Activities of the Open-Ended Online Forum (2014-2016)

POSTED ON BEHALF OF MARIA MERCEDES ROCA (MODERATOR)

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Dear participants of the Online Forum,

I thank the Secretariat for inviting me to serve as the moderator of this discussion to gather views, information and reference materials on risk assessment of organisms developed through synthetic biology. The objective of this discussion is to brain-storm on ideas related to the risk assessment of organisms modified using synthetic biology with a view to helping the Parties to the Cartagena Protocol and Convention consider if further work in this area is needed.

If you may recall, at its meeting held in Brasilia in November 2015, the AHTEG agreed to prepare an outline for guidance on “risk assessment of organisms produced through synthetic biology”, subject to the outcomes of the twentieth meeting of the SBSTTA which was scheduled to be held from 25 to 29 April 2016. The outline would be submitted to the COP-MOP for its consideration on the development of further guidance on the topic.

At its meeting two weeks ago, the SBSTTA gave us the “green light” to proceed with this work by noting that the methodologies for risk assessment under the Cartagena Protocol may need to be updated and adapted for current and future developments and applications of synthetic biology, and that coordination is needed among current and future processes under the Convention and its Protocols, including with the AHTEG on Risk Assessment and Risk Management.

The AHTEG on Synthetic Biology proposed the following operational definition: “synthetic biology is a further development and new dimension of modern biotechnology that combines science, technology and engineering to facilitate and accelerate the understanding, design, redesign, manufacture and/or modification of genetic materials, living organisms and biological systems”.  That AHTEG had opposing views about whether “risk assessment practices currently in place to evaluate LMOs are appropriate to evaluate organisms of synthetic biology.”  I would like to invite you to share views, sources of information and reference materials on risk assessment of organisms developed through synthetic biology.

PLEASE NOTE: You are kindly asked to limit the scope of your interventions to issues related to the risk assessment of living modified organisms that are particularly important because they were developed using synthetic biology.

Based on the results of this discussion, a group of volunteers within the AHTEG, will develop a draft plan for updating our current guidance, if needed, to incorporate synthetic biology, which will be proposed to you for further discussion under this forum. The AHTEG will then consider the draft plan at its face-to-face meeting to be held this coming July, and a final plan will be submitted to the COP-MOP at its meeting in December 2016, and the Parties will decide whether or not changes to the current guidance are needed and, if so, how it could be developed. 

I look forward to your interventions and a vibrant and fruitful discussion.

Best regards,
Maria Mercedes

Dear Mercedes and fellow participants:
Synthetic biology is still an ill-defined fuzzy term which, depending on having a consensus definition which has not been reached yet, may or may not overlap with the CPB definition of Modern Biotechnology.
The notion of synthetic biology initially “became viral” after reports of viruses or very simple bacteria having completely synthetic genomes. Current examples of such kind of synthetic biology are scarce and refer to laboratory microorganisms that are far from being intended to be released in the environment (or even able to survive!). They do not constitute enough precedents. This is the moment to oversee the advances in this technology, we cannot yet reach conclusions regarding if these organisms will ever find real world applications, what are going to be their differential characteristics compared to conventional counterparts and LMOs and even less to speculate how such organisms may or not represent differential risks to biodiversity or general guidance on their risk assessment.
Premature and speculative work may be neighboring science-fiction and their outcome may prematurely impose inadequate previsions. Inadequate previsions may be either risky or disproportionate (or a combination of both for different aspects).
Shortly after consideration of the issue begun, it become increasingly evident that such organisms are far away from becoming real functional products to be released in the environment anytime soon; but some are really urged to push for the topic, then the concept of SynBio is being bended to include simpler technologies, and nowadays it can be found examples in the literature where an LMO harboring a few transgenes with synergistic effect is called an example of Synthetic Biology… what does exist today in the laboratories and have some chances of being released for early experimental field trials (LMOs with stacked genes, artificial chromosomes, etc.) are clearly encompassed by the CBP LMO definition and current LMO risk analysis practices of countries having real institutional experience on risk assessment of modern biotechnology.
Please allow expressing a concern regarding this forum, regarding that the only mention about synthetic biology in the final report of the COP-MOP 7, is: “Recommends to the Conference of the Parties to the Convention on Biological Diversity a coordinated approach with the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety on the issue of synthetic biology, taking into account that the provisions of the Protocol may also apply to living organisms resulting from synthetic biology.” Therefore, it doesn´t emerge from COP-MOP 7 the instruction to the AHTEG on Assessment and Risk Management to prepare an outline for guidance on “risk assessment of organisms produced through synthetic biology”.
On the other side, it is noteworthy to mention that the last report of the CBD ad hoc technical expert group on synthetic biology includes the following recommendation: “Urge Parties to address synthetic biology in a coordinated manner within the context of the objectives of the Convention and its Protocols, particularly by tapping into existing processes, such as the AHTEG on Risk Assessment and Risk Management and the AHTEG on Socio-economic Considerations under the Cartagena Protocol”. However, this is a “draft” recommendation, since it still has to be considered and adopted by the next COP; if that happens, then it would be the appropriate moment for Parties to consider it for a possible decision under the MOP, which finally could change the mandate of the AHTEG under the CPB, enabling it to work on this at that moment in time. Therefore, several decision steps seem to have been overridden.
Thanks for the opportunity to contribute. We will be following this work and the forum with interest - and perhaps the jury of the Nebula Prize too ;).
Martin Lema
Argentina

Dear participants,

First of all in respect of some of my colleagues in the brazilian delegation that participated in the SBSTTA 20 and our government that despite all our economical and political problems supported our participation I would like to express my frustration in the way the discussion about a SynBio Guidance was conducted. In the suggested recommendation was written:  

(a) Invites the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety to address synthetic biology in a coordinated manner, particularly by tapping into existing processes, such as the Ad Hoc Technical Expert Group on Risk Assessment and Risk Management for the development of guidance dedicated to risk assessment regarding living modified organisms developed through synthetic biology and the Ad Hoc Technical Expert Group on Socio-economic Considerations under the Cartagena Protocol, as appropriate.

And the position from Brazil in the SBSTTA was that there was no technical justification for a SynBio guidance at this moment. After some manifestations regarding the decision BS-VII/12 from other countries the paragraph was changed to: 

(d) Welcomes the recommendation of the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety, in its decision BS-VII/12, on a coordinated approach on the issue of synthetic biology, including its work on risk assessment and risk management [as well as socio-economic considerations, as appropriate], and invites the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety to take into account in its future deliberations relevant information resulting from the processes under the Convention.

I would like to make it clear that there was no technical discussion in the contact group between those that want a guidance and those that do not want as we expect for a scientific and technical body like SBSTTA. The only think it was that the paragraph was changed and the language used was taken as a ´green light´ for a guidance to be developed few days after the meeting was over. Maybe I´ve being naive about decisions in this international environment but I have to express my concern about the lack of transparence in this process and how unconfortable and discouraging this is for us that were seriously spending time and resources trying to build a constructive discussion.      

Having said that, my impression about a SynBio guidance at this moment is that is going to the same way as the ´boxes´ in the RoadMap: will not add any value to the risk assessment framework. Simply because of few reasons already recognized by Parties in the SBSTTA recommendation (doc UNEP/CBD/SBSTTA/REC/XX/8):

- There is not an acceptable definition for SynBio: there is a definition proposed by SynBio AHTEG but the paragraph is with brackets in the SBSTTA Recommendation meaning the CBD Parties will rediscuss and reach a compromisse solution during COP. It seems very premature COP-MOP deciding about a guidance for something that is still being defined under COP;

- SynBio organisms are LMOs: The SBSTTA Recommendation “Takes note of the conclusion of the AHTEG on Synthetic Biology that living organisms developed through current applications of synthetic biology, or that are currently in the early stages of research and development, are similar to living modified organisms as defined in the Cartagena Protocol;”

- There is already the Anexx III and a RoadMap for LMO RA applicable to SynBio organisms: The SBSTTA Recommendation “Notes that the general principles and methodologies for risk assessment under the Cartagena Protocol and existing biosafety frameworks provide a good basis for risk assessment regarding living organisms developed through current applications of synthetic biology, or that are currently in the early stages of research and development, but such methodologies may need to be updated and adapted for current and future developments and applications of synthetic biology;”

The first questions for a guidance to be elaborated should be: Which aspects of RA for SynBio organisms that are no covered in the RoadMap? And that leads to another questions: Is anyone that is advocating for a new guidance already tested the RoadMap with a SynBio organism?

And those questions are much better answered by the SynBio AHTEG that curiously are the SynBio specialists but, in the case of the guidance, they will not elaborate or collaborate with it, although they will take care of all the other subjects related with SynBio under CBD as described in the Term of Reference in the Recommendation UNEP/CBD/SBSTTA/REC/XX/8. 

Best regards,
Luciana P. Ambrozevicius / Ministry of Agriculture - Brasil

Dear All,

First of all my sincere appreciation to Maria for taking on this role of moderator, knowing how overloaded she already is with her teaching and other academic obligations.

As Maria’s email tells us, the objective of this discussion is to gather views, information and reference materials on risk assessment of organisms developed through synthetic biology, in order to assist the MOP in its considerations whether further work on guidance in this area is needed.

As discussed in the earlier on line discussions on SB, for the foreseeable future, SB involves the use of LMOs, i.e. existing domestic systems and the Biosafety Protocol apply, which means prior risk assessment, taking into account the relevant characteristics of the host organism(s), the introduced or modified trait(s), the resulting organism, the intended use and the potential likely receiving environment.

For all the reasons mentioned by Martin and Luciana, I believe that it is too early to judge whether Annex III, and any agreed guidance based on it, would not be sufficient to conduct a risk assessment for organisms developed through synthetic biology.

Following Helmut’s urge to work in the spirit of compromise, I believe that in order to help the MOP in its deliberations, we best follow Luciana’s suggestion to start our discussion by exploring which specific aspects of organisms that have actually been developed to date through SB would not be adequately taken into account Annex III, and any agreed guidance based on it.

Looking forward to the continuation of this discussion and wishing all a good weekend

Piet

Dear Maria and other participants,

I share the concern of Martin Lema and others that the term synthetic biology is not well defined yet. Although the AHTEG on synthetic biology has proposed an operational definition of synthetic biology, it failed to suggest any inclusion and exclusion criteria. The group also failed, in my view, to identify any example of living organism, developed through the use of synthetic biology techniques, that does not fall under the definition of LMO in Cartagena Protocol.

Until further clarification is made on "what constitutes synthetic biology", and until we are otherwise mandated by future COP-MOP, we should strictly stick to the definition of LMO in the Protocol, i.e., a living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology (as defined in the Protocol).

To be constructive, I would propose that the main meat of the guidance, if COP-MOP decides to develop such guidance, should be a guide to deal with

i) possibly higher degree of genetic deviation in LMOs from available comparators.

ii) possible need for a "concurrent" risk assessment of larger number of variant LMOs which, for example, are to be subjected to field trials.

Nobuyuki Fujita (National Institute of Technology and Evaluation, Japan)

Regards to everyone.
• I agree with Martin Lema [#7860]that synbio is an imprecise term.  It is helpful to view genetic technologies as a continuum with organisms produced by synthetic biology being further along that continuum than most of the LMOs that we’ve assessed to date. Differentiating between organisms at extreme ends of the scale is straightforward but drawing a line at some point on this scale between them is not scientifically credible nor is it helpful for risk assessment purposes. 
• For risk assessment purposes, the RA/RM AHTEG has taken a pragmatic and systematic approach i.e. to assess the Roadmap in the light of particular LMOs (selected because they appear to pose particular challenges to risk assessors).  I’m not aware that LMOs, which could be considered products of synbio, have been considered and gaps in the Roadmap identified. 
• Attempting to draft guidance on an arbitrary classification of LMOs, which have very different characteristics and uses, does not make sense, particularly as it’s not clear what gaps in the Roadmap for LMO risk assessment this guidance is designed to address. As risk assessments are specific to particular LMOs and their uses, it is more constructive to continue to identify challenges that are exemplified by particular types of LMOs and to determine whether these are adequately covered by the existing guidance. This is important because it is likely that most challenges are not specific to organisms produced by synbio per se.  For example, selecting relevant comparators to use in risk assessments is often raised as an issue for synbio organisms but this issue does not apply to all synbio organisms, neither is it specific to organisms produced by synbio. 
• I also support Martin’s point [#7860]that it’s important to be realistic about what LMOs are likely to be released into the environment in the foreseeable future. The Roadmap and any additional guidance associated with it needs to be practical and have a sound scientific basis (preferably based on practical experience).  In this regard it is helpful to base considerations on actual examples (which challenge the current Roadmap).
• Our moderator asked  us to share information on risk assessments involving synbio. Recently,  we considered an application for a confined field trial involving LM Camelina  lines. These LMOs contain 7 biosynthetic genes from non-plant sources and together, they  introduce a novel metabolic pathway for the production of fatty acids in plants. Whilst the majority of assessors did not consider this an example of synbio, a minority did. This example did not challenge the existing approach to risk assessing LMOs that the Roadmap describes. (https://www.gov.uk/government/publications/genetically-modified-organisms-rothamsted-research-16r801).
• The RA/RM AHTEG has a mandate from Parties to update the Roadmap to ensure that, as far as possible,  it is applicable to a range of LMOs. It is not clear why LMOs developed by synbio should be treated any differently. The SBSTTA recommendations appear to have been interpreted in a way that gives this different approach the ‘green light’.  I hope my post adds to the previous posts [#7860], [#7861]  [#7862] and [#7863] that explain why developing new guidance at this stage, is at best, premature.

Louise

Dear participants,
First of all thanks to our moderator - Maria Mercedes -  for taking time in this period of the Forum.
I would like to share the concern of some previous participants like Martin Lema [#7860], Piet [#7864], and Fujita [#7865], since I do agree that synthetic biology is not well defined yet.
My main intervention in this discussion on "Submission of views... synthetic biology" goes specially supporting the concern and frustration expressed by my Brazilian colleague Luciana [#7861]. Being part of some previous Brazilian delegations at MOP meetings, and following closely the Open Ended Fora (since almost the first one) I have been many times discouraged because the main items for discussion as well as many impressions and suggestions presented by participants are nor well addressed (or even addressed at all) neither they are clearly discussed and or included/excluded in the final documents. Which are the criteria to include or exclude any consideration presented during the discussions on line? How can we feel as real part of the discussion when the documents do not reflect the level of agreement or disagreement during the Forum?
As Piet and Luciana well presented, in order to help the MOP in its deliberations regarding SB, we best start by exploring which specific aspects of organisms that have actually been developed to date through SB would not be adequately taken into account Annex III, and any agreed guidance based on it.

Thanks for the opportunity to contribute, and will be following this work

Deise Capalbo

Dear Maria Mercedes and all,

Thank you Maria Mercedes for your effort in this forum.
I agree with Martin Lema’s and others concerns related to the scope –and of course definition- of synthetic biology.
And we must remember that we are dealing also with IP concerns.
Theoretically, we should be looking forward to define some balance between benefits of innovation and how to deal with possible risks. The first thing to work in is to define which are really the important questions needing answers. It is such a  broad issue…..
As Nobuyuki Fujita says we should focus (as defined in the Protocol) on living organisms that possesses a novel combination of genetic material obtained through the use of modern biotechnology
Are all the traits in the different possible methods that are developed through synthetic biology considered non-transgenic? (e.g. the Cibus non transgenic flax with a glyphosate resistance trait developed by targeting mutations (“spelling changes”) in native gene targets).
Should we consider preventive measures vs. mitigation measures?
Should Biosafety issues be depending (and related) to applications?
I also agree with Piet, Luciana and Deise that in relation with synthetic biology, we should focus mainly in considering which aspects of organisms developed through SB should have different guidance, or if the guidance based on Annex III is sufficient for a risk assessment.

Best regards, abrazo

Elizabeth

POSTED ON BEHALF OF JIM LOUTER
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First of all let me say that I am very appreciative of the moderation being performed by Maria Mercedes and by her efforts to keep the discussion on track and that she reminded participants that “we are asked to limit the scope of your interventions to issues related to the risk assessment of living modified organisms that are particularly important because they were developed using synthetic biology”.

Secondly, I am also very appreciate of the many thoughtful, respectful and in-depth comments made by Martin Lema, Luciana Ambrozevicius, Louise Ball and others who have posed foundational questions about the task of this particular discussion especially with respect to the ‘definition’.  I support their positions.

However, as a participant in the AHTEG on Synthetic Biology last autumn and in the SBSTTA discussions last month, and having participated in the lengthy discussions on definition, (and which were again left in square brackets at the SBSTTA), I am still left with the feeling that we can’t let go of the definition issue yet and it is important because it defines the scope and therefore is central to the “issues related to the risk assessment of LMOs that are important because they were developed using synthetic biology”.  It is interesting to note, as was observed by a Nordic country in the contact group, that the definition of ‘biotechnology’ in the Convention is similarly broad and covers everything the AHTEG identified as synthetic biology.  In the contact group we had, I thought, reached consensus that we were talking about a ‘description’ and not a ‘definition’ but someone that got lost in the published text (but I still believe it is the more accurate term).

As a Canadian, and a risk assessment practitioner, I can say that that are no “issues related to the risk assessment of LMOs that are important because they were developed using synthetic biology” that are science-based or that would give me cause for concern that our risk assessment paradigm was inadequate.  Canada might have some administrative concerns, or certain information requirements may need to be adjusted, or different scientific expertise acquired, but the scientific risk assessment framework would still be the same. As was said by Canada in the Plenary and in the contact group, ALL regulatory systems, domestic and international, need to take new information into account, to keep them up-to-date.  If you can do so and make them ‘technology’ independent, then that would be advantageous.  We should keep the focus on the resulting organism while considering which technology was applied to it (regulate the product while not ignoring process).  For example, (and assuming we could agree that this example was indeed an example of synthetic biology or an LMO or both), if an organism had extensive metabolic pathway engineering done to it, then more information would be needed to describe each of those changes and that would take more time and potentially more risk assessors staff to evaluate.  Perhaps more or different expertise would be required. 

Scope of what is synthetic biology remains the issue and the square bracketed ‘definition’ does not help us. 

Cheers,
Jim Louter, Biotechnology Section, Environment and Climate Change Canada

Dear all,

First thanks to Maria for moderating this discussion and for the possibility of participating in this forum.

I share the concerns expressed by Martin Lema and several other participants that for Synthetic Biology no accepted definition exist. Actually, there is a lack of consensus on whether synthetic biology constitutes a new and emerging issue.

According to the SBSTTA recommendations outcome document, it notes:
• “Living organisms developed through current applications of synthetic biology are similar to living modified organisms as defined in the Cartagena Protocol on Biosafety, whereas non-living components (such as a DNA molecule) and products/outputs of synthetic biology (such as a chemical substance) do not fall under the scope of the Cartagena Protocol but may be regulated under other processes;”
• “Notes that the general principles and methodologies for risk assessment under the Cartagena Protocol and existing biosafety frameworks provide a good basis for risk assessment regarding living organisms developed through current applications of synthetic biology, or that are currently in the early stages of research and development, but such methodologies may need to be updated and adapted for current and future developments and applications of synthetic biology;”
Considering that currently and in the near future there are no identified application of Synthetic biology that wouldn’t fall into the definition of LMO and that wouldn’t have a good basis of risk assessments through existing biosafety frameworks/risk assessment as in annex III. I see no point in developing new guidance. As Luciana suggested, there are a few questions that come first before developing new guidances that should be taken into consideration.

all the best, Lúcia

Dear all,

We are halfway through these discussions and we have another week to go before the current on-line forum closes. I sincerely thank those participants who have taken the time to share their views and experience, including those who have expressed their concerns and frustration at the process and invite others to participate.

Before I offer clarifications on the objective of this forum and the process we are required to follow, I would like to address  concerns by Luciana (#7861) and a specific question by Deise (# 7869) who asks which is the criteria (by moderators and the group who later drafts the conclusions)  to include or exclude any considerations during these on-line discussions. The only acceptable criteria is to be totally transparent and include (in a summary) all views presented. I pledge my commitment to the transparency of this process.

All commentators agree so far, that there is no clear definition of what synthetic biology is, and since a consensus has not been reached, it is premature to develop  new risk assessment guidance for LMOs  produced by synthetic biology.

I particularly thank  Louise (#7866) for providing a specific example of a “living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology as defined by the Protocol” that a minority of assessors considered a product of synthetic biology.

Several participants  (#7861, 7864, 7866, 7869, 7870) noted  that the COP-MOP should make the decision on whether or not guidance on synthetic biology is needed and that this forum should start “by exploring which specific aspects of organisms that have actually been developed to date through SB would not be adequately taken into account Annex III, and any agreed guidance based on it” and focus on “considering which aspects of organisms developed through SB should have different guidance, or if the guidance based on Annex III is sufficient for a risk assessment”.

This is exactly how the process is and what the forum is invited to do. A decision whether to develop guidance on this topic will NOT be made by the AHTEG but by the COP-MOP.

Thus, it is useful to remind ourselves that the AHTEG is required  to prepare an “outline” highlighting any specific aspects of organisms developed through synthetic biology that would not be adequately taken into account Annex III or the Roadmap.

The process decided by the AHTEG in response to decision BS-VII/12 is  in line with the comments posted in this online forum so far,  to the effect that the online forum and AHTEG are simply providing information to the COP-MOP. The outline will be submitted to the COP-MOP, and it is the COP-MOP who will consider the information and may decide whether or not the information provided supports the development of guidance on risk assessment of organisms developed through synthetic biology.

I trust this clarification allows for the continuation of a constructive discussion.

Best regards to all,

Maria Mercedes

Dear Maria

First I would like to take advantage of this opportunity to thank you for taking on this role of moderator,

I have been following the discussion closely and I believe it is not heading in the direction where it is supposed to.

I would like to remind ourselves of 2 relevant decisions that are quite important for our deliberation on synthetic biology here.

CBD. COP decision XII/24. Point 3
“The Conference of the Parties,
3.  Urges Parties and invites other Governments to take a precautionary approach, in accordance with paragraph 4 of decision XI/11, and:
- To establish, or have in place, effective risk assessment and management procedures and/or regulatory systems to regulate environmental release of any organisms, components or products resulting from synthetic biology techniques, consistent with Article 3 of the Convention;
- To approve organisms resulting from synthetic biology techniques for field trials only after appropriate risk assessments have been carried out in accordance with national, regional and/or international frameworks, as appropriate;
- To carry out scientific assessments concerning organisms, components and products resulting from synthetic biology techniques with regard to potential effects on the conservation and sustainable use of biodiversity, taking into account risks to human health and addressing, as appropriate, and according to national and/or regional legislation, other issues such as food security and socioeconomic considerations with, where appropriate, the full participation of indigenous and local communities;
- To encourage the provision of funding for research into synthetic biology risk assessment methodologies and into the positive and negative impacts of synthetic biology on the conservation and sustainable use of biodiversity, and to promote interdisciplinary research that includes related socioeconomic considerations;
- To cooperate in the development and/or strengthening of human resources and institutional capacities, including on methodologies for risk assessments in synthetic biology and its potential impacts on biodiversity, in developing countries, in particular the least developed countries and small island developing States, and countries with economies in transition, including through existing global, regional and national institutions and organizations and, as appropriate, by facilitating civil society involvement. The needs of developing country Parties, in particular the least developed countries and small island developing States among them, and Parties with economies in transition, for financial resources; access to and transfer of technology consistent with Article 16 of the Convention; establishing or strengthening UNEP/CBD/COP/12/29 Page 179 regulatory frameworks; and the management of risks related to the release of organisms, components and products resulting from synthetic biology techniques, should be taken fully into account in this regard;”

CPB COP-MOP BS-VII/12. Para 17
”The Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety,
17. Recommends to the Conference of the Parties to the Convention on Biological Diversity a coordinated approach with the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety on the issue of synthetic biology, taking into account that the provisions of the Protocol may also apply to living organisms resulting from synthetic biology. ”

I would strongly disagree on the say that “it is premature to develop new risk assessment guidance for LMOs produced by synthetic biology. While, the mandate of parties to the Cartagena protocol which are at the same time parties to the CBD on how to deal with synthetic biology is clearly settled in the first decision. I believe we are here to assist parties to fulfill their mandate in establishing quality risk assessment concerning organisms, components and products resulting from synthetic biology techniques with regard to potential effects on the conservation and sustainable use of biodiversity and not to criticize parties decisions.

Warm regards,
O.A.El-Kawy

Dear all,
First thanks to Maria, our moderator, for her summary of the previous interventions and letting us focus on one specific question. Her question is to highlight specific aspects of organisms developed through synthetic biology that would not be adequately taken into account in Annex III or the Roadmap, so that the AHTG can use this for an “outline'.

As indicated by Martin Lema [#7860], to be able to answer this question it comes back to the definition of synthetic biology, which is interpreted in a different way by many people. In this respect the operational definition proposed by the AHTEG synbio (“synthetic biology is a further development and new dimension of modern biotechnology …’) can be used as a starting point for streamlining discussions under the CBD and Cartagena Protocol. As in any other definition of synthetic biology it reflects that there is no cut-off point between a LMO and an organism obtained by SynBio, which was also pointed out by Louise Ball [#7866]. The example given by her, a LM crop modified to express a new biosynthetic pathway, is a good example of the ‘further developed’ LMO which is still captured by Annex III and the Road map. Other examples could be biosensors, that can be foreseen to be introduced into the environment to ‘sense’ specific chemicals, or for bioremediation purposes. These are considered by some as obtained by synthetic biology. Most likely these micro-organisms would be modified by adding constructs with a specific function or even multiple functions. These biosensors can be assessed following Annex III and the Roadmap. In case of uncertainty, for example in case of multiple modifications, more data can be requested to be able to assess environmental safety in an adequate way. This is still in line with the approach described in the Road map. These LMOs are covered by the Roadmap and no specific guidance is necessary.

Given the few examples that may be foreseen for the near future, and the diverse nature of these organisms, it seems not possible to highlight specific aspects of organism developed through synthetic biology that are not adequately taken into account in Annex III or the Roadmap.

Kind regards,
Boet

Dear Maria Mercedes, dear participants.
Having carefully read the contributions from all of you above. I come the conclusion we should clearly point to at least a few examples of “extraordinary” synbio organisms with a plausible chance to reach the field release phase and objectively check if they can have risks assessed by the regular LMO risk assessment roadmap or if they pose unsurpassable challenges. If we can´t provide evidence that these organisms do exist, the forum will have no use. Could any of you provide such extraordinary examples so we could start discussing in real bases (if if we don´t have a clear mandate for it)?
Kindly
Paulo Andrade

Dear all

Thank you for the interesting discussions to date.

I think it is worth reminding ourselves that the topic of organisms produced through synthetic biology has not come out of nowhere, but is a result of a COP-MOP mandated process over several years, and was discussed at least since the first meeting of the previous AHTEG in 2009, in their priority setting exercise of the topics for development of guidance material. Please recall that the previous AHTEG had prioritized topics for the development of further guidance, on the basis of the priorities and needs indicated by the Parties, with the view of moving towards achieving the operational objectives 1.3 and 1.4 of the Strategic Plan and its outcomes as per Decision BS-VI/12. The relevant Subgroup of the current AHTEG then identified several topics, including LMOs produced through synthetic biology (which had earlier been prioritized by the previous AHTEG) as potential candidates for integration into the road map as additional guidance.

Contrary to those who contend that there is no agreed definition of synthetic biology, there is an operational definition that has been agreed by the AHTEG on Synthetic Biology. At the SBSTTA 20 meeting, there was difference in opinion as to the language surrounding the operational definition, on whether to acknowledge and note that additional work may be required, or to use it.  But there was no significant disagreement about the actual wording of the operational definition that was agreed by the AHTEG on Synthetic Biology.

At the SBSTTA 20 meeting, there was no disagreement that the methodologies for risk assessment under the Cartagena Protocol may need updating and adapting for current and future developments and applications of synthetic biology, or that are currently in the early stages of research and development. One clear example is the case of organisms produced and modified through synthetic biology for which there is no comparator.

So I am of the view that the mandate before us is clear, and that we need to discuss and help the AHTEG in its preparation of the outline on the topic for the COP-MOP, in order to facilitate its consideration and further development of the topic as separate guidance.

Kind regards,

Lim Li Ching
Third World Network

Dear All,

First I want to express my warm thanks to Maria for guiding us in this exchange of views and for her latest clarification concerning the scope of the discussion.

Since the primary objective of this forum is to share views, sources of information and reference materials on risk assessment of organisms developed through SynBio, let me refer to two documents to which my Unit contributed. Although these papers were drafted a few years ago, they still contain information and messages that are relevant to our discussion:
- Pauwels, Willemarck, Breyer, Herman (2012). Synthetic Biology. Latest developments, biosafety considerations and regulatory challenges. Ref: D/2012/2505/46. http://www.biosafety.be/PDF/120911_Doc_Synbio_SBB_FINAL.pdf
- Pauwels, Mampuys, Golstein, Breyer, Herman, Kaspari, Pagès, Pfister, van der Wilk, Schönig (2013) Event report: SynBio Workshop (Paris 2012) – Risk assessment challenges of Synthetic Biology. Journal für Verbraucherschutz und Lebensmittelsicherheit - Journal of Consumer Protection and Food Safety 8(3): 215-226. http://rd.springer.com/article/10.1007%2Fs00003-013-0829-9

I also share the large majority of views expressed so far that there is at this stage no scientifically sound arguments to consider the development of further guidance on this topic. In particular:
- Whatever the definition to be adopted, SynBio is a broad operational concept that encompasses various techniques, approaches, end products, and uses. SynBio per se does not appear to be an appropriate trigger to discuss whether or not a new guidance should be developed to support the risk assessment under the CPB.
- An additional guidance should only be envisaged and developed, if needed, on specific LMOs or risk assessment aspects that were identified as posing particular challenges when using the Roadmap. This is the pragmatic and sound approach used so far (for stacked events, LMOs with tolerance to abiotic stress, LM trees, LM fish) and we should not deviate from it. For the reason mentioned above organisms developed through SynBio definitively do not fit within this approach.
- An additional guidance should only be developed when concrete examples are identified where Annex III and the Roadmap are insufficient to perform a scientifically sound risk assessment. It is true that SynBio was identified by some Parties as a possible topic for development of guidance material. But an additional guidance cannot be developed on theoretical cases, general assumptions or wishful thinking. If such concrete examples exist it is therefore very important that they are shared and discussed within this forum.
- Some possible risk assessment “challenges” have been mentioned such as the lack of relevant comparators or the insertion of multiple genetic modifications. Another one that could be mentioned is the intentional release of micro-organisms, due to the relatively limited experience in assessing the potential risks posed by such micro-organisms and the complexity of environmental microbiology. However, besides the fact that it remains to be demonstrated whether such aspects are not captured by Annex III and the Roadmap, these possible “challenges”, as pointed out by previous participants, are not specific to SynBio organisms neither they apply to all SynBio organisms. Once again SynBio does not appear to be a good trigger.
- The overwhelming majority of current and near future uses of organisms developed through SynBio (will) take place in closed installations where containment and confinement measures can be applied in a realistic, risk-proportionate and case-by-case manner. The very few examples of environmental releases with so-called SynBio organisms that were assessed so far have been adequately covered by Annex III and the Roadmap, and “unusual” environmental applications of SynBio are not expected to materialize before several years.

For all these reasons I am of the opinion that SynBio as such is not a relevant issue to be a topic for a separate guidance.

Kind regards,

Didier

Dear all,

First of all, I would thank Maria Mercedes for their moderation of this discussion, I also appreciate all the opinions expressed by the participants of this forum.

From my point of view, I consider important the synthetic biology because it is a technology that is developing really fast and it will have different applications. I consider useful the “Draft recommendation on synthetic biology and their terms of reference”. This document could be special useful for countries that do not have experience on synthetic biology.

For another hand, as many participants of this discution, I am a regulator, so, I´m not an expert in this field, because of that, I recommend that the discussion of the different aspect that should be consider in SB must be carry by experts, inviting them to contribute with new points of view and approaches.

Finally, I consider better to have a reference guidance now, than spend time reviewing and improving again and again the document (that could be never consider finish), because synthetic biology is still in development and the new techniques and advances of the science could modify their implications. For that reason I invite you to adopt the current guidance and improve it with new topics and term with the developing of new advances and knowledge.

Kind regards to all,

Rafael Romero

Dear all,

First of all, I would thank Maria Mercedes for their moderation of this discussion, I also appreciate all the opinions expressed by the participants of this forum.

From my point of view, I consider important the synthetic biology because it is a technology that is developing really fast and it will have different applications. I consider useful the “Draft recommendation on synthetic biology and their terms of reference”. This document could be special useful for countries that do not have experience on synthetic biology.

For another hand, as many participants of this discution, I am a regulator, so, I´m not an expert in this field, because of that, I recommend that the discussion of the different aspect that should be consider in SB must be carry by experts, inviting them to contribute with new points of view and approaches.

Finally, I consider better to have a reference guidance now, than spend time reviewing and improving again and again the document (that could be never consider finish), because synthetic biology is still in development and the new techniques and advances of the science could modify their implications. For that reason I invite you to adopt the current guidance and improve it with new topics and term with the developing of new advances and knowledge.

Kind regards to all,

Rafael Romero

Thanks to all contributors for this dynamic exchange that is well directed by the moderator. I fear my contribution can only reemphasize what many have said, but I like to add some insights from the discussion that occurred with the European Federation of Biotechnology (EFB), Europe’s non-profit federation with more than 100 Institutional members from across Europe and more than 30,000 personal members.

Definition
Most of the contributions (e.g. [#7860] [#7861] [#7864] [#7865] [#7866] [#7918] [#7871] [#7909]) stressed the lack of a clear, sound definition; at the same time pointing out that AHTEG’s operational definition is too broad. I admit to be confused by the operational definition, as potentially every biological entity, even those developed with so-called traditional methods, will be arguably within scope. E.g. an in vitro selection of a virus-free plantlet is a combination of science, technology and “engineering” (not further specified) and which facilitates the manufacturing of healthy plant material. If it is the intention to provide guidance to less experienced risk assessors, then we must be diligent in avoiding confusion. This was also a fundamental comment EFB made on the definition proposed by the European Scientific Committee on Health and Environmental Risks (SCHER), Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) and Scientific Committee on Consumer Safety (SCCS).

Furthermore it seems that there is confusion between processes and products. In my opinion synthetic biology should be seen as the study/application of synthetic life forms, i.e. it is related to entities not to techniques. However, others seem to adhere to more process oriented approaches, even going as far as AHTEG’s operational definition in indicating that “synthetic biology is… a new dimension of modern biotechnology”. Likely this is at the basis for creative indications such as “synthetic biology techniques” [#7873] and “organisms provenient from Synthetic Biology (SBO)” [#7909]. I believe that much of the discussion on overlap between LMO and “organisms developed using synthetic biology” can be retraced to the confusion between process and product, which can only be addressed by clearly formulating the different concepts in a scientifically correct way.

To conclude the part on definition, I like to point out that EFB flagged the confusion between synthetic and synthesized. Synthesizing a genetic sequence in vitro doesn’t make is synthetic per se. There is no scientific basis for making a distinction between isolated, recombinant or synthesised DNA parts as they are all based on the same structure, the same information, etc. Conversely, a completely new chemical structure for hereditary material is proposed (xenobiology) or a cell is assembled of unrelated building blocks (protocells) would be clear cases of synthetic biology.


Risk assessment methodology
As pointed out in many contributions (e.g. [#7860] [#7861] [#7864] [#7861] [#7918] [#7880] [#7909]) and in a very applied way in the recent exchanges on the experience with farnesene-producing GM yeast, all of the available so-called “organisms produced by synthetic biology” are without any doubt LMO. This is likely to remain so given the broad definition of ‘biotechnology’ in the Convention.

As they are LMO it may not seem surprising that the risk assessment practices currently in place to evaluate LMOs were deemed appropriate [#7860] [#7861] [#7864] [#7865] [#7866] [#7918] [#7871] [#7909]. The risk assessment methodology that risk assessors and AHTEG have developed is not unique to LMO; rather it is applicable to any kind of hazard. It provides a logic and systematic approach and it should therefore not be questioned if the methodology is adequate or applicable. Similarly the identification of protection goals should not be different as these should be determined by overall policy decisions independent of the possible influencing factors. Rather the focus should be on hazards and/or mechanisms to induce harm specifically associated with use of certain techniques or their products. This need for focus was indicated in several contributions [#7861] [#7864] [#7918] [#7887] [#7889] [#7891] [#7916] [#7919].

Will certain applications of synthetic biology bring new challenges and require new approaches in risk assessment? I support Breyer [#7887] and Keese [#7897] pointing out the case of organisms produced and modified through synthetic biology for which there is no comparator. Applications of xenobiology and development of artificial cells are a few examples of where no clear “natural” comparator is available.

Finally, I support the bullet points proposed by Breyer [#7887]

Thank you again for the interesting exchange and succes with the challenging task to integrate all inputs in a workable outcome.

Patrick Rüdelsheim
Perseus, Belgium

Dear colleagues,

in the very first place I wish to thank Maria for moderating this forum and the clarifications on the processes this online forum is integrated in.

My name is Swantje Strassheim and I work for the German Federal Office of Consumer Protection and Food Safety (BVL), which is the leading federal authority with regard to genetic engineering in Germany and as such responsible e.g. for the authorization of experimental releases of LMO. I am charged with the monitoring of Synthetic Biology on behalf of the German Central Committee for Biological Safety (ZKBS).

In Germany, several research groups are working on projects referred to as “synthetic biology”, but so far, we have not encountered any difficulties applying our GMO risk assessment regime to the organisms created so far.

As such, I agree with the majority of statements made in this online forum that at this time point no additional guidance for synthetic biology is needed. So far, we consider organisms produced with the help of synthetic biology as LMOs as defined in the Cartagena Protocol and agree that these can be assessed adequately by Annex III and the Roadmap.
I particularly agree with Paulo Andrade [#7882] and Didier Breyer [#7887] that we should investigate whether there are concrete examples of organisms produced with the help of synthetic biology and with a reasonable possibility to reach the field release phase that cannot be assessed by Annex III and the Roadmap. Synthetic biology per se should not trigger deliberations on new guidance, since there is no clear differentiation between “modern biotechnology” and “synthetic biology”. The definition proposed by the AHTEG synthetic biology is very broad and cannot provide this differentiation. This has been criticized by several Parties in the SBSTTA contact group and was, amongst others, a reason for not reaching consensus on how to use this operational definition.


Best regards,
Swantje Strassheim

Dear All,

First, let me express my deepest gratitude to Maria for chairing this discussion in such a thoughtful and constructive way, both in her initial remarks as well as her subsequent clarification to keep us on the path to a fruitful discussion.

I have followed the discussion with great interest and find myself nodding in agreement so many times.   Most recently, I agree with the comments of Didier Breyer [#7887], and I appreciate that he has added some references to the discussion.  I also agree wholeheartedly with his concise statement that “at this stage no scientifically sound arguments to consider the development of further guidance on this topic.” I support all of Didier’s sub-bullets that give more specific examples, also.
 
To be somewhat brief, let me also note my support for the previous comments in this discussion by Piet van der Meer [#7864], Louise Ball [#7866] , Nobuyuki Fujita [#7865], Deise Capalbo [#7869], Elizabeth Hodson [#7870], Lúcia de Souza [#7871], Boet Glandorf [#7880], Paulo Andrade [#7882], and Swantje Strassheim [#7889].

I agree with the comments made by many others thus far in the discussion, including the early comments by Martin Lema [#7860] and Luciana Ambrozvecius [#7861]  that the report from the CBD AHTEG on synthetic biology (UNEP/CBD/SYNBIO/AHTEG/2015/1/3; (https://www.cbd.int/kb/record/meetingDocument/106031) provided recommendations to the CBD Conference of the Parties (COP), and as such would need to be adopted by the Parties at COP13 prior to any actions taken.   Additionally, the SBSTTA20 report on synthetic biology (UNEP/CBD/SBSTTA/REC/XX/8; https://www.cbd.int/doc/?meeting=sbstta-20) noted in its recommendations to the COP, “The general principles and methodology for risk assessment under the Cartagena Protocol and existing biosafety frameworks provide a good basis for risk assessment regarding living organisms developed through current and near future applications of synthetic biology, but such methodologies may need to be updated and adapted for current and future developments and applications of synthetic biology;”.  This should not be perceived as a “green light” to proceed with work, as the recommendation must be taken up by the Parties at COP13.

With this in mind, from a procedural standpoint it appears to be premature for the RA/RM AHTEG to take up work on synthetic biology.  This topic is currently being discussed under the Convention on Biological Diversity (CBD).  As such, the Parties to the CBD have not agreed that synthetic biology is a new and emerging issue under the Convention per the criteria of Decision IX/29 (https://www.cbd.int/decision/cop/?id=11672).  Furthermore, the Parties to the Convention have not decided to move this topic to either Protocol or their AHTEGs. 

Regarding the nature of the Guidance document, I would like to echo Louise’s point [#7866], that the basic Guidance document was to be broadly applicable to a range of LMOs. The AHTEG on Risk Assessment and Management is on its second draft iteration of the basic Guidance document and has not yet reached consensus on this document.  We should not delay ongoing work by straining already burdened resources with additional work that does not have a clear analytical foundation and for which the practical application is not identified. 

Maria noted in opening the discussion that the members of the AHTEG expressed a variety of views about whether “risk assessment practice currently in place to evaluate LMOs are appropriate to evaluated organisms of synthetic biology”.  I share the views of many that it is difficult to point to any concrete examples in which the current LMO assessment tools are inadequate for evaluating a range of organisms produced via synthetic biology.

Best regards,

David Heron

Dear all,

My deepest appreciation also to Maria for moderating this forum.  I have been following with interest the discussion so far, with opinions from a scientific and procedural perspective.

Starting from the introductory remarks, Maria explained that 

1.  The AHTEG, at its meeting in November 2015 agreed to prepare an outline for guidance on risk assessment of organisms developed through synthetic biology, subject to the SBSTTA meeting in April.
2.  The SBSTAA gave us the "green light" for this process.

As I read this explanation, I questioned whether we really have the choice not to prepare an outline for additional guidance at this time.  However, this was clarified to me by Dave Heron's contribution that the agreement by the AHTEG is not yet in force until adopted by the parties at COP 13.  I also agree with Dave's view that in fact the SBSTAA report does not provide this "green light" (with all respect to Maria's conclusion), since it only mentions that there MAY need to be an update, but does not mandate that one should be done at this time.  Furthermore, the SBSTAA report states that "The sharing of experience and information among Parties is crucial and needs to be encouraged, including information on actual risk assessments and gaps in existing national, regional and/or international instruments to regulate the organisms, components or products derived from synthetic biology techniques..."  It seems to me that from the experience that has been shared to date, it is clear that there has been no difficulty conducting risk assessments of organisms developed through synthetic biology (however it is defined), using the current risk assessments for LMOs, and therefore does not reveal any gaps that require filling by additional guidance.

Therefore, I believe that by recommending that no additional guidance is necessary at this time, we are consistent with COP decision XII/24. Point 3.  To date, based on experience, we do have in place effective risk assessment, management procedures, etc., as evidenced by the information provided by those who have done risk assessments in line with the procedures currently in the Protocol.  Furthermore, this position is also consistent with COP-MOP BS-VII/12. Para 17, since the approach of being judicious about the proliferation of additional guidance is being done to achieve precisely the kind of coordination that leads to effective regulation.

Regards to all,

Hector

Dear colleagues,

I would like to first thank Maria Mercedes for accepting to moderate this discussion and also the Secretariat for their organization. I would also like to thank the members who have already shared their views.

We have just finalized a one-week capacity building course in synthetic biology with focus on biosafety issues and the contribution to addressing societal challenges - See more at: http://genok.com/arkiv/5121/#sthash.Zzs8Yyve.dpuf. A report of this course and the previous course for the African region (held in September 2015) will be written soon.

Following the objective of this discussion, I would like to share my view point which has been much built from sharing experiences in theses courses, each constituted from delegates, regulators, scientists and NGOs from more than 10 countries.

I would like to first highlight the fact that risk assessment is a pre-market step and, therefore, should be developed before any synthetic biology product reaches market. It is not true these products are far away from becoming real products. In fact, Brazil already has approved a synthetic biology microorganism back in 2010. This is farnesene-producing yeast from Amyris. Not only the scientific community refers to it as a synthetic biology organism but also the company and the Biosafety Commission in Brazil. It is classified under the research area of metabolic engineering in synthetic biology field. But of course this yeast is in the gray area in which it is also a LMO. However, the 30 steps of genetic modifications, mutations, selections, crossing, etc and the introduction of several genes and regulatory elements clearly shows that this organism is much more complex in terms of its transgenic constitution than the experience many developed countries have with GM crops harboring one or two transgenes.

Noteworthy, we brought this yeast as a case study to be discussed in the two courses we organized. In both courses we had a similar outcome, the participants somewhat felt the wild-type microorganism might not be sufficient or relevant to conduct the risk assessment.

I thank some of the colleagues who questioned which aspects of RA for SynBio organisms could not covered in the RoadMap. Many of our colleagues, including myself have participated in the synbio forum and have pointed to the fact that new synbio organisms might not have a proper comparator and that this might challenge current RA frameworks including the Guidance. It it my idea we could start from that and discuss how we could adapt current methodologies in the case of no proper comparator. I see much gain when both the synbio and the RARM forum and AHTEG come together to work on the issue.

It is definitely not too early to discuss RA guidance for synbio. In fact, it seems to me that the discussion over the mandate of the forum/AHTEG actually delays the main objective of the current discussion, which is simply to brain-storm and “gather views, information and reference materials on risk assessment”. We might come up with the conclusion of no new guidance or indeed new guidance but we wont conclude anything if we focus on the debate over the mandate of the forum which is clear as legitimate as the concern on the potential threats of synbio to conservation and sustainable use of biological diversity.

Best regards,

Sarah

Dear all
Many thanks Maria Mercedes for moderating this discussion, which I have been following with close interest.
It would seem that there is broad agreement that most living organisms that arise from the application of synthetic biology (whatever the definition is) would seem to still result in an LMO as defined under the Cartagena Protocol. Therefore, it would seem that we are tasked with identifying any distinguishing characteristic of these organisms that might benefit from additional guidance. I would agree with Didier Breyer [#7887] and Sarah Agapito-Tenfen [#7895] r [#7891] that a relevant comparator is a challenge within the current guidance and its narrow emphasis on (near) isogenic lines. It might be useful to produce guidance on the use of alternative comparators. This could be based on the taxonomic status of the LMO derived from synthetic biology. For example, if the LMO is classified as belonging to an existing species, then that species can used as the baseline comparator. This approach is the default position adopted by the Australian Risk Analysis Framework http://www.ogtr.gov.au/internet/ogtr/publishing.nsf/content/raffinal5-toc and consistent with the standard position of producing biology documents for use in risk assessments of LMOs that are typically conducted at the species level; such as the widely endorsed OECD consensus documents. If the LMO is distinctive at the species level, but belongs to an existing genus, family, class, family etc then that higher order category can be used as the comparator. For example, an LMO approved for use in contained facilities in Australia intends to reconstruct a retrovirus from genomic fragments in the bat genome. This risk assessment used the family Retroviridae as the comparator. Alternatively, the Australian Risk Analysis Framework provides an absolute scale for evaluating consequences, obviating any need for a comparator.
Best regards
Paul

Dear participants,

We took up the case of farnesene-producing yeast mentioned by Sarah Agapito-Tenfen [#7895] in a study commissioned by Japanese government. Aside from the fact that the yeast is for contained use, for which whether or not to conduct risk assessment is in the sole discretion of the country, the yeast has gone through full-featured risk assessment including environmental risk assessment before it was approved for commercial use. I admire the way that the company and Brazilian authority have followed, and this is a typical way by which we accumulate knowledge on newer applications on case by case basis, before we can develop a science-based risk assessment guidance, SOP or whatever (although I don't think this yeast poses any novel or additional risk as was the conclusion of Brazilian authority). I am afraid that developing a guidance without knowledge from such pioneering works will end up with a guidance which only discourages innovations.

Nobuyuki Fujita

Dear all,

I would like to thank Maria for moderating this discussion and also Secretariat for organization.

From interesting and lively debate so far it would seem that there is a broad agreement that most living organisms developed through current and near future applications of synthetic biology are similar to living modified organisms as defined in the CPB.

As was already mentioned recently by Boet [#7880] the AHTEG SynBio proposed operational definition saying that »synthetic biology is a further development and new dimension of modern biotechnology that combines …” what from our understanding does not exclude the application of GM risk assessment and safety guidelines developed over the past years by relevant bodies to synthetic biology nor extensions of that work.

Furthermore, synthetic biology enables rapidly advancing nature of GM technologies and adds an important nuance that supports the need for on-going updates of risk assessment methods. It could be also recognised that synthetic biology evolves from and share much of the methodologies and tools with genetic engineering.

So, complexity and uncertainty may be confronted within the risk/safety assessment of synthetic biology, and even current risk assessment is already (will be soon) challenged with what was recently mentioned by Didier [#7887],Sara [#7895], Lim Li Ching [#7885], Boet [#7880], Louise Ball [#7866] and can be linked not solely with the lack of comparator species but also with the increasing number of genetic modifications and engineered living organisms, etc.

Based on what have been said above and on many times and in many platforms which exposed facts that synthetic biology is a very rapidly developing field (e.g. http://syntheticbiology.org/) it seems not too early or premature to discuss, brain-storm and gather views, information and reference materials on risk assessment and help the AHTEG under CPB in its preparation of the outline on this topic.

Kind regards to all,

Martin

Dear Participants,

First of all my sincere appreciation to Dr. Maria Roca for your effort in this forum and the clarification of questions about the topic. Second, I would like to thank all the participants to share your point of view about Synthetic Biology (SynBio). And last but not least, thanks for the opportunity to participate.

I have followed the scientific evolution and use of synBio and the discussion about this issue with great interest in previous meetings and Open-Ended Online Forum of CBD (COP7; SBSTTA 19 and 20; Online Forum of RA&RM and Synthetic Biology).

I have some points that I would like to share:

a) Absence of consensus on Synthetic Biology Definition;
I fully support Martin Lema [#7860], Luciana Ambrozevicius [#7861], Nobuyuki Fujita [#7865], Louise Ball [#7866], Deise Capalbo [#7869], Elizabeth Hodson [#7870], Lúcia de Souza [#7871], Boet Glandorf [#7880], Didier Breyer [#7887], and Swantje Strassheim [#7889] about the absence of consensus of SynBio.

In despite of the hard work done in the Online Forum and the AHTEG of SynBio, we did not reach a common definition and this was an issue of great debate in the contact group of SBSTTA 20. I would like to call your attention  to some important work that have tried answering this question and could be useful:

2014 - Final Opinion on Synthetic Biology 1 - European union
http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_044.pdf

2014 - Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options – J. Graig Venter Institute
http://www.jcvi.org/cms/fileadmin/site/research/projects/synthetic-biology-and-the-us-regulatory-system/full-report.pdf

2012 - Synthetic biology - A review of the technology, and current and future needs from the regulatory framework in Great Britain
http://www.hse.gov.uk/research/rrpdf/rr944.pdf

Like some previous participants highlighted, and I agree, the lack of consensus in SynBio definition occurs because of the second point, the…

b) Absence of differences between Living Modified Organisms (LMOs) and Organisms provenient from Synthetic Biology (SBO);
As concluded by the AHTEG, which as the name says has the background and technical expertise and also recommended by the SBSTTA 20, SBOs are similar to LMOs:

“Takes note of the conclusion of the AHTEG on Synthetic Biology that living organisms developed through current applications of synthetic biology, or that are currently in the early stages of research and development, are similar to living modified organisms as defined in the Cartagena Protocol;”

As pointed out by Lúcia de Souza [#7871], David Heron [#7890], and some delegates (Brazil, Canada, Australia, Japan, New Zealand,…) in COP7 and SBSTTA 19 and 20, the Parties to the CBD have not agreed that synthetic biology is a new and emerging issue under the Convention.

SynBio should not be viewed as a “new and emerging issue”. In fact, SynBio is the normal evolution of the techniques that are  used  to modify the genome of organisms. The techniques and tools are different and more accurate but the objective is the same.

Considering that there is no consensus definition and that the technical group  indicated  that SBOs are similar to LMOs, we have the 3º point…

c) Premature guidance for SynBio and the use of principles and methodologies to make the Risk Assessment
I fully agree with the reasons given by Martin Lema [#7860], Luciana Ambrozevicius [#7861], Piet van der Meer [#7864], Louise Ball [#7866], and the other participants that consider premature and/or inadequate the development of a new guidance for SynBio.
Additionally, since there is no difference between SBO and LMO, the general principles, methodologies and knowledge of the risk assessment used for LMO can be used for SBO. This fact is corroborated by the conclusion of the AHTEG and recommendation by the SBSTTA 20:

“Notes that the general principles and methodologies for risk assessment under the Cartagena Protocol and existing biosafety frameworks provide a good basis for risk assessment regarding living organisms developed through current applications of synthetic biology, or that are currently in the early stages of research and development, but such methodologies may need to be updated and adapted for current and future developments and applications of synthetic biology;”

The sharing of information on practical cases of risk analysis of SBO using the framework of some national legislations should shed more light on the actual need or not for specific new guidance for SBO.

Like Nobuyuki Fujita [#7899] pointed it is important clarify that in Brazil the Biosafety Law (http://www.wipo.int/wipolex/en/text.jsp?file_id=272171) does not distinguish  between natural recombinant molecule and synthetic recombinant molecule. Therefore, the National Technical Commission on Biosafety (CTNBio) considers SBO as part of LMO and uses the same framework, as it was mentioned by Louise Ball [#7866] in the excellent example of introduction of a novel metabolic pathway for the production of fatty acids in plants in the UK.

d) Products and Components provenient from Synthetic Biology do not fall under the scope of the Cartagena Protocol on Biosafety
Finally, it is important to highlight the conclusion of Synbio AHTEG and the recommendation of SBSTTA 20 mentioned before by Lúcia de Souza [#7871] that non-living components and products do not fall under the scope of CPB:

“Living organisms developed through current applications of synthetic biology are similar to living modified organisms as defined in the Cartagena Protocol on Biosafety, whereas non-living components (such as a DNA molecule) and products/outputs of synthetic biology (such as a chemical substance) do not fall under the scope of the Cartagena Protocol but may be regulated under other processes;”

Best regards,
Marcelo Freitas

Dear Maria, dear participants,
Let me first thank to Maria for  taking up a difficult  task of being a chairperson of this Fora and for preparing a mid-term summary of the discussion. I'd also like to thank all of the participants for the contributions.
I believe all of the arguments have some sense in a way from a certan perspective. It seems we all share the view that the Anex III and a RoadMap for LMO RA is still fully applicable to SynBio organisms. However, synthetic biology is undoubtedly a rapidly developing field and as noted also in The SBSTTA Reccomendations: »such methodologies may need to be updated and adapted for current and future developments and applications of synthetic biology« I'm of the oppinion that we should embrace this oportunity and all help to produce a sensible outline. This work could bring better awareness, understanding and finally acceptance/recognition of the synthetic biology per se. I support the theme of the difficulties with the choice of the adequate comparators to be a first stone in the development of the outlines.
Best wishes Ruth

Dear Colleagues.
I would like to reinforce Nobuyuki Fujita´s opinion on the absence of concrete differences between the risk assessment of a transgenic GM microorganism and the one presented as synbio microorganism by the company to CTNBio (Brazil). In spite of the many genetic changes (which were obtained either by conventional genetic changes – mutations – or by transgenesis, which, in yeasts is a very simple step), the final phenotype poses no real challenge for the regulator and the comparator is easily identified. It was just much work, but not difficult or challenging.
As one of the analysts of this GM yeast, I could assess all the details, from construction methods to phenotypic changes and could easily and safely come to the conclusion that the variety poses no additional risks to the environment. I really don’t think the farnese-producing GM yeast (or any other similar GM, either based on yeast, algae or other well known microorganism) will pose any new, challenging question to the risk assessor.

Kindly
Paulo Andrade

First of all,  my sincere appreciation to Dr. Maria Roca for your effort in this forum and the clarification of questions about Symbio and my colleagues for the important contribution.

It is important notice that BS is a normal extension of technological development and the organisms produced using this technology can be seamlessly submitted by the principles of risk assessment of P. Cartagena. The discussions about this issue and the concept for BS, so far, are speculative and therefore not a formal agenda item, for this reason I consider not an official mandate parties. There was no agreement between the parties - take notes by Lucia de Souza [# 7871], David Heron [# 7890], and some delegates (Brazil, Canada, Australia, Japan, New Zealand at COP7 and SBSTTA 19 and 20, where the Parties to the CBD have not agreed that synthetic biology is a new and emerging issue under the Convention.

It is very important to observe that the most of produced synthetic organisms are defectives and do not release to environment. If they are designed for environmental use, there is already a number of computational behavior simulator programs because it is inaugurated a phase of science known as digital ecology). If these organisms are accidentally released to the environment, certainly they will be very bad competitors with wild type.

Therefore, I reiterate the comments of Martin Lema [# 7860], Luciana Ambrozevicius [# 7861], Piet van der Meer [# 7864], Louise Ball [# 7866], Marcelo Freitas [# 7909] and the other participants that consider premature and / or inadequate development of a new guidance for Synbio.

The legislation in Brazil does not Distinguish between natural and synthetic recombinant molecule. Therefore, the National Technical Commission on Biosafety (CTNBio) considers SBO part of the LMO and uses the same framework. Thus, the principles of existing risk assessment in Brazil are sufficient to meet the BS organisms. The purified substances from these organisms follow the legal and regular principles of record (because they are not living entities).

First of all,  my sincere appreciation to Dr. Maria Roca for your effort in this forum and the clarification of questions about Symbio and my colleagues for the important contribution.

It is important notice that BS is a normal extension of technological development and the organisms produced using this technology can be seamlessly submitted by the principles of risk assessment of P. Cartagena. The discussions about this issue and the concept for BS, so far, are speculative and therefore not a formal agenda item, for this reason I consider not an official mandate parties. There was no agreement between the parties - take notes by Lucia de Souza [# 7871], David Heron [# 7890], and some delegates (Brazil, Canada, Australia, Japan, New Zealand at COP7 and SBSTTA 19 and 20, where the Parties to the CBD have not agreed that synthetic biology is a new and emerging issue under the Convention.

It is very important to observe that the most of produced synthetic organisms are defectives and do not release to environment. If they are designed for environmental use, there is already a number of computational behavior simulator programs because it is inaugurated a phase of science known as digital ecology). If these organisms are accidentally released to the environment, certainly they will be very bad competitors with wild type.

Therefore, I reiterate the comments of Martin Lema [# 7860], Luciana Ambrozevicius [# 7861], Piet van der Meer [# 7864], Louise Ball [# 7866], Marcelo Freitas [# 7909] and the other participants that consider premature and / or inadequate development of a new guidance for Synbio.

The legislation in Brazil does not Distinguish between natural and synthetic recombinant molecule. Therefore, the National Technical Commission on Biosafety (CTNBio) considers SBO part of the LMO and uses the same framework. Thus, the principles of existing risk assessment in Brazil are sufficient to meet the BS organisms. The purified substances from these organisms follow the legal and regular principles of record (because they are not living entities).

First of all,  my sincere appreciation to Dr. Maria Roca for your effort in this forum and the clarification of questions about Symbio and my colleagues for the important contribution.

It is important notice that BS is a normal extension of technological development and the organisms produced using this technology can be seamlessly submitted by the principles of risk assessment of P. Cartagena. The discussions about this issue and the concept for BS, so far, are speculative and therefore not a formal agenda item, for this reason I consider not an official mandate parties. There was no agreement between the parties - take notes by Lucia de Souza [# 7871], David Heron [# 7890], and some delegates (Brazil, Canada, Australia, Japan, New Zealand at COP7 and SBSTTA 19 and 20, where the Parties to the CBD have not agreed that synthetic biology is a new and emerging issue under the Convention.

It is very important to observe that the most of produced synthetic organisms are defectives and do not release to environment. If they are designed for environmental use, there is already a number of computational behavior simulator programs because it is inaugurated a phase of science known as digital ecology). If these organisms are accidentally released to the environment, certainly they will be very bad competitors with wild type.

Therefore, I reiterate the comments of Martin Lema [# 7860], Luciana Ambrozevicius [# 7861], Piet van der Meer [# 7864], Louise Ball [# 7866], Marcelo Freitas [# 7909] and the other participants that consider premature and / or inadequate development of a new guidance for Synbio.

The legislation in Brazil does not Distinguish between recombinant and synthetic recombinant molecule. Therefore, the National Technical Commission on Biosafety (CTNBio) considers SBO part of the LMO and uses the same framework. Thus, the principles of existing risk assessment in Brazil are sufficient to meet the BS organisms. The purified substances from these organisms follow the legal and regular principles of record (because they are not living entities).

Dear Ms. Chang, dear colleagues at this forum, dear Mrs. Maria Roca.
I am enjoying the discussion and learning from all of you, and this is privilege. Some four days ago I posted a message to this forum asking for a specific example of a synbio organism that could not be evaluated using the regular step-by-step procedure of risk assessment, as established in the AHTEG guidance and elsewhere. One example was forwarded by Ms. Sarah Agapito-Tenfen, the farnesene-producing GM yeast. However, as pointed out by Noboyuki Fujita and by myself, the Brazilian CTNBio found it to be no special challenge, in spite of the complex genetic modification. Moreover, the comparator was evident: a regular, non GM yeast. As Ms. Li Ching Lim seems to know another specific, concrete example for which no comparator is available, I would be immensely grateful to her as to share this information with the forum. In my point of view, we can´t proceed discussing regulating synbio product in a specific regulatory framework if we can´t produce at least one solid example which poses new, unanticipated challenges to the risk assessor. I thank you in advance, Ms. Chang, and congratulate all my colleagues who posted such vivid and instructive information to the forum.
Kindly
Paulo Andrade , Dept. Genetics, Federal University of Pernambuco, Recife, Brazil

Dear participants,

Thank you for the opportunity to contribute to this discussion. I agree with the majority of posts in this online discussion so far (#7860, #7861, #7864, #7866, #7880, #7887, #7889, #7890, #7891, #7920) that it would be premature to develop risk assessment guidance specifically for synthetic biology for the following reasons:

- There is no agreed definition of synthetic biology
It is evident in the draft recommendations from SBSTTA-20 (UNEP/CBD/SBSTTA/20/L.16) that consensus could not be reached on the acceptability of the operational definition produced by the AHTEG on Synthetic Biology. However, it is not evident in that document that there was consensus among many Parties that it would be more appropriate to refer to it as a ‘description’ rather than a definition. This reflects the diversity of views as to what constitutes synthetic biology, and (as pointed out by #7866 and #7880) the difficulty in differentiating between LMOs along a continuum of technological development. The example given in #7866 demonstrates this, with assessors of the same LMO differing on whether they considered it to be synthetic biology. Considering all of this, how can gaps in the current guidance (to be filled by the additional guidance for synthetic biology) be identified, and useful content for the guidance be defined? It is arbitrary and scientifically unsound to develop guidance simply for ‘synthetic biology’ in the abstract.

- There is no agreement there are gaps in the current Guidance
To justify developing additional guidance for synthetic biology, clear examples of challenges that are not adequately addressed by the Guidance need to be identified (as noted by #7861, #7864, #7869, #7870, #7880, #7882, #7887, #7889, #7924). The majority of examples provided in this online discussion (#7866, #7880, #7889, #7920) indicate that gaps do not exist in current risk assessment approaches  for LMOs developed using current biotechnological methods (whether these are synthetic biology or not). Challenges for risk assessment associated with synthetic biology LMOs mentioned in this online discussion include availability of appropriate comparators (e.g. #7885, #7897) and uncertainty (e.g. #7887). However, these are included in Annex III (the basis of the Guidance), and they are not challenges specific to synthetic biology (as noted by #7887). Annex III prescribes a case-by-case approach and measures for reducing uncertainty including the provision of additional data (as noted by #7880) and risk management strategies and/or monitoring. Further, Annex III does not prescribe comparators that must be used nor preclude the flexible real-world approaches on a case-by-case basis described in #7897.

- There is a need to consider relevant applications
As pointed out in #7887, the majority of current and foreseeable synthetic biology applications involve LMOs in containment and not environmental releases. The example provided in this online discussion of farnesene-producing yeast (#7895, #7899) is produced by industrial fermentation. The ‘advance informed procedure’ of the Cartagena Protocol, which requires risk assessment (Arts 7, 10, 15), applies to LMOs to be introduced into the environment (Art 7(1)) and not contained uses of LMOs (Art 6). As pointed out in #7899, contained use is regulated according to domestic standards not Annex III.

Further, the point made in #7860 and #7866 that guidance should not be developed on the basis of speculative applications, or applications that are only conceptual now and unlikely to be released into the environment in the foreseeable future, support my comment above about developing guidance in the abstract.

In closing I support the comments of #7861 and #7890 in relation to there being no discussion or agreement amongst the Parties at SBSTTA that specific guidance for synthetic biology was necessary, and it is not clear from where the ‘green light’ for the AHTEG on Risk Assessment and Risk Management was derived. The SBSTTA document does call for a ‘coordinated approach’ between AHTEGs (pending adoption by the Parties at COP13). In my mind, a ‘coordinated approach’ would involve allowing registered participants of the synthetic biology online forum to contribute their views on this online discussion topic.

Kind regards,
Felicity Keiper

Dear all,

I sincerely thank all who have taken the time to share their views and knowledge with the forum.

With a few hours to go before the current on-line forum closes, I invite registered members to this forum who have remained silent, to share your views with everyone. I acknowledge that remaining silence does not equate to agreeing, yet your opinion has to be heard to be registered in the documents.

As moderator, again I pledge my commitment to transparency in reporting everyone´s views accurately when the invited sub-group on synthetic biology drafts the outline document to be presented to the AHTEG at the face to face meeting in Mexico City in July 2016.

Here are a few raw statics of the discussion of the last two weeks:  30 interventions were made from 18 countries (not all parties or representing governments) and 5 statements from representatives of civil society groups. 13 statements came from the Americas (Canada – Argentina, mostly from Brazil), 7 from Europe, 2 from Japan (same participant), 1 from Australia and 1 from Africa (Mauritania). Small developing countries or least developed countries where not represented in the forum. 

Key areas of discussions can be summarized as follows:

1. A minority of participants (4 /30) advocated for developing guidance for risk assessment for products of synthetic biology arguing that this was mandated. Others disagreed, especially delegates from Brazil. 

2. The vast majority of participants stated that there is no consensus on the definition of synthetic biology and a clear line cannot be drawn between modern biotechnology and synthetic biology

3. Likewise the majority stated that all products developed by modern biotechnology /synthetic biology to date are adequately covered by Annex III of the Cartagena Protocol and by the Roadmap.

4. Specific cases where no comparator exist to conduct a risk assessment were suggested but  not presented at this forum

5. No specific examples of synthetic biology products developed to date were presented at this forum posing  special challenges for risk assessment that are not covered by Anex III or other internationally accepted  risk assessment approaches.

As a general conclusion, the majority of participants are of the opinion that it is premature to develop alternative risk assessment guidance for products of synthetic biology, and that current approaches within and outside the Cartagena Protocol are adequate to date.

In the spirit of transparency and compromise and so  that we may go forward with our task, I  offer these preliminary conclusions to give participants the chance to correct or add other important points that were missed before the forum closes and address other areas of concern.

At this stage, before the wider sub-group discusses the results of this forum  for drafting the outline (to be discussed in July in Mexico City), I take full responsibility for any mistakes, omissions and misinterpretations on statements by participants. I apologize in  advance for any genuine mistake or misinterpretation. 

I wish you all a pleasant Sunday and warmly thank you again for your thoughtfulness, time  and effort in contributing to this forum. I am currently writing from Mexico and hope to see many of you in Cancun in 2016.

Maria Mercedes

Dear Participants

I would like to thank Maria Mercedes Roca for her excellent summary of the discussions to this point and also thank her for the invitation to those of us who have remained silent so far, to share our opinions with the group.  I have been following the discussions with great interest (though have only recently registered so that I am able to comment). 

I, like several others who have contributed to this discussion, was also a participant of the AHTEG on Synthetic Biology.  I have found this exchange of opinions among those participating in the Risk Assessment Online Forum to be very helpful.

I am among those who believe that no clear line can be drawn between modern biology and synthetic biology.  I am also of the opinion that it is premature to develop specific risk assessment guidance for synthetic biology at this time.  Nor can I think of an example of a product developed to date that would pose a special risk assessment challenge because it was developed using the tools and approaches of synthetic biology.

Sincerely,
Bob Friedman