Topic 4: Part B, sections 10 to 13
Mr. Stephane Bilodeau,
Secretariat of the Convention on Biological Diversity#11765
Secretariat of the Convention on Biological Diversity#11765
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Part B: Risk Assessment of a living modified Anopheles containing an engineered gene drive for malaria control
10. Conducting the risk assessment of EGD-LM Anopheles
11. Monitoring EGD-LM Anopheles released in the environment
12. Related issues
13. References
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10. Conducting the risk assessment of EGD-LM Anopheles
11. Monitoring EGD-LM Anopheles released in the environment
12. Related issues
13. References
Participants are requested to follow the forum guidelines:
1. Briefly introduce themselves when posting their first message, including their name, country and institutional affiliation.
2. Keep their messages short, concise and focused.
3. Ensure that the messages are relevant to the topic/question being discussed.
4. Make sure that the text or files attached do not contain viruses, corrupted files or any other similar file deficiencies.
5. Be respectful of others’ points of views.
My name is Christoph Then, I am working for Testbiotech, a science based CSO in Germany (http://www.testbiotech.org).
As we have shown in our previous input (https://www.testbiotech.org/node/3037), the case of Anopoheles gambiae is especially suited to deal with first experiences in risk assessment of EGD-LMO. There are some interesting lessons learned from the existing data that maybe absent in other cases and can inform the risk assessment as planned by the AHTEG.
In any case, in performing this specific risk assessment, specific attention will be needed to include all relevant aspects of uncertainties and unknowns. For the overall conclusions, not only the data that are available are crucial, but also those which are missing. Therefore, adequate tools are needed that allow to systematically address uncertainties and unknowns throughout the whole process of risk assessment, on all relevant steps. Furthermore, it also has to be considered if effective measures will be available to end the field trials in case adverse effects get noticed.
Finally, in regard to potential long-term risks, also interactions with other LMOs and cumulative effects should be considered (see Koller et al., 2023, attached).
All steps in risk assessment should be performed in the light of the precautionary principle. To prevent future damage to humans, the environment and nature, not only the already known dangers have to addressed, but also potential hazards and risks that have not yet been fully researched. In addition, effective measures must be in place, in case necessary, to be able to intervene if damage occurs. From the work of the ATHEG so far, it seems that these pillars of the precautionary principle are of uttermost importance in the context of any potential releases of EGD-LMO.
As we have shown in our previous input (https://www.testbiotech.org/node/3037), the case of Anopoheles gambiae is especially suited to deal with first experiences in risk assessment of EGD-LMO. There are some interesting lessons learned from the existing data that maybe absent in other cases and can inform the risk assessment as planned by the AHTEG.
In any case, in performing this specific risk assessment, specific attention will be needed to include all relevant aspects of uncertainties and unknowns. For the overall conclusions, not only the data that are available are crucial, but also those which are missing. Therefore, adequate tools are needed that allow to systematically address uncertainties and unknowns throughout the whole process of risk assessment, on all relevant steps. Furthermore, it also has to be considered if effective measures will be available to end the field trials in case adverse effects get noticed.
Finally, in regard to potential long-term risks, also interactions with other LMOs and cumulative effects should be considered (see Koller et al., 2023, attached).
All steps in risk assessment should be performed in the light of the precautionary principle. To prevent future damage to humans, the environment and nature, not only the already known dangers have to addressed, but also potential hazards and risks that have not yet been fully researched. In addition, effective measures must be in place, in case necessary, to be able to intervene if damage occurs. From the work of the ATHEG so far, it seems that these pillars of the precautionary principle are of uttermost importance in the context of any potential releases of EGD-LMO.
As I have raised with regard to section 5, that is even more relevant to this section, there is no specific assessment point raised to address potential adverse impacts on human health. This is particularly pertinent for gene drive applications designed to address health issues, and by design will mediate pathogens. There are numerous plausible risk pathways that may result, for example, pathogen evolution in response to the gene drive (e.g. with altered pathogenicity, evasion of vaccine-induced immunity etc), alterations in human immunity, niche replacement. It is vital that any RA will specifically address how gene drives may interfere with disease burden with regard to target and non-target vector controlled disease), in addition to the current risk pathways assessed for LMOs e.g. generation of novel toxins/allergens.
More specifically, for example section 10.2 (or a separate section) should include unintended impacts on human health, including unintended impacts on the target pathogen, non-target pathogens (e.g. other pathogens carried by the target organism), human immunity and disease burden.
Many thanks
More specifically, for example section 10.2 (or a separate section) should include unintended impacts on human health, including unintended impacts on the target pathogen, non-target pathogens (e.g. other pathogens carried by the target organism), human immunity and disease burden.
Many thanks
I am John Connolly, working with Target Malaria at Imperial College London.
For Section 10, and indeed Section 5, methodology is not different from other LMOs but differences may arise in the consideration of impacts due to the temporal and spatial dimensions of gene drive constructs (Connolly, 2022). It is not clear why containment is mentioned here. Containment refers to a physical structure, which not applicable in this context if the guidance is focused on RA for release. The meaning or purpose should be clarified or the mention removed. Similarly, the mention of “unmanaged and managed ecosystems” is not clear in its relevance. This seems to be a concept mostly relevant to agriculture and it is not clear how this would apply to gene drive organisms.
For Section 10.2, Step 2, these are considerations that are necessary for risk assessment of all LMOs. While these issues are not specific to gene drive LMOs, how applicable or relevant each dimension is will depend on the specific gene drive LMO being considered. It is difficult to generalize considerations, though as for other steps, it is the spatial and temporal dimensions of the proposed gene drive LMO that may render the consideration of these issues somewhat different from another LMO. However, vertical gene transfer and persistence of the transgene in the environment may be intended outcomes for some gene drive applications for malaria vector control (Connolly, 2021, 2023). Impacts on species composition can also occur from the use of insecticide-based malaria vector control (Qureshi and Connolly, 2022), so risk assessment needs to be grounded in comparison with the impacts of current practices in the field.
For Section 10.3, It seems there is no step 3 in this section. It seems odd to layout a process and diverge from it so quickly, so perhaps if there is a reason for skipping step 3 in the case of mosquitoes, it would be useful to explain the reasoning in the document. As noted under Section 5 step 1, it is not clear why containment is mentioned here. Containment refers to a physical structure, which not applicable in this context if the guidance is focused on RA for release. The meaning or purpose should be clarified or the mention removed.
Also noted in Step 5 regarding mitigation strategies, there are no single answers to this question. There is ongoing and active research in recognition that this is a topic of great interest. But mitigation strategies will depend on the risks identified, the construct, the species etc., and so will need to be considered case by case.
Resistance is an important consideration and will need to be part of the assessment for efficacy as well as risk. However, this also affects other tools that are currently in use as alternatives to gene drive technologies, so part of the consideration of resistance should also take into account the susceptibility to resistance of alternatives.
References
Connolly JB, Mumford JD, Fuchs S, Turner G, Beech C, North AR, Burt A. (2021). Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa. Malar J. 2021 Mar 29;20(1):170. doi: 10.1186/s12936-021-03674-6.
Connolly JB, Mumford JD, Glandorf DCM, Hartley S, Lewis OT, Evans SW, et al (2022). Recommendations for environmental risk assessment of gene drive applications for malaria vector control. Malar J. 2022 May 25;21(1):152. doi: 10.1186/s12936-022-04183-w.
Connolly JB, Romeis J, Devos Y, Glandorf DCM, Turner G, Coulibaly MB. (2023). Gene drive in species complexes: defining target organisms. Trends Biotechnol. 2023 Feb;41(2):154-164. doi: 10.1016/j.tibtech.2022.06.013.
Qureshi A, Connolly JB. A systematic review assessing the potential for release of vector species from competition following insecticide-based population suppression of Anopheles species in Africa. Parasit Vectors. 2021 Sep 8;14(1):462. doi: 10.1186/s13071-021-04975-0.
For Section 10, and indeed Section 5, methodology is not different from other LMOs but differences may arise in the consideration of impacts due to the temporal and spatial dimensions of gene drive constructs (Connolly, 2022). It is not clear why containment is mentioned here. Containment refers to a physical structure, which not applicable in this context if the guidance is focused on RA for release. The meaning or purpose should be clarified or the mention removed. Similarly, the mention of “unmanaged and managed ecosystems” is not clear in its relevance. This seems to be a concept mostly relevant to agriculture and it is not clear how this would apply to gene drive organisms.
For Section 10.2, Step 2, these are considerations that are necessary for risk assessment of all LMOs. While these issues are not specific to gene drive LMOs, how applicable or relevant each dimension is will depend on the specific gene drive LMO being considered. It is difficult to generalize considerations, though as for other steps, it is the spatial and temporal dimensions of the proposed gene drive LMO that may render the consideration of these issues somewhat different from another LMO. However, vertical gene transfer and persistence of the transgene in the environment may be intended outcomes for some gene drive applications for malaria vector control (Connolly, 2021, 2023). Impacts on species composition can also occur from the use of insecticide-based malaria vector control (Qureshi and Connolly, 2022), so risk assessment needs to be grounded in comparison with the impacts of current practices in the field.
For Section 10.3, It seems there is no step 3 in this section. It seems odd to layout a process and diverge from it so quickly, so perhaps if there is a reason for skipping step 3 in the case of mosquitoes, it would be useful to explain the reasoning in the document. As noted under Section 5 step 1, it is not clear why containment is mentioned here. Containment refers to a physical structure, which not applicable in this context if the guidance is focused on RA for release. The meaning or purpose should be clarified or the mention removed.
Also noted in Step 5 regarding mitigation strategies, there are no single answers to this question. There is ongoing and active research in recognition that this is a topic of great interest. But mitigation strategies will depend on the risks identified, the construct, the species etc., and so will need to be considered case by case.
Resistance is an important consideration and will need to be part of the assessment for efficacy as well as risk. However, this also affects other tools that are currently in use as alternatives to gene drive technologies, so part of the consideration of resistance should also take into account the susceptibility to resistance of alternatives.
References
Connolly JB, Mumford JD, Fuchs S, Turner G, Beech C, North AR, Burt A. (2021). Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa. Malar J. 2021 Mar 29;20(1):170. doi: 10.1186/s12936-021-03674-6.
Connolly JB, Mumford JD, Glandorf DCM, Hartley S, Lewis OT, Evans SW, et al (2022). Recommendations for environmental risk assessment of gene drive applications for malaria vector control. Malar J. 2022 May 25;21(1):152. doi: 10.1186/s12936-022-04183-w.
Connolly JB, Romeis J, Devos Y, Glandorf DCM, Turner G, Coulibaly MB. (2023). Gene drive in species complexes: defining target organisms. Trends Biotechnol. 2023 Feb;41(2):154-164. doi: 10.1016/j.tibtech.2022.06.013.
Qureshi A, Connolly JB. A systematic review assessing the potential for release of vector species from competition following insecticide-based population suppression of Anopheles species in Africa. Parasit Vectors. 2021 Sep 8;14(1):462. doi: 10.1186/s13071-021-04975-0.
Dear Participants of the online forum on risk assessment,
My name is Mrs Blessing Aligwekwe, an Assistant Director working for the National Biosafety Management Management Agency of Nigeria. My background is Botany, with an M.Sc in Managing the Environment (Pathway: GM Crop Risk Assessment) and 14 years of biosafety experience.
I have the following suggestions:
In section 10.3, step 4 and step 5: Risk management strategies, “Ecosystem impacts of EGD-LM mosquito elimination mechanism” should be added, this can form bullet 4. Let’s remember the entire 10.3 should be included in PART C proposed here.
In 10.1. Step 1: Characterization of the EGD-LM mosquito, “Potential interaction between EGD-LM mosquito and non-modified strains and the resulting effects should be included. This can form bullet number 2.
I sincerely appreciate the organizers of this forum. Thank you for work well done.
My name is Mrs Blessing Aligwekwe, an Assistant Director working for the National Biosafety Management Management Agency of Nigeria. My background is Botany, with an M.Sc in Managing the Environment (Pathway: GM Crop Risk Assessment) and 14 years of biosafety experience.
I have the following suggestions:
In section 10.3, step 4 and step 5: Risk management strategies, “Ecosystem impacts of EGD-LM mosquito elimination mechanism” should be added, this can form bullet 4. Let’s remember the entire 10.3 should be included in PART C proposed here.
In 10.1. Step 1: Characterization of the EGD-LM mosquito, “Potential interaction between EGD-LM mosquito and non-modified strains and the resulting effects should be included. This can form bullet number 2.
I sincerely appreciate the organizers of this forum. Thank you for work well done.
Topic 3: Part B, sections 10-12
Hello everyone. My name is Adam Cornish and I work in the Office of Agricultural Policy at the U.S. Department of State and serve as the U.S. national focal point for the Cartagena Protocol on Biosafety. I am pleased to see the continued discussion on the forum and thank the moderators for their work and the thoughtful comments of the other participants in the forum.
Section 10.2. Step 2: What is the purpose of including unintentional transboundary movements of an EGD-LM Mosquito in the guidance materials? First, Section 10.2 is focused on unintended effects to biological diversity, which is unrelated to the presence of geographical boundaries. Second, this guidance is intended to provide risk assessment best practices specific to EGD-LM Mosquito – risk management related to unintentional transboundary movement of LMOs is already covered under Article 16 of the Protocol. We do not believe that there are characteristics unique to EGD-LM Mosquito that would require additional guidance.
Section 10.3. Step 4. and Step 5: We note that monitoring is the focus of section 11 and suggest that monitoring be removed from Steps 4 and 5. Regarding the effectiveness and availability of conventional mosquito control methods, it is worth noting the importance of appropriate comparators and, in cases where the use of an EGD-LM Mosquito would have a benefit to biodiversity conservation, the risk associated with not approving the use of the product would need to be fully considered.
Section 11: Monitoring is important and depends on the trait introduced into the EGD-LM Mosquito and the associated risks to biodiversity conservation. Monitoring should be directed to a specific question or concern and, in the absence of either, should be minimized to reduce burden on Parties and their regulatory authorities.
Hello everyone. My name is Adam Cornish and I work in the Office of Agricultural Policy at the U.S. Department of State and serve as the U.S. national focal point for the Cartagena Protocol on Biosafety. I am pleased to see the continued discussion on the forum and thank the moderators for their work and the thoughtful comments of the other participants in the forum.
Section 10.2. Step 2: What is the purpose of including unintentional transboundary movements of an EGD-LM Mosquito in the guidance materials? First, Section 10.2 is focused on unintended effects to biological diversity, which is unrelated to the presence of geographical boundaries. Second, this guidance is intended to provide risk assessment best practices specific to EGD-LM Mosquito – risk management related to unintentional transboundary movement of LMOs is already covered under Article 16 of the Protocol. We do not believe that there are characteristics unique to EGD-LM Mosquito that would require additional guidance.
Section 10.3. Step 4. and Step 5: We note that monitoring is the focus of section 11 and suggest that monitoring be removed from Steps 4 and 5. Regarding the effectiveness and availability of conventional mosquito control methods, it is worth noting the importance of appropriate comparators and, in cases where the use of an EGD-LM Mosquito would have a benefit to biodiversity conservation, the risk associated with not approving the use of the product would need to be fully considered.
Section 11: Monitoring is important and depends on the trait introduced into the EGD-LM Mosquito and the associated risks to biodiversity conservation. Monitoring should be directed to a specific question or concern and, in the absence of either, should be minimized to reduce burden on Parties and their regulatory authorities.
Hello, this is Hector Quemada again, posting briefly on this section. This section is presented as a case study, and therefore should not be considered guidance per se for any particular case of a gene drive containing Anopheles mosquito.
My name is Samson Simon, I work for the German Federal Agency for Nature Conservation (BfN) as a biosafety expert.
As Anopheles gambiae is a species complex the question of target vs non-target organism is important (cf. post #11827: "In the case where the organism is part of a species complex where not all the species are relevant, how to define the ‘target organism’? Should the definition be restricted to those which are vectors to humans?"). Engineered gene drives based on homing are less prone to resistance mutations depending on the conservation of the target site, reflecting how essential a gene is. The problem here is, that good target sites in essential genes tend to be highly conserved in species, between species of the complex and on a case by case basis also outside the complex. Sequence conservation is a factor in estimating the probability of a potential transfer of the gene drive into non-target species, especially if those can interbreed in the wild (even if this is only occasional). Here a precise definition of the target species within the complex (which species is really the target of the gene drive?) will help to define species affected by unintended gene transfer and assess the risk involved in this process. In my opinion, a species of the complex, which is not a human vector, cannot be defined as a target species (in this case example).
As Anopheles gambiae is a species complex the question of target vs non-target organism is important (cf. post #11827: "In the case where the organism is part of a species complex where not all the species are relevant, how to define the ‘target organism’? Should the definition be restricted to those which are vectors to humans?"). Engineered gene drives based on homing are less prone to resistance mutations depending on the conservation of the target site, reflecting how essential a gene is. The problem here is, that good target sites in essential genes tend to be highly conserved in species, between species of the complex and on a case by case basis also outside the complex. Sequence conservation is a factor in estimating the probability of a potential transfer of the gene drive into non-target species, especially if those can interbreed in the wild (even if this is only occasional). Here a precise definition of the target species within the complex (which species is really the target of the gene drive?) will help to define species affected by unintended gene transfer and assess the risk involved in this process. In my opinion, a species of the complex, which is not a human vector, cannot be defined as a target species (in this case example).
Hello. My name is ROUAMBA Wend-Rabo Mathurin, from Burkina Faso's National Biosafety Agency. I have about ten years' experience in the regulation of GMOs in Burkina Faso. I took part in two last COP meetings as my country's representative. It's a pleasure for me to take part in this online forum on drive gene organisms, for which my country is likely to be the first to have to assess a dossier (the case of the Anopheles mosquito currently under development).
Several contributors have already made some very interesting comments on the document before us. For my part, based on the moderator's questions, I can say that in general terms the guide is very useful in its current format in that it gives a general overview of the steps to be followed in risk assessment and the specific aspects to be considered.
In Sections 10 to 13, several countries have successful examples of involving a wide range of experts in the formulation of risk assessment problems. Some countries, has a National Biosafety Scientific Committee which brings together experts from different fields. If necessary, other experts can be involved in the evaluation of dossiers. In other countries, the experts in charge of dossier evaluation are chosen according to the type of dossier. However, the sensitive nature of certain information (confidential information) and conflicts of interest may limit the participation of certain experts. In addition, particular emphasis needs to be placed on public participation/consultation in the decision-making process, how to do it and how to take public comments into account. This may contribute to a better formulation of certain problems or the consideration of certain risks.
Several contributors have already made some very interesting comments on the document before us. For my part, based on the moderator's questions, I can say that in general terms the guide is very useful in its current format in that it gives a general overview of the steps to be followed in risk assessment and the specific aspects to be considered.
In Sections 10 to 13, several countries have successful examples of involving a wide range of experts in the formulation of risk assessment problems. Some countries, has a National Biosafety Scientific Committee which brings together experts from different fields. If necessary, other experts can be involved in the evaluation of dossiers. In other countries, the experts in charge of dossier evaluation are chosen according to the type of dossier. However, the sensitive nature of certain information (confidential information) and conflicts of interest may limit the participation of certain experts. In addition, particular emphasis needs to be placed on public participation/consultation in the decision-making process, how to do it and how to take public comments into account. This may contribute to a better formulation of certain problems or the consideration of certain risks.
I will not again introduce myself, but I will take the opportunity to thank the Secretariat and Luciana for moderating the forum and for providing me with the opportunity to comment.
This section of the forum is intended to address sections 10-13 of the proposed outline. In general, the outline is not very robust. It is not well ordered to reflect a risk assessment process and it is weighted heavily to focus on certain phenomenon that may or may not be important for risk assessment while ignoring most of the structure and processes that make risk assessments effective.
Section 10, for example. Almost all of the information that is useful for risk assessment comes from a discussion of the introduced organism, the trait it carries, and the nature of the environment it is released into. This is a single bullet point in the outline labelled 10.1. Section 10.2 is labelled "unintended effects on biological diversity" and goes on to list a series of phenomena, many of which are not effects and several of which may not be considered unintended. For example, persistence of the transgene in the ecosystem may well be an intended for an EGD. Likewise, vertical gene transfer is not an "effect" it is an occurrence, and by definition it is an intended occurrence of a gene drive - otherwise it is not a gene drive. This kind of mis-statement of occurrences as effects is a direct result of the lack of agreement as to what are the protection goals being considered.
Section 10.3 is intended to address risk management and acceptability of risks, but it presents a disjointed list of potentially interesting topics with no clear relationship to risk management - because no risks are being identified.
Section 11 consists solely of monitoring, but monitoring is also addressed in section 10.3.
In reviewing the outline, it has fundamental issues that need to be addressed before substantial work could begin with the hope of producing useful guidance for risk assessment of EGD-LM Anopheles. As it exists now, the outline does not describe a useful guidance document. These conversations will likely be difficult, but I can't imagine a mechanism for producing useful guidance that can proceed without first developing a shared understanding of the purpose of the document and incorporating a better understanding of the risk assessment process into the proposed outline.
This section of the forum is intended to address sections 10-13 of the proposed outline. In general, the outline is not very robust. It is not well ordered to reflect a risk assessment process and it is weighted heavily to focus on certain phenomenon that may or may not be important for risk assessment while ignoring most of the structure and processes that make risk assessments effective.
Section 10, for example. Almost all of the information that is useful for risk assessment comes from a discussion of the introduced organism, the trait it carries, and the nature of the environment it is released into. This is a single bullet point in the outline labelled 10.1. Section 10.2 is labelled "unintended effects on biological diversity" and goes on to list a series of phenomena, many of which are not effects and several of which may not be considered unintended. For example, persistence of the transgene in the ecosystem may well be an intended for an EGD. Likewise, vertical gene transfer is not an "effect" it is an occurrence, and by definition it is an intended occurrence of a gene drive - otherwise it is not a gene drive. This kind of mis-statement of occurrences as effects is a direct result of the lack of agreement as to what are the protection goals being considered.
Section 10.3 is intended to address risk management and acceptability of risks, but it presents a disjointed list of potentially interesting topics with no clear relationship to risk management - because no risks are being identified.
Section 11 consists solely of monitoring, but monitoring is also addressed in section 10.3.
In reviewing the outline, it has fundamental issues that need to be addressed before substantial work could begin with the hope of producing useful guidance for risk assessment of EGD-LM Anopheles. As it exists now, the outline does not describe a useful guidance document. These conversations will likely be difficult, but I can't imagine a mechanism for producing useful guidance that can proceed without first developing a shared understanding of the purpose of the document and incorporating a better understanding of the risk assessment process into the proposed outline.
Dear colleagues,
My name is Ricarda Steinbrecher, am a biologist and molecular geneticist and have introduced myself previously under topic 1 of the online forum discussion.
Whilst Topic 2 (all of section 5) is missing headings and bullet points specific to ERA of EGD-LMOs (and which will need to be established and filled by the AHTEG), section 10 in Topic 4 seems to be even more devoid of engineered gene drive specific aspects and issues. The fact that steps within the “conducting the risk assessment” sections of part A and part B are so different is problematic. I find that they should be nearly the same except the section in part B should be much more explicit in what is required and what are issues for RA/RM of EGD-LM mosquitoes (and not just EGD-LM Anopheles).
Section 10.1 (lines 108-110) should for example look wider into the role of mosquitoes (which would be specific mosquitoes) within ecosystems, including their larvae, which areas or niches they occupy and what would fill those niches, and have that knowledge for all areas where the mosquito and crossable related mosquitoes are present or could move to. It should include building a picture so that the consequences not only for the direct environment can be covered, but also knock-on-effects also beyond where the mosquitoes are present (esp. if food webs are affected) – e.g. considering impacts on migratory species and -if affected- the impacts along the whole route of migration.
This section should for example also result in providing detailed data and analysis on the breadth of genetic diversity within the specific mosquito species (across all the area where it is present) as well as all the genotypes (and their diversity) within other crossable mosquito species. This would be important for later hazard identification and risk assessment steps.
In short, section 10.1. is insufficient at present.
As I find the outline under topic 4 and its whole structure highly insufficient I cannot provide comments in terms of lines and subsections. The fact that whole populations are intentionally being modified in the wild, and this being done in a self-spreading manner into populations with unestablished genetic diversity across undefined areas and with open time frames - requires a different approach to understanding and identifying risks. This is currently not reflected in the outline.
This said, I would like to support some of the points present in the outline, such as line 115, as this relates also to instances and a time when the gene drive may have stopped working, yet the transgenes as well as other genetic modifications initiated by for example CRISPR/Cas based gene drives. This point will need further elaboration.
The point of “evolutionary response” (line 116) will be crucial as part of risk assessment as evolutionary responses across space and time are possible for many different aspects, including development of resistance to the gene drive or altered mating behaviour or niche replacements etc.
Line 121 refers to another important element, namely halting gene drives and reversibility of gene drive actions and eliminations of EGD-LM mosquitoes. This should however not only be an exercise of looking at mechanisms to do so, but a requirement for release.
With kind regards.
My name is Ricarda Steinbrecher, am a biologist and molecular geneticist and have introduced myself previously under topic 1 of the online forum discussion.
Whilst Topic 2 (all of section 5) is missing headings and bullet points specific to ERA of EGD-LMOs (and which will need to be established and filled by the AHTEG), section 10 in Topic 4 seems to be even more devoid of engineered gene drive specific aspects and issues. The fact that steps within the “conducting the risk assessment” sections of part A and part B are so different is problematic. I find that they should be nearly the same except the section in part B should be much more explicit in what is required and what are issues for RA/RM of EGD-LM mosquitoes (and not just EGD-LM Anopheles).
Section 10.1 (lines 108-110) should for example look wider into the role of mosquitoes (which would be specific mosquitoes) within ecosystems, including their larvae, which areas or niches they occupy and what would fill those niches, and have that knowledge for all areas where the mosquito and crossable related mosquitoes are present or could move to. It should include building a picture so that the consequences not only for the direct environment can be covered, but also knock-on-effects also beyond where the mosquitoes are present (esp. if food webs are affected) – e.g. considering impacts on migratory species and -if affected- the impacts along the whole route of migration.
This section should for example also result in providing detailed data and analysis on the breadth of genetic diversity within the specific mosquito species (across all the area where it is present) as well as all the genotypes (and their diversity) within other crossable mosquito species. This would be important for later hazard identification and risk assessment steps.
In short, section 10.1. is insufficient at present.
As I find the outline under topic 4 and its whole structure highly insufficient I cannot provide comments in terms of lines and subsections. The fact that whole populations are intentionally being modified in the wild, and this being done in a self-spreading manner into populations with unestablished genetic diversity across undefined areas and with open time frames - requires a different approach to understanding and identifying risks. This is currently not reflected in the outline.
This said, I would like to support some of the points present in the outline, such as line 115, as this relates also to instances and a time when the gene drive may have stopped working, yet the transgenes as well as other genetic modifications initiated by for example CRISPR/Cas based gene drives. This point will need further elaboration.
The point of “evolutionary response” (line 116) will be crucial as part of risk assessment as evolutionary responses across space and time are possible for many different aspects, including development of resistance to the gene drive or altered mating behaviour or niche replacements etc.
Line 121 refers to another important element, namely halting gene drives and reversibility of gene drive actions and eliminations of EGD-LM mosquitoes. This should however not only be an exercise of looking at mechanisms to do so, but a requirement for release.
With kind regards.
Dear colleagues,
My name is Christophe Boëte and I have introduced myself in a previous post.
To complement Dr Steinbrecher's post concerning the 'evolutionary response' (line 116), this should not only include the one of the mosquitoes but also the potential of the malaria parasite and this could be clearly specified in the outline.
Regards,
My name is Christophe Boëte and I have introduced myself in a previous post.
To complement Dr Steinbrecher's post concerning the 'evolutionary response' (line 116), this should not only include the one of the mosquitoes but also the potential of the malaria parasite and this could be clearly specified in the outline.
Regards,
