Question 1: What specific elements are important to include in the outline for these additional voluntary guidance materials?
Zakir Jafry,
Secretariat of the Convention on Biological Diversity#11509
Secretariat of the Convention on Biological Diversity#11509
hace 3 añoshace 3 años
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Argentina does not support the creation of additional guidelines for living modified organisms containing engineered gene drives. If the product is an LMO, countries already have regulatory frameworks to evaluate them (countries that do not have it, can use the guidelines of the Cartagena Protocol).
In the case of GM mosquitoes, Argentina includes them within its regulations for the evaluation of GM animals.
LMOs organisms containing gene drives can be evaluated under existing risk assessment processes for LMOs.
Argentina suggests that gene drive must remain within the scope of the text of the Convention (Art. 8 (g) which speaks of LMOs resulting from biotechnology, not biotechnology in general). It should not leave the language open to other new technologies such as the NBTs.
In the case of GM mosquitoes, Argentina includes them within its regulations for the evaluation of GM animals.
LMOs organisms containing gene drives can be evaluated under existing risk assessment processes for LMOs.
Argentina suggests that gene drive must remain within the scope of the text of the Convention (Art. 8 (g) which speaks of LMOs resulting from biotechnology, not biotechnology in general). It should not leave the language open to other new technologies such as the NBTs.
--- Posted on behalf of Dr. Luciana Pimenta Ambrozevicius, Brazil ---
Dear Participants,
There are many different types of engineered gene drive constructs, for many different uses and contexts. Therefore, engineered gene drive risk assessment must be science-based and consistent with the principle of case-by-case assessment. The RA based on the problem formulation approach provides flexibility and a fit-for-purpose framework for case-specific assessments.
The outline of the voluntary guidance could include, among others:
- Key concepts: e.g. comparative approach (a range of comparators can be considered in ERA for engineered gene drive applications), familiarity (with the biology of the recipient organism, the introduced trait and the receiving environment)
- Description of steps in the Problem Formulation approach:
(i) Identification of protection goals (related with the 3 objectives of CBD)
(ii) Determination of assessment endpoints
(iii) Identification of potential adverse effects on the assessment endpoints
(iv) Identifying of pathways to harm to the assessment endpoints and formulating risk hypotheses for each step of the pathway (using a realistic worst case scenario and elements relevant to evaluating the risk hypotheses)
- Examples with specific types of engineered gene drives (case studies using the problem formulation approach)
Also, could there be a role for the benefits to be possibly considered? Although much progress has been made, there are also challenges including increased insecticide resistance in mosquitoes, increased drug resistance in parasites and maintenance of funding, particularly in the developing countries. There have also been advances in developing more efficient engineered gene drives in fruit flies and Anopheline mosquitoes, which could be transferred to other vectors, including other Anopheline species transmitting malaria, arboviruses vectored by Ae. aegypti, trypanosomes causing Chagas and others.
I look forward to hearing your views,
Luciana
Dear Participants,
There are many different types of engineered gene drive constructs, for many different uses and contexts. Therefore, engineered gene drive risk assessment must be science-based and consistent with the principle of case-by-case assessment. The RA based on the problem formulation approach provides flexibility and a fit-for-purpose framework for case-specific assessments.
The outline of the voluntary guidance could include, among others:
- Key concepts: e.g. comparative approach (a range of comparators can be considered in ERA for engineered gene drive applications), familiarity (with the biology of the recipient organism, the introduced trait and the receiving environment)
- Description of steps in the Problem Formulation approach:
(i) Identification of protection goals (related with the 3 objectives of CBD)
(ii) Determination of assessment endpoints
(iii) Identification of potential adverse effects on the assessment endpoints
(iv) Identifying of pathways to harm to the assessment endpoints and formulating risk hypotheses for each step of the pathway (using a realistic worst case scenario and elements relevant to evaluating the risk hypotheses)
- Examples with specific types of engineered gene drives (case studies using the problem formulation approach)
Also, could there be a role for the benefits to be possibly considered? Although much progress has been made, there are also challenges including increased insecticide resistance in mosquitoes, increased drug resistance in parasites and maintenance of funding, particularly in the developing countries. There have also been advances in developing more efficient engineered gene drives in fruit flies and Anopheline mosquitoes, which could be transferred to other vectors, including other Anopheline species transmitting malaria, arboviruses vectored by Ae. aegypti, trypanosomes causing Chagas and others.
I look forward to hearing your views,
Luciana
Hello everybody, my name is Christoph Then and I am a member of ENSSER (The European Network of Scientists for Social and Environmental Responsibility) and representing Testbiotech (http://www.testbiotch.org) in this discussion. Testbiotech compiled recent information in a backgrounder for this forum https://www.testbiotech.org/node/3037. In our backgrounder, we outline the need for assessing next generation effects and cut-off criteria that allow to take decisions in the face of larger uncertainties.
Good day everyone, my name is Thato Mogapi, from the Department of Forestry, Fisheries and the Environment in South Africa.
Our team is responsible for implementing the provisions on genetically modified organisms (living modified organisms) under the biodiversity legislation which provides for an environmental impact assessment (EIA) to be conducted in cases where the Minister has reason to believe that release of the modified organism into the environment may pose a threat to any indigenous species or the environment. South Africa's Environmental Risk Assessment Framework guidance document identified several potential EIA triggers, including: where there is potential negative impact on listed threatened or protected species; and where the proposed release is for modified organisms that have wild relatives, or that have the potential to become invasive. While to date, none of the LMOs that have gone through the regulatory system have triggered an EIA, LMOs containing gene drives may trigger an EIA as they may fall in these categories.
In terms of specific elements to be included in the outline for additional voluntary guidance materials, some of these were reflected in the “study on risk assessment application of Annex I of decision CP 9/13 to LMOs containing engineered gene drives”. Consideration should be given to the gene drive system (stability), the genes, the host organism, the introduced trait, the target organism, the receiving environment, effects on non-target organisms, resistance development, unintended consequences in a sense that how will you curb the spread given that we are dealing with an organisms that can spread to other areas. Thus the different steps of the risk assessment (problem formulation including defining assessment and measurement endpoints), risk assessment, risk management including post-release monitoring) would need to be outlined taking the aforementioned elements into consideration.
Our team is responsible for implementing the provisions on genetically modified organisms (living modified organisms) under the biodiversity legislation which provides for an environmental impact assessment (EIA) to be conducted in cases where the Minister has reason to believe that release of the modified organism into the environment may pose a threat to any indigenous species or the environment. South Africa's Environmental Risk Assessment Framework guidance document identified several potential EIA triggers, including: where there is potential negative impact on listed threatened or protected species; and where the proposed release is for modified organisms that have wild relatives, or that have the potential to become invasive. While to date, none of the LMOs that have gone through the regulatory system have triggered an EIA, LMOs containing gene drives may trigger an EIA as they may fall in these categories.
In terms of specific elements to be included in the outline for additional voluntary guidance materials, some of these were reflected in the “study on risk assessment application of Annex I of decision CP 9/13 to LMOs containing engineered gene drives”. Consideration should be given to the gene drive system (stability), the genes, the host organism, the introduced trait, the target organism, the receiving environment, effects on non-target organisms, resistance development, unintended consequences in a sense that how will you curb the spread given that we are dealing with an organisms that can spread to other areas. Thus the different steps of the risk assessment (problem formulation including defining assessment and measurement endpoints), risk assessment, risk management including post-release monitoring) would need to be outlined taking the aforementioned elements into consideration.
Greetings colleagues of the forum
My name is Jack Heinemann. I am a professor of molecular biology and genetics at the University of Canterbury in Aotearoa New Zealand. I am a past member of the AHTEG on Risk Assessment and Risk Management. I also joined the recent past forum on Synthetic Biology. I am grateful to participants for sharing their insights, expertise, and resources.
Describing the genetic constructs and understanding them in the context of the engineered organism as part of a risk assessment is essential, and this point is made in many posts. What is far more challenging, and thus the critical 'feedstock' for the risk assessment (and the almost forgotten "risk management" half of the forum's title), is post-release evolution. "A GD [gene-drive] is a technology capable to reproduce itself and potentially undergo mutational changes over time. Not only do GDs affect the environment, the environment affects the GDs as well. Thus, a GD engineered in the laboratory, once released will be confronted with evolutionary processes. It is hard to predict how the genetic information of the drive will be influenced by mutation and selection processes post-release." 10.7717/peerj.6793
Constructing guidance on such a big area of unknown science will also be hard. Even the most sophisticated predictive evolution models, such as used to forecast next season viral strains for vaccine preparation, are less than perfect despite being a far simpler system to model. Therefore, more than previous guidance, this exercise should thoroughly develop understanding of the limits of knowledge and the areas of uncertainty. A key challenge for the guidance particularly for the task of risk management is, as Ms. Mogapi [#11556] has indicated, identifying and validating assessment and measurement endpoints.
I look forward to reading further contributions to the forum.
Jack
My name is Jack Heinemann. I am a professor of molecular biology and genetics at the University of Canterbury in Aotearoa New Zealand. I am a past member of the AHTEG on Risk Assessment and Risk Management. I also joined the recent past forum on Synthetic Biology. I am grateful to participants for sharing their insights, expertise, and resources.
Describing the genetic constructs and understanding them in the context of the engineered organism as part of a risk assessment is essential, and this point is made in many posts. What is far more challenging, and thus the critical 'feedstock' for the risk assessment (and the almost forgotten "risk management" half of the forum's title), is post-release evolution. "A GD [gene-drive] is a technology capable to reproduce itself and potentially undergo mutational changes over time. Not only do GDs affect the environment, the environment affects the GDs as well. Thus, a GD engineered in the laboratory, once released will be confronted with evolutionary processes. It is hard to predict how the genetic information of the drive will be influenced by mutation and selection processes post-release." 10.7717/peerj.6793
Constructing guidance on such a big area of unknown science will also be hard. Even the most sophisticated predictive evolution models, such as used to forecast next season viral strains for vaccine preparation, are less than perfect despite being a far simpler system to model. Therefore, more than previous guidance, this exercise should thoroughly develop understanding of the limits of knowledge and the areas of uncertainty. A key challenge for the guidance particularly for the task of risk management is, as Ms. Mogapi [#11556] has indicated, identifying and validating assessment and measurement endpoints.
I look forward to reading further contributions to the forum.
Jack
Dear colleagues and especially in this case Dr. Pimenta Ambrozevicius
Thank you for the helpful list of suggested elements for the guidance.
My response is on the comparative approach. It, for various reasons including the issue I raise in posting #11560, will be useful but likely less conclusive than for other LMO assessments. I think therefore that gene drive assessment and management will need to also rely upon alternative approaches to assessment. These alternative approaches will depend upon greater uptake of descriptive molecular biology techniques (eg, as being demonstrated for plant LMOs https://doi.org/10.1186/s12302-023-00715-6) and post-release monitoring of highly responsive assessment endpoints. The latter will need to be sensitive enough to detect changes prior to any exponential phase of spreading. This guidance could help to inform on such matters.
With best wishes
Jack
Thank you for the helpful list of suggested elements for the guidance.
My response is on the comparative approach. It, for various reasons including the issue I raise in posting #11560, will be useful but likely less conclusive than for other LMO assessments. I think therefore that gene drive assessment and management will need to also rely upon alternative approaches to assessment. These alternative approaches will depend upon greater uptake of descriptive molecular biology techniques (eg, as being demonstrated for plant LMOs https://doi.org/10.1186/s12302-023-00715-6) and post-release monitoring of highly responsive assessment endpoints. The latter will need to be sensitive enough to detect changes prior to any exponential phase of spreading. This guidance could help to inform on such matters.
With best wishes
Jack
Greetings to all the participants in this forum
I’m Emmanuel González-Ortega. I’m a research profesor at Universidad Autónoma Metropolitana in Mexico City, México and representing CECCAM (Centro de Estudios para el Cambio en el Campo Mexicano) -an independent research center studying issues related to agriculture in Mexico- in this forum.
A relevant consideration in the construction of guidance materials for Risk assessment and risk management is the potential change in the zoonotic potential of insects (i.e. mosquito) carrying GDs and infectous vector-borne diseases in the context of climate change 10.3390/vetsci6020040 , 10.1016/S1473-3099(19)30161-6, 10.1186/s13071-020-04360-3 10.1038/s41467-020-16010-4 , 10.1016/j.pt.2017.11.006, since the mechanism and behavior of gene drives in populations could change or show increased instability due to weather/ecologic conditions.
Best regards,
Emmanuel
I’m Emmanuel González-Ortega. I’m a research profesor at Universidad Autónoma Metropolitana in Mexico City, México and representing CECCAM (Centro de Estudios para el Cambio en el Campo Mexicano) -an independent research center studying issues related to agriculture in Mexico- in this forum.
A relevant consideration in the construction of guidance materials for Risk assessment and risk management is the potential change in the zoonotic potential of insects (i.e. mosquito) carrying GDs and infectous vector-borne diseases in the context of climate change 10.3390/vetsci6020040 , 10.1016/S1473-3099(19)30161-6, 10.1186/s13071-020-04360-3 10.1038/s41467-020-16010-4 , 10.1016/j.pt.2017.11.006, since the mechanism and behavior of gene drives in populations could change or show increased instability due to weather/ecologic conditions.
Best regards,
Emmanuel
Current risk assessment undertaken in accordance with Annex III under the Cartagena Protocol are broadly adequate for organisms containing engineered gene drives.
So, new guidelines need to add value, i.e, the materials should focus on issues that are clearly specific to gene drive organisms. These would include issues related to the temporal and spatial spread of gene drive organisms, molecular characterization and monitoring efforts. As much as possible the guidelines should be useful to RA for all types of gene drive organisms.
Sincerely
So, new guidelines need to add value, i.e, the materials should focus on issues that are clearly specific to gene drive organisms. These would include issues related to the temporal and spatial spread of gene drive organisms, molecular characterization and monitoring efforts. As much as possible the guidelines should be useful to RA for all types of gene drive organisms.
Sincerely
Hello, colleagues - my name is Stephanie James and I work at the Foundation for the National Institutes of Health in Bethesda, MD, USA. Because gene drive-modified organisms have yet to be deployed in natural settings, empirical field data on their fate in, and impact on, the receiving environment is lacking. However, most engineered gene drive systems currently under consideration are developed to mimic natural drive mechanisms. The dynamics and evolutionary fate of many of these natural gene drive systems have been well studied and can provide an important knowledge base for predicting the behavior of similar synthetic drive systems. Risk assessment should full advantage of the science, scholarship and knowledge related to both natural and synthetic gene drives.
References:
A gene drive is a gene drive: the debate over lumping or splitting definitions. https://www.nature.com/articles/s41467-023-37483-z
Natural and synthetic gene drives. https://royalsociety.org/blog/2020/01/natural-and-synthetic-gene-drives/
References:
A gene drive is a gene drive: the debate over lumping or splitting definitions. https://www.nature.com/articles/s41467-023-37483-z
Natural and synthetic gene drives. https://royalsociety.org/blog/2020/01/natural-and-synthetic-gene-drives/
My name is Stephanie James and I work at the Foundation for the National Institutes of Health. I appreciate the comment of Luciana Pimenta Ambrozevicius suggesting that a range of comparators can be considered in ERA for engineered gene drive applications. For gene drive-modified mosquitoes, it has been suggested that, in addition to unmodified mosquitoes of the same species, two other relevant comparators for ERA could be:
- insecticides that kill adult or larval mosquitoes (as a comparator for engineered drive approaches aimed at population suppression)
- the natural gene drive system upon which the synthetic drive is based (such as naturally occurring homing or toxin-antidote type drives)
References:
1) Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing https://www.liebertpub.com/doi/full/10.1089/vbz.2019.2606?rd=1&t=64&akid=5816.0.yt-rl9
2) Larval mosquito management and risk to aquatic ecosystems: A comparative approach including current
tactics and gene‑drive Anopheles techniques https://scholarworks.montana.edu/xmlui/bitstream/handle/1/17344/peterson-mosquito-2022.pdf?sequence=1
3) Natural and synthetic gene drives. https://royalsociety.org/blog/2020/01/natural-and-synthetic-gene-drives/
4) A gene drive is a gene drive: the debate over lumping or splitting definitions. https://www.nature.com/articles/s41467-023-37483-z
- insecticides that kill adult or larval mosquitoes (as a comparator for engineered drive approaches aimed at population suppression)
- the natural gene drive system upon which the synthetic drive is based (such as naturally occurring homing or toxin-antidote type drives)
References:
1) Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing https://www.liebertpub.com/doi/full/10.1089/vbz.2019.2606?rd=1&t=64&akid=5816.0.yt-rl9
2) Larval mosquito management and risk to aquatic ecosystems: A comparative approach including current
tactics and gene‑drive Anopheles techniques https://scholarworks.montana.edu/xmlui/bitstream/handle/1/17344/peterson-mosquito-2022.pdf?sequence=1
3) Natural and synthetic gene drives. https://royalsociety.org/blog/2020/01/natural-and-synthetic-gene-drives/
4) A gene drive is a gene drive: the debate over lumping or splitting definitions. https://www.nature.com/articles/s41467-023-37483-z
Hi everyone! I'm Enrykie Fortajada, a Fellow from the National Committee on Biosafety of the Philippines. Another element to consider in the additional guidance materials is the conduct of surveillance to track and monitor the number of LMOs containing engineered gene drives released in the environment/target site as well as the mechanism to monitor how effective the LMOs with gene drive at reducing the number of target vector/organism.
Good day to all,
my name is Anita Greiter and I work at Environment Agency Austria on biosafety issues.
May I kindly ask for some details regarding the next steps in the development/commissioning of the outline and its discussion in relation to the process outlined in Decision CBD/CP/MOP/DEC/10/10?
Thank you very much, Anita
my name is Anita Greiter and I work at Environment Agency Austria on biosafety issues.
May I kindly ask for some details regarding the next steps in the development/commissioning of the outline and its discussion in relation to the process outlined in Decision CBD/CP/MOP/DEC/10/10?
Thank you very much, Anita
Dear colleagues,
My name is Anastasia Matthies (German Federal Office for Consumer Protection and Food Safety) and my working area is risk assessment of LMOs. With the view to the Question 1, I expressly support the posts #11544, #11556, which emphasize the importance of problem formulation step in the risk assessment of living modified organisms containing engineered gene drives. Comprehensive and clear description of principles for hazard identification, definition of protection goals and assessment endpoints, and formulation of plausible pathways to harm, will support users of the guidance to focus the risk assessment on those characteristics and factors of gene drive organisms, which are important for decision making.
Environmental protection goals set out by legislation establish which aspects of the environment need to be protected, therefore the consideration of regional legislations in the identification of appropriate assessment endpoints is crucial to ensure a targeted assessment of gene drive organisms in context of the expected receiving environments.
My name is Anastasia Matthies (German Federal Office for Consumer Protection and Food Safety) and my working area is risk assessment of LMOs. With the view to the Question 1, I expressly support the posts #11544, #11556, which emphasize the importance of problem formulation step in the risk assessment of living modified organisms containing engineered gene drives. Comprehensive and clear description of principles for hazard identification, definition of protection goals and assessment endpoints, and formulation of plausible pathways to harm, will support users of the guidance to focus the risk assessment on those characteristics and factors of gene drive organisms, which are important for decision making.
Environmental protection goals set out by legislation establish which aspects of the environment need to be protected, therefore the consideration of regional legislations in the identification of appropriate assessment endpoints is crucial to ensure a targeted assessment of gene drive organisms in context of the expected receiving environments.
Hi I am Brinda Dass working at the Foundation of the National Institutes of Health in Maryland, USA. I would like to share the following
I am supportive of Ms. Matthies comment #11581 and the same mentioned also in #11544 and #11556 related to the importance of problem formulation in LMO risk assessment. This process should also incorporate the outcomes of appropriate stakeholder engagement such that the pathways to harm explored take into consideration the wide array of concerns that are noted. As a scientific endeavor the pathway generation process will then allow a determination of which are the plausible pathways to potential harm and these can be taken forward into more detailed analysis.
• 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. John B Connolly, John D Mumford, Silke Fuchs, Geoff Turner, Camilla Beech, Ace R North, Austin Burt. DOI: 10.1186/s12936-021-03674-6
• Problem formulation for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016-2018. Teem JL, Ambali A, Glover B, Ouedraogo J, Makinde D, Roberts A. Malar J. 2019 Oct 15;18(1):347. doi: 10.1186/s12936-019-2978-5
• 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. John B Connolly, John D Mumford, Silke Fuchs, Geoff Turner, Camilla Beech, Ace R North, Austin Burt. DOI: 10.1186/s12936-021-03674-6
• Problem formulation for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016-2018. Teem JL, Ambali A, Glover B, Ouedraogo J, Makinde D, Roberts A. Malar J. 2019 Oct 15;18(1):347. doi: 10.1186/s12936-019-2978-5
Hello, regarding the message by Stephanie James (#11577) and her suggestion to compare engineered gene drive with (I quote) "the natural gene drive system upon which the synthetic drive is based (such as naturally occurring homing or toxin-antidote type drives)" I wanted to share with you this publication by M. Wells and R. Steinbrecher, PNAS, 2022. Indeed, when favouring a terminology that presents engineered gene drive systems as repurposed natural entities, there is a risk that, in risk assessment, this discourages the necessary scrutiny we need to have which engineered gene drives.
Wells MA, Steinbrecher RA. Natural selfish genetic elements should not be defined as gene drives. Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2201142119. doi: 10.1073/pnas.2201142119.
https://www.pnas.org/doi/10.1073/pnas.2201142119
Wells MA, Steinbrecher RA. Natural selfish genetic elements should not be defined as gene drives. Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2201142119. doi: 10.1073/pnas.2201142119.
https://www.pnas.org/doi/10.1073/pnas.2201142119
----Posted on behalf of Mr. Kamal Kumar Rai---
Food is one of the main socio-cultural and economical factors and ecological chains for all livingbing and has connected with the health of individuals in society and in ecosystems. The correlations and other consequences of food in a system need to be considered in a mechanism of assessment and carefully analyzed as a dynamic approach. The food webs and its other chains could be the elements and their functional connectivities in different factors such as health, socio-economic, culture, spiritual and relationship of IPLCs with Mother Nature and universe. IPLCs food culture and systems are distincts and bear a diverse, indigenous farming systems linkages with languages, spirituality, ritual, ceremonial, expression, behaviors, religious, beliefs, land preparation, seeding, harvesting and preparation food as safety, healthy and nutrition as values and IPLCs traditional way of life symbiotic relationship with food and systems of farming that must be considered in the risks assessment and risks management.
Food is deeply connected with micro biomes and natural systems associated with traditional knowledge, practices and innovation of IPLCs can be other elements that need taking account of the risks assessment and management.
Thanks with regards
Kamal Kumar Rai
IPLC
Food is one of the main socio-cultural and economical factors and ecological chains for all livingbing and has connected with the health of individuals in society and in ecosystems. The correlations and other consequences of food in a system need to be considered in a mechanism of assessment and carefully analyzed as a dynamic approach. The food webs and its other chains could be the elements and their functional connectivities in different factors such as health, socio-economic, culture, spiritual and relationship of IPLCs with Mother Nature and universe. IPLCs food culture and systems are distincts and bear a diverse, indigenous farming systems linkages with languages, spirituality, ritual, ceremonial, expression, behaviors, religious, beliefs, land preparation, seeding, harvesting and preparation food as safety, healthy and nutrition as values and IPLCs traditional way of life symbiotic relationship with food and systems of farming that must be considered in the risks assessment and risks management.
Food is deeply connected with micro biomes and natural systems associated with traditional knowledge, practices and innovation of IPLCs can be other elements that need taking account of the risks assessment and management.
Thanks with regards
Kamal Kumar Rai
IPLC
----Posted on behalf of Mr. Kamal Kumar Rai---
Cartagena Protocol on Biosafety Article 26, Socio-economic Consideration, IPLC knowledge systems could be element for the additional guidance
Thanks with regards
Kamal Kumar Rai
IPLCs
Cartagena Protocol on Biosafety Article 26, Socio-economic Consideration, IPLC knowledge systems could be element for the additional guidance
Thanks with regards
Kamal Kumar Rai
IPLCs
As mentioned by a number of posts (#11583, #11581, #11544 and #11556), problem formulation is a crucial first step of risk analysis. As part of problem formulation, the context of any assessment needs to be determined. This would take into account the ‘value” of the organism (including whether it is native or introduced) and also whether there are current control methods (such as insecticide spraying).
The following publications would be useful for the risk context as they describe reduction/eradication of mosquitoes and impacts of current mosquito control practices:
Holding back the tiger: Successful control program protects Australia from Aedes albopictus expansion | PLOS Neglected Tropical Diseases https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005286
Releasing incompatible males drives strong suppression across populations of wild and Wolbachia-carrying Aedes aegypti in Australia | PNAS. https://www.pnas.org/doi/full/10.1073/pnas.2106828118
Ecology: A world without mosquitoes | Nature -older article citing a number of useful research papers
https://www.nature.com/articles/466432a/
Mosquito Eradication: The Story of Killing Campto Brian H. Kay and Richard C. Russell | American Entomologist | Oxford Academic (oup.com) Eradication of introduced Australian species Aedes camptorhynchus from New Zealand. https://academic.oup.com/ae/article/61/3/192/2194577
Red flag for green spray: adverse trophic effects of Bti on breeding birds - Poulin - 2010 - Journal of Applied Ecology - Wiley Online Library. https://besjournals.onlinelibrary.wiley.com/doi/10.1111/j.1365-2664.2010.01821.x
The following publications would be useful for the risk context as they describe reduction/eradication of mosquitoes and impacts of current mosquito control practices:
Holding back the tiger: Successful control program protects Australia from Aedes albopictus expansion | PLOS Neglected Tropical Diseases https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005286
Releasing incompatible males drives strong suppression across populations of wild and Wolbachia-carrying Aedes aegypti in Australia | PNAS. https://www.pnas.org/doi/full/10.1073/pnas.2106828118
Ecology: A world without mosquitoes | Nature -older article citing a number of useful research papers
https://www.nature.com/articles/466432a/
Mosquito Eradication: The Story of Killing Campto Brian H. Kay and Richard C. Russell | American Entomologist | Oxford Academic (oup.com) Eradication of introduced Australian species Aedes camptorhynchus from New Zealand. https://academic.oup.com/ae/article/61/3/192/2194577
Red flag for green spray: adverse trophic effects of Bti on breeding birds - Poulin - 2010 - Journal of Applied Ecology - Wiley Online Library. https://besjournals.onlinelibrary.wiley.com/doi/10.1111/j.1365-2664.2010.01821.x
Thank you for the interesting and informative discussion thus far! I’m Lim Li Ching, from the Third World Network. I have been a member of the previous AHTEG on Synthetic Biology and the AHTEG on Socio-economic Considerations.
In addition to the points already raised, I think that there are other related issues that are particularly relevant to risk assessment of LMOs containing engineered gene drives.
Others have already pointed to the issue of uncertainties and limits of knowledge (#11560, #11552), including the need for ‘cut-off criteria’. These are critical overarching issues already flagged in the previous Guidance on Risk Assessment of LMOs, but are even more relevant for LMOs containing engineered gene drives, given the high potential for exponential spread and challenges with spatial/temporal controllability, next generation effects and implications for/on evolutionary processes. The new guidance would serve well to elaborate further on these points, including on how to systematically integrate uncertainties and address knowledge gaps in the risk assessment process.
In discussions around LMOs containing engineered gene drives, the issues of public participation and socio-economic considerations, especially with regard to the value of biodiversity to indigenous peoples and local communities, have long been raised as essential elements (see also #11590, #11591). While the new guidance is expected to of course focus on risk assessment and risk management, and arguably, monitoring in the context of risk assessment (e.g. #11556, #11561), these related issues are important to flag in the context of the overall rights and obligations under the Protocol.
In particular, the process of risk assessment would well benefit from participatory input, including in the planning phases, as envisaged by problem formulation (#11581, #11583) processes. But I’d like to also point to the broader notion of 'problem formulation and options assessment' (e.g. Nelson et al. 2009, DOI: 10.1111/j.1748-720X.2009.00444.x), which importantly includes governance aspects such as the role of participation, not just in problem formulation, but also in options assessment.
In this regard, key questions to ask are, what exactly is the problem, what options exist to solve it and how does a gene drive compare with other solutions? (see Dressel, H. (ed.) 2019, https://genedrives.ch/report/). The evaluation of a range of alternative options for meeting needs alongside the option under appraisal was recommended by the ‘Late Lessons from Early Warnings’ research (Harremoës et al. 2001, https://www.eea.europa.eu/publications/environmental_issue_report_2001_22). This would entail serious consideration of all the alternatives that could be used or developed in order to tackle identified problems, including, in the case of vector control, social determinants of health, such as alleviating poverty or providing access to healthcare and water.
In addition to the points already raised, I think that there are other related issues that are particularly relevant to risk assessment of LMOs containing engineered gene drives.
Others have already pointed to the issue of uncertainties and limits of knowledge (#11560, #11552), including the need for ‘cut-off criteria’. These are critical overarching issues already flagged in the previous Guidance on Risk Assessment of LMOs, but are even more relevant for LMOs containing engineered gene drives, given the high potential for exponential spread and challenges with spatial/temporal controllability, next generation effects and implications for/on evolutionary processes. The new guidance would serve well to elaborate further on these points, including on how to systematically integrate uncertainties and address knowledge gaps in the risk assessment process.
In discussions around LMOs containing engineered gene drives, the issues of public participation and socio-economic considerations, especially with regard to the value of biodiversity to indigenous peoples and local communities, have long been raised as essential elements (see also #11590, #11591). While the new guidance is expected to of course focus on risk assessment and risk management, and arguably, monitoring in the context of risk assessment (e.g. #11556, #11561), these related issues are important to flag in the context of the overall rights and obligations under the Protocol.
In particular, the process of risk assessment would well benefit from participatory input, including in the planning phases, as envisaged by problem formulation (#11581, #11583) processes. But I’d like to also point to the broader notion of 'problem formulation and options assessment' (e.g. Nelson et al. 2009, DOI: 10.1111/j.1748-720X.2009.00444.x), which importantly includes governance aspects such as the role of participation, not just in problem formulation, but also in options assessment.
In this regard, key questions to ask are, what exactly is the problem, what options exist to solve it and how does a gene drive compare with other solutions? (see Dressel, H. (ed.) 2019, https://genedrives.ch/report/). The evaluation of a range of alternative options for meeting needs alongside the option under appraisal was recommended by the ‘Late Lessons from Early Warnings’ research (Harremoës et al. 2001, https://www.eea.europa.eu/publications/environmental_issue_report_2001_22). This would entail serious consideration of all the alternatives that could be used or developed in order to tackle identified problems, including, in the case of vector control, social determinants of health, such as alleviating poverty or providing access to healthcare and water.
Hello to everyone. My name is Angela Lozan, PhD, associate professor, researcher, project manager, I work for the National Office for Environmental Projects Implementation of the Ministry of Environment of Moldova. Have quite long experience as a regulatory, university teacher and project coordinator.
In support of #11156, #11593 and others, I consider important to include in the outline for additional voluntary guidance materials assessment of post release gene drives into the environment. Gene drive transgenes for vector control are more likely to be designed to disperse beyond immediate release locations and persist for many years in target populations; this makes assessment of ecological risks with a broader scope of spatial and temporal considerations for gene drive applications particularly important. Before such gene drives could be considered for field release, potential impacts from the intervention, including legal issues, (e.g. potential consequences of transboundary movement), socioeconomic effects (e.g. potential changes in insecticide use) and biosafety (e.g. risks to human health and the environment), must first be identified, assessed and, where appropriate, managed.
In support of #11156, #11593 and others, I consider important to include in the outline for additional voluntary guidance materials assessment of post release gene drives into the environment. Gene drive transgenes for vector control are more likely to be designed to disperse beyond immediate release locations and persist for many years in target populations; this makes assessment of ecological risks with a broader scope of spatial and temporal considerations for gene drive applications particularly important. Before such gene drives could be considered for field release, potential impacts from the intervention, including legal issues, (e.g. potential consequences of transboundary movement), socioeconomic effects (e.g. potential changes in insecticide use) and biosafety (e.g. risks to human health and the environment), must first be identified, assessed and, where appropriate, managed.
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.
First, I would like to offer my thanks to our moderator, Luciana Ambrozevicius, for her role guiding us through these important questions that will help to structure the development of an outline for additional guidance materials on risk assessment of living modified organisms containing engineered gene drives.
My comments respond to both Question 1 “specific elements to include” and Question 4 “what existing guidelines, guidance document, and experiences” should be considered.
An overarching consideration is that these new voluntary guidance materials must recognize that both gene drive technologies and corresponding assessment methods to evaluate their risks and potential benefits have been advancing, and will continue to improve. When the Risk Assessment AHTEG last met in 2020, the state of the art was well summarized in two documents:
1) Study on Risk Assessment: Application of annex I of decision CP 9/13 to living modified organisms containing engineered gene drives (Smets & Rudelsheim, 2020) https://bch.cbd.int/protocol/risk_assessment/cp-ra-ahteg-2020-01-04-en-2.pdf
2) 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 (European Food Safety Authority (EFSA), 2020) https://www.efsa.europa.eu/en/efsajournal/pub/6297
Since that time, capabilities have only improved; I will focus my comments on the advances since the AHTEG last met. I believe it is important for CBD voluntary guidance materials to consider the following:
First, the CBD is not the only international body addressing the governance of gene drive technologies. It is vital that CBD guidance at a minimum consider, and preferably be harmonized with, guidance from WHO, which has extensive expertise in control of mosquito-borne disease. A key document, as pointed out by our moderator (#11547), Eder Toppa (#115720), and Angela Lozan (#11598), is:
Guidance framework for testing of genetically modified mosquitoes (WHO, 2021). https://www.who.int/publications/i/item/9789240025233 Importantly, the WHO guidance covers both safety evaluation (risk assessment) and efficacy evaluation, i.e., the benefits of the intervention. Ethical considerations and stakeholder engagement are also included. In addition, gene drive organisms are one a series of vector control interventions actively under review by WHO’s Vector Control Advisory Group (VCAG) https://www.who.int/groups/vector-control-advisory-group.
Quite a few postings point out the importance of a “problem formulation” approach for guiding risk assessments, including Luciana Ambrozevicius (#11544), Thato Mogapi (#11556), Anastasia Matthies (#11581) and others. This is a rigorous, science-based approach for identifying potential harms from a specific proposed application. An exhaustive and excellent example for a nonthreshold, suppression drive being developed by Target Malaria is:
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 (Connolly et al., 2021). https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03674-6%23Sec24 The authors point out that much of the analysis will be relevant for other drive types, as well. One of the authors, Silke Fuchs, points out (#11589) that both the development of the gene-drive organism and assessment of risk are ongoing and together form an iterative process that relies on each other. These perspectives should be included in the guidance: risk assessment must be grounded in sound science, be performed case-by-case, and is an important tool for both regulators and technology developers.
Risk assessments should consider perspectives of multiple stakeholders, thus the guidance would benefit from the inclusion of methods to enable that, as pointed out by Brinda Dass (#11583), Lim Li Ching (#11593), and others. Valuable lessons from Target Malaria can be found in
Operationalizing stakeholder engagement for gene drive research in malaria elimination in Africa—translating guidance into practice (Pare Toe et al., 2022). https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04241-3
Finally, the guidance must be general enough to be useful for the wide variety of gene drives under development today and anticipated for the future. Two excellent reviews of the technology are Engineering the Composition and Fate of Wild Populations with Gene Drive (Hay et al., 2021) https://www.annualreviews.org/doi/abs/10.1146/annurev-ento-020117-043154 and
Gene drives gaining speed (Bier, 2022). https://www.nature.com/articles/s41576-021-00386-0 As pointed out by Werner Schenkel (#11580), these molecular mechanisms can be binned by phenotypic category: population suppression vs population modification, nonlocalized vs. localized approaches (low threshold vs high threshold), and self-limiting vs self-sustaining. The specific molecular mechanism is important, of course, but new ones will no doubt be developed over the coming years. By focusing on these phenotypic categories, the guidance will maintain its usefulness for a longer period of time.
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.
First, I would like to offer my thanks to our moderator, Luciana Ambrozevicius, for her role guiding us through these important questions that will help to structure the development of an outline for additional guidance materials on risk assessment of living modified organisms containing engineered gene drives.
My comments respond to both Question 1 “specific elements to include” and Question 4 “what existing guidelines, guidance document, and experiences” should be considered.
An overarching consideration is that these new voluntary guidance materials must recognize that both gene drive technologies and corresponding assessment methods to evaluate their risks and potential benefits have been advancing, and will continue to improve. When the Risk Assessment AHTEG last met in 2020, the state of the art was well summarized in two documents:
1) Study on Risk Assessment: Application of annex I of decision CP 9/13 to living modified organisms containing engineered gene drives (Smets & Rudelsheim, 2020) https://bch.cbd.int/protocol/risk_assessment/cp-ra-ahteg-2020-01-04-en-2.pdf
2) 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 (European Food Safety Authority (EFSA), 2020) https://www.efsa.europa.eu/en/efsajournal/pub/6297
Since that time, capabilities have only improved; I will focus my comments on the advances since the AHTEG last met. I believe it is important for CBD voluntary guidance materials to consider the following:
First, the CBD is not the only international body addressing the governance of gene drive technologies. It is vital that CBD guidance at a minimum consider, and preferably be harmonized with, guidance from WHO, which has extensive expertise in control of mosquito-borne disease. A key document, as pointed out by our moderator (#11547), Eder Toppa (#115720), and Angela Lozan (#11598), is:
Guidance framework for testing of genetically modified mosquitoes (WHO, 2021). https://www.who.int/publications/i/item/9789240025233 Importantly, the WHO guidance covers both safety evaluation (risk assessment) and efficacy evaluation, i.e., the benefits of the intervention. Ethical considerations and stakeholder engagement are also included. In addition, gene drive organisms are one a series of vector control interventions actively under review by WHO’s Vector Control Advisory Group (VCAG) https://www.who.int/groups/vector-control-advisory-group.
Quite a few postings point out the importance of a “problem formulation” approach for guiding risk assessments, including Luciana Ambrozevicius (#11544), Thato Mogapi (#11556), Anastasia Matthies (#11581) and others. This is a rigorous, science-based approach for identifying potential harms from a specific proposed application. An exhaustive and excellent example for a nonthreshold, suppression drive being developed by Target Malaria is:
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 (Connolly et al., 2021). https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03674-6%23Sec24 The authors point out that much of the analysis will be relevant for other drive types, as well. One of the authors, Silke Fuchs, points out (#11589) that both the development of the gene-drive organism and assessment of risk are ongoing and together form an iterative process that relies on each other. These perspectives should be included in the guidance: risk assessment must be grounded in sound science, be performed case-by-case, and is an important tool for both regulators and technology developers.
Risk assessments should consider perspectives of multiple stakeholders, thus the guidance would benefit from the inclusion of methods to enable that, as pointed out by Brinda Dass (#11583), Lim Li Ching (#11593), and others. Valuable lessons from Target Malaria can be found in
Operationalizing stakeholder engagement for gene drive research in malaria elimination in Africa—translating guidance into practice (Pare Toe et al., 2022). https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04241-3
Finally, the guidance must be general enough to be useful for the wide variety of gene drives under development today and anticipated for the future. Two excellent reviews of the technology are Engineering the Composition and Fate of Wild Populations with Gene Drive (Hay et al., 2021) https://www.annualreviews.org/doi/abs/10.1146/annurev-ento-020117-043154 and
Gene drives gaining speed (Bier, 2022). https://www.nature.com/articles/s41576-021-00386-0 As pointed out by Werner Schenkel (#11580), these molecular mechanisms can be binned by phenotypic category: population suppression vs population modification, nonlocalized vs. localized approaches (low threshold vs high threshold), and self-limiting vs self-sustaining. The specific molecular mechanism is important, of course, but new ones will no doubt be developed over the coming years. By focusing on these phenotypic categories, the guidance will maintain its usefulness for a longer period of time.
Regards to all,
Bob Friedman
Dear all,
I am Barbara Pilz of the Foundation of Future Farming/Save Our Seeds.
The development of a voluntary guidance on risk assessment of gene drives should prioritise a comprehensive and precautionary approach to address potential adverse impacts. This should encompass not only biological and technical aspects but also consider the broader socioeconomic context, decision-making processes, and ethical issues. To achieve this, several key factors need to be included in the guidance:
1. Precautionary Approach: The guidance should be founded upon the precautionary principle, which emphasises the need for thorough risk assessment, management, and the implementation of horizon scanning, monitoring, and assessment measures. These measures should aim to prevent, manage, or control potential adverse effects arising from the use of gene drives.
2. Off-Target Effects: The guidance should address the potential risks associated with off-target effects. This includes evaluating the likelihood of unintended consequences on target and non-target organisms and ecosystems. The guidance should encourage global reporting of all gene drive research and related field trials, which should include precise descriptions of the organisms, gene drive constructs, and the intended purposes.
3. Uncontrollability, Irreversibility, and Outcrossing Species Boundaries: The guidance should consider the risks of gene drives spreading beyond the intended area, becoming uncontrollable, or irreversibly affecting the environment, thus establishing requirements for retrievability and controllability of gene drive organisms (e.g. sufficiently verified methods for their removal from nature, possibility to limit their effect and spread in nature). Furthermore, it should account for the possibility of gene drives crossing species boundaries and evaluate the potential ecological and human implications of such events.
4. Limitations of Knowledge: Recognising that our understanding of gene drives, their interaction with ecosystems, and their potential impacts are still evolving, the guidance should emphasise the need for updating risk assessments based on new findings.
5. Socioeconomic Considerations: The guidance should go beyond biology and technical testing guidelines to address socioeconomic and ethical implications, such as potential effects on indigenous peoples and local communities and economies, cultural practices, and power dynamics within and in relation to affected communities.
6. Decision-Making and Community Involvement: The guidance should highlight the importance of inclusive decision-making processes, taking into account the perspectives of potentially affected communities. This includes ensuring that stakeholders (and right holders) are thoroughly informed of all potential risks.
7. Free Prior and Informed Consent (FPIC) as a Guide to Methodologies for Inclusion and Respect for Community Decisions: The guidance should provide clear methodologies to ensure that affected populations are meaningfully involved in decision-making and technology assessment processes, respecting their autonomy and cultural practices and in line with the principle of Free Prior and Informed Consent (FPIC).
8. Critical Voices and Transparency: To maintain trust and accountability, the guidance should promote the inclusion of critical voices and ensure that discussions about risks, uncertainties, and potential negative consequences are transparent. It should also take into account conflicts of interest, particularly related to funding, affiliation, and intended purpose of gene drives release.
In light of the above, it is crucial for guidance on gene drives to recognise the current inability to control, recall, or reverse gene drive organisms (GDOs) in nature. Meaning that traditional risk assessment and modelling approaches designed for genetically modified organisms are not yet sufficient for a safe deployment. Prior to any release of GDOs, it is necessary to establish internationally agreed-upon procedures and guidelines for uniformly document and assess the environmental risks posed by these organisms (in addition to potential any case-by-case assessment).
Guidance on risk assessment should fully implement the precautionary principle and strive to uphold the right to free, prior, and informed consent (FPIC) of potentially affected indigenous peoples and local communities. Moreover, monitoring and identification procedures must be established to record and track the dispersal and behaviour of potential GDOs across various ecosystems and over time. In this context, the international community should commit to developing and maintaining contingency plans to address risks and adverse impacts associated with the use of gene drives.
External Sources:
Henn, V., M. Imken. 2021. Gene Drive Organisms: A new dimension of genetic engineering. Save Our Seeds. Retrieved from https://www.stop-genedrives.eu/wp-content/uploads/2021/06/GeneDriveOrganisms_-A-New-Dimension-of-Genetic-Engineering_210615.pdf.
I am Barbara Pilz of the Foundation of Future Farming/Save Our Seeds.
The development of a voluntary guidance on risk assessment of gene drives should prioritise a comprehensive and precautionary approach to address potential adverse impacts. This should encompass not only biological and technical aspects but also consider the broader socioeconomic context, decision-making processes, and ethical issues. To achieve this, several key factors need to be included in the guidance:
1. Precautionary Approach: The guidance should be founded upon the precautionary principle, which emphasises the need for thorough risk assessment, management, and the implementation of horizon scanning, monitoring, and assessment measures. These measures should aim to prevent, manage, or control potential adverse effects arising from the use of gene drives.
2. Off-Target Effects: The guidance should address the potential risks associated with off-target effects. This includes evaluating the likelihood of unintended consequences on target and non-target organisms and ecosystems. The guidance should encourage global reporting of all gene drive research and related field trials, which should include precise descriptions of the organisms, gene drive constructs, and the intended purposes.
3. Uncontrollability, Irreversibility, and Outcrossing Species Boundaries: The guidance should consider the risks of gene drives spreading beyond the intended area, becoming uncontrollable, or irreversibly affecting the environment, thus establishing requirements for retrievability and controllability of gene drive organisms (e.g. sufficiently verified methods for their removal from nature, possibility to limit their effect and spread in nature). Furthermore, it should account for the possibility of gene drives crossing species boundaries and evaluate the potential ecological and human implications of such events.
4. Limitations of Knowledge: Recognising that our understanding of gene drives, their interaction with ecosystems, and their potential impacts are still evolving, the guidance should emphasise the need for updating risk assessments based on new findings.
5. Socioeconomic Considerations: The guidance should go beyond biology and technical testing guidelines to address socioeconomic and ethical implications, such as potential effects on indigenous peoples and local communities and economies, cultural practices, and power dynamics within and in relation to affected communities.
6. Decision-Making and Community Involvement: The guidance should highlight the importance of inclusive decision-making processes, taking into account the perspectives of potentially affected communities. This includes ensuring that stakeholders (and right holders) are thoroughly informed of all potential risks.
7. Free Prior and Informed Consent (FPIC) as a Guide to Methodologies for Inclusion and Respect for Community Decisions: The guidance should provide clear methodologies to ensure that affected populations are meaningfully involved in decision-making and technology assessment processes, respecting their autonomy and cultural practices and in line with the principle of Free Prior and Informed Consent (FPIC).
8. Critical Voices and Transparency: To maintain trust and accountability, the guidance should promote the inclusion of critical voices and ensure that discussions about risks, uncertainties, and potential negative consequences are transparent. It should also take into account conflicts of interest, particularly related to funding, affiliation, and intended purpose of gene drives release.
In light of the above, it is crucial for guidance on gene drives to recognise the current inability to control, recall, or reverse gene drive organisms (GDOs) in nature. Meaning that traditional risk assessment and modelling approaches designed for genetically modified organisms are not yet sufficient for a safe deployment. Prior to any release of GDOs, it is necessary to establish internationally agreed-upon procedures and guidelines for uniformly document and assess the environmental risks posed by these organisms (in addition to potential any case-by-case assessment).
Guidance on risk assessment should fully implement the precautionary principle and strive to uphold the right to free, prior, and informed consent (FPIC) of potentially affected indigenous peoples and local communities. Moreover, monitoring and identification procedures must be established to record and track the dispersal and behaviour of potential GDOs across various ecosystems and over time. In this context, the international community should commit to developing and maintaining contingency plans to address risks and adverse impacts associated with the use of gene drives.
External Sources:
Henn, V., M. Imken. 2021. Gene Drive Organisms: A new dimension of genetic engineering. Save Our Seeds. Retrieved from https://www.stop-genedrives.eu/wp-content/uploads/2021/06/GeneDriveOrganisms_-A-New-Dimension-of-Genetic-Engineering_210615.pdf.
Dear colleagues
I am Professor Ossama Abdelkawy, a research scientist and policy advisor with a background in molecular biology and pharmaceutical sciences. I was a member of several former AHTEGs on Risk assessment and Risk management (RA&RM) of LMOs established under the CBD and tasked with developing guidance materials on RA&RM.
Before answering the first discussion question, I will elaborate more on what has already been conducted under the previous AHTEGs based on the parties' instructions and topics identified by the Parties to require additional guidance on RA&RM in order not to try to reinvent the wheel.
A Roadmap for risk assessment of living modified organisms was developed, and it covered
1. Overarching issues in the risk assessment process (- Protection goals, assessment endpoints, and measurement endpoints, - Quality and relevance of information, and - Identification and consideration of uncertainty)
2. Planning phase of the risk assessment (- Establishing the context and scope, - Problem formulation, and - The Choice of comparators)
3. Conducting the risk assessment and its steps
- Step 1: "Identification of any novel genotypic and phenotypic characteristics associated with the living modified organism that may have adverse effects on biological diversity in the likely potential receiving environment, also taking into account risks to human health,"
- Step 2: "Evaluation of the likelihood of adverse effects being realized, taking into account the level and kind of exposure of the likely potential receiving environment to the living modified organism."
- Step 3: "Evaluation of the consequences should these adverse effects be realized."
- Step 4: "Estimation of the overall risk posed by the living modified organism based on the evaluation of the likelihood and consequences of the identified adverse effects being realized."
- Step 5: "Recommendation as to whether or not the risks are acceptable or manageable, including, where necessary, identification of strategies to manage these risks."
To complement the Roadmap, additional guidance documents were produced on specific types of LMOs and traits identified by Parties, which required additional points to consider due to their uniqueness. These included Risk assessment of:
1. living-modified plants with stacked genes or traits,
2. living-modified plants with tolerance to abiotic stress,
3. living-modified trees,
4. living-modified mosquitoes species that act as vectors of human and animal diseases
The produced additional guidance documents tried to complement aspects not well addressed under the Roadmap due to the nature of the type of the LMO or introduced trait. All of them followed the same structure/ format (Background, Introduction, the Planning phase of the risk assessment, Conducting the risk assessment)
An Additional guidance document was produced on 'monitoring living modified organisms released into the environment.' This covered (- Introduction, Objective and scope, Monitoring and its purposes, Development of a monitoring plan (Choice of indicators and parameters for monitoring, Monitoring methods, baselines including reference points, and duration of monitoring, Selecting monitoring methods, Establishing baselines, including reference points, Establishing the duration and frequency of monitoring), Choice of monitoring sites, Reporting of monitoring results).
Parties identified additional topics as requiring additional guidance. The list was long; I recall we had more than ten topics. The AHTEG developed an outline only (not a full guidance) for one or two topics due to time constraints, among other issues.
Now getting back to the first question on what specific elements are important to include in the outline for the additional guidance materials. I think it needs to start by highlighting what makes them different and why they require special attention and additional guidance. It should complete and add on the elements that are present in the Roadmap, the guidance document on monitoring, and the one on LM mosquitos.
I believe what is unique about living modified organisms (LMOs) containing engineered gene drives is that the application of self-propagating artificial genetic elements is meant to move the process of genetic engineering from the laboratory into the fields. This will have implications and new questions to be asked in risk assessment. Some of those questions may require additional research not just in assessing the risk assessment by also in managing risk and monitoring sometimes in the absence of adequate knowledge on the role of the target organisms in ecology, the impact on non-target organisms and human health, robust data to predict long-term effects, performing long-term case-specific monitoring and the lack of availability of sufficiently effective methods to prevent and/or mitigate adverse effects if observed after release.
Questions on the availability of other options, like trying to produce a vaccine rather than reducing the vector population or reducing vectors' populations using other techniques, become more valid. Questioning the assumptions made by experts involved in the Development of the LMOs including assumptions regarding the strain and the insertion site of the artificial gene constructs, potential for exponential spread and challenges with spatial/temporal controllability, next-generation effects, and implications for/on evolutionary processes, are also crucial. The new guidance should serve well to elaborate on these points, including how to systematically integrate uncertainties and address knowledge gaps in the risk assessment process.
O.A.El-kawy
I am Professor Ossama Abdelkawy, a research scientist and policy advisor with a background in molecular biology and pharmaceutical sciences. I was a member of several former AHTEGs on Risk assessment and Risk management (RA&RM) of LMOs established under the CBD and tasked with developing guidance materials on RA&RM.
Before answering the first discussion question, I will elaborate more on what has already been conducted under the previous AHTEGs based on the parties' instructions and topics identified by the Parties to require additional guidance on RA&RM in order not to try to reinvent the wheel.
A Roadmap for risk assessment of living modified organisms was developed, and it covered
1. Overarching issues in the risk assessment process (- Protection goals, assessment endpoints, and measurement endpoints, - Quality and relevance of information, and - Identification and consideration of uncertainty)
2. Planning phase of the risk assessment (- Establishing the context and scope, - Problem formulation, and - The Choice of comparators)
3. Conducting the risk assessment and its steps
- Step 1: "Identification of any novel genotypic and phenotypic characteristics associated with the living modified organism that may have adverse effects on biological diversity in the likely potential receiving environment, also taking into account risks to human health,"
- Step 2: "Evaluation of the likelihood of adverse effects being realized, taking into account the level and kind of exposure of the likely potential receiving environment to the living modified organism."
- Step 3: "Evaluation of the consequences should these adverse effects be realized."
- Step 4: "Estimation of the overall risk posed by the living modified organism based on the evaluation of the likelihood and consequences of the identified adverse effects being realized."
- Step 5: "Recommendation as to whether or not the risks are acceptable or manageable, including, where necessary, identification of strategies to manage these risks."
To complement the Roadmap, additional guidance documents were produced on specific types of LMOs and traits identified by Parties, which required additional points to consider due to their uniqueness. These included Risk assessment of:
1. living-modified plants with stacked genes or traits,
2. living-modified plants with tolerance to abiotic stress,
3. living-modified trees,
4. living-modified mosquitoes species that act as vectors of human and animal diseases
The produced additional guidance documents tried to complement aspects not well addressed under the Roadmap due to the nature of the type of the LMO or introduced trait. All of them followed the same structure/ format (Background, Introduction, the Planning phase of the risk assessment, Conducting the risk assessment)
An Additional guidance document was produced on 'monitoring living modified organisms released into the environment.' This covered (- Introduction, Objective and scope, Monitoring and its purposes, Development of a monitoring plan (Choice of indicators and parameters for monitoring, Monitoring methods, baselines including reference points, and duration of monitoring, Selecting monitoring methods, Establishing baselines, including reference points, Establishing the duration and frequency of monitoring), Choice of monitoring sites, Reporting of monitoring results).
Parties identified additional topics as requiring additional guidance. The list was long; I recall we had more than ten topics. The AHTEG developed an outline only (not a full guidance) for one or two topics due to time constraints, among other issues.
Now getting back to the first question on what specific elements are important to include in the outline for the additional guidance materials. I think it needs to start by highlighting what makes them different and why they require special attention and additional guidance. It should complete and add on the elements that are present in the Roadmap, the guidance document on monitoring, and the one on LM mosquitos.
I believe what is unique about living modified organisms (LMOs) containing engineered gene drives is that the application of self-propagating artificial genetic elements is meant to move the process of genetic engineering from the laboratory into the fields. This will have implications and new questions to be asked in risk assessment. Some of those questions may require additional research not just in assessing the risk assessment by also in managing risk and monitoring sometimes in the absence of adequate knowledge on the role of the target organisms in ecology, the impact on non-target organisms and human health, robust data to predict long-term effects, performing long-term case-specific monitoring and the lack of availability of sufficiently effective methods to prevent and/or mitigate adverse effects if observed after release.
Questions on the availability of other options, like trying to produce a vaccine rather than reducing the vector population or reducing vectors' populations using other techniques, become more valid. Questioning the assumptions made by experts involved in the Development of the LMOs including assumptions regarding the strain and the insertion site of the artificial gene constructs, potential for exponential spread and challenges with spatial/temporal controllability, next-generation effects, and implications for/on evolutionary processes, are also crucial. The new guidance should serve well to elaborate on these points, including how to systematically integrate uncertainties and address knowledge gaps in the risk assessment process.
O.A.El-kawy
Dear colleagues,
First, I would like to thank Luciana for moderating this very important topic and for bringing some insights into the discussions. My name is Sarah Agapito, I am a plant biologist with research dedicated to transgene/gene-editing genetic regulation as well as genomic characterization and response metabolism analysis. I am a Research Professor at NORCE Norwegian Research Centre in Norway. I was also a member of the former synbio AHTEG.
I would like to highlight some elements already described by our colleagues and perhaps give some insight into new ones:
- Investigation of post-release evolution. This will be an extremely relevant aspect considering that such LMOs are intended to spread after release. Most relevant, aspects of scape and survival, cross-species mating, etc are also relevant.
- Impact of environmental factors on gene-drives behavior/expression should also be considered and these might reach completely different ecosystems, urban areas, different biomes etc.
- Impact on different food webs which have functional connections to the LMO web.
- Broader participation of IPLCs throughout the process of LMO approval as these communities will be affected but also because they possess knowledge that goes beyond the known scientific disciplines.
There is also an aspect related to the LMO detection and identification that should be considered. To date, most of our experience on screening, detecting, identifying, and quantifying LMOs is dedicated to genetically modified plants containing transgenic sequences. Since LMOs containing gene-drives represent a broader range of organisms and different genetic modifications, some attention must be given to detection methodologies to trace and monitor these organisms and their descendants in the environment.
I would also like to mention the availability of new descriptive molecular biology techniques, as mentioned before in the group (https://doi.org/10.1186/s12302-023-00715-6) which has been developed for plants and could be adapted to LMOs containing gene-drives for the purpose of characterizing the genetics of these organisms for dedicated risk hypothesis. But also, as mentioned, for post-release monitoring purposes.
Finally, given the novelty of such applications limits of knowledge and the areas of uncertainty should be properly addressed.
Thank you for the opportunity to contribute to these highly relevant discussions.
Best regards,
Sarah
First, I would like to thank Luciana for moderating this very important topic and for bringing some insights into the discussions. My name is Sarah Agapito, I am a plant biologist with research dedicated to transgene/gene-editing genetic regulation as well as genomic characterization and response metabolism analysis. I am a Research Professor at NORCE Norwegian Research Centre in Norway. I was also a member of the former synbio AHTEG.
I would like to highlight some elements already described by our colleagues and perhaps give some insight into new ones:
- Investigation of post-release evolution. This will be an extremely relevant aspect considering that such LMOs are intended to spread after release. Most relevant, aspects of scape and survival, cross-species mating, etc are also relevant.
- Impact of environmental factors on gene-drives behavior/expression should also be considered and these might reach completely different ecosystems, urban areas, different biomes etc.
- Impact on different food webs which have functional connections to the LMO web.
- Broader participation of IPLCs throughout the process of LMO approval as these communities will be affected but also because they possess knowledge that goes beyond the known scientific disciplines.
There is also an aspect related to the LMO detection and identification that should be considered. To date, most of our experience on screening, detecting, identifying, and quantifying LMOs is dedicated to genetically modified plants containing transgenic sequences. Since LMOs containing gene-drives represent a broader range of organisms and different genetic modifications, some attention must be given to detection methodologies to trace and monitor these organisms and their descendants in the environment.
I would also like to mention the availability of new descriptive molecular biology techniques, as mentioned before in the group (https://doi.org/10.1186/s12302-023-00715-6) which has been developed for plants and could be adapted to LMOs containing gene-drives for the purpose of characterizing the genetics of these organisms for dedicated risk hypothesis. But also, as mentioned, for post-release monitoring purposes.
Finally, given the novelty of such applications limits of knowledge and the areas of uncertainty should be properly addressed.
Thank you for the opportunity to contribute to these highly relevant discussions.
Best regards,
Sarah
Dear colleagues,
My name is Ricarda Steinbrecher, I am biologist and molecular geneticist and have been nominated by the Federation of German Scientists; I have been a member of the previous AHTEG on Synthetic Biology as well as a former AHTEG on risk assessment & risk management.
I would like to add some additional aspects to the interesting discussion on this thread, and make some comments on points raised.
I regard it as important, that any guidance developed will attempt to cover the big points and issues, those that are of relevance to gene drives and gene drive organisms (GDOs) in general.
Whilst there are 6 mosquito species being worked on, including both for population suppression/eradication and population modification and using different gene drive systems, there are 10 other diptera being targeted for gene drive development (number excluding the model organism Drosophila melanogaster) in a total of 32 insect targets (Wells & Steinbrecher 2022, attached). In a wider horizon scanning survey we found that there are also 42 proposed non-insect targets, with Mus musculus (the house mouse) being the most researched and the furthest developed (Wells & Steinbrecher 2023, attached). All these are potentially intended for the release into the wild, though technical and biological hurdles and biosafety concerns are still dominating.
The important issue of (uncontrolled) spread has been raised by a number of participants, including the concern of how to ‘curb the spread’ when facing unintended consequences (Ms. Thato Mogapi, #11556), which I believe is at the heart of gene drive biosafety concerns. For me the aspect here is that of:
=> how to halt and how to reverse a gene drive, which in fact are two different things, as stopping a gene drive from spreading further would still leave a large group (sub-population) of living modified organisms in the environment, possibly capable of passing on the modifications by mendelian patterns. I also very much appreciate the bringing up of the issue of stability or ‘instability over time’, as that is potentially a likely scenario, and has just been reported for the double-sex gene drive in Anopheles gambiae (WHO 2022).
(World Health Organisation, 2022, https://www.who.int/publications-detail-redirect/9789240066021)
Different voices in the gene drive community have stated that a prerequisite for any gene drive or GDO release would be to have the antidote available, a reliable and failproof system to stop and to reverse a gene drive. Given the ambitions to ensure biosafety, any GDO risk assessment should also look at the availability of and the reliability and safety of a halting/reversal system and ensure there is a reliable and safe recall system in place. Even if the GDO spreads far and wide.
In this context, two publication on the windborne long-distance migration of malaria mosquitoes:
- Huestis et al. (2019). Nature 574, 404–408 (2019). https://doi.org/10.1038/s41586-019-1622-4
- Sanoga et al> (2021). Journal of medical entomology, 58(1), 343–349. https://doi.org/10.1093/jme/tjaa137
Briefly, 4 more specific elements to include in the outline for guidance materials:
1) The role and place of the host/target organism in the ecosystem/environment, in the wild, including in its native range should it be an AIS (alien invasive species). This is not about keystone species, but rather to fully understand where in the food web and interaction web a target organism is based/placed or a modified species might be placed/based.
2) Niche replacement(s): what will for example replace the organism that has been taken out? E.g. with agricultural pests, if taken out via gene drive, what will come in its place? And what about ecological rebound effects if an ‘eradicated’/ suppressed species comes back?
3) What would be the consequence if the species as such would go extinct?
4) How certain are we of any of the answers, data, or knowledge? – In this I agree with Mr. Jack Heinemann, #11560 – “Therefore, more than previous guidance, this exercise should thoroughly develop understanding of the limits of knowledge and the areas of uncertainty”.
Finally, I would like to share my concern about the notion that engineered gene drives are just mimicking natural phenomena, and are built and designed accordingly. None of the selfish genetic elements are purpose-built to modify or eradicate a population, but rather embedded in evolutionary processes and systems. Indeed, there will be evolutionary responses to genetically engineered gene drives and t GDOs, and we cannot predict them, neither on a molecular level, nor on a behavioural level or on a selection level. This is an area of science that still has serious gaps of knowledge.
With kind regards,
Ricarda Steinbrecher
My name is Ricarda Steinbrecher, I am biologist and molecular geneticist and have been nominated by the Federation of German Scientists; I have been a member of the previous AHTEG on Synthetic Biology as well as a former AHTEG on risk assessment & risk management.
I would like to add some additional aspects to the interesting discussion on this thread, and make some comments on points raised.
I regard it as important, that any guidance developed will attempt to cover the big points and issues, those that are of relevance to gene drives and gene drive organisms (GDOs) in general.
Whilst there are 6 mosquito species being worked on, including both for population suppression/eradication and population modification and using different gene drive systems, there are 10 other diptera being targeted for gene drive development (number excluding the model organism Drosophila melanogaster) in a total of 32 insect targets (Wells & Steinbrecher 2022, attached). In a wider horizon scanning survey we found that there are also 42 proposed non-insect targets, with Mus musculus (the house mouse) being the most researched and the furthest developed (Wells & Steinbrecher 2023, attached). All these are potentially intended for the release into the wild, though technical and biological hurdles and biosafety concerns are still dominating.
The important issue of (uncontrolled) spread has been raised by a number of participants, including the concern of how to ‘curb the spread’ when facing unintended consequences (Ms. Thato Mogapi, #11556), which I believe is at the heart of gene drive biosafety concerns. For me the aspect here is that of:
=> how to halt and how to reverse a gene drive, which in fact are two different things, as stopping a gene drive from spreading further would still leave a large group (sub-population) of living modified organisms in the environment, possibly capable of passing on the modifications by mendelian patterns. I also very much appreciate the bringing up of the issue of stability or ‘instability over time’, as that is potentially a likely scenario, and has just been reported for the double-sex gene drive in Anopheles gambiae (WHO 2022).
(World Health Organisation, 2022, https://www.who.int/publications-detail-redirect/9789240066021)
Different voices in the gene drive community have stated that a prerequisite for any gene drive or GDO release would be to have the antidote available, a reliable and failproof system to stop and to reverse a gene drive. Given the ambitions to ensure biosafety, any GDO risk assessment should also look at the availability of and the reliability and safety of a halting/reversal system and ensure there is a reliable and safe recall system in place. Even if the GDO spreads far and wide.
In this context, two publication on the windborne long-distance migration of malaria mosquitoes:
- Huestis et al. (2019). Nature 574, 404–408 (2019). https://doi.org/10.1038/s41586-019-1622-4
- Sanoga et al> (2021). Journal of medical entomology, 58(1), 343–349. https://doi.org/10.1093/jme/tjaa137
Briefly, 4 more specific elements to include in the outline for guidance materials:
1) The role and place of the host/target organism in the ecosystem/environment, in the wild, including in its native range should it be an AIS (alien invasive species). This is not about keystone species, but rather to fully understand where in the food web and interaction web a target organism is based/placed or a modified species might be placed/based.
2) Niche replacement(s): what will for example replace the organism that has been taken out? E.g. with agricultural pests, if taken out via gene drive, what will come in its place? And what about ecological rebound effects if an ‘eradicated’/ suppressed species comes back?
3) What would be the consequence if the species as such would go extinct?
4) How certain are we of any of the answers, data, or knowledge? – In this I agree with Mr. Jack Heinemann, #11560 – “Therefore, more than previous guidance, this exercise should thoroughly develop understanding of the limits of knowledge and the areas of uncertainty”.
Finally, I would like to share my concern about the notion that engineered gene drives are just mimicking natural phenomena, and are built and designed accordingly. None of the selfish genetic elements are purpose-built to modify or eradicate a population, but rather embedded in evolutionary processes and systems. Indeed, there will be evolutionary responses to genetically engineered gene drives and t GDOs, and we cannot predict them, neither on a molecular level, nor on a behavioural level or on a selection level. This is an area of science that still has serious gaps of knowledge.
With kind regards,
Ricarda Steinbrecher
Good day everyone,
My name is Albert Anthony, a Scientific Officer with National Biosafety Management Agency, Nigeria. post-release is tasking and also a serious risk for risk assessment and also most less attended to risk management is the post release development. An emerging technology like gene drive skillful of undergoing sudden change in genetic make-up of the organism due to genotype by environmental interaction. it is tough to envisage how the genetic information of the gene drive will be influenced by selection pressure and other vices of mutation. It is pertinent for more weight be tailored towards post-release assessment/management.
Thanks for the opportunity to participate in this forum.
My name is Albert Anthony, a Scientific Officer with National Biosafety Management Agency, Nigeria. post-release is tasking and also a serious risk for risk assessment and also most less attended to risk management is the post release development. An emerging technology like gene drive skillful of undergoing sudden change in genetic make-up of the organism due to genotype by environmental interaction. it is tough to envisage how the genetic information of the gene drive will be influenced by selection pressure and other vices of mutation. It is pertinent for more weight be tailored towards post-release assessment/management.
Thanks for the opportunity to participate in this forum.
My name is Samson Simon, I work for the German Federal Agency for Nature Conservation (BfN) as a biosafety expert.
The guidance material, even though covering a narrow scope, should consider the general differences between LMOs containing engineered gene drives and other LMOs. LMOs containing engineered gene drives might lead to intentional transboundary movements of LMOs, they might be intended to persist indefinitely (both in time and space) in the environment, they are intended to genetically modify wild living populations, while reversal and other risk management strategies might be challenged by the gene drives intrinsic properties (Simon et al. 2018 DOI: 10.15252/embr.201845760).
The voluntary guidance material could contain a general section on state of the art on risk assessment tools and practices in the field of LMOs relevant for engineered gene drives, importantly modelling approaches and it should give a clear indication of their current capabilities and shortcomings. Models are an important tool for the development of gene drive applications. However, models also have the potential to be used for risk assessment. It is important to clearly state, which of those purposes (development or risk assessment) the model shall serve.
Although the number of mathematical models for gene drives is growing steadily, they are, like all models, based on simplified assumptions. Therefore, it is pivotal to understand how those assumptions are reflected in the parameters used. Important parameters, such as complex dispersal behaviour, violation of panmixis or complex mating systems and behaviour, are not sufficiently considered so far (DOI: 10.1016/j.ecolmodel.2023.110285 Frieß et al. 2023; Verma et al. 2023 DOI: 10.1086/722157).
The following open questions could be considered regarding efficacy modelling for risk assessment: Under which assumptions can models be reliably enough to allow predictions that can be used in risk assessment? Can models give sound indications of how a gene drive will behave in the environment in the long term? Is model validation possible in practice so that good modelling can be followed practice (e.g. EFSA Journal DOI 10.2903/j.efsa.2014.3589)? Which basic requirements have to be set for models that support risk assessment in the case of an authorisation procedure?
Ecological models for predicting effects on species compositions and ecosystems are still in its infancy and most modelling approaches in the field of LMOs containing engineered gene drives are dealing with gene drive efficacy. The guidance could discuss whether ecological models exist that allow meaningful predictions relevant for specific protection goals. Can ecological models be used to predict long-term and ecosystem effects of a gene drive release?
Concerning the comparative approach in risk assessment: gene drives are intended to change organisms in such a way (e.g. forced dispersal, change in sex ratio) that substantial equivalence with the parent organism usually no longer exists. A comparison with this organism does not allow any conclusions for risk hypotheses outside the (eco-)toxicological/allergenic field. The greatest effects on ecosystems through GDO are expected through indirect effects. The question remains how to deal with missing comparators in the risk assessments.
The guidance material, even though covering a narrow scope, should consider the general differences between LMOs containing engineered gene drives and other LMOs. LMOs containing engineered gene drives might lead to intentional transboundary movements of LMOs, they might be intended to persist indefinitely (both in time and space) in the environment, they are intended to genetically modify wild living populations, while reversal and other risk management strategies might be challenged by the gene drives intrinsic properties (Simon et al. 2018 DOI: 10.15252/embr.201845760).
The voluntary guidance material could contain a general section on state of the art on risk assessment tools and practices in the field of LMOs relevant for engineered gene drives, importantly modelling approaches and it should give a clear indication of their current capabilities and shortcomings. Models are an important tool for the development of gene drive applications. However, models also have the potential to be used for risk assessment. It is important to clearly state, which of those purposes (development or risk assessment) the model shall serve.
Although the number of mathematical models for gene drives is growing steadily, they are, like all models, based on simplified assumptions. Therefore, it is pivotal to understand how those assumptions are reflected in the parameters used. Important parameters, such as complex dispersal behaviour, violation of panmixis or complex mating systems and behaviour, are not sufficiently considered so far (DOI: 10.1016/j.ecolmodel.2023.110285 Frieß et al. 2023; Verma et al. 2023 DOI: 10.1086/722157).
The following open questions could be considered regarding efficacy modelling for risk assessment: Under which assumptions can models be reliably enough to allow predictions that can be used in risk assessment? Can models give sound indications of how a gene drive will behave in the environment in the long term? Is model validation possible in practice so that good modelling can be followed practice (e.g. EFSA Journal DOI 10.2903/j.efsa.2014.3589)? Which basic requirements have to be set for models that support risk assessment in the case of an authorisation procedure?
Ecological models for predicting effects on species compositions and ecosystems are still in its infancy and most modelling approaches in the field of LMOs containing engineered gene drives are dealing with gene drive efficacy. The guidance could discuss whether ecological models exist that allow meaningful predictions relevant for specific protection goals. Can ecological models be used to predict long-term and ecosystem effects of a gene drive release?
Concerning the comparative approach in risk assessment: gene drives are intended to change organisms in such a way (e.g. forced dispersal, change in sex ratio) that substantial equivalence with the parent organism usually no longer exists. A comparison with this organism does not allow any conclusions for risk hypotheses outside the (eco-)toxicological/allergenic field. The greatest effects on ecosystems through GDO are expected through indirect effects. The question remains how to deal with missing comparators in the risk assessments.
Dears,
Many thanks for the interesting points you raised in this part of the forum.
We would like to share some additional thoughts with you building on the following publications:
-2023 – Engagement on risk assessment for gene drive mosquitoes by EFSA and Target Malaria – Environmental Science & Policy – http://dx.doi.org/10.1016/j.envsci.2023.02.009
-2022 – Risk management recommendations for environmental releases of gene drive modified insects – Biotechnology Advances – http://dx.doi.org/10.1016/j.biotechadv.2021.107807
-2021 – Potential use of gene drive modified insects against disease vectors, agricultural pests and invasive species poses new challenges for risk assessment – Critical Reviews in Biotechnology – http://dx.doi.org/10.1080/07388551.2021.1933891
-2021 – Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance – Trends in Biotechnology – http://dx.doi.org/10.1016/j.tibtech.2020.11.015
-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 Journal – http://dx.doi.org/10.2903/j.efsa.2020.6297
Deliver additional voluntary guidance materials that are useful and practical, while avoiding duplication of efforts and standards: Engineered gene drive technologies are evolving rapidly, and may deliver a range of gene drive products with different designs and modes of action. To address the rapid pace of scientific advances in the field of engineered gene drives and the diversity of potential engineered gene drive products, additional voluntary guidance materials would need to offer an overarching framework, outlining general principles and methodology for risk assessment, that is adaptive to the specific properties of gene drive products under assessment. Moreover, it would be helpful to test existing (risk assessment) guidelines as suggested by Josphat N Muchiri in [#11621], and build on them to avoid duplication of efforts and standards, and strive for complementarity in terms of concepts/paradigms as suggested by Brinda Dass in [#11582].
Consider risk assessment experience gained: International/regional entities (such as NASEM, 2016; AHTEG 2020; EFSA, 2020; WHO, 2021) indicated that: (1) the risk assessment of gene drive modified insects (GDMIs, including mosquitoes) can build on existing risk assessment frameworks for genetically modified insects (GMIs) that do not contain an engineered gene drive; and (2) be informed by experience releasing insects for biological and genetic disease vector/pest control. For example, there is substantial experience with releasing insects for genetic and biological disease vector/pest control, including their risk assessment and post-release monitoring (where applicable), from which lessons can be learnt. This experience can be useful to identify some potential hazards, exposures and risks for GDMIs, and develop relevant, effective and efficient additional voluntary guidance materials. Thus, it is appropriate to draw on the experience from current insect disease vector/pest control strategies, seek relevant precedents from more or less similar situations, and use this experience to inform the risk assessment of GDMIs. However, caution is required as the specific control systems are likely to differ in various aspects. Additional voluntary guidance materials could explore such aspects further.
Provide recommendations on how to best implement problem formulation and make it operational using the pathway to harm approach: Several authors have shown that problem formulation (the initial risk assessment step) offers a fit-for-purpose and scientifically robust framework for case-specific risk assessment of GDMI environmental releases. The stepwise approach followed in the problem formulation facilitates the systematic identification of potential harms and associated uncertainty, as well as their routes of exposure, while being transparent about the assumptions made during the process. Recently, Connolly et al. (2021) reported 46 plausible pathways to harm, which were systematically and comprehensively mapped through a problem formulation approach, for a hypothetical environmental release of an investigational gene drive product to suppress malaria-transmitting mosquitoes and thus reduce malaria transmission in West Africa. So, overall, the problem formulation approach provides a helpful framework to organise existing knowledge and identify relevant new knowledge and uncertainties on GDMIs to support case-specific risk assessments and decision-making. Additional voluntary guidance materials may provide recommendations on how to best implement problem formulation and make it operational using the pathway to harm approach.
Provide guidance on how to define harm: While problem formulation is conceptually straightforward, its implementation is often hindered by an absence of clear policy goals and regulatory decision-making criteria on what constitutes harm (e.g. setting of specific/operational protection goals, limits or thresholds of concern, trigger values for action or acceptance of risk, judgments on sufficiency of scientific knowledge and agreement on the extent uncertainty should be reduced for regulatory decision-making) that are needed to guide interpretation of scientific information in risk assessment. Even in jurisdictions with well-developed regulatory systems, such criteria are often general, requiring refinement for operational use. If what constitutes harm is not clearly defined, risk assessors have no effective way to decide whether particular potential effects of a GDMI environmental release are relevant to risk assessment. While causal pathways to harm have a scientific rationale, the definition of harm is subjective and rooted in societal values. Therefore, it would be helpful if additional voluntary guidance materials would explore such aspects and give recommendations on how to best address them.
Provide guidance on modelling, monitoring and their interplay: Risk assessment for environmental releases of some GDMIs is expected to require greater reliance on (pre-release) modelling and (post-release) monitoring to address uncertainty, compared with GMIs that do not contain an engineered gene drive or other self-limiting genetic control approaches. Improving the integration of modelling and monitoring through a more dynamic, iterative interplay between risk assessment and risk management would reduce risk uncertainty associated with the environmental release of some GDMIs. However, for this approach to be more or fully effective, both modelling and monitoring capabilities would need to be enhanced further (see also Samson Simon in [#11622]). Perhaps additional voluntary guidance materials could explore such aspects and give recommendations on how to best address them.
Integrate recommendations on phased testing: As is the case for any other genetically modified organism (GMO) and as outlined in the revised guidance framework for testing genetically modified mosquitoes (GMMs) for use against disease vectors developed by the WHO (2021), a stepwise approach should be followed for the environmental risk assessment of gene drive modified mosquitoes (GDMMs) for environmental release. According to the WHO (2021) framework, testing must proceed iteratively through multiple phases (contained laboratories, indoor cages and insectaries; physically and/or ecologically confined/isolated field trials (e.g. large cages, physical islands); small-scale open release trials; large-scale open release trials; and environmental releases), with each phase involving a larger spatial and temporal scale and a higher degree of human or environmental exposure and realism. Relevant data gathered under controlled, contained conditions would provide confidence that the GDMM can safely progress to the next testing and release phase. The WHO updated its guidance framework to incorporate specific considerations for engineered gene drives, as some of them are predicted to have potential impacts during several of the multiple phases of the testing framework. This stepwise approach would enable separating environmental releases of GDMMs spatio-temporally, to make risk mitigation achievable and commensurate with levels of stakeholder acceptance of stated uncertainty. However, it will require regular review (based on new empirical and post-release monitoring data) to assess whether to move forward to a larger and/or longer release scale to be conducted at a single site or multiple sites. It would be most helpful to extend the considerations outlined in the updated WHO guidance framework to agricultural insects and other arthropod pests.
Provide guidance on how to consider risk-benefits/comparison with alternative interventions, including inaction: Risk debates about GMOs, including GDMIs, often expand to considering whether emerging biotechnologies contribute to sustainable development goals, and how potential risks and benefits associated with the deployment of such biotechnologies are distributed. In most jurisdictions, however, regulatory systems for GMOs are designed to consider primarily potential risks and their likelihoods, but not potential benefits and costs. Consequently, whether a proposed GDMI environmental release is likely to meet wider socioeconomic and ecological aspirations and other policy targets is not explicitly addressed in the risk analysis process. Moreover, potential risks and their likelihoods are not necessarily being compared with those of commonly applied management interventions (such as the use of insecticides, bed nets, sterile insect technique, Wolbachia-mediated incompatible insect technique, Wolbachia-mediated pathogen interference, potential vaccines) or alternative management interventions (such as GMIs that do not contain an engineered gene drive). Both types of intervention have their own potential risks and costs in terms of ongoing adverse impacts and/or management resources. Additional voluntary guidance materials could explore such aspects and give recommendations on how to best address them.
Provide recommendations for effective stakeholder engagement: To allow for risk concerns to be fully explored and defined, stakeholder engagement (through the active participation of interested and affected actors) is advocated before and during the problem formulation. Additional voluntary guidance materials could explore such aspects and provide recommendations on how to make stakeholder engagement operational and when to apply it.
Relevant references:
-2021 – Systematic identification of plausible pathways to harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa – Malaria Journal – https://doi.org/10.1186/s12936-021-03674-6
-2021 – Guidance Framework for testing of genetically modified mosquitoes – WHO – https://apps.who.int/iris/rest/bitstreams/1347934/retrieve
-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 Journal – http://dx.doi.org/10.2903/j.efsa.2020.6297
-2020 – Report of the Ad Hoc Technical Expert Group, CBD/CP/RA/AHTEG/2020/1/5 – https://www.cbd.int/doc/c/a763/e248/4fa326e03e3c126b9615e95d/cp-ra-ahteg-2020-01-05-en.pdf
-2016 – Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values – National Academies Press – https://nap.nationalacademies.org/catalog/23405/gene-drives-on-the-horizon-advancing-science-navigating-uncertainty-and
We hope the information shared will be helpful.
Wishing you all the best,
Yann Devos (Senior scientific officer in the Chief Scientist Office of the European Food Safety Authority (EFSA)) and Alexandre Huchelmann (Policy officer in the Biotechnology Unit of the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission)
Many thanks for the interesting points you raised in this part of the forum.
We would like to share some additional thoughts with you building on the following publications:
-2023 – Engagement on risk assessment for gene drive mosquitoes by EFSA and Target Malaria – Environmental Science & Policy – http://dx.doi.org/10.1016/j.envsci.2023.02.009
-2022 – Risk management recommendations for environmental releases of gene drive modified insects – Biotechnology Advances – http://dx.doi.org/10.1016/j.biotechadv.2021.107807
-2021 – Potential use of gene drive modified insects against disease vectors, agricultural pests and invasive species poses new challenges for risk assessment – Critical Reviews in Biotechnology – http://dx.doi.org/10.1080/07388551.2021.1933891
-2021 – Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance – Trends in Biotechnology – http://dx.doi.org/10.1016/j.tibtech.2020.11.015
-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 Journal – http://dx.doi.org/10.2903/j.efsa.2020.6297
Deliver additional voluntary guidance materials that are useful and practical, while avoiding duplication of efforts and standards: Engineered gene drive technologies are evolving rapidly, and may deliver a range of gene drive products with different designs and modes of action. To address the rapid pace of scientific advances in the field of engineered gene drives and the diversity of potential engineered gene drive products, additional voluntary guidance materials would need to offer an overarching framework, outlining general principles and methodology for risk assessment, that is adaptive to the specific properties of gene drive products under assessment. Moreover, it would be helpful to test existing (risk assessment) guidelines as suggested by Josphat N Muchiri in [#11621], and build on them to avoid duplication of efforts and standards, and strive for complementarity in terms of concepts/paradigms as suggested by Brinda Dass in [#11582].
Consider risk assessment experience gained: International/regional entities (such as NASEM, 2016; AHTEG 2020; EFSA, 2020; WHO, 2021) indicated that: (1) the risk assessment of gene drive modified insects (GDMIs, including mosquitoes) can build on existing risk assessment frameworks for genetically modified insects (GMIs) that do not contain an engineered gene drive; and (2) be informed by experience releasing insects for biological and genetic disease vector/pest control. For example, there is substantial experience with releasing insects for genetic and biological disease vector/pest control, including their risk assessment and post-release monitoring (where applicable), from which lessons can be learnt. This experience can be useful to identify some potential hazards, exposures and risks for GDMIs, and develop relevant, effective and efficient additional voluntary guidance materials. Thus, it is appropriate to draw on the experience from current insect disease vector/pest control strategies, seek relevant precedents from more or less similar situations, and use this experience to inform the risk assessment of GDMIs. However, caution is required as the specific control systems are likely to differ in various aspects. Additional voluntary guidance materials could explore such aspects further.
Provide recommendations on how to best implement problem formulation and make it operational using the pathway to harm approach: Several authors have shown that problem formulation (the initial risk assessment step) offers a fit-for-purpose and scientifically robust framework for case-specific risk assessment of GDMI environmental releases. The stepwise approach followed in the problem formulation facilitates the systematic identification of potential harms and associated uncertainty, as well as their routes of exposure, while being transparent about the assumptions made during the process. Recently, Connolly et al. (2021) reported 46 plausible pathways to harm, which were systematically and comprehensively mapped through a problem formulation approach, for a hypothetical environmental release of an investigational gene drive product to suppress malaria-transmitting mosquitoes and thus reduce malaria transmission in West Africa. So, overall, the problem formulation approach provides a helpful framework to organise existing knowledge and identify relevant new knowledge and uncertainties on GDMIs to support case-specific risk assessments and decision-making. Additional voluntary guidance materials may provide recommendations on how to best implement problem formulation and make it operational using the pathway to harm approach.
Provide guidance on how to define harm: While problem formulation is conceptually straightforward, its implementation is often hindered by an absence of clear policy goals and regulatory decision-making criteria on what constitutes harm (e.g. setting of specific/operational protection goals, limits or thresholds of concern, trigger values for action or acceptance of risk, judgments on sufficiency of scientific knowledge and agreement on the extent uncertainty should be reduced for regulatory decision-making) that are needed to guide interpretation of scientific information in risk assessment. Even in jurisdictions with well-developed regulatory systems, such criteria are often general, requiring refinement for operational use. If what constitutes harm is not clearly defined, risk assessors have no effective way to decide whether particular potential effects of a GDMI environmental release are relevant to risk assessment. While causal pathways to harm have a scientific rationale, the definition of harm is subjective and rooted in societal values. Therefore, it would be helpful if additional voluntary guidance materials would explore such aspects and give recommendations on how to best address them.
Provide guidance on modelling, monitoring and their interplay: Risk assessment for environmental releases of some GDMIs is expected to require greater reliance on (pre-release) modelling and (post-release) monitoring to address uncertainty, compared with GMIs that do not contain an engineered gene drive or other self-limiting genetic control approaches. Improving the integration of modelling and monitoring through a more dynamic, iterative interplay between risk assessment and risk management would reduce risk uncertainty associated with the environmental release of some GDMIs. However, for this approach to be more or fully effective, both modelling and monitoring capabilities would need to be enhanced further (see also Samson Simon in [#11622]). Perhaps additional voluntary guidance materials could explore such aspects and give recommendations on how to best address them.
Integrate recommendations on phased testing: As is the case for any other genetically modified organism (GMO) and as outlined in the revised guidance framework for testing genetically modified mosquitoes (GMMs) for use against disease vectors developed by the WHO (2021), a stepwise approach should be followed for the environmental risk assessment of gene drive modified mosquitoes (GDMMs) for environmental release. According to the WHO (2021) framework, testing must proceed iteratively through multiple phases (contained laboratories, indoor cages and insectaries; physically and/or ecologically confined/isolated field trials (e.g. large cages, physical islands); small-scale open release trials; large-scale open release trials; and environmental releases), with each phase involving a larger spatial and temporal scale and a higher degree of human or environmental exposure and realism. Relevant data gathered under controlled, contained conditions would provide confidence that the GDMM can safely progress to the next testing and release phase. The WHO updated its guidance framework to incorporate specific considerations for engineered gene drives, as some of them are predicted to have potential impacts during several of the multiple phases of the testing framework. This stepwise approach would enable separating environmental releases of GDMMs spatio-temporally, to make risk mitigation achievable and commensurate with levels of stakeholder acceptance of stated uncertainty. However, it will require regular review (based on new empirical and post-release monitoring data) to assess whether to move forward to a larger and/or longer release scale to be conducted at a single site or multiple sites. It would be most helpful to extend the considerations outlined in the updated WHO guidance framework to agricultural insects and other arthropod pests.
Provide guidance on how to consider risk-benefits/comparison with alternative interventions, including inaction: Risk debates about GMOs, including GDMIs, often expand to considering whether emerging biotechnologies contribute to sustainable development goals, and how potential risks and benefits associated with the deployment of such biotechnologies are distributed. In most jurisdictions, however, regulatory systems for GMOs are designed to consider primarily potential risks and their likelihoods, but not potential benefits and costs. Consequently, whether a proposed GDMI environmental release is likely to meet wider socioeconomic and ecological aspirations and other policy targets is not explicitly addressed in the risk analysis process. Moreover, potential risks and their likelihoods are not necessarily being compared with those of commonly applied management interventions (such as the use of insecticides, bed nets, sterile insect technique, Wolbachia-mediated incompatible insect technique, Wolbachia-mediated pathogen interference, potential vaccines) or alternative management interventions (such as GMIs that do not contain an engineered gene drive). Both types of intervention have their own potential risks and costs in terms of ongoing adverse impacts and/or management resources. Additional voluntary guidance materials could explore such aspects and give recommendations on how to best address them.
Provide recommendations for effective stakeholder engagement: To allow for risk concerns to be fully explored and defined, stakeholder engagement (through the active participation of interested and affected actors) is advocated before and during the problem formulation. Additional voluntary guidance materials could explore such aspects and provide recommendations on how to make stakeholder engagement operational and when to apply it.
Relevant references:
-2021 – Systematic identification of plausible pathways to harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa – Malaria Journal – https://doi.org/10.1186/s12936-021-03674-6
-2021 – Guidance Framework for testing of genetically modified mosquitoes – WHO – https://apps.who.int/iris/rest/bitstreams/1347934/retrieve
-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 Journal – http://dx.doi.org/10.2903/j.efsa.2020.6297
-2020 – Report of the Ad Hoc Technical Expert Group, CBD/CP/RA/AHTEG/2020/1/5 – https://www.cbd.int/doc/c/a763/e248/4fa326e03e3c126b9615e95d/cp-ra-ahteg-2020-01-05-en.pdf
-2016 – Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values – National Academies Press – https://nap.nationalacademies.org/catalog/23405/gene-drives-on-the-horizon-advancing-science-navigating-uncertainty-and
We hope the information shared will be helpful.
Wishing you all the best,
Yann Devos (Senior scientific officer in the Chief Scientist Office of the European Food Safety Authority (EFSA)) and Alexandre Huchelmann (Policy officer in the Biotechnology Unit of the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission)
Dear participants
I´m Carolina Villafañe from The Ministry of Environment of Colombia, and I am in charge of Biosafety issues and, The Cartagena Protocol.
Additional to the scientific and technical aspects to be developed for each "gene drive-organism system" for the risk assessment method, identified according to the proposed methodology in the intervention #11631.
The additional voluntary guidance materials should consider include population genetic approximations, in relation to the gene drive spreading into a population, gene flow between LMO and wild or domesticated relatives, or into their gene pool.
Another important aspect to consider is the synergy that could have a gene drive with other genes or other gene drives when they are spreading into a population genome or inclusive into nontarget genomes, in the ecosystem.
Finally but not least important, depending on the "gene drive-organism system", the guidance materials should have some technical criteria to determine if the LMO could be considered as a "double-use technology or material" in the context of biological weapons.
Thank you
I´m Carolina Villafañe from The Ministry of Environment of Colombia, and I am in charge of Biosafety issues and, The Cartagena Protocol.
Additional to the scientific and technical aspects to be developed for each "gene drive-organism system" for the risk assessment method, identified according to the proposed methodology in the intervention #11631.
The additional voluntary guidance materials should consider include population genetic approximations, in relation to the gene drive spreading into a population, gene flow between LMO and wild or domesticated relatives, or into their gene pool.
Another important aspect to consider is the synergy that could have a gene drive with other genes or other gene drives when they are spreading into a population genome or inclusive into nontarget genomes, in the ecosystem.
Finally but not least important, depending on the "gene drive-organism system", the guidance materials should have some technical criteria to determine if the LMO could be considered as a "double-use technology or material" in the context of biological weapons.
Thank you
Greetings colleagues!!
My name is Efrain Torres Ariza from Colombia. I am a biologist with experience in pest and LMO risk assessment and in sanitary and phytosanitary regulations for international trade. I currently work in the genetic resources group of the Ministry of the Environment.
My suggestions for volunteer guides are as follows:
In the particular case of mosquitoes, it is important to take into account that living modified organisms that contain gene drivers will be released into the environment in native populations and once this occurs, there will be no control over the unwanted effects caused by this introduction, nor how much the effect will last or how far it will spread. Therefore, it is suggested to include in the guides general guidelines on aspects of the ecology and biology of these organisms that should be considered.
It should be noted that robust data on the behavior and effects of gene drive modified mosquitoes or other organisms released into wild populations under natural conditions are not yet available. The largest number of studies are in laboratory conditions, therefore, there is high uncertainty about the effects.
An important factor in the evaluation of the propagation of a gene drive is that an in-depth analysis is made of the dispersal and establishment pathways of the target species. Since in the case of species such as Ae. albopictus and Ae. Aegypti, historical data shows that the wide global distribution of these species is due to anthropic factors such as international trade and transport of products where these insects can go as stowaways.
The guides should contain general guidelines with possible risk management and communication options and strategies, based on scientific, technical and legal information.
My name is Efrain Torres Ariza from Colombia. I am a biologist with experience in pest and LMO risk assessment and in sanitary and phytosanitary regulations for international trade. I currently work in the genetic resources group of the Ministry of the Environment.
My suggestions for volunteer guides are as follows:
In the particular case of mosquitoes, it is important to take into account that living modified organisms that contain gene drivers will be released into the environment in native populations and once this occurs, there will be no control over the unwanted effects caused by this introduction, nor how much the effect will last or how far it will spread. Therefore, it is suggested to include in the guides general guidelines on aspects of the ecology and biology of these organisms that should be considered.
It should be noted that robust data on the behavior and effects of gene drive modified mosquitoes or other organisms released into wild populations under natural conditions are not yet available. The largest number of studies are in laboratory conditions, therefore, there is high uncertainty about the effects.
An important factor in the evaluation of the propagation of a gene drive is that an in-depth analysis is made of the dispersal and establishment pathways of the target species. Since in the case of species such as Ae. albopictus and Ae. Aegypti, historical data shows that the wide global distribution of these species is due to anthropic factors such as international trade and transport of products where these insects can go as stowaways.
The guides should contain general guidelines with possible risk management and communication options and strategies, based on scientific, technical and legal information.
Dear All,
I am a multidisciplinary researcher with a Ph.D. in Biomedical Sciences and another Ph.D. in Mathematics, among others, and was nominated by ENSSER. I also joined the recent past forum on Synthetic Biology. I am grateful to participate here and appreciate the many valuable comments.
Given the very nature of gene-drives, I posit it is relevant to appreciate that the most challenging questions likely arise because of the convergence of traditionally isolated subjects and objectives. As such, it would be instructive to ask what lessons can be learned from past large-scale interventions, or those in related disciplines, that critically rely on interactions between organisms and their environment (as has been considered a major issue with GDs, e.g. # #11560).
1. For example, parallels between large-scale vaccination programs (to drive immunity through a population) and gene-drives cannot be overlooked. Apropos vaccines, taking the polio virus as an example, targeted large-scale polio vaccinations have long thought to be successful. Albeit, after decades of interventions, it turns out this virus just cannot be eradicated! NPR just posted an article (https://www.npr.org/sections/goatsandsoda/2023/04/10/1168141163/the-dream-of-wiping-out-polio-might-need-a-rethink), describing some challenges which seem very much related, to what we may be facing with gene-drives, and analogous potentials/dangers of fertile escape mutants/offspring/persistence development has been noted by quite a few in this forum (e.g. # 11604). Thus, past failures in different contexts may harbor valuable lessons that may more or less directly be applied to gene-drives. It seems that drawing relevant analogs between gene-drives and some of the following would be instructive:
o Vaccine-derived poliovirus infections triggered by viral escape mutants: notably, despite enormous efforts, while the wild poliovirus has been brought to the brink of eradication, the virus refuses to go over the edge; apparently the virus can survive and replicate in an immunodeficient person and seems to have changed to a more dangerous virus that can cause paralysis, now causing a new problem altogether.
o “Intelligence” of viruses. Even though we don’t even regard viruses as living beings, we now know of numerous instances where they have escaped various vaccination programs, whether these involve the poliovirus, the influenza, coronaviruses, and others. That the virus has been “smarter” than technology/our interventions is a common statement made in these contexts. With gene-drives, what is the “intelligence” to be targeted? Only that of the target organism, or the “intelligence” inherent in the network of interactions they are part of?
2. Rapidly changing knowledge: in all those situations where we are dealing with complex biological interrelationships, existing knowledge has often proven to be incomplete or even false. Many of the unknowns are controversial – until they are not. Arguably, there are always players and interactions that previously were never being considered or not regarded as important: for example, the mode of systemic immunization has long been taken for granted. Yet, a key hidden player is the mucosal immune system, which for respiratory viruses, according to Dr. Fauci and collaborators (https://doi.org/10.1016/j.chom.2022.11.016), turned the existing vaccines into “a scientific and public health failure that must be urgently addressed." Analogously, while some already regard the known unknowns of gene drives a major challenge, what about the unknown unknowns?
3. The challenges and limits of modeling with gene-drives have also been noted by several in this forum (e.g. #11622). I echo these concerns as models and their interpretations, in a “real-life” context, can result not only in scenarios that were not envisioned previously, but also in some that are really “counter-intuitive.” For example, when assessing the potential of some SARS-CoV-2 vaccine-escape mutants to become a new and potentially more dangerous variant of concern, some of the underlying parameters are seemingly opposite to what may believe. This may be illustrated via an Austrian study (https://doi.org/10.1038/s41598-021-95025-3) where the authors found that new dangerous variants may indeed be encouraged by vaccination, and that therefore, additionally, other steps (non-pharmaceutical interventions other than vaccination) are needed as sort of a rescue: “A counterintuitive result of our analysis is that the highest risk of resistant strain establishment occurs when a large fraction of the population has already been vaccinated but the transmission is not controlled [by nonpharmaceutical interventions].” In the context of gene-drives, this would mean that down the road we might need to substantially rely on additional interventions than those introduced (i.e., the gene-drive technologies per se)! What would those additional safety measures be, which by way of analogy, would need to be beyond genetics?
4. How do we assess unintended and adverse events of gene-drives? The question of how “causation” in biology is evaluated and determined is vastly complex, incomplete, and often just not doable; this was, among others, one of the key findings of a conference by ENSSER in 2021 (https://ensser.org/events/2021/invitation-public-event-context-causality-and-consequences-from-robust-evidence-to-timely-action-in-biology-ecology-law-and-public-policy/). Notably, biological phenomena are stochastic and consist of countless interrelationships. Statistical modeling with just a few dependent variables has proven extremely challenging, leading to conditional probabilities and other strange notions that most find extremely counter-intuitive. Now, with regards to gene-drives, the number of variables that we must consider, will likely explode, which unavoidably will cause us to default to over-simplifications that arguably may be everything but realistic.
5. What is the margin of error? In the forum, the need for clear and relevant endpoints, proxies, and their limits, has been noted by many. Concerns about worst case effects have been noted by several in this forum but they remain poorly defined, even though these may range from deaths of sentiment beings to the disruption of balance of what many regard as sacred (sacred harmony of Mother Nature e.g #11606); given the challenge and limits of what exactly to measure, unintended effects should also include notions such as interrelationships in terms of electromagnetic frequencies and behavioral changes of directly/indirectly affected organisms.
6. Lessons learned in medicine, e.g. related to disease development and treatment. E.g., Candida has long been known as a human pathogen, which has previously triggered the notion it should be killed with treatments such as antibiotics; however, newer findings clearly show that without presence of various Candida species, their absence leads to previously unrecognized pathological conditions. The same way, it is now recognized that killing off some of the “bad bugs” in our microbiome is not the best approach, as e.g. practiced via microbial transplants and other measures that aim to strengthen the “good bugs” rather than killing off what we regard as bad.
7. The challenge of niche formation has also been discussed in the form extensively: I support the notion raised previously that specific “critters” may have “value” even if we don’t recognize them as such yet. One of their values may be in contributing to some sort of balance – even if it means to prevent the occurrence of something worse.
8. Our analysis and assessment should be based on a holistic approach, including religious and spiritual beliefs. Several in this forum have noted the divinity of Mother Nature, or whatever the language used. Now, if we did regard the divinity of every plant and flower and bug, and of us as well, how would be approach the task of targeting the most challenging problems of gene-drives? Would we even feel we may find alternative solutions?
With best wishes,
Siguna
I am a multidisciplinary researcher with a Ph.D. in Biomedical Sciences and another Ph.D. in Mathematics, among others, and was nominated by ENSSER. I also joined the recent past forum on Synthetic Biology. I am grateful to participate here and appreciate the many valuable comments.
Given the very nature of gene-drives, I posit it is relevant to appreciate that the most challenging questions likely arise because of the convergence of traditionally isolated subjects and objectives. As such, it would be instructive to ask what lessons can be learned from past large-scale interventions, or those in related disciplines, that critically rely on interactions between organisms and their environment (as has been considered a major issue with GDs, e.g. # #11560).
1. For example, parallels between large-scale vaccination programs (to drive immunity through a population) and gene-drives cannot be overlooked. Apropos vaccines, taking the polio virus as an example, targeted large-scale polio vaccinations have long thought to be successful. Albeit, after decades of interventions, it turns out this virus just cannot be eradicated! NPR just posted an article (https://www.npr.org/sections/goatsandsoda/2023/04/10/1168141163/the-dream-of-wiping-out-polio-might-need-a-rethink), describing some challenges which seem very much related, to what we may be facing with gene-drives, and analogous potentials/dangers of fertile escape mutants/offspring/persistence development has been noted by quite a few in this forum (e.g. # 11604). Thus, past failures in different contexts may harbor valuable lessons that may more or less directly be applied to gene-drives. It seems that drawing relevant analogs between gene-drives and some of the following would be instructive:
o Vaccine-derived poliovirus infections triggered by viral escape mutants: notably, despite enormous efforts, while the wild poliovirus has been brought to the brink of eradication, the virus refuses to go over the edge; apparently the virus can survive and replicate in an immunodeficient person and seems to have changed to a more dangerous virus that can cause paralysis, now causing a new problem altogether.
o “Intelligence” of viruses. Even though we don’t even regard viruses as living beings, we now know of numerous instances where they have escaped various vaccination programs, whether these involve the poliovirus, the influenza, coronaviruses, and others. That the virus has been “smarter” than technology/our interventions is a common statement made in these contexts. With gene-drives, what is the “intelligence” to be targeted? Only that of the target organism, or the “intelligence” inherent in the network of interactions they are part of?
2. Rapidly changing knowledge: in all those situations where we are dealing with complex biological interrelationships, existing knowledge has often proven to be incomplete or even false. Many of the unknowns are controversial – until they are not. Arguably, there are always players and interactions that previously were never being considered or not regarded as important: for example, the mode of systemic immunization has long been taken for granted. Yet, a key hidden player is the mucosal immune system, which for respiratory viruses, according to Dr. Fauci and collaborators (https://doi.org/10.1016/j.chom.2022.11.016), turned the existing vaccines into “a scientific and public health failure that must be urgently addressed." Analogously, while some already regard the known unknowns of gene drives a major challenge, what about the unknown unknowns?
3. The challenges and limits of modeling with gene-drives have also been noted by several in this forum (e.g. #11622). I echo these concerns as models and their interpretations, in a “real-life” context, can result not only in scenarios that were not envisioned previously, but also in some that are really “counter-intuitive.” For example, when assessing the potential of some SARS-CoV-2 vaccine-escape mutants to become a new and potentially more dangerous variant of concern, some of the underlying parameters are seemingly opposite to what may believe. This may be illustrated via an Austrian study (https://doi.org/10.1038/s41598-021-95025-3) where the authors found that new dangerous variants may indeed be encouraged by vaccination, and that therefore, additionally, other steps (non-pharmaceutical interventions other than vaccination) are needed as sort of a rescue: “A counterintuitive result of our analysis is that the highest risk of resistant strain establishment occurs when a large fraction of the population has already been vaccinated but the transmission is not controlled [by nonpharmaceutical interventions].” In the context of gene-drives, this would mean that down the road we might need to substantially rely on additional interventions than those introduced (i.e., the gene-drive technologies per se)! What would those additional safety measures be, which by way of analogy, would need to be beyond genetics?
4. How do we assess unintended and adverse events of gene-drives? The question of how “causation” in biology is evaluated and determined is vastly complex, incomplete, and often just not doable; this was, among others, one of the key findings of a conference by ENSSER in 2021 (https://ensser.org/events/2021/invitation-public-event-context-causality-and-consequences-from-robust-evidence-to-timely-action-in-biology-ecology-law-and-public-policy/). Notably, biological phenomena are stochastic and consist of countless interrelationships. Statistical modeling with just a few dependent variables has proven extremely challenging, leading to conditional probabilities and other strange notions that most find extremely counter-intuitive. Now, with regards to gene-drives, the number of variables that we must consider, will likely explode, which unavoidably will cause us to default to over-simplifications that arguably may be everything but realistic.
5. What is the margin of error? In the forum, the need for clear and relevant endpoints, proxies, and their limits, has been noted by many. Concerns about worst case effects have been noted by several in this forum but they remain poorly defined, even though these may range from deaths of sentiment beings to the disruption of balance of what many regard as sacred (sacred harmony of Mother Nature e.g #11606); given the challenge and limits of what exactly to measure, unintended effects should also include notions such as interrelationships in terms of electromagnetic frequencies and behavioral changes of directly/indirectly affected organisms.
6. Lessons learned in medicine, e.g. related to disease development and treatment. E.g., Candida has long been known as a human pathogen, which has previously triggered the notion it should be killed with treatments such as antibiotics; however, newer findings clearly show that without presence of various Candida species, their absence leads to previously unrecognized pathological conditions. The same way, it is now recognized that killing off some of the “bad bugs” in our microbiome is not the best approach, as e.g. practiced via microbial transplants and other measures that aim to strengthen the “good bugs” rather than killing off what we regard as bad.
7. The challenge of niche formation has also been discussed in the form extensively: I support the notion raised previously that specific “critters” may have “value” even if we don’t recognize them as such yet. One of their values may be in contributing to some sort of balance – even if it means to prevent the occurrence of something worse.
8. Our analysis and assessment should be based on a holistic approach, including religious and spiritual beliefs. Several in this forum have noted the divinity of Mother Nature, or whatever the language used. Now, if we did regard the divinity of every plant and flower and bug, and of us as well, how would be approach the task of targeting the most challenging problems of gene-drives? Would we even feel we may find alternative solutions?
With best wishes,
Siguna
I am truly grateful to the many colleagues who are bringing forth important perspectives on this complex topic. I am Dr. Jack Heinemann, a professor of molecular biology and genetics at the University of Canterbury.
Two posts [#11554, #11626] in the forum have raised the idea of a benefit analysis as part of the consideration in guidance on risk assessment and risk management. To my mind a risk assessment and a benefit analysis (as in a “cost-benefit” scenario) are very different things, they depend upon dissimilar (though perhaps overlapping) methodology and fields of expertise. However, a benefits component would probably draw more on the socio-economic experts than, sadly, has so far been routine for a scientific risk assessment. The similarities or an RA and a BA are mostly in the “hazard identification” and “benefit identification” steps as far as I can tell.
Under the Protocol, benefits can already be considered by a decision-maker. How a decision-maker does this is not specified.
I think that both the decision-maker and the risk assessor would have to be kept separate from the benefit assessor, just as the risk assessor is separated from the decision-maker in most operational models. The benefits assessment would have to be supported by rigorous scientific method.
Now for the more difficult parts. Would a benefit analysis be a comparative benefit analysis? In which case, what is the comparator? If ‘inaction’ [#11626] were the comparator, then do we compare it to the past inaction that may have led to the proposed need for an LMO?
How the benefit is described (benefit formulation?) determines how the benefit is perceived (https://doi.org/10.1016/j.cosust.2022.101222). The comparator would be very different if benefit were described as “reduced numbers of vectors” or as “reduction in vector transmitted infections”. Moreover, for the latter, is the comparator the status quo or is it the best available medicine and infrastructure that already exists somewhere (but has not been made available) to the intended receiving environment (in other words, maldistribution from past inaction)?
There are other challenges if benefit is asserted as an absolute value not normalised to a comparator. Then almost any assertion could be made to be true. For example, perhaps tying yourself to a car seat with bailing twine would provide a benefit in some minor subset of vehicle accidents, but a claim of safety could lead to lower use of proper seatbelts and overall more injury and death.
Who monitors the benefit after it has been taken into consideration by an assessor? In some jurisdictions there are formal monitoring requirements that follow a favourable decision based at least in part on a scientific risk assessment, and for others, an ongoing duty of care should a product expected to be safe later be found to cause harm. Will there be a benefit management plan to create a parallel with a risk management plan?
What would be the assessment endpoints for a benefit analysis? What if the benefit is sustainable yield improvements during drought in rain-fed crop fields in Africa? This measurement has massive uncertainties at testing stages, and yield is multifactorial meaning that even after release there could be false negative or false positive findings. How long must the benefit be verified for it to be sustainable? These issues are even more pronounced for gene drive LMOs.
To the degree that proposed benefits of a product never eventualised, or were quantitatively less beneficial than anticipated, how is this incorporated into a pre-market risk assessment? Is this left to laws about false advertising? If so, what if the product was not commercial but public? Would there need to be a bond, repaid when the benefit was realised?
Benefit is not the opposite of risk. A car does not become safer because it is being used as an ambulance. Likewise, the scale of a risk does not change because of the scale of a benefit. The Protocol seems to balance these two different things by allowing decision-making informed by a risk assessment.
These are the questions I have when it comes to incorporating a benefit assessment into a risk assessment. Would a change also be needed to Annex III?
Best wishes
Jack
Heinemann, JA and Hiscox, TC
Rethinking the drivers of biotechnologies: a paradigm for holistic climate change solutions. Current Opinion in Environmental Sustainability. Volume 59, 2022,101222.
https://doi.org/10.1016/j.cosust.2022.101222.
(https://www.sciencedirect.com/science/article/pii/S1877343522000744)
Abstract: Humanity is under pressure to identify sustainable climate change mitigation strategies that also progress developmental and environmental goals. Urgency creates greater risk of superficial actions that could accelerate climate change. We use recent advances in plant productivity through enhanced photosynthesis to demonstrate the pitfalls of defining objectives as a vacant biotechnological service. Recast as a goal to improve well-being and nutrition, climate change-exacerbating trade-offs are easier to avoid and payoffs include climate change mitigation. These insights emerge from linking new work in both molecular biology and anthropology. We suggest a strategy for addressing the adverse effects of climate change that better accommodates the voices of nontechnical public and has a superior navigational memory that optimises progress towards sustainable solutions.
Two posts [#11554, #11626] in the forum have raised the idea of a benefit analysis as part of the consideration in guidance on risk assessment and risk management. To my mind a risk assessment and a benefit analysis (as in a “cost-benefit” scenario) are very different things, they depend upon dissimilar (though perhaps overlapping) methodology and fields of expertise. However, a benefits component would probably draw more on the socio-economic experts than, sadly, has so far been routine for a scientific risk assessment. The similarities or an RA and a BA are mostly in the “hazard identification” and “benefit identification” steps as far as I can tell.
Under the Protocol, benefits can already be considered by a decision-maker. How a decision-maker does this is not specified.
I think that both the decision-maker and the risk assessor would have to be kept separate from the benefit assessor, just as the risk assessor is separated from the decision-maker in most operational models. The benefits assessment would have to be supported by rigorous scientific method.
Now for the more difficult parts. Would a benefit analysis be a comparative benefit analysis? In which case, what is the comparator? If ‘inaction’ [#11626] were the comparator, then do we compare it to the past inaction that may have led to the proposed need for an LMO?
How the benefit is described (benefit formulation?) determines how the benefit is perceived (https://doi.org/10.1016/j.cosust.2022.101222). The comparator would be very different if benefit were described as “reduced numbers of vectors” or as “reduction in vector transmitted infections”. Moreover, for the latter, is the comparator the status quo or is it the best available medicine and infrastructure that already exists somewhere (but has not been made available) to the intended receiving environment (in other words, maldistribution from past inaction)?
There are other challenges if benefit is asserted as an absolute value not normalised to a comparator. Then almost any assertion could be made to be true. For example, perhaps tying yourself to a car seat with bailing twine would provide a benefit in some minor subset of vehicle accidents, but a claim of safety could lead to lower use of proper seatbelts and overall more injury and death.
Who monitors the benefit after it has been taken into consideration by an assessor? In some jurisdictions there are formal monitoring requirements that follow a favourable decision based at least in part on a scientific risk assessment, and for others, an ongoing duty of care should a product expected to be safe later be found to cause harm. Will there be a benefit management plan to create a parallel with a risk management plan?
What would be the assessment endpoints for a benefit analysis? What if the benefit is sustainable yield improvements during drought in rain-fed crop fields in Africa? This measurement has massive uncertainties at testing stages, and yield is multifactorial meaning that even after release there could be false negative or false positive findings. How long must the benefit be verified for it to be sustainable? These issues are even more pronounced for gene drive LMOs.
To the degree that proposed benefits of a product never eventualised, or were quantitatively less beneficial than anticipated, how is this incorporated into a pre-market risk assessment? Is this left to laws about false advertising? If so, what if the product was not commercial but public? Would there need to be a bond, repaid when the benefit was realised?
Benefit is not the opposite of risk. A car does not become safer because it is being used as an ambulance. Likewise, the scale of a risk does not change because of the scale of a benefit. The Protocol seems to balance these two different things by allowing decision-making informed by a risk assessment.
These are the questions I have when it comes to incorporating a benefit assessment into a risk assessment. Would a change also be needed to Annex III?
Best wishes
Jack
Heinemann, JA and Hiscox, TC
Rethinking the drivers of biotechnologies: a paradigm for holistic climate change solutions. Current Opinion in Environmental Sustainability. Volume 59, 2022,101222.
https://doi.org/10.1016/j.cosust.2022.101222.
(https://www.sciencedirect.com/science/article/pii/S1877343522000744)
Abstract: Humanity is under pressure to identify sustainable climate change mitigation strategies that also progress developmental and environmental goals. Urgency creates greater risk of superficial actions that could accelerate climate change. We use recent advances in plant productivity through enhanced photosynthesis to demonstrate the pitfalls of defining objectives as a vacant biotechnological service. Recast as a goal to improve well-being and nutrition, climate change-exacerbating trade-offs are easier to avoid and payoffs include climate change mitigation. These insights emerge from linking new work in both molecular biology and anthropology. We suggest a strategy for addressing the adverse effects of climate change that better accommodates the voices of nontechnical public and has a superior navigational memory that optimises progress towards sustainable solutions.
Dear colleagues, my name is Keith Hayes, I am a team leader and senior research scientist with the Australian Commonwealth Science and Industrial Research Organisation (CSIRO). I was a member of the former AHTEG on risk assessment & risk management, and my team and I have conducted independent risk assessments for proposed field releases of Target Malaria’s stage 1 (Dominant Sterile Male) and stage 2 (Paternal Male Bias) constructs.
I would like to thank our moderator Luciana for guiding this discussion, and also thank all of the other participants for their contributions to this forum.
Question 1
At the time of my writing this, previous posts had identified 35 publications as relevant to Question 1. Only three, however, are identified more than once (Table Q1). A synthesis of the main messages and any commonalities within this body of literature might therefore prove useful. Rather than add further literature suggestions I’d like to identify relevant elements based on my experiences of conducting hazard analysis and probabilistic risk assessments for transgenic mosquitoes.
In the first instance I support previous posts that highlight the utility of the pathways to harm concept, and the necessity of engaging with affected communities and stakeholders when identifying the risk assessment endpoints within these pathways. In some instances, however, we have found stakeholders concerns to be expressed (or at least recorded) in ways that are ambiguous and must be interpreted before being incorporated into the risk assessment. I suspect therefore that there is scope for additional guidance on how to clarify stakeholder concerns, elucidate the conceptual models that underlie these concerns, identify suitable assessment endpoints and thereby help stakeholders better participate in the initial problem formulation phase of a risk assessment.
The risk methodology challenges posed by gene drive modified organisms stem primarily from their potential to occupy a large spatio-temporal footprint. Predicting the likelihood of adverse events within biological systems, over large space and time scales, is difficult. This has led to a renewed emphasis on quantitative models within the gene-drive risk assessment literature, and this undoubtedly presents an opportunity for synthesis to identify critical parameters and important knowledge gaps (see for example Frieß et al. (2023) and Combs et al. ({Accepted})). Techniques for representing the uncertainty in these parameters, and identifying the limitations of models, could be useful raw material for additional guidance that is designed to facilitate capacity building.
In this context, I also believe that consensus documents on relevant organisms (such as Organisation for European Cooperation and Development (2018)) could play a greater support role by reporting laboratory and field estimates of critical parameters such as the probability of assortative mating, rates of hybridisation, transgene fitness costs, transgene stability, drive resistance rates, the probability of long range dispersal, and inter- and intra-specific competition. This would of course require consensus documents, or some similar type of document, to be periodically updated to ensure that they maintained their status as an authoritative source of information for modelers, risk analysts and bio-safety regulators.
Finally there is still considerable scope for aggregating risk-relevant data sets at risk-relevant scales - such as continent wide time series observations of species abundance and composition - in open source databases such as Vector Base (https://vectorbase.org/vectorbase/app). These types of data sets help risk analysts characterise the inherent variability of biological parameters and assess the accuracy of model predictions. It also important that field observations taken before, during and after phased release strategies, are recorded in these databases so that experiences with transgenic organisms outside of the laboratory can gradually accumulate and be made freely available.
REFERENCES
Frieß, Johannes L., Carina R. Lalyer, Bernd Giese, Samson Simon, and Mathias Otto. 2023. “Review of Gene Drive Modelling and Implications for Risk Assessment of Gene Drive Organisms.” Ecological Modelling 478 (April): 110285. https://doi.org/10.1016/j.ecolmodel.2023.110285.
Combs, Matthew A., Andrew J. Golnar, Justin M. Overcash, Alun Lloyd, Keith R. Hayes, David A. O’Brochta, and Kim M. Pepin. {Accepted}. “Leveraging Eco-Evolutionary Models for Gene Drive Risk Assessment.” Trends in Genetics, {Accepted}.
Organisation for European Cooperation and Development. 2018. Safety Assessment of Transgenic Organisms in the Environment, Volume 8. OECD. https://doi.org/10.1787/9789264302235-en.
APPENDIX
Table Q1: Summary of citations identified by participants in relation to Question 1 during the open-ended online forum on risk assessment risk assessment of living modified organisms containing engineered gene drives
Reference Count
Benevenuto2023 2
Connolly2021 2
EPGMOG2020 2
Bartlow2019 1
Bier2021 1
Devos2021 1
Devos2021a 1
Devos2022 1
EPPPPR2014 1
Franklinos2019 1
Friess2019 1
Friess2023 1
Hartley2023 1
Hay2021 1
Huestis2019 1
Iwamura2020 1
James2020 1
James2023a 1
Madzokere2020 1
NASEM2016 1
Nelson2009 1
Peterson2022 1
Sanogo2020 1
SCBD2020 1
Simon2018 1
Switzerland2019 1
Teem2019 1
Tjaden2018 1
Verma2023 1
Wells2022 1
WTF2021 1
WVCAG2022 1
I would like to thank our moderator Luciana for guiding this discussion, and also thank all of the other participants for their contributions to this forum.
Question 1
At the time of my writing this, previous posts had identified 35 publications as relevant to Question 1. Only three, however, are identified more than once (Table Q1). A synthesis of the main messages and any commonalities within this body of literature might therefore prove useful. Rather than add further literature suggestions I’d like to identify relevant elements based on my experiences of conducting hazard analysis and probabilistic risk assessments for transgenic mosquitoes.
In the first instance I support previous posts that highlight the utility of the pathways to harm concept, and the necessity of engaging with affected communities and stakeholders when identifying the risk assessment endpoints within these pathways. In some instances, however, we have found stakeholders concerns to be expressed (or at least recorded) in ways that are ambiguous and must be interpreted before being incorporated into the risk assessment. I suspect therefore that there is scope for additional guidance on how to clarify stakeholder concerns, elucidate the conceptual models that underlie these concerns, identify suitable assessment endpoints and thereby help stakeholders better participate in the initial problem formulation phase of a risk assessment.
The risk methodology challenges posed by gene drive modified organisms stem primarily from their potential to occupy a large spatio-temporal footprint. Predicting the likelihood of adverse events within biological systems, over large space and time scales, is difficult. This has led to a renewed emphasis on quantitative models within the gene-drive risk assessment literature, and this undoubtedly presents an opportunity for synthesis to identify critical parameters and important knowledge gaps (see for example Frieß et al. (2023) and Combs et al. ({Accepted})). Techniques for representing the uncertainty in these parameters, and identifying the limitations of models, could be useful raw material for additional guidance that is designed to facilitate capacity building.
In this context, I also believe that consensus documents on relevant organisms (such as Organisation for European Cooperation and Development (2018)) could play a greater support role by reporting laboratory and field estimates of critical parameters such as the probability of assortative mating, rates of hybridisation, transgene fitness costs, transgene stability, drive resistance rates, the probability of long range dispersal, and inter- and intra-specific competition. This would of course require consensus documents, or some similar type of document, to be periodically updated to ensure that they maintained their status as an authoritative source of information for modelers, risk analysts and bio-safety regulators.
Finally there is still considerable scope for aggregating risk-relevant data sets at risk-relevant scales - such as continent wide time series observations of species abundance and composition - in open source databases such as Vector Base (https://vectorbase.org/vectorbase/app). These types of data sets help risk analysts characterise the inherent variability of biological parameters and assess the accuracy of model predictions. It also important that field observations taken before, during and after phased release strategies, are recorded in these databases so that experiences with transgenic organisms outside of the laboratory can gradually accumulate and be made freely available.
REFERENCES
Frieß, Johannes L., Carina R. Lalyer, Bernd Giese, Samson Simon, and Mathias Otto. 2023. “Review of Gene Drive Modelling and Implications for Risk Assessment of Gene Drive Organisms.” Ecological Modelling 478 (April): 110285. https://doi.org/10.1016/j.ecolmodel.2023.110285.
Combs, Matthew A., Andrew J. Golnar, Justin M. Overcash, Alun Lloyd, Keith R. Hayes, David A. O’Brochta, and Kim M. Pepin. {Accepted}. “Leveraging Eco-Evolutionary Models for Gene Drive Risk Assessment.” Trends in Genetics, {Accepted}.
Organisation for European Cooperation and Development. 2018. Safety Assessment of Transgenic Organisms in the Environment, Volume 8. OECD. https://doi.org/10.1787/9789264302235-en.
APPENDIX
Table Q1: Summary of citations identified by participants in relation to Question 1 during the open-ended online forum on risk assessment risk assessment of living modified organisms containing engineered gene drives
Reference Count
Benevenuto2023 2
Connolly2021 2
EPGMOG2020 2
Bartlow2019 1
Bier2021 1
Devos2021 1
Devos2021a 1
Devos2022 1
EPPPPR2014 1
Franklinos2019 1
Friess2019 1
Friess2023 1
Hartley2023 1
Hay2021 1
Huestis2019 1
Iwamura2020 1
James2020 1
James2023a 1
Madzokere2020 1
NASEM2016 1
Nelson2009 1
Peterson2022 1
Sanogo2020 1
SCBD2020 1
Simon2018 1
Switzerland2019 1
Teem2019 1
Tjaden2018 1
Verma2023 1
Wells2022 1
WTF2021 1
WVCAG2022 1
Dear colleagues,
My name is Chikelu Mba. With a PhD in Plant Breeding and Genetics, I am the Team Leader for Seeds and Plant Genetic Resources in the Plant Production and Protection Division of the Food and Agriculture Organization of the United Nations (FAO), Rome, Italy.
I would like to commend the secretariat of the CBD for organizing this consultation and Dr. Luciana Pimenta Ambrozevicius for being a most capable moderator.
I am new to the AHTEG but have enjoyed very much this opportunity to ‘meet’ the subject matter specialists and be introduced to this throve of knowledge products, which have been shared ever so generously. While the discussions have focused almost exclusively on gene drives in mosquitoes, it is probable that the genome editing of agricultural species will engender similar conversations in the future. I intend therefore to remain engaged with this community of practice in the hopes that the lessons that I am learning will be put to practical use ultimately.
With warm regards and best wishes,
Chike
My name is Chikelu Mba. With a PhD in Plant Breeding and Genetics, I am the Team Leader for Seeds and Plant Genetic Resources in the Plant Production and Protection Division of the Food and Agriculture Organization of the United Nations (FAO), Rome, Italy.
I would like to commend the secretariat of the CBD for organizing this consultation and Dr. Luciana Pimenta Ambrozevicius for being a most capable moderator.
I am new to the AHTEG but have enjoyed very much this opportunity to ‘meet’ the subject matter specialists and be introduced to this throve of knowledge products, which have been shared ever so generously. While the discussions have focused almost exclusively on gene drives in mosquitoes, it is probable that the genome editing of agricultural species will engender similar conversations in the future. I intend therefore to remain engaged with this community of practice in the hopes that the lessons that I am learning will be put to practical use ultimately.
With warm regards and best wishes,
Chike
Thanks everyone for this continued discussion,
There seems to be a framing that suggests that risks are limited to adverse effects on the environment, while potential human health impacts are implicitly beneficial. I would like to thus raise some concerns regarding potential adverse impacts on health that also need to be included in the guidance, in line with the Protocol’s provisions “taking also into account risks to human health”.
Methods are still lacking to assess the potential impacts of gene drives on vector capacity or pathogenicity. There remains a lack of standardised protocols for assessing vector competence or pathogen resistance development with regard to population modification strategies. Other potential impacts, such as pathogen resistance to gene drive systems, are not currently considered in risk assessment protocols, and would likely be undetected prior to release. Moreover, issues such as vector capacity are partially mediated by environmental factors, raising uncertainties that may challenge risk assessment. How such factors may evolve over time adds additional uncertainties.
Studies also suggest that releases of self-sustaining gene drives may lead to co-existence of both wild-type and gene drive organisms. This co-existence has been predicted with modelling studies to result in ‘chaser’ dynamics, whereby local elimination would result in gaps in populations and wild-type rebounds to fill the localised empty niches (https://doi.org/10.1111/mec.15788). Such complexities need to be taken into consideration, and further implies a continued requirement to ensure that such organisms do not escape over a long-term basis, in contradiction to the design aim of elimination. For health applications, risk assessment for suppression drives should therefore not assume that exposure would be reduced based on an intended aim that the target organism would be eliminated. Moreover, how such unstable dynamics may impact local disease dynamics is also relevant.
This leads me to the critical points raised by my colleague Lim Li Ching on assessing safer alternatives, as well as by Professor Heinemann on the issue of benefits, and what comparators are used to assess potential benefits, and what is deemed as ‘inaction’. Similar framings have been included in the WHO guidance, such as using go/no-go criteria for moving candidates to field trials. The go/no-go safety criterion for moving a gene drive-modified investigational product to field testing has been proposed as ‘‘will do no more harm to human health than wild-type mosquitoes of the same genetic background and no more harm to the eco-system than other conventional vector control interventions’’. But this fails to acknowledge the above risks and uncertainties that cannot be easily determined prior to release and that may adversely impact disease. Moreover, restricting comparators for this safety standard to the most harmful current vector control methods or disease-carrying wild type mosquitoes, ignores other alterative, and safer public health interventions and vector control practices. As recently demonstrated by countries such as China, malaria eradication was achieved with a multi-pronged approach using existing tools and strategies that include increased political and financial commitments and coordination, free access to healthcare, incorporation of indigenous medical knowledge in the form of artemisinin-based treatments, poverty alleviation, increased diagnostics and surveillance, sanitation programs, and community involvement https://doi.org/10.1186/s40249-021-00882-9.
It is my view that discussions around benefits are incorrectly reducing disease to a solely biological phenomenon that can only be addressed by narrow technical interventions, without addressing fundamental socio-economic, political, as well as commercial determinants of disease, with potential for significant opportunity costs to overall health and well-being. Opportunity costs are another risk that may arise if gene drives result in neglecting focus and investment in solutions that are already known to be effective, and/or indeed could be further validated and expanded, for example in the case of local indigenous medicines that could be invested in.
Finally, with gene drive products expected to only last a limited time (aiming for 3 years before resistance develops), what is considered successful needs to be carefully defined. Over what time span? Over what area of release? If chaser dynamics are the norm for example, what is the expected impact on disease transmission, over which areas/times etc? how will a control area be defined and protected from genes drive organism contamination?
Cheers
Eva
There seems to be a framing that suggests that risks are limited to adverse effects on the environment, while potential human health impacts are implicitly beneficial. I would like to thus raise some concerns regarding potential adverse impacts on health that also need to be included in the guidance, in line with the Protocol’s provisions “taking also into account risks to human health”.
Methods are still lacking to assess the potential impacts of gene drives on vector capacity or pathogenicity. There remains a lack of standardised protocols for assessing vector competence or pathogen resistance development with regard to population modification strategies. Other potential impacts, such as pathogen resistance to gene drive systems, are not currently considered in risk assessment protocols, and would likely be undetected prior to release. Moreover, issues such as vector capacity are partially mediated by environmental factors, raising uncertainties that may challenge risk assessment. How such factors may evolve over time adds additional uncertainties.
Studies also suggest that releases of self-sustaining gene drives may lead to co-existence of both wild-type and gene drive organisms. This co-existence has been predicted with modelling studies to result in ‘chaser’ dynamics, whereby local elimination would result in gaps in populations and wild-type rebounds to fill the localised empty niches (https://doi.org/10.1111/mec.15788). Such complexities need to be taken into consideration, and further implies a continued requirement to ensure that such organisms do not escape over a long-term basis, in contradiction to the design aim of elimination. For health applications, risk assessment for suppression drives should therefore not assume that exposure would be reduced based on an intended aim that the target organism would be eliminated. Moreover, how such unstable dynamics may impact local disease dynamics is also relevant.
This leads me to the critical points raised by my colleague Lim Li Ching on assessing safer alternatives, as well as by Professor Heinemann on the issue of benefits, and what comparators are used to assess potential benefits, and what is deemed as ‘inaction’. Similar framings have been included in the WHO guidance, such as using go/no-go criteria for moving candidates to field trials. The go/no-go safety criterion for moving a gene drive-modified investigational product to field testing has been proposed as ‘‘will do no more harm to human health than wild-type mosquitoes of the same genetic background and no more harm to the eco-system than other conventional vector control interventions’’. But this fails to acknowledge the above risks and uncertainties that cannot be easily determined prior to release and that may adversely impact disease. Moreover, restricting comparators for this safety standard to the most harmful current vector control methods or disease-carrying wild type mosquitoes, ignores other alterative, and safer public health interventions and vector control practices. As recently demonstrated by countries such as China, malaria eradication was achieved with a multi-pronged approach using existing tools and strategies that include increased political and financial commitments and coordination, free access to healthcare, incorporation of indigenous medical knowledge in the form of artemisinin-based treatments, poverty alleviation, increased diagnostics and surveillance, sanitation programs, and community involvement https://doi.org/10.1186/s40249-021-00882-9.
It is my view that discussions around benefits are incorrectly reducing disease to a solely biological phenomenon that can only be addressed by narrow technical interventions, without addressing fundamental socio-economic, political, as well as commercial determinants of disease, with potential for significant opportunity costs to overall health and well-being. Opportunity costs are another risk that may arise if gene drives result in neglecting focus and investment in solutions that are already known to be effective, and/or indeed could be further validated and expanded, for example in the case of local indigenous medicines that could be invested in.
Finally, with gene drive products expected to only last a limited time (aiming for 3 years before resistance develops), what is considered successful needs to be carefully defined. Over what time span? Over what area of release? If chaser dynamics are the norm for example, what is the expected impact on disease transmission, over which areas/times etc? how will a control area be defined and protected from genes drive organism contamination?
Cheers
Eva
I would like to echo comments on the issue of post release evolution already comprehensively raised by other commentors [#11560, #11614] and the related issue of genetic instability that has recently been reported for a leading gene drive mosquito candidate (see comment by Dr Ricarda Steinbrecher [#11616]) and the potential increased reliance on modelling with the attendant issues as raised by Dr Otto [#11622]. The guidance needs to incorporate such uncertainties with proposals such as cut-off criteria as developed by Testbiotech and raised in comment [#11552].
Another concern is the potential for combinatorial effects. With resistance development expected, it appears that developers are envisioning multiple product releases for each vector (of which there are multiple), with the potential to result in unanticipated effects of interacting drives. As already documented for ‘neutralising’ drives, this can lead to complex and unintended genetic changes https://doi.org/10.1016/j.molcel.2020.09.003.
There is still a lack of mitigation measures for gene drive organisms. The development of anti-CRISPR mosquitoes, if effective, would only inactivate the drive mechanism. There are currently no means to recall or revert gene drive organisms to restore wild type populations.
Another concern is the potential for combinatorial effects. With resistance development expected, it appears that developers are envisioning multiple product releases for each vector (of which there are multiple), with the potential to result in unanticipated effects of interacting drives. As already documented for ‘neutralising’ drives, this can lead to complex and unintended genetic changes https://doi.org/10.1016/j.molcel.2020.09.003.
There is still a lack of mitigation measures for gene drive organisms. The development of anti-CRISPR mosquitoes, if effective, would only inactivate the drive mechanism. There are currently no means to recall or revert gene drive organisms to restore wild type populations.
Hello all, the comments #11601 bring the follow aspects:
Socioeconomic Considerations/ Decision-Making and Community Involvement/ Critical Voices and Transparency
• Genetically modified mosquito: The Malaysian public engagement experience. https://doi.org/10.1002/biot.201200282
• The unreachable doorbells of South Texas: community engagement in colonias on the US-Mexico border for mosquito control. https://doi.org/10.1186/s12889-022-13426-z
• OPEN LETTER How to engage communities on a large scale? Lessons from World Mosquito Program in Rio de Janeiro, Brazil. https://doi.org/10.12688/gatesopenres.13153.2
• Informed consent and community engagement in open field research: lessons for gene drive Science. https://doi.org/10.1186/s12910-019-0389-3
• Ethics of community engagement in field trials of genetically modified mosquitoes. https://doi.org/10.1111/dewb.12147
• Community Engagement and Field Trials of Genetically Modified Insects and Animals. DOI: 10.1002/hast.808
• Oxitec and MosquitoMate in the United States: lessons for the future of gene drive mosquito control. https://doi.org/10.1080/20477724.2021.1919
• What Makes Community Engagement Effective?: Lessons from the Eliminate Dengue Program in Queensland Australia. https://doi.org/10.1371/journal.pntd.0003713
• Designing a Community Engagement Framework for a New Dengue Control Method: A Case Study from Central Vietnam. doi:10.1371/journal.pntd.0002794
• Community acceptance of yeast interfering RNA larvicide technology for control of Aedes mosquitoes in Trinidad. https://doi.org/10.1371/journal.pone.0237675
• Towards a framework for community engagement in global health research. https://doi.org/10.1016/j.pt.2010.02.009
• California Residents’ Perceptions of Gene Drive Systems to Control Mosquito-Borne Disease. doi: 10.3389/fbioe.2022.848707
The comments about mathematical models #11622, there are some information
Models Concepts
• Two step male release strategy using transgenic mosquito lines to control transmission of vector-borne diseases. https://doi.org/10.1016/j.actatropica.2013.09.023
• MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations. DOI: 10.1111/2041-210X.13318
• The Effect of Mating Complexity on Gene Drive Dynamics. https://doi.org/10.1086/722157
• Gene drives gaining speed. https://doi.org/10.1038/ s41576-021-00386-0
I am also suggesting this articles that show a post release monitoring study.
Post release Monitoring
• Effect of interruption of over-flooding releases of transgenic mosquitoes over wild population of Aedes aegypti: two case studies in Brazil. https://doi.org/10.1111/eea.12618
• Localized Control of Aedes aegypti (Diptera: Culicidae) in Miami, FL, via Inundative Releases of Wolbachia-Infected Male Mosquitoes. https://doi.org/10.1093/jme/tjz051
• Monitoring Needs for Gene Drive Mosquito Projects: Lessons From Vector Control Field Trials and Invasive Species. https://doi.org/10.3389/fgene.2021.780327
• Joint FAO/IAEA Coordinated Research Project on “Mosquito Handling, Transport, Release and Male Trapping Methods” in Support of SIT Application to Control Mosquitoes. https://doi.org/10.3390/insects14020108
I also found this book that can be useful.
Book
Gene Drives at Tipping Points Precautionary Technology Assessment and Governance of New Approaches to Genetically Modify Animal and Plant Populations. https://doi.org/10.1007/978-3-030-38934-5
Socioeconomic Considerations/ Decision-Making and Community Involvement/ Critical Voices and Transparency
• Genetically modified mosquito: The Malaysian public engagement experience. https://doi.org/10.1002/biot.201200282
• The unreachable doorbells of South Texas: community engagement in colonias on the US-Mexico border for mosquito control. https://doi.org/10.1186/s12889-022-13426-z
• OPEN LETTER How to engage communities on a large scale? Lessons from World Mosquito Program in Rio de Janeiro, Brazil. https://doi.org/10.12688/gatesopenres.13153.2
• Informed consent and community engagement in open field research: lessons for gene drive Science. https://doi.org/10.1186/s12910-019-0389-3
• Ethics of community engagement in field trials of genetically modified mosquitoes. https://doi.org/10.1111/dewb.12147
• Community Engagement and Field Trials of Genetically Modified Insects and Animals. DOI: 10.1002/hast.808
• Oxitec and MosquitoMate in the United States: lessons for the future of gene drive mosquito control. https://doi.org/10.1080/20477724.2021.1919
• What Makes Community Engagement Effective?: Lessons from the Eliminate Dengue Program in Queensland Australia. https://doi.org/10.1371/journal.pntd.0003713
• Designing a Community Engagement Framework for a New Dengue Control Method: A Case Study from Central Vietnam. doi:10.1371/journal.pntd.0002794
• Community acceptance of yeast interfering RNA larvicide technology for control of Aedes mosquitoes in Trinidad. https://doi.org/10.1371/journal.pone.0237675
• Towards a framework for community engagement in global health research. https://doi.org/10.1016/j.pt.2010.02.009
• California Residents’ Perceptions of Gene Drive Systems to Control Mosquito-Borne Disease. doi: 10.3389/fbioe.2022.848707
The comments about mathematical models #11622, there are some information
Models Concepts
• Two step male release strategy using transgenic mosquito lines to control transmission of vector-borne diseases. https://doi.org/10.1016/j.actatropica.2013.09.023
• MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations. DOI: 10.1111/2041-210X.13318
• The Effect of Mating Complexity on Gene Drive Dynamics. https://doi.org/10.1086/722157
• Gene drives gaining speed. https://doi.org/10.1038/ s41576-021-00386-0
I am also suggesting this articles that show a post release monitoring study.
Post release Monitoring
• Effect of interruption of over-flooding releases of transgenic mosquitoes over wild population of Aedes aegypti: two case studies in Brazil. https://doi.org/10.1111/eea.12618
• Localized Control of Aedes aegypti (Diptera: Culicidae) in Miami, FL, via Inundative Releases of Wolbachia-Infected Male Mosquitoes. https://doi.org/10.1093/jme/tjz051
• Monitoring Needs for Gene Drive Mosquito Projects: Lessons From Vector Control Field Trials and Invasive Species. https://doi.org/10.3389/fgene.2021.780327
• Joint FAO/IAEA Coordinated Research Project on “Mosquito Handling, Transport, Release and Male Trapping Methods” in Support of SIT Application to Control Mosquitoes. https://doi.org/10.3390/insects14020108
I also found this book that can be useful.
Book
Gene Drives at Tipping Points Precautionary Technology Assessment and Governance of New Approaches to Genetically Modify Animal and Plant Populations. https://doi.org/10.1007/978-3-030-38934-5
Dear colleagues,
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 biosafety policies and regulations, as well as in the COPs and MOPs since COP1. I have served on a former AHTEG on risk assessment.
First, my thanks to the Secretariat and to the moderator for allowing some extra time for this forum, because the last two weeks have been packed with discussions in multiple international fora, such as the OECD.
I have read with interest the contributions to this Question 1 and share the following observations.
As the elements that I wanted to suggest have already been mentioned (see for example the comprehensive overview by DeVos, #11626), I limit my submission to highlighting the importance of some elements:
a) the concept of identifying scientifically plausible pathways to harm as the starting point of the risk assessment, bearing in mind that not everything that is theoretically conceivable is scientifically plausible. It is theoretically conceivable that the current climate change is not caused by human activity, but that version is not scientifically plausible. Lastly, as an aside, I wish that people would stop using the non-sensical term ‘problem formulation’. In the ERA process we do not formulate problems, we formulate questions. (Problem formulation is what some constancies do when they want to convince a client that it has a problem that their consultancy can solve..).
b) the general principle that ERA must be ‘scientifically sound’, as specified in Annex III CPB. ‘Soundness’ relates to the protection goals of the underlying legal system. I therefore support the suggestion by Hayes (#116410) that there is scope for additional guidance materials on how to handle stakeholder concerns.
Finally, and an observation about the next steps.
It is very important to remain mindful of the fact that voluntary guidance that had been discussed for many years in on-line fora and AHTEGs, in the end was not adopted by the COPMOP. As discussed in COPMOP2016, there were multiple reasons why many parties were unhappy with the result of well the over a decade of discussions, one of which was that the originally focused exercise of producing a ’roadmap’ over time ballooned into many different directions. I would therefore strongly recommend that this process stays as close to CPB decision 10/10, which 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”. It is important to recognise that the decision refers to developing materials to support ERA in accordance with Annex III, i.e. the decision is not to develop new or alternative risk assessment. I praise the moderator and the CBD Secretariat for keeping this focus by asking in Question 1 for ‘specific elements’.
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 biosafety policies and regulations, as well as in the COPs and MOPs since COP1. I have served on a former AHTEG on risk assessment.
First, my thanks to the Secretariat and to the moderator for allowing some extra time for this forum, because the last two weeks have been packed with discussions in multiple international fora, such as the OECD.
I have read with interest the contributions to this Question 1 and share the following observations.
As the elements that I wanted to suggest have already been mentioned (see for example the comprehensive overview by DeVos, #11626), I limit my submission to highlighting the importance of some elements:
a) the concept of identifying scientifically plausible pathways to harm as the starting point of the risk assessment, bearing in mind that not everything that is theoretically conceivable is scientifically plausible. It is theoretically conceivable that the current climate change is not caused by human activity, but that version is not scientifically plausible. Lastly, as an aside, I wish that people would stop using the non-sensical term ‘problem formulation’. In the ERA process we do not formulate problems, we formulate questions. (Problem formulation is what some constancies do when they want to convince a client that it has a problem that their consultancy can solve..).
b) the general principle that ERA must be ‘scientifically sound’, as specified in Annex III CPB. ‘Soundness’ relates to the protection goals of the underlying legal system. I therefore support the suggestion by Hayes (#116410) that there is scope for additional guidance materials on how to handle stakeholder concerns.
Finally, and an observation about the next steps.
It is very important to remain mindful of the fact that voluntary guidance that had been discussed for many years in on-line fora and AHTEGs, in the end was not adopted by the COPMOP. As discussed in COPMOP2016, there were multiple reasons why many parties were unhappy with the result of well the over a decade of discussions, one of which was that the originally focused exercise of producing a ’roadmap’ over time ballooned into many different directions. I would therefore strongly recommend that this process stays as close to CPB decision 10/10, which 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”. It is important to recognise that the decision refers to developing materials to support ERA in accordance with Annex III, i.e. the decision is not to develop new or alternative risk assessment. I praise the moderator and the CBD Secretariat for keeping this focus by asking in Question 1 for ‘specific elements’.
I am Camilla Beech, an independent regulatory consultant with a long history of working with genetically modified insects, and currently working with the Imperial College London based Target Malaria consortium.
I’d like to support the discussion introduced in response #11599 regarding other international bodies addressing the governance of gene drive technologies in mosquitoes. All novel vector control technologies that are first in class, such as gene drives for mosquito population reduction and population replacement are evaluated rigorously through WHO processes such as the vector control advisory committee (VCAG) for public health utility and the vector control pre-qualification process. A cost-benefit analysis is also included in WHO policy decisions. The World Health Organisation (WHO) has had a long history of examining the control of mosquito borne disease, and has issued guidance as mentioned in the previous posting. Any new elements of guidance must be aligned to but not duplicate the WHO guidance mentioned previously..
Existing guidance documents on risk assessment for gene drive is broadly applicable and should follow the well trodden problem formulation approach as described in Connolly et al 2021 [ https://doi.org/10.1186/s12936-021-03674-6 } and Connolly 2022 [Recommendations for Environmental Risk Assessment of Gene Drive Applications for malaria Vector control https://doi.org/10.1186/s12936-022-04183-w]. Furthermore any guidance should take into account the iterative nature of risk assessment, responding to new scientific knowledge, as has been stated several times in this thread.
I’d like to support the discussion introduced in response #11599 regarding other international bodies addressing the governance of gene drive technologies in mosquitoes. All novel vector control technologies that are first in class, such as gene drives for mosquito population reduction and population replacement are evaluated rigorously through WHO processes such as the vector control advisory committee (VCAG) for public health utility and the vector control pre-qualification process. A cost-benefit analysis is also included in WHO policy decisions. The World Health Organisation (WHO) has had a long history of examining the control of mosquito borne disease, and has issued guidance as mentioned in the previous posting. Any new elements of guidance must be aligned to but not duplicate the WHO guidance mentioned previously..
Existing guidance documents on risk assessment for gene drive is broadly applicable and should follow the well trodden problem formulation approach as described in Connolly et al 2021 [ https://doi.org/10.1186/s12936-021-03674-6 } and Connolly 2022 [Recommendations for Environmental Risk Assessment of Gene Drive Applications for malaria Vector control https://doi.org/10.1186/s12936-022-04183-w]. Furthermore any guidance should take into account the iterative nature of risk assessment, responding to new scientific knowledge, as has been stated several times in this thread.
Dear Participants,
I would like to kindly remind you that the forum will close tomorrow (Tuesday 25 April 2023) at 17:00 EDT. There is still time to share your valuable inputs, focusing on the specific elements to consider in the outline of the 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.
Best regards,
Luciana
I would like to kindly remind you that the forum will close tomorrow (Tuesday 25 April 2023) at 17:00 EDT. There is still time to share your valuable inputs, focusing on the specific elements to consider in the outline of the 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.
Best regards,
Luciana
My name is Martin Batic, and I am the head of the Biotechnology Section at the Ministry of Environment, Climate and Energy, which is responsible for the biosafety framework in Slovenia. I have a PhD in biotechnological sciences. I have many years of experience in the field of biosafety, biotechnology, and environmental risk assessment of LMOs and I am a national focal point for the Cartagena Protocol.
Many contributions have already suggested elements for a voluntary guidance document on gene drive, which I would agree with. So, in general, I would support the idea that gene drive risk assessment should be science-based to identify potential harms and should be consistent with the principle of case-by-case assessment, as mentioned in post #11544, #11599 and others. However, there are still areas of uncertainty and knowledge gaps whose thorough understanding should be part of the guidance. On the other hand, the guidance should not ignore post-release monitoring and evaluation, as mentioned in posts #11556, #11560 and others.
Best regards,
Martin
Many contributions have already suggested elements for a voluntary guidance document on gene drive, which I would agree with. So, in general, I would support the idea that gene drive risk assessment should be science-based to identify potential harms and should be consistent with the principle of case-by-case assessment, as mentioned in post #11544, #11599 and others. However, there are still areas of uncertainty and knowledge gaps whose thorough understanding should be part of the guidance. On the other hand, the guidance should not ignore post-release monitoring and evaluation, as mentioned in posts #11556, #11560 and others.
Best regards,
Martin
My name is Andreas Heissenberger and I am Unit Head Landuse & Biosafety at the Environment Agency Austria. I am biochemist and ecologist by training and work in the field of LMOs for more than 25 years now.
Much has been said by other experts in this forum which I will not repeat here. However, I want to reflect on some considerations regarding important elements for the outline for the voluntary guidance materials on risk assessment of LMOs containing engineered gene drives.
• As has been mentioned by others (e.g. #11560, #11614, #11603) there is a not-negligible difference in the application of LMOs containing engineered drives to LMOs that are used right now: They are designed to spread in the environment once they are released. The guidance materials should therefore take into account the specific objectives of gene drive applications and the fundamental differences in the application with respect to current LMOs, e.g. the aim to introduce environmental effects like the suppression of a species or the release into non-managed environments. In addition, their behaviour and possible post-release changes in the environment are hardly predictable by limited scale trials in contained systems – therefore risk management plays an even more important role than with “standard” LMOs.
• In that respect also considerations regarding appropriate methodologies and considerations with respect to the appropriate temporal and spatial scale of the assessment and the post release monitoring are vital
• The guidance materials should identify information needs for the risk assessment of LMOs with engineered gene drives related to their possible effects on food webs and ecosystems as a whole (as touched upon by post #11592), e.g. information regarding the specific role of the species targeted by the gene drive, knowledge on biology, ecology, its role in the ecosystem, including information on behaviour and interactions with other species as well as information on closely related species.
• In that context and as mentioned also by others, problem formulation and the identification of protection goals is important. As mentioned in UNEP/DBD/BS/COP-MOP/8/8/Add.1 protection goals may also be informed by national policies and legislation.
• Other important issues are the effectiveness of the gene drive, including the potential for resistance development, evolutionary consequences (e.g. evolutionary responses of the pathogens due to changes in its vector population), or the possibility to reverse the gene drive.
• It is also important not to focus on one application of LMOs containing gene drives, just because it is the most advanced (i.e. mosquitos to eradicate diseases). There are other applications also targeted at the eradication of populations, namely invasive alien species, which do cover a large range of species, including mammals and which might have considerable effects on the environment, but which are probably requiring different risk assessment methods and certainly different risk management methods.
Benefits however, should not be considered in the voluntary guidance materials on risk assessment, as this issue should be dealt with under Article26 of the Cartagena Protocol (socio-economic considerations).
Much has been said by other experts in this forum which I will not repeat here. However, I want to reflect on some considerations regarding important elements for the outline for the voluntary guidance materials on risk assessment of LMOs containing engineered gene drives.
• As has been mentioned by others (e.g. #11560, #11614, #11603) there is a not-negligible difference in the application of LMOs containing engineered drives to LMOs that are used right now: They are designed to spread in the environment once they are released. The guidance materials should therefore take into account the specific objectives of gene drive applications and the fundamental differences in the application with respect to current LMOs, e.g. the aim to introduce environmental effects like the suppression of a species or the release into non-managed environments. In addition, their behaviour and possible post-release changes in the environment are hardly predictable by limited scale trials in contained systems – therefore risk management plays an even more important role than with “standard” LMOs.
• In that respect also considerations regarding appropriate methodologies and considerations with respect to the appropriate temporal and spatial scale of the assessment and the post release monitoring are vital
• The guidance materials should identify information needs for the risk assessment of LMOs with engineered gene drives related to their possible effects on food webs and ecosystems as a whole (as touched upon by post #11592), e.g. information regarding the specific role of the species targeted by the gene drive, knowledge on biology, ecology, its role in the ecosystem, including information on behaviour and interactions with other species as well as information on closely related species.
• In that context and as mentioned also by others, problem formulation and the identification of protection goals is important. As mentioned in UNEP/DBD/BS/COP-MOP/8/8/Add.1 protection goals may also be informed by national policies and legislation.
• Other important issues are the effectiveness of the gene drive, including the potential for resistance development, evolutionary consequences (e.g. evolutionary responses of the pathogens due to changes in its vector population), or the possibility to reverse the gene drive.
• It is also important not to focus on one application of LMOs containing gene drives, just because it is the most advanced (i.e. mosquitos to eradicate diseases). There are other applications also targeted at the eradication of populations, namely invasive alien species, which do cover a large range of species, including mammals and which might have considerable effects on the environment, but which are probably requiring different risk assessment methods and certainly different risk management methods.
Benefits however, should not be considered in the voluntary guidance materials on risk assessment, as this issue should be dealt with under Article26 of the Cartagena Protocol (socio-economic considerations).
Dear All,
my name is Werner Schenkel I am working in risk assessment and risk management for der German competent authority (Federal Office of Consumer Protection and Food Safety) for 18 years.
First of all, I would like to commend the participants of this forum for the wealth of insightful and well-founded information and arguments. I also thank our moderator for her commitment and for focusing the forum here on specific elements to be included in the outline.
Several contributors have argued, that loosing focus and scope in the development of additional guidance materials may delay results, compromise practical usability and put acknowledgement of resulting materials at risk.
For this reason, I support the recommendation of Pieter van der Meer (#11650) for this process to stay close to CPB decision 10/10 and the Annex III to the Protocol as baseline for risk assessment.
Regarding specific element to be included in the outline I commend Yann Devos (#11626) for clearly naming elements and providing sound reasoning for these.
Although problem formulation is an approach, that is not new or specific to the risk assessment of gene drive organisms many contributors (#11544, #11556, #11581; #11583, #11592, #11626) identified it as an approach well suited to identify factors specific to LMO containing gene drives and thus guide the risk assessment. I do fully agree.
Modelling is an element that may be of specific importance in risk assessment of gene drive organisms, as mentioned by Simon #11622, Devos #11626 and Hayes #11641. I support inclusion of an element dealing with the reasonable and responsible use of models in this context.
Recommendations on phased testing is an element that should be included, as there may arise challenges that are specific for LMO containing gene drives, as has been mentioned earlier (#11626). The WHO (2021) Guidance Framework for testing of genetically modified mosquitoes, which has already been identified as key document by the moderator and others can provides a good background for this element.
Post release monitoring might pose challenges specific to monitoring of LMO containing engineered gene drives. The outline should therefore include a specific element regarding these challenges as already mentioned by #11556, #11561, #11575, #11599, #11626 and others. As Ossama AbledKawy (#11603) pointed out, an additional guidance document on monitoring of LMO released into the environment is already available, covering general aspects.
Finally, I would like to endorse comments stating, that additional voluntary guidance materials need to provide added value (EderToppa #11575) and avoid duplication of efforts and standards (Yann Devos #11626).
Kind regards and all the best to you,
Werner Schenkel
my name is Werner Schenkel I am working in risk assessment and risk management for der German competent authority (Federal Office of Consumer Protection and Food Safety) for 18 years.
First of all, I would like to commend the participants of this forum for the wealth of insightful and well-founded information and arguments. I also thank our moderator for her commitment and for focusing the forum here on specific elements to be included in the outline.
Several contributors have argued, that loosing focus and scope in the development of additional guidance materials may delay results, compromise practical usability and put acknowledgement of resulting materials at risk.
For this reason, I support the recommendation of Pieter van der Meer (#11650) for this process to stay close to CPB decision 10/10 and the Annex III to the Protocol as baseline for risk assessment.
Regarding specific element to be included in the outline I commend Yann Devos (#11626) for clearly naming elements and providing sound reasoning for these.
Although problem formulation is an approach, that is not new or specific to the risk assessment of gene drive organisms many contributors (#11544, #11556, #11581; #11583, #11592, #11626) identified it as an approach well suited to identify factors specific to LMO containing gene drives and thus guide the risk assessment. I do fully agree.
Modelling is an element that may be of specific importance in risk assessment of gene drive organisms, as mentioned by Simon #11622, Devos #11626 and Hayes #11641. I support inclusion of an element dealing with the reasonable and responsible use of models in this context.
Recommendations on phased testing is an element that should be included, as there may arise challenges that are specific for LMO containing gene drives, as has been mentioned earlier (#11626). The WHO (2021) Guidance Framework for testing of genetically modified mosquitoes, which has already been identified as key document by the moderator and others can provides a good background for this element.
Post release monitoring might pose challenges specific to monitoring of LMO containing engineered gene drives. The outline should therefore include a specific element regarding these challenges as already mentioned by #11556, #11561, #11575, #11599, #11626 and others. As Ossama AbledKawy (#11603) pointed out, an additional guidance document on monitoring of LMO released into the environment is already available, covering general aspects.
Finally, I would like to endorse comments stating, that additional voluntary guidance materials need to provide added value (EderToppa #11575) and avoid duplication of efforts and standards (Yann Devos #11626).
Kind regards and all the best to you,
Werner Schenkel
----Posted on behalf of Mr. Kamal Kumar Rai---
On the behalf of IPLCs ATHEG member 2020, I received Tainting 2022 and also have been involved on various discussion on gene drive, containing engineered gene drive. My quires were behavior and relationship within and other species and its impacts study is missing, gapes or need to do. I agree with Andreas Heissenberger,
Thanks with regards
Kamal
IPLC
On the behalf of IPLCs ATHEG member 2020, I received Tainting 2022 and also have been involved on various discussion on gene drive, containing engineered gene drive. My quires were behavior and relationship within and other species and its impacts study is missing, gapes or need to do. I agree with Andreas Heissenberger,
Thanks with regards
Kamal
IPLC
My name is Dr. Guy Reeves, from the Max Planck Institute for Evolutionary Biology (Germany), I am an evolutionary geneticist with interests techniques intended to act autonomously in the environment. I am a named inventor on a granted patent related to gene drive (EP2934093B1), and as such could be seen to have a declared conflict of interest.
Topic: Unintentional transboundary movement
valuable contributions on the same topic by Silke Fuchs #11589, Angela Lozan #11596 Samson Simon #11622
——-
As pointed out by Werner Schenkel #11580 (and reiterated by Robert Friedman #11599]) gene drives can usefully be categorised (with admittedly subjective boundaries for the most part), examples given were
localized / nonlocalized approaches
self-limiting /self-sustaining
low threshold (or no-threshold) / high threshold
In thinking about additional guidance and how to prioritise, it would appear useful to consider that transition between at least some of the categories may occur subsequent to releases due either to (1) mutation in the field, or (2) mis-parametrisation of the drive properties in regulatory documents for a range of reasons (including failing to appreciate relevant standing genetic variation in target population(s)).
Furthermore, such transitions are not equally likely in each directions, as an illustration:-
-the transition from low threshold (or no-threshold) drives to high(er) threshold drives is probably more likely than in the reverse direction
-the transition from localised to non-localised or less-localised drives is intuitively more likely than in the reverse direction
- transitions between self-limiting drives to more self-sustaining drives is harder to make predictions about.
If the potential for transitions between categories is accepted it would appear prudent to focus on those where the most guidance will be required. In this case non-localised no or low threshold drives. This focus is further justified by the fields focus on such drives an example being SDGD- which is presumably a candidate for release by Target Malaria
Simoni, Alekos, Andrew M. Hammond, Andrea K. Beaghton, Roberto Galizi, Chrysanthi Taxiarchi, Kyros Kyrou, Dario Meacci, et al. 2020. ‘A Male-Biased Sex-Distorter Gene Drive for the Human Malaria Vector Anopheles Gambiae’. Nature Biotechnology, May, 1–7. https://doi.org/10.1038/s41587-020-0508-1.
One of the most enduringly remarkable features of the field of gene drive might be that despite the long repeated recognition that unapproved transboundary movement (in this context the movement between sovereign nations) is an issue, the vast majority of treatments are superficial or appear to imply that this issue will be dealt with at some future point. Given the fields current focus on low threshold (or no-threshold) drives with little or no localisation potential, this is appearing an increasingly striking omission. Even in thoughtful documents by organisations that are fundamentally intended to coordinate between nations, little or nothing substantive is said about how to address this issue. This is at least as far as I am aware; I am very happy to be corrected on this point if I have missed something.
An example is the following report.
African Union. 2018. ‘Gene Drives for Malaria Control and Elimination in Africa’. https://www.nepad.org/publication/gene-drives-malaria-control-and-elimination-africa.
notable quotes, at least in my reading, are limited to the following
“Gene drive strategies differ in ‘strength’ and have different thresholds beyond which they would continue to spread unassisted in nature. Weaker drive systems, sometimes also referred to as high threshold systems, are slower to increase in frequency in a target population, less likely to spread to neighbouring populations and require a higher number of releases to be effective. On the other hand, current technologies proposed for malaria elimination are strong drives, also referred to as low threshold gene drives, in which releases of even a small number of individual gene-drive mosquitoes can lead to an extensive spread in populations. Because of this high probability of spread, such low-threshold gene drives also carry significant potential for malaria control. It is estimated that even releases in less than 10% of the wild population of mosquitoes, given optimal conditions, could spread sufficiently and lead to malaria eradication within a few years (Eckhoff et al., 2016). “
From page 17 of the report (African Union 2018):
“Unlike in the phased-development of drugs or vaccines, the stages of gene drive development will likely overlap. For example, once the gene drive mosquitoes are released in small scale at stage two, successful outcome may mean that they spread beyond the initial areas of release, and would effectively transform into a large-scale release. “
From page 19 of the report (African Union 2018):
“Being organisms that are mobile and that the transgenic construct will spread through interbreeding populations, which cannot be contained within a single country, transboundary issues have to be taken into consideration in the regulation and deployment of transgenic insects. In this case, a regional regulatory approach will be relevant instead of only having independent national regulatory systems as has been the case with GM crops. A regional approach is also required because the spread of malaria cuts across several countries in a REC and yet it will be practically impossible to conduct confined trials in each of the malaria-infested countries. Implementation of such technologies would have more impact if done at regional level than just in one country. This will require building strong collaborations among countries and harmonizing technical requirements and processes for regulating transgenic insects, the most practical being at the regional level.”
From page 25 of the report (African Union 2018)
The quote text from page 19 could be read as equating uncontrolled transboundary movement as success. If it is assumed that all countries in a region act with unanimity on releases it is possible to maintain that there is no an issue to resolve, however is this really a plausible scenario? It would appear to me that additional voluntary guidance materials on this topic would provide considerable added value (EderToppa #11575) and would not be duplicated (Yann Devos #11626) in other processes I am aware of.
For example in the “Background materials linked to the Guidance on Risk Assessment of Living Modified Organisms” linked to by this forum there are no documents for the topic of “Unintentional transboundary movement” (while other topics have 30 documents)
https://bch.cbd.int/onlineconferences/ra_guidance_references.shtml
On the topic of Unintentional transboundary movement and why despite decades of technical developments discussion has largely been sidestepped; I would make the observation that it is a continuation of a similarly skimmed-over issue of failing to explicitly article how local human communities might signal the refusal to consent to a release (or even in what circumstances it could be withdrawn). This absence is strikingly contrasted be the extensive and repeated articulation of how community consent might be signalled, eloquently summarised by many of the articles cited by Margareth Capurro, #11649.
To my knowledge the most substantive treatment of the complex issue of unintentional transboundary can be found in.
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.
I would observe that with the continued absence of binding obligations or even norms to prospectively notify potentially impacted nations that are in the region of releases, there is considerable potential for misunderstanding and conflict. Furthermore, it would seam self-evident that post-release monitoring of the extent of gene drive spread has to be entirely independent of the organisation responsible for releases, I am unaware of any guidance on this topic - I am happy to be corrected if I have missed it.
——-
While not necessarily connected to above point, it is the case that self-sustaining approaches intended to act autonomously in the environment, can facilitate regulatory strategies that are not available to most LMO release applicants to date. Namely incentives to tend to under-report the extent to which a drive will spread in regulatory documents for small experimental field trials, with the (conscious or unconscious) expectation that regulators may feel pressured to retrospectively approve a drive’s presence over wide areas (see quote from page 19 of African Union report .above). This may be particularly the case, if the escape from the approved area was successful in its aim of controlling a devastating disease like malaria (even temporarily).
Thanks
Guy Reeves
Max Planck Institute for Evolutionary Biology (Germany)
Topic: Unintentional transboundary movement
valuable contributions on the same topic by Silke Fuchs #11589, Angela Lozan #11596 Samson Simon #11622
——-
As pointed out by Werner Schenkel #11580 (and reiterated by Robert Friedman #11599]) gene drives can usefully be categorised (with admittedly subjective boundaries for the most part), examples given were
localized / nonlocalized approaches
self-limiting /self-sustaining
low threshold (or no-threshold) / high threshold
In thinking about additional guidance and how to prioritise, it would appear useful to consider that transition between at least some of the categories may occur subsequent to releases due either to (1) mutation in the field, or (2) mis-parametrisation of the drive properties in regulatory documents for a range of reasons (including failing to appreciate relevant standing genetic variation in target population(s)).
Furthermore, such transitions are not equally likely in each directions, as an illustration:-
-the transition from low threshold (or no-threshold) drives to high(er) threshold drives is probably more likely than in the reverse direction
-the transition from localised to non-localised or less-localised drives is intuitively more likely than in the reverse direction
- transitions between self-limiting drives to more self-sustaining drives is harder to make predictions about.
If the potential for transitions between categories is accepted it would appear prudent to focus on those where the most guidance will be required. In this case non-localised no or low threshold drives. This focus is further justified by the fields focus on such drives an example being SDGD- which is presumably a candidate for release by Target Malaria
Simoni, Alekos, Andrew M. Hammond, Andrea K. Beaghton, Roberto Galizi, Chrysanthi Taxiarchi, Kyros Kyrou, Dario Meacci, et al. 2020. ‘A Male-Biased Sex-Distorter Gene Drive for the Human Malaria Vector Anopheles Gambiae’. Nature Biotechnology, May, 1–7. https://doi.org/10.1038/s41587-020-0508-1.
One of the most enduringly remarkable features of the field of gene drive might be that despite the long repeated recognition that unapproved transboundary movement (in this context the movement between sovereign nations) is an issue, the vast majority of treatments are superficial or appear to imply that this issue will be dealt with at some future point. Given the fields current focus on low threshold (or no-threshold) drives with little or no localisation potential, this is appearing an increasingly striking omission. Even in thoughtful documents by organisations that are fundamentally intended to coordinate between nations, little or nothing substantive is said about how to address this issue. This is at least as far as I am aware; I am very happy to be corrected on this point if I have missed something.
An example is the following report.
African Union. 2018. ‘Gene Drives for Malaria Control and Elimination in Africa’. https://www.nepad.org/publication/gene-drives-malaria-control-and-elimination-africa.
notable quotes, at least in my reading, are limited to the following
“Gene drive strategies differ in ‘strength’ and have different thresholds beyond which they would continue to spread unassisted in nature. Weaker drive systems, sometimes also referred to as high threshold systems, are slower to increase in frequency in a target population, less likely to spread to neighbouring populations and require a higher number of releases to be effective. On the other hand, current technologies proposed for malaria elimination are strong drives, also referred to as low threshold gene drives, in which releases of even a small number of individual gene-drive mosquitoes can lead to an extensive spread in populations. Because of this high probability of spread, such low-threshold gene drives also carry significant potential for malaria control. It is estimated that even releases in less than 10% of the wild population of mosquitoes, given optimal conditions, could spread sufficiently and lead to malaria eradication within a few years (Eckhoff et al., 2016). “
From page 17 of the report (African Union 2018):
“Unlike in the phased-development of drugs or vaccines, the stages of gene drive development will likely overlap. For example, once the gene drive mosquitoes are released in small scale at stage two, successful outcome may mean that they spread beyond the initial areas of release, and would effectively transform into a large-scale release. “
From page 19 of the report (African Union 2018):
“Being organisms that are mobile and that the transgenic construct will spread through interbreeding populations, which cannot be contained within a single country, transboundary issues have to be taken into consideration in the regulation and deployment of transgenic insects. In this case, a regional regulatory approach will be relevant instead of only having independent national regulatory systems as has been the case with GM crops. A regional approach is also required because the spread of malaria cuts across several countries in a REC and yet it will be practically impossible to conduct confined trials in each of the malaria-infested countries. Implementation of such technologies would have more impact if done at regional level than just in one country. This will require building strong collaborations among countries and harmonizing technical requirements and processes for regulating transgenic insects, the most practical being at the regional level.”
From page 25 of the report (African Union 2018)
The quote text from page 19 could be read as equating uncontrolled transboundary movement as success. If it is assumed that all countries in a region act with unanimity on releases it is possible to maintain that there is no an issue to resolve, however is this really a plausible scenario? It would appear to me that additional voluntary guidance materials on this topic would provide considerable added value (EderToppa #11575) and would not be duplicated (Yann Devos #11626) in other processes I am aware of.
For example in the “Background materials linked to the Guidance on Risk Assessment of Living Modified Organisms” linked to by this forum there are no documents for the topic of “Unintentional transboundary movement” (while other topics have 30 documents)
https://bch.cbd.int/onlineconferences/ra_guidance_references.shtml
On the topic of Unintentional transboundary movement and why despite decades of technical developments discussion has largely been sidestepped; I would make the observation that it is a continuation of a similarly skimmed-over issue of failing to explicitly article how local human communities might signal the refusal to consent to a release (or even in what circumstances it could be withdrawn). This absence is strikingly contrasted be the extensive and repeated articulation of how community consent might be signalled, eloquently summarised by many of the articles cited by Margareth Capurro, #11649.
To my knowledge the most substantive treatment of the complex issue of unintentional transboundary can be found in.
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.
I would observe that with the continued absence of binding obligations or even norms to prospectively notify potentially impacted nations that are in the region of releases, there is considerable potential for misunderstanding and conflict. Furthermore, it would seam self-evident that post-release monitoring of the extent of gene drive spread has to be entirely independent of the organisation responsible for releases, I am unaware of any guidance on this topic - I am happy to be corrected if I have missed it.
——-
While not necessarily connected to above point, it is the case that self-sustaining approaches intended to act autonomously in the environment, can facilitate regulatory strategies that are not available to most LMO release applicants to date. Namely incentives to tend to under-report the extent to which a drive will spread in regulatory documents for small experimental field trials, with the (conscious or unconscious) expectation that regulators may feel pressured to retrospectively approve a drive’s presence over wide areas (see quote from page 19 of African Union report .above). This may be particularly the case, if the escape from the approved area was successful in its aim of controlling a devastating disease like malaria (even temporarily).
Thanks
Guy Reeves
Max Planck Institute for Evolutionary Biology (Germany)
My name is Marja Ruohonen-Lehto, and I work as a Senior Adviser at the Finnish Environment Institute in Helsinki, Finland. I have a PhD in genetics and have worked on biosafety issues for more than 25 years. I have been a member of previous AHTEGs on risk assessment and risk management and have participated in the Cartagena COP-MOP negotiations since 2006.
I have followed with great interest these discussions and do not have much to add, and I try to refrain from repeating what others have said. I would like to support the following interventions, in particular: # 11556, # 11560, # 11561, # 11575, # 11581, # 11603, # 11614, # 11616, # 11622, # 11661 and # 11667. A well-structured risk-assessment process is vital (based on problem formulation, well-defined protection goals, carefully identified assessment endpoints and plausible pathways to harm). It is important that the guidance also covers general issues of gene drives while having a specific focus on mosquitoes. This will make it useful for other types of applications as well, e.g., for the control of invasive alien species and pests. Further, like stated in intervention # 11667 the guidance materials should take into account the specific objectives of gene drive applications and their aim to introduce environmental effects like the suppression of a species or the release into non-managed environments – quite different from the present LMO applications. The interventions on modelling and uncertainty are very relevant – these two topics should be covered by the guidance document. See # 11622 for specific suggestions on how to structure the guidance and what could be included in the general section of the guidance.
Many thanks colleagues, this vivid discussion will be of great use for our future work.
I have followed with great interest these discussions and do not have much to add, and I try to refrain from repeating what others have said. I would like to support the following interventions, in particular: # 11556, # 11560, # 11561, # 11575, # 11581, # 11603, # 11614, # 11616, # 11622, # 11661 and # 11667. A well-structured risk-assessment process is vital (based on problem formulation, well-defined protection goals, carefully identified assessment endpoints and plausible pathways to harm). It is important that the guidance also covers general issues of gene drives while having a specific focus on mosquitoes. This will make it useful for other types of applications as well, e.g., for the control of invasive alien species and pests. Further, like stated in intervention # 11667 the guidance materials should take into account the specific objectives of gene drive applications and their aim to introduce environmental effects like the suppression of a species or the release into non-managed environments – quite different from the present LMO applications. The interventions on modelling and uncertainty are very relevant – these two topics should be covered by the guidance document. See # 11622 for specific suggestions on how to structure the guidance and what could be included in the general section of the guidance.
Many thanks colleagues, this vivid discussion will be of great use for our future work.
Dear colleagues
At a couple of points along this discussion I've read comments about previous AHTEG Guidance and it being characterised as somehow not appreciated by the Parties. While it was robustly debated by the COPMOP along the way, as any developing framework should be, my memory of events does not correspond with the narrative that it was “not adopted”.
The COPMOP6 Commended its progress. The testing of the Guidance produced was welcomed by Parties in COPMOP7 and this led to more Parties, other Governments and relevant organisations, being invited to test or use it. It did extremely well in the peer-review process and was further enhanced as a result. Then the COPMOP8 took note of the product and Parties, other Governments, and relevant organisations invited to take it into account as a tool to assist risk assessment.
With best wishes to all
Jack
At a couple of points along this discussion I've read comments about previous AHTEG Guidance and it being characterised as somehow not appreciated by the Parties. While it was robustly debated by the COPMOP along the way, as any developing framework should be, my memory of events does not correspond with the narrative that it was “not adopted”.
The COPMOP6 Commended its progress. The testing of the Guidance produced was welcomed by Parties in COPMOP7 and this led to more Parties, other Governments and relevant organisations, being invited to test or use it. It did extremely well in the peer-review process and was further enhanced as a result. Then the COPMOP8 took note of the product and Parties, other Governments, and relevant organisations invited to take it into account as a tool to assist risk assessment.
With best wishes to all
Jack
As can be found in the official COPMOP documentation : the COPMOP in which the last version of the draft guidance was discussed, COPMOP2016 in Cancun, did not adopt the guidance.
In fact the COPMOP did not even 'welcome' or 'acknowledge' the draft guidance.
The COPMOP2016 just 'took note' of the draft guidance, and dissolved the AHTEG.
Best regards to all
Piet van der Meer
In fact the COPMOP did not even 'welcome' or 'acknowledge' the draft guidance.
The COPMOP2016 just 'took note' of the draft guidance, and dissolved the AHTEG.
Best regards to all
Piet van der Meer
