To facilitate a gathering of additional  information, participants are asked to consider the following points in relation to this topic:
1. Review the potential positive and negative impacts of this trend and issue in synthetic biology on each of the three objectives of the Convention.

2. What is the timeframe for release or potential impact of self-spreading vaccines for wildlife? Please provide examples of specific applications. 

3. What are the potential gaps or challenges for risk assessment, risk management and regulation for this topic in synthetic biology? Evaluate the availability of tools to detect, identify and monitor the organisms, components and products of synthetic biology.

4. Review the potential social, economic, cultural, ethical, political, human health and/other relevant impacts of this trend and issue. What are the relevant considerations for IPLCs, women and youth?

5. Is the trend and issue attempting to address specific problems, and if so, what are these problems and their underlying causes? How else could these problems or causes be addressed?

6. What lessons can be learned of similar tools, techniques or applications in other domains? How might those lessons from elsewhere be relevant or shed insight in assessing this topic in the context of the aims of the Convention on Biological Diversity? 

7. Where are limits of knowledge with respect to this trend and issue? Are there any other considerations that would be important to raise?

Dear colleagues,

It is my pleasure to welcome you to the Open-ended Online Forum on Synthetic Biology. The forum will be open from 6 to 15 November at 17.00 EST. I will be moderating the discussion and will provide support should the need arise. Please also bear in mind the forum guidelines that you can find on the website.

Thank you in advance for your engagement and I am looking forward to productive discussions!

Kind regards,
Florian Rabitz

The issue I want to raise is the strategic/philosophical approach the CBD and hence the world takes towards Synbio.

We live in the "Anthropocene", defined so because of the (massive) impact of the human species on the planet. Pristine ecosystems don't exist / haven't existed for some time now.  Our food crops and animals (and pets and pests & diseases) are often dramatically different from their original forms. The onset of climate change is only going to significantly increase this impact.

But for too many of the publics across the globe, this human impact was limited to domestication of certain species, in defined 'humanised' locations where the human population was more dense, naively secure in the knowledge that there were wild sanctuaries spotted around the globe that would maintain a reserve of pre-human 'natural'.

The point I am wanting to make is that while human-induced change has been seen (by the layperson) as 'unnatural' and often bad (myopically ignoring the wealth & capabilities the world has created)), we have a massive task in public awareness (particularly in this theme, but in almost all aspects of Synbio) if we want to change the view to human-induced change is good (ie. a key tool for 'saving the planet').

For such public awareness, in my view, we need to have a strategic and science-based vision of why we are doing this (ie enabling Synbio), of where we are going and of how far we will go. While the 3 objectives of the CBD are very relevant, does the conservation of biological diversity, mean the same to a layperson (possibly thinking only of existing biodiversity - eg. save the polar bear) as to an expert (recognising the continually evolving/changing nature of biodiversity).

While this exercise (online forum, etc) could feed into this, I am not yet seeing movement towards a unified vision & purpose of Synbio. In my opinion, approving or not approving any synbio application without a strategic and explicit global vision is too ad hoc and will enhance differences in opinion. (I recognise the importance of national sovereignty, but...)

My name is Dr. Guy Reeves, recently moved from the from Max Planck Institute for Evolutionary Biology (Germany) to the head quarters of the same organisation I am an evolutionary biologist with interests in viral techniques intended for environmental modification.

Given the unusually limited number of postings to this forum I think it is important to speculate for the record why that may be.

(1)While I am a .gov nominated expert , unusually I did not receive any notification of the opening or existence of this forum until 13/11/2023 (just 1 full day before its original closing and 8 days since the session opened), I checked my email and spam box it appears that I did not get any notification. I cannot say if I am the only person.
Any topic that includes the word “vaccine” is rightly approached with a particular sense of personal responsibility . This is regardless of the fact that self-spreading vaccines share very few of the properties of vaccines as the world commonly understands the word (see section below). As experts we are also rightly very wary of offering (public) opinions on topics we are not confident about.
The .pdf file  (self-spreading vaccines.pdf )linked the the first post in this forum is a very good introduction, but I still think the above point holds.

While it is also speculation on my part, the currently low response rate to this topic, should be viewed in the context of the above two points combined with a general lack of awareness and knowledge of this highly specialist topic. Consequently, it is highly questionable if the low response rate should be interpreted as general lack of concern, or that CBD processes to deal with this topic are in place (despite regulatory committee reports explicitly stating that we remain unprepared e.g. CBD 2007. ‘Report of the Canada-Norway Expert Workshop on Risk Assessment for Emerging Applications of Living Modified Organisms UNEP/CBD/BS/COP-MOP/4/INF/13’, 39. https://www.cbd.int/kb/record/meetingDocument/58217?RecordType=meetingDocument&Event=BSRARM-01. This is particularly the case,   given the reported scaling up for deployment of at least one of these projects (which has the potential to preclude trails of conventionally deployed human Lassa fever vaccines in the only region where such trials could be conducted ).

(2) For the above reasons it could  well be that an open-forum is not the best way to illicit responses on this topic.  A more active engagement process where experts can decide wether or not their responses are made public might be worth considering?

The .pdf file  (self-spreading vaccines.pdf )linked the the first post in this forum is a very good introduction, but I still think the above points about the reasons for limited posts still hold.

—Time frame—
The Lassa fever virus vaccine for release into wild rat populations is reported by the CEO to potential investors (January 2023)


“ We are in the process transferring the technology to a West-African manufacturer … so that particular tech-transfer can be scaled up and then there is a possibility then obviously having somebody who can manufacture at scale to make that vaccine available in the region”.


see time point 6:10 (but see also explanatory section starting at 2:38)
https://www.youtube.com/watch?v=KHFjabspTcM

or see also
https://thevaccinegroup.com/tvg-successfully-completes-darpa-funded-transmissible-lassa-fever-vaccine-project/
https://static1.squarespace.com/static/5d927ef93f54836cb17542c1/t/5e74072e6f3a42255b9573fe/1584662333204/BIG+WIN-New+Countermeasures.pdf
https://thevaccinegroup.com/science/
note vaccine development platform that is “Evolved to spread easily through host population.”

Simply put, self-spreading vaccines are live laboratory modified viruses that are developed to spread between vertebrate hosts when released into the environment. Furthermore, that they rely on this property to (in theory) autonomously achieve population wide immunisation of wild populations and potentially also subsequent generations.
Self-spreading vaccines are always live viral vaccines that are genetically modified (i.e. LMOs). Where reported, development has occurred in biosafety level 3 or 4 facilities (Bárcena et al., 2000; Tsuda et al., 2011), though they are intended for release into the environment to spread with epidemic like properties.

Self-spreading viral techniques for use in the environment are not technically new, but until now there has been a well established norm among virologists that their use or development is highly problematic relative to existing available alternatives (Lentzos 2022).





Are self-spreading vaccines really “vaccines” as nearly everybody in the world understands the word?

YES they are intended to raise some degree of protective immune response.

They are not “vaccines” in the sense that all licensed vaccines to date are vaccines (including successfully ones licensed as oral baits). This  still has the potential to undermine vaccine confidence as a whole.
NO .They are intentionally transmissible their immune effects and side effects are not likely to be predictable
NO .There is no proposal of how they are regulated, including safety testing to the standards of conventional vaccines (they actually need higher standards due to their evolvability and the fact that they are almost by definition likely to come into contact with both the target wildlife species AND humans).
NO .They evolve between individuals  exposed  to the “vaccine” (rapidly it is not a single thing / product)
NO .It is far from clear in what circumstances they might be perceived to be trustworthy?

Thanks

Guy





Bárcena, J., M. Morales, B. Vázquez, J. A. Boga, F. Parra, J. Lucientes, A. Pagès-Manté, J. M. Sánchez-Vizcaíno, R. Blasco, and J. M. Torres. 2000. Horizontal Transmissible Protection against Myxomatosis and Rabbit Hemorrhagic Disease by Using a Recombinant Myxoma Virus. J Virol. 74:1114–1123. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC111445/

F. Lentzos, E. P. Rybicki, M. Engelhard, P. Paterson, W. A. Sandholtz, R. G. Reeves, Eroding norms over release of self-spreading viruses. Science. 375, 31–33 (2022). Available from: http://web.evolbio.mpg.de/HEVIMAs/

————————————————
I am reposting responses to an earlier 2023 online forum which directly address many of the explicit questions in this forum.  Some posts have been abstracted to focus on self-spreading vaccines-  please refer to original post in the original form for the full text of the Author
https://www.cbd.int/synbio/current_activities/open-ended_online_forum/?threadid=2557


Post should appear in the sequence they appeared in the original earlier forum.
—————————————————————————-

RE: TOPIC 1: Question 1a) What are some examples of near-future applications? And what is the timeframe for release of the applications, either for research or commercialization (0 to 5 years; 5 to 10 years; 10+ years)? [#2633]
Dear distinguished colleagues, my name is Dr Eva Sirinathsinghji, I am a biosafety research associate/consultant at Third World Network (TWN), with background training in molecular neurogenetics. I served on the 2019 AHTEG on risk assessment and management that focussed on LMOs containing engineered gene drives and LM fish. I look forward to learning and discussing these critical issues. I’m structuring my comments around the trends identified by the 2019 AHTEG.

Trend 1: Increased field testing of organisms, components and products derived from new developments in synthetic biology

LMO viruses  (also applicable to trend 2 identified by the AHTEG):
Three such spreadable ‘vaccine’ virus projects appear to be already underway, including a field trial approval in 2019 in the US for the release of a living modified raccoon poxvirus to be used in bats to combat white nose syndrome. This trial appears to have been approved (APHIS, 2019, https://www.regulations.gov/docket/APHIS-2019-0043/document). Two further projects are being developed by US and UK research institutions, with the intention to release GM viruses in South American and West African regions, targeting the rabies virus in bats, and the Lassa fever virus in rodents, respectively. https://doi.org/10.1126/science.abo1980 https://www.preemptproject.org/about
Virus-based gene drive applications for human therapies appear to have also been recently approved for trials in at-risk people, with potential for this type of technology to be also e applied to other applications with potential impact on biodiversity. https://grantome.com/grant/NIH/DP1-DA051144-01

————————————————
I am reposting responses to an earlier 2023 online forum which directly address many of the explicit questions in this forum.  Some posts have been abstracted to focus on self-spreading vaccines-  please refer to original post in the original form for the full text of the Author
https://www.cbd.int/synbio/current_activities/open-ended_online_forum/?threadid=2557


Post should appear in the sequence they appeared in the original earlier forum.
—————————————————————————-

RE: TOPIC 1: Question 1a) What are some examples of near-future applications? And what is the timeframe for release of the applications, either for research or commercialization (0 to 5 years; 5 to 10 years; 10+ years)? [#2650]
Self-spreading vaccines for release into the environment near-future application: in process of transferring the technology to manufacturer for scale-up.

Hello…
Thanks to everyone for a stimulation discussion so far.
My name is Dr. Guy Reeves, from the Max Planck Institute for Evolutionary biology (Germany), I am an evolutionary genenetitst with interests in viral techniques intended for environmental modification. I am an inventor on a granted patent related to gene drive (EP2934093B1).

This post to a significant extent echos parts of Dr Eva Sirinathsinghji above.

In that past three years it has been reported by a commercial company that they have developed two self-spreading vaccines. One for Lassa fever virus in West African rat species and another for Ebola virus in primates.

—Time frame—
The Lassa fever virus vaccine for release into wild rat populations is reported by the CEO to potential investors (January 2023)


“ We are in the process transferring the technology to a West-African manufacturer … so that particular tech-transfer can be scaled up and then there is a possibility then obviously having somebody who can manufacture at scale to make that vaccine available in the region”.



see time point 6:10 (but see also explanatory section starting at 2:38)
https://www.youtube.com/watch?v=KHFjabspTcM

or see also
https://thevaccinegroup.com/tvg-successfully-completes-darpa-funded-transmissible-lassa-fever-vaccine-project/
https://static1.squarespace.com/static/5d927ef93f54836cb17542c1/t/5e74072e6f3a42255b9573fe/1584662333204/BIG+WIN-New+Countermeasures.pdf
https://thevaccinegroup.com/science/
note vaccine development platform that is “Evolved to spread easily through host population.”

Simply put, self-spreading vaccines are live laboratory modified viruses that are developed to spread between vertebrate hosts when released into the environment. Furthermore, that they rely on this property to (in theory) autonomously achieve population wide immunisation of wild populations and potentially also subsequent generations.
Self-spreading vaccines are always live viral vaccines that are genetically modified (i.e. LMOs). Where reported, development has occurred in biosafety level 3 or 4 facilities (Bárcena et al., 2000; Tsuda et al., 2011), though they are intended for release into the environment to spread with epidemic like properties.

Self-spreading viral techniques for use in the environment are not technically new, but until now there has been a well established norm among virologists that their use or development is highly problematic relative to existing available alternatives (Lentzos 2022).


—To date no self-spreading vaccine has been licensed (for either medical or veterinary use), despite claims otherwise by proponents of self-spreading viral approaches —.
The only ambiguous case is 2019 USA approval of the experimental release of the self-spreading Live Raccoon Poxvirus Vector (RCN-CAL/SP) in bats as an conservation measure, where it was stated that

“Because the issues raised by field testing and by issuance of a license are identical, APHIS has concluded that the EA that is generated for field testing would also be applicable to the proposed licensing action. Provided that the field test data support the conclusions of the original EA and the issuance of a FONSI, APHIS does not intend to issue a separate EA and FONSI to support the issuance of the product license, and would determine that an environmental impact statement need not be prepared. APHIS intends to issue a veterinary biological product license for this vaccine following completion of the field test provided no adverse impacts on the human environment are identified and provided the product meets all other requirements for licensing.”
https://www.regulations.gov/document/APHIS-2019-0043-0001

This statement by APHIS and the timeframe mentioned in statements by the CEO reproduced at the start of this posting raise the question of wether self-spreading viral approaches can be planing to follow the highly regulated and internationally notified testing and licensing process that vaccines follow (including the high successful oral bait vaccines for rabies which are not self-spreading).



—Relevance to CBD —
To date, proposed modified self-spreading viral approaches for use in wildlife can usefully be placed in one of two types (Lentzos 2022):
1 Experimental approaches to kill or sterilize mammalian wildlife or pests as a means to reduce their population sizes, also called wildlife management.

2 Experimental approaches to vaccinate mammalian wildlife to protect them from disease or to limit their capacity to act as reservoirs for vectored diseases.

The topic of this posting is class 2

Regulators have for decades repeatedly noted the potentially profound consequences of such viral techniques for use in biodiversity, older but thoughtful examples include (CBD 2007 or WHO 1993) . The obvious issues raised remain unresolved with no obvious current effort to address them, despite ongoing development efforts.



Given the inherent difficulty in field testing a technology that is to a significant extent designed to “get away” and the absence of any international notification for cross-border export of self-spreading vaccines or experimental releases of veterinary self-spreading vaccines. It appears the case that as the broader vaccine community focuses on moving away from higher risk approaches where effective alternatives can be developed (e.g. replacing live attenuated vaccines generated by selection), there is a considerable potential for the whole world to be surprised by a very small group of funders and mostly evolutionary biologists moving rapidly in the direction of increasing the risk profile of vaccines.

This meeting is occurring during the duration of this forum and provides some insight into the current interest in these techniques.

https://transmissiblevaccines.org/workshop-dev-vaccines/

1.
Bárcena, J., M. Morales, B. Vázquez, J. A. Boga, F. Parra, J. Lucientes, A. Pagès-Manté, J. M. Sánchez-Vizcaíno, R. Blasco, and J. M. Torres. 2000. Horizontal Transmissible Protection against Myxomatosis and Rabbit Hemorrhagic Disease by Using a Recombinant Myxoma Virus. J Virol. 74:1114–1123. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC111445/

CBD 2007. ‘Report of the Canada-Norway Expert Workshop on Risk Assessment for Emerging Applications of Living Modified Organisms UNEP/CBD/BS/COP-MOP/4/INF/13’, 39. https://www.cbd.int/kb/record/meetingDocument/58217?RecordType=meetingDocument&Event=BSRARM-01.
F. Lentzos, E. P. Rybicki, M. Engelhard, P. Paterson, W. A. Sandholtz, R. G. Reeves, Eroding norms over release of self-spreading viruses. Science. 375, 31–33 (2022). Available from: http://web.evolbio.mpg.de/HEVIMAs/


WHO 1993 Informal Consultation on Reproductive Control of Carnivores, Geneva, 16 June 1993 :. 1993. https://apps.who.int/iris/handle/10665/60995.

Tsuda, Y., P. Caposio, C. J. Parkins, S. Botto, I. Messaoudi, L. Cicin-Sain, H. Feldmann, and M. A. Jarvis. 2011. A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus. T. W. Geisbert, editor. PLoS Negl Trop Dis. 5:e1275.





——————-











Note that self-spreading vaccines are also described as: transmissible, contagious, horizontally-transferable, self-disseminating and founder-based vaccines. Recently a hypothetical term “transferable vaccine” has also be introduced to denote live self-spreading vaccines where transmission only occurs to individuals in direct contact with the originally inoculated individuals (Nuismer and Bull, 2020; Technology Networks, 2022). However, we are unaware of any evidence that such a class of viruses exists--particularly as viral transmissibility is always a dynamic parameter in complex environmental situations--. A precise definition of sefl-spreading vaccines can be found in box 1 of (Lentzos 20022).





Currently, there are 4 proposals for self-spreading vaccines, only one of which has resulted in recent approved releases.

1 Vaccinate African primates to inhibit their infection by the Ebola virus with the aim to limit their capacity to act as a wildlife reservoir for transmission to humans (PREEMPT, 2018; TVG, 2021; PREEMPT, 2022).
2 Vaccinate a number of rat species in West Africa to inhibit their infection by the Lassa fever virus with the aim to limit their capacity to act as a wildlife reservoir for transmission to humans (PREEMPT, 2018; PREEMPT, 2022; Regulatory News Service, 2022).
3 Vaccinate numerous North American bat species to reduce their susceptibility to an emergent fungal infection for the purposes of bat conservation. This proposal has resulted in the release of a genetically modified raccoon pox virus starting in 2019 (Rocke et al., 2019; USDA-APHIS, 2019).
4 Vaccinate various vampire bat species, that are mostly currently restricted to Central and South America, to inhibit their infection by the Rabies virus with the aim to limit their capacity to act as a wildlife reservoir for transmission to humans, but has primarily a bat conservation motivation, as highly effective human vaccines for rabies could be made available to human communities (Bakker et al., 2019; Streicker et al., 2022).


Angulo, E., and J. Bárcena. 2007. Towards a unique and transmissible vaccine against myxomatosis and rabbit haemorrhagic disease for rabbit populations. Wildl. Res. 34:567. doi:10.1071/WR06160. Available from: http://www.publish.csiro.au/?paper=WR06160
Angulo, E., and B. Gilna. 2008. When biotech crosses borders– international governance of self-dispersive GMOs purposefully released for public health, controlling invasive species and pests, and treating wildlife. Nature Biotechnology. doi:10.1038/nbt0308-277. Available from: https://www.nature.com/articles/nbt0308-277
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Bárcena, J., M. Morales, B. Vázquez, J. A. Boga, F. Parra, J. Lucientes, A. Pagès-Manté, J. M. Sánchez-Vizcaíno, R. Blasco, and J. M. Torres. 2000. Horizontal Transmissible Protection against Myxomatosis and Rabbit Hemorrhagic Disease by Using a Recombinant Myxoma Virus. J Virol. 74:1114–1123. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC111445/
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Lentzos, F., E. P. Rybicki, M. Engelhard, P. Paterson, W. A. Sandholtz, and R. G. Reeves. 2022. Eroding norms over release of self-spreading viruses. Science. 375:31–33. doi:10.1126/science.abj5593. Available from: https://www.science.org/doi/10.1126/science.abj5593
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(edited on 2023-03-27 11:38 UTC+1 by Dr. Guy Reeves, Germany)
posted on 2023-03-27 10:51 UTC+1 by Dr. Guy Reeves, Germany

————————————————
I am reposting responses to an earlier 2023 online forum which directly address many of the explicit questions in this forum.  Some posts have been abstracted to focus on self-spreading vaccines-  please refer to original post in the original form for the full text of the Author
https://www.cbd.int/synbio/current_activities/open-ended_online_forum/?threadid=2557


Post should appear in the sequence they appeared in the original earlier forum.
—————————————————————————-
RE: TOPIC 1: Question 1a) What are some examples of near-future applications? And what is the timeframe for release of the applications, either for research or commercialization (0 to 5 years; 5 to 10 years; 10+ years)? [#2651]
Questions in response to posting by Dr Eva Sirinathsinghji on 2023-03-24 17:14

Dr Eva Sirinathsinghji

I read your posting with great interest. Clearly what you are referring to as “spreadable vaccine viruses” are the same as “self-spreading vaccines” I also mention in my later post. As you clearly say this technology is clearly relevant to the objectives of the convention in that there are applications intended for use in the environment in managed and wild populations.
Question:
1 I was wondering if you had an opinion on wether the current developers of these techniques can be reasonably considered at the “early stages of research and development (R and D) ” or if there are indications that they have progressed beyond this stage?

2 Given the potential of self-spreading technologies to make transboundary movements, are you aware of any existing requirements or initiatives to register exports of transmissible live viruses or notify experimental releases targeting animals ?

3 Given the that the nations currently developing self-spreading vaccines are mostly choosing not to address the many needs within their own boarders, do you see this as an issue for the convention? It is potentially notable that earlier (subsequently abandoned) programs in the 2000s in Spain and Australia were to address domestic issues.

Thanks
Dr Guy Reeves
Max Planck Institute for Evolutionary biology (Germany)
posted on 2023-03-27 11:37 UTC+1 by Dr. Guy Reeves, Germany

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I am reposting responses to an earlier 2023 online forum which directly address many of the explicit questions in this forum.  Some posts have been abstracted to focus on self-spreading vaccines-  please refer to original post in the original form for the full text of the Author
https://www.cbd.int/synbio/current_activities/open-ended_online_forum/?threadid=2557


Post should appear in the sequence they appeared in the original earlier forum.
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RE: TOPIC 1: Question 1a) What are some examples of near-future applications? And what is the timeframe for release of the applications, either for research or commercialization (0 to 5 years; 5 to 10 years; 10+ years)? [#2653]
Thank you for raising these questions on the self-spreading vaccines, which in my opinion highlight the urgent need for such horizon scanning processes as we are discussing here. It appears that some of these vaccine projects are indeed already at the trial stage, and from the information shared in your post, perhaps even at the stage of moving towards manufacturing. Given their potential for uncontrolled spread and transboundary movement, our view is that they need to feature much more prominently in biosafety discussions. As LMO viruses are involved, the provisions of the Cartagena Protocol should apply, particularly if such LMOs are intentionally exported, although there would be challenges raised by unintentional transboundary movements that may result from any field trials. Some of these are very similar to that of gene drive organisms, for which TWN has explored the regulatory landscape: See https://biosafety-info.net/wp-content/uploads/2019/10/Biosafety-briefing_-gene-drives-summary.pdf and https://biosafety-info.net/wp-content/uploads/2019/10/Biosafety-briefing_gene-drives-key-elements.pdf

The advanced nature of these projects, alongside other synbio technologies, raises several long standing critiques of global health projects that may not serve the priorities of communities that are targeted for intervention. As said in other posts for Topic 2, e.g. Lim Li Ching [#2638], Dr Wakeford [#2619], Prof Heinemann [2617] and Prof AbdelKawy [#2624], horizon-scanning processes thus need to involve meaningful participation from a diverse and broad range of actors, including potentially affected communities, indigenous peoples and local communities. Assessing multiple dimensions that encompass current state of knowledge (and gaps), including cultural, socio-economic as well as health and the environment vis-à-vis the three objectives of the Convention is crucial for such projects. Such processes need to include advancements in R&D, negative results as well as gaps in knowledge that can be used to assess projects in a timely manner, in anticipation of technologies and not instead playing catch up on those that appear to be advancing rapidly.

Thanks Eva

posted on 2023-03-27 17:04 UTC+1 by Dr. Eva Sirinathsinghji, Third World Network

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I am reposting responses to an earlier 2023 online forum which directly address many of the explicit questions in this forum.  Some posts have been abstracted to focus on self-spreading vaccines-  please refer to original post in the original form for the full text of the Author
https://www.cbd.int/synbio/current_activities/open-ended_online_forum/?threadid=2557


Post should appear in the sequence they appeared in the original earlier forum.
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RE: TOPIC 1: Question 1a) What are some examples of near-future applications? And what is the timeframe for release of the applications, either for research or commercialization (0 to 5 years; 5 to 10 years; 10+ years)? [#2690]
Dear Colleagues,
My name is Luke Alphey, I am a geneticist, currently employed at the University of York, with over 30 years’ experience of insect genetics. I am also a member of the UK Scientific Advisory Committee on Genetic Modification (Contained Use), which advises the UK Competent Authority on contained use of genetic modification/LMOs, including the possibility of accidental release.
Regarding potential applications, I would highlight the use of transmissible vaccines and gene drive mosquitoes, each of which have been commented on previously in the thread
Transmissible vaccines (“self-spreading vaccines”: Guy Reeves #2650 discussed these in some detail noting that several different terms are in use). These have considerable potential for vaccinating hard-to-reach wildlife populations. Developmental timescale is hard to predict; as Guy notes, developer comments seem to imply potentially within the next 5 years. I’m glad that Guy mentioned them as I feel I have seen less discussion of these than for some of the other technologies in these threads, which are important but perhaps already widely discussed. Transmissible vaccines have a wide range of potential properties; my understanding of current research programmes in this area is that they are managed very responsibly by the scientists involved, but regulation of such vaccines may be less well developed than for other technologies under consideration here.
Gene drive mosquitoes: Stephanie James [#2679] correctly notes that these have been discussed for some time, with multiple analyses leading to the positive conclusion from (e.g.) the World Health Organization and the African Union that new technologies such as genetically- and gene drive-modified mosquitoes should be investigated for their potential contribution to the continued fight against malaria and other vector-borne diseases of public health concern (citations in #2679). Despite such endorsement, deployment seems unlikely within the next 5 years, though some limited trials may occur within that timescale, perhaps of system components rather than complete systems.
Similar to Delphine Beeckman [#2683], in my experience both academic and industrial researchers in these area have a great sense of responsibility, carefully comply with extant legislation, including in relation to transportation and trans-boundary movement as well as national regulations, and consider and mitigate well in advance potential hazards. Delphine presents this more eloquently than I!
Fairly modest differences in application, for example the vector used for a transmissible vaccine, can substantially alter the risk profile. This points to careful case-by-case analysis and regulation, particularly in the early days, rather than any blanket approval for a technology (or indeed non-approval). This need for case-by-case analysis was made also by Galina Mozgova [#2660] and elsewhere.
Best regards,
Luke Alphey
posted on 2023-03-30 18:11 UTC+1 by Prof Luke Alphey, University of York

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I am reposting responses to an earlier 2023 online forum which directly address many of the explicit questions in this forum.  Some posts have been abstracted to focus on self-spreading vaccines-  please refer to original post in the original form for the full text of the Author
https://www.cbd.int/synbio/current_activities/open-ended_online_forum/?threadid=2557


Post should appear in the sequence they appeared in the original earlier forum.
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RE: TOPIC 1: Question 1a) What are some examples of near-future applications? And what is the timeframe for release of the applications, either for research or commercialization (0 to 5 years; 5 to 10 years; 10+ years)? [#2729]
Dear participants, it has been a great opportunity to read the views from participants from around the globe with different priorities and expectations, nevertheless sharing the ambition to contribute to the progress of the CBD objectives.

I am Patrick Rüdelsheim, Belgian, holding a PhD in Biology and lecturing at the University of Ghent and the University of Antwerp. My main professional activity is assisting researchers and developers in risk assessment and management of biologicals as well as compliance with biotechnology regulations. As such I have followed the Synthetic Biology developments closely and was honoured to serve as technical editor of the CBD Technical Series 100 publication.

This exchange has provided a terrific overview of developments, some still very conceptual, that highlight the broadness of the field. Grouping technology developments, the AHTEG identified 7 trends, to inform a process for horizon scanning, monitoring and assessment. As a trend refers to a general pattern or direction of change, I like to point out on the fact that different submissions to this forum are likely not illustrating a trend, are not new and/or are not in scope. For instance, null-segregants can hardly be submitted as a new element, since it has been discussed as soon as the GM plants were introduced.

Similarly, specific developments may point to new approaches. Yet specific cases should not automatically be considered a new trend. Several of the technologies may be breakthroughs and hold promises, yet will remain – as others have pointed out multiple reasons why- for considerable time in the research phase. They may also remain the exception only to be used to address very specific issues (e.g. when to use what type of gene drive system) and would not qualify as a “trend”.

Some applications are depicted as new trends, whereas they are part of evolving developments. E.g. self-spreading vaccines mark an important step for which clearly benefits/risks must be weighed. Genetically modified vaccine for veterinary use, specifically for wildlife immunization, have been released before (see e.g. https://www.biosafety.be/content/commercialisation-gmo-medicinal-products-some-figures) and self-spreading vaccines can build on this experience.

Finally, bringing developments outside of the lab is likely in many cases not a new trend. If the purpose of an application is to have products for outdoor deployment (e.g. improved crops, disease vector control, biodiversity conservation,..), reaching confined outdoor testing and eventually large scale deployment would be inherent. It marks projects reaching a level of maturity, rather than a new trend. Conversely, some applications are intended for contained use only and other shave pointed out the relevance of contained use regulations and practices as advocated by e.g. biosafety associations and the WHO.

In this respect, there is high value to provide different views on new ideas and technological developments and this forum is significantly contributing to this effort. The task ahead should result in filtering those which are truly “trends” and which should be considered as new and emerging issues that may impact, positively and/or negatively, the CBD goals.
posted on 2023-03-31 14:23 UTC+1 by Dr. Patrick RUDELSHEIM, Belgium

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I am reposting responses to an earlier 2023 online forum which directly address many of the explicit questions in this forum.  Some posts have been abstracted to focus on self-spreading vaccines-  please refer to original post in the original form for the full text of the Author

https://www.cbd.int/synbio/current_activities/open-ended_online_forum/?threadid=2555



Post should appear in the sequence they appeared in the original earlier forum.
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RE: TOPIC 1: Question 2. Are there any trends that were not identified by the AHTEG that should also be considered? [#2739]

Hello…
Thanks to everyone for a stimulation discussion so far.
My name is Dr. Guy Reeves, from the Max Planck Institute for Evolutionary biology (Germany), I am an evolutionary genenetitst with interests in viral techniques intended for environmental modification. I am an inventor on a granted patent related to gene drive (EP2934093B1).



1 Trend to no-longer address domestic needs for controversial experimental techniques- inviting accusations of “regulatory tourism”

For many experimental technologies that are being presented as safe, flexible and transformative, as often the case for many new technologies. This raises an obvious question; In what circumstances would there be no or few motivating applications within the developer nations boarders ? The exclusive or near exclusive motivating of the earliest experimental proposals mentioned here appears to be most acute for experimental techniques that are intended to act autonomously in the environment, current notable examples include gene-drive and self-spreading vaccines. The principle proposals for early applications in both these examples focus on West Africa and South America, yet the developer labs and funders are almost exclusively located outside these areas. In the case of both gene-drive and self-spreading vaccines it is easy to conceive of pressing needs within Europe and the USA that could in theory be addressed by these techniques.e.g control of Lyme Disease, Rabies, Rocky Mountain spotted fever, Rift valley fever, Q fever and many other mostly veterinary diseases. It is the case that historically it is objectively the case that it is rare that safe, flexible and transformational technologies are gifted to other countries, even at experimental stages of their development. For example objectively the greatest absolute benefit of semiconductor technologies would likely have been accrued in countries with lower GDPs. However, the developer nations chose to develop and apply this technology within their own boarders and then sold the resulting products to the world. While it may be the case that healthcare is an exception to this otherwise ubiquitous mercantile rule of the world, there is considerable value in explicitly stating why addressing needs within the borders of funding nations has been rejected in favour of those in other countries. It should be expected that experiments in autonomously acting technologies in the environment are likely to prove as much experiments in regulatory credibility and the capacity to manage misinformation hazards as they are experiments designed to generate scientific data. Expecting at the earliest stages explicit plans detailing the anticipated regulatory pathways would enable funders and broader stakeholders to identify the most credible proposals which have the prospect of progressing in a timely manner. In addition it would be valuable to highlight any regulatory differences between proposed released regimes and that existing in the technology developer nations. This would act as a means to avoid the charges of “regulatory tourism”. In addition to identify instances where a lack of confidence in the ability to convince their fellow citizens of the proportionality of field trial risks my lead them to (consciously or more likely unconsciously) to mostly promote applications in other countries. I
Note that while arguments about the legitimate rights of all communities across the globe to access the enormous benefits of scientific developments, this is often not applicable to highly experimental techniques (often with a high degree of uncertainty in their outcomes). A potentially more appropriate question to ask is, which countries and communities should be encouraged to assume the biological and societal risks of experiments in their environment or even communities.


2 Horizon scanning fails to recognise norm-erosion

Horizon scanning as a term has been appropriated from a presumably military metaphor and implies that what is being looked for is far in the distance and in the direction you are facing. However, there is a class of technological concerns that might be better viewed as both near and to the rear i.e. behind us. Technologically long feasible approaches may have been rejected based on a widespread consensus / norm that they are undesirable or even unsafe. Given the two decades long history of synthetic biology (doi: 10.1038/msb4100073) it is quite possible that the process of norm-erosion will become an increasingly important sub-class of focus. In 2022 a group of colleagues and myself wrote about an example of norm-erosion (amongst a small group of scientists) in the context of self-spreading vaccines.

Lentzos, F., E. P. Rybicki, M. Engelhard, P. Paterson, W. A. Sandholtz, and R. G. Reeves. 2022. Eroding norms over release of self-spreading viruses. Science. 375:31–33. doi:10.1126/science.abj5593. open-access from http://web.evolbio.mpg.de/HEVIMAs/
see also
10.1126/science.abo1980 and .

It is very likely that norm-erosion is already a process that warrants explicitly integrating into horizon scanning procedures. Not least as rapid development and deployment can occur as often no technological break through is required.
While it is speculation, it is likely that its importance extends well beyond the example of self-spreading. Indeed the current proposal to push transgenes into wild American chestnut tree populations is not based on any recent technological breakthrough and it is arguably the case that 20 years ago this proposal would have been considered unacceptable by even technology proponents.


3 Regulatory documents and final projects are not being made public in a timely manner

For technologies where development horizons are short or where patenting considerations may delay submission of peer-reviewed publications. Regulatory documents or final reports submitted to funders may be the only information.

A It is notable that the first open field trial of a self-spreading vaccine in 1999 on a Spanish Island predated any scientific publication (Torres et al., 2001, doi:10.1016/S0264-410X(01)00184-0).
B There is no detailed information available on the presumably ongoing releases of a self-spreading bat vaccine in the USA. This is despite a redacted risk assessment having been prepared, it was subsequently withdrawn https://www.regulations.gov/document/APHIS-2019-0043-0002

Freedom of information requests, in countries where such a right exists, often take years (examples can be provided). The absence of a free flow of information about techniques being tested in the environment is both hard to explain and does not project confidence to the scientific community or public at large.

Thanks

Guy Reeves


posted on 2023-03-31 17:06 UTC+1 by Dr. Guy Reeves, Germany

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. In my contribution, I refer to points 2., 3. and 7 of the questions raised by the moderator.

A proof of concept to develop self-disseminating vaccines to be applied in wildlife was published in 2020 (Nuismer & Bull, 2020). It involves a transmissible recombinant vector. According to the authors, a virus vector with potential for superinfection and lack of protective immunity of the target populations is an advantage. Since that, several publications have dealt with the concept (Lentzos et al., 2022, Griffiths et al., 2023, Schreiner et al., 2023).

The release of recombinant transmissible viruses may be technically feasible, however, it poses major challenges to risk assessment with evolutionary dimensions that clearly touch limits of knowledge. There are several layers of complexity that have to be taken into account in regard to the recombinant vector such as the risk of unknown evolution and virulence upon release.

Transmissible vaccines are engineered to be contagious, and are potentially capable of indefinite self-dissemination within the target (or off-target) populations. There is no doubt that the self-spreading dynamics of a virus repeatedly passing from host-to-host goes along with a substantial potential to alter its biological properties once released into the environment. Since the spatio-temporal distribution may be unlimited and implies an unlimited number of passages, the monitoring of long-term effects (and in case, the mitigation of harm) will not be feasible. Therefore, coevolution may change the immune reaction of the host to the vector, the immunogenic properties of the recombinant vaccine and its pathogenicity.

Further, there is the possibility that the immunogenic insert could be co-opted by the viral vector to expand its ecological niche by allowing access to new tissues or even hosts. Other questions concern the biology of the hosts, its ecology and populations dynamics and potential transmission of the vaccine to other species, including humans.

In consequence, the release of such self-disseminating Synbio vaccines should not be envisaged for the near future. There is no risk assessment methodology in place that would allow to demonstrate safety for health and the environment before a transmissible recombinant Synbio vaccine may be released into the environment, and, if any, only limited possibility for monitoring and mitigating of potential harm.

Griffiths ME, Meza DK, Haydon DT, Streicker DG. Inferring the disruption of rabies circulation in vampire bat populations using a betaherpesvirus-vectored transmissible vaccine. Proceedings of the National Academy of Sciences. 2023; 120(11):e2216667120. https://doi.org/10.1073/pnas, 2216667120 PMID: 36877838

Nuismer, S. L.  & Bull J.J. (2020) Self-disseminating vaccines to suppress zoonoses. Nat. Ecol. Evol. 4, 1168–1173 (2020).

Lentzos F., Rybicki E.P., Engelhard M., Paterson P., Sandholtz W.A., Reeves G. (2022) Eroding norms over release of self-spreading viruses, Science, 375 (6576), https://www.science.org/doi/10.1126/science.abj5593

Schreiner CL, Basinski AJ, Remien CH, Nuismer SL (2023) Optimizing the delivery of self-disseminating vaccines in fluctuating wildlife populations. PLoS Negl Trop Dis 17(8): e0011018. https://doi.org/10.1371/journal.pntd.0011018

I am an independent trans-disciplinary researcher (Ph.D. in Mathematics and Ph.D. in Biomedical Sciences) and was nominated by ENSSER (The European Network of Scientists for Social and Environmental Responsibility).

I would like to refer to points 3, 6 and 7 of the questions raised by the moderator.

I am also the author of “Challenges and Opportunities of mRNA Vaccines Against SARS-CoV-2 – A Multidisciplinary Perspective” which was published by Springer earlier this year (439 p., 61 illus., https://link.springer.com/book/10.1007/978-3-031-18903-6).

Even though self-spreading vaccines harbor numerous unique properties, nonetheless, as some applications of self-spreading vaccines are meant to protect certain animals against infectious disease (e.g. as detailed in #1273), a few insights may even be gleaned from recent years. Specifically, in terms of immune responses, several important questions may be rooted in established unknowns and concerns.

• How is it evaluated/established that the evoked immune responses will be protective? How can it be ensured that it will be enough of an immune response (so it is helpful) but not too much (i.e. not harmful)?
• Will it be protective in terms of various scaling issues? I am referring to Jack Heinemann’s scaling notion – which includes a host of processes, interactions and other considerations relevant to vaccines in greater generality (detailed in chapter 7 in the book); for instance, is it protective over time and for the entire population, including their many differences (age, weight/nutrition status, previous immunity, other infections or issues, etc)?
• Why is there any reason to believe the expected immune response from self-spreading vaccines  will be better than what in recent years has been recognized as a particular challenge – that of vaccinating into a pandemic? Point is that in the wild, the pathogens are already out there. If the targeted organisms are all vaccinated while they are already surrounded by those pathogens, how will it be possible for them to develop adaptive immune memory (which does take time)?
• How do we know which arm(s) of the immune system will really be triggered – for those that are targeted as well as for off-target species? Note, for example, that even with SARS-CoV-2, one of the best studied viruses ever, it took years to figure out that this virus may not merely infects human but also bacterial cells (e.g. Brogna C, Brogna B, Bisaccia DR, Lauritano F, Marino G, Montano L, Cristoni S, Prisco M, Piscopo M (2022) Could SARS-COV-2 have bacteriophage behavior or induce the activity of other bacteriophages? Vaccines 10(5):708).
• What about immune responses for those organisms (on and off-target) that cannot mount the modeled immune response?
• Is there any guarantee the immune response will be sterilizing? Is there any guarantee such a vaccination strategy won’t result in “leaky” vaccines?
• What is the rationale that the self-spreading behavior of those vaccines will give durable protection to the entire population? Note that this issue has during the pandemic years by some been described as counter-intuitive. Specifically, various studies have confirmed that the more individuals are vaccinated, the greater the likelihood for pathogenic escape and the establishment of more dangerous escape mutants. A study from the Institute of Science and Technology in Austria (https://ist.ac.at/en/news/counterintuitive-dynamics-threaten-the-end-of-the-pandemic/) put it this way for Covid: “If there are many people infected with the original strain of the virus, there are plenty of opportunities for the virus to mutate…. we also found a counterintuitive result: At the end of a vaccination campaign, when a lot of people are already vaccinated and there are still a lot of other people infected with the original virus, a vaccine-resistant strain not only has a higher chance to occur but also an evolutionary advantage against the original strain.” How is it that self-spreading vaccines would not be susceptible to such a situation?
• Self-spreading vaccines are meant to evolve. In which way can they really evolve? How could they possibly evolve in a way as to not succumb to the potential vaccine-mismatch as just described?
• What does it mean if there are pathogenic escape mutants that happen at scale? What would it take, even theoretically, to counteract those new – dominant - escape mutants?
• If both the self-spreading vaccine and the targeted pathogens evolve, will this lead to unpredictable/ adverse cumulative effects in terms of immune responses or other undesirable events?
• Will it not automatically be the case that some/many organisms will have a frequent or ongoing encounter with the vaccine vector? Thus, they will be continuously exposed to the same antigens. What will that do to their immune response (immune imprinting? tolerance development? excessive immune reactions, etc?) 
• Given that everything is connected, it must be assumed that some of the exposures will involve humans as well. Will this mean we will find ourselves in sort of an ongoing pandemic, truly by our own making?
• What is the exact mechanism by which the presumed protective effect on future generations happens? How can it be guaranteed that very young and developing organisms are ok with inherited/transmitted vaccines, load of antigens, or even unspecified immune reactions?
• What are inherent breaks/stops to limit the spread of self-spreading vaccines, especially in case of pathogen escape or development of adverse events following “vaccination?” What is the recall mechanism for those viral vaccine vectors?
• How can the vaccine vectors be purged from the environment?
• What is the concern of persistence of such LMOs across the entire ecosystem (indeed, that is One Health!) The point is that those LMOs would be present at a significantly large scale. What will this do to e.g. new niche formations, those vectors introducing genotoxic effects to off-target species (recombination issues, horizontal gene transfer etc), the development of new pathogens, …?


Thank you for your attention.
Siguna

Thank you Dr Christoph Then you for this critical information. I am in particular intrigued by your important observation and the provocative statement that you derived from the 2020 Nat. Ecol. Evol. paper ("a virus vector with potential for superinfection and lack of protective immunity of the target populations is an advantage.")

At the risk of being repetitive (as this may have been observed in the follow-up articles you mentioned), I believe it is worthwhile to look at this foundational paper by Nuismer, S. L.  & Bull J.J.: Self-disseminating vaccines to suppress zoonoses. Nat. Ecol. Evol. 4, 1168–1173 (2020).

Several scenarios overthrow the described model, e.g.

(1) If you do not have a “homogenous and well-mixed” population where “the vaccine can be continuously introduced into the reservoir population.” In practice, you will never find such an idealized situation.

(2) A specific concern, described by the authors is that of prevailing host-immunity to either vector or pathogen. Again, in real life, I don’t see why this could not be the case? The suggested solution to this scenario is what you quoted – vaccines that offer superinfection and apparent lack of protective immunity. However, this case seems to only have been discussed in the context of the reproductive number R0 (the important point is that existing host-immunity will slow the spread of the vaccine through the population and defeat the goal of eradicating the pathogen). However, if you indeed have vaccine vectors capable of superinfection/providing lack of protection, then this means that you do not have sufficient host-immunity to neutralize the pathogen. But then, by necessity, you have pathogen evolution and escape – and again, the model would not work.

It seems therefore that there are some foundational gaps in the model itself?

But perhaps I am missing something?

Thank you!
Siguna

My name is Jack Heinemann. I’m a member of former AHTEGs on Risk Assessment and Risk Management, an academic with expertise in using gene technology, and I regularly publish on the topic of regulation, risk assessment, and GMOs.

I’ve really appreciated the interventions made by others on this topic. As Guy Reeves indicated [#3073], the initially slow uptake by forum participants could be due to how new these emerging topics are. I want to thank Siguna Müller [#3091] for her intervention which helped to me to see how I could contribute.

I’d like to highlight several points made by, among other people, Guy Reeves, Siguna Mueller, Christoph Then, and Luke Alphey. My contribution thus being more to help curate what I think are seminal points.

1. We may not all mean the same thing when we say ‘vaccine’.

This point is related to Luke Alphey’s observation that “Transmissible vaccines have a wide range of potential properties”. As a case in point, already 20 years ago a GM plant that produced an immune-stimulating protein was developed for use against the possum, an invasive pest in New Zealand (https://www.nzherald.co.nz/nz/ge-carrots-could-clobber-possums/MENTTBBDUFLGLRBCW3XSVQMFGQ/). Ingestion exposure was causative of an auto-immune response in females to their own eggs. Over time the property of causing ingestion-related auto-immune-stimulation was referred to as a kind of vaccination (rather than as some kind of allergic reaction).

This potential self-spreading "allergen" intended for conservation purposes never made it to market. The example illustrates that depending on what elements a gene technology has in common with other widely used terms, it can be cast as similar to those and potentially influence scoping decisions.

While I personally might agree with more restrictive definitions of self-spreading (viral) vaccines, I do not see any compulsion for every developer to subscribe to them or having a history of doing so, departing from the limitations of producing a ‘protective’ immune response using only inoculation via a viral infection.

2. Not all self-spreading vaccines are infectious or viruses (possum “vaccine” in NZ)

There is much attention in this forum to infectious vectors such as viruses. However, self-spreading can occur by different means. Conjugative plasmids found in gram-negative bacteria transfer into the cells of all other forms of life, but are not by convention referred to as viruses. Plants that express immune-stimulating proteins are self-spreading, and therefore so is the ‘vaccine’, but the route of exposure is not infection.

3. Not all “immunizations” must depend on a mammalian immune system.

This point leads on from Dr Müller’s post [#3091]. For example, the CRISPR/Cas system is frequently referred to as the bacterial immune system. Regardless of the diversity of opinion on any specific reference, when the concept of a vaccine is to elicit a kind of resistance to either an infection or to bind a particular molecule, that outcome may not be caused by what all of us at this point in time would consider a response consistent with the notion of a vaccine. Scope is determined by who defines the immune system.

4. Released elements can evolve.

By design, we are talking about constructs that can change because they are self-spreading. That property makes them eligible to evolve. Their evolutionary trajectory will be determined by a variety of environmental factors, both internal and external to the organism/vector. Those factors and the outcome of them acting as selective forces are not predictable from a description of the original product.

The point I am raising is that even framing the discussion within the shadow of pre-market risk assessment frameworks is problematic. For products of this kind, risk assessment must be ongoing and flexible, taking into account new environmental conditions, new environments, mutations, and responses both intended and unintended by the target organisms.

Thank you all again for interesting discussion.
Jack

Dear CBD Secretariat, dear colleagues,

I would like to thank you for the remarkably valuable exchange in this thread so far. My name is Margret Engelhard, and I work at the German Federal Agency for Nature Conservation, where I head the Division “Assessment Synthetic Biology and Enforcement Genetic Engineering Act”. I’m a member of the current mAHTEG and have also in the previous Synthetic Biology AHTEGs.

Our Agency has commissioned a horizon scanning project on genetically modified viruses from the Environmental Agency Austria, and my comments and additions to the previous contributions are largely based on results from this ongoing research project.

I would like to thank the Secretariat for compiling issues brought up within the mAHTEG in the Issue Brief linked in the first post in this forum, this is very helpful; I try in parts to refer directly to its contents.

1. Point 1, Impacts on the objectives of the Convention
a. Biodiversity
i. Potential consequences of releasing self-spreading vaccines (SSV) depend on the purpose of the specific applications. Categories (see also post [#3075] by Guy Reeves): (i) the currently developed SSVs for immunisation against communicable zoonotic pathogens, and (ii) SSVs developed for other purposes, e.g. virally vectored immunocontraception which are developed to reduce target animal populations. Spread of SSV agents developed for the latter purpose outside of the intended area of application could have unintended negative consequences on animal populations in their areas of origin.
ii. Unpredictable effects, such as physiological and ecosystem dynamics: Unintended adverse consequences of SSVs, including potential harm to biodiversity, have long been taken seriously because the impact of SSVs is inherently difficult to predict and assess (e.g., WHO 1993; CBD 2007; see also comments to Point 3). It is also hard to predict whether intended effects will be realised in the environment.
b. Sustainable use of the components of biodiversity
i. The ecological and social sustainability of genetically modified virus applications in general and of applications of SSV specifically is difficult to assess. Generally, approaches for the assessment of sustainability of LMO applications are not well developed, and most of the respective work in recent years has focussed on crops. Thus, for applications of SSV, no appropriate framework for sustainability analysis is currently available. To assess the sustainability of interventions based on SSVs it is necessary to establish an approach which also takes into consideration alternative interventions and their advantages, disadvantages and the level of uncertainty that is associated with the respective assessments.
2. Timeframes:
a. The timeline that is set out in the Issue Brief relates to the technological development.
i. Examples include the transmissible vaccines which are currently developed to reduce the occurrence of relevant pathogens (Lassa fever virus or Ebola virus) in their animal reservoirs (rodents and apes, monkeys and bats, respectively).
ii. According to information released by the developers (TVG Lassa fever vaccine makes progress - The Vaccine Group, https://thevaccinegroup.com/lassa-fever-vaccine-makes-progress), initial studies conducted with a modified cytomegalovirus from Natal multimammate mice (Mastomys natalensis) (Hansen et al. 2023) have shown that the designed vaccine virus is transmissible, immunogenic and did reduce the infection and excretion levels of Lassa virus subsequent to challenge of immunised rats with Lassa virus. Further testing is underway and preparations for manufacturing of the vaccine in West Africa have already started (see also Guy Reeves [#3072]). Another report addresses the development of a transmissible vaccine targeting vampire bat-transmitted rabies based on a Desmodus rotundus betaherpesvirus (DrBHV) (Griffiths et al. 2023).
iii. Applications of SSVs for other purposes have also been investigated, including virally vectored immunocontraception for control of invasive alien species (Hardy et al. 2006; Redwood et al. 2007). Some of the approaches showed insufficient fertility control levels (van Leeuwen & Kerr 2007, Mckenzie et al. 2006). Due to major challenges regarding efficacy (i.e. insufficient duration of sterility) and delivery (i.e. ineffective transmission of the viral vector), as well as concerns about the non-retrievability of genetically modified viruses once released in wild populations (see Lentzos et al. 2022 and references therein), research and development interest seems to have faded. However, there can be a resurge of interest if the technical problems that resulted in a low efficacy of the previously developed applications can be solved.
b. On the societal level, the timeline is longer than on the technical level. Reasons include that (i) risk assessment, risk management and regulation are not in place; (ii) significant cultural and conceptual issues have not been addressed; and (iii) it is unclear how FPIC could be ensured.
3. Gaps or challenges for risk assessment, risk management and regulation
a. SSVs pose significant challenges for risk assessment which need to be addressed prior to any authorisation of releases of SSV applications. National and international cooperation seems crucial for addressing these challenges, with a view to the situation that limited resources are available in individual countries and particularly in countries where the currently discussed applications may be applied. If applications are developed in different countries than the country of release an adequate level cooperation and coordination between the involved institutions and countries need to be ensured.
b. A number of gaps and challenges are already indicated in the Issue Brief. Other aspects are mentioned e.g. in (Sandbrink et al. 2021; Ynga-Durand et al. 2019; Nuismer and Bull 2020). Here I want to expand on some aspects:
c. Lack of stability of modified viruses: As also elaborated by Christoph Then in Post [#3086], a main concern is the genetic stability of SSV constructs and the possible evolutionary changes that may happen after release in the environment through mutation, recombination and complementation. The SSV developed to treat Lassavirus host animals, for example, is based on a design which promotes the gradual loss of the antigen expression cassette which is inserted into the Mastomys specific cytomegalovirus. Thus, it is crucial to know the loss rate after release into wild host populations and whether the loss actually leads to reversion to the parental cytomegalovirus as described by the developer. It needs to be assessed whether genetic changes occurring in the released SSVs would impact on the efficacy of the application or lead to unintended effects.
d. Because of the expected changes of SSV after release, risks assessment cannot be based solely on the basis of data pertaining to the originally released SSV; ongoing monitoring of its development would be a requirement.
e. Rapid spread depending on viral vector: The rates of transmission of the SSVs in wild populations of the target hosts are highly relevant for efficacy and safety. Substantial uncertainties exist concerning the dynamics of transmission of SSVs in wild populations, e.g. as noted by Griffiths et al. (2023) for herpesvirus based SSVs in vampire bats. The actual spread of SSV agents in release areas and in the respective target populations thus remains difficult to predict or model; the intended rate of reversion to the unmodified vector virus is difficult to control and significant uncertainties are associated with changes of the SSV agent due to interaction with related viruses occurring.
f. The capacity for superinfection is regarded as a crucial aspect for SSV applications e.g. SSVs based on cytomegaloviruses, but may be difficult to predict with the necessary certainty for SSVs released into the environment. With cytomegaloviruses also immunomodulatory effects and possible oncogenic effects need to be considered (Ynga-Durand et al. 2019).
g. Wide host specificity for some viruses: Another critical issue for the assessment of SSVs are the level of environmental exposure and their host range. Although a narrow host range is aimed at in some applications, such as the SSV application targeting Lassa virus hosts; it needs to be confirmed that the SSV is indeed species-specific under conditions of release. Other applications which are developed using viruses with a broader host range e.g. to target a wider range of host species need to be assessed for unintended effects due to the broader host range or due to changes which may increase the host range.
h. Horizontal gene transfer
i. The application of SSVs may promote evolutionary changes in the targeted pathogens, which may impact their level of infectivity and pathogenicity. Such changes are considered to occur at a higher rate in RNA viruses (such as Lassa fever virus).
j. A comprehensive overview of SSV applications as a first step to assessing their impacts is not available. The report provided on Synthetic Biology by SCBD in 2022 identified some of these applications and indicated challenges e.g. for risk assessment that may be posed by these applications (SCBD 2022). In addition to the activities by the SCBD, horizon scanning activities are pursued at the EU level, e.g. by EFSA (van der Vlugt 2020; and ongoing activities). However, a more comprehensive overview on relevant genetically modified virus applications is still required to focus further work, e.g. aiming at a better regulatory preparedness of risk assessors.
k. Risk management challenges can be expected during both testing and application in the environment; the safe testing of SSVs in a step-by-step approach may not be feasible due to the risk of unintended spread of the SSVs in less contained stages. Due to likely persistence of the SSVs an accidental release may be difficult to detect, manage and may be impossible to reverse.
l. With regard to risk management, self-spreading agents will pose more challenges than LMOs which have less ability to spread and persist in natural environments. The challenges can be compared with the ones arising for LMOs containing gene drives.
m. For SSVs with a higher potential for spread and persistence in animals with a larger area of occurrence, transboundary spread may be an issue and the ability to control such transboundary movements of SSVs seems rather limited.
n. Guidance for environmental effects of release of viruses (e.g. non-target effects) is either non-existent or limited (CBD 2007). Points from the 2007 meeting that are still relevant include
i. Viruses are different from most other (micro-)organisms with respect to transboundary movement, persistence/latency, infectious processes and basis for host preferences. Viruses are biologically unique in other respects as well, e.g. frequency of mutation, recombination and horizontal gene transfer. All of these aspects also apply to SSV.
ii. The issue of ecological and environmental effects has not been given sufficient consideration and insufficient consideration has also been given to the spread of viruses across biological borders
iii. Risk assessment should be complemented by meaningful monitoring and surveillance programs.
iv. Monitoring: the existence of the virus in asymptomatic populations is not studied. Epidemiological data commonly address only the incidence of the expression of a disease.
o. Some international bodies, such as OIE, Codex Alimentarius, EMEA, and WHO provide partial guidance by focussing on clinical aspects. For example, some issues like viral shedding to the environment will have relevance for both clinical and environmental assessment.
p. The available guidance for risk assessment of GM viruses needs to be further developed – e.g. as indicated by the EFSA Scientific Committee (2020) for the EU.
q. The European Medicines Agency EMA’s 2004 guidance for genetically modified veterinary vaccines is under revision (https://www.ema.europa.eu/en/live-recombinant-vector-vaccines-veterinary-use-scientific-guideline#current-effective-version-section
r. It is open how SSV can be prevented from spreading over national borders (CBD/AHTEG 2019, Annex 1, 48). It is also unclear how potential transboundary movements by SSV could be dealt with (CBD 2007; Henderson and Murphy 2007) . Art. 17 of the CPB only provides for notification and information obligations in the event of unintentional transboundary movements of LMOs. In order to ensure an adequate level of protection (cf. Art. 1 CPB), there would, however, be a need to create participation opportunities in the run-up to such a release where this involves the long-term uncontrolled spread, as well as to establish effective protective measures in order to prevent them impacting foreign territories.
s. Precautionary principle: As SSV bear the potential for significant and irreversible environmental harm, and risk assessment and management of SSV are highly problematic, strict precautionary conditions are needed.
4. Potential social, economic, cultural, ethical, political, human health and/other relevant impacts
a. SSV for use in wildlife inevitably bring up the issue of SSV for use in humans. Concerns that have been brought forward with regard to application in humans may also be relevant for applications in wildlife.
b. Not only (i) potential consequences, but also (ii) underlying goals of interventions and (iii) characteristics of the technologies employed are subject to normative evaluation.
i. The most pertinent characteristic of SSV consequences is that their prediction involves insecurities. Any evaluation of the desirability of the potential consequence is thus made on a weak empirical fundament.
ii. On a more general level, SSVs could impact many people who have not chosen to deploy them, throwing up questions of justice.
iii. Goals such as combatting disease are generally considered valuable. However, they need to be evaluated against the backdrop of underlying causal factors, the societal context and alternatives (see Point 5). The aspect of dual use potential brought can also be relevant here.
iv. The technology of SSV is special in its potency as well as in the plasticity of its elements. It would be a highly relevant case for philosophical inquiry to characterise the ambivalence in a technology that produces potentially highly potent entities with an unstable, dynamic, and evolving existence. This characterisation of the technology throws up a large range of questions with heavy normative weight, such as some of the questions listed by Siguna Müller in Post [#3091].
c. An “erosion of norms” (Lentzos 2022) in the sense of decreased risk-aversiveness can entail decreased acknowledgement of insecurities. Strict adherence to the precautionary principle and development of appropriate guidance are needed to avoid that releases take place in windows of opportunities generated by a combination of norm erosion and readily available technology (see also Guy Reeves’ elaboration in [#3080]).
d. Development of SSV for release in other countries than that which develop them entails potential for power asymmetries. This situation therefore requires strong standards for cooperation and commitment to equal security, risk assessment and risk management standards in all involved countries. An analogous situation can occur between people within a country, highlighting the need for robust participatory approaches.
e. As brought forward by Eva Sirinathsinghji in the post from the March online-forum reposted under [#3077] (and by others in the March forum, as quoted by her), the assessment of SSV needs to involve “meaningful participation from a diverse and broad range of actors, including potentially affected communities, indigenous peoples and local communities”. This pertains not only to details of applications, but also to how the problems that the applications address are framed in the first place, and by whom. Democratic processes can safeguard that technologies are evaluated at an early stage and that global health projects adequately target the challenges and serve the priorities of the affected communities (see also Point 5).
f. Before any release of SSV could be considered, robust guidelines would be needed for participatory activities and FPIC. In establishing guidelines for FPIC and for the exchange of knowledge and evaluation across cultures more generally, care must be taken to ensure that power imbalances do not invalidate the processes, and that procedures of organisation, facilitation and communication are valid.
g. Transparency in research, development, funding and decision-making is important to ensure robust horizon scanning and assessment. However, as brought forward by Guy Reeves in Post [#3080], systems for reliable and timely access to information need to be improved.
5. Problems addressed / alternatives
a. The reasoning put forward for a possible release of SSVs targeting pathogens are focused on the current challenges to predict and to prevent outbreaks of zoonotic diseases and the costs in life as well as the economic costs inflicted onto the affected people and societies. The use of SSVs is assumed to be a more effective way to vaccinate wild animal species which are reservoirs for the respective pathogens than other means of interventions (including non-transmissible vaccines or other methods reducing the number of rats infected with Lassa virus). The assumption is that the use of SSV can significantly reduce future exposure of humans to these pathogens. However, it is unclear whether these predictions are robust and sufficient to determine whether the respective applications can indeed be regarded as sustainable. Whether the required efficacy of SSV applications would be achieved over a time period necessary to have a sustained effect on lowering pathogen reservoir levels is difficult to predict and model. A possible loss of efficacy of a specific application is important for the consideration of sustainability. Without efficacy, sustainability may not be achieved. Thus, a positive effect in terms of higher safety of humans and lesser costs for medical systems may not be taken for granted without further data.
b. Overall considerations should include whether vaccination approaches actually address root causes for the infection of humans with zoonotic diseases, which in some cases is due to the increasing encroachment of human settlements and activities into wildlife habitats which leads to higher probability of contacts. Vaccines based on SSVs may fix a detrimental consequence of such developments but would not address other negative aspects associated with this development.
6. Lessons to be learned
a. SSV can build on the experience with genetically modified vaccines for veterinary use.
b. The available knowledge concerning other applications designed for spreading in targeted animal populations and environments, such as gene drive LMOs, as well as the experience with invasive organisms should be considered for the assessment.
7. Limits of knowledge, other considerations
a. My intervention here has focussed on viruses, starting from an understanding similar to Guy Reeves’ in [#3072]. However, I would like to thank Jack Heinemann [#3094] for bringing up the topic that not all self-spreading vaccines are infectious or viruses. This is an important aspect for further assessment.
b. As also noted by Reeves in in [#3072], the techniques in this trend are not all new; what is new is rather the perceived impetus in a scientific niche to now develop them more intensively for release into the environment, although it has for a long time been held among virologists that this would not be sufficiently safe (Lentzos 2022).
c. Lack of stability of modified viruses: The instability and evolution of released viruses has been brought up by Jack Heinemann in the previous post in this thread and indeed by most of the contributions. I have listed in in Point 3 above, but in addition to being relevant for risk assessment, management and regulation, it is on a fundamental level a central characteristic of SSV that significantly limits what can be known in advance of a release.

Thank you very much - please find the references in the attachment.

Dear colleagues,
My name is Dr. Swantje Schroll and I work at the German Federal Office of Consumer Protection and Food Safety as a scientific officer in the office of the German Central Committee for Biological Safety (ZKBS, https://www.zkbs-online.de/ZKBS/EN/Home/home_node.html), where I have been responsible for risk assessment of Synthetic Biology for the last ten years.
The ZKBS has been carrying out a monitoring of Synthetic Biology since 2009 and has published three monitoring reports so far (BCH records BCH-LAW-DE-110828-2 , BCH-LAW-DE-113533-3 , and BCH-LAW-DE-261162-1 ). In these reports, the ZKBS has focused on the question whether the outputs of Synthetic Biology so far can be considered as genetic engineering. For this monitoring, the ZKBS and its secretariat explore and review recent literature, participate in symposia and workshops and have organized two symposia to gain more detailed insight into Synthetic Biology.
As has been mentioned in other online fora several times, a missing precise and commonly accepted definition of Synthetic Biology complicates the identification of trends and topics for a general and comprehensive horizon scanning. For example, self-spreading viruses certainly need special attention as they are intended to spread in wild populations. However, they are manufactured using classical genetic engineering methods which are employed in laboratories worldwide on a daily basis and are classical LMOs underlying the regulations of the Cartagena Protocol. The Lassa virus vaccine, for example, consists of a cytomegalovirus in which one transgene from the Lassa virus genome has been inserted. What is new about those viruses is their potential release into the environment. Consequently, it would be preferable to identify such topics of relevance for the three objectives of the Convention under the “New and Emerging Issues”-mechanisms instead of identifying them as Synthetic Biology.

Best regards,
Swantje

My name is Dr Siguna Mueller. I am an independent trans-disciplinary researcher (Ph.D. in Mathematics and Ph.D. in Biomedical Sciences) and was nominated by ENSSER (The European Network of Scientists for Social and Environmental Responsibility).

I would like to thank everyone for the interesting discussion that raise important questions, such as the observation made by several that there is no clarity as to what is meant by self-spreading vaccines. This term must be clearly defined by the CBD. The present situation creates numerous ambiguities related to risk-assessment as well as regulatory and oversight gaps, especially when applied as a LMO product or one that is meant to act in various forms as gene-therapy to induce medicinal features or for immunocontraception.

Regarding Q5: I am surprised that there has also not been intense debate over the absolute necessity of SSVs. 

Here we have the premise that technologies that will spread various essentially man-originated genetic materials and resulting products which even theoretically raise numerous concerns are desperately needed. The claimed reason as to why the entire ecosystem and all of life on earth must be subject to those “urgent” and large- scale interventions all hinge upon one argument (as seen in virtually all projects/sources that I consulted on this topic): to prevent another spillover, purportedly as we have seen with the Covid pandemic.

It really raises the parallel question to the one first articulated by Dr Guy Reeves [#3073]. Why is there so little discussion, reflection, and questioning about the premise of the believed necessity of SSVs ? Any typical person on the street knows by now that the question about the origin of SARS-CoV-2 has not been settled. There have long been several studies and investigations by the Lancet Commission, the FBI, and an assessment by the Energy Department that have concluded, with various levels of confidence, that this virus is a lab construct.

In this context, I would like to point to my article, recently published in Frontiers (https://www.frontiersin.org/articles/10.3389/fbioe.2023.1209054/full), which carefully lays out yet another explanation – not of the origin of the entire virus but that of its most critical genetic fingerprint (the sequence surrounding and encompassing the FCS). At the core of my analysis is (1) the finding that the novel insert was radically unexpected in terms of gene-function (https://www.frontiersin.org/articles/10.3389/fmicb.2023.1073789/full) and (2), the observation that we do not know enough about the interaction of man-made genetic elements and those with existing living beings (including viruses). In particular, CoV recombination has only in recent years been shown to be driven by different factors than long thought. It is indeed evolution and selective pressure that drive CoV recombination. I lay out several clear pathways how such recombination with specific synthetic genetic elements studied in a lab context could have led to a recombination event that led to arguably the key novelty of the SARS-CoV-2 genome.

I make strong points why and how this could have happened in a lab. But the analogous developments could be realized effectively out in the open environment via SSVs, albeit not with a low likelihood, as indeed the entire self-spreading vaccine technology triggers numerous scaling variables and aspects. The man-originated genes and resulting proteins that would be introduced at scale will have plenty of opportunity to interact with other life forms – again, in ways that contradict many of the current beliefs of what is or is not possible.

As long as the origin of SARS-CoV-2 does not include the very possibility of such genetic recombination events (as I and others argue), and many others, one of the most critical weak spots of self-spreading vaccines will remain inadequately appreciated. And in case those unanticipated interactions in nature create a novel pathogen, then the argument will likely be made that it is “from nature” and that the rollout of self-spreading vaccines needs to yet be enhanced. The disconnect should be obvious but unless articulated and discussed, will, again, not be widely appreciated, and the result may be the doubling down of some technologies that likely increase the very thing they aim to protect against.
In the light of major knowledge gaps that STILL exist regarding SARS-CoV-2’s origin (which has been extensively studied), it seems difficult to take specific assertions that have been made regarding SSVs as sufficiently established. For instance, promises that they are highly specific to host species, that off-species spread is prevented (https://thevaccinegroup.com/science/), or that the genetically manipulated vectors used will “gradually” lose the added genes (e.g. https://thevaccinegroup.com/lassa-fever-vaccine-makes-progress) and others should be clearly demonstrated in the framework of LMOs, gene-therapies, etc, as appropriate.

Lack of clear definitions will also negatively affect downstream processes beyond R&D. I don’t even want to begin to think about how all of the inherent knowledge gaps and the ill-defined regulatory framework of self-spreading vaccines could be maliciously exploited by hijacking/converting these technologies as bioweapons to disrupt animal and human health, the environment, political and societal structures, local and global trade and economy, to religious aspects and the individual human rights and liberties. Some ideas of RELATED misuse potentials (informed by the panemic) I have summarized here: https://link.springer.com/chapter/10.1007/978-3-031-26034-6_10

Thank you.
Siguna

Dear colleagues,

my name is Kristin Hagen, and I work in Division “Assessment Synthetic Biology and Enforcement Genetic Engineering Act” at the German Federal Agency for Nature Conservation. I would like here to respond specifically to the points raised by Ben David Durham [#3072], quoting in part from a Viewpoint paper published by our Agency last fall (BfN 2022). I agree that the philosophical approach that the CBD takes towards SynBio is an important issue, and I believe it responds to Point 4 in the threads that are up for discussion.

Ben David Durham rightly points to the central premises of the “Anthropocene argument”: (p1) Firstly, that pristine ecosystems no longer exist. (p2) Secondly, that this is due to the impact of the human species on the planet. This pertains to organisms and ecosystems intentionally or unintentionally altered by direct human influence, but also to more ubiquitous effects of pollutions, marine pollution, fragmentation of the landscape and climate change (see e.g. Preston 2018 for a comprehensive account). On the basis of these premises, the argument leads to a conclusion that I will, however, question: (c1) Attempts to preserve pristine nature and allow it to change on its own are futile and naive. Sometimes, a second conclusion is: (c2) Humans need to take a more actively intervening and designing stance towards nature.

I agree with the two premises to some extent, but they warrant some qualification which in my opinion undermines the argument and the conclusions:

(Re p1) It is true (and almost tautological, given the identification of climate change as human-induced) that _completely_ pristine ecosystems (in the sense that they are completely unaffected by impacts of humans) do not exist. However, it is incorrect that there is therefore no longer _any_ pristine nature worthy of being valued and of protection.

One reason is that concepts such as untouched nature and wilderness can be understood in the sense that there are _components_ of natural dynamic processes, spontaneity or natural environments in their pristine and evolving state. This is akin to the “continually evolving/changing nature of biodiversity” referred to by Ben David Durham. It is precisely this diversity, networking and ability to react to environmental changes that form the basis for both the resilience and the dynamic adaptability of nature – and arguably, of its intrinsic value (a concept referred to in Recital 1 of the Preamble of the CBD). Ecosystems that are _relatively_ untouched by humans provide considerable scope for such natural processes, so that nature’s unique character can often endure and evolve. Natural dynamics such as evolutionary processes can (and should) be valued and protected.

Another reason why the first premise (p1) is contested is that pristine nature and wilderness have been understood in nature conservation for a long time as concepts that are subject to considerable cultural influence (e. g. BMU and BfN 2014), and that many ecosystems can rightly be referred to as nature-culture hybrids. Some ideas of nature categorically even reject _any_ strict division or demarcation between humans and nature. In any case, a purely binary distinction between natural and unnatural/artificial is inaccurate in both conceptual and empirical terms, and naturalness can in most cases better be conceived in degrees (cf. also hemeroby concepts in ecology). The protection of (largely) unused, non-fragmented areas that are used to make sure that natural processes can take place with a minimum of human influence is therefore still very much practicable, and also does not conflict with the conservation of less pristine nature, for instance in cultivated landscapes and urban natural settings.

(Re p2) This is a qualification that is less central for the argument, but important to consider in relation to perspectives of IPLC, the Global South, and people of low income/consumption: The concept of an age of the “Anthropocene”, a term originally proposed for a new geochronological epoch, is controversial not only because it does not differentiate between ecosystems that are affected to different degrees, but it also does not differentiate between the impacts of different economic systems (Manemann 2014). The concept alludes to the comprehensive, global consequences of _all_ human activity, but the majority of impact has arisen from the activities of a very small minority of the world’s population.

Because of the qualification to premise 1, it does not follow from the factual extensive loss of pristine nature that there is nothing left to value and to preserve. Even less does it follow that the best strategy in light of the loss of pristine nature and of biodiversity is to intervene even more profoundly in nature (this conclusion has been termed the “Anthropocene fallacy” by Toepfer 2020; cf. also Sandler 2017 & 2019). In fact, experience tends to teach us the contrary. While it is true that humans have managed to generate wealth and capabilities, it is also true that a lot of human-induced change has had (profound) adverse effects, even when the intentions have been good (European Environment Agency 2001, 2013). Arguably, this is part of the causal bouquet of the current biodiversity and climate crises. Insufficient risk-aversiveness and humbleness, together with an instrumentally narrow understanding of nature have contributed to the destruction of nature and of the environment (cf. Meyer-Abich 1997). In SynBio, there are some powerful visions of feasibility and a strong belief in the human capacity for design, judgement, and ultimately, improving nature’s very processes (e.g. Church and Regis 2012; Doudna and Sternberg 2017; cf. also critical Then 2020, p. 8).

I therefore agree that we need to engage in a fundamental debate on how synthetic biology, including new genetic engineering technologies, is understood in relation to nature. However, I do not share Ben David Durhams conclusion that the necessary outcome of this debate will be that “human-induced change is good (i.e. a key tool for 'saving the planet')”, or even a unified vision for enabling SynBio on CBD level. Rather, we will need to discuss, for example, views of genes as programming, organisms and ecosystems as production systems and humans as designers of nature. There will need to be an open, inclusive and critical discourse, drawing on a long history of analysis of both normative and empirical aspects in the variety of concepts of nature and biodiversity, and of knowledge and technology. The debate will be science-based in a multi- and transdisciplinary way and also include traditional knowledges. On this basis, the CBD SynBio strategies can be aligned with its foundational values.

Thank you again for the discussion and for opening it to conceptual issues,
Kristin Hagen


BfN (Federal Agency for Nature Conservation) (2022): Genetic engineering, nature conservation and biological diversity: The boundaries of design. Viewpoint. Bonn. DOI: 10.19217/pos222. https://bit.ly/gen-engin-conserv

BMU; BfN (2014): 2013 Nature Awareness Study. Population survey on nature and biological diversity. Berlin and Bonn https://www.bfn.de/sites/default/files/2022-09/2013-nature-awareness-study-bmu.pdf
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Dear Participants of the Open-ended Online Forum on Synthetic Biology,

Thank you for your interventions and active engagement.
The forum is now closed for comments.

Thank you,
The Secretariat