of potentially different regulations and protection goals elsewhere (see above, including issue of oversight).
A3.2: (Lines 17-19): this section has to include the issue of lack of knowledge (including known and “unknown unknowns”) and lack of understanding, which is not the same as ‘quality’ or ‘relevance’ of information, nor is it the same as ‘uncertainty’. Line 19 may want to also include the term ‘knowledge’.
A3.3: (lines 20-23: Uncertainty). This is an important section. It should also include the point of uncertainty assessment, as without assessment only assumptions can be made, which would in the context of the precautionary principle have to err on the side of caution. Line 22 could thus say: Consideration, treatment and assessment of uncertainty. Line 23 eludes to a section on uncertainty in the context of modelling (or vice versa). This section has to include looking at the appropriateness and inappropriateness of the use of modelling in risk assessment, and to which extent it might have a role or not. Thus the heading needs to be either more general or more wordy and inclusive.
There was a suggestion [#11784] to change line 21 to Categories of “relevant” uncertainty. I think it is better to keep it wide and start looking broadly (in the context of EGDs and RA) where uncertainties occur, how to categorise them and then to see how to assess and analyse such uncertainties and how to conclude which ones are of relevance.
The suggestion of using modelling to reduce uncertainty [#11792] has been put forward at times especially when there is no actual scientific experimental field data (due to refraining from experiments due to risks). This will be an important debate, where one will also need to look how modelling may actually bring in its own risks and create its own uncertainties, thus questioning the wider role of modelling in risk assessment. Modelling has clear limits and limitations and this needs to be covered. The term ‘modelling’ only comes up in this one line of the outline. If it is being suggested as a means to ‘reduce uncertainty’ then it needs to be assessed and discussed -together with other methodologies - under a new section of “risk assessment methodologies – their usefulness and limits”.
A3.4 (NEW) (lines 23 bis….) A section is missing on (potential) lack of (appropriate) evidence and data and how to deal with this.
A3.5. (NEW) (lines 23 bis bis). A section is missing on cut-off criteria, meaning when and how to declare that there are insufficient means or data or certainty to provide a reliable risk assessment and thus not to grant a release permit.
I support the suggestion to add a section on Risk Assessment Methodology (#11786 & #11796)
with kind regards,
First of all I want to thank the Secretariat for putting together the online forum's content and Luciana for stepping up once more to moderate this discussion.
Here are my thoughts on the structure of the draft outline of the Additional voluntary guidance materials and some of the issues raised by the forum participants.
The overall format of the document is logical, with Part A covering broad ERA of EGD-LM issues before moving on to case studies of particular EGD-LMs.
I appreciate the reference to the roadmap on risk assessment and risk management of LMOs, which I believe were developed to be consistent with the provisions of the Cartagena Protocol, especially its Annex III. It makes sense to use it as a starting point for the Guidance on EGD-LMOs that we are discussing here, mandated by Decision CP-10/10 on risk assessment and risk management (Articles 15 and 16). I do not see this as a duplication of content but rather an opportunity to use the structure laid out in the Roadmap and the Guidance, including the treatment of uncertainties, and populate it with content specific to EGD-LMO risks.
I also want to highlight that the "Guidance on risk assessment for living modified organisms and monitoring in the context of risk assessment" ("Guidance") and the "Roadmap for risk assessment of living modified organisms" ("Roadmap") is not a draft. Parties to the Protocol have invited interested Parties, other Governments, and relevant organizations to take the Guidance into account as a voluntary tool to assist in conducting risk assessment in accordance with the Cartagena Protocol (Decision BS-VIII/12). Indeed, many Parties, particularly from the Global South, do just this.
Let's not also forget the negotiation history, where the Guidance in its earlier version was welcomed (Decision BS-V/12), its progress commended (Decision BS-VI/12), the results of the testing of the Guidance welcomed and Parties, other Governments, and relevant organizations invited to test or use it in actual cases of risk assessment and as a tool for capacity-building activities in risk assessment (Decision BS-VII/12). The produced guidances were drafted and revised by two subsequent AHTEGs, they were peer-reviewed and subjected to several rounds of discussions and testing by parties.
Here are my thoughts on the structure of the draft outline of the Additional voluntary guidance materials and some of the issues raised by the forum participants.
The overall format of the document is logical, with Part A covering broad ERA of EGD-LM issues before moving on to case studies of particular EGD-LMs.
I appreciate the reference to the roadmap on risk assessment and risk management of LMOs, which I believe were developed to be consistent with the provisions of the Cartagena Protocol, especially its Annex III. It makes sense to use it as a starting point for the Guidance on EGD-LMOs that we are discussing here, mandated by Decision CP-10/10 on risk assessment and risk management (Articles 15 and 16). I do not see this as a duplication of content but rather an opportunity to use the structure laid out in the Roadmap and the Guidance, including the treatment of uncertainties, and populate it with content specific to EGD-LMO risks.
I also want to highlight that the "Guidance on risk assessment for living modified organisms and monitoring in the context of risk assessment" ("Guidance") and the "Roadmap for risk assessment of living modified organisms" ("Roadmap") is not a draft. Parties to the Protocol have invited interested Parties, other Governments, and relevant organizations to take the Guidance into account as a voluntary tool to assist in conducting risk assessment in accordance with the Cartagena Protocol (Decision BS-VIII/12). Indeed, many Parties, particularly from the Global South, do just this.
Let's not also forget the negotiation history, where the Guidance in its earlier version was welcomed (Decision BS-V/12), its progress commended (Decision BS-VI/12), the results of the testing of the Guidance welcomed and Parties, other Governments, and relevant organizations invited to test or use it in actual cases of risk assessment and as a tool for capacity-building activities in risk assessment (Decision BS-VII/12). The produced guidances were drafted and revised by two subsequent AHTEGs, they were peer-reviewed and subjected to several rounds of discussions and testing by parties.
Good day to all,
My name is Galina Mozgova. I am geneticist working more than twenty years in the Institute of Genetics and Cytology of the National Academy of Sciences, and have been working in biosafety and risk assessment more than ten years, biosafety expert and Member of the National Council on GEO. I also participated in the AHTEG on RA in 2012-2016, and currently a member of both AHTEG on RA&M and mAHTEG on synthetic biology.
First of all, I would like to thank the Moderator and the Secretariate for work and to the participants for valuable and interesting comments.
Looking at the structure of the additionally voluntary guidance, I see at this moment a good skeleton for the future work. I support [#11834] that it would be helpful to place in line 8 links to the other decisions on engineered gene drives.
It is also very good that main principles of the RA according to the Annex III will be clarified (line 10). Regarding lines 11 and 37 I believe that they should be kept, fully supporting reasoning of colleagues provided in posts [#11834, #11837], and add that principles, methodology and points to consider of the general guidance on RA are harmonized with Annex III. As far as I understand, this will not be a rewrite of the guidance, but a logical mention in the introduction of an effective tool (voluntary guidance) for a general risk assessment, which is already used by a number of countries, harmonized with the Annex III, and which, among other things, is not separated from other international guidelines, mentions them, taking them into account, and also refers to guidance from other processes when referring to the, for example, guidance for assessing risks to human health to avoid duplication and compliance with the scope of the protocol (Article 4 of the CP). And as a logical continuation of line 11, it would be very good to briefly tell the reader about relevant guidance from other processes (line 12).
In this discussion block, I would also like to write that I fully support the need to add a section on Risk Assessment Methodology [#11786, #11796, #11834], very important chapter that needs to be carefully worked experts from all fields of science relevant to EGD risk assessment.
Best regards,
Galina
My name is Galina Mozgova. I am geneticist working more than twenty years in the Institute of Genetics and Cytology of the National Academy of Sciences, and have been working in biosafety and risk assessment more than ten years, biosafety expert and Member of the National Council on GEO. I also participated in the AHTEG on RA in 2012-2016, and currently a member of both AHTEG on RA&M and mAHTEG on synthetic biology.
First of all, I would like to thank the Moderator and the Secretariate for work and to the participants for valuable and interesting comments.
Looking at the structure of the additionally voluntary guidance, I see at this moment a good skeleton for the future work. I support [#11834] that it would be helpful to place in line 8 links to the other decisions on engineered gene drives.
It is also very good that main principles of the RA according to the Annex III will be clarified (line 10). Regarding lines 11 and 37 I believe that they should be kept, fully supporting reasoning of colleagues provided in posts [#11834, #11837], and add that principles, methodology and points to consider of the general guidance on RA are harmonized with Annex III. As far as I understand, this will not be a rewrite of the guidance, but a logical mention in the introduction of an effective tool (voluntary guidance) for a general risk assessment, which is already used by a number of countries, harmonized with the Annex III, and which, among other things, is not separated from other international guidelines, mentions them, taking them into account, and also refers to guidance from other processes when referring to the, for example, guidance for assessing risks to human health to avoid duplication and compliance with the scope of the protocol (Article 4 of the CP). And as a logical continuation of line 11, it would be very good to briefly tell the reader about relevant guidance from other processes (line 12).
In this discussion block, I would also like to write that I fully support the need to add a section on Risk Assessment Methodology [#11786, #11796, #11834], very important chapter that needs to be carefully worked experts from all fields of science relevant to EGD risk assessment.
Best regards,
Galina
My name is Nicolas Defarge, molecular and computational biologist. I started working around 15 years ago in the field of Toxicology then ecotoxicology of pesticides and GMOs (LMOs) aiming at improvement of RA and ERA of those.
I have been nominated by the European Network of Scientists for Social and Environmental Responsability (ENSSER), who published a comprehensive report on GD (available at https://ensser.org/publications/2019-publications/gene-drives-a-report-on-their-science-applications-social-aspects-ethics-and-regulations/).
Section 1 to 3:
First of all, to reply to our moderator (“Is there any aspect of uncertainty in the case of engineered gene drive LMOs that is different from other LMOs?”), let me recall that Synthetic gene drive (GD) systems constitute a form of novel invasive environmental biotechnology with far-reaching consequences beyond those of other known genetically modified organisms (LMOs). While (agricultural) LMOs contain a delimited-finite trait and not intended to replicate (here the spread of a transgene from a crop to a wild relative by gene flow was considered to be a risk to be avoided!), EGD-LMOs are intended to spread and replicate in the environment. Indeed, the open release of GDOs is intended to re-engineer whole ecosystems, and therefore the role of the Precautionary Principle is particularly important. A precautionary approach involves adopting a cautious attitude towards risk that takes pre-emptive measures to avoid harm. As it is an explicit commitment for all signatories to the UN Convention on Biological Diversity (CBD) and its Cartagena Protocol, it should not be challenged here.
Regarding modelling: Since models are designed for efficiency measurement purposes, their relevance for Environment Risk Assessement may be limited but some models perform better on this point than others, as reviewed in the article by Friess et al., 2023. Review of gene drive modelling and implications for risk assessment of gene drive organisms (https://doi.org/10.1016/j.ecolmodel.2023.1102859).
Still in section 3, l.14, the ENSSER report cited below, as well as the horizon scanning published by Wells and Steinbrecher (2022) available at https://www.econexus.info/files/gene_drive_insect_table_econexus_2022.pdf provide comprehensive informations on EGD terminilogy, types and general characteristics.
I also support the suggestion to add a section on Risk Assessment Methodology (#11786, #11796, #11834).
Best regards,
Nicolas
I have been nominated by the European Network of Scientists for Social and Environmental Responsability (ENSSER), who published a comprehensive report on GD (available at https://ensser.org/publications/2019-publications/gene-drives-a-report-on-their-science-applications-social-aspects-ethics-and-regulations/).
Section 1 to 3:
First of all, to reply to our moderator (“Is there any aspect of uncertainty in the case of engineered gene drive LMOs that is different from other LMOs?”), let me recall that Synthetic gene drive (GD) systems constitute a form of novel invasive environmental biotechnology with far-reaching consequences beyond those of other known genetically modified organisms (LMOs). While (agricultural) LMOs contain a delimited-finite trait and not intended to replicate (here the spread of a transgene from a crop to a wild relative by gene flow was considered to be a risk to be avoided!), EGD-LMOs are intended to spread and replicate in the environment. Indeed, the open release of GDOs is intended to re-engineer whole ecosystems, and therefore the role of the Precautionary Principle is particularly important. A precautionary approach involves adopting a cautious attitude towards risk that takes pre-emptive measures to avoid harm. As it is an explicit commitment for all signatories to the UN Convention on Biological Diversity (CBD) and its Cartagena Protocol, it should not be challenged here.
Regarding modelling: Since models are designed for efficiency measurement purposes, their relevance for Environment Risk Assessement may be limited but some models perform better on this point than others, as reviewed in the article by Friess et al., 2023. Review of gene drive modelling and implications for risk assessment of gene drive organisms (https://doi.org/10.1016/j.ecolmodel.2023.1102859).
Still in section 3, l.14, the ENSSER report cited below, as well as the horizon scanning published by Wells and Steinbrecher (2022) available at https://www.econexus.info/files/gene_drive_insect_table_econexus_2022.pdf provide comprehensive informations on EGD terminilogy, types and general characteristics.
I also support the suggestion to add a section on Risk Assessment Methodology (#11786, #11796, #11834).
Best regards,
Nicolas
Dear online forum participants,
My name is Felicity Keiper and I am participating in this forum as a representative of the Global Industry Coalition (GIC). I have participated in the risk assessment programs of work under the Cartagena Protocol since 2008, and I am a current member of the AHTEG on Risk Assessment and Risk Management and the multidisciplinary AHTEG on Synthetic Biology. I appreciate the opportunity to contribute to this work, and thank the Secretariat and moderator for supporting this online discussion series.
This is my first post in this discussion, and I will begin with general comments on Part A of the draft outline. This Part replicates the structure of a previous “Guidance” document developed over several years in risk assessment programs of work under the Cartagena Protocol (CP). We agree with the reservations expressed by many other participants about this approach (#11784, #11786, #11798, #11802, #11804, #11814, #11821, #11824, #11829, #11830). Firstly, because that document was never accepted or endorsed by CP Parties (see CP COP-MOP8 decision VIII/12). It is therefore not an authoritative source on risk assessment according to CP Annex III – at best, it is one source of existing relevant information amongst many other relevant sources. Secondly, because an “additional guidance material” is not another generic guidance or a recreation of what already exists, it should supplement this – this is indicated in the Term of Reference for the AHTEG (CP Decision 10/10) reproduced below:
“Develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol. A specific focus of this material should be engineered gene drive mosquitos taking into account the current experience with the organism, the type of gene drive and specific issues of risk assessment, identified in annex I to decision CP-9/13, including existing reports, general considerations of living modified organisms containing engineered gene drives, and existing national and regional risk assessment experiences.”
This Term of Reference frames the purpose of this work and its specific focus on EGD-LMO mosquitoes. It is evident in this discussion that there are different views on what the purpose is, with the views of #11824 and #11829 reflecting our understanding of the mandate: to provide information and examples of best practices that could be useful for informing risk assessment of EGD-LMO mosquitoes in accordance with Annex III. The purpose is not to prescribe how to do a risk assessment, conduct an actual risk assessment, or prescribe decision making.
Regarding “taking into account the current experience”, there is already a significant body of relevant work, as evidenced by the references contributed to this discussion (see #11792, #11793, #11794, #11803, #11814, #11817, #11820, #11821) and the extensive lists compiled from the information submissions and online discussions earlier this year (see the “synthesis” documents provided with this online discussion). For this work to supplement what already exists, it should specifically address any identified elements of Annex III for which “additional” guidance materials are warranted, i.e. they are lacking in existing relevant materials or they need updating.
We agree with the many other participants (e.g., #11786, #11793, #11795, #11816) that recommend restructuring of Part A. Key resources for this work have been cited, including the WHO Guidance Framework for Testing Genetically Modified Mosquitoes (2021, second edition) that specifically deals with phased testing and risk assessment of EGD-LMOs (#11820, #11829, #11830). Another key resource is the recently published OECD Consensus Document on Environmental Considerations for the Release of Transgenic Plants (OECD 2023; also referred to by #11801, #11802, #11820, #11830). This document presents a logical structure with key concepts for planning an environmental risk assessment, and it was developed over many years by regulators with extensive practical experience.
Reference: OECD (2023) Safety Assessment of Transgenic Organisms in the Environment, Volume 10: OECD Consensus Document on Environmental Considerations for the Release of Transgenic Plants, Harmonisation of Regulatory Oversight in Biotechnology, OECD Publishing, Paris, https://doi.org/10.1787/62ed0e04-en
My name is Felicity Keiper and I am participating in this forum as a representative of the Global Industry Coalition (GIC). I have participated in the risk assessment programs of work under the Cartagena Protocol since 2008, and I am a current member of the AHTEG on Risk Assessment and Risk Management and the multidisciplinary AHTEG on Synthetic Biology. I appreciate the opportunity to contribute to this work, and thank the Secretariat and moderator for supporting this online discussion series.
This is my first post in this discussion, and I will begin with general comments on Part A of the draft outline. This Part replicates the structure of a previous “Guidance” document developed over several years in risk assessment programs of work under the Cartagena Protocol (CP). We agree with the reservations expressed by many other participants about this approach (#11784, #11786, #11798, #11802, #11804, #11814, #11821, #11824, #11829, #11830). Firstly, because that document was never accepted or endorsed by CP Parties (see CP COP-MOP8 decision VIII/12). It is therefore not an authoritative source on risk assessment according to CP Annex III – at best, it is one source of existing relevant information amongst many other relevant sources. Secondly, because an “additional guidance material” is not another generic guidance or a recreation of what already exists, it should supplement this – this is indicated in the Term of Reference for the AHTEG (CP Decision 10/10) reproduced below:
“Develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol. A specific focus of this material should be engineered gene drive mosquitos taking into account the current experience with the organism, the type of gene drive and specific issues of risk assessment, identified in annex I to decision CP-9/13, including existing reports, general considerations of living modified organisms containing engineered gene drives, and existing national and regional risk assessment experiences.”
This Term of Reference frames the purpose of this work and its specific focus on EGD-LMO mosquitoes. It is evident in this discussion that there are different views on what the purpose is, with the views of #11824 and #11829 reflecting our understanding of the mandate: to provide information and examples of best practices that could be useful for informing risk assessment of EGD-LMO mosquitoes in accordance with Annex III. The purpose is not to prescribe how to do a risk assessment, conduct an actual risk assessment, or prescribe decision making.
Regarding “taking into account the current experience”, there is already a significant body of relevant work, as evidenced by the references contributed to this discussion (see #11792, #11793, #11794, #11803, #11814, #11817, #11820, #11821) and the extensive lists compiled from the information submissions and online discussions earlier this year (see the “synthesis” documents provided with this online discussion). For this work to supplement what already exists, it should specifically address any identified elements of Annex III for which “additional” guidance materials are warranted, i.e. they are lacking in existing relevant materials or they need updating.
We agree with the many other participants (e.g., #11786, #11793, #11795, #11816) that recommend restructuring of Part A. Key resources for this work have been cited, including the WHO Guidance Framework for Testing Genetically Modified Mosquitoes (2021, second edition) that specifically deals with phased testing and risk assessment of EGD-LMOs (#11820, #11829, #11830). Another key resource is the recently published OECD Consensus Document on Environmental Considerations for the Release of Transgenic Plants (OECD 2023; also referred to by #11801, #11802, #11820, #11830). This document presents a logical structure with key concepts for planning an environmental risk assessment, and it was developed over many years by regulators with extensive practical experience.
Reference: OECD (2023) Safety Assessment of Transgenic Organisms in the Environment, Volume 10: OECD Consensus Document on Environmental Considerations for the Release of Transgenic Plants, Harmonisation of Regulatory Oversight in Biotechnology, OECD Publishing, Paris, https://doi.org/10.1787/62ed0e04-en
My name is Christoph Then, this is my second post on this topic during this online forum. Thanks for picking up the discussion on next generation effects and cut-off criteria. It seems, further explanations are needed. It is not correct that the identification of uncertainties will make it generally impossible to derive to conclusions. Much more it is the level of uncertainty that has to be analysed in quantity and quality, to find out which further data would be needed, if these data can be made available and if the finally provided information will allow to draw robust conclusions.
In context of EGD-LMOS, there are specific challenges that have to be considered: There are typical characteristics of EGD-LMOs will cause a higher degree of uncertainty if compared to those from other gene drives or annual LMO crop plants. Some of these differences are summarized in a publication from 2020 (Then et al., 2020, https://doi.org/10.1002/ieam.4278). Relevant issues are for example the self-replication of the insertions of transgenes (or synthetic genes), a high number of crossings that is typically necessary to achieve the desired effect, potential releases into complex environments (in terms of potential biological interactions and abiotic factors), the biology of the target species (and its relative off-target species), heterogeneous genetic backgrounds (in target or also off-target species) and a lack of sufficient spatio-temporal control. These factors alone or in combination can cause a degree of uncertainty which makes it specifically challenging or impossible to reach to reliable conclusions. In our recent backgrounder (https://www.testbiotech.org/node/3037) we also show that some of these issues and related uncertainties are also highly relevant for the case of a ‘target malaria’ project on Anopheles gambiae.
In context of EGD-LMOS, there are specific challenges that have to be considered: There are typical characteristics of EGD-LMOs will cause a higher degree of uncertainty if compared to those from other gene drives or annual LMO crop plants. Some of these differences are summarized in a publication from 2020 (Then et al., 2020, https://doi.org/10.1002/ieam.4278). Relevant issues are for example the self-replication of the insertions of transgenes (or synthetic genes), a high number of crossings that is typically necessary to achieve the desired effect, potential releases into complex environments (in terms of potential biological interactions and abiotic factors), the biology of the target species (and its relative off-target species), heterogeneous genetic backgrounds (in target or also off-target species) and a lack of sufficient spatio-temporal control. These factors alone or in combination can cause a degree of uncertainty which makes it specifically challenging or impossible to reach to reliable conclusions. In our recent backgrounder (https://www.testbiotech.org/node/3037) we also show that some of these issues and related uncertainties are also highly relevant for the case of a ‘target malaria’ project on Anopheles gambiae.
My name is Felicity Keiper and I am participating in this forum as a representative of the Global Industry Coalition (GIC). I have made general comments on Part A on the draft outline in a previous post (#11847), and with this post I have specific comments on sections 1-3.
Section 1
Borrowing from the approach taken in the OECD Consensus Document (OECD, 2023), we suggest that Part A of the draft outline includes a “Purpose of the document” section, replacing the current section 1. This section should clearly set out what the document aims to do, consistent with the AHTEG Term of Reference in CP Decision 10/10 Annex para 1(d). As I described in my previous post, we believe that the purpose is to provide information and examples of best practices that could be useful for informing risk assessment of EGD-LMO mosquitoes in accordance with Annex III (in agreement with #11824 and #11829). We agree also with #11784 that this section should include a statement that these additional guidance materials are not intended to be prescriptive.
Section 2
We suggest that there are two (not three) sub sections in section 2:
2.1 “Annex III of the Cartagena Protocol” (per line 10); and
2.2 “Relevant existing guidance” (edit line 12).
Line 10: we suggest that this section (our proposed section 2.1) sets out the general principles in Annex III. This would assist with balanced consideration of themes that are emerging in this discussion such as disproportionate treatment of uncertainty and application of the precautionary approach/principle. In this vein, we do not support suggestions to incorporate “precautionary principle” into any of the section titles or having a standalone section dedicated to it. The scope of the guidance is informing risk assessment and not directing application of the precautionary approach and/or decision making.
Line 11: delete this dot point. As already noted, there are issues with relying on the previous Guidance document and there should be less emphasis on this source of information.
Section 3
Again, borrowing from the structure of the OECD Consensus Document (OECD, 2023), we suggest that sections 3 and 4 are merged into one “Planning an environmental risk assessment” section. This section would include the key overarching issues/considerations for EGD-LMO mosquitoes, as guided by Annex III.
Line 14: also discuss intended uses and likely receiving environments within this section.
Lines 15-16: we agree with suggestions that these concepts should be discussed together with the content currently in section 4.2 (per #11786, also #11820).
Lines 20-23: we support the consideration of uncertainty in the additional guidance, and strongly agree with others emphasizing that uncertainty is not unique to EGD-LMOs (#11792, #11794, #11798, #11802, #11814, #11821, #11829), that there is a need to draw from a range of sources to inform risk assessment, and that experience from other fields (e.g. biological and chemical control methods) and modelling may have important roles. We disagree with proposals for including “cut-off criteria” (per #11780, #11781, #11789, #11790, #11809, #11810) in connection with uncertainty and application of the “precautionary principle” – this is beyond risk assessment and directing decision making (as noted by #11801). We also do not support adding subjective language such as “limitations of” with reference to modelling to the section title (per #11809).
Reference: OECD (2023) Safety Assessment of Transgenic Organisms in the Environment, Volume 10: OECD Consensus Document on Environmental Considerations for the Release of Transgenic Plants, Harmonisation of Regulatory Oversight in Biotechnology, OECD Publishing, Paris, https://doi.org/10.1787/62ed0e04-en
Section 1
Borrowing from the approach taken in the OECD Consensus Document (OECD, 2023), we suggest that Part A of the draft outline includes a “Purpose of the document” section, replacing the current section 1. This section should clearly set out what the document aims to do, consistent with the AHTEG Term of Reference in CP Decision 10/10 Annex para 1(d). As I described in my previous post, we believe that the purpose is to provide information and examples of best practices that could be useful for informing risk assessment of EGD-LMO mosquitoes in accordance with Annex III (in agreement with #11824 and #11829). We agree also with #11784 that this section should include a statement that these additional guidance materials are not intended to be prescriptive.
Section 2
We suggest that there are two (not three) sub sections in section 2:
2.1 “Annex III of the Cartagena Protocol” (per line 10); and
2.2 “Relevant existing guidance” (edit line 12).
Line 10: we suggest that this section (our proposed section 2.1) sets out the general principles in Annex III. This would assist with balanced consideration of themes that are emerging in this discussion such as disproportionate treatment of uncertainty and application of the precautionary approach/principle. In this vein, we do not support suggestions to incorporate “precautionary principle” into any of the section titles or having a standalone section dedicated to it. The scope of the guidance is informing risk assessment and not directing application of the precautionary approach and/or decision making.
Line 11: delete this dot point. As already noted, there are issues with relying on the previous Guidance document and there should be less emphasis on this source of information.
Section 3
Again, borrowing from the structure of the OECD Consensus Document (OECD, 2023), we suggest that sections 3 and 4 are merged into one “Planning an environmental risk assessment” section. This section would include the key overarching issues/considerations for EGD-LMO mosquitoes, as guided by Annex III.
Line 14: also discuss intended uses and likely receiving environments within this section.
Lines 15-16: we agree with suggestions that these concepts should be discussed together with the content currently in section 4.2 (per #11786, also #11820).
Lines 20-23: we support the consideration of uncertainty in the additional guidance, and strongly agree with others emphasizing that uncertainty is not unique to EGD-LMOs (#11792, #11794, #11798, #11802, #11814, #11821, #11829), that there is a need to draw from a range of sources to inform risk assessment, and that experience from other fields (e.g. biological and chemical control methods) and modelling may have important roles. We disagree with proposals for including “cut-off criteria” (per #11780, #11781, #11789, #11790, #11809, #11810) in connection with uncertainty and application of the “precautionary principle” – this is beyond risk assessment and directing decision making (as noted by #11801). We also do not support adding subjective language such as “limitations of” with reference to modelling to the section title (per #11809).
Reference: OECD (2023) Safety Assessment of Transgenic Organisms in the Environment, Volume 10: OECD Consensus Document on Environmental Considerations for the Release of Transgenic Plants, Harmonisation of Regulatory Oversight in Biotechnology, OECD Publishing, Paris, https://doi.org/10.1787/62ed0e04-en
Dear all,
My name is Christophe Boëte and I am a research scientist based à the Institute of Evolutionary Science of Montpellier (ISEM), France and I have been nominated by the French goverment.
Thanks to the moderator and the secretariat for their work.
As the guidance is to be developed with a focus on mosquitoes carrying gene drives, I think it is important to mention that this comes with the particularity (among others) that their development is not only considered for their spread in space and time but with the aim to affect the epidemiology of malaria in the case of Anopheles. (see Boëte & Koella, Malaria Journal 2002)
Importantly they are often in a given location several species that are vectors of malaria (primary and secondary vectors) and that the current development for EGD for Anopheles mosquitoes are not targeting secondary vectors. This is an important aspect to be considered in the risk assessment as suppression or modification strategies of a major vector may lead to their replacement by so-called secondary vectors, potentially leading then to a reduced or no impact on malaria epidemiology. That is probably an uncertainty for EGD mosquitoes that is different from other LMOs.
Boëte, C., Koella, J.C. A theoretical approach to predicting the success of genetic manipulation of malaria mosquitoes in malaria control. Malar J 1, 3 (2002). https://doi.org/10.1186/1475-2875-1-3
My name is Christophe Boëte and I am a research scientist based à the Institute of Evolutionary Science of Montpellier (ISEM), France and I have been nominated by the French goverment.
Thanks to the moderator and the secretariat for their work.
As the guidance is to be developed with a focus on mosquitoes carrying gene drives, I think it is important to mention that this comes with the particularity (among others) that their development is not only considered for their spread in space and time but with the aim to affect the epidemiology of malaria in the case of Anopheles. (see Boëte & Koella, Malaria Journal 2002)
Importantly they are often in a given location several species that are vectors of malaria (primary and secondary vectors) and that the current development for EGD for Anopheles mosquitoes are not targeting secondary vectors. This is an important aspect to be considered in the risk assessment as suppression or modification strategies of a major vector may lead to their replacement by so-called secondary vectors, potentially leading then to a reduced or no impact on malaria epidemiology. That is probably an uncertainty for EGD mosquitoes that is different from other LMOs.
Boëte, C., Koella, J.C. A theoretical approach to predicting the success of genetic manipulation of malaria mosquitoes in malaria control. Malar J 1, 3 (2002). https://doi.org/10.1186/1475-2875-1-3
My name is Anke Hein. I have several years of experience in the area of LMO risk assessment and regulation and currently work for the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection. This is my first participation in the open ended online forum and I would like to thank for the opportunity to contribute to the discussions.
I would like to address some of the moderator’s questions.
Is the proposed format useful, with Part A containing the steps for RA of LMOS containing engineered gene drive and Part B presenting a case study?
If the temporal and spatial dimensions of LMOs containing gene drive are important aspects during risk assessment of this organism, are those being adequately captured with the proposed items?
The overall structure of the outline addresses general considerations EGD-LMO in Part A, chapter 3 which I support. From my point of view, it is necessary to add general considerations (line 13/14) on possible effects on ecosystems and biodiversity in section 3 and keep the focus on protection goals (line 15). In my view, this is essential in order to obtain a more comprehensive overview of possible adverse environmental impacts regarding the complexity of genetic changes, propagation and influence on ecological interactions, which challenges current risk assessment and methodology.
Part B: I agree in principle with various comments that extensive duplications in the guidance material are not generally required. However, there is a lack of experience with the release of GDO. EGD systems are very diverse and highly complex due to their self-propagation and possible further genetic evolution. Therefore, in my view, risk assessment cannot be based on conclusions from individual case studies at this time. Case studies should therefore be considered only as additional helpful information to complement the design of the risk assessment.
I would like to address some of the moderator’s questions.
Is the proposed format useful, with Part A containing the steps for RA of LMOS containing engineered gene drive and Part B presenting a case study?
If the temporal and spatial dimensions of LMOs containing gene drive are important aspects during risk assessment of this organism, are those being adequately captured with the proposed items?
The overall structure of the outline addresses general considerations EGD-LMO in Part A, chapter 3 which I support. From my point of view, it is necessary to add general considerations (line 13/14) on possible effects on ecosystems and biodiversity in section 3 and keep the focus on protection goals (line 15). In my view, this is essential in order to obtain a more comprehensive overview of possible adverse environmental impacts regarding the complexity of genetic changes, propagation and influence on ecological interactions, which challenges current risk assessment and methodology.
Part B: I agree in principle with various comments that extensive duplications in the guidance material are not generally required. However, there is a lack of experience with the release of GDO. EGD systems are very diverse and highly complex due to their self-propagation and possible further genetic evolution. Therefore, in my view, risk assessment cannot be based on conclusions from individual case studies at this time. Case studies should therefore be considered only as additional helpful information to complement the design of the risk assessment.
This is Brinda Dass from the Foundation for The National Institutes of Health. I have commented previously on this forum.
I would like to thank the moderator for providing additional framing of the discussion and respond more specifically to some of her points below-
- Is the proposed format useful, with Part A containing the steps for RA of LMOS containing engineered gene drive and Part B presenting a case study?
There has been quite some discussion on purpose of the guidelines (#11824, 11829, 11847) and I agree that we should abide by the terms of reference in the COP 10/10 document and keep to identifying information, data, and knowledge gaps and additional resource needs specific to risk assessment of EGD mosquitoes. There is no benefit to restating matters that are well delineated in Annex III as this is meant to be additional, voluntary guidance. The goal is not to instruct Parties on how to conduct a risk assessment but to point them to areas where EGD mosquitoes could be different from non-driving GM mosquitoes or other LMOs for risk assessment purposes as well as why and potential ways to address the assessment under such circumstances or differences. With that in mind I would suggest subsuming the case study of Anopheles (Part B) into the main text of the additional voluntary guidelines where it could inform as an exemplar among other types of GM mosquitoes to highlight differences between EGDMs and GMMs. Part A should be restricted to EGD mosquitos at a high level. The document should not be prescriptive as this would make it less effective to address a wide variety of gene drive types for case specific or case by case evaluations. It would also need to be revised potentially more often to retain utility as the science progresses.
If it is determined that EGD mosquitoes will be used as a case study in a separate Part B then care should be taken to highlight the areas of potential difference from existing non gene drive GM mosquitoes and LMOs rather than repeat Annex III contents.
- Considering the mandate from decision CP-10/10 with the special focus on engineered gene drive mosquitoes and the existence of international guidelines such as the WHO Guidance Framework for Testing Genetically Modified Mosquitoes, are the draft outline covering aspects related with the three objectives of the Convention and not duplicating the work?
The current draft outline (amended to have the scope described above as EGDM gaps with Anopheles as one possible exemplar) aligns overall with the standard risk assessment paradigm as described at a high level in Annex III and therefore relates well with the 3 objectives of the Convention. Again a plea to not repeat the basic process of conducting a risk assessment as that will remain the same for EGDMs and there is no need to reiterate (so there is not much to gain by having a section describing risk assessment methodology as suggested in #11840). Additionally, this point means that it also meets the needs to consider the Precautionary Principle as that undergirds the objectives of the Convention. Comments on this forum about using a tiered approach (e.g. WHO framework) and weight of evidence as well as looking to other fields that operate in deep uncertainty such as finance for examples of how best to navigate uncertainty in a new field with data paucity and low to no use history would similarly support being precautious. Thus there is limited utility to having a separate section on the Precautionary Principle and its application.
I would like to thank the moderator for providing additional framing of the discussion and respond more specifically to some of her points below-
- Is the proposed format useful, with Part A containing the steps for RA of LMOS containing engineered gene drive and Part B presenting a case study?
There has been quite some discussion on purpose of the guidelines (#11824, 11829, 11847) and I agree that we should abide by the terms of reference in the COP 10/10 document and keep to identifying information, data, and knowledge gaps and additional resource needs specific to risk assessment of EGD mosquitoes. There is no benefit to restating matters that are well delineated in Annex III as this is meant to be additional, voluntary guidance. The goal is not to instruct Parties on how to conduct a risk assessment but to point them to areas where EGD mosquitoes could be different from non-driving GM mosquitoes or other LMOs for risk assessment purposes as well as why and potential ways to address the assessment under such circumstances or differences. With that in mind I would suggest subsuming the case study of Anopheles (Part B) into the main text of the additional voluntary guidelines where it could inform as an exemplar among other types of GM mosquitoes to highlight differences between EGDMs and GMMs. Part A should be restricted to EGD mosquitos at a high level. The document should not be prescriptive as this would make it less effective to address a wide variety of gene drive types for case specific or case by case evaluations. It would also need to be revised potentially more often to retain utility as the science progresses.
If it is determined that EGD mosquitoes will be used as a case study in a separate Part B then care should be taken to highlight the areas of potential difference from existing non gene drive GM mosquitoes and LMOs rather than repeat Annex III contents.
- Considering the mandate from decision CP-10/10 with the special focus on engineered gene drive mosquitoes and the existence of international guidelines such as the WHO Guidance Framework for Testing Genetically Modified Mosquitoes, are the draft outline covering aspects related with the three objectives of the Convention and not duplicating the work?
The current draft outline (amended to have the scope described above as EGDM gaps with Anopheles as one possible exemplar) aligns overall with the standard risk assessment paradigm as described at a high level in Annex III and therefore relates well with the 3 objectives of the Convention. Again a plea to not repeat the basic process of conducting a risk assessment as that will remain the same for EGDMs and there is no need to reiterate (so there is not much to gain by having a section describing risk assessment methodology as suggested in #11840). Additionally, this point means that it also meets the needs to consider the Precautionary Principle as that undergirds the objectives of the Convention. Comments on this forum about using a tiered approach (e.g. WHO framework) and weight of evidence as well as looking to other fields that operate in deep uncertainty such as finance for examples of how best to navigate uncertainty in a new field with data paucity and low to no use history would similarly support being precautious. Thus there is limited utility to having a separate section on the Precautionary Principle and its application.
Further related to the moderator's comments related to points 1-3 of the proposed draft outline, my comments are below-
Section 1 to 3:
- Is there any aspect of uncertainty in the case of engineered gene drive LMOs that is different from other LMOs? What is the role of modeling, a tier-based testing approach and other tools to reduce uncertainty?
The aspect of overall uncertainty arises from this being the first time an LMO that is not self-limiting in some manner being proposed for testing which would necessitate a component of open release trial. The inability to include use history and a paucity of direct product derived data to address the dispersal, and temporal and spatial spread related risk hypotheses (due to no open field studies) makes for greater uncertainty in some pathways to harm when compared to existing LMOs. Performing an extensive pathway to harm exercise along with other methodologies such as expert elicitations and sensitivity analyses will support determining the range of uncertainty for critical steps in each pathway. The bounds on the uncertainty determinations will depend on factors such as the quality of evidence and whether it is direct or indirect allowing for precaution to be considered in the final analysis.
Modeling will allow the testing of a variety of assumptions and simulating different conditions which will again provide bounds for the possible outcomes. When used with tiered testing, assumptions can be tested and prior data can be updated with field derived data to strengthen the model and its results. Models for spread and dispersal are not uncommon in other fields such as plume modeling where results are used to inform decision making.
In summary, tiered testing, expert elicitation, probabilistic methods, models are all methodologies for navigating uncertainty with a goal to provide support for decision making. Reports from risk assessments are also at heart decision support tools.
Thanks
Brinda Dass, FNIH
Section 1 to 3:
- Is there any aspect of uncertainty in the case of engineered gene drive LMOs that is different from other LMOs? What is the role of modeling, a tier-based testing approach and other tools to reduce uncertainty?
The aspect of overall uncertainty arises from this being the first time an LMO that is not self-limiting in some manner being proposed for testing which would necessitate a component of open release trial. The inability to include use history and a paucity of direct product derived data to address the dispersal, and temporal and spatial spread related risk hypotheses (due to no open field studies) makes for greater uncertainty in some pathways to harm when compared to existing LMOs. Performing an extensive pathway to harm exercise along with other methodologies such as expert elicitations and sensitivity analyses will support determining the range of uncertainty for critical steps in each pathway. The bounds on the uncertainty determinations will depend on factors such as the quality of evidence and whether it is direct or indirect allowing for precaution to be considered in the final analysis.
Modeling will allow the testing of a variety of assumptions and simulating different conditions which will again provide bounds for the possible outcomes. When used with tiered testing, assumptions can be tested and prior data can be updated with field derived data to strengthen the model and its results. Models for spread and dispersal are not uncommon in other fields such as plume modeling where results are used to inform decision making.
In summary, tiered testing, expert elicitation, probabilistic methods, models are all methodologies for navigating uncertainty with a goal to provide support for decision making. Reports from risk assessments are also at heart decision support tools.
Thanks
Brinda Dass, FNIH
I would like to fully support the comments on the issue of uncertainty raised by #11848, #11844, #11834 and #11853 on the conceptual and biological novelties of gene drives in their design intention to spread and persist, with the aim of modifying entire populations of wild species. The added element of modifying disease vectors where potential issues such as niche-replacement may come into effect, distinguishes them from LMOs that have been assessed previously, as raised by Mr Boëte.
The self-spreading nature of gene drives also raises fundamental challenges to the ability to perform phased testing, as any release, even as part of a field trial, is effectively an open environmental release. This is further compounded by our inability to recall or reverse a gene drive organism. In the case of mosquitoes, pesticides would be the only current means to mitigate a release that has gone awry, and they have failed to date to eliminate mosquito populations. Any introgression of a gene drive construct into insecticide resistant populations would add yet more challenges to their removal.
Thanks
Eva, TWN
The self-spreading nature of gene drives also raises fundamental challenges to the ability to perform phased testing, as any release, even as part of a field trial, is effectively an open environmental release. This is further compounded by our inability to recall or reverse a gene drive organism. In the case of mosquitoes, pesticides would be the only current means to mitigate a release that has gone awry, and they have failed to date to eliminate mosquito populations. Any introgression of a gene drive construct into insecticide resistant populations would add yet more challenges to their removal.
Thanks
Eva, TWN
In response to novelty of EGDMs with regard to potential niche replacement as it relates to disease vectoring mosquito species management and genetically modified mosquitoes I would posit that there is extended experience from the use of GM SIT Aedes aegypti in Brazil (both field trial/experimental use and direct to consumer product use that is more current in terms of product use and availability). Evidence does not suggest that suppression of Ae. aegypti has resulted in niche replacement with other Aedes species such as Ae. albopictus.
Pest Manag Sci. 2016 Mar; 72(3): 618–628.
Published online 2015 Oct 16. doi: 10.1002/ps.4151
Thanks again
brinda dass, FNIH
Pest Manag Sci. 2016 Mar; 72(3): 618–628.
Published online 2015 Oct 16. doi: 10.1002/ps.4151
Thanks again
brinda dass, FNIH
Greetings to all, I am Lim Li Ching from the Third World Network. I’ve been active in biosafety discussions since the 3rd meeting of the Intergovernmental Committee for the Cartagena Protocol on Biosafety in 2002. I am a previous member of the AHTEGs on Synthetic Biology and on Socio-economic Considerations.
Thank you for the opportunity to participate in this discussion, and to the Moderator and Secretariat.
I agree with comments (e.g. #11834, #11837, # 11840) that it would be good to specifically reference the ‘Guidance on risk assessment for living modified organisms and monitoring in the context of risk assessment’ and the ‘Roadmap for risk assessment of living modified organisms’, given that the mandate for the development of the guidance on EGD-LMOs comes from the Parties to the Protocol.
- With due respect to comments #11784 and #11814, the Guidance is NOT a draft, and as elaborated by #11834, #11837, there is a history where the same Parties have variously welcomed, taken note of, and invited its use and taking into account to assist Parties in conducting risk assessment in accordance with the Cartagena Protocol.
- While appreciating the reference to other relevant guidance (line 12) and the useful resources shared by many participants, to my knowledge, the Guidance and Roadmap are the only documents specifically developed to be consistent with the provisions and Annex III of the Protocol. They should therefore be specified in Lines 11 and 37 of the draft outline.
- And I simply echo others’ comments that this is not an exercise of duplication of content, for there will be specific considerations, risks and uncertainties related to EGD-LMOs, while using the framing provided by the Protocol.
May I add that the mandate given is to “develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol” and that “A specific focus of this material should be engineered gene drive mosquitos…”.
- Thus, I also wonder, like #11839, #11854 and #11856 why there seems to be a narrowing or restricting to a specific case study of Anopheles mosquitoes in Part B, as merely focusing on this one case study may not be fully instructive to risk assessment of EGD-LMOs, or other gene drive mosquitos.
I also agree with #11834 and #11840 that it would be pertinent to refer to other relevant COP decisions in line 8, some of which specifically address EGD-LMOs (for e.g. Decision 14/19) and others within the context of the Convention’s discussions on synthetic biology (e.g. Decision XII/24, Decision XIII/17).
Setting the objective and scope with the above points in mind, would lead to considerations of risk assessment of EGD-LMOs that are contextually aligned with the Protocol, and the relevant COP and COP-MOP decisions.
- As such, I agree with #11797; the Cartagena Protocol squarely addresses adverse effects and risks, and does not lay down any provisions on balancing risk acceptability with potential benefits (“risks vs. benefits”). So, like #11810, I think line 97 can be deleted, as the issue of acceptability of risks is captured in Step 5. Consideration of benefits, if at all, must be based on an assessment of claims of benefits and not merely on unevidenced goals and/or claims by developers of potential benefits – this is an aspect noted by the AHTEG on Socioeconomic Considerations in its ‘Guidance on the Assessment of Socio-Economic Considerations in the Context of Article 26 of the Cartagena Protocol on Biosafety”.
- Further, related issues of socio-economic considerations, including as specified variously in COP decisions as socio-economic, cultural and ethical considerations, and the free, prior and informed consent of indigenous peoples and local communities or the national equivalent, need to be well elaborated in Section 6.
Thank you and kind regards.
Thank you for the opportunity to participate in this discussion, and to the Moderator and Secretariat.
I agree with comments (e.g. #11834, #11837, # 11840) that it would be good to specifically reference the ‘Guidance on risk assessment for living modified organisms and monitoring in the context of risk assessment’ and the ‘Roadmap for risk assessment of living modified organisms’, given that the mandate for the development of the guidance on EGD-LMOs comes from the Parties to the Protocol.
- With due respect to comments #11784 and #11814, the Guidance is NOT a draft, and as elaborated by #11834, #11837, there is a history where the same Parties have variously welcomed, taken note of, and invited its use and taking into account to assist Parties in conducting risk assessment in accordance with the Cartagena Protocol.
- While appreciating the reference to other relevant guidance (line 12) and the useful resources shared by many participants, to my knowledge, the Guidance and Roadmap are the only documents specifically developed to be consistent with the provisions and Annex III of the Protocol. They should therefore be specified in Lines 11 and 37 of the draft outline.
- And I simply echo others’ comments that this is not an exercise of duplication of content, for there will be specific considerations, risks and uncertainties related to EGD-LMOs, while using the framing provided by the Protocol.
May I add that the mandate given is to “develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol” and that “A specific focus of this material should be engineered gene drive mosquitos…”.
- Thus, I also wonder, like #11839, #11854 and #11856 why there seems to be a narrowing or restricting to a specific case study of Anopheles mosquitoes in Part B, as merely focusing on this one case study may not be fully instructive to risk assessment of EGD-LMOs, or other gene drive mosquitos.
I also agree with #11834 and #11840 that it would be pertinent to refer to other relevant COP decisions in line 8, some of which specifically address EGD-LMOs (for e.g. Decision 14/19) and others within the context of the Convention’s discussions on synthetic biology (e.g. Decision XII/24, Decision XIII/17).
Setting the objective and scope with the above points in mind, would lead to considerations of risk assessment of EGD-LMOs that are contextually aligned with the Protocol, and the relevant COP and COP-MOP decisions.
- As such, I agree with #11797; the Cartagena Protocol squarely addresses adverse effects and risks, and does not lay down any provisions on balancing risk acceptability with potential benefits (“risks vs. benefits”). So, like #11810, I think line 97 can be deleted, as the issue of acceptability of risks is captured in Step 5. Consideration of benefits, if at all, must be based on an assessment of claims of benefits and not merely on unevidenced goals and/or claims by developers of potential benefits – this is an aspect noted by the AHTEG on Socioeconomic Considerations in its ‘Guidance on the Assessment of Socio-Economic Considerations in the Context of Article 26 of the Cartagena Protocol on Biosafety”.
- Further, related issues of socio-economic considerations, including as specified variously in COP decisions as socio-economic, cultural and ethical considerations, and the free, prior and informed consent of indigenous peoples and local communities or the national equivalent, need to be well elaborated in Section 6.
Thank you and kind regards.
My name is Marja Ruohonen-Lehto, and I have more than 25 years of experience with biosafety and LMO risk assessments. I work for the Finnish Government, and I am a previous and present member of the RARM AHTEG. Many thanks to the Secretariat and Luciana for facilitating and providing useful questions to keep us focused.
I have followed this discussion with great interest. I am especially thankful for the comments that have provided information on e.g., how to assess uncertainty; what are the possibilities and at the same time challenges of modelling, what are the unique characteristics of organisms containing engineered gene drives; what has been decided in the previous COP-MOP meetings, and the development process of the voluntary risk assessment guidance.
It is also important to remember what the COP-MOP10 decision says in its annex, point c: “Develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol. A specific focus of this material should be engineered gene drive mosquitos taking into account the current experience with the organism, the type of gene drive and specific issues of risk assessment, identified in annex I to decision CP-9/13, including existing reports, general considerations of living modified organisms containing engineered gene drives, and existing national and regional risk assessment experiences”.
Many thanks for all the thoughtful comments, additional information, and useful references.
I have followed this discussion with great interest. I am especially thankful for the comments that have provided information on e.g., how to assess uncertainty; what are the possibilities and at the same time challenges of modelling, what are the unique characteristics of organisms containing engineered gene drives; what has been decided in the previous COP-MOP meetings, and the development process of the voluntary risk assessment guidance.
It is also important to remember what the COP-MOP10 decision says in its annex, point c: “Develop additional voluntary guidance materials for conducting case-by-case risk assessments of living modified organisms containing engineered gene drives in accordance with Annex III to the Protocol. A specific focus of this material should be engineered gene drive mosquitos taking into account the current experience with the organism, the type of gene drive and specific issues of risk assessment, identified in annex I to decision CP-9/13, including existing reports, general considerations of living modified organisms containing engineered gene drives, and existing national and regional risk assessment experiences”.
Many thanks for all the thoughtful comments, additional information, and useful references.
My name is Thato Mogapi from the Department of Forestry, Fisheries and the Environment in South Africa. Thank you for the opportunity to participate on this forum and make input on the draft outline of the additional voluntary guidance materials.
Firstly just to provide a general comment. Having considered para c of the terms of reference for the AHTEG, it is our understanding that as a voluntary document, the additional guidance materials are intended to supplement existing guidance. Given that this should be conducted in accordance with Annex III, notwithstanding the fact that the COPMOP8 guidance was “noted” as a voluntary guidance document, we support suggestions that it can serve as a starting point as we have found some elements contained therein useful for LM crops, such as the problem formulation aspects. However, and as pointed out by others on the forum, the nature of EGD-LMOs and their risk profile is such that they go beyond the scope of Annex III. Thus, there is a need to draw from best practices for conducting a risk assessment under other processes. This is where guidelines such as the World Health Organisation’s “Guidance framework for testing genetically modified mosquitoes, second edition” and regional guidelines such as the AUDA-NEPAD Guidelines for Risk Analysis for the Testing and Deployment of Genetically Modified Mosquitoes are useful resources to support this process. Furthermore, given the similarities with the some of the intended applications of EGD-LMOs, consideration should also be given to existing risk analysis frameworks applied for release of biological control agents, as pointed out by others (The relevant International Standards for Phytosanitary Measures (ISPMs) of the International Plant Protection Convention). The additional guidance can reflect on various risk assessment concepts without duplicating what is contained in other guidance material.
References
Guidance framework for testing genetically modified mosquitoes, second edition. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO.
African Union Development Agency - NEPAD. 2022. Guidelines for Risk Analysis for the Testing and Deployment of Genetically Modified Mosquitoes. AUDA-NEPAD, Midrand, South Africa.
Firstly just to provide a general comment. Having considered para c of the terms of reference for the AHTEG, it is our understanding that as a voluntary document, the additional guidance materials are intended to supplement existing guidance. Given that this should be conducted in accordance with Annex III, notwithstanding the fact that the COPMOP8 guidance was “noted” as a voluntary guidance document, we support suggestions that it can serve as a starting point as we have found some elements contained therein useful for LM crops, such as the problem formulation aspects. However, and as pointed out by others on the forum, the nature of EGD-LMOs and their risk profile is such that they go beyond the scope of Annex III. Thus, there is a need to draw from best practices for conducting a risk assessment under other processes. This is where guidelines such as the World Health Organisation’s “Guidance framework for testing genetically modified mosquitoes, second edition” and regional guidelines such as the AUDA-NEPAD Guidelines for Risk Analysis for the Testing and Deployment of Genetically Modified Mosquitoes are useful resources to support this process. Furthermore, given the similarities with the some of the intended applications of EGD-LMOs, consideration should also be given to existing risk analysis frameworks applied for release of biological control agents, as pointed out by others (The relevant International Standards for Phytosanitary Measures (ISPMs) of the International Plant Protection Convention). The additional guidance can reflect on various risk assessment concepts without duplicating what is contained in other guidance material.
References
Guidance framework for testing genetically modified mosquitoes, second edition. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO.
African Union Development Agency - NEPAD. 2022. Guidelines for Risk Analysis for the Testing and Deployment of Genetically Modified Mosquitoes. AUDA-NEPAD, Midrand, South Africa.
My name is Thato Mogapi from the Department of Forestry, Fisheries and the Environment in South Africa. I have already posted a general comment on this topic. With regards to the structure for sections 1 to 3, we suggest a slight restructuring as follows:
• Suggest introducing a Background Section which briefly provides background on relevant decisions, including CP-10/10 and other relevant paragraphs in decisions on EGD-LMOs, in particular, those on the precautionary approach and undertaking risk assessment.
• The current Section 1. Objective and scope of these additional voluntary guidance materials (line 7) would be best placed last (as section 3) before the “Overarching issues in the risk assessment process on EGD-LMOs”. The Objective and scope should be as articulated in para c of the terms of reference for the AHTEG, including clarifying how other existing guidance documents from other processes will be used and what the additional guidance will not cover.
• The current Section 2. Introduction (line 9) can follow the background suggested above. This section can focus on introducing EGD-LMOs, including the gene drive concept and terminology (currently line 14), types of application, modern biotechnology techniques used to develop EGD-LMOs; risk assessment approaches, including relevant guidance under the Cartagena Protocol (line 10-11) and from other processes (line 12).
• The subsections under the current Section 3. Overarching issues in the risk assessment process on EGD-LMOs (line 13) should avoid duplication with what is contained in other guidance documents and should focus only on novel features relevant to EGD-LMOs. The point on “engineered gene drive terminology, types and general characteristics” (line 14) should rather go to the introduction as suggested above. Section 3.1 on Protection goals, assessment endpoints and measurement endpoints (line 15) may not need to be discussed here but rather under section 4. Planning phase of the risk assessment of EGD-LMOs (line 24), already focusing on aspects relevant to EGD-LMOs. Definitions or description of terms or concepts can be placed in text boxes or footnotes if need be. For section 3.3. Identification and consideration of uncertainty (line 20), levels of uncertainty should be determined at every step of the risk assessment taking into consideration available evidence from various sources as well as identified gaps. As pointed out by others, the guidance should provide information on how uncertainty can be addressed, drawing from other processes and experiences, including how to set criteria to determine degree of uncertainty to guide decision-making.
• Suggest introducing a Background Section which briefly provides background on relevant decisions, including CP-10/10 and other relevant paragraphs in decisions on EGD-LMOs, in particular, those on the precautionary approach and undertaking risk assessment.
• The current Section 1. Objective and scope of these additional voluntary guidance materials (line 7) would be best placed last (as section 3) before the “Overarching issues in the risk assessment process on EGD-LMOs”. The Objective and scope should be as articulated in para c of the terms of reference for the AHTEG, including clarifying how other existing guidance documents from other processes will be used and what the additional guidance will not cover.
• The current Section 2. Introduction (line 9) can follow the background suggested above. This section can focus on introducing EGD-LMOs, including the gene drive concept and terminology (currently line 14), types of application, modern biotechnology techniques used to develop EGD-LMOs; risk assessment approaches, including relevant guidance under the Cartagena Protocol (line 10-11) and from other processes (line 12).
• The subsections under the current Section 3. Overarching issues in the risk assessment process on EGD-LMOs (line 13) should avoid duplication with what is contained in other guidance documents and should focus only on novel features relevant to EGD-LMOs. The point on “engineered gene drive terminology, types and general characteristics” (line 14) should rather go to the introduction as suggested above. Section 3.1 on Protection goals, assessment endpoints and measurement endpoints (line 15) may not need to be discussed here but rather under section 4. Planning phase of the risk assessment of EGD-LMOs (line 24), already focusing on aspects relevant to EGD-LMOs. Definitions or description of terms or concepts can be placed in text boxes or footnotes if need be. For section 3.3. Identification and consideration of uncertainty (line 20), levels of uncertainty should be determined at every step of the risk assessment taking into consideration available evidence from various sources as well as identified gaps. As pointed out by others, the guidance should provide information on how uncertainty can be addressed, drawing from other processes and experiences, including how to set criteria to determine degree of uncertainty to guide decision-making.
Subject: Draft does not appear to explicitly link risk assessment documents to how they are linked to key articles of the treaty (specifically 4, 17, 25 and 27) this is problematic and a missed opportunity.
My name is Dr. Guy Reeves, from the Max Planck Institute for Evolutionary biology (Germany), I am an evolutionary biologist with interests in viral techniques intended for environmental modification. I am an inventor on a granted patent related to gene drive (EP2934093B1).
While I certainly acknowledge that the Cartagena Protocol on Biosafety is seen as a source of information on risk assessments, the fact is that a fundamental purpose of the text of the treaty is focused on establishing a detailed procedural framework to ensure parties can take sovereign decisions on wether to allow the import and environmental release of LMO /EGD-LM s in its territory (page 674 Beck 2021). The importance of the Cartagena Protocol in protecting the environment (and sovereignty? ) in the context of gene drive is repeated and long standing, well preceding the following the example
Marshall, John M. 2010. ‘The Cartagena Protocol and Genetically Modified Mosquitoes’. Nature Biotechnology 28 (9): 896–97. https://doi.org/10.1038/nbt0910-896.
Clearly the focus of the “DRAFT OUTLINE ” is risk assessment, but failing to resolve how and risk assessment documents are important to the treaty aims represents a missed opportunity .
Examples of Fundamentally Transboundary and timely notification articles of the treaty-
-article 4
This Protocol shall apply to the transboundary movement, transit, handling and use of all living modified organisms that may have adverse effects on the conservation and sustainable use of biological diversity, taking also into account risks to human health.
-also article 14 , article 17 , article 20 and article 25
The opportunity to explicitly describe how and in what circumstances the Cartagena Protocol (through the generation of risk assessments ) can be used to protect the environment and sovereignty should not be missed (and how the drafting of risk assessments need to be informed by this). Certainly not to largely regenerate documents that have already been published by the World Health Organization, the Secretariat of the Convention on Biological Diversity, Perseus, National Academies of Sciences, Engineering, and Medicine, Australian Office of the Gene Technology Regulator, Australian Academy of Sciences, European Food Safety Authority, UNEP/CBD/BS/COP-MOP/8/8/Add.1 ….among others.
Despite the value of the text of the Cartagena Protocol on Biosafety, there is a continued drift away from the text of the treaty, —and how and when it is important—. For example are the notification requirements and when are they manifest . This can arguably be reflected in insightful comments of Mr. Pieter van der Meery #11784
“It is good that the document stays at many places close to the actual language of the CPB, but there are other places where that should be strengthened.”
I agree with the need to further strengthen the language. Specifically, I would like to see separate headings of sections of part A with treaty articles and how they shape risk assessments ( eg article 4, article 14 , article 17 , article 20 and article 25)
The drift away from the text of the treaty, —and how and when it is important- is apparent in the “DRAFT OUTLINE ” and also in comments to the forum. For example.
“Adam Cornish #11819 which
Section 10.2. Step 2: What is the purpose of including unintentional transboundary movements of an EGD-LM Mosquito in the guidance materials? First, Section 10.2 is focused on unintended effects to biological diversity, which is unrelated to the presence of geographical boundaries. Second, this guidance is intended to provide risk assessment best practices specific to EGD-LM Mosquito – risk management related to unintentional transboundary movement of LMOs is already covered under Article 16 of the Protocol. We do not believe that there are characteristics unique to EGD-LM Mosquito that would require additional guidance. “
Personally, I would say that without considering how risk assessment documents need to be shaped by at least article 4, article 14 , article 17 , article 20 and article 25 (transboundary movement and notification), the value of the documents will be diminished. In this light I would expand consideration of transboundary movement in Part B and more importantly extensively frame this discussion in Part A.
General reference Chapter 3 and summary of results section
Beck, Felix. 2022. Self-Spreading Biotechnology and International Law: Prevention, Responsibility, and Liability in a Transboundary Context. 1st edition. Beiträge Zum Ausländischen Öffentlichen Recht Und Völkerrecht, volume 316. Baden-Baden: Nomos. https://doi.org/10.5771/9783748913528.
My name is Dr. Guy Reeves, from the Max Planck Institute for Evolutionary biology (Germany), I am an evolutionary biologist with interests in viral techniques intended for environmental modification. I am an inventor on a granted patent related to gene drive (EP2934093B1).
While I certainly acknowledge that the Cartagena Protocol on Biosafety is seen as a source of information on risk assessments, the fact is that a fundamental purpose of the text of the treaty is focused on establishing a detailed procedural framework to ensure parties can take sovereign decisions on wether to allow the import and environmental release of LMO /EGD-LM s in its territory (page 674 Beck 2021). The importance of the Cartagena Protocol in protecting the environment (and sovereignty? ) in the context of gene drive is repeated and long standing, well preceding the following the example
Marshall, John M. 2010. ‘The Cartagena Protocol and Genetically Modified Mosquitoes’. Nature Biotechnology 28 (9): 896–97. https://doi.org/10.1038/nbt0910-896.
Clearly the focus of the “DRAFT OUTLINE ” is risk assessment, but failing to resolve how and risk assessment documents are important to the treaty aims represents a missed opportunity .
Examples of Fundamentally Transboundary and timely notification articles of the treaty-
-article 4
This Protocol shall apply to the transboundary movement, transit, handling and use of all living modified organisms that may have adverse effects on the conservation and sustainable use of biological diversity, taking also into account risks to human health.
-also article 14 , article 17 , article 20 and article 25
The opportunity to explicitly describe how and in what circumstances the Cartagena Protocol (through the generation of risk assessments ) can be used to protect the environment and sovereignty should not be missed (and how the drafting of risk assessments need to be informed by this). Certainly not to largely regenerate documents that have already been published by the World Health Organization, the Secretariat of the Convention on Biological Diversity, Perseus, National Academies of Sciences, Engineering, and Medicine, Australian Office of the Gene Technology Regulator, Australian Academy of Sciences, European Food Safety Authority, UNEP/CBD/BS/COP-MOP/8/8/Add.1 ….among others.
Despite the value of the text of the Cartagena Protocol on Biosafety, there is a continued drift away from the text of the treaty, —and how and when it is important—. For example are the notification requirements and when are they manifest . This can arguably be reflected in insightful comments of Mr. Pieter van der Meery #11784
“It is good that the document stays at many places close to the actual language of the CPB, but there are other places where that should be strengthened.”
I agree with the need to further strengthen the language. Specifically, I would like to see separate headings of sections of part A with treaty articles and how they shape risk assessments ( eg article 4, article 14 , article 17 , article 20 and article 25)
The drift away from the text of the treaty, —and how and when it is important- is apparent in the “DRAFT OUTLINE ” and also in comments to the forum. For example.
“Adam Cornish #11819 which
Section 10.2. Step 2: What is the purpose of including unintentional transboundary movements of an EGD-LM Mosquito in the guidance materials? First, Section 10.2 is focused on unintended effects to biological diversity, which is unrelated to the presence of geographical boundaries. Second, this guidance is intended to provide risk assessment best practices specific to EGD-LM Mosquito – risk management related to unintentional transboundary movement of LMOs is already covered under Article 16 of the Protocol. We do not believe that there are characteristics unique to EGD-LM Mosquito that would require additional guidance. “
Personally, I would say that without considering how risk assessment documents need to be shaped by at least article 4, article 14 , article 17 , article 20 and article 25 (transboundary movement and notification), the value of the documents will be diminished. In this light I would expand consideration of transboundary movement in Part B and more importantly extensively frame this discussion in Part A.
General reference Chapter 3 and summary of results section
Beck, Felix. 2022. Self-Spreading Biotechnology and International Law: Prevention, Responsibility, and Liability in a Transboundary Context. 1st edition. Beiträge Zum Ausländischen Öffentlichen Recht Und Völkerrecht, volume 316. Baden-Baden: Nomos. https://doi.org/10.5771/9783748913528.
My name is Lilian Chimphepo, working under the Ministry of Natural Resources and Climate Change in Malawi. Serving as the Biosafety Registrar for over seven years and also serving as a National Focal Point for the Cartagena Protocol on Biosafety.
Topic 1. Part A, Section 1-3
The proposed outline is covering very important introductory information that will help to direct the user well. I would like to make the following proposition for consideration, I have been following the contributions with keen interest. I would like to appreciate the inclusion of uncertainties considering that we are dealing with engineered gene drives with limited history of safe use, if appropriate, I proposed to include qualification of uncertainties using modelling methodologies and also including monitoring of uncertainties. Once uncertainties have been identified it is important to monitor them for any adverse effects
On subtopic 3.1. Protection goals, assessment endpoints and measurement endpoints
Line 16 ‘’ Descriptions of these relevant concept” it may be important not only to describe the concept but also to explain their relevance and how they are determined.
on Topic 2, Part A Section 4-6
Regarding Step 5. on recommendation as to whether or not the risks are acceptable or manageable, there may be need to include risk communication as one of the sub-topics under this heading. Risk communication is very important even as we engage stakeholders in risk assessment, and it foster transparency and help to build trust.
Thank you
Topic 1. Part A, Section 1-3
The proposed outline is covering very important introductory information that will help to direct the user well. I would like to make the following proposition for consideration, I have been following the contributions with keen interest. I would like to appreciate the inclusion of uncertainties considering that we are dealing with engineered gene drives with limited history of safe use, if appropriate, I proposed to include qualification of uncertainties using modelling methodologies and also including monitoring of uncertainties. Once uncertainties have been identified it is important to monitor them for any adverse effects
On subtopic 3.1. Protection goals, assessment endpoints and measurement endpoints
Line 16 ‘’ Descriptions of these relevant concept” it may be important not only to describe the concept but also to explain their relevance and how they are determined.
on Topic 2, Part A Section 4-6
Regarding Step 5. on recommendation as to whether or not the risks are acceptable or manageable, there may be need to include risk communication as one of the sub-topics under this heading. Risk communication is very important even as we engage stakeholders in risk assessment, and it foster transparency and help to build trust.
Thank you
Dear all,
Many thanks to the moderator and the CBDSec for extending the deadline for this on-line debate. The exchanges since the previous deadline show that this extra time was worthwhile.
I take this extra time to share some general observations. I post these general observations under topic 1, but they apply equally to the other topics. (I add a side note that I hope that next on-line debates will have a ‘general’ thread where we can share generic observations).
A first general observation relates to the suggestions that the guidance materials should reference and/or copy parts of the guidance that despite many years of work under COPMOP was not endorsed by COPMOP. I believe that there are compelling procedural, substantive and pragmatic arguments not to do so.
The procedural argument is that for guidance to be ‘guidance under the Cartagena Protocol’ it will have to have been endorsed by COPMOP. As we all know, COPMOP did not endorse that guidance, but rather ‘took note of’ the existence of that guidance and ended that particular process.
The substantive argument is that the 2016 COPMOP discussions made clear that several delegations were of the view that that guidance was a mix of useful parts, not so useful parts, confusing parts, and parts that were not consistent with the CPB and/or accumulated experience, which is not a good basis to base further discussions on.
The pragmatic argument is that one of the reasons why the process on the earlier guidance - which had started with great enthusiasm, mine included - stranded in COPMOP2016 is because the whole process had ballooned from a straightforward ‘roadmap’, which was an excellent suggestion from the Dutch delegation, into a document that tried to address too many things inside and outside risk assessment. COPMOP2018 and COPMOP 2020 are therefore to be commended to make this a well-delineated exercise that focuses on risk assessment, that within the field of risk assessment focuses on gene drives, that within the field of gene drives focuses on a specifically described category of gene drives, and that asks for guidance materials, not to develop guidance as such.
I believe that if we want to get something tangible out of this process and avoid COPMOP2016 situations , we must keep that focus. This means first of all focusing on risk assessment and not including things that are – although very important in their own right - not part of risk assessment, such as the precautionary approach (which is – although based on risk assessment - about decision making/risk management and not about risk assessment itself), article 26 (which is about decision making) et cetera.
In short, I would urge to give this process a chance of success by staying focused on what COPMOP has asked, i.e. guidance materials to aid case-by-case risk assessment for mosquitoes with engineered gene drives. I commend the colleagues who did exactly that, e.g. suggesting guidance materials such as information on possible comparators.
A second general observation relates to the comments that talked about gene drives ‘aimed at modifying/eradicating species’. To keep matters focused, we should remember that we are talking about applications aimed at modifying/eradicating populations, not entire species.
A third general observation relates to comments that Annex III on risk assessment was not drafted with the concept of gene drives in mind, and that Annex III is therefore of limited or no use. These are incorrect assumptions. Those of you who, like I, participated in the negotiations on Annex III will remember that the notion of applications aimed at influencing species were very much part of the scientific discussions underpinning Annex III. Examples such as the application of myxomatosis for rabbit control and many forms of biological pest control in agriculture were frequently used in discussing and testing the robustness of Annex III. The conclusion of those exercises was invariably that the methodology of risk assessment as outlined in Annex III can also be applied to cases of LMOs aimed at modifying or eradicating populations.
That said, it is certainly true is that the information needed to make informed conclusions in gene drive cases is clearly different from, for example, a case of Bt maize. This is why additional guidance materials will be very welcome.
Best regards to all!
Piet van der Meer
Many thanks to the moderator and the CBDSec for extending the deadline for this on-line debate. The exchanges since the previous deadline show that this extra time was worthwhile.
I take this extra time to share some general observations. I post these general observations under topic 1, but they apply equally to the other topics. (I add a side note that I hope that next on-line debates will have a ‘general’ thread where we can share generic observations).
A first general observation relates to the suggestions that the guidance materials should reference and/or copy parts of the guidance that despite many years of work under COPMOP was not endorsed by COPMOP. I believe that there are compelling procedural, substantive and pragmatic arguments not to do so.
The procedural argument is that for guidance to be ‘guidance under the Cartagena Protocol’ it will have to have been endorsed by COPMOP. As we all know, COPMOP did not endorse that guidance, but rather ‘took note of’ the existence of that guidance and ended that particular process.
The substantive argument is that the 2016 COPMOP discussions made clear that several delegations were of the view that that guidance was a mix of useful parts, not so useful parts, confusing parts, and parts that were not consistent with the CPB and/or accumulated experience, which is not a good basis to base further discussions on.
The pragmatic argument is that one of the reasons why the process on the earlier guidance - which had started with great enthusiasm, mine included - stranded in COPMOP2016 is because the whole process had ballooned from a straightforward ‘roadmap’, which was an excellent suggestion from the Dutch delegation, into a document that tried to address too many things inside and outside risk assessment. COPMOP2018 and COPMOP 2020 are therefore to be commended to make this a well-delineated exercise that focuses on risk assessment, that within the field of risk assessment focuses on gene drives, that within the field of gene drives focuses on a specifically described category of gene drives, and that asks for guidance materials, not to develop guidance as such.
I believe that if we want to get something tangible out of this process and avoid COPMOP2016 situations , we must keep that focus. This means first of all focusing on risk assessment and not including things that are – although very important in their own right - not part of risk assessment, such as the precautionary approach (which is – although based on risk assessment - about decision making/risk management and not about risk assessment itself), article 26 (which is about decision making) et cetera.
In short, I would urge to give this process a chance of success by staying focused on what COPMOP has asked, i.e. guidance materials to aid case-by-case risk assessment for mosquitoes with engineered gene drives. I commend the colleagues who did exactly that, e.g. suggesting guidance materials such as information on possible comparators.
A second general observation relates to the comments that talked about gene drives ‘aimed at modifying/eradicating species’. To keep matters focused, we should remember that we are talking about applications aimed at modifying/eradicating populations, not entire species.
A third general observation relates to comments that Annex III on risk assessment was not drafted with the concept of gene drives in mind, and that Annex III is therefore of limited or no use. These are incorrect assumptions. Those of you who, like I, participated in the negotiations on Annex III will remember that the notion of applications aimed at influencing species were very much part of the scientific discussions underpinning Annex III. Examples such as the application of myxomatosis for rabbit control and many forms of biological pest control in agriculture were frequently used in discussing and testing the robustness of Annex III. The conclusion of those exercises was invariably that the methodology of risk assessment as outlined in Annex III can also be applied to cases of LMOs aimed at modifying or eradicating populations.
That said, it is certainly true is that the information needed to make informed conclusions in gene drive cases is clearly different from, for example, a case of Bt maize. This is why additional guidance materials will be very welcome.
Best regards to all!
Piet van der Meer
Dear all, I'm Carolina Torres Trueba, from Ecuador, representing Island Conservation, an international NGO dedicated to eradicating invasive species and restoring fragile ecosystems on islands. I have been following the dialogue of SynBio and Risk Assessment since 2015. I want to thank the Secretariat for creating the opportunity for further discussion on this forum. Most of what I wanted to say and share has already been posted by different people. I want to support comments #11820, #11830, #11829, #11814. Uncertainty is a common factor in any risk assessment process, not unique to gene drive technologies. Similar to other Living Modified Organisms (LMOs), the degree of uncertainty is intrinsically linked to the quality and comprehensiveness of data available. The level of confidence in risk assessment outcomes improves as the quality of data increases, effectively reducing uncertainty.
Greetings again all,
Thanks to all participants for their thoughtful contributions and references! I’m coming in under the wire with a final response as the forum is closing in mere minutes. I’ll keep it short. Allow me, for whatever weight it is worth, just to say I broadly support the contributions made since my last post of Hector Quemada (#11821), Karen Hokanson (#11824), Robert Friedman (#11829), Eder Toppa (#11830), Felicity Keiper (#11847, #11849), Brinda Dass (#11857, #11858), and Thato Mogapi (#11865).
Kind regards to all,
Aaron Roberts
IEPI, McMaster University
Thanks to all participants for their thoughtful contributions and references! I’m coming in under the wire with a final response as the forum is closing in mere minutes. I’ll keep it short. Allow me, for whatever weight it is worth, just to say I broadly support the contributions made since my last post of Hector Quemada (#11821), Karen Hokanson (#11824), Robert Friedman (#11829), Eder Toppa (#11830), Felicity Keiper (#11847, #11849), Brinda Dass (#11857, #11858), and Thato Mogapi (#11865).
Kind regards to all,
Aaron Roberts
IEPI, McMaster University
Dear colleagues,
After following the discussion, I would like to add to my first contribution and to support the contributions of John Connolly (#11803), Ernst Wimmer (#11811), Stephanie James (#11813), and Brinda Dass (#11820, #11823, #11860) who provided useful technical and practical aspects that should be considered in the additional voluntary guidance materials.
I agree with all previous contributions of colleagues who do not consider it to be useful to replicate the 2016 Guidance, and who highlighted the constructive role of uncertainty in risk assessment processes (#11858, #11792, #11794, #11798, #11802, #11814, #11821, #11829) and made respective practical suggestions how to restructure the draft outline.
Regarding the purpose of the additional voluntary guidance materials and echoing the contributions of Andrew Roberts, Karen Hokanson, Robert Friedman and Brinda Dass (#11824, #11829, #11847, #11857), I support the suggestion to put the emphasis of additional guidance materials on collecting information that could be useful for risk assessment of EGD-LMOs and providing a high quality document illustrating tools (among others by means of examples) to support an effective case-specific risk assessment of EGD-LMOs. Thereby, recalling Decision CP-10/10, para 10 (i) (“ relevant supplemental information on LMO-EDG should be collected and shared via dedicated web pages in the Biosafety Clearing-House to facilitate easy access and raise awareness of available information that is relevant for risk assessment of living modified organisms … containing engineered gene drives”) the guidance materials will avoid duplication to the existing Guidance and can hint to a source of relevant information that can be assessed and updated regularly.
Regards,
Anastasia Matthies
After following the discussion, I would like to add to my first contribution and to support the contributions of John Connolly (#11803), Ernst Wimmer (#11811), Stephanie James (#11813), and Brinda Dass (#11820, #11823, #11860) who provided useful technical and practical aspects that should be considered in the additional voluntary guidance materials.
I agree with all previous contributions of colleagues who do not consider it to be useful to replicate the 2016 Guidance, and who highlighted the constructive role of uncertainty in risk assessment processes (#11858, #11792, #11794, #11798, #11802, #11814, #11821, #11829) and made respective practical suggestions how to restructure the draft outline.
Regarding the purpose of the additional voluntary guidance materials and echoing the contributions of Andrew Roberts, Karen Hokanson, Robert Friedman and Brinda Dass (#11824, #11829, #11847, #11857), I support the suggestion to put the emphasis of additional guidance materials on collecting information that could be useful for risk assessment of EGD-LMOs and providing a high quality document illustrating tools (among others by means of examples) to support an effective case-specific risk assessment of EGD-LMOs. Thereby, recalling Decision CP-10/10, para 10 (i) (“ relevant supplemental information on LMO-EDG should be collected and shared via dedicated web pages in the Biosafety Clearing-House to facilitate easy access and raise awareness of available information that is relevant for risk assessment of living modified organisms … containing engineered gene drives”) the guidance materials will avoid duplication to the existing Guidance and can hint to a source of relevant information that can be assessed and updated regularly.
Regards,
Anastasia Matthies
