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Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6761]
Dear participants,

Welcome to the first round of discussion implementing the Decision XII/24 of COP 12. It is an honour and pleasure for me to have been selected as moderator for one of the three opening discussions under the forum and on such important topic “Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques”.

The scope of this discussion is to provide information that will be relevant to the work of the Ad Hoc Technical Expert Group (AHTEG) on Synthetic Biology. The results of this round of discussion would be useful to evaluate the similarities and differences between living modified organisms (LMOs), as defined in the Cartagena Protocol on Biosafety, and organisms, components and products of synthetic biology techniques. 

Please note that, in the context of this discussion, “components” can be understood as parts that are used in a process (i.e. synthetic biology or modern biotechnology), and “products” as the resulting output of a process. Moreover, to facilitate the discussion, I would like to propose that both “components” and “products” are NOT living entities. For instance, a naked DNA molecule would be an example of a “component” of synthetic biology, whereas a chemical fragrance would be an example of a “product”. 

A report recently published by the CBD Secretariat, proposes that the techniques and tools of synthetic biology represent an expanding frontier of biotechnology, but current applications can be considered to remain within the Cartagena Protocol’s definition of modern biotechnology (https://www.cbd.int/doc/publications/cbd-ts-82-en.pdf).

The Cartagena Protocol applies to the transboundary movement, transit, handling and use of all LMOs that may have adverse effects on the conservation and sustainable use of biological diversity, taking also into account risks to human health. Under the Protocol, LMOs are defined as “any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology”.

Furthermore, ‘Modern biotechnology’ is defined in the Cartagena Protocol as

“The application of:

a. In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA) and direct injection of nucleic acid into cells or organelles, or
b. Fusion of cells beyond the taxonomic family,

that overcome natural physiological reproductive or recombination barriers and that are not techniques used in traditional breeding and selection.”

To help focus the discussion, you may refer to the guiding questions below in preparing your interventions:

• What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?

• Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology?What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?

• How do the different areas of synthetic biology, including DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering, protocell construction and xenobiology, overlap or differ from modern biotechnology as defined in the Cartagena Protocol?

The forum will take place for the next two weeks. Your points of view and feedback will be appreciated and I sincerely hope that we can build a fruitful discussion that helps us to develop further conceptual clarity in order to be useful for the next discussions inside the AHTEG on synthetic biology.

I encourage you to participate actively.

Kinds regards,

M. Andrea Orjuela-R.
posted on 2015-04-27 01:11 UTC by Ms. María Andrea Orjuela Restrepo, Mexico
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6772]
Dear participants,
My name is Frank Hartung and I am Scientist at the Julius Kuehn-Institute (Federal Research Centre for Cultivated Plants) dealing with Biosafety in Plant Biotechnology. My main research focus is on DNA recombination and the applicability of New Plant Breeding Techniques. We are working on somatic and meiotic recombination in plants and the applicability of new genome editing techniques.
At first I would propose my opinion concerning the definition and evaluation of Synthetic Biology. As others already said there is no exact definition of Synthetic Biology nowadays and I would agree with Bruce Dannenberg and others that a definition regarding the impact of SB on biological diversity should focus on the product and not on the technology used.
As far as I can see most of the techniques used for production of synthetic ciology compoments or products are based in biotechnology and modern biotechnology (i.e. synthesis of gene constructs, cloning and expression in microorganisms, transplantation into yeast or plants). Therefore, I would argue that organisms developed through synthetic biology would fall in at least two classes.
First, if the components are based in modern biotechnology the end product will be an LMO as defined in the Cartagena Protocol. This would be my suggestion for what is similar between LMOs and SBOs? (maybe we need a term for organisms developed through synthetic which would be most simply an SBO (of course just a suggestion but I would omit SDO for “synthetically designed organism” as it has a very negative connotation)).
Second, if unnatural components (i.e. Xenobiology) are used to produce a living organism this would be in my opinion something new and quite different to an LMO (and this would need a new term). This might also be the case if protocells are used which do not consist out of components which are common in natural biology.
To make this clear, I would argue that synthetic biology which is based on modern biotechnology is just a matter of degree and the product, which can be an LMO or just a component of an LMO should be handled as a product of modern biotechnology , whereas really new components (or organisms) have to be analyzed and handled differently. To exemplify this, you can create a really dangerous LMO regardless if synthetic biology is involved or not. So for me the impact (may it positive or negative) on biological diversity is the same in synthetic biology and modern biotechnology and should be assessed on the level of the end product. If the end product is a living organism which contains components of synthetic biology which are occurring in natural organisms (i.e. DNA-based circuits, a new metabolic pathway or an engineered genome) I would discuss it as an LMO.
If the end product is a living organisms build up out of new kinds of protocells or xenobiological components, I would discuss it as something unprecedented. In this case we have to discuss which kind of precaution has to be applied on such organisms and components and this discussion has to be focused regarding if such an organism will be just for contained use or for a release into the environment. The impact for biological diversity might be very different comparing such organisms to LMOs as defined in the Cartagena Protocol.
Kind regards,
Frank Hartung
posted on 2015-04-27 09:53 UTC by Mr. Frank Hartung, Germany
This is a reply to 6772 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6774]
Dear Forum on Synthetic Biology participants
I am very happy to join the online forum and i want to thank the Secretariat and the forum participants for this opportunity to share views and experience on Synthetic Biology
I am Dr Gado Zaki Biosafety Focal Point of Niger and UEMOA national Biosafety Program Coordinator
The field of Synthetic Biology  is recent, it will be usefull to review the technical series by including scientific stakeholders and focus discussions on the impact of such organisms for the conservation of Biological Diversity in comparision with LMOs as defined by the Cartagena Protocol
Best regards
Dr Gado
posted on 2015-04-27 12:06 UTC by Mr. Mahaman Gado Zaki, Niger
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6781]
Dear colleagues,
My name is Nikolay Tzvetkov and I work at the Biodiversity Unit of Bulgarian Ministry of Environment and Water.
Regarding the question whether Synthetic Biology organisms (SBOs)are within the scope of LMO as defined in Art. 3 of Cartagena protocol, most SBOs are product of modern biotechnology techniques as defined in the Protocol. So they should be considered LMOs as well. Even further in definition of modern biotechnology, it is not restricted only techniques involving natural nucleic acids, such as DNA and RNA, so organisms that contain non-natural nucleotides fall within the scope. Same applies to organisms that contain and utilize non-natural amino acids and other metabolites. Actually very few of the organisms that are produced via synthetic biology techniques will outside the scope of Cartagena protocol.
As for the components and products if they are not living organisms under Art. 3 of the Protocol, they are outside its scope.
It is a different question whether the standard approaches of Risk Assessment and Management can be applied to some of the SBOs, although my feeling is that in most cases they will be applicable, perhaps with some modifications.
Best Regards,
Nikolay
posted on 2015-04-27 13:23 UTC by Mr. Nikolay Tzvetkov, Bulgaria
This is a reply to 6772 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6782]
POSTED ON BEHALF OF SATURNINA HALOS

----

Dear fellow participants,

My name is Saturnina Halos and though I used to undertake biotechnology research and teaching, I am currently involved more on  modern biotechnology regulation. Hence this interest in this topic. I agree with colleague, Frank Hartung that in terms of biodiversity concerns, we should focus on the product of synthetic biology and not the process. Also, that the product should be living, reproduces outside of the laboratory and may be released into the environment.
posted on 2015-04-27 13:34 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 6772 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6800]
Dear participants of the online forum on synthetic biology,

I am Dr. Hideyuki Shirae belongings in Japan Bioindustry Association.  
It is great pleasure for me to take this opportunity to join this online forum and please accept my sincere gratitude to Secretariats and other participants on this forum.

I would like to express my opinion about the topics 2. I think that the "organisms" are synonymous with LMOs in Cartagena Protocol.  As referred to many reports regarding synthetic biology, they used some type of containers containing small molecules and the “Components”.  For example, building a genetic circuit is used a chassis as a container.  Designing and establishing metabolic engineering pathway is used some host cells, such as Escherichia coli and Saccharomyces cerevisia, as containers.  Making a prototype cell is used particles with double layer phospholipid membranes as containers.  The chassis and particles (protocells) are not “organisms”.

Then avoiding the deadrock of further discussion, I agree with Dr. Frank Hartung and we should focus on the product of synthetic biology and not the process (technology) .
Thanks Dr. Hartung for your suggention.

In addition, we disagree to define the broad definition of the synthetic biology as like an opinion document that was recently published by the European Community and start the forum discussion because everybody has different thought  and image about the synthetic biology.   The broad definition makes confusion.

I feel that the “Components” are regarded as some kind of parts and their libraries designed in order to characterize the “Products”.

In order to discriminate the modern biotechnology under the Cartagena Protocol from the synthetic biology, “Components” should be divided into two types, molecules(or oligonucleotides) derived from natural nucleotides, ACGT, and molecules derived from oligonucleotides which, at least, contain more than one unnatural form nucleotides and/or chemically synthesized molecules. The synthesized molecules are involving in parts libraries(promoter libraries, enhancer libraries, silencer libraries, frequently expressed codon usage libraries and so on). 

The “Products” are made from any container including “Components” inside the container.  However, the “Products” derived from LMO inserted “Components” made by only natural nucleotides, AGCT” into are not regarded as the one derived from “Synthetic Biology. The “Products” have already regulated by Cartagena Protocol.  Therefore, that should not be discussed in CBD with different issues not appropriate.

In this discussion of online forum in CBD, we should be focus on the “Products” which combined “Components” containing more than one any unnatural molecules(oligonucleotides) with LMOs or other containers, such as chassis and particles with double layer phospholipid membrane.

I understand that there many different opinions and views about the above opinions.  I look forward to other comments and opinions. 

Best regards to all.

Hideyuki
posted on 2015-04-28 01:29 UTC by Mr. HIDEYUKI SHIRAE, Japan
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6806]
Dear colleagues,

My name is Piet van der Meer, and my daily activities revolve around teaching biosafety the Ghent University and the Free University of Brussels in Belgium and providing support to governments and international organisations.  I participate in this forum for the Public Research and Regulation Initiative (PRRI), which is an international NGO by and for public researchers active in research on modern biotechnology for the public good.

Synthetic biology is gaining increasing interest of public researchers worldwide, as it can - inspired by nature - be used to redesign biological systems in order to better understand life processes and perform beneficial functions. SynBio is widely considered to be among the top emerging technologies with the greatest potential to provide solutions to the most compelling social, economic and environmental challenges (see also: http://www.prri.net/synthetic-biology/).

PRRI is therefore very pleased with public discussions as this on line debate on synthetic biology, and commends the CBD Secretariat for organising this debate and the moderators for making their time and expertise available.

Having said that, I also have to share that I am concerned about the approach taken for this on line debate.

Over the years I have participated – and am participating  at this very moment - in many on line discussions under the Biodiversity Convention and the Biosafety Protocol, and I noted that this discussion on Synbio takes a different approach by inviting parallel discussions on three different topics.

While we have already seen quite some fascinating exchanges, I urge the moderators and CBD Sec to slightly change the modus operandi for this debate to discussing only one topic at the time and that the fist topic should be topic 3, i.e. about an operational or working definition.

My reasons for this suggestion are:

1. Discussing various topics at the same time results in duplication and confusion. We can already see that some interventions are pasted under multiple topics, and that the topic of one discussion (e.g. definition) is also discussed under the thread of another.
2. This kind of on line discussions have a logical sequence, whereby typically the first topic is ‘definition’, i.e. what the participants mean by synthetic biology when they make interventions, and whether there are common elements in the various descriptions of SynBio. It is not helpful to discuss similarities between organisms produced through SynBio and LMOs if we do not know what people mean when they refer to Synbio. From the various posts we can see that SynBio means different things to different people, which is a good  reason to take a step back there and reflect on that, before discussing other topics.
3. It is already quite some work to adequately follow and contribute to one thread under a particular topic, let alone three.  This is compounded by the fact that at this very moment there are also on line discussions going on other topics such as on socio-economic considerations in decision making, environmental risk assessment, and biosafety related databases. This coinciding of on line debates on many different topics is counterproductive to the very purpose of on line discussions.

I apologise for having to place this post under all three topics of this online debate, but I would like to draw the attention of all participants to this. For similar reasons, I will also bring the general concern about coinciding on line debates to the CBD Secretariat.

I hope that in this on line discussion the moderators will agree to discuss one topic at the time and that we continue first with the discussion on what is now topic 3, e.g. the discussion about an operational definition, to which I will make substantive contributions later in the debate.

Looking forward to some excellent debates, and with greetings to all!

Piet
posted on 2015-04-28 07:33 UTC by Mr. Piet van der Meer, Ghent University, Free University of Brussels, Belgium, PRRI
This is a reply to 6806 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6816]
Dear participants,

My name is Luciana Ambrozevicius and I work for the Ministry of Agriculture in Brazil. I´m also a member of our National Biosafety Technical Commission (CTNBio) responsible for GMO risk assessment. I´ve being participating in the CPB on line forum about risk assessment since 2011.

My opinion about the discussion is that the current format is very difficult to follow and the main idea of each topic is being lost. I totally agree with Piet´s intervention (≠6805) ´ to slightly change the modus operandi for this debate to discussing one topic at the time´. I also have three main considerations that support the idea of having a more focused and logical format discussion:

- The importance and potential broad applications of the subject discussed in this forum

- The importance of the contribution of the on line forum for the AHTEG meeting (Sep/2015) and the impact of the outcomes of this meeting for Parties decisions (COP – Dec/2016)

- The modus operandi that will be adopted for this on line forum for all the topics that will be discussed in the next months (till 6 July)

Thank you.

Kind regards,
Luciana Ambrozevicius.
posted on 2015-04-28 13:16 UTC by Ms. Luciana Ambrozevicius, Brazil
This is a reply to 6816 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6817]
My name is Gutemberg Sousa and I am analyst at National Technical Commission on Biosafety Brazil. Also support the format proposed by Drs. Piet's, Hans and Luciana. Its important to establish a clear mandate to the ATHEG well with solid definitions of synthetic biology.
posted on 2015-04-28 14:14 UTC by Mr. Gutemberg Delfino Sousa, Brazil
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6823]
Dear participants of the online forum on synthetic biology

I’m Dr Lázaro Regalado from the Cuban National Center for Biosafety (Ministry of Science, Technology and Environment). It’s an honor to participate in this Forum where we share a task to be responsible for the protection of the environment and the human health.

I would like to point out some indicative ideas:
Topic 2: Similarities and differences between living… modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques
• What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?
• Similarities between livings modified organisms and organisms resulting of synthetic biology techniques: (Indicative)
* Organisms, resulting from both technologies are manmade hence the fact that they are artificially created and do not represent the natural world.
* Both lead to obtain organisms of considerable societal value, which at the same time raised concerns due to security issues (Biosafety and Biosecurity)
* For the time being they cannot be properly retained once released, regardless of the technology used.
* ...

• Differences between livings modified organisms and organisms resulting of synthetic biology techniques: (Indicative)
* Synthetic biology might add new unnatural base pairs to expand on the standard two-base-pair genetic alphabet (A-T and G-C) in DNA.
* Synthetic biology uses unnatural molecules to mimic natural molecules to create artificial life.
* Most part of the techniques used to obtain products are different (LMO by modern biotechnology and synthetic biology uses natural molecules in a system that acts artificially….)
* ..

• Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology?

No, the techniques are those that may be different but the result is the same as a living organism with its potential benefits and challenges constituted by their potential for damage to biodiversity and human health should be subjected to risk assessments from the very beginning of the research design itself to make decisions at early stage and should continue to have provided an adequate risks management. Hence the fact that synthetic biology should be subject to regulations and control and adequate supervision.
Under the Convention biotechnology is defined as “...any technological application that uses biological systems, living organisms, or derivatives thereof, to make or modify products or processes for specific use”. Synthetic biology falls within the scope of this broad definition.
There are several applications where synthetic biology and biological diversity may intersect. Such results or applications may impact biodiversity, either positively or negatively, at various levels including at the level of genes, species and ecosystems.


What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?
• Similarities between, the components and products of “modern biotechnology”, and components and products of synthetic biology techniques: (Indicative)
* Both lead to applications and products of considerable societal value, which at the same time raised concerns.
* Products, resulting from both technologies do not exist in the natural world.
* They cannot be properly retained once released regardless of the technology used.
* ..

• Differences between, the components and products of “modern biotechnology”, and components and products of synthetic biology techniques: (Indicative)
* Synthetic biology uses unnatural molecules to mimic natural molecules to create artificial life.
* Most part of the techniques used to obtain products are different (LMO by modern biotechnology and synthetic biology uses natural molecules in a system that acts artificially….)
* Synthetic biology might add new unnatural base pairs to expand on the standard two-base-pair genetic alphabet (A-T and G-C) in DNA.
* ..

Respectfully,
Dr Regalado
posted on 2015-04-28 19:45 UTC by Mr. Lazaro Regalado, Cuba
This is a reply to 6781 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6825]
POSTED ON BEHALF OF JONATHAN MUFANDAEDZA

----

I am DR Jonathan Mufandaedza, a nanobiotechnologist and I work with the National Biotechnology Authority of Zimbabwe. I am a Regulator  and Registrar of biotechnology  processes and products in Zimbabwe. It is with a great interest to be part and parcel of this discussion. let me indicate that the Cartagena protocol definition of an LMO to a greater extend covers synthetic biology processes and products. Most Synthetic biology organisms are covered within the scope of LMOs, but it is worth noting that this is another dimension of biotechnology with potential for further growth. What we should focus on are the products of synthetic biology rather  than the processes because the process techniques implicated in synthetic biology are strongly identified with those used in the development of LMOs or modern biotechnology. Singling out the products of synthetic biology would help us develop specific approaches of risk assessment and management. Furthermore from a nanobiotechnology perspective, both LMOs and SBOs occupy some nanobiospace which can be manipulated interconvertibly.In short the two related. I agree with NIKOLAY (post #6781).
posted on 2015-04-28 20:37 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 6825 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6843]
Dear participants,

I’m Leonardo Bocanegra from the Research Institute on Biological Resources from Colombia. It’s an honor to participate in this Forum.

First it should be noted that at present synthetic biology does not get completely artificial organisms, actually it has been created is artificial genetic material, and this material is inserted into bacterial cells in which have been removed to their original genetic material, existing an important point here is that the organism that are obtained in both cases are Genetically Modified Organisms (GMO´s).

On the other hand, the Cartagena Protocol uses the term "techniques of in vitro nucleic acid", which implies all possible manipulations that can be made on nucleic acids regardless of their configuration and the synthetic biology seeks to design, build and redesign organisms by manipulating their genetic material for a new gene expression and a new phenotypic characteristic.

In light of the foregoing, it can be said that currently there are more similarities between GMOs and SynBio organism. However, in methodological approaches as xenobiology the genetic material does not exist in nature, being this approach not contemplated in the definitions contained in the Cartagena Protocol in spite of the fact that the genetic expression of the new nucleotide composition could be carried out by GMO.
posted on 2015-04-29 14:16 UTC by Mr. José Leonardo Bocanegra Silva, Colombia
This is a reply to 6843 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6864]
Dear all

The organisms, components and products of synthetic biology techniques are products of ‘modern biotechnology’ as defined under the Cartagena Protocol on Biosafety and the Codex Alimentarius Principles for the Risk Analysis of Foods Derived from Modern Biotechnology. Any organism modified using in vitro nucleic acid techniques should be considered a ‘synthetically modified organism’, whether or not there is a novel combination of genetic material. These techniques would include genome editing technologies such as cisgenic, intragenic, reverse breeding, TALEN, meganucleases, ZFN and CRISPR/Cas.

In so far as organisms resulting from synthetic biology techniques meet the definition of LMOs under the Cartagena Protocol on Biosafety, then they are also LMOs. It should be pointed out however, that the Cartagena Protocol only addresses products thereof under its Article 20, Annex I and Annex III, so its scope is limited in relation to the components and products of synthetic biology.

As such, the organisms, components and products of synthetic biology techniques make up a broader category than ‘living modified organisms’ (LMOs) as defined under the Cartagena Protocol.  

kind regards
Lim Li Ching
Third World Network
posted on 2015-04-30 06:54 UTC by Ms. Li Ching Lim, Third World Network
This is a reply to 6864 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6870]
I eco with Ching and think that the Cartagena Protocol and its supplementary Protocol partially cover the issue of synthetic Biology and I believe that there is a need to consider:
1. Extending requirements for advance informed agreement and risk assessment procedures to synthetic genetic parts in order to cover gaps that otherwise permit evasion of the rules agreed under the protocols. One gap arises from new techniques that make it possible to import DNA sequences over the internet, such that no physical transfer takes place. A second gap arises from related techniques that allow an LMO to be imported as a set of parts ready to be reconstituted, rather than a whole viable organism. These threats to the objectives of the protocol could be addressed by extending advance informed agreement rules so that they also apply to:
       a. Agents that construct an LMO, whether from electronic code or genetic parts; and
       b. Agents that export genetic parts that are "latently viable" (parts deemed to possess sufficient latent potential to form or promote the formation of a viable organism).
2. Excluding from the ‘contained use’ provisions, synthetic genetic parts and living modified organisms produced by synthetic biology, in order to address the new containment challenges they pose - at least until effective containment methods can be demonstrated. Thus the Article 6.2 exemption from having to obtain advance informed agreement for contained use would not apply.

O.A.El-Kawy
(edited on 2015-04-30 10:59 UTC by Mr. Ossama AbdelKawy)
posted on 2015-04-30 10:58 UTC by Mr. Ossama AbdelKawy, Mauritania
This is a reply to 6870 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6872]
Any modified orgaism using in vitro nucleid acid technique should be considered a synthetically modified organism and among points to consider, the risk assessment process to synthetic biology organisms is needed in accordance with the Cartagena Protocolof biosafety
Kind regards
Gado
posted on 2015-04-30 11:51 UTC by Mr. Mahaman Gado Zaki, Niger
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6879]
Dear chair and all others partipating in this online forum,
My name is Boet Glandorf, and I work as a senior risk assessor in the Dutch GMO Office at the National Institute of Public Health and the Environment for more than 15 years.

Here my ideas about the topic under discussion.
• What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?
• Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology?

Answer:
At the moment, we consider that all organisms produced with synthetic biology  fall within the definition of a LMO. Taking into accountt the developments in synthetic biology we foresee that this will not change in the near future.

• What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?

Answer:
The components used in ‘modern biotechnology’ and for synthetic biology can be quite similar and this does not depend on the fact that synthetic sequences are used. Both components used in ‘modern biotechnology’ and in synthetic biology can be synthetic, since nowadays many sequences used to create LMOs are synthesized and can consist of parts of several different genes or are based on reshuffled genes. The same accounts for the use of DNA-based circuits or metabolic pathway engineering. The main difference between an LMO and a synthetic organisms are assumed to be the ‘de novo’ design of synthetic organisms using components that do not have any comparison to a ‘known’ function or a ‘natural comparator’ (like XNA, novel designed nucleic acids).

Products either produced from organisms that are obtained by synthetic biology or produced by LMOs seem to be quite similar at this moment. Most products are based on already existing products or adapted versions. Differences may occur in case the novel components present in synthetically produced organisms lead to completely new products that so far did not exist in nature.

• How do the different areas of synthetic biology, including DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering, protocell construction and xenobiology, overlap or differ from modern biotechnology as defined in the Cartagena Protocol?

Answer:
See above
posted on 2015-04-30 13:27 UTC by Ms. Boet Glandorf, Netherlands
This is a reply to 6879 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6884]
Dear participants,

I would like to reiterate what was said by Dr. Boet Glandorf, which currently agrobiotechnologies are incorporating synthetic nucleic acid sequences even the nature sequences are modified by bioinformatics procedures to improve its action, so the application of synthetic biology it is not new and now these products are marketed like LMO in the agriculture. Indeed we should revisit the issue of the application of approaches such as Xenobiology where a change of the nucleotide bases (XNA) is made and this is new and different regarding to modern biotechnology and its methodologies. Based on the foregoing, incorporate current developments in synthetic biology within the scope of the Cartagena Protocol on Biosafety is an appropriate approach like a first step, however, when analyzing definitions and approach that it has been given to this Protocol where exist a relevance to a technique (recombinant DNA), the instruments become outdated, since science is dynamic and the techniques change every day.
(edited on 2015-04-30 15:56 UTC by Mr. José Leonardo Bocanegra Silva)
posted on 2015-04-30 15:45 UTC by Mr. José Leonardo Bocanegra Silva, Colombia
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6893]
Hello everybody,

My name is Caroline Burgeff.  I work in Conabio (Mexico) mainly in GMO risk assessment and biosafety issues and I have an agronomy/plant molecular biology/biotechnology background.
I am grateful  to de SCBD for the opportunity to join this online forum, to the moderators for their guidance in this process and to every participant for exchanging their views  on the subjects discussed here.

As an operational definition of  SB  has not been settled yet in this context, and  in order to  try to bring some elements  for this second topic proposed,  for this post I am considering,  as a reference  to SB, the areas of research described in the CBD  document  prepared on  the subject (CBD technical series 82 on synthetic biology)

• What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?

In order to present some elements for this question, it is useful first to separate “organisms” from “components and products” :

As many other participants have indicated before, most of the organisms generated through SB (cf CBD Technical Series 82)  can be directly considered as  LMO.  In the particular case of xenobiology,  it  will  depend in the interpretation that  is given to the “LMO” and the “Modern Biotechnology” definitions inside the Cartagena Protocol.  These definitions indicate ““Living modified organism” means any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology; “,  while the definition of Modern biotechnology  includes  “…a. In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA)….”.   So organisms derived  from xenobiology could be considered  or not  to be LMOs depending on  how “wide” is the interpretation  given to the term  “including”  inside the latter  definition. 
In the case organisms generated through xenobiology are not considered to be LMOs, they should anyway  be  evaluated for potential effects  on biodiversity and the sustainable use of its components.

In relation to “components and products”  It is necessary to have clarity concerning  what the terms refer to.  In particular, in the case of products  it is not clear to me  if they can always be considered  “non living entities”. There are cases where products could be living organisms; one example to consider  is  the product of agricultural LMOs actually being cultivated, that  is usually a  grain/commodity   that is  biologically a seed,  that is a living organism.  From this point of view the CP definition  of a “living organism”  is a good reference to keep in mind.

• Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology? What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?

To answer the first question of this bullet, an  established definition  of synthetic biology might be necessary, and  as all of the possible future technological developments  cannot be predicted, I think this needs to be kept as an open question.

In relation to the second question of the bullet,  the “nature” and the “basic function” of the components (eg. Nucleic acids) are similar between modern biotechnology and synthetic biology (although the case of xenobiology components could  be discussed).   On the other hand, the  design and combination of different elements that constitute the components, as they are considered in SB,  can lead to novel  particular products/molecules not initially present in nature (such as novel proteins or  chemical products  arising from  new or modified metabolic pathways).

• How do the different areas of synthetic biology, including DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering, protocell construction and xenobiology, overlap or differ from modern biotechnology as defined in the Cartagena Protocol?

This question can be broadly discussed with the first question for this topic;  as it was said before,  most of the  organisms generated through SB can be considered as  LMO as   they are  “biological entities capable of transferring or replicating genetic material” which  have “a novel combination of genetic material” through the “application of in vitro nucleic acid techniques…”.  
These definitions do not  make a difference  in regards to the  origin of the  “novel combination of genetic material”  (whether it comes from a natural source or if it is synthetized in a lab), the quantity of genetic material  inserted, or the  eventual  existence of functional interactions  between  elements inside the genetic material.  So considering this, most of the SB areas mentioned overlap with modern biotechnology as defined in the Cartagena Protocol. As  it was mentioned before, xenobiology could be considered a particular case.

Best regards,
Caroline
posted on 2015-04-30 21:51 UTC by Ms. Caroline Burgeff, Mexico
This is a reply to 6825 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6894]
Dear colleages,

My name is Noris Calderón and I am working at the Ministry of Environment and Natural Resources and from México.

I agree with Dr. Jonathan post#6825.

I consider that the differences abouth organisms, components and products derived from synthetic biology are a result of a predictive process compared with other tools of modern biotechnology and these kind of products should have to present a low level of uncertainty in the risk assessment.

Best regards to all.

Noris
posted on 2015-04-30 22:57 UTC by Ms. Noris Dalia Calderon, Mexico
This is a reply to 6894 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6901]
Dear colleagues,

my name is Helmut Gaugitsch and I am working at the Environment Agency Austria,  inter alia on GMO/LMO risk assessment and monitoring. My unit has also been working in the area of assessing methodologies for risk assessment of products from new plant breeding techniques. In addition I have the honour to serve as the chair of the Ad Hoc Technical Expert Group (AHTEG) on risk assessment and risk management under the Cartagena Protocol on Biosafety.

I would like to thank the Secretariat for setting up this important discussion and the Chair for ably guiding us through it. I have followed with interest the so far very lively debate and would like to add my voice at this stage in particular to topic 2 “Similarities and differences between LMOs (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology”.

First of all components and products of Synbio techniques may need to be differentiated from organisms resulting from synbio techniques, because components and products may be non-living entities.
Second, according to my experience currently all the living organisms derived from synthetic biology, which are quite far developed, are organisms which would fall under the definition of LMOs according to the Cartagena Protocol on Biosafety and therefore would also fall under the scope of the Protocol. This assessment I think concurs with what many other colleagues have mentioned so far in this forum. Of course there is a lot of research going on and we have to observe if that assessment holds true also for future applications of synbio and the resulting organisms.

I am looking forward to the further debate and I will post my views on topic 3 (operational definition) later in the debate as suggested by the Secretariat and the Chair.

Kind regards

Helmut Gaugitsch, Environment Agency Austria
posted on 2015-05-01 11:00 UTC by Mr. Helmut Gaugitsch, Austria
This is a reply to 6901 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6906]
My name is Genya V. Dana, Senior Science Policy Officer in the Office of the Science & Technology Adviser to the Secretary of State, U.S. Department of State. My scientific training is in environmental risk assessment of biotechnology, and I serve as an adviser to the U.S. government on international policy considerations related to synthetic biology. I am pleased to join the discussion on the forum, and thank the moderators for their work and the thoughtful comments of the other participants in the forum.

We have some discomfort making statements about the number and kinds of products of biological engineering (or synthetic biology, to use the terminology of the forum) that may come under the Cartagena Protocol on Biosafety. The use of biological engineering tools and techniques may result in many kinds of products, and, without knowing what the future holds, it seems unwise to make statements that “most” or “many” products will fall under the Protocol. The Protocol defines living modified organisms (LMOs) as any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology. Living modified organisms are a specific subset of products obtained through the use of biological engineering and thus may fall within the definition of the Protocol. It is important to note that the Protocol applies to certain activities related to LMOs that may have adverse effects on the conservation and sustainable use of biological diversity, taking into account risks to human health, but the Protocol does not apply to pharmaceutical applications for humans that are addressed by other relevant international agreements or organizations. LMOs in transit or destined for contained use are exempted from the Protocol’s advanced informed consent procedures.

We are concerned that the current language in Decision XII/24 is overly broad when describing the topic of “synthetic biology.” It is unclear, for example, what is meant by “components” of synthetic biology and why they should be included in the discussion. Biological engineering uses commercially available products such as plasmids, reagents, and oligonucleotides, and we are opposed to pulling such commonly-used research and development tools into a discussion on biological engineering and the conservation and sustainable use of biological diversity. The United States focuses on the products of biological engineering when evaluating safety, not the tools or process by which the product is produced. Many such products are produced and used in contained facilities and have no interaction with biological diversity, and we are concerned that conversations in the Convention on biological engineering may capture many standard research (e.g., plant breeding) and manufacturing processes and tools that have no connection to the objectives of the Convention and its Protocols.
posted on 2015-05-01 16:18 UTC by Ms. Genya Dana, United States of America
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6909]
Once again many thanks to the secretariat for the opportunity to consider this question and to Ms. María Andrea Orjuela Restrepo for leading off this Discussion. My name is Jim Thomas. I am the Programme Director with the ETC Group, An international Civil Society Organization that has been closely tracking developments in Synthetic Biology for about a decade. We are founding members of the International Civil Society Working Group on Synthetic Biology and the Synbiowatch collaborative. Our documents on the topic can be accessed at http://www.etcgroup.org/issues/synthetic-biology and further materials and resources are available at http://www.synbiowatch.org. I am submitting these comments only on behalf of ETC Group.

Before addressing the more specific questions posed by Ms Orjuela Restrepo I believe  however  it is important to firstly bear in mind that while the Cartegena Protocol on Biosafety is a significant and highly relevant legal instrument when considering the matter of oversight of Synthetic Biology, it is also of limited scope since the protocol exists only to address issues of biosafety arising from transboundary transfer of LMO’s. Those biodiversity impacts that may arise from economic and production shifts that follow from the application of Synthetic biology are not clearly within the scope of the protocol, nor are the impacts on fair and equitable sharing of benefits and risks arising from the utilization of the technologies. While its important to consider the relevance of LMO’s as defined in the Cartegena Protocol, Parties and others should guard against assuming that the most pressing biodiversity-related issues raised by LMO’s produced by Synthetic biology will be dealt with there. Only biosafety issues will be addressed in that forum. In that regard i find very useful the reminder by Dr Lazaro regal do that the Convention has its own definition of Biotechnology:

Secondly, even before we ask whether various techniques and products of Synthetic biology amount to LMO’s, I feel its important to reiterate  the limitations of the Cartegena protocol in dealing with the current generation of Synthetic biology organisms, components and products even where they do amount to LMO’s:

a) The Cartegena Protocol does not appear to apply to the virtual (digital) transfer of LMO’s. If an engineered organism is constructed, tested and developed  in one location, and subsequently sequenced and that sequence digitally  transmitted by internet to be reconstructed in a second location  - this may amount to digital transboundary movement of genetic material but since no physical material is transferred the protocol’s provisions are not triggered. Entire DNA sequences and engineered organisms would have been exported without prior informed consent from the receiving country.

b) The Cartegena Protocol does not cover the transfer of constituent ‘parts’ of an LMO - e.g. biobricks or engineered sequences of synthetic DNA. As described in our submission of 2011 (The Potential Impacts of Synthetic Biology on The Conservation and Sustainable Use of Biodiversity, Submission to CBD SBSTTA by The International Civil Society Working Group on Synthetic Biology - https://www.cbd.int/doc/emerging-issues/Int-Civil-Soc-WG-Synthetic-Biology-2011-013-en.pdf). This risks the problem of being able to export all the parts of an LMO ready for re-assembly while evading the protocol. In 2011 we gave the example of creating a ‘kit set’ of the parts of a living Modified organism that while not living were ‘latently viable’ and would easily become an LMO if combined together by an entity in a receiving country with even minimal skill in the art. Since 2011, this scenario has begun to become real. For example The Glowing Plant Company is offering to ship do-it-yourself kits to genetic engineering amateurs in order to transform Arabidopsis plants to glow in the dark using sequences of synthetic DNA that are contained in the kit. Since nothing in the kit amounts to an LMO per se, the export of such a kit across international borders would not trigger the provisions of the Cartagena protocol.

c) Article 6.2 of the Cartegena protocol waives the requirement for advance informed consent where the LMO is destined for contained use in accordance with the standard of the party of import  ( a physical facility effectively  limiting the exchange with the environment). Since much of the current commercial use of Synthetic Biology is in bioreactor systems this means that much of current commercial use of Synthdtic biology organisms will fall outside the scope of the protocol. As explained in the 2011 submission  by The International Civil Society Working Group on Synthetic Biology this risks both the possibility that existing containment measures are ineffective in light of changes to the organism resulting from synthetic biology but also that agents may engage in regulatory arbitrage, initially  importing under contained use conditions to avoid international risk assessment provisions applying and then subsequently releasing the LMO under domestic laws that may be weaker than the risk assessment process specified ar Annex III of the the protocol.

I note that Dr Ossama Abdelkary of Mauritania has already made similar note of these limitations and am grateful to him for doing so - they are significant challenges.

With this in mind my answers to the more specific questions posed by Ms Orjuela Restrepo are as follows:

It is  clear that the range of techniques today available to modify and engineer living organisms and genetic systems is far wider and more powerful than existed when the Cartegena protocol was under negotiation. Thus the definition of LMO’s adopted by the parties to the protocol is necessarily limited by what was existing at that time and may in any case be in need of some updating now or in the near future. This discussion on Synthetic Biology, which is in effect the term most commonly applied to the digital and automated upgrading of genetic engineering platforms in light of new techniques provides the Convention with an opportunity to ensure that its work remains relevant and able to address the changing nature of Modern biotechnology going into the future.

In our view many of the techniques currently used by synthetic biologists to create engineered genetic systems or using what Dr Bocanegra helpfully defined as ‘artificial genetic material’  do use ‘in vitro nucleic acid techniques’ to produce living organisms “that possesses a novel combination of genetic material obtained through the use of modern biotechnology. These techniques go significantly beyond  recombinant deoxyribonucleic acid (DNA), direct injection of nucleic acid into cells or organelles and Fusion of cells beyond the taxonomic family and it may be useful for the protocol to further enumerate other common or new techniques in light of the changing situation - however we trust that the term ‘including’ does not leave techniques that are unnamed also outside of the scope. An updateable annexe of known ‘in vitro nucleic acid techniques’ , including for example genome editing techniques, may be useful for example.

I do also agree with the sentiment expressed by many respondents that products produced via Synethtic Biiology ‘should’ be regarded as LMO’s However there are some areas of Synthetic biology where it should be clarified that this definition applies or else the definition be slightly expanded for clarity.

For example:

There is ongoing work in the field of Synthetic biology that  is concerned with synthesis and modification of elements of genetic systems other than DNA or RNA molecules themselves (i.e. other than nucleic acids). This includes development of synthetic ribosomes, of novel and engineered amino acids, of protocells and cell-free systems as well as work to alter the epigenetic elements of the genome, such as altering methylation in order to change gene expression. Examples of Epigenome engineering targeting DNA methylation and chromatin structure includes work done by the Penn University IGEM team in 2013 (http://2013.igem.org/Team:Penn/Abstract) and a recent paper by James Collins and his colleagues “Chromatin regulation at the frontier of synthetic biology” -Nature Reviews Genetics 16, 159–171 (2015) doi:10.1038/nrg3900. Recent work on generating synthetic ribosomes is described here: http://www.northwestern.edu/newscenter/stories/2013/06/mimicking-living-cells-synthesizing-ribosomes.html . Of course since ribosomes are RNA-based it should follow that synthetic ribosomes are ‘nucleic acid techniques ’ - but lets make sure that is clearly named as the case.

Related to this epigenetic engineering is use of the RDDM technique (RNA Directed DNA Methylation) which uses small interfering RNA strands to alter DNA methylation and therefore gene expression. RDDM is not strictly an ‘in vitro’ technique since the short synthetic RNA strands applied to the organism would be applied in situ/ in-vivo  (e.g. in an open field or in a vat) and not at the germline, and it may be open to controversy over whether it is a ‘nucleic acid technique’ (since it uses RNA) or not (since the main mode of action is epigenetic). It is clearly a synthetic biology approach - in that it attempts to exercise predictable control over the expression of genetic systems and relies upon synthesis (in this case synthesis of interfering RNA strands) to do so.

By a similar approach the in-vivo  (as opposed to in-vitro) use of genome editing techniques such as CRISPR-CAS9 may also raise concern. While genome editing approaches such as CRISPR-CAS9, TALENS and ZFN are commonly used by synthetic biologists for targeted in-vitro modification of the germ line , there is also an increasing amount of work on in-vivo application of CRISPR-CAS9- primarily for gene therapy use but also for modifying plant and animal tissues. These could become a use of synthetic biology to create targeted mutations  for either agriculture, forestry or conservation purposes that would not strictly be an ‘in vitro’ nucleic acid technique. For example see   J Integr Plant Biol. 2014 Apr;56(4):343-9. doi: 10.1111/jipb.12152. Epub 2014 Mar 6.
Self-processing of ribozyme-flanked RNAs into guide RNAs in vitro and in vivo for CRISPR-mediated genome editing.
Gao Y1, Zhao Y.


Similar definitional concerns may arise in the case of directed evolution techniques being applied in-vivo. Directed Evolution (both in-silico and in the lab) is a common approach in the field of Synthetic biology , using massive automation of genome disruption to produce large libraries of variants for screening. While directed evolution techniques usually involve engineering many variants of gene sequences into a host (thereby an in vitro approach) - it may be that with fast reproducing species such as algae and methods to create rapid and targeted mutants it may equally effective to apply targeted disruption to whole cells.

I note that there has been some discussion over whether xenobiological approaches generate LMO’s - since most Xenobiology concerns  novel nucleotides (e.g. XNA, mirror biology, PNA etc) one would hope that those are still regarded as ‘nucleic acids’ (as pointed out by Frank Hartung) - however it may be more useful to explicitly refer to ‘artificial genetic (and epigenetic?) materials’ (as suggested by Dr Bocanegra)

Finally I strongly support the concern raised by Lim Li Ching of Third World Network that in the context of Syn Bio an LMO/SBO/SMO must not only be regarded as those that contain ‘a novel combination of genetic material’. High profile approaches to ‘re-edit’ pigeon genomes to match the genome of the passenger pigeon, elephant genomes to match the mammoth genome or more prosaically re-editing viral and microbial genomes to mimic existing strains might all be argued to not have ‘a novel combination’ but would clearly be Synthetic Biology and raise significant issues. Would ‘refactoring’ of genomes (i.e. removing material) count as ‘a novel combination of genetic material’ or just less? yet refactoring and minimal genomes are a widely agreed examples of synthetic biology.

Many thanks

Jim Thomas
ETC Group
posted on 2015-05-01 17:56 UTC by Mr. Jim Thomas, ETC Group
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6928]
Dear participants,

I would like to share some ideas about the topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques).


The Cartagena Protocol defines “Living modified organism” as any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology. Also, the living organism develops through synthetic biology has a novel combination of genetic material derivate from the use of modern biotechnology. However, synthetic biology redesigns or rebuilds metabolic pathways, builds functional genomes from pieces of synthesized DNA; creates the simplest possible components to sustain reproduction, self-maintenance, metabolism and evolution; and develops life forms based on biochemistry not found in nature.  Hence, synthetic biology builds molecules derived from natural nucleotides and molecules from oligonucleotides (i.e. one unnatural form nucleotide or chemically synthesized molecules).

The biosynthetic technology uses information on DNA to build novel products and also uses nanotechnology, so this technology has more variables to change process to obtain many products. Also, it has been catalyzing by computational modeling, bioinformatics. The risk assessment should be on the base the product not to prevent impacts on biodiversity, ecosystems and human health.

Likewise, the components and products of modern biotechnology in Cartagena Protocol are derived from LMO, use natural molecules, but in synthetic biology include also novel products and components that not existing in nature. However, the results give organisms or products that not exist in nature.

Finally, DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering and protocell construction present overlap Cartagena Protocol; nonetheless xenobiology, differ from modern biotechnology as defined in the Cartagena Protocol.

Best regards,

Dr. Marina Rosales Benites de Franco
IUCN’s Commission on Ecosystem Management
(edited on 2015-05-02 05:22 UTC by Ms. Marina Rosales Benites de Franco)
posted on 2015-05-02 05:21 UTC by Ms. Marina Rosales Benites de Franco, IUCN
This is a reply to 6928 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6930]
Thank you again, Maria Andrea Orjuela Restrepo for this opportunity to participate. I am Elpidio Peria from the Biodiversity Management Bureau of the Department of Environment and Natural Resources of the Philippines. I reproduced your questions and my answers follow, for easier reading.

What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?

It will appear from the discussions  that the point of similarity between LMOs as defined by the Cartagena Protocol  and the living organisms that are currently developed through synthetic biology is that they are using modern biotechnologies.

But that is only up to a certain point, since if we look closely at some of the supporting technologies that underpin synthetic biology which are  enumerated in the CBD Technical Report No. 82, like,   computational modelling, bio-informatics and information sciences and “biological teleportation”, they are mainly facilitated with the help of  information technologies. Does classic genetic engineering that is mediated through information technologies, including the internet, still modern biotechnology? This does not seem to be contemplated or may have been foreseen by the definition of modern biotechnology in the Cartagena Protocol. (see   also Mackenzie Ruth, Burhenne-Guilmin, Francoise, La Viña, Antonio G.M., and Werksman, Jacob D., in cooperation with Ascencio, Alfonso, Kinderlerrer, Julian, Kummer, Katarina, and Tapper, Richard (2003)., An Explanatory Guide to the Cartagena Protocol on Biosafety. IUCN, Gland, Switzerland and Cambridge, UK, see pp. 46-51)

Another differentiation is that the  organisms, components and products of synthetic biology sometimes do not result in novel combinations of genetic material, as in fact most of them, especially those that are replacements of biochemical compounds found in nature such as vanillin, etc. and also,   the techniques of modern biotechnology are oftentimes not the same as the techniques of synthetic biology, especially gene editing techniques such as CRISPR, ZFN, etc 
Ultimately,  Lim Li Ching  of Third World Network’s point that the organisms, components and products of synthetic biology techniques make up a broader category than ‘living modified organisms’ (LMOs) as defined under the Cartagena Protocol is well-taken. This is actually the same point Dana Carvey of the US is saying, though for different reasons (some of these products are produced and used in contained facilities and have no interaction with biological diversity, and that some of these products that may be LMOs under the Cartagena Protocol are actually outside the scope of the Protocol because of their pharmaceutical applications for  humans)



• Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology? What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?

Like what Caroline Burgeff of Mexico has said, this is an open question. What will matter is the appreciation of the two ways which the CBD Technical Report says is the distinction between synthetic biology and classic genetic genetic engineering : (1) in terms of the methods that are adopted; and (2) the sophistication and complexity of the work.

Depending on the methodologies that may become dominant in the applications that will have sustainable commercial potential in the near future, either the similarities or differences highlighted above will remain  and become more distinct or these similarities and differences will become blurred as to be indistinguishable from each other.



MODERATOR’S FOCUSING QUESTIONS:

1) Some of you suggest that the discussion about effects on biodiversity would be centered on products of synthetic biology. In this point I think that is important to define clearly the terms: component and product. I have the idea that many of you think in product as an organism but certainly is possible to obtain different kind of products by synthetic biology, not only organisms. The Dr. Hideyuki Shirae`s definitions would help us but I think that would be interesting to know another points of view.

While it would seem difficult and perilous and may serve to impede the development of these technologies, the incorporation of the principles and approaches in responsible innovation as I have earlier articulated should be crucial in addressing the future societal concerns that we will encounter, thus it is important we don’t only focus on products but also on the various processes and methodologies, emerging or incipient they may be, on synthetic biology.

We are actually now faced with Collingridge’s Dilemma, stated by  David Collingridge in his book The Social Control of Technology  (1980) :

‘The social consequences of a technology cannot be predicted early in the life of the technology. By the time undesirable consequences are discovered, however, the technology is often so much part of the whole economics and social fabric that its control is extremely difficult. This is the dilemma of control. When change is easy, the need for it cannot be foreseen; when the need for change is apparent, change has become expensive, difficult and time consuming’’   (quote from  Wolfgang Liebert and  Jan C. Schmidt, (2010), Collingridge’s Dilemma and technoscience, an attempt to provide a clarification from the perspective of the philosophy of science, Poiesis Prax (2010) 7:55–71, DOI 10.1007/s10202-010-0078-2)


It is therefore important we don’t only look at the products of the technologies relating to synthetic biology.

2) If the adopted position is focus on products as I saw in several interventions, is important discuss about the products that have “components”, which refers to “molecules derived from oligonucleotides which at least contain more than one unnatural form nucleotides and/or chemically synthesized molecules”  as Dr. Shirae said. It is possible to define clear limits to said that those products have or have not to fall inside Cartagena Protocol?

YES, it’s possible to define clear limits to what’s in or  out of the Cartagena Protocol. The Cartagena Protocol has many exclusions already pointed out by Ms. Lim Li Ching of Third World Network and Dana Carvey of the US, and also the examples and questions of Dr. OA El-Kawy of Mauritania, thus, any such products or components that don’t come within the scope of the Protocol needs to be dealt with through another instrument or process. I recall there was an earlier intervention on this that perhaps another protocol within the CBD  may tackle these exclusions. But that’s another topic for our later discussion.

Thank you.
posted on 2015-05-02 10:05 UTC by Mr. Elpidio Peria, Philippines
This is a reply to 6901 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6935]
Dear Participants and the Chair on this on line forum,

Thank you for the Secretariat for setting up this online forum and the Chair for his helpful assistant in this forum.

Reading the opinion of Mr. the Helmut Gaugitsch’s (#6901), I feel curious about the opinion because he stated “components and products may be non-living entities.”.  If so, the organisms which are made by the synthetic biology and do not make any “Products (non-living entities)” are out of the scope of “Products” in synthetic biology.  I have different thoughts as I stated in the first portion of this discussion.    We have been obtaining a lot of profits from modern biotechnology and also will have been obtaining more profits from the synthetic biology techniques.  On the other hand, we should watch for the technology that it will not use for some harmful procedures and making products.  I fully agree the risk assessment for the “Products” derived from synthetic biology must be performed by the product-based method.  Therefore, I think the definition of “Products” is much important. 

Regarding the non-living entities, there have already been existed lots of regulations to evaluate chemicals, food, any information on the internets and other entities.  We do not need discussing such existing regulations in this forum and COP again.   As I stated in the first part of this forum, “Products” must be the reproducing entities including Living Modified Organisms (LMO) for further risk assessment.  The difference between the LMOs (as defined in the Cartagena Protocol) and “Products” of synthetic biology” is whether “Products” are designed or redesign the living systems and characterized by the novel “Components” or not.    

After May 3, this discussion will move to Topics 3 in accordance with the Chair’s (or Moderator?) announcement.  In Topics 3, we should discuss the clear definition of “Products” in synthetic biology, besides the definition of “synthetic biology”.  Then we had better going back to Topics 1.

Thank you all.    
   Hideyuki
posted on 2015-05-03 00:24 UTC by Mr. HIDEYUKI SHIRAE, Japan
This is a reply to 6935 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6939]
Dear Hideyuki, dear all,

thank you Hideyuki for reflecting on my recent posting (your message #6935), which shows that I may not have been sufficiently clear in my comment, apologies!

To my understanding, the term "products" may be used in two distinct ways in the context of modern biotechnology, and that may be a cause of confusion. The first way of using the term "products" refers to something originating from LMOs, but that itself is no longer living entities, such as, for example, flour made of genetically modified corn. This is how I used the term in my last intervention. Another way to use the term "products" refers to the LMO itself or, to use an example that is analogous to the above, the genetically modified corn itself. I guess there is no right or wrong way of using the term but it is important to have a common understanding about the context in which it is being used. This may not necessarily mean that a definition for "products" is needed as it may be sufficient to explain in which context the term is being used, but we may want to enter this debate in the context of session 3 later this week.

I hope I could clarify my intervention and explain the possible cause of misunderstanding and I am looking forward to the further debate.

Thank you and kind regards

Helmut Gaugitsch
posted on 2015-05-03 08:17 UTC by Mr. Helmut Gaugitsch, Austria
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6942]
My name is Mike Paton, I am a policy advisor on microbiology (including LMOs and synthetic biology) in the UK’s principal workplace safety regulator (Health and Safety Executive). I have a scientific background in molecular microbiology, supplemented by many years’ experience as a biosafety regulator. I am pleased to participate in the synthetic biology on-line discussion forum and thank the moderators and other participants for their interesting and important contributions.

Current organisms generated by synthetic biology are captured by UK and EU regulatory frameworks, and as agreed by most respondents, are captured by the provisions of the Cartagena Protocol for Biosafety. The CBD defines genetic material in terms of functional units of heredity, which would encompass DNA, RNA and XNA. The Cartagena Protocol defines an LMO as any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology. There is a discussion as to whether this only relates to ‘novel combinations’ as mentioned by several respondents.

The reference to organisms, components and products of synthetic biology, is broader than that covered by Cartagena. As pointed out by Genya Dana, Jim Thomas and others, Cartagena only applies to LMOs. However, where the Protocol does apply, its obligations extend beyond only the need to ensure safe transboundary movement (ie to “ensure that the development, handling, transport, use, transfer and release of any living modified organisms are undertaken in a manner that prevents or reduces the risks to biological diversity, taking also into account risks to human health”).  Similarly, where exemptions apply (eg LMOs for contained use), this exemption only relates to provisions of the advance information agreement whilst the other general provisions will still apply.

From the submissions so far, there is ambiguity in the use of the words ‘products’ and ‘components’. When mentioned in Cartagena, a product is assumed to be an LMO, whereas, as helpfully clarified by Helmut Gaugitsch, its use in the context of synthetic biology is of broader scope. It may be helpful to clarify how participants are using the words ‘product’ and ‘components’ in their submissions. This may help the process (in topic 3) towards an operational definition of synthetic biology.

Our interpretation is similar to that of the moderator, the term ‘component’ is intended to refer to the molecular tools (eg genetic sequences, genes, chassis, circuits, plasmids) - these may either be cloned or synthesised copies of sequences that occur in nature, or they may be newly designed on a computer. When introduced into an organism, the component becomes an LMO. Other components of synthetic biology may include novel amino acids, novel proteins and/or combinations of these that have been engineered to form a cell-like structure (protocell) as well as xeno nucleic acids. As such, the ‘components’ of synthetic biology do not pose any biosafety risks to biodiversity of themselves because they are inert chemicals, used in small quantities and generally regulated as commercial biological products for use in a laboratory. As pointed out by Genya Dana, this broad definition covers a multitude of reagents for modern biotechnology, which were not intended to fall under the Convention and its Protocols.

Our interpretation of the word ‘product’ can include organisms, LMOs and components as well as resultant biomolecules (mainly because it is often associated with a commercialized or marketed entity). Such biomolecules and other organic chemicals that are manufactured by organisms as a result of synthetic biology (eg. vanillin, artemisin, squalene, resveratrol, nootkatone, algal oil etc). Todd Kuiken helpfully provides a link to Tables listing all such products that are known to be in development or already commercially available. It may be useful to agree on a term that captures the aforementioned biomolecules, for example ‘commercial compounds’.

Several additional points have been raised in relation to components or ‘commercial compounds’. As interpreted by Jim Thomas, and others, such ‘commercial compounds’ are not covered by Cartagena. However, once assembled into an LMO (regardless of whether from digital, synthetic or natural sequence material) I think  the general provisions (including biosafety risk assessment) of Cartagena and the wider obligations of CBD would still apply. The concerns expressed in terms of socio-economic impact, require case by case assessment (eg life cycle analyses) to facilitate further discussions. Edward Hammond and others, have highlighted the potential for the inequitable use of components. This needs further discussion but may be better couched in terms of Nagoya rather than Cartagena Protocol.

Many thanks
posted on 2015-05-03 11:22 UTC by Mr. Michael Paton, United Kingdom of Great Britain and Northern Ireland
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6944]
Dear participants,

I am grateful with your opinions and thoughtful comments. As you know the discussion now will move to topic 3. As many of you pointed out, working in a consensus definition of Synthetic Biology would be useful for maybe, going back and building some important definitions as “Products” and “components” in the context of SynBio and Cartagena Protocol.

I consider important to do an indicative summary about some points for keep in mind, maybe a key issues that could be revisited later:

1)Most of the opinions denote that LMOs is a term that includes the current products of SynBio.
2)A general viewpoint is the need to focus on product more than methodologies to talk about effects on environment.
3)The meaning of the terms “components and products” until now, is not clear as pointed out by Caroline Burgeff and Genya V. Dana.
4)As Lim Li Ching mentioned: “the Cartagena Protocol only addresses products thereof under its Article 20, Annex I and Annex III, so its scope is limited in relation to the components and products of synthetic biology”.
5)Could be useful to consider the different and wide kind of “products” that currently are on the horizon or on the market to reconsider the terminology that has to be used and the applicability of actual RA methodologies on products of SynBio  (One example was pointed out by Todd Kuiken, inside the discussion of topic 3 and can be consult on http://www.synbioproject.org/cpi/applications/).
6)In relation with Risk Assessment approaches, those that currently are applied seem to be useful with some modifications.
7)O.A. El-Kawy indicate the need to extend requirements for AIA and Risk Assessment procedures in order to prevent gaps that could be originated in "Contained Use" and/or  use of “Digital transboundary movement of genetic material” and the “transfer of constituent ´parts´of an LMO” as Jim Thomas and Elpidio Peria denoted.
8) Xenobiology products could not be included under Cartagena Protocol but this have to be revisited as Leonardo Bocanegra indicated.

As an aditional comment I want to point out that is important to remember that currently some products of SynBio are into the scope of another treaties or agreements: Codex Alimentarius, Agreement on the Application of Sanitary and Phytosanitary Measures of the World Trade Organization, International and those provide mechanisms, procedures or institutions that can address potential negative effects associated with the application of SynBio techniques; and this have to take into account in relation with the interaction between the CDB and its derivatives and their relations with other legal frameworks at global, regional and national levels. 

I am looking forward to the further debate,

Kind regards

M. Andrea
(edited on 2015-05-03 19:45 UTC by Ms. María Andrea Orjuela Restrepo)
posted on 2015-05-03 17:13 UTC by Ms. María Andrea Orjuela Restrepo, Mexico
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6956]
Dear Colleagues,

I am Dr Gulay Mann, a principal research scientist at the DSTO.

I would like to start the discussion by providing a historical background. The first use of the phrase “synthetic biology” dates back to the very early 1900’s when Stéphane Leduc, a French biologist, used it in his papers titled “Théorie physico-chimique de la vie et générations spontanées” (Leduc, 1910) and “La Biologie Synthétique (Leduc, 1912). However, Leduc’s definition of synthetic biology encompassed physical forces governing life. Use of the phrase “synthetic biology” as we know it now was first popularised in 1974 when Wacław Szybalski described a field where engineering principles can be fully applied to biology: “Up to now we are working on the descriptive phase of molecular biology. ... But the real challenge will start when we enter the synthetic biology phase ... We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes.”… (Wacław Szybalski, 1974).

Since then, synthetic biology has progressed to the point that today it is a cutting edge field attracting significant attention from both the research community and the broader community.

The emergence of synthetic biology was driven by four major motivations. The first was to attempt to understand complex biological systems by taking them apart, studying their individual parts and then trying to rebuild them. The second was to enable living organisms to better perform useful roles by manipulating them at the molecular level. Given the appropriate selective pressures, this process would naturally take place over a long period of time (natural selection); synthetic biology approaches can significantly expedite this process (Serrano 2007). Third is to generate standardized building blocks that can be used to build functional biological systems to test our current understanding. The fourth motivation is the potential use of synthetic biology as a technology platform for specific useful purposes, including information processing, energy and food production, environmental sensors, etc.

Whilst the emergence of synthetic biology was driven by these motivations, the progress of the field was facilitated by two key technologies: (1) Automated DNA synthesis, a key enabling technology required to build code for the various biological devices which allowed the field to develop beyond conventional biotechnology. Customised DNA synthesis allows the construction of genetic elements and can be tailored to carry out specific existing and novel functions. (2) Automated DNA sequencing, which allows synthetic biologists to confirm that the sequences they have constructed are correct.

In my view, the synthetic biology is not a science discipline nor is it a new science per se, but it is a collection of tools and techniques used across a range of technologies, for both basic and applied research. It builds on the advances in molecular biology and biotechnology; however; the key element that sets apart synthetic biology from other more conventional approaches is the focus on standardization and abstraction of modular biological components (minimal parts of enzymes, genetic circuits, and reporter protein coding DNA etc.). As the individual smaller biological components are studied, tested and understood at a sufficient level, then they can be assembled into larger biological devices that can achieve to solve a particular problem.

One of the most significant aspects of SB is to build tools that claim to make biology easier to engineer. Fuelled by the reductionist approach synthetic biologists became very good at pulling biological systems apart to study their individual components, however understanding of how these individual parts go back together is lagging behind because of the complexity of biological organisms and the environments they must adapt. Re-building the biological systems that carry out specific functions provides a rigorous test of our understanding of the system under study so is not merely an engineering objective, it also generates new knowledge.

The latter approach of rebuilding biological systems can benefit from a community that works together to design, re-build and test various biological systems and share their results in an open-source platform. The international Genetically Engineered Machines (iGEM) competition (http://igem.org/Main_Page) is an attempt to develop such a community. It not only helps synthetic biology to grow rapidly but also enables systematic engineering of biology while supporting development of relevant tools in an open-source platform.

Given that synthetic biology is made up of tools and techniques from a wide range of scientific disciplines and it is an approach to making biology easier to engineer, the biosafety assessments, rules and regulations needs to cover the applications and the products achieved so far. With this view in mind, the suggestion of a case by case, science-based risk-assessment of synthetic biology applications to identify actual risks to biodiversity is valid.

The Cartagena Protocol on Biosafety, the safety rules/regulations relating to GMOs/LMOs covers the synthetic biology applications so far.

However, the rapid progresses have been made by the SB approaches make it valid that we need to revisit our discussions at regular intervals.

Leduc, S. Théorie physico-chimique de la vie et générations spontanées. Vol. 1. Poinat, (1910).
Leduc, S. La biologie synthétique. Vol. 2. Paris: A. Poinat, (1912).
Serrano, L. Synthetic biology: promises and challenges. Mol. Syst. Biol. 3, 158 (2007).

Regards,
Gulay
posted on 2015-05-04 00:04 UTC by Ms. Gulay Mann, Defence Science and Technology Organistaion
This is a reply to 6956 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6958]
First of all, I will like to thank Andrea Orjuela for moderating this topic.

My name is Jorge-Antonio ROJAS-BELTRAN, I am from the San Simón University (Cochabamba-Bolivia). I am coordinator of the “Bio-Nanotech Applied to Agriculture Research Center”

Synthetic biology is part of modern biotechnology. However, the term of “Living Modified Organism” (LMO), regardless of any definition that can be given, is not useful to name the biological systems created by synthetic biology. All the words that compose the term LMO have been overtaken by synthetic biology. Let analyze word by word:

1. Living organisms. In synthetic biology, not necessarily the "products" will be generated using living organisms. In synthetic biology, we can work with components of living organisms (tissues, organelles) to generate products. This possibility will be enhanced in the future, as biotechnology and nanotechnology will approach more and more.

2. Modified. In synthetic biology, we not only modify organisms, but we can create organisms and other biological systems.

Then, we need to find another term for biological systems created by synthetic biology. In this sense, I think that a word that must necessarily be present in this term is "creation", it should replace "modification", which is the fundamental difference between the LMOs and biological systems created by synthetic biology. The term "living organism" should also be replaced. Particularly, I like the term "biological system" to replace the term "living organism" which is already used in some definitions of synthetic biology. Therefore, I propose that the term Living Modified Organisms (LMOs) will be replaced by the term "Created Biological Systems" (CBS). From this term, we can easily derive a definition of synthetic biology:

Synthetic biology or biological engineering (less ambiguous term for me), is a technology that allows create biological systems capable of generating useful products for humanity.
posted on 2015-05-04 02:06 UTC by Mr. Jorge Antonio Rojas Beltrán, Bolivia (Plurinational State of)
This is a reply to 6864 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#6992]
POSTED ON BEHALF OF XU JING IN REPLY TO MESSAGE #6864

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Dear participants,

I am Xu Jing from Chinese Research Academy of Environmental Sciences (CRAES).

I am of the view that the Cartagena Protocol and its supplementary Protocol is partially cover the issue of synthetic biology. I echo with Lim from TWN and some others that the organisms, components and products of synthetic biology techniques have a broader category than LMOs in Cartagena Protocol.

According to CBD, genetic material means any material of plant, material of plant, animal, microbial or other origin containing functional units of heredity, which would encompass DNA, RNA and XNA. The difference between LMOs and synthetic organisms is that the design of synthetic organisms using components that do not have any comparison in nature, for example, XNA which is made up from Xenobiology (different regarding to modern biotechnology in CBD and the Cartagena Protocol).

Kind regards

Xu Jing
posted on 2015-05-04 16:10 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 6928 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7001]
POSTED ON BEHALF OF JONATHAN MUFANDAEDZA IN REPLY TO POST #6928

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dear all
i agree with marina franco that indeed nanotechnology in combination with biotechnology(nanobiotechnology) will contribute towards synthetic biology products. should i therefore also suggest that our defintions on similarities on LMOs and synthetic biology products also accounts for the role of nanobiotechnology. The products of synthetic biology will be influenced by these current technologies and to a greater extend and therefore regulatory and biosafety system should take this into account.
thanks
dr jonathan mufandaedza
national biotechnology authority of zimbabwe
posted on 2015-05-04 20:56 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 7001 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7055]
Dear colleagues,

My name Ricarda Steinbrecher, with the Federation of German Scientists (VDW).

Please let me share with you my thoughts on this topic.

Organisms, components and products of synthetic biology techniques cover a much wider range than LMOs, as LMOs clearly only refer to Living Organisms, not to components or products.

For example, synthetic biology also utilises cell free systems containing genetic information/sequences, which thus do not fall under the definition of an LMO. However, in case of contact with the environment, DNA or RNA would still be readily available for appropriation by other organisms from such cell free systems which would very likely not be regarded as ‘biological entities’ (see use of terms for  ‘living organism, Cartagena Protocol on Biosafety).

Article 3 (Use of Terms) of the Cartagena Protocol states:
g)  "Living modified organism" means any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology;
(h) "Living organism" means any biological entity capable of transferring or replicating genetic material, including sterile organisms, viruses and viroids;
(i) "Modern biotechnology" means the application of:
a. In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA) and direct injection of nucleic acid into cells or organelles, or
b. Fusion of cells beyond the taxonomic family,
that overcome natural physiological reproductive or recombination barriers and that are not techniques used in traditional breeding and selection;


Given the current availability and utilisation of techniques of “modern biology” – as defined under the Protocol, the majority of organisms resulting from synthetic biology would at present be covered by the definition of an LMO, but this is not true of all – and does also not cover future developments.  The definitions under article 3 (see above, especially underlined sections) limit the extent to which a modified organism may be called an LMO. The definition of “modern biotechnology”, for example, with the proviso of “that overcome natural physiological reproductive or recombination barriers” creates a substantial grey zone with much room for interpretation, with some organisms resulting from synthetic biology clearly not being covered – and thus not being eligible as an LMO. 

Epigenetic changes are excluded from cover
For example, organisms with epigenetic changes introduced through transient delivery of dsRNA resulting in gene silencing over at least a number of generations (RNA-dependent DNA methylation (RdDM)), do not fall under the definition of LMOs (as defined in the Cartagena Protocol), as there is, for example, no “novel combination” of genetic material. The methylation of the Cytosine nucleotide for example does not change the DNA sequence but rather prevents the gene from being activated and transcribed. Thus this form of an SB organism is not covered as an LMO and hence no risk assessments are required  – irrespective of risks and potential negative impacts.

On this item I agree with others on this forum, that organisms derived through techniques of synthetic biology using in vitro nucleic acid techniques – such as genome editing techniques – should be regarded as a synthetically modified organisms, irrespective of whether or not there is a novel combination of genetic material, and whether or not it would fulfil the definition of an LMO.


Circumventing regulation
Furthermore, moves are now afoot to have GMOs resulting from certain in vitro nucleic acid techniques and applications excluded from the European GMO regulations based on legalistic arguments that they do not meet the definitions of a GMO (eg NBT Platform, April 2014).  This is also where it is clearly very important to ensure that the process of engineering a GMO is considered in any assessment. To consider only the product and not the process involved, as is preferred by some, is failing to recognise that the process itself does lead to quantitative and qualitative changes, other than just the “addition” of the intended trait. Non-target effects as well as transformation induced mutations, but also pleiotropic effects of an introduced gene or regulatory interference are sufficient reasons for all genetically engineered organisms –irrespective of definitions- to undergo a full risk assessment and require an AIA. In this, the technology has to remain as the trigger for risk assessment, and irrespective of similarities or differences between LMOs and “organisms, components and products of synthetic biology techniques”, the task and obligation is to ensure that non slips through the net of risk assessment and AIA requirement either due to insufficient definitions or misconceptions of risk.

Arguments have been made, for example, that one-base changes or other smaller changes of the DNA sequence should not be regarded as an LMO, as they are more akin to mutations that occur naturally.  From my experience, single point alterations of DNA can completely change the function of the resulting protein, for example in the case of the factor IIIV gene, where a single point mutation can lead haemophilia (bleeding disorder). The fact that so-called  “precision” techniques are being utilised, such as genome editing, does not mean the organisms has not been genetically modified. To the contrary, genome editing is very clearly a genetic engineering technique, and strongly utilised in the field of synthetic biology and needs to be covered by its terminology/definition, regulation and risk assessments. The arguments of precision stop at the most basic level, namely at the DNA level and only at the point of intended “editing”.  Yet genome-editing is not free from off-target effects and furthermore, as already mentioned under topic 1, the assumption that more precision translates into more predictability stability and safety is largely a narrative and not based on any data. It is not possible to extrapolate “precision” and/or predictability from the minute molecular level (eg a specific DNA sequence alteration) to cellular processes, and higher levels such as the genome, the epigenetic landscape, the organism, the ecosystems or the socio-economic conditions that differ around the world.  It is actually into all these levels that organisms, compounds and products of SB need to be contextualised.

Similarities between LMOs and organisms resulting from synthetic biology
lie largely in the use of the same or similar techniques of in vitro nucleic acid techniques resulting in the modification of the genetic material of an organism.

However, the vocabulary and concepts used are at times   quite distinct and indicate a very different mindset and approach to organisms, living systems, their integrity and their place within biodiversity, eg by referring to organisms as machines, with all the assumptions about human control and instrumentality inherent in this metaphor.

Synthetic biology introduces a step change (qualitatively and quantitatively) with respect to LMOs, which needs to be captured both for regulatory and risk assessment purposes.

with kind regards,

Ricarda
posted on 2015-05-06 11:46 UTC by Ms. Ricarda Steinbrecher, Federation of German Scientists (Vereinigung Deutscher Wissenschaftler)
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7057]
Dear participants,
I am Swantje Strassheim and I work for the German Federal Office of Consumer Protection and Food Safety in the department for genetic engineering. I am charged with the monitoring of Synthetic Biology on behalf of the German Central Committee for Biological Safety (ZKBS).

I will try to answer some of the questions posed by María Andrea Orjuela Restrepo:

What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?
Similarities: LMOs as well as living organisms currently developed through synthetic biology possess “a novel combination of genetic material”. Therefore, they both fall under the definition of LMOs given in the Cartagena protocol.
Differences: Here I agree with Lázaro Regalado that in synthetic biology, in contrast to “traditional” LMOs, unnatural base pairs can be used to create new nucleic acids.
Synthetic Biology also has the aim to create streamlined chassis organisms possessing only a few genes necessary for survival as a platform for different applications. These chassis organisms with a reduced genome can also be considered as organisms with “a novel combination of genetic material” since the order of the genes of a chassis organisms will be rearranged in comparison to the natural genome.

What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?
Regarding this question I agree with Genya Dana that commercially or openly available components such as plasmids, reagents or even biobricks should not be part of a discussion on modern biotechnology and its relationship to biodiversity.

How do the different areas of synthetic biology, including DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering, protocell construction and xenobiology, overlap or differ from modern biotechnology as defined in the Cartagena Protocol? 
The areas of synthetic biology that create an organism with “a novel combination of genetic material” overlap with modern biotechnology as defined in the Cartagena protocol. To my mind, these areas are: synthetic metabolic pathway engineering, genome-level engineering and xenobiology. In the case of protocells, de novo creation of a living organism will be possible in the future and we might not be able to tell whether the genetic material used in the protocell is “a novel combination of genetic material”.
posted on 2015-05-06 12:31 UTC by Ms. Swantje Strassheim, Germany
This is a reply to 7057 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7067]
Dear participants,

According to the definition I´d proposed (Topic 3) my understanding is that ´all organisms from Synthetic Biology are LMOs but not all LMOs are Synthetic Biology´ that means that LMOs are a broad group that incorporate many different techniques and synthetic biology are only one of those.

Regarding the difference I agree with Dr. Boet that the main difference between LMO and a synthetic organism is ´the ´de novo´ design of synthetic organisms using components that do not have any comparison  to a ´know´ function or a ´natural comparator´ but at the moment all the products from synthetic biology are based on already existing products or adapted versions. Possible new products that do not exist in nature could be better assessed using the regulatory framework applied for chemical substances, for example.

Thank you.

Best regards,
Luciana/Ministry of Agriculture – Brazil
posted on 2015-05-06 18:39 UTC by Ms. Luciana Ambrozevicius, Brazil
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7103]
Dear all, my name is Matteo Lener, I work on the risk assessment of GMOs since 1999, and I have a scientific background in molecular and cellular biology, I’m working at the Italian Institute of Environmental Protection and Research. Considering that the three parallel discussions on this Forum are partially overlapping topics, I’m going to try to reply remaining strictly linked to the premise of this topic and its questions.
I generally agree with the comments of Caroline Burgeff, Boet Glandorf, and Mike Paton.
Answers:
1. What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?
Starting from the definitions of “components” given by the moderator and of “living organism”, “LMO”, and "Modern biotechnology" given in the Cartagena Protocols, together with the definition of "Genetic material" in the text of the Convention, I think that organisms currently developed through synthetic biology could be considered LMOs as defined in the Cartagena Protocol.
2. Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology?
I think that the SB organisms in the near future still would fall under the LMOs definition.
3. What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?
Taking into account that we don’t have a clear definition of SB yet, I consider that products of “modern biotechnology”, as defined in the Cartagena Protocol, are LMOs, while the products of SB can be living organisms or NOT living entities, as defined by the moderator at the beginning of the Forum on this topic. In the case of living organism see the response at the question 1.
4. How do the different areas of synthetic biology, including DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering, protocell construction and xenobiology, overlap or differ from modern biotechnology as defined in the Cartagena Protocol?
In my opinion the majority of the SB techniques can be included in the “modern biotechnology”, even if a strict interpretation of its definition seems to exclude those techniques that don’t use nucleic acid.
posted on 2015-05-08 11:49 UTC by Mr. Matteo Lener, Italy
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7104]
Dear all,

My name is Jaco Westra from the Dutch Governmental Institute of Public Health and the Environment (RIVM), Centre for the Safety of Products and Substances. I am working as a policy advisor to the Ministry and coordinate the RIVM activities in the field of Synthetic Biology. I have a background of 20 years in risk assessment and policy analysis and policy development.

I am very pleased to be given the opportunity to join the discussion and I can hopefully add a useful viewpoint to the wealth of arguments being put forward in the forum already.

I have some general aspects which I would like to add to the discussion
o Currently, LMO and organisms developed through synthetic biology are identical. That is, the definition of LMO is sufficiently broad to encompass organisms developed through synbio techniques.
o Much of the assessment will boil down to the interpretationof the definitions on LMO and modern biotechnology, and the words and terms contained within these definitions. The definition of LMO seems sufficiently broad also to cover future developments, but might depend on the precise explanation of the term 'genetic'. Assuming that with 'genetic' a general inheritable chemical coding mechanism is meant, the LMO definition will cover a future organisms as well.
o The definition of modern biotechnology makes use of the term 'nucleic acid' which presumably is a specific range of defined chemical molecular entities, and is therefore most likely restrictive in the sense that not all future synbio developments will be covered. If the term is not specifically defined, it might be worthwhile considering giving it an interpretation within the protocol that is sufficiently broad to also cover future synbio organisms. This aspect also touches upon the discussion related to  'component'.
o From a product perspective there seems to be no difference between a product from modern biotechnology and a product from synthetic biology. But again a specific interpretation of e.g. the 'nucleic acid' term in the definition may result in less overlap.


These are my thoughts so far. I am looking forward to a continued and fruitful discussion.

Respectfully,

Jaco Westra
posted on 2015-05-08 12:18 UTC by Mr. Jaco Westra, Netherlands
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7105]
Dear Participants,

My name is Dr.Todd Kuiken. I am an environmental scientist and the principal investigator of the Woodrow Wilson Center's Synthetic Biology Project. (http://www.synbioproject.org) I would like to thank the moderator and the other participants for such a robust and exciting discussion.

For the most part I believe that synthetic biology does not present any significant differences when compared to living modified organisms as defined in the Cartagena Protocol, if one took a broad interpretation of the definition, particularly part 2., “Fusion of cells beyond the taxonomic family”. A potential difference could present itself if one takes a strict reading of the definition presented for this discussion: “components” are parts used in a process (e.g. a naked DNA molecule), and “products” are the resulting output of a process (e.g. a chemical fragrance). Moreover, both “components” and “products” are NOT living entities”.
 
This difference presents itself with the development of CRISPR nuclease Cas9 and the potential applications/products that it enables. Esvelt et al. 2014 described the theory behind the technology and its theoretical use as a method for spreading altered traits through wild populations over many generations.  Less than a year later this theory was shown to work at an average 97% effective rate (Gantz and Bier, 2015). The difference between current LMOs lies within the particular traits the technology enables in the resultant “product”, which is a living organism. The resultant “product” is a “living” entity which incorporates the “components” of synthetic biology, which are then transferred, via CRISPR Cas9, through the reproductive mechanism of the organism.  So here you have an example where the “components”, the CRISPR Cas9 (which are arguable non-living”), enabling the gene editing (the process) to take place within a living organism (the product). Then that entire “non-living” component is transferred through the reproductive cycle to the resultant living organism which then continues the process.  So in essence you have a living vector which is producing the synthetic biology component in the environment (if the application is released and is being used for disease vector control for example). 

I do not believe the current definitions of the Cartagena Protocol capture such an application. However, the rapid development and uptake of CRISPR Cas9 shows how futile it is to try and develop such a process definition around this particular technology or any rapidly changing technology.  One which will transcend any such definition developed before the ink dries on the paper. One should focus on the traits, not the techniques, which are being developed, incorporated and/or transferred into an “object” (be it living or not) which is intended to be released into the environment in order to evaluate for any potential impacts (see Oye et al. 2014 and Wilson Center 2014).

Gantz, V.M and Bier, E. 2015. The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations. Science. Vol. 348(6233), 442-444. Available: http://www.sciencemag.org/content/348/6233/442.abstract

Esvelt, K.M. et al. 2014. Concerning RNA-guided gene drives for the alteration of wild populations. eLife. Available: http://elifesciences.org/content/early/2014/07/15/eLife.03401

Oye, K. et al. 2014. Regulating Gene Drives. Science. Vol. 345(6197), 626-628. Available: http://www.sciencemag.org/content/345/6197/626

Woodrow Wilson Center. 2014. Creating a Research Agenda for the Ecological Implications of Synthetic Biology. Available: http://www.synbioproject.org/publications/creating-a-research-agenda-for-the-ecological-implications-of-synthetic-biology/
posted on 2015-05-08 15:30 UTC by Mr. Todd Kuiken, North Carolina State University
This is a reply to 7105 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7125]
Dear all,
I support Jaco Westra [#7104] and others who state that that the answer to the question will largely depend on the interpretation of the definitions of a ‘LMO’ and of ‘modern biotechnology’, and the words and terms contained within these definitions. If the definition of an LMO is interpreted in a general way, LMOs will also encompass also future organisms obtained by synthetic biology. Therefore the definition of a LMO should not be interpreted 'to the letter', but taking into account the meaning of the definition.  For example, the use of XNA can be interpreted to be the ‘application of in vitro nucleic acid techniques’. Following the same logic, a synthetic organism developed from scratch, constructed with biobricks,  can be considered as resulting from a ‘Fusion of cells beyond the taxonomic family‘ as also indicated by Todd Kuiken [#7105].  The definition of a LMO was developed  keeping in mind the first generation of LMOs, but can also be interpreted in light of current and future developments. In this way also future organism from synthetic biology  will be covered by this definition.
Kind regards, Boet
posted on 2015-05-09 16:53 UTC by Ms. Boet Glandorf, Netherlands
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7133]
Dear participants,

My name is Felicity Keiper and I have expertise in agricultural biotechnology research, LMO risk assessment and regulatory policy. Thank you for the opportunity to comment on this topic, I hope the following comments are useful.

• What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?
• Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology?
As stated by many other forum participants in this topic (and for the other topics), the tools and techniques that may be used in synthetic biology applications are within the scope of ‘modern biotechnology’ as defined by the Cartagena Protocol, with the resulting living products within the definition of ‘LMO’. Further, the definition of ‘genetic material’ in the Convention does not exclude synthetically derived nucleic acid sequences. This evaluation does not change if future or potential developments in synthetic biology are considered.

• What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?
• How do the different areas of synthetic biology, including DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering, protocell construction and xenobiology, overlap or differ from modern biotechnology as defined in the Cartagena Protocol?
As noted above, a living ‘product’ of synthetic biology is an LMO within the scope of the Cartagena Protocol. To consider the similarities and differences between present-day LMOs and those that may be the products of synthetic biology, the focus needs to be on the characteristics of the product, and not defined by and limited to the ‘components’ or technologies involved in its creation. This is necessary considering that LMOs (including the living products of synthetic biology) may be created using common tools of ‘modern biotechnology’, and utilize similar components, e.g. synthetic nucleic acid sequences. In this context, ‘product’ is used to refer to the resulting organism (i.e. the LMO) and its characteristics, as opposed to a commercial product, and ‘component’ refers to the product’s composite parts.

The primary difference between present-day LMOs and products of synthetic biology is likely to be the availability of an appropriate comparator organism for the purposes of risk assessment under the Cartagena Protocol. This does not, however, exclude the products of synthetic biology from the scope of the Cartagena Protocol or create new risks. Rather, the risk assessment will require consideration and adaptation on a case-by-case basis, as already envisaged for particular LMOs under the Cartagena Protocol.

Best regards,
Felicity Keiper
Bayer CropScience
posted on 2015-05-10 08:40 UTC by Ms. Felicity Keiper, Bayer CropScience
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7135]
Dear fellow participants,

My name is Margret Engelhard, I am working at The German Federal Agency for Nature Conservation in the area of GMO Regulation and Biosafety.

For the identification similarities and differences between living modified organisms and organisms, of synthetic biology techniques, I suggest to focus on characteristic features of organisms produced by synthetic biology that are relevant for biodiversity. Here features that are new to synthetic biology when compared to genetic engineering are suggested: 

Although synthetic biology builds on many of the techniques of genetic engineering, it aims at the design and construction of new biological parts, devices and systems. Thus, it goes far beyond mere modification of existing cells by inserting or deleting single or a few genes. Instead, cells will be equipped with new functional devices or even complete biological systems will be designed. Therefore, in comparison to genetic engineering, organisms produced by synthetic biology are characterized by a much larger depth of intervention into the organism. The resulting synthetic organisms may have only very little in common with any other organism and predictions on the behavior of these synthetic cells cannot simply be drawn from the behavior of any of the donor organisms that have been used for the creation of synthetic cells.

Another critical dimension of synthetic biology is the introduction of unnatural chemical compounds into living systems. This results in cells, whose metabolism or genetic material is incompatible with that of natural biological systems. Although this orthogonality of xeno-organisms are sometimes discussed as a means to enhance biosafety , such organisms may have a yet unpredictable impact on the ecosystem if released into the environment. This comes along with a lack of detection methodology for xeno-organisms.

In general, the more orthogonal synthetic organisms are to their natural counterparts, the more unfamiliar they are, not only for the ecosystem and its biodiversity but also for both scientists and the public. Therefore knowledge that comes with practical experience is lacking. This unfamiliarity results in an enhanced uncertainty with respect of risk assessment and the assessment of the impact on biodiversity, since any predictions are normally modelled along the known properties of related organisms we are familiar with.

I will come up with a suggestion for an operational definition in the third Topic of the online forum that makes uses of the above mentioned features.

Best regards,
Margret Engelhard
posted on 2015-05-10 12:29 UTC by Ms. Margret Engelhard, Germany
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7144]
Dear all, participants, María Andrea, Secretariat!Good afternoon to all!

I am Francisca Acevedo, and work in Mexico at CONABIO, an institution dedicated to gather knowledge on biodiversity and its use. CONABIO has been involved in biosafety for a long while now, and I have been leading a group dedicated to risk assessment on the release of LMO into the environment for twelve years.

I am only joining the discussions till the very end, but would like to contribute on a subject of great concern for me/us who are involved in risk assessment on a daily basis.

My experience tells me that it is very difficult to come to terms in having a "common understanding" of the possible risks involved in releasing LMO into the environment. Those who manage LMO and potentially could/are be interested in releasing them into the environment (or not, by managing them in confined settings) do not necessarily understand and therefore share the concerns others have. This translates into sometimes having lagoons of needed information in the applications that the proponents present to the regulatory body (as an example, we have compared the kind of detailed information provided in some countries compared to others, and it is definitely not the same, missing out on data which should be presented in Mexico…….).

This reflection takes me to share with you one of the issues that I am concerned with. Assuring the right standards of needed information, both in quantity but more importantly, quality, that really respond to the determining issues involved in LMO releases (understanding a broad definition of Synthetic Biology where its products fall into the scope of the Cartagena Protocol), where the main goals are assuring that "using synthetic biology" does not in any way pose non manageable risks (and therefore potential negative effects) related to the conservation and sustainable use of biodiversity.

Kind regards to all.

Francisca
posted on 2015-05-10 17:56 UTC by Ms. Francisca Acevedo, Mexico
This is a reply to 6761 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7146]
Dear participants,

I am so happy because we have a lot of interest points of view not only in this forum but also inside other fora, most of them very related.

We will soon wrap up so is important that you give a brief comments if you would still have any comments or responses.

Many thank to all of you, for all your comments, arguments, and useful links and documents.

Best regards,

M. Andrea
posted on 2015-05-10 18:23 UTC by Ms. María Andrea Orjuela Restrepo, Mexico
This is a reply to 7146 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7150]
Dear All

I am Thomas Heams, assistant professor in functional animal genomics in AgroParisTech (the Paris Institute of Technology for Life, Food and Environmental Sciences) and INRA (the french National Institute for Agricultural Research), two public institutions for Education and Research. It's an honour and a pleasure for me to be part of this forum.

Thanks to all of you for all these rich and inspiring contributions, and thanks to the moderators for the good job done. And I do apologize for this late contribution.

Regarding this topic “Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques ”, lot of elements have been debated here.

I agree with the fact that so far, many current LMOs coming from SB do fall into the current Cartagena protocol definitions of LMOs. I also agree with the comments regarding the special case of xenobiology (use of non natural nucleotids of amino-acids) that needs to be carefully adressed. The cutting-edge research on protocells should also be taken in consideration with this respect. It is an inventive field of research in which the elementary bricks can be very different from the one used by the living world.

In a prospective way, I would guess that challenges in the near future might not come from the definition of the biobricks, should they be natural or “artificial”, but from their dynamic associations. Biological life is not, and by far, a collection of machines, neither a collection of biobricks. Life comes from the dynamic interactions between them, their historicity, their connectivity, their potential from transformation (e.g. their evolvability). Sticking to a brick-based definition might be efficient for a while, but may prove problematic if/when new combination of bricks could/would have by themselves features and properties that resemble the ones of biological life.

My recommendation would then be that potential new definitions be aware of this aspect of the problem.

Best
Thomas
posted on 2015-05-10 18:59 UTC by Mr. Thomas Heams, AgroParisTech
This is a reply to 7146 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7156]
I am Alessandra Salamini, working for Monsanto and representing CropLife International. I am a plant molecular biologist by training and my professional expertise is in the area of regulatory policy and risk assessment of plant biotech products.

In order to appropriately address topic 2, it is important to keep in mind the definition of LMO provided in the Cartagena Protocol and the scope of the Protocol. Therefore, I am going to address similarities and differences between living modified organisms and organisms produced by synthetic biology.

We agree with many other participants that the diverse range of tools that may be used in synthetic biology applications currently build upon and include those defined as modern biotechnology and produce organisms that by definition are LMOs. The fact that an in vitro nucleic acid technique uses a sequence isolated from another organism or a synthetically composed sequence is irrelevant within this definition. In both cases, it results in an organism with a novel combination of genetic material through the use of modern biotechnology (i.e., LMO) that falls under the scope of the Cartagena Protocol. When looking at potential developments of synthetic biology, we think this conclusion is going to apply for the foreseeable future.
posted on 2015-05-10 20:24 UTC by Ms. Alessandra Salamini, Monsanto
This is a reply to 7156 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7160]
Let me first introduce myself. I am Marja Ruohonen-Lehto and I work at the Finnish Environment Institute in Helsinki, Finland. My background is in genetics, microbiology and virology. My duties include risk assessment of LMOs, national and international obligations on species protection and genetic resources. I also have the honor and challenging task to represent WEOG in the AHTEG on Risk Assessment and Risk Management under the Cartagena Protocol on Biosafety. I have prepared this short intervention together with my colleague Katileena Lohtander-Buckbee who has a background in systematic botany and ecology and deals with issues related to risk assessment of LMOs and access and benefit sharing of genetic resources (Nagoya Protocol).

We have followed the discussions with great interest. Many excellent and clarifying comments have already been provided. We will give our comments below to the specific questions presented by our moderator.

1. What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?
ANSWER: Bearing in mind the definitions given by our moderator in the beginning of our discussions and the definitions of the Cartagena Protocol and the Convention, the organisms developed so far using SynBio techniques can be considered LMOs. And this is not likely to change in the near future. The risk assessment framework of the CP is applicable to “SynBio organisms”. As we have stated in our comment to topic 1 and as has been stated by others, the RA will face challenges especially in the comparative approach used for present-day LMOs.

2. Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology?
ANSWER: See above. We think that any organism can be assessed using the Cartagena risk assessment framework. Data requirements will probably need some adjustment and will have to be further clarified.

3. What are the similarities and differences between the components and products of “modern biotechnology”, as defined in the Cartagena Protocol, and the components and products of synthetic biology?
ANSWER: It is clear from our discussions that we probably need a clear definition of “product” for our discussions. The definition of a “component” seems to be more “straight forward”. We think that the components used in modern biotechnology and SynBio are quite similar. The only exception so far would be xenobiology i.e. using fully new type of nucleic acids (XNA). And if we use the definition of our moderator on “products”, they are quite similar too. And like with components, the differences between products of modern biotechnology and SynBio may be envisaged from organisms with fully new type of nucleic acids (XNA).

4. How do the different areas of synthetic biology, including DNA-based circuits, synthetic metabolic pathway engineering, genome-level engineering, protocell construction and xenobiology, overlap or differ from modern biotechnology as defined in the Cartagena Protocol?
ANSWE: We think that the majority of the SynBio techniques can be encompassed in the “modern biotechnology” definition. The present-day protocells (non-living, not containing DNA) do not, according to our understanding, fall under the definition of "modern biotechnology" in the Cartagena Protocol.

Looking forward to our future discussions,

Marja Ruohonen-Lehto and Katileena Lohtander-Buckbee
posted on 2015-05-10 22:51 UTC by Ms. Marja Ruohonen-Lehto, Finland
This is a reply to 7160 RE: Topic 2: Similarities and differences between living modified organisms (as defined in the Cartagena Protocol) and organisms, components and products of synthetic biology techniques (27 April – 11 May 2015) [#7167]
Dear All

I am Peter Leadlay, a chemical biologist and Professor of Biochemistry at the University of Cambridge, UK.  I have been working on the engineering of modular systems in bacteria that synthesise antibiotics and other bioactive natural products for 25 years. I co-founded a biotech company based on my research, and co-funded another.   My comments below echo many previous contributions.

• What are the similarities and differences between LMOs, as defined in the Cartagena Protocol, and the living organisms that are currently being developed through synthetic biology?

Modern biotechnology is robustly defined in the Cartagena Protocol and I see no significant difference, in the context of the CBD, between the living modified organisms (LMOs) generated by genetic engineering methods available in 1990 and those being generated now (including by all the current strands of synthetic biology).  I believe that current regulation of GMOs is adequate to be applied to LMOs whether produced using really new techniques or from different (e.g. CAD/engineering) scientific standpoints. I agree with previous contributors that LMOs should be considered separately from non-living products or components, because the risks are very different.   A non-living chemical entity capable of interacting with organisms at any level, including that of the genome, should be subject to chemical risk assessment. Risk assessment of both chemicals and LMOs is challenging but these challenges must not be overstated.

• Taking into account the previous question, would your evaluation of the above similarities and differences between LMOs and living organisms developed through synthetic biology change when considering the foreseeable technological developments of synthetic biology?

Modern biotechnology as defined in the Protocol encompasses all synthetic biology processes and techniques practicable within (what I consider) a reasonable research time horizon.  Even synthetic genomics, or the incorporation of XNA or of non-natural amino acids into conditionally-functional model organisms involves at some stage "in vitro nucleic acid techniques".  I disagree with those who suggest a list of individual techniques is required. 

• What are the similarities and differences between the components and products of "modern biotechnology", as defined in the Cartagena Protocol, and the components and products of synthetic biology?

I agree with those previous contributors who have pointed out that non-living products of LMOs are in general not intended to be covered by the Cartagena Protocol. Also, it is in practice impossible to draw any line between the mass of chemicals used as tools in modern biotechnology and the subset intended to be used (or that could conceivably be used) as components to edit or construct an LMO. Non-living chemicals and dead organisms should not be defined, treated or regulated (e.g. blanket need for advanced informed agreement) as though they were LMOs.
posted on 2015-05-11 00:53 UTC by Mr. Peter Leadlay, University of Cambridge