In their report, the 2019 AHTEG on Synthetic Biology identified an non-exhaustive list of trends that could inform the process for broad and regular horizon scanning, monitoring and assessment. Thus, to inform the work of the multidisciplinary AHTEG, participants are kindly requested to provide information on the trends identified, their relevance and when applications are likely to be available under these areas.

2. Are there any trends that were not identified by the AHTEG that should also be considered?

----Posted on behalf of Dr. Martin Cannell---

Welcome to the Open-Ended Online Forum on Synthetic Biology!

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Could you provide a link to the AHTEG document that identifies those trends?
Thank you!
Gerd Winter

Dear all
For the convenience of the distinguished members of the online forum, I am including a link where you can access the mentioned AHTEG meeting report and the considerations on Synthetic Biology https://www.cbd.int/meetings/SYNBIO-AHTEG-2019-01
Best regards,

Dear Mr. Winter, A link to the AHTEG report as well as to the Technical series on Synthetic Biology has been provided on the landing page of this forum.
https://www.cbd.int/synbio/current_activities/open-ended_online_forum/
Kind regards,
Secretariat team

Dear Mrs .Odette Manirakiza,
Plese note that you have until 5 pm (EST) on 31st March to post and participate on the forum.
Kind regards,
Secretariat team

Karoui et al., (2019) reported the Future Trends in Synthetic Biology. It provided relevant information which may helpful for AHTEG. This is the doi address:  https://doi.org/10.3389/fbioe.2019.00175
Other related papers. Future trends in synthetic biology in Asia
(https://doi.org/10.1002/ggn2.10038)
Trends and Outlooks in Synthetic Biology: A Special Issue for Celebrating 10 Years of Life and Its Landmarks
https://doi.org/10.3390/life12020181

As shown in our recent backgrounder (https://www.testbiotech.org/node/3036), the interactions of Synbio organisms that are introduced into a shared environment is an issue that will require in-depth consideration for risk assessment and risk management.

Dear colleagues,

The development of LMO/synbio microorganisms that may soon be trialled is a topic that requires increasing attention, especially considering that some applications are explicitly designed to spread in the open environment. Recombinant viruses for example, can widely expose a target population within a single generation, and moreover with a potential to spread to non-target species in spill-over events. Such applications have the ability to potentially spread quickly/widely, and have highly uncertain potential impacts.

As raised by Christoph Then [#2609], there is also an increasing need to deal with potential interactions of different synbio organisms in the environment. For example, it is widely anticipated that multiple gene drive products will be required for each species of disease vector, given technical problems such as the evolution of gene drive resistance. Assessments of these technologies should thus take into consideration such scenarios, e.g. the interaction of genetic elements from different gene drive constructs within mosquito species.

The advancement of synbio techniques is simultaneously allowing for an increased scale of human intervention into nature that warrants consideration as a risk (see Heinemann et al., 2021 https://doi.org/10.1525/elementa.2021.00086), as well as the potential for unanticipated effects as a result of interacting synbio organisms.

Thanks very much.

Hi comrades,
My names are Otim Geoffrey, the Founder and CEO of SynBio Africa-a synthetic biology entity focused on creating awareness and knowledge sharing towards the acceptance and development of synthetic biology in Africa.
I would like to give my submission on the above question.
Based on the available information, there may be several trends that were not identified by the AHTEG but that could also be considered in the horizon scanning process on synthetic biology under the CBD.
Some possible trends that could be considered include:
1. Emerging applications of synthetic biology: As synthetic biology continues to evolve, new applications and uses may emerge that could have significant impacts on biodiversity. For example, recent developments in genome editing technologies have the potential to revolutionize agriculture, but could also have unintended consequences for biodiversity.
2. Technological convergence: Synthetic biology is increasingly converging with other technologies, such as artificial intelligence and nanotechnology, which could lead to new applications and implications for biodiversity. This convergence could also create new regulatory and policy challenges that need to be addressed.
3. Global governance and regulation: The AHTEG report acknowledged the need for improved governance and regulation of synthetic biology, but there may be additional trends and developments in this area that should also be considered. For example, there is a growing recognition of the need for global governance frameworks for emerging technologies, which could have implications for synthetic biology under the CBD.
4. Public engagement and awareness: Synthetic biology is a rapidly evolving field, and there may be a need to improve public awareness and engagement on the potential risks and benefits of synthetic biology for biodiversity. This could involve developing new communication strategies and engagement approaches to promote public dialogue and participation.

Additional SynBio trends (New technological developments/ New applications of existing technologies) that should be considered in horizon scanning include:
- RNA interference – foliar applications and transgenic approaches
- Transient expression – methods to cause non-inheritable or temporary changes to genome (VIGS, viral-mediated transformation, etc)
- Complex examples of genome editing (e.g. de novo domestication/evolution), gene editing outside of plants
- Sterile insect technique (self-limiting insects)
- Engineering photosynthetic pathways (synthetic by-pass)
- Artificial chromosomes
- Hacjimojis DNA (expanded DNA and RNA letters)
- Paratransgenesis
- Living (construction) materials
- Xenobot example
- Novel protein engineering
- RNA circuits
- Delivery systems (viral, nanoparticles)
- Bioelectronics (DNA storage, bioactive cells)
- The use of big data
- Horsepox virus, virus and virus-like applications
- Greater mention of DIY Biology – wider access to technology and genomic sequences

O.A.El-kawy

Hello again colleagues

I would like to place the production of null (negative) segregants on the list of emerging trends that are not explicitly mentioned by the AHTEG. A null segregant emerges from at least two interventions at the gene level (10.17159/assaf.2016/0011). Many intend the outcome of these interventions to be a product that has been restored to a status exempt (or excluded) from GMO regulations.

It might be questioned why these are a trend that is worthy of separate, explicit, coverage because each of the interventions may fall within the coverage of the AHTEG. My response would be that null segregants:
• are organisms with a novel combination of genetic material, within the history of the legislative interpretation of the text adopted by the Protocol (https://doi.org/10.3389/fgeed.2022.1064103);
• are complex products of modern biotechnology in their own right and carry a series of changes that may cause unanticipated effects in combination at scale in the environment. In this regard, I add this to the “interactions” issues referred to in Mr Then’s post [#2609].
• may be released in combinations that allow for an adverse effect to emerge as a combination of activities of separate organisms. Again expanding on Mr Then’s post of unanticipated interactions, there may be unanticipated outcomes of intended interactions between multiple different synbio organisms. For example, as Dr. Sirinathsinghji mentions [#2637], combinations of microogranisms or combinations of microorganisms and either plants or animals.
• may be exempted from national legislation and defined out of scope of any regulation or compliance with advanced informed agreement. This is one aspect I believe to be in harmony with the list begun by Mr Otim [#2640].

Thanks to all who have posted. I appreciate the ideas and perspectives that have been offered on this forum.

Jack

I am Amelie Wamba, Coordinator of the Gene Drive project at the Pan-African Mosquito Control Association (PAMCA). I have a background in sciences and just recently finished my PhD in Biochemistry. I had my first experience with global policy at the last UN COP-15 in Montreal.

I am sorry for mostly being a lurker here as I am learning by reading the different conversation threads. I would like to express my gratitude for providing a platform for researchers and academicians to widen their scope and experience in the world of policy-making and regulation that greatly affect their work. This is a great learning experience and valuable knowledge in advancing my career and understanding of the intricacies of things from a multidisciplinary angle. I am learning a lot from following the threads of conversations ongoing here and although most of these terms are new, I am happy to do some research to better understand the work and complexities around development and adoption of policies.

Talking about Innovative Technologies like synthetic biology, I agree on their added value to research and the potential the have in solving some major public health concerns. In the context of Africa where I work, there is a great need for education at all levels. It requires an extra effort to break down complex knowledge on innovative and technological innovations as a potential tool kit to current issues in public health. I would like to request this be taken into consideration in the next AHTEG if it hasn't already, and include a glossary or some guidelines on how the different stakeholders and especially the potential end-users of these technologies could participate from a point of understanding and confidence in these proposed solutions.

I therefore echo what my seniors and colleagues here have already said about the need for capacity building across a broad spectrum ranging from the technological aspects, operational, communications, policy, regulation, media involvement, stakeholder engagement, monitoring and evaluation. It would be wonderful if not only capacity is built but also the infrastructural development to accompany the development and implementation of these technologies in Africa.

In Africa, there is a growing interest among the youth to actively participate in African-led solutions and capacity in these different aspects would equip Africans to adapt these innovative solutions to the context of their different countries, communities and landscapes. Also, it should be noted that Africa is not very advanced in these innovative technologies even at the level of education and engagement which could enable the conversation to be ongoing in different spheres in Africa.

I stand available and eager to join such efforts and initiatives through which I could build capacity and better contribute to efforts geared towards solving public health issues in Africa. I am happy to learn from the experience of the seniors here and would like to express my gratitude for your tutelage in advance. Please free to share with me any documents or links that could be useful to enhance my understanding and intellectual growth.

Thank you very much.

My warmest greetings!
I am Onyeka Nwosu, a Senior Scientist with the National Biosafety Management Agency (NBMA), Nigeria. I am actively involved in the regulation of modern and emerging Biotechnology including risk assessment reviews as well as in the development of regulatory guidance on modern and emerging biotechnology.

In furtherance to the trends Identified by AHTEG on synthetic biology, I think the issue of dual use purpose should be well considered especially in the regulation of SynBio with particular emphasis on the use of SynBio technologies on high risk pathogenic microorganisms. Therefore, for effective risk assessment to govern Synthetic Biology, a collaborative and multi-institutional approach may apply. This approach will be mainly aimed to mitigate public and environment health concerns, with specific consideration centred upon Biosafety and Biosecurity.
Biosafety in terms of the potential for accidental/unintentional risk events to occur during contained use activity and environment release while Biosecurity in terms of the potential for deliberate misuse of SynBio enabling technologies for nefarious purposes.

As a regularory scientist involved in the development of a National Guideline for SynBio that will atleast enable contained use activity of SynBio in Nigeria, these key risk assessment views has been put into full consideration.

Dear colleagues,

Thank you for your valuable information.
I would also like to highlight two new trends that perhaps were not fully considered by the AHTEG in 2019 that have been previously mentioned in this discussion.

1. Technological convergence of biotechnology and nanotechnology for, for example, the use of nucleic acids and active ingredients and nanoparticles as carriers for genetic engineering.

2. The use of null-segregant strategy, well described in post #2645. This seems to be a trend in plant breeding using CRISPR/Cas9 technology (https://doi.org/10.3389/fpls.2019.01150).

Sorry for my brevity.

Best regards,
Sarah

Warmest greetings everyone,

I would like to echo Mr Nwosu’s post [#2663] on the issue of contained use.

Considering the active development of synbio/LMO organisms explicitly designed to spread and persist, including those with potentially extremely rapid spread e.g. self-spreading vaccines, monitoring of contained use of synbio organisms is currently lacking. Such technologies and others e.g. gene drive organisms, warrant measures to protect against accidental escape, including during transportation process (inc. transboundary movements). Such processes should be accompanied by meaningful public participation to ensure that research and development trajectories incorporate and address citizens’ concerns and views from the start.

I would also like to echo posts [#2645] and [#2681], on the increasing trend of developing null segregants. As TWN has written previously, such organisms still carry a novel combination of genetic material with the attendant risks e.g. on-target unintended effects resulting from erroneous DNA repair e.g. genetic rearrangements, deletions, insertions, translocations and chromosome loss. https://biosafety-info.net/wp-content/uploads/2020/12/Biosafety-Briefing-English.pdf

In relation are also techniques that are being deployed to circumvent any introduction of DNA during the engineering process e.g. by using purified ribonucleoprotein (RNP) complexes for genome editing.  As shown in a recent study, transgenic DNA was also incorporated into organisms following prime editing techniques where no DNA was introduced, with insertions of guide RNA-derived DNA copies (Nature Biotechnology, 2021) https://doi.org/10.1038/s41587-021-00901-y. Even without the introduction of DNA, such “DNA-free” techniques may also succumb to the unintended impacts including insertion of foreign genetic material amongst other complex genetic outcomes.

Thanks
Eva

Dear participants,

My name is Luciana Ambrozevicius, I work for the Ministry of Agriculture and Livestock in Brazil. 

In my opinion additional trends to inform the horizon scanning process are:

(i) The fact that the value of the synthetic biology market has increased exponentially without a significant participation of developing countries: The global synthetic biology market was estimated to be valued at USD 6.8 billion in 2020 and is projected to grow at a compound annual growth rate of 23.9 % during the period of 2020 - 2025. Despite its potentially global deployment, research and development in synthetic biology mostly occurs in a limited number of countries  (CBD Technical Series No. 82 on Synthetic Biology)

(ii) In the next decade for the Kunming-Montreal GBF is necessary to add more efforts and funds towards the implementation of Articles 16, 17, 18 and 19 that could be informed by the horizon scanning: Developing countries are to be provided “fair and most favourable terms” to access to and transfer of technologies (Article 16, par. 2) that “are relevant to the conservation and sustainable use of biological diversity or make use of genetic resources and do not cause significant damage to the environment” (Article 16, par. 1). Article 19 also specifically addresses developing countries, holding that Parties “shall take all practicable measures to promote and advance priority access on a fair and equitable basis by Contracting Parties, especially developing countries, to the results and benefits arising from biotechnologies based upon genetic resources provided by those Contracting Parties” (Article 19, par. 2), and that they shall “provide for the effective participation in biotechnological research activities by those Contracting Parties, especially developing countries, which provide the genetic resources for such research, and where feasible in Contracting Parties” (Article 19, par. 1).

(iii) To consider the third objective of the Convention - access and benefit-sharing mechanism: The synthetic biology is the basis for the bioeconomy and its multiple applications including food security, health, industrial restructuring, and energy security expected to produce economic growth and job creation, and create value through investment in innovative research and to improve environmental sustainability. This is of great importance for developing and megadiverse countries and to connect the compromisses under CBD with SDGs such as poverty eradication and zero hunger.

(iv) The importance of communication: developing effective mechanisms to proactively communicate the potential benefits and risks of synthetic biology will be critical to earning and maintaining public trust. Without effective community engagement and strong societal oversight, it may be difficult to apply synthetic biology and realise its potential benefits (https://acola.org/wp-content/uploads/2018/12/2018Sep-ACOLA-Synthetic-Biology_Report.pdf)

Thanks.
Luciana

Dear participants,
I appreciate your wonderful idea.
I am Dr. Bong Hyun Sung at Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB).

How about discussing Biofoundry?
Several synthetic biology technologies developed are expected to be accelerated through biofoundry. As AI, automation, and other equipment are widely used, the technology gap will become more severe. But biodiversity will be expanded rapidly.

Thank you.

Hello. I am Dr. Reynante L. Ordonio. I am a career scientist from the Philippine Rice Research Institute (PhilRice) working on GMO (e.g., Golden Rice, HIZR) deregulation and deployment and I also helped in crafting the Philippines’ policy on New Plant Breeding Techniques (e.g., gene editing). Currently, synthetic biology is not covered by the existing regulations in the Philippines. We have “synthetic genomics” though, which may be overlapping with synthetic biology but is more reserved and can produce GMO or non-GMO as final product.  
Overall, I think that the AHTEG has done a good job in coming up with the trends in Synthetic Biology based on the 2019 report. However, there are instances when a cited work is not a full-pledged synthetic biology work. Let me cite the work of Noyce et al. (2018) which was mentioned in the report. I believe that this is a case of synthetic genomics, which is a new plant breeding technique (NBT) that can produce a non-GMO by faithfully synthesizing and assembling the genome of an organism. It can also produce a GMO if a specific sequence from another unrelated species was integrated into the assembled genome. The latter is true in the case of Noyce et al. (2018) because as they said, “large (10–30 kb) fragments of DNA were synthesized based on the HPXV sequence along with two 157 nt VACV terminal sequences, and were recombined into a live synthetic chimeric HPXV (scHPXV). Sequencing of the 212 kbp scHPXV confirmed it encoded a faithful copy of the input DNA.” Although the fragments were synthetic, they are faithful copies of natural viral genome fragments that made it in the assembly or final product; thus resulting in a GMO (with novel combination of genetic materials). Had there been modifications in the individual synthetic fragments (e.g. unnatural base pairs, codon optimization, etc.), then it would be considered synthetic biology. But since there is faithful copying, it was only as if two naturally occurring DNA fragments have come together using modern biotech (in vitro genome synthesis and assembly). The resulting final product conveniently fits the definition of a GMO and so, will be covered by the existing GMO regulation. Just because the fragments were synthesized does not mean that they are automatically part of synthetic biology because synthetic DNA fragments (e.g., oligos for PCR and cloned inserts) have already been in use since the 1980s. Synthetic biology is just a new paradigm and so, we should strive not to mix it up and confuse with the existing GM and some new plant breeding techniques like gene editing. I also hope that products of modern biotech that genetically resemble conventional crops will not be branded as “synthetic” because this will have an impact on public acceptability.
Another work cited in the report that does not appear to be SynBio is the work of Ranberg et al. (2016) as cited by Reed and Osborne (2018). The work is an NBT, particularly Agroinfiltration since transient expression was employed. Based on their methodology, there was no engineering at the DNA level. They simply amplified and expressed genes using plasmid to arrive at “new-to-nature”combinations (e.g., OssynCPS/SsSCS, ZmAN2/SsSCS, TwTPS21/CfTPS3, and TwTPS14/SsSCS). The resulting plant could have been a GMO but the objective was only transient expression and the plants are meant to become non-viable.

Lastly, I would like to input these works: Danila, F., Schreiber, T., Ermakova, M., Hua, L., Vlad, D., Lo, S., Chen, Y., Lambret‐Frotte, J., Hermanns, A. S., Athmer, B., von Caemmerer, S., Yu, S., Hibberd, J. M., Tissier, A., Furbank, R. T., Kelly, S., & Langdale, J. A. (2022). A single promoter‐TALE system for tissue‐specific and tuneable expression of multiple genes in rice. In Plant Biotechnology Journal (Vol. 20, Issue 9, pp. 1786–1806). Wiley. https://doi.org/10.1111/pbi.13864
Synthetic auxin sensor: Perico, C., Tan, S., & Langdale, J. A. (2022). Developmental regulation of leaf venation patterns: monocot versus eudicots and the role of auxin. In New Phytologist. Wiley. https://doi.org/10.1111/nph.17955
Thank you very much for allowing me to share my views.

Dear colleagues,
In addition to the new trends identified by the participants, I would like to pay attention to the application of genome editing in relation to the genome of organelles (chloroplasts, mitochondria) and plastid engineering, as this may have great impact on the adaptation of organisms to changing environments and climate change. At the same time, it is also important to evaluate influence of such developments on the three objectives of the Convention.

Biosensors for environmental applications also should be paid more attention, as these developments are very promising for environmental applications (I have made a link to the environmental applications in #2660). In addition, as was pointed by Prof. Mark Styczynski [#2708] such developments are well invested, so we can expect their use in the foreseeable future. At the same time, I`m fully agree that all impacts of such technologies should be carefully considered, including risk assessment and ethical considerations.

In the end, I think that more attention should be paid for horizontal scanning of synbio applications for microorganisms, including microscopic algae for evaluation of developments that may enter the practical domain and be intended to be released in semi-controlled or uncontrolled environments. Since such organisms have a very high potential to spread, reproduce, they are difficult to control in unmanaged environments, I believe that risk assessments, monitoring plans, control plans, detection methods and emergency approaches should be developed for them. Each new organism should be thoroughly assessed including environmental risk assessment.

Best,
Galina

Dear all,

This has been a very interesting discussion in that it indicates that narrowing of what constitutes a trend to only technological developments themselves would be counterproductive to the task of horizon scanning, monitoring and especially assessment.

Whilst “interactions and cumulative effects” -introduced by Christoph Then, #2609- might not be a “trend” in the narrow sense of ‘technology development’, it would be an important point to consider, especially in the assessment. However, the more a technology is used and introduced, the more there will be not only a scale effect to risk (Heinemann et al. 2021 - https://doi.org/10.1525/elementa.2021.00086), but also a trend towards increased interactions and cumulative effects. This issue is further raised and expanded in the posts #2637 and #2645 by Eva Sirinathsinghji and Jack Heinemann. It hence appears we require sets of different types of trends that will help different levels of reflection as well as of horizon scanning, monitoring and assessment.

Otim Geoffrey (#2640) raises an important point, namely that of convergence, which was to a certain degree also brought in by Galina Mozgova (post #2602, Topic 1, Question 1a) - regarding increasingly close relationship with AI, machine learning etc. and also relating to trend d (sophistication). Yet technology convergence has its own dimension, so it is something that should be picked up by the AHTEG for discussion.

I agree with Onyeka Nwosu’s intervention (#2663) on the need to include the issue of dual use into consideration. There seems to be indeed a trend, whether looking at HEGAAs, gene drives, or -as mentioned in [#2663]- pathogenic microorganisms.  And linked to this may be the need, as was suggested, of including additionally a different collaborative and multi-institutional approach, which however should not be reduced to this, but take the multi/inter/intra-disciplinary approach even further. The issue of dual use potential/purpose was already highlighted by the National Academy of Sciences , Engineering, and Medicine report on gene drives in 2016 https://doi.org/10.17226/23405.

This trend, as well as that of interactions and cumulative effects, highlight the difficulty of evaluating potential positive and potential negative impacts of technologies or individual applications – as covered under Topic 1, question 1b.

Thank you for bringing up the issue of null-segregant strategies (posts #2645 and #2681), which I agree is a strong trend both in the literature as in presentations and regulatory discussion, and it is indeed one, that has not been given sufficient attention as yet. It is a trend linked to unsubstantiated assumptions that firstly only “foreign DNA” has the potential for giving rise to risk and that secondly the processes used are neutral and should be disregarded. The equation would thus be: no foreign DNA = no risk irrespective of process used. This is against the background of scientific data that shows that processes utilised in the genetic engineering procedures, such as agrobacterium or particle bombardment mediated delivery of constructs (e.g. CRISPR/Cas), or tissue culture and protoplast methodologies, give rise to a substantial amount of genome-wide mutations. Working with grapevine, Wang et al. 2021 for example reported 9,325-12,959 process-induced point mutations, with 230-377 of these in coding regions, additional to one ‘off-target’ mutation. https://doi.org/10.1038/s41438-021-00549-4. This is also against the background of new findings that show that smallest point mutations can have a negative effect, even if they are so-called silent or synonymous mutations, as I referred to in my post under topic 1,1a. See Shen et al. 2022 - https://doi.org/10.1038/s41586-022-04823-w

Another trend to be considered would be that of turning to gene drives as a form of pesticide. In our gene drive horizon scanning survey we found this to be wide-spread view in much of the literature on gene drives (i.e. getting rid of pests). The fact that there are 32 insect species/taxa and 42 non-insect species/taxa identified in the scientific literature that are either proposed for or under current gene drive development illustrate this trend. Please see my post under T1-1a for further details. Were gene drives to be viewed and utilised as previous pesticides were, this would have deep impacts vis a vis the three objectives of the Convention. I will post our latest publication on non-insect targets under thread 1,1a later today, as it covers this point in the conclusions.

Another trend is that of using or proposing to use genetic modification to create sterility to enable the wide-spread use of non-native plants – e.g. non-native fast growing trees for plantation use- that otherwise could become a threat as invasive species, (again, see my post under the T1-1a thread).

There is also a move towards ‘enabling’ technologies, such as anti-CRISPR/Cas or anti gene-drives or also above-mentioned sterility, to allow for the wide spread use of synbio application in the open. These ‘enabling’ technologies are thought to provide a fail-safe mechanism as to be able to stop further spread or activity of a synbio mechanism or synbio-LMO.

With kind regards,
Ricarda Steinbrecher

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

My name is Prof. Dr. Kazuo Watanabe, University of Tsukuba, Japan and a PRRI member.  I appreciate the valuable interventions with follow up comments from all participants. And sorry for late participation due to some technical errors. I have been with RA&RM on LMOs since the Jakarta Mandate of CBD for establishing and implementing CPB, and I served as a member in RA&RM AHTEG of CPB during 2008 to 2012. At the time, already Synthetic biology (here after synbio) was raised as a future technology potential and it had been briefly reviewed at the time. While it is depending on how synbio is termed or defined, different views may recognize many of the presently on-going R&D in the world would have a lot of components with synbio, and likely some would regard present products available in market as synbio products again upon how one can categories what would be synbio. It is important overview a wide coverage of information and public recognition of the subjects towards focusing at the next rounds of discussion, but important issue here this forum is how the members consider under CBD objectives, and stretching beyond the CBD scope would not be a goal of this of forum.
There are a lot have been placed in the horizon scanning session, and needless to say, different components of approaches and examples have been provided in open resources as some of interventions quoted. Individual interviews, literature survey, open for a like this on-line session, trend analyses and related scenarios (not an imaginary scientific fiction story) could be more discussed as a part of exercise on how to identify the validity and efficacy in specific HS implementation under the scope of CBD. Thanks for your attention.

Hello everyone.  My name is Jen Rowland and I’m a Science Advisor in the New Technologies and Production Methods Division of the Foreign Agricultural Service at the U.S. Department of Agriculture.  I am pleased to see the continued discussion on the forum and thank the moderators for their work and the thoughtful comments of the other participants in the forum.

The United States understands synthetic biology as it is discussed in the research and development community to encapsulate a continuum of biological engineering tools and techniques leading to progressively advanced biotechnology products.  Research in the field of biotechnology and genetic engineering improves our understanding of biological systems and contributes to efforts addressing food security, environmental, energy, and health challenges.  Indeed, over forty years of research, education, and product development using recombinant DNA techniques have led to clear benefits relevant to the Convention’s objectives, and these benefits will continue to emerge with continued application of biotechnology tools and techniques. 

As part of Executive Order 14081 “Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy,” the United States recently invited public input on how advances in biotechnology and biomanufacturing can help achieve goals previously out of reach.  This Request For Information is one formal way that the U.S. government conducts horizon scanning.

In the United States’ experience with emerging trends, and when making a policy decision regarding the safe handling and use of an organism, it is most valuable to consider: 1) the characteristics of the organism in question, and 2) the novelty of those characteristics.  There are numerous internationally recognized resources in existence that provide frameworks for how to consider the characteristics of organisms:

United States Environmental Protection Agency (EPA):
https://www.epa.gov/risk/risk-assessment-guidelines

International Plant Protection Convention (IPPC): 
https://www.ippc.int/en/core-activities/capacity-development/training-material-pest-risk-analysis-based-ippc-standards/ 

http://www.fao.org/docrep/009/a0450e/a0450e00.htm 

http://www.acfs.go.th/sps/downloads/34163_ISPM_11_E.pdf 

Organization for Economic and Cooperation and Development (OECD): 
http://www.oecd.org/chemicalsafety/biotrack/oecdandrisksafetyassessmentinmodernbiotechnology.htm  

World Organization for Animal Health (OIE): 
http://www.oie.int/en/our-scientific-expertise/specific-information-and-recommendations/invasive-alien-animal-species/ 

World Health Organization (WHO): 
http://www.who.int/tdr/publications/year/2014/guide-fmrk-gm-mosquit/en/

My name is Ernst Wimmer and I am Professor for Developmental Biology at the Georg-August-University Göttingen, Germany. My research includes applied approaches in insect biotechnology to establish modern genetic pest management methods. For the Open-ended Online Forum on Synthetic Biology, I was nominated by the German Federal Ministry of Education and Research.

Regarding the discussion on “null segregants” or “no foreign DNA” organisms, I would like to refer to comment [#2661]. I completely agree that such null segregants or foreign DNA-free organisms need to be carefully evaluated before use in any way. However, the fixation on the process of how these organisms came about and its different categorization based on that, I do not understand and completely object to. Traditional hybridization or mutagenesis by radiation/chemicals caused much more additional mutagenesis background and unknown background activity as targeted genome editing tools do. In the end, the product and its interaction with the environment must be evaluated irrespective of its derivation.

From [#2661]:
“First, I want to agree with the other participants that the uncontrolled release of living-modified organisms (LMO) must be prevented, and risk-benefit assessments need to be conducted before any field testing of LMOs. However, risk assessments of LMOs cannot be based on the technologies that were used to create the organism. Instead, an organism's biological properties must be the primary attributes for the evaluation, regardless of their origin. …
LMOs created with the means of synthetic biology do not pose an inherent threat because of the underlying technology, ... Such simplifications neglect the potential benefits synthetic biology can have on the three main objectives of the CBD. Carefully conducted risk-benefit assessments with a solid scientific foundation on the biological properties of LMOs thus need to be the preferred method in the regulatory processes of synthetic biology.”

Dear participants

I´m Carolina Villafañe from The Ministry of Environment of Colombia, and I am in charge of Biosafety issues and, The Cartagena Protocol.

Another trend that should be considered by the ATHEG is bout what developments arise from nonparties countries and what is the possibility that those developments are used by these countries in their own territories.

This trend is proposed to consider the inevitable transboundary movements of some Synbio´s products, and the environmental effects too, that could affect a country without the possibility to detect on time the presence of those products or do a claim and establish responsibilities or compensation for damages caused by Synbio´s products.

As CBD´s Parties, we have been working on how abording these technologies for more than ten years, but the Convention's decisions only have incidence for country parties. The scientific advance is faster than the regulatory developments and with the current developments in Synbio´s products that are focused for example on microorganisms or for example gene drives, the regulatory developments do not have a sense if are only for the Parties of the Convention.

I think we must raise and coordinate the regulatory efforts with other worldwide organizations and nonparties governments, because of the capacity and biological nature of some Synbio´s developments that could be considered like a product with a high potential to produce worldwide consequences.

In this context, I would take into account the important points of view of Mr. Jack Heinemann (#263), Dr. Ricarda Steinbrecher (#2730), and Dr. Guy Reeves (#2739).

Thank you.

SynBio presents potential biosafety and biosecurity risks. Biosecurity risks refer to unauthorized access, loss, theft, misuse, diversion or intentional release. If a biosecurity accident happens, it would pose a huge threat to humans and nature. Therefore, it is crucial to establish a set of regulations and management practices for the biosecurity risks of SynBio. In this paper, we summarized the sources of the biosecurity risks of SynBio, from its research materials, products, technologies, information on synthetic biology.

Biosecurity risk is defined as unauthorized access, loss, theft, misuse, diversion or intentional release, etc. Over the years, biosecurity risks of SynBio has mainly focused on the theft and misuse of fixed, current, and intangible assets in SynBio laboratories, including SynBio components (Minimal genome, Orthogonal biosystems/xenobiology, protocells, etc.), SynBio products, and SynBio technologies.  In some cases, SynBio might present bioweapon risk, as it might be used to re-create known pathogens, make existing pathogens more dangerous, or create new pathogens for some purposes.

It would be interesting to refer to this article on Regulation and management of the biosecurity for synthetic biology - Xiaomei Zeng et al.
  https://www.sciencedirect.com/science/article/pii/S2405805X22000291

Dear colleagues,
As Geoffrey Otim [#2640] points out, trends can be in different realms ranging from the technological advances, via application types, to trends in governance and regulation and in public engagement. I will add a few thought mostly on topics that have already been brought up by others:

- Most of the trends identified by the last AHTEG have been accelerated since than, both on the level of quantities and of range of applications. For transient modification using RNAi spray or genetically engineered viruses

- We have also identified trend of eroding norms as has already been brought forward by one of my coauthors Guy Reeves [#2739]:
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.

- Null- (or negative) segregants are likely to become more common and pose regulatory challenges, as brought up by Jack Heinemann [#2645] and Sarah Agapito [#2681], and contextualised by Ricarda Steinbrecher [#2724]. Over the past years, this topic has also come up with regard to animals. For example, the EU Commission Standing Committee on Plants, Animals, Food and Feed has discussed the case of null segregant laying hens (https://www.huminnpoultry.com/project-sexing; https://patentscope2.wipo.int/search/en/detail.jsf?docId=WO2020178822).

- Interaction effects at the ecological level, as Christoph Then [#2609], Jack Heinemann [#2645] and Ricarda Steinbrecher [#2724] rightly point out, necessitate the consideration of trends beyond the mere technological characterisation.

- The impact of converging technologies, as brought up by Sarah Agapito [#2681] and Geoffrey Otim [#2640], is likely to further increase, especially at the nano scale.

Dear online forum participants,

My name is Felicity Keiper and I am participating in this forum as a representative of the Global Industry Coalition (GIC). We have commented on Questions 1(a) and 1(b), and for this question submit that by our own assessment (which is detailed in our submission of information in this program of work), we did not identify new “trends”. Rather, what is evident is further refinement of established technologies and progress towards implementation for some applications, with the latter demonstrating that development is not as “rapid” and “easy” as often claimed in this forum. This is helpfully explained in #2666 in regard to progress in gene drive research.

In our comments for Topic 1, Question 1(b) we question the relevance of the “trend” of “increasing sophistication of methods”. Technological development is a continuum that is not unique to synthetic biology – this is a logical progression towards improved efficiency and predictability of outcomes. We view synthetic biology as part of the continuum of biotechnological development spanning more than four decades since recombinant DNA applications became feasible in the 1970s, and this includes the constantly advancing and accumulating knowledge and understanding in biological engineering. Importantly, existing GMO/LMO regulatory mechanisms continue to apply (as reported in #2672).

We also wish to address the proposal that null segregants are a new trend that should also be considered (e.g. #2645, #2681, #2688, #2724, #2756. Null segregants cannot be described as “new” (as recognized in #2729), and it is also not “new” that they are not considered to be within GMO/LMO regulatory scope by several regulatory authorities. This is not a new development, nor a “trend”, and classifying something as a “trend” on the basis of not agreeing with the determination of competent authorities not to regulate it as GMO/LMO is not the intended purpose of the horizon scanning process.

Regards,
Dr Felicity Keiper

----Posted on behalf of Dr. Martin Cannell---

Dear Participants,
I appreciate the efforts in sharing references and views on trends in synthetic biology that were not identified by the AHTEG on synthetic biology in 2019. Thank you for the useful  ideas and suggestions that support the conclusions of the AHTEG on synthetic biology in 2019. It seems that the use of synthetic biology is converging on other fields and producing new types of products, components and organisms. The field is also designing, re-designing, inventing and re-inventing many applications and biological processes that may warrant further consideration.  The importance of greater engagement with the public and capacity-building were highlighted in this regard. With the assistance of the Secretariat, I will include the additional  examples and references into the summary of the online discussions for further deliberations by the multidisciplinary AHTEG.
Best regards,
Martin