Past Activities 2017-2018

POSTED ON BEHALF OF BENSON KINYAGIA
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Welcome to the fourth round of the forum discussions.

My name is Benson Kinyagia and I work in the Kenya National Commission for Science Technology and Innovation as a Principal Scientist in charge of Biodiversity and other Natural Resources and I am a lead expert in Environmental Impact Assessment and Environment Audit. I have been involved in development of legal frameworks to regulate GMOs and other aspects of modern biotechnology. I am in charge of the synthetic biology programme in Kenya and a member of the Ad Hoc Technical Expert Group on Synthetic Biology. My educational background is in Botany and Biosafety in Agriculture and Environment. My work experience is in Policy development in Biosciences and Natural Resources management. This topic of the discussion is drawn from the AHTEG terms of reference which specifies that the AHTEG in paragraph 1 (C) should “gather information on risk management measures, safe use and best practices for safe handling of organisms, components and products of synthetic biology;”

In the decision XIII/17, the Parties to the Convention noted that the general principles and methodologies for risk assessment under the Cartagena Protocol and existing biosafety frameworks provides 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. On the other hand, it should also be noted that there has been limited discussion so far under the CBD on if and how the general principles for existing risk management measures are also applicable to synthetic biology. The decision also encourages Parties in paragraph 9(c) to cooperate in “updating and adapting current methodologies for risk assessment of living modified organisms to organisms resulting from synthetic biology, as appropriate;” and Invites Parties to submit to the Executive Secretary in paragraph 10(c) “Experiences in conducting risk assessments of organisms, components and products of synthetic biology, including any challenges encountered, lessons learned and implications for risk assessment frameworks;” and in paragraph 10(d) “Examples of risk management and other measures that have been put in place to avoid or minimize the potential adverse effects of organisms, components and products of synthetic biology, including experiences of safe use and best practices for the safe handling of organisms developed through synthetic biology;”

The focus of this discussion is, therefore, on risk management, and safe handling and use of organisms, components and products of synthetic biology. While risk management measures are commonly used when referring to living organisms, it is also equally important to discuss measures for the safe handling and use of the components and products of synthetic biology (i.e. the non-living parts and outputs of synthetic biology). Furthermore, it is also important to focus the discussion on living organisms developed through synthetic biology that are intended for contained use as well as for intentional introduction into the environment.

To help focus the discussion, I would like to invite you to consider the following guiding questions in your interventions:

• To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?
• To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?
• Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?
• Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?
• What specific new areas of research are needed, if any, in order to ensure the safe use of current and near future applications of synthetic biology?

You are also welcome to submit guidelines and guidance on risk management measures that may be applicable to organisms, components and products of synthetic biology.

I invite you to take advantage of this last round of discussion to actively participate but kindly ask you to really stay within the topic, using the guiding questions above as much as possible, in order to facilitate the work of the AHTEG in an efficient and effective manner. I also urge participants to be clear, succinct and objective in your interventions.

Finally I value all your contributions in the previous three rounds of discussions and hope this final discussion will enrich our understanding and guide the AHTEG on the way forward.

Regards
Benson

Dear all participants

I would like congratulation Mr Benson Kinyagia for chairing the last issue of this forum. I know that many people have done good job previously and I want again push all of us to continue our challenge.

Jean Bruno Mikissa

I am a lawyer who has followed the development of the regulation of biotechnology since many decades. I am therefore familiar with the intricacies of interdisciplinary work and regret that the discussion rounds on SynBio as related to the Cartagena Protocol have attracted so few lawyers. After all, when it comes to define terms such as LMOs, risk assessment and risk management this is not only a matter of science (or of logic, dear Prof. Vogel) but also of law. Needless to say that a term defined by science can be very differently defined by law.  Against all logic the law can also make a thing that does not exist in reality feign the thing to exist.

Concerning the present topic I also welcome Mr. Benson Kinyagia to moderate the new discussion round. I however have some concerns if his restatement of the questions that shall be answered reflect well what - it appears to me - was asked by decision XIII/17. It seems what is demanded to study is both risk assessment and risk management. Maybe Mr. Kinyagia understands risk management to cover both assessment and management but this would not be in line with the internationally agreed terminology.

In any way I believe we are asked to first discuss if the current methodology of risk assessment must be enhanced because it heavily relies on the comparison of the modified organism with the parent organism and may need new rules and even tests that cope with the increasing artificiality of the new constructs. Concerning risk management it appears to me that it is too narrowly construed if we were only to look at adapting safety measures, as Mr. Kinyagia proposes. According to the international and domestic regulatory context risk management includes the weighing up of risks with other concerns, such as socio-economic ones, agricultural policy considerations, ethical concerns, etc. It would be good if this discussion round could be used to collect experiences and views from different countries and disciplines also in that regard.
I like to add that in my view Mr. Kinyagia is right in suggesting to including into the scope of our discussion also the safe handling of components and (non-living) products of SynBio. I believe even if these are not LMOs we should exchange views on whether the increasing trade in such parts poses any risks, and if so how this could be assessed and managed. One should be aware in comparative terms that the regulation of chemicals (such as by the EU REACH Regulation) focuses on the trade in substances, and only as a second concern on trade in complex products.

Coincidentally, just a few minutes before reading Mr Gerd Winter's comment (#8764), I looked up the CBD's definition of 'risk management' and found reference to it in COP VI/23 shown below:

[Definition of risk management linked to VI/23  annex, in footnote to introduction of the annex]
vii. “"risk analysis" refers to: (1) the assessment of the consequences of the introduction and of the likelihood of establishment of an alien species using science-based information (i.e., risk assessment), and (2) to the identification of measures that can be implemented to reduce or manage these risks (i.e., risk management), taking into account socio-economic and cultural considerations.

So the above seems to state that risk analysis implies both 1) assessment of the consequences of introduction and establishment of an alien species and 2) identification of measures to reduce or manage these risks (i.e., risk management), which includes their socio-economic & cultural considerations. 

So, shall we understand "risk management" to mean "risk analysis" (as defined above) in answering Questions 1,2 and 4 of Topic 4?

Prof. Winter considers a problem inherent to interdisciplinary discussions: the fallacy of equivocation [#8764]. Many participants in this forum may wrongly assume that everyone is attributing the same meaning to the terms discussed, especially those which seem self-defining. The discovery of distinct meanings for the same term may come as a surprise. It will also raise the question: which meaning should take priority? 

Lawyers will not hesitate to answer: the legal meaning. For policy implementation, they are correct. For policymaking, they are so wrong as to be not even wrong. Legal definitions can lie at the root of policy failure. Nevertheless, persistent lawyers will invoke stare decisis and intone that precedent be respected. They will deploy the art of rhetoric for which they can boast a comparative advantage. Foundational errors are thus preserved.

In earlier comments, I referenced the “Enlightenment Fallacy”, which is to believe that reason will be used in discourse to reveal reality, rather than to manipulate it [#8475 of Opening of Discussion in Topic 1 and #8732 of Opening of Discussion in Topic 3]. George Soros perceived the fallacy contemplating Big Oil’s role in climate change (2008). He coupled the Enlightenment Fallacy with the Post-Modern Fallacy, which is to believe that reality can be whatever one wishes. To the extent that a legal definition departs from reality, obeisance to precedent hazards the Post-Modern Fallacy. The outstanding example of this one-two punch is Article 2 of the CBD. Genetic resources are defined as material for the purposes of R&D and anyone who protests is urged to “move on” by an argument that reduces to stare decisis. N.B. Even legal scholars have ripped into the abuse of stare decisis (see, for example, Seidman 2013).

The topic at hand is risk which falls squarely within the domain of economics. Inasmuch as economics exhibits methodological imperialism (Hirsleifer 1985), an ingenue might think that her discipline would guide discussion and inform the decisions of the COP. For example, cognitive biases in perceiving risks are highly germane to assessment and management. The respective literature is so well tested that the psychologist Daniel Kahneman won the 2002 Nobel Memorial Prize in Economics for his pioneering work with Amos Tversky. Nevertheless, their insights are no where referenced, almost as if psychology and economics did not exist [#8475 of Opening of Discussion Topic 1]. 

I return to Prof. Winter’s opening paragraph in comment [#8764].  It laments the absence of lawyers in these discussions. Less represented than the lawyers are the economists. Of the 338 people in the list of participants, I believe that we the economists number just one. Our almost complete absence is remarkable inasmuch as the objectives of the CBD and the issues of risk are quintessentially economic. Whereas the explanation for the lawyers’ absence may be the impossibility of billable hours, the absence of economists cannot be so explained. Most economists are salaried in universities or public institutions. Why do they not find fertile ground in exploring the economics of the CBD and its protocols? I suggest that refereed publications are not enough. Impact factors matter. Economic research on policymaking is only fully recognized when it results in policy implementation. Perhaps sensing that economics will not resonate, economists desist shortly after they have tested the waters of the CBD. In other words, they heed their own advice of “sunk costs”.

As the Online Forum on Synthetic Biology comes to a close, one may ask: How do we make sense of it all? Dr. Roca has inveighed against “sanitized versions” in the official reports and I agree. Can one make sense of the diversity of opinions without sanitizing disagreements? An answer lies not in law or economics but biology, which is fitting. Theodosius Dobzhansky wrote “nothing in biology makes sense except in the light of evolution” (1973). The conceptual structure of that most famous title can serve us well. Similarly apropos is the opinion of Garrett Hardin that theory is a great compactor (1993, p. 103). Although synthesis can compact the postings in the light of theory, the question arises: which theory?

Inspired by the comments of Dr. Roca, I suggest that participants make sense of what was said in the light of his or her discipline. Any such endeavor will not duplicate the pending task of the Secretariat to issue an Official Synthesis of the online discussions. The  reason why is simple: the official syntheses are not written through any disciplinary lens whatsoever. In fact, they do not even synthesize, as that word is commonly understood. They laboriously classify comments and compile (Vogel et al, 2018. p. 387).

Below are titles suggested for anyone inclined to truly synthesize. They are confined to 15 words which complies with international standards for indexing bibliographic references:

“Unauthorized synthesis on the 2017 Online Discussion on Synthetic Biology: In the light of law”;
“Unauthorized synthesis on the 2017 Online Discussion on Synthetic Biology: In the light of economics”;
“Unauthorized synthesis on the 2017 Online Discussion on Synthetic Biology: In the light of linguistics”;
“Unauthorized synthesis on the 2017 Online Discussion on Synthetic Biology: In the light of evolution”.

Recognizing that definitions in a framework convention are NOT (repeat NOT) “non-negotiable” in a Rawlsian sense (1971), the most important synthesis may well be: 

“Unauthorized synthesis on the 2017 Online Discussion on Synthetic Biology: In the light of philosophy”.

I sincerely hope such syntheses will be attempted. Should publications eventuate, the delegates to the COP will be able to choose insights from wherever the most light shines.

Lastly, a warning about the bibliographic entries for the postings. The 2013 Online Discussion on Article 10 of the Nagoya Protocol is largely inaccessible. Only the last postings appear in the portal of the Secretariat (see, for example, https://absch.cbd.int/forums/art10_groups). The SEARCH key is also of no avail. Anyone interested in synthesizing the 2017 Online Discussion on Synthetic Biology would be well advised to download all the postings as well as the list of participants. Should the 2017 Online Discussion on Synthetic Biology suffer a fate similar to that of the 2013 Online Discussion on Article 10 of the Nagoya, bibliographic entries can end with “(postings on file with author)”.


Dobzhansky, Theodosius (1973). "Nothing in Biology Makes Sense Except in the Light of Evolution", American Biology Teacher,  35 (3): 125–129.

Hardin, Garrett (1993). Living Within Limits. New York: Oxford University Press.

Hirshleifer, Jack (1985). “The Expanding Domain of Economics”. American Economic Review, vol. 75, issue 6, 53-68.

Rawls, John (1971). A Theory of Justice. Cambridge: Harvard University Press.

Seidman, Louis Michael (2013). On Constitutional Disobedience, New York: Oxford University Press.

Soros, George (2008). The Crash of 2008 and What it Means: The New Paradigm for Financial Markets. New York: PUBLICAFFAIRS.

Vogel, Joseph Henry, Klaus Angerer, Manuel Ruiz Muller and Omar Oduardo-Sierra (2018). “Bounded Openness as the Global Multilateral Benefit-Sharing Mechanism for the Nagoya Protocol”. Pages 377-394 in Charles R. McManis and Burton Ong (eds) Routledge Handbook on Biodiversity and the Law. New York: Routledge.

Dear participants,

Congratulations to Mr Benson Kinyagia for moderating this important issue, I think it’s a wise decision of secretariat for his high rank in Kenya, skills and experience, representing also the African continent.

Although it's more complex than this I will try to follow the guiding questions:

• To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?

The most important in my view start with the conception of near, medium and even long term application of Symbio, to look only at the current state is a limitation that could be costly for biodiversity and the human health, an interesting approach in this regard can be found in Preparing for Future Products of Biotechnology http://www.nap.edu/24605 “The task of this committee was to look into the future and describe the possible products of biotechnology that will arise over the next 5–10 years” ….“Given the rapid (and often unforeseen) advances of the past 5–10 years, it is clear that making accurate predictions of what will be possible is a difficult task, but some trends are clear: there will be a profusion of new products that will in many cases be very different in terms of their type, scope, and complexity, and the number of actors who will be able to contribute to biotechnology will be even more diverse as engineering biology becomes more accessible. At the same time, there is increased public awareness (and in some cases controversy), and the regulatory agencies are faced with the challenge of balancing the many competing interests from industry, society, government, and academia.”
Therefore, generally speaking the current risk assessment and risk management and their tools must be complemented at least as a first step and updated later to face not only biosafety problems but also biosecurity issues (the combination of this related disciplines is known with the term of biorisk) In addition there is a parallel need of research and development of tools that cover possible new discoveries. On the other hand, current and recent standards and guidelines could help on voluntary bases if adopted or adapted. Governance strategies and plans should complement the efforts to work safely, to avoid escapes (accidental or intentional) mainly in the contention phase of research and event before.
“From a biorisk perspective, the ability to create de novo biological systems and organism with unknown and potentially harmful properties is a potential biosafety risk to the researcher, the community and the environment” Applied Biosafety Vol.18,No 4, 2013.
“The safe use of new biotechnology products requires rigorous, predictable, and transparent risk-analysis processes whose comprehensiveness, depth, and throughput mirror the scope, scale, complexity, and tempo of future biotechnology application” Preparing for Future Products of Biotechnology http://www.nap.edu/24605
There is not a proper risk management without risk assessment, it’s a part of it that we should see as a process  “To fulfill its objective, risk assessment entails, as appropriate…: A recommendation as to whether or not the risks are acceptable or manageable, including, where necessary, identification of strategies to manage these risks…” Annex III RISK ASSESSMENT Cartagena Protocol on Biosafety.
“The Protocol also requires Parties to adopt measures and strategies for preventing adverse effects and for managing and controlling risks identified by risk assessments” Risk Assessment and Risk Management   https://bch.cbd.int/protocol/cpb_art15.shtml
In principle, in order to protect the environment, the challenges constituted by the potential of SB organisms and products resulting from synthetic biology for damage to biodiversity and human health should be subjected to risk assessments process from the very beginning of the research design itself, to make decisions at early stage, as a prerequisite for approval regardless of their intended peaceful use, current risk management measures and best practices that are in use for “traditional” LMOs are currently useful to cover a wide range of cases, perhaps most cases, for the time being, an issue that need more research an evaluation but less likely for the near future applications of synthetic biology.
“For example, one SB application currently under development, “cyberplasm” converges synthetic biology, biomimicry, nanotechnology, and robotics to construct a micro-scale robot designed to be capable of sensing environmental chemicals for remediating purposes (Voigt 2012). It has been proposed for use in detecting and treating pathogens within plants and animals in situ. Cyberplasm is a biohybrid that integrates engineered bacteria, yeast, and mammalian cells to undertake device-like functions modeled after the sea lamprey. It is expected to be in full development with a functional prototype by 2017” A decision analytic model to guide early-stage government regulatory action: Applications for synthetic biology by B. Trump et al. Regulatory action: Synthetic biology, 2017 John Wiley & Sons Australia, Ltd
In this sense and in advance, a group of researchers have developed a multi-criteria decision analysis model (MCDA) “this investigation of policy options for the future governance of cyberplasm is just one example of the benefit of MCDA as an option to inform initiatives of early-stage governance of technologies while they are still in pre-production. SB technologies, nanotechnologies, and other revolutionary technological applications are being developed at a frenetic pace” A decision analytic model to guide early-stage government regulatory action: Applications for synthetic biology by B. Trump et al. Regulatory action: Synthetic biology, 2017 John Wiley & Sons Australia, Ltd

• To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?

The above approach basically applies also to this issue with the differences that products and components are not covered by the Cartagena Protocol but for the CBD. Nevertheless in my view we should not separate, as a rule, agents, components and parts in a wider risk assessment with an holistic approach including among others ecosystems (..a dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. CBD)

• Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?

Part of the answer is reflected in the framework of the first guiding question and also depends on risk assessment with a holistic approach.
“The International Risk Governance Council (IRGC) has recommended that when risk problems involve high uncertainty and ambiguity, processes limited to traditional agency and expert-driven risk analysis based on quantitative data will not suffice (International Risk Governance Council [IRGC] 2006, 2015). If there is a high degree of uncertainty, hazard criteria of reversibility, persistence, and ubiquity should be considered. Also, risk management should include more cautionary approaches, such as close monitoring, small steps in introducing the hazard, strict containment, and systems that can absorb or tolerate surprises and that are resilient, flexible, and adaptive” A decision analytic model to guide early-stage government regulatory action: Applications for synthetic biology by B. Trump et al. Regulatory action: Synthetic biology, 2017 John Wiley & Sons Australia, Ltd
The strategies and plans for the governance should allow regulators and authorities to have additional or intrinsic tools and prerogatives (legally binding) to manage different scenarios at the light of new developments, accidents or incidents, reports of a follow up, not safe facilities in their level of biosafety for instance a not certify facility, mainly BSL-3 facilities, reports of negative effects on biodiversity during contained use, production scales, or during the release (if approved). For instance an umbrella provision “Notwithstanding the provisions of this Regulation, the National Biosafety Centre for exceptional reasons of security and taking into account the particular conditions of each facility may demand compliance with specific requirements in the process of risk assessment for granting the authorization. These requirements must be detailed in the conditions of validity of such authorizations” Resolution 103/2002: REGULATION FOR THE ESTABLISHMENT OF REQUIREMENTS AND BIOSAFETY PROCEDURES IN THE FACILITIES ....(Design Requirements, Procedures and Equipments in Facilities. Biosafety levels from low to high scales. This and other related resolutions are under the framework of the Cuban DECREE LAW No. 190 OF BIOLOGICAL SAFETY, January 28, 1999.

• Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?

Here again we face the limitation regarding time frame as explained in previous thoughts and here again apply some of the previous opinions.
Schmidt et al. contend that SB requires “new methods of risk assessment to decide whether a new SB technique […] is safe enough (for human health, animals and the environment) for the use in restricted and/or less restricted environments” (2009, p.178)  “While many effective governance structures for managing technological developments are currently in place around the world, there may be a need to evolve and forecast governance actions because of the revolutionary nature of SB technologies like cyberplasm” A decision analytic model to guide early-stage government regulatory action: Applications for synthetic biology by B. Trump et al. Regulatory action: Synthetic biology, 2017 John Wiley & Sons Australia, Ltd. In this specific paper, as an example and due to the nature and complexity of this discovery the current risk management measures may not be enough and should be complemented with other measures and tools. “As engineered microorganisms such as cyberplasm are envisioned to be biohybrids, it is likely that such technologies will “belong in a different risk category….. and will not fit risk assessment approaches for living, genetically engineered, or other organisms where risks associated with gene flow and invasiveness are of concern”

• What specific new areas of research are needed, if any, in order to ensure the safe use of current and near future applications of synthetic biology?

The areas of research in Synbio are as much as different disciplines complementing this multidisciplinary emerging technology, any advance resulting of research is useful to understand better its potentials including the issue of safe use.
In January 2014 a workshops brought together synthetic biologists, evolutionary biologists, ecologists, environmental scientists, and social scientists as well as representatives from government, the private sector, academia, environmental organizations and think tanks that identified:
Priorities Research Areas which are in my view reasonable and indicatives, I mean perhaps not exhaustive.
“Workshop participants identified the following areas as hurdles to understanding the potential ecological effects associated with the release of organisms modified using synthetic biology.
1) Comparators:
2) Phenotypic characterization
3) Fitness, genetic stability, and lateral gene transfer
4) Control of organismal traits
5) Monitoring and surveillance:
6) Modeling:
7) Standardization of methods and data: What research is needed in order to standardize testing methods, data reporting, and organism characterization for ecological evaluations? How should data collection and integration be handled? Who is responsible for developing, promoting, and enforcing standards? ”
SYNTHETIC BIOLOGY PROJECT / CREATING A RESEARCH AGENDA FOR THE ECOLOGICAL IMPLICATIONS OF SYNTHETIC BIOLOGY.  SYNBIO 7/May 2014  http://www.synbioproject.org
I would like to add one more as a priority research area: 8) The issue of Protocells.

• You are also welcome to submit guidelines and guidance on risk management measures that may be applicable to organisms, components and products of synthetic biology.

• NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (April 2016) http://www.osp.od.nih.gov/
• Canadian Biosafety Standard, Second Edition, 2015
http://canadianbiosafetystandards.collaboration.gc.ca/
• Laboratory biorisk management standard CWA 15793:2008
• Laboratory biorisk management CWA 16393 January 2012
Guidelines for the implementation of CWA 15793:2008
• Risk management ― Risk assessment techniques ISO/IEC 31010: 2015`
• NC 1134:2016 (GESTIÓN DEL RIESGO BIOLÓGICO EN LOS LABORATORIOS (EN-CWA 15793: 2011, MOD) Laboratory Biorisk Management Standard. (Spanish) http://www.nc.cubaindustria.cu
• NC 1135: 2016 (GESTIÓN DEL RIESGO BIOLÓGICO EN EL LABORATORIO— GUÍA PARA LA APLICACIÓN DE LA NC 1134: 2016 (EN-CWA 16393: 2012, MOD) Laboratory Biorisk Management ― Guidelines for the implementation of the NC 1134: 2016. (Spanish) http://www.nc.cubaindustria.cu
• LINEAMIENTOS PARA LA GESTIÓN DE RIESGO BIOLÓGICO. (AMEXBIO_LGRB:2016. ASOCIACIÓN MEXICANA DE BIOSEGURIDAD AC. http://www.amexbio.mex (Spanish)
• NC-ISO 31000: 2015  GESTIÓN DEL RIESGO — PRINCIPIOS Y DIRECTRICES  (ISO 31000: 2009, IDT) Risk management — Principles and guidelines (Spanish) http://www.nc.cubaindustria.cu
• NC-ISO/IEC 31010: 2015  GESTIÓN DEL RIESGO - TÉCNICAS DE APRECIACIÓN DEL RIESGO (ISO/IEC 31010: 2009, IDT) Risk management ― Risk assessment techniques (Spanish)   http://www.nc.cubaindustria.cu
• Summary and Comparative Analysis of Nine National Approaches to Ecological Risk Assessment of Living Modified Organisms in the Context of the Cartagena Protocol on Biosafety, Annex III. cbd biosafety technical series 02,  2012 by the Secretariat for the Convention on Biological Diversity All rights reserved. Published 2012 


Respectfully,
Dr Lazaro Regalado

POSTED ON BEHALF OF MARIA MERCEDES ROCA
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Dear participants,

My thanks and appreciation to Mr Benson Kinyagia for moderating this third round:

• To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?

Lacking the flair and erudition of Prof. Vogel’s postings, not being a native English speaker and not being a lawyer or economist, but a humble biologist (virologist/plant trained in risk analysis by economists), I strongly support Prof. Vogel’s repeated sensible statements. He warns us and calls for caution and not charging ahead with given tasks  -- to tick them as “done” and for presenting documents at the next COP/MOP -- without stopping first and assessing the flaws in our process and our discussions.  My husband is a risk analysist economist and I often have discussions on these topics with him, thus I sympathize with Profs. Winter and Vogel’s sentiments about the lack of economists and lawyers in these discussions. Ultimately, our discussion will shape legally binding policy and will affect the economies and biodiversity in our countries.

As many postings remind us, definitions matter a great deal and legal definitions have profound impacts on policy.  What comes out of these specific discussions will eventually become policy on synthetic biology and will affect many stakeholders, including our public research institutions, local universities and small start-up biotech companies – driven mainly by our young biotechnologists.  In our developing countries, they are currently mainly students or new graduates, but will soon become the future drivers of these technologies, needed to face the many challenges of the environment, energy, agriculture and food production, human health and the bio-industry of the 21st century. We need new technologies and new paradigms for our very troubled planet, plagued by overpopulation, climate change (and also terrible earthquakes in Mexico, from where I write). 

We are no longer just regulating the big and powerful agricultural companies, like we did in the era of “traditional LMOs”. The stakes are even higher this time, and we cannot afford to make the same mistakes of the past for policy development.

This is especially true for least developed countries that may not have the local expertise to develop their own policies on synthetic biology (whatever we mean by it), as industrialized countries - especially the European Union and non-parties, have the luxury of doing. Dr. Lazaro Regalado (# 8768) reminds us that “the Protocol requires Parties to adopt measures and strategies for …”. In other words, once contentious and politically volatile issues are discussed in these fora (with many biases), and documents are presented and approved at COP-MOPs, these issues become policy that may be costly,  difficult, if not impossible to undo,  when not crafted correctly.

We may follow the same tortuous path we did with risk assessment and risk management for  “traditional LMOs” and are in danger of making the same mistakes in failing to craft coherent and effective policy for synthetic biology.  To illustrate this point, parties at MOP 8 in Cancun (mainly developing countries in Latin America and non-parties with ample experience in “traditional LMOs”), did not endorse the official Risk Assessment and Risk Management Guidance.  The AHTEG “wasted” valuable years and resources when the Guidance was not adopted by parties. Many developing countries still have no internationally approved guidance on how to conduct risk assessment on “traditional LMOs”. We are now discussing how to conduct risk assessment and monitoring for “living organisms developed through current and near future applications of synthetic biology”.  We have not resolved the first issue of “traditional LMOs”, yet continue to discuss a second and more complex issue.

Policy has deep repercussions in countries’ economies as they adopt -  or fail to adopt - “risky” or “useful” technologies.  The perception of risk, or usefulness, of a given technology, is a biased (and risky!) process.   Economists will also remind us of the risk and cost of inaction and of maintaining the status quo. To illustrate with an example: spraying plant insect pests and human vectors of diseases like malaria,  dengue and Zika  with insecticides in the tropics, may harm biodiversity than using GM technologies. 
Starting with flawed paradigms regarding the biased perception of risk,  precaution, justice or fairness and flawed definitions based on these biased perceptions, have led to rather incoherent and inoperative biosafety systems in developing countries in my region (Central America and Andean countries). Indeed,   biased principles such as the Precautionary Principle and the Precautionary Approach,  so often invoked as absolute truth in these discussions (in my humble view, a very Eurocentric principle for these discussions)  are now widely applied in developing countries with widely different interpretations and shaping policy in unexpected ways.
To illustrate this point, Perú has moratoria on the use of all GM crops until 2020  (please correct me If I am wrong on the date) and  Ecuador has an explicit prohibition in its constitution to use all  Genetically Modified Organisms  “that are hazardous to human health and the environment”.  Furthermore,  Article 401 of the Republic of Ecuador’s  Constitution  “ …declara al Ecuador libre de cultivos y semillas transgénicas y prevé que, excepcionalmente, y solo en caso de interés nacional debidamente fundamentado por la Presidencia de la República y aprobado por la Asamblea Nacional, se podrán introducir semillas y cultivos genéticamente modificados”. Bolivia, on the other hand, allows commercial GM soy planting, but prohibits GM maize planting, yet imports GM maize grain for food processing from neighboring Argentina and Brazil that have no prohibitions on these two GM crops.   A similar situation occurs between the US and Mexico, where Mexico imports GM maize grain for food and feed  but bans its cultivation.

Many farmers in countries where the technology is prohibited, simply plant some of this illegal GM  seed (illegal in their countries, but legal in neighboring countries), to benefit from better technology and to be competitive.  Governments of countries in Central and South America are put in a very awkward and difficult legal situation, especially when it comes to monitoring and management illegal planting. Complying with these monitoring requirements and surveying  these illegal plantings has now become a huge economic and legal  burden for them,  as they are required by law to deal with these issues, yet they (silently)  acknowledge that the technology is beneficial for their farmers, as it is for farmers of the neighboring countries where the technology is legal.  Resources are limited and problems abound in developing countries that need to monitor real hazardous problems like pests, diseases and pathogens that threaten human, animal and plant health. Countries in other more temperate latitudes where soy and maize are not planted or are not a backbone of an economy based on agriculture and farming,  can afford to have very stringent biosafety policies regarding monitoring of traditional LMOs.
By comparison, countries that have legally approved GM crops are benefiting their farmers and often the environment too, by the use of these new agricultural  technologies. 

http://nepad-abne.net/wp-content/uploads/2015/10/B4FA-Analyses-FINAL.pdf
Analyses: Africa’s future ...can biosciences contribute? Essays compiled by Patrick Mitton and David Bennett, St Edmund’s College, Cambridge,  2015
ISBN 978-0-9932932-3-8.

I fully recognize that many of my statements are biased, as I am a professional in agriculture and an academic working with biotechnology students.  As humans, we all have agendas and we all have biases, so I humbly recognize mine. We need to agree on these issues and it is very hard to do so. Let us hope and respectfully request that the reporting of these discussions is transparent and what is presented at COP14-MOP9, reflects these biases, the lack of consensus and the lack of input from lawyers and economists.

Best regards to all,

Maria

Dear All

I would like to introduce a Testbiotech report which I co-authored. It discusses the risks of organisms that are genetically engineered using SynBIo methods, such as CRISPR-Cas9. In interested please visit http://www.testbiotech.org/node/2078, or let me know if I should send it.

After analysing recent literature for this report, we concluded that current methods of risk assessment for genetically engineered organisms in the EU (and elsewhere) are to some extent inadequate for dealing with these organisms.

For example, new methods such as -omics technologies (transcriptomics, proteomics, metabolomics and the like) would be needed to detect relevant biological effects. As yet, these kind of  data are not requested by the EU for the risk assessment of genetically engineered organisms. Other problems concern changes in the microbiomes of fungi, plants and animals. Disturbances or interruptions of the biological communication networks within the ecosystems are also relevant. These hazards are, as yet, not considered in mandatory risk assessments as established in the EU and elsewhere.

In general, it can be more difficult to detect unintended effects in organisms derived from gene-editing than in those derived from transgenic plants. Thus, we have to strengthen the precautionary principle and work towards assessing the risks properly.

Whatever the case, we should define clear cut-off criteria to prevent releases of organisms that cannot be controlled in their spatio-temporal aspects or can not be assessed properly due to current limits of knowledge

With kind regards

Christoph Then

Dear participants my greetings to all of you;

First of all I would like to thanks Maria Mercedes Roca for their comments and her will to  participate in this online forum even in a moment of sadness and pain due to the earthquakes in Mexico. My solidarity with the Mexican people and my sorrow for the victims.

Mexico has an strong biosafety association (Amexbio:  http://www.amexbio.mex ) and a Bulletin  of the Academy of Sciences (The Number 55 was dedicated to the gene editing) Boletín informativo de la Academia Mexicana de Ciencias. Edición genética con la técnica CRISPR/Cas9 No 55 / Mayo 2016. Regarding our task about the issue of risk management Amexbio in 2016 adapted the Laboratory biorisk management standard CWA 15793:2008 in to a Guideline (LINEAMIENTOS PARA LA GESTIÓN DE RIESGO BIOLÓGICO. (AMEXBIO_LGRB:2016. ASOCIACIÓN MEXICANA DE BIOSEGURIDAD AC. http://www.amexbio.mex

The history of this standard goes back to 2007 with its first draft emerged in Europe, after a wide participation of experts was adopted as an agreement and ratified in 2011, later adopted by Spain as a Standard and also by Cuba and Mexico…., a tool of the traditional biosafety that now unites this discipline with biosecurity to treat risks and their management in a more comprehensive way, is very useful as a complement to the risk analysis and risk management, endorsed and supported by the International Federation of Biosafety Association (IFBA) should soon become an ISO Standard, an example, not always found, of how the less advanced countries can benefit from common knowledge in order to protect the laboratory workers, the environment and consequently the biodiversity.

Best regards,
Dr Lázaro Regalado

Many thanks to Dr. Benson Kinyagia for chairing the session and to the Secretariat for affording this opportunity to participate.

Already we have multiple posts that have attempted to change the subject, and although I prefer to address the topic we have been given, I do have to take a moment to point out that the risk assessment paradigm used for LMOs is robust, and adequate to assess the risks of other organisms that might be developed using whatever we define as "synthetic biology methods." 
 
Regarding the suggestion in post #8770 that organisms produced using CRISPR-Cas9 techniques (which may or may not be considered “Synthetic Biology” depending on the nature of the resulting organism and the definition being applied) require the use of omics technologies for risk assessment; I think this is false.  It defies reason that we can adequately assess the risks of an organisms that has been bombarded with x-rays or other forms of radiation to produce thousands of genomic aberrations without these technologies, but if we make a single planned change for a known purpose then we must conduct a proteomic/genomic/transcriptomic analysis.  Like many such suggestions, it fails to consider the context for the assessment or the experience we have in conducting assessments for living things (LMOs or otherwise).  It also confuses the nature of risk assessment, framing it as an investigation into every facet of the new organisms rather than a focused look at potential sources of harm. 

"To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?"

The most frequent risk management measure for “traditional” LMOs is containment – during research and development and prior to regulatory authorization.  These measures are informed by our knowledge of how living things (or infectious agents in the case of viruses) move, spread and replicate in the environment.  I am not aware of any product of synthetic biology that would be expected to require containment measures that are unlike any organism with which we have previous experience.  So management measures currently in practice – for LMOs as well as any other organism which requires containment – should be sufficient to contain organisms resulting from synthetic biology.

Other risk management measures depend on the type of risk being managed, and must continue to be identified on a case by case basis.  However, I have not yet heard any example of an organism developed through synthetic biology that poses risks that are of a completely alien nature to the types of risks posed by organisms with which we already have experience. 

"To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?"

The handling of chemical substances is well understood, regardless of the way the chemical is produced.  Chemical safety is a mature field, and I am not aware of any developments in synthetic biology which suggest chemical products will be outside the range of our experience with other chemicals.  As far as the safe handling of DNA molecules and component parts of synthetic biology, these are either organisms which can be managed as organisms (based on our prior extensive experience in managing organisms), or else they are inert molecules that don’t pose any risk in and of themselves. 

"Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?"

Safety measures are constantly being adapted to fit case specific circumstances.  This will continue in all cases, as well as for cases involving synthetic biology.  However, I don’t anticipate that specific safety measures will need to be adapted for “synthetic biology.”

"Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?"

No, I cannot. 

"What specific new areas of research are needed, if any, in order to ensure the safe use of current and near future applications of synthetic biology?"

I would never oppose research of any sort, and there are many areas of investigation that might prove useful for facilitating risk assessments in the future.  However, I am not aware of any area of research that would broadly benefit future safe use of synthetic biology applications, nor am I aware of any specific knowledge gap that must necessarily be addressed prior to risk assessment.

I would like to make one final point. I am grateful to the Secretariat for conducting this series of online discussions, and I sincerely believe that they have provided a valuable contribution to ongoing dialogue around emerging technologies.  However, I think one of the clearest messages that can be gleaned is that “synthetic biology” is not particularly useful as a way of meaningfully categorizing risks that an organism might pose.  The different types of organisms that might be produced using synthetic biology run the gamut from microbes to plants, to insects, and these organisms having nothing in common in respect to the way they interact with the environment and biodiversity.  The fact that they may be grouped together as “produced through synthetic biology” is not very informative for risk assessment or risk management, to the point where it is essentially meaningless.  Case by case assessment based on the nature of the organism and its intended use will continue to be the only way to assess risks from organisms.  This is not a new conclusion, but it is frequently overlooked in the rush to categorize things for convenience.

Dear Colleagues,
First of all, congratulations to Benson for moderating the discussion on this very important topic that is of particular relevance for our work on synthetic biology.
Regarding the questions asked I think that most current and near future applications of synthetic biology will be relatively well covered by the risk assessment and management methodologies developed for traditional LMOs. Some modifications might be necessary to account for the specific properties of some groups of organism.
To the best of my knowledge most current applications of synthetic biology involve fermentation like cultivation of microorganisms under contained conditions in order to produce different chemical compounds. Those products, at least on EU level, will be covered by the pretty extensive existing legislation on chemicals, plant protection products, food additives, medicinal products, etc.
Dr Regalado (#8768) raised an important question related to biosecurity, the prevention of criminal or malicious use of synthetic biology. This is a problem related other technologies as well and probably is better addressed at forums dealing with criminal and public order tissues as they have the necessary competence.
A specific area that may require further work is related to those technologies that are specifically aim to have effect on natural populations such as gene drives. Those effects can be beneficial (e.g. eradication of invasive alien species, making organisms insusceptible to pathogens, etc.) or harmful (e.g. uncontrolled spread of the drive and eradication of non-target population of target species or of non-target species, removal of food base for non-target organisms, etc.) and their scale will vary depending on the particular populations and organisms targeted. Majority gene drive systems currently considered involve creation of LMO (those utilizing naturally occurring inheritable microorganisms, such as Wolbachia or balanced chromosomal translocation might be exceptions) and thus fall under the scope of the Cartagena Protocol. It is also notable that once released into the environment the organisms containing gene drives are expected to be very hard to control or remove and can affect biological diversity beyond national boundaries or the populations originally targeted.
To the best of my knowledge no guidance documents which specifically address risk assessment of organisms that contain gene drives are available at present. The necessity of broad (international) cooperation when assessing the risks for the environment from gene drives in order to realize their potential benefits while adequately managing the risks has been noted by the leading scientists in the field, learned societies, national political bodies and scientific advisory committees (e.g. Akbari et al. 2015; NASEM, 2016; Norwegian Biotechnology Board Statement 2017; UK House of Lords Report 2015).
References
Akbari, O.S., Bellen, H.J., Bier, E., Bullock, S.L., Burt, A., Church, G.M., Cook, K.R., Duchek, P., Edwards, O.R., Esvelt, K.M. and Gantz, V.M., 2015. Safeguarding gene drive experiments in the laboratory. Science, 349(6251), pp.927-929.
Champer, J., Buchman, A. and Akbari, O.S., 2016. Cheating evolution: engineering gene drives to manipulate the fate of wild populations. Nature reviews. Genetics, 17(3), pp.146-159.
National Academies of Sciences, Engineering, and Medicine, 2016. Gene drives on the horizon: advancing science, navigating uncertainty, and aligning research with public values. National Academies Press.
The Norwegian Biotechnology Advisory Statement on Gene Drives, 2017. http://www.bioteknologiradet.no/filarkiv/2017/02/Statement-on-gene-drives.pdf
House of Lords Report on Genetically modified Insects, 2015. http://www.parliament.uk/genetically-modified-insects

Dear all

I fully agree   with the post (#8772), personnaly I think that the discussion is very usefull and we can go ahead.

Dear colleagues--

I would like to add my thanks to Benson Kinyagia for moderating this final session of the online forum.  My guess is that the reason many of us have been slower to contribute to this session is that so much on this topic has already been discussed during the previous three sessions of the online forum.  The COP’s request was to “gather information on risk management measures, safe use, and best practices for safe handling of organisms, components, and products of synthetic biology”.  By my informal count, views relevant to the topic have been raised over 100 times during our online discussions so far, both directly as “risk management” and under the closely related topics of “governance” and “regulation” of synthetic biology.

I will start by addressing the issue raised by Nikolay Tzvetkov [#8773]: the need for guidance documents that specifically address organisms that contain gene drives. I agree that this is one of the few areas where additional guidance is needed, but would like to point out that much work is already underway.  In a recent Correspondence in Nature Biotechnology, 32 coauthors and I reviewed existing guidance documents for research on, and testing of, genetically engineered insects (including guidance by regional and international institutions, such as the CBD and World Health Organization).  Most of these documents addressed earlier generations of the technology; several directly addressed gene drives.  http://www.nature.com/nbt/journal/v35/n8/full/nbt.3926.html (I have attached a copy for those who do not have access to this journal.)  We identify what we believe are the most important guidance gaps that need to be filled.  But more important, much of this work is already underway.  One key example: the 2014 “Guidance Framework for Testing Genetically Modified Mosquitos” developed by WHO and the Foundation for the NIH (FNIH) is in process of being updated by FNIH to include insects modified with gene drives. 

Lazaro Regalado [#8768] discusses another useful document, the recent US National Academy of Sciences 2017 report, “Preparing for Future Products of Biotechnology”.  The report reviews the biotechnology products already on the market, under development, and on the horizon.  It then reviews the current US regulatory system and suggests “opportunities for enhancement”.  The report was requested by the US government as part of an effort started in 2015 to modernize the US regulatory system for biotechnology.  Again, the important point is that work is ongoing within the US agencies to ensure that our regulatory system can adequately handle future products developed using synthetic biology methods.

During the previous sessions, several others pointed out activities within their countries to review developing biotechnologies and anticipate potential governance challenges.  Boet Glandorf and Jaco Westra [#8439] describe activities in the Netherlands to anticipate environmental and safety challenges and reference several excellent reports.  Joyce Tait [#8641], representing the UK Synthetic Biology Leadership Council, includes activities in the UK to devise governance approaches that are proportionate and appropriate for next generation biotechnologies.

Directly answering one of Benson’s guiding questions: “Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?”  I am certain that there will be some future developments that will require new approaches.  However, I think the more important question is whether our governance systems are anticipating and able to adapt to new developments.  I see that happening in many countries around the world.  Other participants in this online forum can, no doubt, provide additional specific examples.

Best regards to all,
Bob Friedman

Dear participants,

I thank Dr. Regalado for his kind words of support for the earthquake victims in Mexico, and I join with words of solidarity for the hurricane victims in the Caribbean and Southern US. With such calamities affecting our planet and the impact on human health and biodiversity, we should take a fresh look where our priorities are in devoting our government effort, time and resources, especially in developing countries. 

Should we devote time and resources to monitor the spread of known harmful human, animal and plant pathogens, or to monitor the spread of possibly hazardous LMOs?  The monitoring technologies are similar for pathogens or for  LMOs.

Dr.Regalado rightly refers to the excellent work of AMEXBIO, the Asociaci[on Mexicana de Biosaguridad (Mexican Biosafety Association). We have had the privilege of working closely with AMEXBIO and have contributed with two risk assessment courses for their members, including one on Genetically Modified Microorganisms and Genetically Modified Mosquitoes,  as well as issues of biosecurity (biorisk).  In these courses ( the last course was in June 2017) we introduced the  concept of Integrated Biosafety Management (assessing the risk of biological organisms) inspired on both  the agricultural concept of “Integrated Crop Management”  the “One Health” concept: 

“One Health is the integrative effort of multiple disciplines working locally, nationally, and globally to attain optimal health for people, animals, and the environment. Together, the three make up the One Health triad, and the health of each is inextricably connected to the others in the triad.One Health - It's all connected”
https://www.avma.org/KB/Resources/Reference/Pages/One-Health.aspx

In other words, biosafety experts should be able to apply the same principles of risk assessment to any hazardous biological organism (GMO, or conventional organism). This is an interesting concept developed by Dr.Paul Keese from Australia and a former RA & RM AHTEG member.

As training material for these AMEXBIO courses, we have used an Environmental Risk Assessment Guide for GMOS, developed by independent risk analysts from Latin America and the USA. This ERA Guide was presented in draft form at the International Symposium for Biosafety of GMOs,  held in Guadalajara, Mexico in June 2017 and organized by the International  Society for Biosafety Research (ISBR). This guide is an English version of the first edition of an ERA Guide for GMOs published in Spanish in 2012.  The second  English edition includes sections on risk assessment of products developed with new molecular biology techniques with a  synthetic biology approach. The Guide also includes a comprehensive glossary of terms used in synthetic biology in English, Spanish and Portuguese.   It also draws on the fact that the internationally accepted general principles of risk assessment applied to  “traditional GMOs”, can also be applied to assess the risk of pathogens and other biological organisms, depending on the context.

Best regards,

Maria

Many thanks to Benson for moderating this discussion and to participants for the contributions made so far. I would like to briefly address the questions outlined in the opening post.

• To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?

I agree with previous posts in current and near-future applications of synthetic biology being generally well-covered by current risk management measures and practices.


• To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?

It appears to me that current measures and practices related to chemical compounds are sufficient for components and products of synthetic biology.


• Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?

In the longer term, it may become difficult to identify suitable comparator species for risk assessment of prospective heavily redesigned or fully synthetic LMOs. I suggest that this challenge be addressed by performing risk assessment on a case-by-case basis according to the traits of the prospective LMO, not based on its relationship to comparators.


• Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?

Physical, physiological, and genetic containment are effective safety measures for any LMO not destined for release into the environment. However, I am not convinced current risk assessment and management strategies are sufficient for LMOs designed to interact with and modify existing ecosystems. As exemplified by gene drives [#8773,8775], such applications already exist.


• What specific new areas of research are needed, if any, in order to ensure the safe use of current and near future applications of synthetic biology?

While some ongoing efforts are aiming at predicting the ecological impact of gene drives and related LMOs destined for environmental release, our understanding remains rudimentary, particularly in the intermediate and long term. I would welcome more research at the interface of synthetic biology and ecology, specifically targeted at the potential roles of gene transfer, direct competition, and habitat modification in interaction between LMOs and other species.


Dr Christian R. Boehm

Hello again everyone.  My name is Jenna Shinen and I am the Life Sciences Specialist in the in the Office of Conservation and Water, at the U.S. Department of State.  I’d like to thank all of the moderators for their work, the thoughtful comments of the other participants in the forum discussions, and the opportunity to share U.S. views and practices on risk management measures.

The United States believes that regulation and oversight of emerging technologies should provide for the safe handling of organisms, protecting safety, health, and the environment while avoiding unjustifiable barriers to innovation, stigmatization of new technologies, or creation of trade barriers.  In our view, regulation and oversight should be based on the best available scientific evidence, and with an awareness of the potential benefits and costs of such regulation and oversight.  We consider that any measures taken should have sufficient flexibility to continually accommodate new knowledge, taking into account the evolving nature of emerging biotechnologies and their applications.

The United States has a coordinated, risk-based system to protect the environment and human and animal health, to assess and manage any potential health and environmental risks posed by biotechnology products, and to ensure biotechnology products are safe for the environment, health, research, production, and trade.  This system facilitates oversight of planned introductions of biotechnology products into the environment and focuses on the characteristics of the biotechnology product, the environment into which it will be introduced, and the application of the product – not the process by which the product is developed. 

The United States believes that transparency in decision making and public dissemination of methodologies used to develop and finalize decisions, are essential to the development and review of national risk assessment efforts.  The United States has a transparent, robust, practical, science-based approach to enable the safe use of organisms for a variety of applications from education, research, medical fields, food production, crop production, and animal husbandry.  This approach embraces the spectrum of tools common to regulatory frameworks, ranging from guidance for best practices, laws that set standards for product attributes, and regulations for specific activities and uses.  The United States has mechanisms in place to ensure safety as well as to detect and monitor adverse health outcomes for humans, plants, animals, and the environment.  We encourage sharing of these best practices.

Established as a formal policy in 1986 under the auspices of the Office of Science and Technology Policy (OSTP) in the Executive Office of the President, the Coordinated Framework for Regulation of Biotechnology describes the federal system for evaluating the safety of products developed using modern biotechnology (https://www.aphis.usda.gov/brs/fedregister/coordinated_framework.pdf).  For example, in the case of genetically engineered plants, the U.S. agencies primarily responsible for oversight of the products of agricultural biological engineering include the Environmental Protection Agency (EPA), the Department of Agriculture's Animal and Plant Health Inspection Service (USDA-APHIS), and the Department of Health and Human Services’ Food and Drug Administration (FDA).  To consider another example, FDA’s regulations for pharmaceutical approvals apply in the case of using genetically engineered microorganisms to produce recombinant human insulin – a product of biotechnology that was first licensed in 1980.

The EPA uses the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) to regulate the distribution, sale, use and testing of pesticidal substances including microorganisms and those plant-incorporated protectants produced in plants.  The EPA uses the Toxic Substances Control Act (TSCA) to oversee the production, importation, and use of microorganisms that are products of biological engineering, prior to commercialization of such organisms, including approval of research projects that intend to release engineered microorganisms into the environment.  New chemical substances that result from biological engineering are also subject to review under related provisions of TSCA.

USDA-APHIS addresses the protection of plant and animal health under several laws, and these laws enable protection regardless of which biological engineering techniques are used.  Directly applicable laws under which APHIS protects plant and animal health are the Plant Protection Act, the Animal Health Protection Act, and the Virus Serum Toxin Act.

The FDA is responsible for ensuring the safety and proper labeling of human and animal foods, with the exception of edible meat and poultry, and processed egg products for human consumption, which fall under the authority of USDA.  All foods, whether imported or domestic, and including those derived from biological engineering techniques, must meet the same rigorous safety standards.  Under the Federal Food, Drug, and Cosmetic Act, it is the responsibility of human and animal food manufacturers to ensure that the products they market are safe and properly labeled.  In addition, any substance meeting the legal definition of a food additive in the United States must receive FDA approval before marketing.  The FDA regulates genetically engineered animals under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act.

In the realm of biomedical research, the National Institutes of Health (NIH) published its first guidelines for the creation and containment of recombinant DNA organisms in 1976.  Updated guidelines, the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), were issued in 2013 to cover research involving recombinant or synthetic nucleic acid molecules, and detail safety practices and containment procedures for basic and clinical research involving recombinant or synthetic nucleic acid molecules, including the creation and use of organisms and viruses containing recombinant or synthetic nucleic acid molecules.  Any entity receiving NIH funding for recombinant or synthetic nucleic acid molecule research is obligated to follow the NIH Guidelines for all research involving recombinant or synthetic nucleic acid molecules, regardless of a specific project’s funding source.  Many companies and other research institutions voluntarily follow the NIH Guidelines as best practice, even if they are not receiving NIH funding.

The U.S. government has also issued voluntary guidance to manufacturers of synthetic DNA (Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA, 2010) to reduce the potential risks arising from the use of synthetic DNA.

Using the current laws and regulations, the United States addresses a range of products developed using biological engineering.  The United States re-evaluates risks, regulations, and approaches as new information and techniques become available.  For example, the Update to the Coordinated Framework for the Regulation of Biotechnology was published in January 2017 (https://www.epa.gov/sites/production/files/2017-01/documents/2017_coordinated_framework_update.pdf), and the National Strategy for Modernizing the Regulatory System for Biotechnology Products, was published September 2016 (https://obamawhitehouse.archives.gov/sites/default/files/microsites/ostp/biotech_national_strategy_final.pdf .)

Moreover, there are a number of international fora and arrangements where nations can share, communicate and develop international guidelines for regulatory frameworks and risk management.  Some, such as the Organization for Economic Co-operation and Development’s (OECD) Environmental Risk Assessment Toolkit, offer guidance on risk assessment and provide consensus information useful in a risk assessment.  The United States participates in the OECD Working Group on Harmonization of Regulatory Oversight in Biotechnology, which produces consensus documents on the biology of organisms as well as guidance documents relevant to risk assessment practices.  In addition, the United States serves as a Vice Chair in the OECD Working Party on Bio, Nano and Converging Technologies (BNCT), in which synthetic biology issues are also addressed.

Regards,
Jenna Shinen

Dear all, colleagues

I fully support Maria s statement [#8777] about the natural disasters in our area and wherever it happens and the content and approaches about risk assessment "biosafety experts should be able to apply the same principles of risk assessment to any hazardous biological organism...." and for their excellent biosafety association and her collaboration as well as the principle of only one health

Kind regards,
Dr Lázaro Regalado

POSTED ON BEHALF OF HIROSHI YOSHIKURA
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1. Operational definition of 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”. It covers wide variety of such organisms including that are produced by application of technologies that are not necessarily “overcome natural physiological reproductive or recombinant barriers (from protocol definition)”. After enactment of Cartagena Protocol, many countries including Japan, adapted their regulations to the Cartagena Protocol including the definition of recombinant DNA organisms. In international forums, for example, FAO/WHO Joint Codex Alimentarius Commission adopted the Cartagena Protocol’s LMO definition for its guidelines on foods derived from modern biotechnology. Everywhere in the world, current regulation, i.e., risk management, of LMOs is based on the Cartagena Protocol definition. If LMOs defined in the current Cartagena Protocol are to be included among the products to be regulated under a new synthetic biology rule, confusion in regulatory space will be immense.
2. As Cartagena protocol Annex III, Risk Assessment, recommends practical approach saying that the risk assessment should be carried out on a “case-by-case basis” based in “the context of the risks posed by non-modified recipients or organisms in the likely potential receiving environments”. This principle could be applicable to any living organisms produced through “modern biotechnology” or by “synthetic biology”. In this sense, I agree with comment #8772. Appropriate application of the principles of the current version of Cartagena protocol will be most useful.
3. As regards criminal or malicious use of synthetic biology, as suggested by #8773, the issue may be better handled in other forums, such as, the InterAcademy Panel on International Issues (IAP) or countries’ national academies, as a matter of dual use issue.

Hiroshi Yoshikura, Emeritus Member of National Institute of Infectious Diseases, Japan (former chair of Codex Task Force on Foods Derived from Modern Biotechnology)

Dear Colleagues,
Mr. Tzvetkov has made some useful points (#8773) regarding the application of existing risk assessment and management methodologies developed for traditional LMO to products of synthetic biology.  He also correctly points to a few recent documents that encourage careful consideration of organisms with gene drives.

I would like to add to Mr. Tzvetkov’s comments (#8773) and to those of Mr. Friedman (#8775) by pointing out the existence of a couple of guidance documents currently available which specifically address risk assessment of organisms that contain gene drives.

First, the Cartagena Protocol’s Guidance for Risk Assessment of LMOs (https://www.cbd.int/doc/meetings/bs/mop-08/official/bs-mop-08-08-add1-en.pdf) very specifically addresses organisms with gene drives.  Section 5 Risk Assessment of Living Modified Mosquito Species That Act as Vectors of Human and Animal Diseases (beginning on p80) specifically refers to mosquitoes with gene drive systems. “Self-propagating strategies, also known as self-sustaining strategies, rely on gene-drive systems that promote the spread and persistence of the transgene through populations of the same mosquito species.”

Second, in 2014, the World Health Organization released the World Health Organization Guidance Framework for testing genetically modified mosquitoes (WHO Guidance Framework) (http://www.who.int/tdr/publications/year/2014/Guidance_framework_mosquitoes.pdf) describing best practices and a four-stage testing pathway for evaluating genetically modified mosquitoes intended for public health applications. 

Third, under the leadership of the Foundation for the National Institutes of Health (fnih.org) an international working group was convened over the last year and a half consisting of experts in mosquito biology, genetics, molecular genetics, ecology and control in addition to experts on containment/quarantine of exotic arthropods, modeling, epidemiology, clinical trial design, statistics and ethics. The working group was charged with considering the resources and activities needed to ensure the safe and efficient field-testing of mosquitoes containing a powerful and efficient synthetic gene drive systems.  The group had three multi-day meetings over the course of a year with ongoing discussions in the interim.  The guidance recommendations of the working group are currently being prepared for publication in early 2018 and they along with the World Health Organization Guidance Framework and Cartagena Protocol’s Guidance for Risk Assessment of LMOs create a solid framework within which research on gene drive applications to critical public health needs such reducing and eliminating mosquito borne human diseases can proceed.

Dear Moderator Benson Kinyagia, participants and colleagues

I would like to raise two issues, the first one to highlight the difference among two concepts related but different. According to WHO:

“Laboratory biosafety” is the term used to describe the containment principles,
technologies and practices that are implemented to prevent unintentional exposure
to pathogens and toxins, or their accidental release. “Laboratory biosecurity” refers to
institutional and personal security measures designed to prevent the loss, theft, misuse,
diversion or intentional release of pathogens and toxins. pag 47
World Health Organization. Laboratory biosafety manual. – 3rd ed.,2004

This definition is related with the dual use dilemma of this emerging technology as Nikolay Tzvetkov [#8773] reminded us “an important question related to biosecurity, the prevention of criminal or malicious use of synthetic biology.” an issue that is better addressed in the framework of BTWC (Biological and Toxin Weapons Convention) where security and disarmament negotiations take place. During the VIII Review Conference of this convention the technique of gene editing was proposed to be analyzed by a group or committee of experts, a Meeting of States Parties will  decide on this issue and others dual use technologies relevant to the treaty in Geneva, December this year.

The second one:
The Cartagena Protocol requires Parties to adopt measures and strategies for preventing adverse effects, in this connection I would like to share a summary of a presentation in a Caribbean Workshop on Synthetic Biology that took place in October last year in Grenada. This part, (see attachment) is about a possible strategy with a holistic view about the governance of Symbio.

Kind regards,
Dr Lázaro Regalado

POSTED ON BEHALF OF BENSON KINYAGIA
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Dear Forum Participants,

Further to my opening message, I would like to remind participants that the discussion on this final topic 4 will remain so up to 2nd October. 

I acknowledge the contributions by Mr. Gerd Winter, [#8764] and Dr Frederic Bass, [#8765] regarding their concern that the focus on risk management is limiting and while I agree that decision XIII/17 invites for study on both risk assessment and risk management I would like to assure them that the AHTEG will be discussing risk assessment issues, taking into account the submissions made by Parties through paragraph 10 of the decision.

That being said, the AHTEG was also specifically requested to discuss risk management measures, safe use and best practices for safe handling of organisms, components and products of synthetic biology and seeing as this topic was not given as much attention in the past as risk assessment, it would be prudent to have a dedicated discussion on this issue.

I would therefore like to encourage all participants to make a contribution to the discussions in order to assist the work of the AHTEG in its upcoming meeting in December.

As previously mentioned, the guiding questions proposed for this discussion are:

1. To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?
2. To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?
3. Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?
4. Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?
5. What specific new areas of research are needed, if any, in order to ensure the safe use of current and near future applications of synthetic biology?
6. You are also welcome to submit guidelines and guidance on risk management measures that may be applicable to organisms, components and products of synthetic biology

Please feel free to expand your interventions beyond the guiding questions to other issues that are directly relevant to managing the risks of organisms, components and products of synthetic biology.

I look forward reading your views on the matter.

Kind regards,
Benson Kinyagia

I would like to add my thanks to Dr. Benson Kinyagia for chairing the session and to the Secretariat for affording this opportunity to participate.

I would like to strongly support Dr. Robert's comments. It is easy to lose sight of the broad existing experience in biosafety and biohazard containment when dealing with the promises and potential risks of a developing technology. Just as important, it is useful to keep in mind that the focus of risk management should be in managing potential risks, not conducting research to see if they can be found.

I would also like to echo Dr. Robert's comments on the lumping of risk management approaches onto a disparate group of organisms and products  based on an imprecise, often process based definition of synthetic biology. While this may not be a unique thought, it is useful to keep in mind that case by case applications of risk analysis have proven to be very useful when applied to LMOs to date.

Thanks,
Phil Macdonald
Director Plant Health and Biotechnology Science Services
Canadian Food Inspection Agency

Dear All,

My thanks to Benson for volunteering to act as moderator of this round and for his focused guiding questions.

My name is Piet van der Meer, and following Benson’s request that we be concise, I refer to my post #8750 to introduce myself.

First some reactions about posts that went beyond Benson’s questions.

As regards criminal or malicious use of synthetic biology I fully concur with Tzvetkov, Regalado and Yoshikura that that question is best addressed in other fora such as the BTWC.

As to Winter’s suggestion that we should first discuss if the current methodology of risk assessment must be enhanced because it heavily relies on the comparison of the modified organism with the parent organism: Comparison is a tool in risk assessment, not an aim in itself. Comparisons are made at different stages of the risk assessment, for different purposes. In the early stages comparisons with the host or parent organisms are made to establish whether the resulting organism has novel characteristics. In the foreseeable cases of SB, we will be dealing with a modification of a host organism, i.e. comparisons can be made as to what the novel characteristics are. Whether those novel characteristics are ‘artificial’ doesn’t matter. In the case of a ‘de novo’ created organism for which no templates of existing genomes were used (i.e. for which there is no host to no compare with), the conclusion may be that the entire organism is novel. The lack of a host to compare with does not mean that risk assessment is not possible, it just means that may you have more or different things to look at.

As  to Then’s suggestion that new methods such as omics technologies would be needed to detect relevant biological effects, and that these data are not requested by the EU for the risk assessment:  the first part of this suggestion illustrates the flawed approach that we often see, i.e. as soon as there are additional technologies available to detect something, then there is a tendency to start requiring those technologies, regardless whether they add anything relevant in all cases. While omics may in some cases provided useful information for a risk assessment, that in itself does not mean that they have to be used. The second part of the statement that omics date are not requested by the EU does not mean that the risk assessment methodology as laid down in Annex III is not adequate. On the contrary, the methodology of Annex III allows for the inclusion of such data where they are relevant.
Likewise, potential changes in the microbiomes, disturbances or interruptions of the biological communication networks within the ecosystems are, depending on the case, also included in the Annex III risk assessment. 

In summary, I fully concur with Roberts’ comment that ” the risk assessment paradigm used for LMOs is robust, and adequate to assess the risks of other organisms that might be developed using whatever we define as "synthetic biology methods", and that ““synthetic biology” is not particularly useful as a way of meaningfully categorizing risks that an organism might pose”.

Turning to Benson’s specific questions:

1) To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?

I concur with all those who have stated that the existing risk management strategies are adequate for the current and near-future applications of synthetic biology.


2) To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?

In ERA for LMOs we take, depending on the case, into account the effects of non-living substances, such as Bt toxins to give an example. While the non-living substances can be part of an assessment of an LMO under the CPB, the non-living products themselves do not trigger an assessment, nor is there need to do so, because for chemicals and substances we have specific product assessment systems. As Roberts accurately pointed out: “the handling of chemical substances is well understood, regardless of the way the chemical is produced.  Chemical safety is a mature field, and I am not aware of any developments in synthetic biology which suggest chemical products will be outside the range of our experience with other chemicals”.

3) Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?

The bottom line is that applications are assessed on a case by case basis, and that where necessary risk management can be tailored to specific cases, comprising of physical, physiological, temporal, genetic and other forms of containment or confinement.

4) Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?

No.

5) What specific new areas of research are needed, if any, in order to ensure the safe use of current and near future applications of synthetic biology?

I agree with Boehm’s suggestion for research of synthetic biology applications specifically targeted at things as habitat modification. 

Wishing you all a good remainder of the weekend !


Piet

I should like to come back to Mr. Benson’s question (2) which reads:
To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?

Mr. van der Meer’s answer to this question is this:
In ERA for LMOs we take, depending on the case, into account the effects of non-living substances, such as Bt toxins to give an example. While the non-living substances can be part of an assessment of an LMO under the CPB, the non-living products themselves do not trigger an assessment, nor is there need to do so, because for chemicals and substances we have specific product assessment systems. As Roberts accurately pointed out: “the handling of chemical substances is well understood, regardless of the way the chemical is produced.  Chemical safety is a mature field, and I am not aware of any developments in synthetic biology which suggest chemical products will be outside the range of our experience with other chemicals”.

In contrast I believe components and products of SynBio are in fact “outside the range of our experience with other chemicals”. The reason is that the pertinent international agreements and national regulation such as the EU REACH Regulation will hardly cover components and products of SynBio other than those products that are captured by specific product related legislation (such as on pesticides, fertilizers, seeds etc.).

The REACH Regulation 1907/06 establishes an obligation to register a substance or mixture only for quantities of one tone and more, a quantity never to be reached at the present stage of SynBio development. See the Regulation’s
Article 6
General obligation to register substances on their own or in mixtures
1. Save where this Regulation provides otherwise, any manufacturer or importer of a substance, either on its own or in one or more mixture(s), in quantities of one tonne or more per year shall submit a registration to the Agency.

The ROTTERDAM CONVENTION on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade requests to notify importing states only for chemicals that are banned or effectively severely restricted. This will hardly be the case concerning components and products of SynBio. See the Convention’s
Article 12
Export notification
1. Where a chemical that is banned or severely restricted by a Party is exported from its territory, that Party shall provide an export notification to the importing Party.

Finally, the Cartagena Protocol is as repeatedly stated in the present discussion round only applicable on living modified organisms. See the Protocol’s
Article 7
APPLICATION OF THE ADVANCE INFORMED AGREEMENT PROCEDURE
1. Subject to Articles 5 and 6, the advance informed agreement procedure in Articles 8 to 10 and 12 shall apply prior to the first intentional transboundary movement of living modified organisms for intentional introduction into the environment of the Party of import.

Dear participants and colleagues,

I would like to thank the opportunity to participate and to share views with this remarkable group of experts
I thank our moderator for his challenging task and for his post [#8784] and in this connection

I want to raise some issues of interest and to add some Guidelines in guiding question 6.
When there are different shades of opinions, and this is normal in science when we face an emerging technology, beyond competing interest, personal agenda and political influence it’s wise to look at the results and opinions of different specialists and researchers in the area of expertise as a result of a meeting, workshop or publications in a sort  of a peer review and try to gather more information, different approaches and research results with the aim to reach a common ground even in the case that there is not all the information or evidence at hand, we are doing this in fact, although sometimes in a partial way. On the other hand I think that there are not experts on SB as such but experts in different areas of expertise related and with basic knowledge in some of the other areas and we should learn for each other. In this connection I would like to focus in some examples:

 Symposiums, attended by approximately  500 participants in total, brought together researchers from numerous disciplines—experts in law, property rights, and ethics; representatives from industry; policymakers; and members of the public—in the first collaboration among the United States, the U.K., and China on synthetic biology. Participants were asked to discuss synthetic biology in terms of its present and future value and to examine the scientific, engineering, societal, and policy implications of this emerging field.
In the area of Regulatory Challenges they stated:
¨Because the boundaries of synthetic biology are so fluid, the field may not fit neatly within existing regulatory frameworks…….Recognizing that science tends to move forward much faster than policy formation, early attention to issues associated with the governance and regulation of synthetic biology seem to be particularly appropriate¨
Positioning Synthetic Biology to Meet the Challenges of the 21st Century: Summary Report of a Six Academies Symposium Series   http://www.nap.edu/catalog.php?record_id=13316


 In a report of a workshop that took place at the University of Bristol, UK, in conjunction with the Social Science Research Group at the University of West England, Bristol and the BrisSynBio1 Synthetic Biology Research Centre on the 8th June 2017. A group of social scientists, philosophers, computational biologists, genetic engineers, and artists working on synthetic biology to stimulate multidisciplinary deliberation and insights into the political challenges and philosophical ideas emerging at the cutting edge of innovation in synthetic biology in their summary conclusions  highlighted:
• The importance of Anticipation, Reflection, Engagement and Action in R&D processes …. The beginning point of all innovation is in the lab and therefore research is an early location to consider ...
• The responsible research and innovation agenda is a step in the right direction for governance of synthetic biology…..
• Considerations of environmental and global justice, including socio-economic, cultural and ethical considerations are unavoidable, and so should be incorporated into any ideal international governance framework for synthetic biology.
• The precautionary principle has been and remains foundational for all risk assessment frameworks governing new technologies, including synthetic biology. Such that activities which pose a significant risk to planetary ecology, or a risk to human dignity simpliciter, shall be preceded by an exhaustive examination; their proponents shall demonstrate that expected benefits outweigh potential harms, and any potential harms should be fully understood and mitigated.
• Continuing levels of politics, conflict and ‘friction’ amongst different economic agendas, world views, systems of knowledge and vested interests within parties to the CBD and across relevant organizations, Indigenous peoples and Local communities will not be easily aligned, therefore a system must be found to accommodate and govern fairly and equitably for all.
Synthetic Biology, Politics, and Philosophy Workshop http://www.bristol.ac.uk/brissynbio/ 

 An interesting approach can be found in a report that reflects a committee’s deliberations regarding the future products of biotechnology that are likely to appear on the horizon, the challenges that the regulatory agencies might face, and the opportunities for enhancing the regulatory system to be prepared for what might be coming.
¨ At a high level, the committee found that there are existing frameworks, tools, and processes for risk analyses and public engagement that can be used to address the many issues that are likely to arise in future biotechnology products in a way that balances competing issues and concerns. However, given the profusion of biotechnology products that are on the horizon, there is a risk that the capacity of the regulatory agencies may not be able to efficiently provide the quantity and quality of risk assessments that will be needed. An important approach for dealing with an increase in the products of biotechnology will be the increased use of stratified approaches to regulation, where new and potentially more complex risk-analysis methods will need to be developed for some¨
¨ Products of biotechnology can be conceptualized as fitting into the depicted columns with the indicated characteristics, moving toward column D as a product increases in complexity and likelihood of providing new challenges for risk assessment.¨ See attachment Product Complexity and Novelty

Another Issue of interest:

Take into account the accidental release at an early stage in the lab. Accidents happen, some of them have institutional and individual responsibilities; in addition we can face an intentional one. To avoid accidents it’s very important a Culture of Laboratory Safety, to have in place implemented the principles of biosafety such as design requirements (Secondary Containment Barriers) according to biosafety levels, Good laboratory practices and techniques, Safety equipments (Primary barriers) and a Laboratory biorisk management standard such as CWA 15793:2008 and CWA 16393 January 2012:
Application ¨The requirements of this standard are generic and are intended to be applicable to all organizations handling biological agents and/or toxins, regardless of type, size and biological agents handled. This standard takes a risk based approach but it does not employ biological agent risk classification or laboratory safety/containment levels, although such approaches can be entirely compatible with this standard. Where any requirements of this standard cannot be applied due to the nature of the organization and its processes, this can be considered for exclusion. Where exclusions are made, claims of conformity to this standard are not acceptable, unless such exclusions do not affect the organization’s ability or responsibility to control biorisk in the manner required by this standard. Any claims of exclusion shall be detailed and justification provided.
Compliance with national and local regulatory standards, regulations and requirements are of primary importance in any programme. Where any part of this standard is in conflict with any legal requirement, the conflicting part of the standard may be eligible for exemption if the legal requirement meets or exceeds the intent of this standard.¨

A biorisk management committee should be established to assist the facility director; funding and training are also relevant to minimize risk and to improve risk management.

¨Biosafety has become more politically important in recent times as well, particularly after multiple high-profile safety failures at federal and military laboratories involving smallpox, anthrax, and flu¨…. there are additional, new opportunities that will be important to pursue to increase safety in the coming years, including dedicating research funds to biosafety; expanding biosafety training into new environments, to reach the growing populations of people who are performing biological work; and leading the world to develop international biosafety norms.¨ A Biosafety Agenda to Spur Biotechnology Development and Prevent Accidents. Health Security Volume 15, Number 1, 2017

¨On 6 September, the Belgium authorities informed the European Commission, the Netherlands, ECDC and WHO about an incident that occurred on 2 September 2014. Following a human error, 45 liters of concentrated live polio virus solution were released into the environment by the pharmaceutical company, GlaxoSmithKline (GSK), in Rixensart, Belgium¨
COMMUNICABLE DISEASE THREATS REPORT Week 37, 7-13 September 2014

6. You are also welcome to submit guidelines and guidance on risk management measures that may be applicable to organisms, components and products of synthetic biology
In addition to my post [#8768] of this round:

1. Laboratory Biosafety and Biosecurity Risk Assessment Technical Guidance Document
International Biological Threat Reduction, Sandia National Laboratories, in collaboration with The International Federation of Biosafety Associations.

2. Guía PARA LA EVALUACIÓN Y GESTIÓN DE RIESGOS ASOCIADOS A LOS ORGANISMOS VIVOS MODIFICADOS. Centro Nacional de Seguridad Biológica CSB, La Habana, 2016.

3. The Philippines Biosafety Guidelines for Contained Use of Genetically Modified Organisms. Revised Edition, September 2014.

Kind regards,
Dr Lázaro Regalado Alfonso

I am Joyce Tait, Director of the Innogen Institute, University of Edinburgh. With thanks to our moderator and also to those who moderated Topics 1 – 3, at this closing point in the discussions I would like to comment particularly on risk management-related issues as requested by our moderator (#8784), including particularly relevant contributions from Topic 2 of this Online Forum (e.g. #8641, #9677, #8681, 8699), and also the numerous contributions related to the definition of ‘synthetic biology’.
‘Risk management’ relates to the process of making risk-related decisions, taking account of data and evidence garnered from risk appraisal, risk characterisation and risk evaluation. This is a relatively straightforward process if data are already available to inform decisions, where there is little uncertainty (as opposed to risk) about future outcomes, and where there is no ambiguity (i.e. absence of multiple interest and value-related perspectives and preferences) (Ortwin Renn, Risk Governance: coping with uncertainty in a complex world. Earthscan, 2008). Uncertainty and ambiguity are inevitable components of most of the contributions to this Online Forum, raising serious challenge for future decision making (see #8700).
One recent attempt to deal with such issues has been supported by the UK Department of Business, Energy and Industrial Strategy (BEIS) and the British Standards Institution (Proportionate and Adaptive Governance of Innovative Technologies (PAGIT), 2017 (https://www.innogen.ac.uk/downloads/FrameworkReport-Final_170717.pdf)). This approach focuses particularly on the adoption of standards and guidelines at early stages of research and development of innovative technologies, allowing many of these uncertainties to be resolved and to guide better decisions on the appropriate regulatory system to be adopted. After a choice of regulatory system has been made, the approach also considers how standards can contribute to adaptation of existing regulatory systems to make them more proportionate to the risks and benefits of a new technology and its products. Current approaches to regulation of new technologies usually involve squeezing the technology to fit the requirements of incumbent regulatory systems; the proposed alternative is to make regulatory systems more adaptive to the properties, opportunities and risks of innovative technologies. Thus, for synthetic biology the greatest risk management challenge is to govern its future development in a way that allows society to benefit from its potential contributions to global biodiversity, or indeed from contributions that are neutral in that respect, while continuing to ensure safety, quality and efficacy, without being prohibitively time-consuming and costly for researchers and companies to implement.
Dealing with the uncertainty and ambiguity challenges raised by synthetic biology and related technologies will be essential to their effective future risk management. However, apart from this case, this online forum has consistently discouraged such contributions, with exhortations to focus on the questions raised at the beginning of each topic. Effective resolution of the risk management dilemma for synthetic biology will depend on finding a way to introduce discussion the future adaptation and proportionality of the CBD and its protocols into the dialogue.

Dear Colleagues,
First of all, special thanks to Bob Friedman (#8775) for providing us with the excellent opinion paper on gene drives in insects and Dr. O’Brochta (#8782) for the update on the current activities on the same topic. Both 2016 Guidance developed under CBD and 2014 WHO Guidance Framework are quite valuable, although in some need for update to reflect the recent developments. I personally don’t believe that general guidance on risk assessment on all gene drives can be produced because the organism and gene drive systems involved are very different. In this sense it is logical that most of the current work is concentrated on mosquitoes which are probably to be the first organisms with gene drives to release on large scale into the environment.
In my previous post (#8773) I was not very clear what I meant by need for documents which specifically address risk assessment of organisms that contain gene drives. The problem that the gene drives pose is not new and neither is the solution. It is how we can safely use and maximize the benefits from living organisms that once released into the wild can be hard to remove, can spread easily and have the potential to cause significant harm to human health and the environment. For me the most typical examples of such organisms are the live attenuated vaccines. Their safe and efficient use are one of the greatest successes of modern biology and a prove that potentially dangerous agents can be used safely. In order to authorize such a vaccine its safety and efficiency have been demonstrated. This is done through a phased process where the results of each phase are used in the next one and information further information of safety and efficiency is gathered. On that basis authorization is granted and conditions for use are defined. This followed by monitoring aiming to identify unexpected rare or long-term effects. Specific data requirements and assessment procedures vary between different products but general framework is essentially the same. I think this is the kind of approach suggested in the 2014 WHO Guidance Framework for testing GM Mosquitoes.
I think it will be useful is to provide guidance or set standards on the minimal data requirements and evaluation procedures for authorization of each phase of testing and large scale releases of organisms containing gene drives, incl. post-release monitoring. Such document might also set standards for consultation with the public and other states that might be affected. I believe that it is possible to develop such general document covering different organisms containing different gene drives. Realistically, authorization of organisms containing gene drives is most likely going to be done under national regulation. But having agreed international standards applied by various jurisdictions will increase the trust of the public and other states and will provide applicants with legal certainty and will reduce their development costs.
Some of the most serious risk related to gene drives are related to potential damage that they can cause to the biological diversity in transboundary context. For that reason, CBD and its Protocols can be among the more appropriate international fora to develop such guidelines or standards in close cooperation with other international and national organisations.
Best Regards to All,
Nikolay

Topic 4: Gathering information on risk management measures, safe use and best practices for safe handling of organisms, components and products of synthetic biology

We thank Mr Benson Kinyagia for moderating this last topic and our fellow contributors for their inputs.

Please find below New Zealand’s responses to the questions posed in this forum. As noted by Dr Friedman (#8775), much of the relevant information has already been discussed extensively in earlier online forums. With regard to our post, much of this is a reiteration of the points we raised in our submission on the topics raised by the CBD Secretariat in Notification 2017-025. Again, New Zealand provides its comments within the context of its legislative framework for the regulation of GMOs and/or LMOs, the Hazardous Substances and New Organisms Act 1996 (the HSNO Act), and the Imports and Exports (Living Modified Organisms) Prohibition Order 2005. Among other things, these legislative instruments give effect to New Zealand’s relevant obligations under the Convention on Biological Diversity and the Cartagena Protocol. Our comments are consistent with, and we are supportive of, the post of Dr Roberts (#8772).

• To what extent are current risk management measures and best practices that are in use for “traditional” LMOs also sufficient to living organisms developed through current and near future applications of synthetic biology?
New Zealand’s view is that all current biotechnological approaches and techniques – including synthetic biology and gene drive – are readily covered under the Cartagena Protocol’s definition of ‘Living Modified Organism’, and thus also in New Zealand by its Hazardous Substances and New Organisms Act, as well as other publicly available risk assessment and risk management guidelines. New Zealand therefore considers that existing risk management measures and best practices used for existing LMOs are sufficient for the risk management of living organisms developed through synthetic biology, as we elaborate further in our responses to the following questions.

• To what extent are current risk management measures and best practices also sufficient to the safe handling and use of the components (e.g. a DNA molecule) and products (e.g. a chemical substance produced by an organism) of synthetic biology?
New Zealand considers that the source of a molecule, whether considered a biological molecule (eg, DNA, proteins, sugars) or otherwise, is irrelevant as regards the assessment of its risk characteristics. Thus, DNA or other molecules produced through aspects of synthetic biology can be readily managed (if required) under existing risk management practices used for chemicals and substances. In New Zealand’s case, for example, the hazards and risks that components and products may present (if any) and their management (if needed) are dealt with in accordance with national legislation (specifically, the hazardous substances provisions of the HSNO Act).

• Do you foresee a need for adapting safety measures in the future as developments in the field of synthetic biology are made?
New Zealand’s approach to risk management is to first differentiate between hazard and risk. Potential and reasonable pathways to harm that may occur are then assessed in the context of the nature of the hazard. Based on this assessment, controls are then imposed if necessary to manage any assessed risk in the context of New Zealand’s risk management goals. This approach is inherently adaptable. As such, it will be suitable in the face of any future developments in synthetic biology. Reiterating our earlier statement in related CBD forums, there are many existing risk assessment and risk management guides that are readily available to Parties (e.g., Australia’s Risk Analysis Framework(1), or the Environmental Risk Assessment Guide(2)), that provide ample direction on the evaluation of scientific uncertainty in both the assessment of risk and its management, as well as subsequent decision-making processes.

• Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?
None.

• What specific new areas of research are needed, if any, in order to ensure the safe use of current and near future applications of synthetic biology?
None. As pointed out by Dr Roberts (#8772), the organisms resulting from synthetic biology will be varied and manifold, and as such is not a useful categorisation as regards risk assessment and risk management. New Zealand assesses all proposed uses of GMOs/LMOs on a case-by-case basis, taking into account the relevant hazards and risks, imposing controls to manage the risks, as appropriate to the specific organism(s) and intended use(s).

1. http://www.ogtr.gov.au/internet/ogtr/publishing.nsf/Content/risk-analysis-framework
2. https://goo.gl/T4uXnl

Mariska Wouters
Ministry for the Environment, New Zealand

Dear participants,
My thanks and appreciation to Mr Benson Kinyagia for moderating this important discussion.
With regards to point 4: Can you provide concrete examples of existing applications of synthetic biology to which risk management measures may not be sufficient to ensure the safe handling and use of living organisms developed through synthetic biology?
I agree with Mr. Nikolay Tzvetkov, Bulgaria (#8773) and Dr Christian Boehm with regards to the issue of gene drives. 
A key question is whether it is even possible to pre-assess the risk of their release. Nonetheless, there are some clear knowledge gaps that we may seek to address with regard to ecological effects. What is the evolutionary trajectory of gene drive components, can they be controlled? And their potential for lateral (or even horizontal) transfer of gene drives to non-target populations? As highlighted by Oye KA, Esvelt K, Appleton E, Catterueda F, Church G. et al. Regulating gene drives, Science, 2015:
“To what extent and over what period of time might cross-breeding or lateral gene transfer allow a drive to move beyond target populations? Might it subsequently evolve to regain drive capabilities in populations not originally targeted?”
We also lack well tested, efficacious containment measures e.g. molecular confinement/reverse drive mechanisms for gene drives which is an area of research that I believe deserves consideration and implementation prior to any environmental release.
With regards to gene edited crops, I support comments by Dr Then. Current RA is not sufficient to address potential adverse effects of off target effects from CRISPR and other techniques, and the use of ‘omics’ techniques is one method of detecting any potential effects.

Dear forum participants,

Our moderator has asked us to focus our discussion on risk management, and safe handling and use of organisms, components and products of synthetic biology. As pointed out by others, this topic has been deliberated previously, and it was included in the recent information submission – risk management of LMOs is addressed in detail in the GIC information submission (http://bch.cbd.int/database/record.shtml?documentid=112053) and the main points are reiterated below.

For LMOs, the Cartagena Protocol requires that risk management “mechanisms, measures and strategies” are imposed to the extent necessary to manage risks that are identified (if any) in a risk assessment (Art 16). The online discussion for Topic 3 did not identify an example of a living organism, existing or in development, that is not an LMO as defined by the Protocol. Further, participants highlighted the applicability of the principles of risk assessment as set out in the Protocol (Art 15, Annex III). It is also our view (#8759) that living organisms resulting from synthetic biology applications are LMOs, and risk assessment can be conducted according to established procedures. Those procedures are based on scientific evidence and do not include the broader considerations listed in #8764. Socio-economic considerations are the topic of Art 26 of the Protocol, whereby Parties may voluntarily take these into account when reaching decisions on LMOs – these considerations are distinct from the risk assessment. A work program for Art 26 was established in 2012 and an AHTEG is continuing its work to provide conceptual clarity on this topic. In practice, many Parties take socio-economic considerations into account in LMO decision making, and these vary according to domestic circumstances and priorities.

For “traditional” LMOs such as LM crops, risk management measures are routinely implemented for releases into the environment in the early phases of testing. These range from confinement strategies and restrictions in use (e.g. small-scale release, physical controls such as greenhouses, fences, isolation distances, pollen traps), monitoring requirements such as monitoring zones and removal of volunteer plants, record keeping and reporting requirements, and contingency plans. For commercial (unconfined) releases, risk management measures have been used on a case-by-case basis, including the introduction of refuge areas, crop rotation, weed control, and reporting requirements. Such measures are often implemented to ensure the long term sustainable use of the LM crop and may not be associated with risk management. The type of risk management measure(s) used should be the most appropriate to adequately address an identified risk, and a combination of measures may be required to ensure a sufficient level of management. The same case-by-case approach applies to environmental releases of LMOs resulting from synthetic biology applications.

Examples of risk management measures can be found in the conditions for LMO field trial release imposed by regulatory authorities, or the conditions imposed by regulators for commercial releases of LMOs. Good examples to consult include the conditions of licenses granted by the Office of the Gene Technology Regulator (OGTR) in Australia (http://www.ogtr.gov.au/internet/ogtr/publishing.nsf/Content/ir-1.), and the field trial requirements of permits issued by the United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS: https://www.aphis.usda.gov/aphis/ourfocus/biotechnology/permits-notifications-petitions/SA_Permits), and the Canadian Food Inspection Agency (CFIA: http://www.inspection.gc.ca/plants/plants-with-novel-traits/applicants/directive-dir2000-07/eng/1304474667559/1304474738697).

The Cartagena Protocol is not the only applicable regulatory mechanism for LMOs resulting from synthetic biology applications. For LMOs that are not intended for environmental release, i.e. to be used in containment only, contained use regulatory frameworks apply. These are based on well-established biosafety guidance developed in the 1980s and periodically updated, with examples including:
- World Health Organization Laboratory Biosafety Manual (3rd ed, 2004)
- US Dept Health and Human Services, Centres for Disease Control and Prevention, National Institutes of Health – Biosafety in Microbiological and Biomedical Laboratories (5th ed, 2009)
- US Department Of Health And Human Services, National Institutes Of Health, NIH Guidelines For Research Involving Recombinant Or Synthetic Nucleic Acid Molecules (2016)

While these are voluntary guidelines, an assessment of national reports in 2016 (UNEP/CBD/BS/COP-MOP/8/10) indicated that 75% of Cartagena Protocol Parties have implemented national regulatory systems for contained uses of LMOs. These regulatory frameworks are characterized by risk group classifications that are assigned on the basis of risk assessment, and containment level requirements. The same approach applies to contained uses of LMOs resulting from synthetic biology applications.

For non-living products of synthetic biology, these are subject, as appropriate, to a complex range of long-established regulatory mechanisms that include the assessment and management of risks. In these discussions this topic has only been addressed in a general way and a specific example of a non-living product that would not fall within the scope of existing sectoral regulatory regimes has not been identified. It should be noted that such regulation is typically based on an assessment of the product’s properties, and not the process by which it was manufactured. It would be duplicative and unnecessary to consider the need for additional risk assessment requirements specifically due to the use of a biological manufacturing process.

As a final point, we would like to comment on off-target effects, which has been raised again in this discussion and directly linked to risk (#8770, #8793). Off-target effects were debated at length in online discussion topic 1, where it was emphasized that not all mutations have an effect on the functioning or characteristics of an organism, and it should not be implied that all have an adverse effect (#8537). As referred to by #8772 and #8785, and stated in Annex III of the Cartagena Protocol, the objective of risk assessment is to evaluate the potential adverse effects presented by the LMO in the context of how it will be used in the receiving environment, it is not a subjective investigation into any potential risk.