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Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6762]
POSTED ON BEHALF OF MART LOOG

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Dear Forum participants,

It is a great honour to serve as the moderator of this discussion.

Among the tasks in its terms of reference, the AHTEG on Synthetic Biology was mandated to “Work towards an operational definition of synthetic biology, comprising inclusion and exclusion criteria, using all relevant information, based on scientific and peer-reviewed studies”.

Operational definitions are important tools in scientific assessments and decision making in that they describe a concept or experimental procedure in a way that it can be unequivocally measured. There is currently no internationally agreed definition of ‘synthetic biology’ as indicated in a report that was recently published by the CBD Secretariat (https://www.cbd.int/doc/publications/cbd-ts-82-en.pdf) which further elaborates that:

“… key features of synthetic biology include the ‘de novo’ synthesis of genetic material and an engineering-based approach to develop components, organisms and products. Synthetic biology builds on modern biotechnology methodologies and techniques such as high throughput DNA technologies and bioinformatics.”


To support of the work of the AHTEG, in this discussion, participants of the Online Forum are invited to make proposals for an operational definition of synthetic biology that:

• Is based on scientific concepts;
• Is applicable to components, organisms and products of synthetic biology;
• Comprises measurable inclusion and exclusion criteria (the inclusion and exclusion criteria are meant as elements, in addition to the definition ‘per se’, that would help in guiding whether or not a component, organism or product falls under synthetic biology); and
• Accounts for current and foreseeable technological developments of synthetic biology, both at the level of research and commercialization.

The Secretariat made available two background documents for our discussion. The first background document is an excerpt (page 15) from the report published by the CBD Secretariat containing examples of definitions for synthetic biology. The second background document is an excerpt (annex III) from an opinion document that was recently published by the European Community and contains a comprehensive compilation of definitions for synthetic biology. The two background documents are available in the page of this discussion at https://bch.cbd.int/synbio/open-ended/discussion.shtml.  

To facilitate the discussion, participants may structure their interjections into three components, as follows:

1) How could “synthetic biology” be best defined in a manner that encompasses the elements in points (i) through (iv) above?

2) What measurable inclusion criteria may be considered in the operational definition of synthetic biology?

3) What measurable exclusion criteria may be considered in the operational definition of synthetic biology?

I look forward to your reading your contributions to this discussion.

Best regards,
Mart Loog
posted on 2015-04-27 01:11 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6766]
Hello,

My name is Bruce Dannenberg and I am the founder and CEO of Phytonix Corporation. Phytonix is developing and commercializing a technology that photobiologically (photosynthetically) directly converts waste carbon dioxide "feedstock"streams  to produce renewable and sustainable chemicals and fuels, such as n-butanol, with oxygen as a co-product. We utilize synthetic biology to engineer photosynthetic bacteria (cyanobacteria) that directly secrete the target chemical within enclosed photobioreactors.

What follows is a definition of Synthetic Biology that I believe is accurate:

“Synthetic biology” in a literal sense is the building or engineering (synthesis) of biological systems, as distinguishable from the description, classification or genomic sequencing of them. Synthetic biology is an extension of the continuum of advances in genetic engineering that include recombinant DNA technology. Synthetic biology envisions the assembly of novel microbial genomes from a set of modular genetic parts. These components may be natural genes (genes from conventional breeding) that are being applied for a new purpose, natural genes that have been redesigned to function more efficiently, or artificial genes or nucleotides that have been designed and synthesized from scratch in the modification of microbes for the generation of renewable chemicals.

                   ***********************************************************

Synthetic biology is transforming the chemical industry by enabling manufacturers to accomplish “synthetic organic chemistry” (the purposeful execution of chemical reactions to obtain a product) using biological catalysts that convert renewable raw materials into products.

Efforts to define synthetic biology have created confusion because the term is sometimes used to describe the methods used to produce engineered organisms and other times to describe advanced biological approaches to synthesis. In order to increase the level of understanding and create maximal social utility, I feel it is important to focus on the products produced by the technology, rather than the details of the specific gene engineering tools used to produce the organisms that synthesize those products.

Kind regards,

Bruce
posted on 2015-04-27 02:07 UTC by Mr. Bruce Dannenberg, Phytonix Corporation
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6767]
Dear participants of the online forum on synthetic biology,

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 am Dr. Hideyuki Shirae belongings in Japan Bioindustry Association.
We have a challenging issue ahead of us, and it is expected that the discussion must be tough things, but I would like to give the opinion that I consider now from the view point of a scientist.

The definition of “Synthetic Biology” is a kind of technology which designs quite novel parts, devices and genetic circuits, and creates some unnatural molecules which there are not in nature.  The technology using natural nucleic bases, AGCT, and nucleotides derived from the natural nucleic bases which can transcribe naturally existing RNAs and translate naturally existing proteins, is in the content of a traditional genetic engineering technology, but not the “Synthetic Biology”.

Recently some gene editing technology come up, and many articles regarding the genetically modified traits are reported.  However, it seems to be different from the techniques derived from synthetic biology because the “Products” made by the gene editing technology do not contain any “Components derived form genetically modified technology.  That means the “Products” made by the gene editing technology regards as the same “Products” derived from naturally occurring gene mutation, and old gene mutation technology, such as UV mutation or drug induced mutation.  I believe the gene editing technology must be excluded from this current discussion, avoiding the confusion and misunderstanding about the real “synthetic biology”.

Best and really looking forward to our combined comments and the discussions until May11, 2015.
posted on 2015-04-27 02:21 UTC by Mr. HIDEYUKI SHIRAE, Japan
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6780]
Dear colleagues,
My name is Nikolay Tzvetkov and I work at the Biodiversity Unit of Bulgarian Ministry of Environment and Water.
I would like to highlight an aspect of synthetic biology that is often missed in the discussions. Modern protein and nucleic acid engineering allows development of biological molecules whose properties have no analogues in nature or are significantly different from natural molecules (e.g. enzymes that catalyse certain types of reactions, sensors and receptors to non-natural molecules, switches, etc.). Such proteins and nucleic acids can be obtained both by in vitro and in vivo evolution and by design. Nice examples are available for example on the David Bakes lab webpage http://www.bakerlab.org/ or on that of Jack Szostak lab http://molbio.mgh.harvard.edu/szostakweb/ .
When such macromolecules are expressed in living cells they can be part of novel circuits or metabolic pathways. What we should consider is whether those cases when proteins or nucleic acids with novel properties are expressed in vivo and are functionally important, as opposite to mere expression of recombinant protein for example, fall within the scope of synthetic biology.
My personal opinion is that although protein and nucleic acid engineering are not part of synthetic biology per se, they are key enabling technologies and their products can turn a cell into a synthetic biology organism.
Best Regards,
Nikolay
posted on 2015-04-27 13:22 UTC by Mr. Nikolay Tzvetkov, Bulgaria
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6788]
POSTED ON BEHALF OF LÁZARO REGALADO

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Hello everyone,

My name is Lázaro Regalado MD Specialist in Microbiology and I’m going to participate in this forum on behalf of the Cuban National Center for Biosafety (Ministry of Science, Technology and Environment).

First of all I would like to thank Secretariat and moderators for the organizations of this online forum and it’s a great pleasure for me to share views with this remarkable community of experts on the fascinating issue of Synthetic Biology.

In terms of defining Synthetic biology, one of the most important and at the same time complex points, we prefer not to address the criteria for inclusion and exclusion as we could happen later the same thing happens now, that`s why  in our view, we should  develop a sufficiently broad definition and as simple as possible with room for all possible techniques, the scope is understood and leave room for its expansion, collect scientific aspects and to provide a framework of ethical and social analysis, so that will go directly to a definition to which we have decided to affiliate as a first step:

¨Synthetic biology aims to design and engineer biologically based parts, novel devices and systems as well as redesigning existing, natural biological systems. Synthetic biology strives to make the engineering of biology easier and more predictable¨ Royal Academy of Engineering (2009)

Best regards,

Dr Regalado
posted on 2015-04-27 18:15 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6790]
Elibio Rech from Embrapa Genetic Resources and Biotechnolgy

In my view, synthetic biology is simply the mature stage of recombinant DNA technology and genetic engineering.

SB definition proposed is suitable.
However, I would recommend: a) adding “… processes and products”…..; b) I would also recommend to delete the term “…develop organisms…”. Basically, SB should allow us to conduct synthetic domestication of useful specific traits

relating SB exclusion and inclusion: current international biosafety rules do cover SB.
posted on 2015-04-27 18:51 UTC by Mr. Elibio Rech, Brazil
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6794]
Hello, my name is Jim Louter and I think I have to jump into this debate as I see my email inbox fill up with new notices of preceding comments!

I work for Environment Canada, the Ministry within the Canadian government charged with responsibility for environmental risk assessment of 'new' organisms (that are not already regulated under one of our agricultural statutes).  This means we conduct environmental risk assessments of many environmental organisms being used in a very wide range of products - we use 'new' to mean (there is a legal definition but I will paraphrase) newly introduced into the Canadian environment by a human and science/engineering facilitated means.  This operational definition completely side-steps the current debate as the full spectrum of organisms from naturally occurring to genetically modified is included using the same risk assessment principles. 

Regardless of the above, I note some who have suggested that the definiton is not important. I wish to offer a counter view to suggest, that in fact, the defintion is critical.  Without knowing the precise scope of what we are talking about, we will be wasting a lot of time.  For those who have worked on the Cartagena Protocol, recall the early discussion on the definition of 'LMO'; without that essential clarification at the beginning, further work on the Protocol would have been almost impossible.

Now, having said that, and seeing the broad range of suggestions for definition of synthetic biology already made (and the difficulty of their acceptance), I see the current task given to this forum to be very difficult.  There has already been many studies and recommendations for a definiton and we could simply choose the least objectionable one.  However, all these approaches have been from 'the top down' - thinking of words and phrases to capture what the author(s) want to include  or exclude.  Another approach is work at it from the other direction - in other words, to create a list of examples of organisms, each with a small, incremental modification/difference, placed in order of that difference, and then see where the 'line' could be drawn in that list to separate the 'synthetic' from the non-synthetic.  Where the line gets drawn by a majority or consensus of participants would then form the basis for a definition. 

thanks for reading

Jim Louter
Environment Canada
http://www.ec.gc.ca/subsnouvelles-newsubs/default.asp?lang=En&n=E621534F-1
posted on 2015-04-27 19:49 UTC by Mr. Jim Louter, Canada
This is a reply to 6794 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6795]
Jim Louter from Environment Canada with another thought:

If we accept the notion that synthetic biology techniques can be applied to both living and non-living systems, then we have to accept the possibility of a two part definition that captures both groups and also, that the risk assessment models for these two groups will be different.
posted on 2015-04-27 20:05 UTC by Mr. Jim Louter, Canada
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6798]
Hello All,

I am Edward Hammond. I am an Advisor to Third World Network and operate a consultancy, Prickly Research, based in Austin, Texas (US).

The route to a simple and effective definition of synthetic biology may lie in clarity about what constitutes a synthetic nucleic acid.

Those activities that involve the use of synthetic nucleic acids and their products can be considered synthetic biology.

In that regard, synthetic nucleic acid molecules can be defined to include those that are chemically or by other means synthesized, including those that are chemically or otherwise modified (by, for example, genome editing technologies), of course including nucleic acids that result from replication of the foregoing.  Other molecules that wholly or partially result from those synthetic nucleic acids are products.

Efforts underway to develop synthetic biology systems that use synthetic bases designed not to pair with naturally occurring ones should also be considered, as it possible that constructs using these bases may have impacts on biodiversity and its sustainable use, either through the direct action of the constructs themselves or through the effects of their products.

Thank you for the opportunity to participate in this forum.

Sincerely,

Edward Hammond
posted on 2015-04-27 22:04 UTC by Mr. Edward Hammond, Third World Network
This is a reply to 6794 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6801]
I’m Dr Lázaro Regalado (Cuban National Centre for Biosafety. Ministry of Science Technology and Environment)
I thank you for your comments and I would like to say that I’m fully agree with the view that the current task on Definition of Synthetic Biology to this forum to be very difficult but at the same time important. We have to find the way to do it and your proposal is very interesting. Nevertheless in my view we should try a sufficiently broad definition and as simple as possible with room for all possible techniques…..
Best regards,
Dr Regalado
posted on 2015-04-28 04:16 UTC by Mr. Lazaro Regalado, Cuba
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6807]
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 07:34 UTC by Mr. Piet van der Meer, Ghent University, Free University of Brussels, Belgium, PRRI
This is a reply to 6807 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6809]
Dear all:

Going to the #6807 intervention by Dr. Piet van der Meer, I agree that these three parallel sessions are cumbersome to deal with.
Also Topics 1 and 2 would be taken after the summary of Topics 3 on definition, as I see that Topics 1 discussion has some feedback of need on the definition / context of synthetic biology.
I would appreciate the moderator and SCBD to reconsider the modality set up of the on-line forum.

regards,

Kazuo Watanabe
Gene Research Center
University of Tsukuba
posted on 2015-04-28 09:56 UTC by Mr. Kazuo Watanabe, Japan
This is a reply to 6794 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6812]
Hello, esteemed participants of this on line forum,

My name is Hans Bergmans. I am a retired LMO risk assessor. I used to work in the GMO Office of the Natl. Institute of Public Health and the Environment in the Netherlands. I am joining this discussion as a member of PRRI. In the past I have been active as a member of the AHTEG on Risk Assessment and Risk Management, as a representative of my government and of my former institute. I wish to expressly state that now I am joining this discussion in my own personal capacity, not as a delegate from my government.

I am grateful for the SCBD for facilitating this on line discussion, and to Mart Loog for moderating the discussion; from my own experience as a moderator of other CPB on line discussions I wish him luck and stamina.

I largely agree with the postings of Jim Louter and Piet van der Meer.
From my experience with the discussions on definitions of a GMO / LMO, or of 'genetic modification', 'genetic engineering', or 'modern biotechnology' (let alone 'traditional' and 'new breeding techniques') it is my conviction that any attempt to reach consensus on a definition is doomed to failure. The field that we are trying to define here, synthetic biology, is extremely broad, and what's more: it is developing rapidly. It is developing in a myriad way and there is a good chance that any definition that we will arrive at today will be severely outdated tomorrow due to new developments.

What's more, definitions are apt to be used in a malicious way, i.e., in a legal manner, as a legalistic argument why a new technique or a novel organism should NOT be under the regulations of the CPB, or under national regulatory oversight. Definitions are only useful if they provide some focus, but in a developing field, a strict definition will sooner be a burden than a useful tool.

Therefore I agree with what Jim Louter suggests.
My argument, that I think goes along the lines of Jim's argument, has TWO STEPS:

STEP 1: The definition of an LMO in the CPB should be interpreted in a broad sense, which will cover any living, i.e., replicating, organism that has heritable modifications in its genetic material, whatever that modification may be and whichever technique has been used to construct the genetic material. Probably all living organisms derived by synthetic biology will be included in this definition.

STEP 2: As Step 1 will likely include also techniques and organisms that make no sense to be included in the definition, Step 1 can ONLY work if it is followed by a FAST and SENSIBLE mechanism, based on the definitions and the provisions in the CPB, to exclude some technique and the organisms derived by that technique from the definition of an LMO in Step 1. This would be much in the way that mutagenesis as a technique is excluded from EU Directive 2001/18/EC.

By this approach we would look at things as they emerge. In this forum we could further discuss the ins and outs of Step 1 and Step 2.
But let me repeat that this approach can only work if we have a quick, science based way to settle disputes, a way to build a logical body of knowledge on what organisms derived by modern technology will constitute an LMO under the CPB.

Hans Bergmans, member of PRRI
(edited on 2015-04-28 10:49 UTC by Mr. Hans Bergmans)
posted on 2015-04-28 10:43 UTC by Mr. Hans Bergmans, PRRI
This is a reply to 6809 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6815]
Dear All
I join Jim, Bruce Kazuo , Hans and others to agree with Piet's suggestion It will be very difficult to reach consensus on definition on synthetic biology
Step 1 the definition of LMOs in the Cartagena Prtocol may probably coverd thel iliving organisms derived by synthetic biology
Best regards
Gado
posted on 2015-04-28 11:53 UTC by Mr. Mahaman Gado Zaki, Niger
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6819]
Dear colleagues,
I completely agree with Hans Bergmans. The definition of LMOs under Art.3 of Cartagena protocol is sufficiently broad to include (almost) all organisms considered to be result of Synthetic biology at present. So it might be really much more productive to identify the cases, if any, when a Synthetic Biology organism is not a LMO.
Best Regards,
Nikolay
posted on 2015-04-28 15:12 UTC by Mr. Nikolay Tzvetkov, Bulgaria
This is a reply to 6819 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6820]
Dear All,

I agree that clarity should be developed regarding which organisms incorporating synthetic modifications are LMOs and which are not, however, I fear that an exercise of proposing cases of organisms with synthetic modifications that are not LMOs might lead us into lengthy discussions on the interpretation of articles of the Cartagena Protocol.

In due course, those discussions may be interesting and worthwhile, but I fear that at this moment they will not serve our immediate purpose of developing a clear definition of synthetic biology. Of course there are areas of overlap between LMOs and organisms with synthetic modifications, and some organisms may be created that surely are both, however, I will suggest that the definition of synthetic biology needs be able to stand independently, and relationships to Cartagena sussed out as we move forward.

Thank you,

Edward Hammond
(edited on 2015-04-28 16:34 UTC by Mr. Edward Hammond)
posted on 2015-04-28 16:18 UTC by Mr. Edward Hammond, Third World Network
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6821]
My name is Ray Layton and I have been involved with different types of risk assessment for over 30 years – mostly with industrial products, pesticides, LMOs, etc.   I appreciate the opportunity to participate in this discussion.

I agree that the task of developing a definition is hard.  At the same time, I believe that the group is not likely to move forward until we get this step out of the way.

Perhaps one way to approach this is to consider a widely accepted definition:

“Synthetic biology aims to design and engineer biologically based parts, novel devices and systems as well as redesigning existing, natural biological systems”

Then break it down to basic elements that would help with the inclusion / exclusion criteria.

1. Must be biological (excludes non-living).

2. Must be the result of a process where the parts were specifically designed and engineered (excludes products derived from random actions followed by selection of some type).

3. Includes novel parts, devices, or systems produced within or produced by living organisms (excludes a non-living part or device placed within a living organism; excludes use of external elements that influence natural mechanisms– for example plant hormones, pheromones, dsRNA/RNAi, etc.).

4. Includes redesign of existing biological systems (excludes development of new biological systems through external selection mechanisms).

If we find it impossible to move from definition to inclusion/exclusion criteria, then let’s modify the definition (or find one and try again).

Raymond Layton, Research Fellow for Environmental Safety, DuPont Pioneer
posted on 2015-04-28 18:11 UTC by Mr. Raymond Layton, DuPont Pioneer
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6826]
POSTED ON BEHALF OF MART LOOG

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Dear colleagues,

My name is Mart Loog, I am professor of molecular systems biology at the Institute of Technology, University of Tartu, Estonia.

I was asked to moderate this topic. As many of you have sent their preliminry opinions, in a longer email later today I will try  to make an interim conclusion and set the new direction for the discussion.

In my opinion, the definition of synthetic biology: synthetic biology is an engineering discipline that seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues.

Best regards,
Mart Loog
posted on 2015-04-28 20:39 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 6762 Views on an operational definition of synthetic biology, comprising inclusion and exclusion criteria; [#6829]
Thank you for the opportunity to comment on this topic. My name is Jim Thomas, I am Programme Director with the ETC Group, we are an international  civil society organisation that has been closely tracking developments in Synthetic Biology since 2006 and are founding members of the International Civil Society Working Group on Synthetic Biology. I am submitting these comments only on behalf of ETC Group.

I have proposed a specific definition below (at 10.) and would invite responses, comments, modifications, additions to that specific definitiona nd teh comments below. I trust that this submission is in time to be considered fully within Dr Loog's round up of comments.

Some observations:

1. An empirically-based definition of Synthetic Biology  is possible and necessary.

Any suggestion that Synthetic Biology is not definable field have little basis in fact. The field of Synthetic Biology is by now well established as a self-identified area of application development, as a self-determined descriptor for hundreds of industrial enterprises, as the term assumed by at least 2 trade organizations and several professional networks, as a description used by  national and regional funding bodies and as field of work within the scientific literature (including unique ‘synthetic biology’ journals , conferences and events (including the IGEM - International Genetically Engineered Machine Competition). Significantly there has been extensive scientometric analysis to determine the elements of a definition for the field - initially by Oldham et al (Oldham P, Hall S, Burton G (2012) Synthetic Biology: Mapping the Scientific Landscape. PLoS ONE 7(4): e34368. April 23rd 2012.) and  more recently by Raimbault and Joly (e.g. Med Sci (Paris) 2013 ; 29 (Hors série n°2) : 47–55
Emergence of synthetic biology: characterization by a scientometric approach  Benjamin Raimbault*,1, Jean-Philippe Cointet2 et Pierre-Benoît Joly). Additionally there is an extensive report on the topic of an operational definition of Synthetic Biology, developed  by 3 European scientific committees. This publication in turn lists at least 35 existing definitions.

2. Synthetic biology comprises both a broad approach and specific tools/techniques - both elements should be reflected.
Unlike a single narrow technique (such as ‘recombinant DNA’) Oldham helpfully describes the term Synthetic Biology as a broader ‘rallying flag’ for a biological-engineering approach articulated around a series of key metaphors (e.g.  genetic circuits, networks, pathways and parts and extending to minimal cells, genome transplantation, synthetic genomes and whole genome engineering). Additionally the scientometric analysis  approach demonstrates that while a diversity of techniques are used, certain techniques recur which in themselves may be considered as indicators that a particular use may involve synthetic biology. The extensive report of the European Commissions Scientific Committees into a definition noted that Synthetic Biology could be described both in terms of key concepts (such as standardization, modularization, orthogonality etc) and also  by tools (design tools, construction tools) as well as  research areas (such as Synthesis, metabolic engineering, xenobiology etc) and indeed the  opinion of the EU’s Scientific Committeon Consumer Safety was that  specific elements  identified by  expert groups (e.g. synthetic, rational design, artificial, modular, complexity, novelty, etc.)   need  to be incorporating into a working  definition.
Choosing between the broad and specific elements of a definition  is important. There are different uses to which a definition could be put and that in turn impacts the construction of the definition as broad or narrow. A definition to support establishment of funding area into research or a university department  can be broad and expansive to encourage broad research avenues. By contrast if the demand for the definition is to provide a reference  on whether or not to apply regulations to specific products or techniques then specificity is helpful. A  problem however is that the field is young and rapidly changing and that the list of techniques, approaches and concepts used by synthetic biologists is still expanding as innovations  continue to emerge in this area. Thus naming specifics techniques alone at this point could appear to prematurely exclude future developments from scope of consideration.

3 The ideal structure of a formal definition is to combine a broad definition with a ‘living list’.

A practical and robust approach to address the rapidly evolving nature of the field, while also being specific is to develop a definition that combines both a broad description of the ‘Syn Bio’ approach, referencing key features of the the field,  with a quite specific non-exclusive  ‘living list’ of common hallmarks, techniques, tools, concepts that could be regarded as example indicators that an organism, product or process may be the result of  Synthetic Biology. This list would be  a ‘living list’ in that it could be updated over time (e.g. contained in an annex open to additional language) and it would be clearly stated that the list of terms within that living list are  non-exhaustive, non-exclusive indicators available as resources  to assist an evaluation of a claim of something  being ’synthetic biology’ or not. The combination of the two (broad definition  and narrow hallmarks) should give ample resources to a regulator or policymaker to answer the question “is this item to be considered ‘Synthetic biology?’

4. Synthetic Biology is firmly nested within ‘Modern Biotechnology’.

At this point the techniques and approaches that are commonly described as Synthetic Biology are ‘in vitro nucleic acid techniques’ and therefore part of ‘modern biotechnology’. This should be part of a definition

5. Synthetic Biology covers synthesis, design and redesign

A common feature of definitions of the field is to include all 3 elements of:
a) Synthesis (including but not limited to artificial synthesis of nucleic acids or other elements of a genetic system - e.g. synthetic ribosomes or synthetic amino acids)
b) Design (including elements of rational design such as modular parts, genetic circuits, synthetic metabolic pathway engineering etc)
c) Redesign (including genome editing, codon optimization , reduced/minimal genomes etc)

6. Definition should refer to biological context - e.g. organisms , cells etc (not just engineering terms/metaphors such as parts, circuits)

7. Synthetic Biology attempts an engineering-based approach to modern biotechnology - rather than just an experimental approach.

8. The products of synthetic biology are not necessarily living.

For example work on cell-free systems is creating Synthetic Biology-based production systems for compounds of interest that utilize microfluidic devices or protocells in place of a living cell. These systems are artificial genetic systems that use genetic components and living processes and have significant issues associated with them but are not in themselves living.

9. Synthetic biology is ‘applied’ but not necessarily ‘for useful purposes’

A number of existing definitions of Synthetic Biology refer to it as being ‘for useful purposes’. The applied nature of Synthetic biology is an important hallmark to draw attention to (as opposed to experimental manipulation of genetic systems to understand life processes) However to use the term ‘useful purposes’ is to impart an inappropriate value judgement on the outcomes. There are certainly trivial applications of Synthetci biology that are non-‘useful’ - e.g. Glowing plants or microorganisms engineered to change the scent of faeces for entertainment purposes. 

10. A proposed definition:

Drawing on an analysis of the existing definitions of Synthetic Biology and  some of the considerations listed above and following discussions on this topic of definition between selected civil society representatives and  party delegates at a one day workshop held in Montreal in June 2014. ETC Group would like to offer the following definition:

“Synthetic biology describes the application of various techniques of modern biotechnology that exercise control in  the design, synthesis or redesign of new biological organisms,  parts, devices and genetic systems at the organismal, cellular or sub cellular level for applied purposes,  Techniques and approaches commonly used for Synthetic Biology are listed at Annex x . Synthetic Biology is particularly, but not exclusively, associated with chemical synthesis or alteration of genetic sequences and nucleic acids, genome editing techniques and an engineering-based approach to the construction of living organisms  resulting in a range of traits, applications and products, living and non-living, and of differing characteristics;”

We would then submit that an Annex x be created that is a  list of terms or ‘hallmarks’ commonly associated with the field of Synthetic Biology:

This list may include the following (but this is not an exhaustive list)

Standardisation, Modularisation, Hierarchical Abstraction, Decoupling of design and fabrication, Orthogonality, Refactoring . genetic circuits, genetic networks, synthetic metabolic pathways, genetic parts, minimal cells, genome transplantation, synthetic genomes and whole genome engineering, Homologous recombination, BioCAD software, Robotic cloning, Metabolic modelling ,Protein engineering, registries of genetic, Parts and device libraries ,engineered Regulatory circuits, DNA synthesis ,Gene and genome assembly, Genome editing, MAGE, CRISPR- CAS9, TALENs, ZFN/zinc finger Nucleases, Molecular profiling, gibson assembly, biobricks, directed evolution, oligo-directed mutagenesis, RdRM, RNAI, Meganuclease directed genome editing, XNA, PNA,  Mirror biology, gene drives, protein engineering, nucleic acid engineering.

etc etc

Best

Jim Thomas
posted on 2015-04-29 02:43 UTC by Mr. Jim Thomas, ETC Group
This is a reply to 6829 RE: Views on an operational definition of synthetic biology, comprising inclusion and exclusion criteria; [#6836]
Dear all

I have been following the discussion and there seems to be some agreement on what synthetic biology is namely the design and redesign of biological systems using engineering principles. The broader definitions seem to encompass every techniques associated with molecular and cellular biology and seems to confuse the novelty of synthetic biology with what has gone on before. It is clear that there has been a continuum of technological developments since the 1970s in our ability to manipulate genetic material that has lead to many useful biotechnological outcomes e.g. production of insulin and bio-therapeutics. By encompassing every technique (via literature surveys) that allows the alteration of genetic material into the definition of synthetic biology confuses what is at the core of the field which is the development of an  engineering framework based on systematic design. Whilst other emerging techniques like CRISPR-Cas have led to recent excitement and controversy, they are enabling tools for a systematic approach. Other techniques like directed evolution are also enabling techniques which within a systematic framework provide approaches for optimisations of specific designs. I think by defining synthetic biology in the broadest possible terms that encompass all development in molecular and cellular biology, genomics, bioinformatics, developmental biology etc is very confusing and is based upon researchers using the term to enhance their published work. As i stated in my earlier post the thrust of mainstream synthetic biology (in the US and UK and elsewhere) is around systematic design with specified aims for the specific application problems.

I have problems with the definition given by Jim Thomas whilst in part tries to captures some of the essence of the new field of synthetic biology but is far too broad to offer a meaningful platform for further discussions as it extends into techniques and technologies which have been around for many years and are not new nor embedded in synthetic biology e.g. to name a few RNAI, protein engineering, nucleic acid engineering. I can see the motivations for some colleagues in trying to embed all developments (past and future) of  modern  molecular biology into synthetic biology but as stated above it does not reflect the main aims of the field and makes discussion around specific applications very diffuse and non-contextual.

I look forward to reading further posts.
posted on 2015-04-29 09:22 UTC by Mr. Paul Freemont, Imperial College London
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6838]
Elibio Rech from EMBRAPA, Brazil

Standard biosafety procedures should also be applied to inclusion/exclusion criteria considering synthetic biology.
posted on 2015-04-29 11:25 UTC by Mr. Elibio Rech, Brazil
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6839]
Dear colleagues,
I personally would consider a Synthetic Biology organism (SBO) any living organism that contains or consists of functionally important components (proteins, nucleic acids, lipids, metabolites, etc.) or processes (metabolic or signal transduction pathways, gene circuits, etc.) that are do not exist in nature or are significantly different from those that exist in nature.
First, we consider only the living organisms.
Second, requirement for the presence of novel (non-natural or very different from natural examples) components or pathways implicitly contains the idea of human engineering involved, that can be either by explicitly designing and engineering or development of suitable selection scheme to exploit random variations.
Third, functional importance excludes those cases where the living cell is just a carrier of the synthetic component or process, but is not (significantly) affected by it, for example just the use as expression system for recombinant protein.
Forth, I would rather not go into the area of utility, because sometimes it is hard to define. For example is just satisfying scientific curiosity utilitarian?
Best Regards,
Nikolay
posted on 2015-04-29 12:20 UTC by Mr. Nikolay Tzvetkov, Bulgaria
This is a reply to 6829 RE: Views on an operational definition of synthetic biology, comprising inclusion and exclusion criteria; [#6841]
Dear colleagues,

I am Rainer Breitling, Professor of Systems Biology at the University of Manchester, UK. My work involves the development of computational tools for synthetic biology, and I am also an expert member of the EU working group on synthetic biology.

I have been following the discussion over the last few days with great interest, and at this point have only a few comments concerning the possible definition of SynBio.

1. To be useful, this definition should be operational, i.e. it should allow us at a later stage to decide which products need to be discussed as being created by synthetic biology. Most of the scientific definitions of SynBio focus too much on intangible aspects and processes and are difficult or impossible to operationalise. One example: defining SynBio as "design and redesign of biological systems using engineering principles" is very inspirational for SynBio practitioners, and captures the scientific thrust of the field very well, but it basically leaves it up to the producer of an LMO to declare whether they used engineering or design principles for their genetic modifications, or not. The same product could result from "systematic design" and from old-fashioned "genetic tinkering" -- and this would potentially conflict with the desire to take a product-based, rather than process-based approach, as expressed in earlier contributions.

2. I agree with earlier suggestions that the vast majority of current SynBio products are LMOs and do not differ from the products of "traditional" biotechnology. A definition of SynBio should be sufficiently broad to capture all these activities, even if this means that there is often no clear distinction between SynBio and biotechnology. At a later stage, the task would then be to identify areas/products where the various technologies associated with SynBio perhaps allow the construction on organisms or systems that move beyond what is covered by current LMO definitions.

3. Using "novelty" as a defining property of synthetic biology organisms might be difficult: by definition, any LMO will have some element of novelty to it, i.e. a combination of components or processes that does not exist in nature. But at which level is this novelty substantial enough to turn an LMO into an SBO? Perhaps one should not be too concerned about this aspect of a definition, but rather concentrate on the later stage of identifying if any of the organisms and/or products of SynBio technologies take us into areas that are not covered by current regulations and considerations around LMOs.

4. The definition proposed by Jim Thomas could be an interesting starting point to consider. It is conceptually very close to the definition of SynBio recently adopted by the EU (http://ec.europa.eu/health/scientific_committees/consultations/public_consultations/scenihr_consultation_21_en.htm ), in the context of risk assessment and biodiversity. It might, however, be helpful to make explicitly clear that a large part of the products resulting from SynBio are not different from the products of earlier biotechnology processes.

Best regards,
Rainer Breitling
posted on 2015-04-29 12:49 UTC by Mr. Rainer Breitling, University of Manchester
This is a reply to 6829 RE: Views on an operational definition of synthetic biology, comprising inclusion and exclusion criteria; [#6842]
POSTED ON BEHALF OF SATURNINA HALOS

---

As well expressed by colleague, Jim Thomas (post #6829), not only is synthetic biology broad, it is evolving and that its products may be living or non-living. However, this discussion is under the auspices of the CBD thus we should focus our concern only on those products that could affect biodiversity. Living, self-reproducing products of synthetic biology would be similar to products of modern biotechnology except that these contain parts or substances that are not found in nature. I think these types of synthetic biology products would raise safety concerns similar to modern biotechnology products and thus fall within the Cartagena Protocol on Biosafety. Concern over non-living products depends on the use of the product and on whether biodiversity is exposed to these products inadvertently or not.
posted on 2015-04-29 14:10 UTC by Ms. Manoela Miranda, UNEP/SCBD
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6845]
Dear Participants,

My name is Todd Kuiken and I am the principal investigator of the Woodrow Wilson Center's Synthetic Biology Project.  I have been following the discussions so far on developing an operational definition of synthetic biology, comprising inclusion and exclusion criteria.  I will be submitting my thoughts on that topic in more detail later, but I wanted to share with you our new synthetic biology products and applications inventory which I think can add some context to this debate.  http://www.synbioproject.org/cpi/

Our data suggests that synthetic biology products and applications are rapidly advancing into food, agriculture, medicine, personal care products, chemicals and more. While our inventory currently identifies 114 applications, it is by no means comprehensive as it can be difficult to identify the specific "synthetic biology" component of some products based on descriptions or definitions provided by manufacturers and researchers.  Based on the suggestions for definitions so far in this discussion I could envision many of the products/applications we currently list being removed as a manufacturer could easily change their description of the product. 

We saw a similar trend happen with our nanotechnology products inventory. (http://www.nanotechproject.org/cpi/)  As regulatory agencies locked into a descriptive definition around size (1-100 nanometers) and public opinion changed around nano; manufacturers simply changed their description of products that once touted nano, while the properties the nano-material imparted into the product remained. 

My thought would be that any definition developed around synthetic biology should focus on the properties the technology platform is imparting into the process used to produce a product, or the properties the technology platform is imparting into the product itself.  Therefore you can focus any risk assessment around those specific properties and not be constrained by a descriptive definition that may exclude certain products or processes, particularly as this is a rapidly advancing and changing field.

Link to synbio inventory: http://www.synbioproject.org/cpi/

Link to nano inventory: http://www.nanotechproject.org/cpi/

I look forward to continuing this robust discussion.

Todd Kuiken, Ph.D.
posted on 2015-04-29 14:39 UTC by Mr. Todd Kuiken, North Carolina State University
This is a reply to 6845 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6850]
Dear participants,

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

Biology seeks to explain existing phenomena, while engineering is intended to create what does not exist. Given this, an agreed definition of synthetic biology has not been achieved, incorporating the two approaches above (biological and engineering), it has not been easy because SynBio is based on the integration of a wide range of disciplines and methodologies to design, build and redesign, all those elements that are part of organisms.

However, it can group the scope of synthetic biology within the following definition: Synthetic biology is the planned design and construction of biological systems and specific biochemicals, to produce new functions, also the SynBio redesigning natural biological systems existing to optimize their useful applications.
posted on 2015-04-29 15:39 UTC by Mr. José Leonardo Bocanegra Silva, Colombia
This is a reply to 6850 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6863]
Dear all participants on this online form,

I understand that synthetic biology is the methodologies either to design non-existing organisms/products in nature with novel pathway, parts, and components, and build them or to redesign s natural biological system, as pointed out by Dr. Leonardo Bocanegra.
And I assume that the one which influences on biodiversity is a product which can reproduce in the environment, such as LMO, but not any methodologies which used in synthetic biology.
Some proposed the definition of synthetic biology in this forum, but their definitions are not unified, and I am afraid that the degree of diference become wider as this forum will go further
I agree with Mr. Hans Bergmans’s opinion [#6812] and his proposed discussion process(Step1 and Step 2) , and this discussion goes to focus on LMOs (and other reproductive non-LMOs if the reproductive non-LMOs would exist).    
                                                                                                                 Hideyuki
posted on 2015-04-30 06:24 UTC by Mr. HIDEYUKI SHIRAE, Japan
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6866]
Synthetic biology broadly refers to the use of computer-assisted, biological engineering to design and construct new synthetic biological parts, devices and systems that do not exist in nature and the redesign of existing biological organisms. While synthetic biology incorporates the techniques of molecular biology, it differs from recombinant DNA technology.

O.A.El-kawy
posted on 2015-04-30 10:11 UTC by Mr. Ossama AbdelKawy, Mauritania
This is a reply to 6866 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6869]
Phytonix Corporations proposes the definition of synthetic biology as an extension of the continuum of advances in genetic engineering that include recombinant DNA technology. We can say that synthetic biology envisions the assembly of novel microbial genomes from modular genetic parts in the modification of microbes for the generation of renewable chemicals. These components may be natural genes that are being applied for a new purpose, natural genes that have been redesigned to function more efficiently, or artificial genes (unnatural) nucleotides that have been designed and synthesized from scratch.
Genetically modified organisms with relatively sophisticated systems for gene expression have been around for almost 40 years. The main difference between GE and synthetic biology is that whereas the former involves the transfer of individual genes, the latter envisions the assembly of novel microbial genomes from modular genetic parts in designing the microbe to generate the desired molecule.
posted on 2015-04-30 10:41 UTC by Mr. Bruce Dannenberg, Phytonix Corporation
This is a reply to 6869 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6876]
Dear Participants,

Some synthetic biology efforts may be oriented toward assembling things that do not already exist (some have called this 'not found in nature'), however, the scope of synthetic biology that we must define is broader.

There is an expanding number of microorganisms that can be synthesized in whole from sequence data, for example, some orthomyxoviridae, coronaviridae, and picornaviridae.  Wholly synthetic viruses are finding use in research, and in development of products (e.g. vaccines). Yet many viruses in these and other potentially synthesizable families are barely characterized, have poorly understood host ranges, and unknown distribution.

For example, the fully (and partially) synthetic influenza viruses used today have significant potential biodiversity effects (e.g. on populations of avian species). These synthetic viruses exactly or inexactly replicate viral RNA found in nature, by design or error, or do all the previous in the same construct.

Beyond what can be made synthetically today, there are sound reasons to expect that the list of organisms that can be synthesized will continue to grow, and that it is likely to progressively include species with larger and more complex genomes. Bacteria, with efforts already underway, quickly come to mind.

There are also extinct species and strains, such as 1918 influenza virus, which was generated from sequences obtained from archival tissue samples some years ago. The potential consequences of synthetically produced pandemic strains are clear enough, but synthetic strains needn't be such dramatic attention-grabbers in order to have biodiversity impact. Any synthetic influenza dissimilar from recently circulating strains and transmissible in avians or mammals might be enough to cause considerable problems.

These are important facets of synthetic biology with potential biodiversity impacts, and they should be reflected in our definition, particularly bearing in mind that the length and complexity of the genomes of synthesizable organisms will continue to grow, as will the number of facilities with the capability to create them.

Thank you,

Edward Hammond

Edit to add useful references:

On synthetic influenza vaccine viruses, see Dormitzer, et al in Sci Transl Med 15 May 2013.

On fully synthetic viruses used in animal research in the Netherlands: Stittelaar, Koert. Director Preclinical Services, Viroclinics Biosciences (Rotterdam). pers. comm. April 2015.

Another example in research, see correspondence between US NIH and St. Jude Children's Research Hospital, concerning biosafety review and lab accident involving ferrets inoculated with synthetic H7N9, here:  http://www.pricklyresearch.com/AutoIndex/index.php?dir=IBC%20-%20NIH%20Correspondence%20reportable%20incidents%202014/

On 1918 influenza: Taubenberger JK et al in Nature. 2005;437:889–93.

On synthetic coronaviruses, see: Becker et al in PNAS 2008;v105 n50, 19944.

On synthetic picornavirus, see: Cello J et al in Science 2002 Aug 9.
(edited on 2015-04-30 19:43 UTC by Mr. Edward Hammond)
posted on 2015-04-30 12:42 UTC by Mr. Edward Hammond, Third World Network
This is a reply to 6766 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6877]
The operational definition should be constructed in such a way that those ultimately charged with its operation are not left to deduce the inspiration/intention of the person/group which created the object.  Such asiprational terms are often appended to the definition (based on engineering disciplines..) or some terms that simply don't 'sound' biological are appended (chemically synthesized nucleic acids or computer designed...) but it is not clear how these modifiers change such practices as risk/benefit assessment. 

As some commentators here have noted, sometimes the researcher/group simply self-nominates into the domain of 'synthetic biology' for any number of underlying motivations.  Consider two scenarios, in one a group sets out to create a sensor circuit using engineering disciplines and will computer design parts to assemble into circuits and test in more than one chassis.  It will sense an input and respond with a readable output signal. They will document the work with electrical engineering truth tables, a transfer function plot and a model that takes their input dna sequences in their combinations and predicts the output function of their circuit.  This looks and feels and sounds like 'synthetic biology'. 

In another scenario a group decides to create a reporter construct and will gain diversity by using sets of double stranded sequences assembled efficiently by Gibson methodology.  They call these sequences promoters, terminators and RBS, they make 'constructs' and they test by a high throughput phenotype screen.  In the end they simply sequence plasmids conveying a range of outputs, produce a representative set of induction curves, and append an Excel table of induction outcomes of 100 combinations of some promoters, terminators and RBS.  They never use the term synthetic biology. 

Should the outcome organisms be treated differently in a review due to the submitter's choice of domain jargon?  To say a sequence is 'designed by a computer' or 'does not exist in nature' means exactly what if one accompanies this with data appropriate for risk/benefit assessment.  And then operationally, does not exist at the gene or codon (or message) level?  This last point is operational because one can use a computer to design a gene sequence and cause it to be chemically synthesized but yield an identical protein to that found in nature, as has been done now for years in the field of molecular biology. At what operational or scientific level would such an activity morph from molecular biology to synthetic biology, if not solely by the self-nomination of the practitioner? 

While engineering metaphors have dominated this decade of the discussion of synthetic biology we must be careful that we are not trying to nuance or find differences say in a house designed by an architect vs a house designed by a general contractor. 

Historically the definitions of recombinant dna focused on operational aspects of exchange of genetic information that could not happen by means known to function in the biological domain at that time.  In simple terms it employed the concept of species level ability to exchange genetic information, and the new techniquest at that time allowed species  to exchange information which was normally precluded.  What is interesting about some of the most advanced applications of synthetic biology today are the recoded variations of E coli coming from groups such as the Church group or the Issacs group, etc.  What is intriguing is that these are now derivatives of E coli which are designed NOT to be able to exchange information with other E coli.  In fact one of the scientists has even posed the question of whether these should even continue to be considered 'e coli'. 

This has far reaching implications in the field of regulation, and i think could be an orthogonal way to post this discussion framework.  In many countries certain strains of E coli have favorable regulatory pathways due to historic use, data on safety/pathogenicity/allergenicity, etc.  So any new submission using one of the traditional 'base' ecoli can build on that history.  But can these pervasively recoded E coli rely on that body of work?  Could something only recoded to prevent translation of 'regular ecoli messages' but which still employs 'natural' amino acids leverage that history?  What about those recoded and reliant on orthogonal amino acids? 

So what this might pose is that one line in the sand for separating 'traditional' molecular biology and synthetic biology is the point at which the resulting organism, irrespective of how they were inspired or how they were actualized, can no longer exchange information or transcribe/translate information with its originating species strain or any other 'natural' species.

When moving back fromthe level of the entire organism, to genes, genetic elements and their combinations into functional elements or pathways it is also helpful to consider that assessments started with 'source of genetic element'.  This in part was to help inform risk/safety assessment by taking into account known hazards from the source organism.  So if you were 'cloning' from a pathogenic strain, how do you know you didn't inadvertently take in your process elements associated with virulence/etc.  Using synthesized elements derived from a genome sequence of the same organism removed the issue of inadvertent transfer of such element purely as a consequence of limitations of cloning tools.  That movement to genome sourced dna sequence allows one to focus on the discrete element itself, and any direct knowledge of its role in virulence/etc.  The ultimate test however was in producing relevant physical data on that gene in the context of the specific product being considered.   Conceptually this is algorithm is not appreciably impacted by further substituting 'computer designed' as the origin.  One can still ask the same questions based on informatics, and then conduct appropriate assessment of the final product.

Thus, the argument about the nature of techniques, and source of inspriation, and such are all interesting but not actually impactful in making distinctions in the scope of synthetic biology vs traditional molecular biology, or as some are suggesting, even other breeding/genome modification techniques which are attempting to be lumped into this new area. 

The main disctinction lies in the converse of the definition of traditional recombinant dna, and in practical terms would be totally obvious that when you use traditional molecular techniques to move a gene into that new organism, that it won't function, by design.   This would unquestionalby be synthetic biology.
posted on 2015-04-30 12:54 UTC by Mr. Steven Evans, Dow AgroSciences
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6880]
An additional thing i fear we can forget is some of the linkage to the past on this discussion.  In the editorial in Gene in 1978 reflecting on the Nobel prizes for restriction enzymes, Szybalski and Shalka closed by postulating that  “[t]he work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes but also has led us into the new era of ‘synthetic biology’ where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated”  [Gene (1978) 4:181-182].    It might be interesting to determine why the term postulated therein (but for those familiar with the history, not exclusively therein) took about three decades to catch on. 

But idea of constructing and combining something new, as opposed to describing and analyzing somethign existing is unambiguously cast.
posted on 2015-04-30 14:20 UTC by Mr. Steven Evans, Dow AgroSciences
This is a reply to 6880 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6882]
As mentioned by other participants in the forum we have been using GE for the last 40 year, where we already have many products in the marked, mainly in the industry and medicine. Synthetic biology is just a different name given for something that we have already been doing. Of course, with the evolution/revolution of new  bioinformatics algorithms/softwares  and new sequencing equipaments we can look at any genome faster and cheaper . This revolution is allowing us to get inspired to re-designing, or just copy molecular modules that nature created through evolution to produce specific metabolites.  With these new tools, we also can create new pathways/molecular modules from scratch as mentioned.   New synthesizing techniques allow us to build large pieces of DNA in hours and test different molecular modules very fast. But it is all the same we have been doing in the last 4-5 decades, just faster and much more efficiently.
posted on 2015-04-30 15:29 UTC by Mr. Alexandre Lima Nepomuceno, Brazil
This is a reply to 6882 Reminder of schedule [#6883]
This is a quick reminder of the timeline  that "participants are strongly encouraged to focus on topics 1 and 2 from now till Sunday, 3 May"  then move to topic 3 from 3 to 11 May.

And our focus is "How to address the relationship between synthetic biology and biological diversity"


As I mentioned earlier, please be concise if possibly and identification of your sources  are appreciated.

Excuse me for the technical intervention for a quick reminder.

Welcome all for those who have just joined the forum.
posted on 2015-04-30 15:44 UTC by Mr. Ryo Kohsaka, Japan
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6890]
I am Hector Quemada, from the Donald Danforth Plant Science Center in the United States.  While our efforts in this discussion focus on defining what Synthetic Biology is or is not, we should keep in mind that we are not doing this merely as an academic exercise.  In my view, this exercise should enable us to determine whether a) Synthetic Biology is an area of research and development that is objectively unique from other already-existing areas, and b) whether the outcomes of this research and development require new approaches to regulation.  After reading the various interventions to date in this online discussion, various relevant documents, and also through my personal involvement with projects in this field, I would argue that what we are talking about when we are discussing Synthetic Biology is not an entity that we can define for the purposes of regulation.  In other words, we are not talking about something like “an LMO”, but rather a general field of endeavor, like “Biology” (the word “synthetic” limiting it to a subset of the broader field).  Synthetic Biology encompasses technical tools/technologies, methods and protocols, conceptual approaches, and even aspirational goals (e.g. greater precision or control of modifications).  Some interventions in this discussion referring to it as “…an extension of the continuum of advances in genetic engineering…, or “…the mature stage of recombinant DNA technology and genetic engineering…” coincide with my view that Synthetic Biology is not a qualitatively different field of endeavor from what has been taking place in other fields, but rather an evolution and synthesis of various disciplines in biology and engineering. Consequently, I don’t think Synthetic Biology by itself is a useful term—however we define it—to guide our decisions on whether new approaches to risk assessment or regulation should be developed.  After all, we already have a term under the Protocol, “LMO”, that I think is defined broadly enough to cover outcomes from this field that are within the scope of the Protocol.  On this point I agree with Hans Bergmans, Mahaman Gado Zaki, and Nikolay Tzvetkov.  Therefore, I support the view expressed by others that existing risk assessment and regulatory approaches applied to LMOs under the Cartagena Protocol or various national regulatory systems should be adequate to address the outcomes of the work in this field.  This is not to say that there will not be challenges presented by specific cases, but the case-by-case approach of risk assessment carried out under the Protocol and other systems allows for that.
posted on 2015-04-30 19:09 UTC by Mr. Hector Quemada, Donald Danforth Plant Science Center
This is a reply to 6890 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6902]
Dear chair, dear all, 
Thanks for this discussion. My name is Boet Glandorf and my work is in risk assessment of LMOs at the Dutch GMO Office. I am of the opinion that for this on-line discussion we need an operational definition of synthetic biology (and not a legislatieve definition) to at least  focus our discussions. Following up on what is mentioned by participants of this forum,  I would agree that definition should be broad. 
A couple of definitions were already suggested. However I would  like to draw your attention to the definition as proposed by the European SCENIHR (http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_044.pdf )

‘SynBio is the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms’.

This definition is only focused on living organisms and disregards non-living organism like protocells. However, this operational definition seems a good starting point for the current discussion in relation to potential impacts of synthetic biology on biological diversity. Considering the scope of the convention we consider that living synthetic organisms may be most relevant
The above mentioned definition may evolve when the field of synthetic biology develops further and our understanding will increase.
At the moment, we consider that organisms produced by synthetic biology are all considered to be LMOs and it is not possible to define exclusion and inclusion criteria.
Kind regards, Boet
posted on 2015-05-01 12:28 UTC by Ms. Boet Glandorf, Netherlands
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6923]
POSTED ON BEHALF OF HIROSHI YOSHIKURA
----------------------------------------------

Dear collegues
My research background is microbiology and I was the chair of the Codex Alimentarius Task Force on Foods derived from Modern Biotechnology.
I appreciate Dr. Freemont’s thoughtful comments [#6814] reviewing the definition of synthetic biology ( SynBio). An aspect unique to SynBio, could be “design based on information science and engineering”, which could have been lowly exploited in the conventional LMO technology.
That said it may be important to ask whether there is any SynBio-derived products existing or under development that cannot be evaluated on the Cartagena Protocol’s principle, “risks should be considered in the context of the risks posed by the non-modified recipient or parental organisms (Annex III Risk Assessment, General principles paragraph 5)”. The Codex Alimentarius’ guidelines on foods derived from modern biotechnology, in addition, defines “conventional counterpart, a related organism/variety, its components and/or products for which there is experience of establishing safety based on common use as food”.
From in these lines, I understand that risk assessment of environmental risks is obliged to rely on our experience in the past and now. Environmental is maintained by interacting multiple factors, many of which are unknown to us. Food or environment is a system of “complexity”, which is difficultly approached analytically examining possible elements one by one.
In this sense, partly agreeing with Dr. Hans Bergmans, I think it will be more useful to ask whether there are any products, existing or being developed, that cannot be covered by the current international or domestic regulations /guidelines (an example attempt is “Synthetic biology and the US biotechnology Regulatory System; challenges and options, J. Craig Venter institute, May 2014”).
Sincerely
Hiroshi Yoshikura
Department of Food Safety, Ministry of Health Labour and Welfare, Japan
posted on 2015-05-01 19:45 UTC by Dina Abdelhakim, SCBD
This is a reply to 6923 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6940]
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 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 also to topic 3 “Operational definition of synthetic biology, comprising inclusion and exclusion criteria”.

I fully acknowledge that this is an emerging field where we will be faced with new developments on a regular basis. In such a situation it is always difficult to come up with a definition as it may be outdated or in need for an update soon. Still I think for reasons of clarity and transparency we need an operational definition of synthetic biology for our current and in particular future debate. That is why I think that this online forum should pave the way for a definition to be suggested soon, e.g. by the upcoming AHTEG meeting, likely to take place in September 2015. Definitions may always be reviewed and updated in the future if needed.

For a workable and broad enough definition a couple of suggestions have been made in this forum already, I would like to point in particular to the definition suggested by an EU Scientific committee, which was referred to for example by Boet Glandorf from the Netherlands in her posting on May, 1 (#6902). I regard this suggested definition as a very appropriate basis for further discussion.

I would also like to comment on the product-based versus process-based approach, which has also been brought forward by some colleagues during this debate. I regard this discussion as a bit unfortunate, as it seems to me as quite an artificial debate. Already in the field of GMOs/LMOs this conflict of process-based vs. product-based has been on the table and I am afraid it has not really helped us in order to reach a common understanding on the question what matters in assessing risks in an appropriate manner.

I think for procees-based vs. product-based it is not either – or but both aspects have to be taken into account when defining a product, establish its characteristics and performing a proper risk assessment. Let me explain a bit further: the process via which an organism and/or a product is modified/established may be an important information for assessing its characteristics and this will inform the risk assessment. In the risk assessment finally we of course look at the product and its characteristics but for that purpose the process via which it has been produced will normally be very relevant. That holds true for genetic modification in its broad meaning, including GMOs/LMOs and should also guide us in the definition and risk assessment of products of synthetic biology.

My suggestion is that we should look both at the product and the process in our future debate and thereby reconcile the two approaches which have been characterised by some as alternatives, while they should in fact be mutually supportive.

I am looking forward to the further debate. Kind regards
Helmut Gaugitsch, Environment Agency Austria
posted on 2015-05-03 08:46 UTC by Mr. Helmut Gaugitsch, Austria
This is a reply to 6940 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6948]
The United States would like to share its perspective on the topic of developing a definition of “synthetic biology”, even though this topic is already very much discussed. We agree with other posters who point out that trying to agree upon a definition is likely to expend a great deal of this group’s energy and we may never come to agreement in this forum.

The United States understands synthetic biology as it is discussed in the research and development community to encapsulate a continuum of biological engineering tools and techniques leading to progressively advanced biotechnology products. As many have pointed out, rapid advances in computer science, biochemistry, and genomics, among many fields, are driving biological engineering, making it difficult and even counterproductive to attempt to develop a formal definition of synthetic biology, let alone inclusion and exclusion criteria, as this definition would become outdated by scientific advances. We note the cautionary tale from Todd Kuiken on nanotechnology, whereby researchers and companies may simply change the name or branding of their work or products in order to avoid oversight that is triggered by a definition. We believe that regulation and oversight must remain flexible enough to respond to changing techniques and increased knowledge and information, and that establishing inclusion and exclusion criteria could lead to situations where products are excluded from regulation or oversight in situations where it is legitimately needed.

Genya
posted on 2015-05-03 20:17 UTC by Ms. Genya Dana, United States of America
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6949]
Dear participants,

I am Dr. Patrick Rüdelsheim. I am a professional service provider in biosafety and biotechnology regulations and I have witnessed the GMO/LMO developments over 25 years and more recently the developments on synthetic biology. Against this background, I can confirm the difficulty that in particular small organizations, humanitarian projects and local developments in non-industrialized countries face when trying to address the consequences of complex and highly polarized legal debates.

Dr. Louise Horsfall and I have been asked to represent the European Federation of Biotechnology (EFB - http://www.efb-central.org) in this on-line discussion. EFB welcomes the initiative and appreciates that the timing of the topics has somewhat been shifted allowing first addressing the definition. This benefited the collection of opinions and suggestions, which so far has been very rich and clearly illustrates the challenge.

Any broad definition is bound to cover organisms that “make no sense” to include as indicated by H. Bergmans (#6812). As he points out, Step 1 can only work if followed by a fast and sensible mechanism to exclude some technique and the organisms derived by that technique from the definition. Nevertheless, we submit that rather than the technique, it should be the characteristics of the resulting genetic modification that are the determining factor for exclusion. H. Gaugitsch argues (#6940) that elements of both process and product must be taken into account. Answering his call for reconciliation, it can be put forward to use product characteristics as defining principle, whereas the technique that has been used to develop the organism can be an element in the risk assessment.

This initiative is based on a proposal for new and emerging issues relating to the conservation and sustainable use of biodiversity. S. Evans (#6880) pointed out that many applications of “synthetic biology” in the broad sense are hardly new. If specific emerging applications (e.g. the de novo synthesis of entire organisms, protocells, organisms with xenobiology) are envisaged, then these can be identified and evaluated on their own benefits and potential impacts on biodiversity. Making an amalgam of the diversity of resulting products under one heading “synthetic biology”, creates confusion and is not scientifically justified.

As this Part of the on-line discussion addresses definition, I like to draw your attention to another confusion of terms. Some participants seem to suggest that “synthetic nucleic acid molecules” include those that are chemically or by other means synthesized. I find no scientific justification for such a generalization: a DNA molecule is a DNA molecule whether isolated from an organism or synthesized. In order to avoid this confusion, it would be better to reserve the term “synthetic nucleic acids” for non-canonical amino acids.

Finally, as pointed out by R. Layton (#6821) the scope should be limited to living organisms.

I look forward to the continuation of this discussion,

Patrick Rüdelsheim
posted on 2015-05-03 21:07 UTC by Dr. Patrick RUDELSHEIM, Belgium
This is a reply to 6948 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6950]
My name is Maria Mercedes Roca.  I  thank the Secretariat for  the opportunity to participate in this forum. I am currently a Visiting Professor in Biotechnology at the Tecnológico de Monterrey (University) in Mexico. I also participate in the Risk Assessment and Risk Management AHTEG and have been a member of the Honduran Biosafety Committee for 12 years. Honduras, as a center of diversification, cultivates LMOs (GM maize) since 2003.   I am also currently coaching iGEM teams (http://www.igem.org) and work closely with students -- an important group of civil society and the future professionals of biotechnology and/or synthetic biology.

I thank Paul Freemont  and Mike Peaton from the UK for their  clear and erudite explanation of what synthetic biology  could mean to the scientific community, and for pointing out the  difference  between “components” and “products” of synthetic biology.

I also acknowledge the important statements by Genya Dana from the USA,  that shed some clarity into the difficult task of defining synthetic biology (or biological engineering).   Thus, I support the suggestion by Piet Van der Meer and many others that discussing Theme 1 “How to address the synthetic biology and biological diversity”  and Theme 2 “similarities and differences between LMOs and organisms, components and products of symbio”, becomes confusing and even counterproductive,  without a clear understanding or agreement of what synthetic biology means for this  diverse group.
 
However, I also acknowledge that to complete our task in this forum, we must reach some kind of consensus and move forward.  I anticipate we may have some difficulties reaching consensus for two  main reasons:

I. LMOs discussed under the Cartagena Protocol have been mainly transgenic crops and animals released into the environment. Industrial agriculture is a contentious subject often mixed with the risks of genetic modification 

As pointed out by Michael Peaton and others, most products derived from synthetic biology are produced under contained conditions in laboratory or industrial settings with strict biosafety rules, and thus pose little danger to biodiversity, since they are not released into the environment.  Ironically, the products of synthetic biology that will necessitate to be released into the environment, will be the very ones needed to bio-remediate contaminated environments, where “natural” organisms cannot cope.  Thus, they are likely to impact biodiversity in a positive manner since doing nothing is a risk in itself.  Thus, a calm and objective risk-benefit analysis needs to be undertaken on case-by case basis, avoiding generalizations and over onerous and costly regulation that can limit innovation and possible future solutions.

II. Our opinion is biased and polarized depending on our background

Reading the many entries from concerned members like Jim Thomas from ETC and others, there seems a clear indication  that the same concerns raised in  the last two decades over the use of GM crops (LMOs or GMOs), and the increase of industrial agriculture – dominated by agroindustry for profit – will be extrapolated to concerns for synthetic biology.  The vast published and peered-review scientific evidence addressing and alleviating these concerns, has been  largely ignored, and the concerns  and debate persist.

Some concerned members in this forum  have started addressing the possible socio-economic impact, fair and equitable sharing of benefits across national boundaries, the role of indigenous communities, centers of origin and other such topics.  The statement by Jorge Antonio Rojas from Bolivia raises the possibility that discussions about the safety of products of synthetic biology, will follow the same tortuous and unscientific path as the GMO debate. If this is the case,  I fear that the discussions of this group may lose scientific rigor and the group is not likely to reach consensus.  Much time, effort and resources will be spent “going round in circles”.

I look forward  to  reading your comments and to the outcome of these discussions.

Maria Mercedes Roca
posted on 2015-05-03 22:04 UTC by Dr. Maria Mercedes Roca, CIBIOGEM, Mexico
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6957]
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 00:07 UTC by Ms. Gulay Mann, Defence Science and Technology Organistaion
This is a reply to 6957 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6959]
First of all, I will like to thank Mart Loog 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 02:09 UTC by Mr. Jorge Antonio Rojas Beltrán, Bolivia (Plurinational State of)
This is a reply to 6959 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6964]
Dear all,
My name is Jean-Christophe Pagès, professor of biochemistry and molecular biology. I am heading the scientific committee of an valuation body for biotechnologies in France, the High Council for biotechnology (HCB). As such we have (and will) discussed and we look with interest to the development of all evolution in the field.

Concerning the definition, I follow Dr JA Machado in its simple formulation of the field. However as pointed by several other contributors the field is wide and the techniques will concern very different types of use:
First it is important to distinguish applications not relying on an "organism": all applications using biological tools (enzyme, small molecules..) with no ability to replicate autonomously. This relates more to bioreactors and should be regarded as such.
For living organisms, we could point:
- Existing organism modified to generate new "products" but with no changes in their ability to grow in a defined environment.
o It will be necessary to define basic criteria confirming this characteristic.
o The definition does not look to the product or the qualification of this organism (GMO….)
- Existing organism modified to generate new "products" but with changes in their ability to grow in a defined environment and to adapt to existing conditions:
o It will be important to characterize, auxotrophy, ability to evolve …
- “New” organisms, with no history of laboratory or environmental knowledge.
The definition should not be binding in a sense that, since the field is moving, a precise definition would miss unanticipated applications.
The definition should consider case-by-case evaluation. It is my understanding that the purpose and the objective of the definition are too allow a classification allowing for the formulation of rules for use and follow-up of the applications by proportional means.
posted on 2015-05-04 05:39 UTC by Mr. Jean-Christophe Pagès, France
This is a reply to 6948 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6993]
Dear All -

I strongly agree with Ms. Davis that our definition for synthetic biology should not exclude anything from regulation or oversight in situations where it is legitimately needed.

I will observe, however, that in consultation with its own scientific community, the US government has defined synthetic nucleic acid molecules for its own domestic synthetic biology oversight purposes, and that all publicly-funded research involving synthetic nucleic acid molecules is required to adhere to US national government rules, by law and/or contractual obligation.

(See: NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules at Section I-B: Definition of Recombinant and Synthetic Nucleic Acid Molecules  URL: http://osp.od.nih.gov/sites/default/files/NIH_Guidelines.html#_Toc351276218)

I offer that information as an indication that a definition may be achieved, and not as broader endorsement of NIH Guidelines, as published research and accident reports have repeatedly indicated serious problems with enforcement and compliance with those rules (see: Biosecurity and Bioterrorism March 2008, 6(1): 19-35.)

Thank you again for the opportunity to contribute to this forum.

Sincerely,

Edward Hammond
posted on 2015-05-04 16:39 UTC by Mr. Edward Hammond, Third World Network
This is a reply to 6949 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#6997]
In addition to Dr. Rüdelsheim’s comments I would like to add my own, as a chosen representative of the European Federation of Biotechnology (EFB - http://www.efb-central.org) and an elected chair of its Bioengineering and Bioprocessing section.

As eloquently expressed by Prof. Roca (#6950) “our opinion is biased and polarized depending on our background”. It is also biased by our concerns for the future and we must be aware that any ‘operational definition’ to be put forth by such a wide consultation process is likely to used in future as a definition of synthetic biology. With this in mind, such a definition must align with that proposed by practitioners in the field of synthetic biology and the widely accepted definition discussed by Prof. Freemont (#6814, Topic 1) serves this purpose well; as far as any single sentence can. The operational definition must not be allowed to be so broad that the word ‘synthetic biology’ could reasonably be substituted with ‘biotechnology’, after all that would negate it being a definition. It would also imply that we are discussing far beyond our remit and should involve the much wider biotechnology community in the forum.
posted on 2015-05-04 19:25 UTC by Dr Louise Horsfall, University of Edinburgh
This is a reply to 6997 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7006]
Dear Colleagues,

My name is Guilherme Oliveira, Senior Researcher of the Oswaldo Cruz Foundation and of Vale Technology Institute. My work relates to the exploration of biodiversity using genomics approaches.

Thank you for the chance to participate and for the very insightful posts. I would like to propose the definition below. It was first inspired Bruce Dannenberg’s definition, refined by all comments and similar to José Leonardo Bocanegra Silva’s definition and of  European SCENIHR.

Synthetic biology is the designing, redesigning or engineering of biological systems using pre-existing or novel components applied for a new purpose, such as the production of novel products, phenotypes or to create new organisms.

Systems - differentiates SB from already well established genetic engineering procedures

I wonder if the the definition of LMOs under Art.3 of Cartagena protocol includes the actual organism as a product.

Kind regards,
Guilherme Oliveira
posted on 2015-05-05 02:27 UTC by Mr. Guilherme Oliveira, Brazil
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7017]
Dear collegues,

My name is Katsiaryna Sidarenka and I am working at the National Co-ordination Biosafety Centre (NCBC) of Belarus.

I think that working on any subject  demands clear and logic definition of the subject itself, otherwise the main goal of all the efforts is not apprehensible.

If to talk about Synthetic Biology, the very core of the question is the main principle, which differs SynBio from all other fields of bioscience activities – the principle of “de novo synthesis”, i.e. creating of something that was never introduced before in bioworld (artificial organisms, sequences,  molecule, etc.).  So complete novicy of the SinBio product (organism, sequence,  molecule, pathway, etc.) should be the main characteristic. All other variables, such as methods, may be very changeable because of the fast science progress. So if we use them in definition – definition gets insecure.

All other inventions mentioned during this Forum to my mind could be classified as LMO because are based on already known and evolutionary tested processes, sequences and molecule and  mechanisms of their functioning are predictable.
posted on 2015-05-05 13:27 UTC by Ms. Katsiaryna Sidarenka, Institute of Genetics and Cytology at the National Academy of Sciences of Belarus
This is a reply to 7006 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7036]
My name is Gerd Winter. I am a lawyer and as such apparently a rare species in this interesting consultation round. I am director of the Research Unit for European Environmental Law (FEU) at the University of Bremen. Having had some experience with the regulation of GMOs as well as with questions of access to genetic resources and benefit sharing I’d like to submit some suggestions.
1. On general definition theory: It does not make sense to find a best term and definition per se. The choice of terms and their definition is always dependent on the given purpose and context. For instance, SynBio can be defined to be “A”, when a programme for research funding  shall be elaborated, it can be “B” if the difference between traditional genetic engineering and new biotechniques shall be characterised, it can be “C” if environmental risks shall be prevented, it can be “D” if ABS issues shall be addressed, etc. In the context of the the Cartagena Protocol it is obvious that the relevant context is the regulation of risks.
2. Assuming that risk regulation is at stake we should distinguish between the scope and the requirements of any regulation. The scope decides about what objects and activities are covered by the regulation. If covered they are subjected to a set of requirements (which can be duties of care and reporting, prior notification or permit conditions,  etc.)
3. I have doubts if it is wise to use the term “synthetic biology” as one that defines the scope of a regulation in the field. The term needed should in some way denote a basic risk that is the reason for a regulation. "Synthetic biology" is much too broad for this. In the GMO regulation the basic risk has been defined as being genetic modification techniques in the EU while in the US it has been a product characteristic of concern (such as a product being a pesticide, a plant for cultivation, a toxic substance, a medicinal drug, etc). How could such basic risk be defined in relation the new developments called synthetic biology? In the first case the technique might be termed “genetic construction” as opposed to “genetic modification”, and the techniques covered might then be listed. In the second case it must carefully be checked if the relevant product risks are captured or if the new technology will yield new product lines that are not yet covered by adequate risk regulation (products for electronic data processing, for bioremediation, etc. being possible examples). In any case, I believe at the stage of risk assessment at the latest there is a need not only to look at the product but also at the techniques of its construction. They provide  important information about hazards and risks.
4. Many commentators have proposed to regulate organisms only. It should however be considered that there may be risks caused by the bringing on the market and subsequent use of non-living bioparts. Some of them which are used for potentially dangerous products may need to be supervised in order to prevent misuses.
5. It has often been suggested that risks from SynBio are already covered by the GMO regimes of the different states. This is not correct in relation for instance to the EU GMO regime. SynBio, insofar as it works on existing living cells and alters their genetic material in a way that does not occur naturally, must indeed be counted as a technique resulting in genetic modification and thus as techniques subjected to the existing EU GMO regime. In particular, organisms in which the genetic content was modified by synthesized material of natural or articifial design are covered, even insofar as new genetic xeno-material is introduced.  By contrast, however, I consider the following SynBio products not to be captured by the EU-GMO regime:

– an organism which was completely synthesized, be it of natural or artificial design
– an organism in which the genetic material was completely replaced by known or artificial genetic material
– an organism into which genetic material was inserted by other techniques than vector systems, micro-injection, non-natural cell-fusion or hybridization
– an organism whose chemical derivatives (amino acids, proteins) were modified
– a protocell
– a minimal cell
– synthesized or extracted bioparts
– an organism whose chemical derivatives (amino acids, proteins) were modified by xenobiochemistry
posted on 2015-05-05 21:11 UTC by Mr. Gerd Winter, University of Bremen
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7045]
Dear Colleagues,
I am Dr Lazaro Regalado Specialist in Microbiology and Expert in Biosafety and Biosecurity from the National Center on Biosafety, Cuban Ministry of Science Technology and Environment

So far, more than 40 interventions on this issue as well as being mentioned in the other two topics, as you may have seen there are different shades of opinion, from those not considered possible to reach the goal set even those who consider it necessary, essential or just crucial, consider some expressions about:

Gerd Winter.
¨On general definition theory: It does not make sense to find a best term and definition per se. The choice of terms and their definition is always dependent on the given purpose and context.¨

Edward Hammond
¨………our definition for synthetic biology should not exclude anything from regulation or oversight in situations where it is legitimately needed……
¨I offer that information as an indication that a definition may be achieved, and not as broader endorsement of NIH Guidelines, as published research and accident reports have repeatedly indicated serious problems with enforcement and compliance with those rules (see: Biosecurity and Bioterrorism March 2008, 6(1): 19-35.)

Dr. Patrick Rüdelsheim
Any broad definition is bound to cover organisms that “make no sense” to include as indicated by H. Bergmans (#6812).

Boet Glandorf
I am of the opinion that for this on-line discussion we need an operational definition of synthetic biology (and not a legislative definition) to at least  focus our discussions.

Jim Thomas,

An empirically-based definition of Synthetic Biology  is possible and necessary.
The ideal structure of a formal definition is to combine a broad definition with a ‘living list’.
Synthetic biology is ‘applied’ but not necessarily ‘for useful purposes’

Ray Layton
I agree that the task of developing a definition is hard.  At the same time, I believe that the group is not likely to move forward until we get this step out of the way.


In my humble opinion we cannot work on something we have not defined, hence the need to find ways to do so, in this sense, the group has moved from simple definitions but an encompassing general and common characteristic to attempts more detailed and also shows different interests and points of view, scientific, from the industry and NGO, computer, legal etc.
In my view we should develop a sufficiently broad definition as simple as possible with room for all possible characteristics, techniques, the scope is understood and leaves room for its expansion, collect scientific aspects and to provide a framework of ethical and social analysis. On the other hand the broad spectrum of proposal should lead to find a common ground.

Best regards,
Lázaro Regalado
posted on 2015-05-06 06:33 UTC by Mr. Lazaro Regalado, Cuba
This is a reply to 7045 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7046]
Hello, I am Hilary Sutcliffe, I run an organisation in the UK which concerns itself with Responsible Innovation - whilst we are not pro or anti any particular technology we promote the use of technology for social benefit, with an accompanying understanding of risks and involvement of stakeholders.

We started our work with Nanotechnology, where the academic and business disinclination to grasp the nettle of defining the technology adequately, resulted in a regulatory definition which was not fit for purpose, confusion among stakeholders and 10 years of indeterminate wrangling instead of getting on with considering what is valuable about the technology, what aspects are concerning and what are not.

A wide group of stakeholders I have spoken to regret this and feel it was time wasted.  Those who are concerned about the risks of the technology feel perhaps that resource could have been focused much earlier on the specific concerns of the technology, those focusing on applications felt too much time was spent arguing about theoretical aspects holding back the practical and safe use of the technology.  

I agree with Lazaro and others.  A definition is essential.  Not least because someone will impose one whether you like it or not, which may or may not be satisfactory.  It is important that all stakeholders come together to work on this, and that the definition is scientifically correct, but also practical, making clear distinctions for the use of regulators and users.  It should happen as a matter of urgency.
posted on 2015-05-06 07:02 UTC by Ms. Hilary Sutcliffe, MATTER
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7058]
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). Thanks to the moderators and other participants for their interesting and important contributions.

Whilst recognising that it is very difficult to arrive at an operational definition of synthetic biology that satisfies the views of all stakeholders, a shared understanding of what constitutes synthetic biology would be helpful for Parties and stakeholders alike.  However it is first important to fully understand the purpose of this exercise and any envisaged applications of a definition. Given the potential breadth and scope of the definition and potential to cut across a range of disciplines and regulatory frameworks, we do not believe that such a definition should be used for regulatory purposes.

The most recent attempt by EU scientific committees resulted in a consensus view that synthetic biology can be defined as: ‘…the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms’. This definition provides context in which synthetic biology will be used and is consistent with the approach for modern biotechnology in EU and Cartagena. The authors acknowledge that this definition may change as the understanding of synbio concepts, tools and applications evolves.
posted on 2015-05-06 13:32 UTC by Mr. Michael Paton, United Kingdom of Great Britain and Northern Ireland
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7061]
Dear participants,

I present some inputs to the topic 3: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria”.

I read the interesting suggestions and comments on topic 3 that give us important inputs. I would like to start saying the operational definition needs to be functional propose. It should help us to build a regulation to prevent the potential negative impacts on biological diversity, taking account the ecosystem services, its structure, and human health; as some participants have proposed.

Synthetic biology uses the modern technology and also builds novel genetic material to develop components, organism and products. It is important consider the proposal by Dr. Regalado, Ms. Genya Dana from USA and others, related with broad definition. The definition should be broader to consider components, organism and products of synthetic biology. Hence, it should be operational and functional, so it may consider the following definition on the base European Commission (2014) and UK Royal Academy of Engineering RAE (2009).

Synthetic Biology means the application of science, technology and engineering:
- Facilitates and accelerate the design, manufacture and/or modification of genetic materials in living organisms to alter living or non-living materials;
- Redesigns existing, natural biological systems; or
- Designs and engineer novel devices and systems.

Best regards,

Dr. Marina Rosales Benites de Franco
IUCN’s Commission on Ecosystem Management
(edited on 2015-05-06 14:53 UTC by Ms. Marina Rosales Benites de Franco)
posted on 2015-05-06 14:52 UTC by Ms. Marina Rosales Benites de Franco, IUCN
This is a reply to 7046 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7062]
Dear participants,

After so many views about BS concept I think they express a common point that seems to be that ´all organisms from BS are LMOs but not all LMOs are BS´. That means that LMOs are a broad group that incorporate many different techniques (e.g. Syntethic Biology, New Plant Breeding Techniques  and many others in the next future) and that leads to the conclusion that the concept of LMO as established in the Art.3 of  Cartagena Protocol could be adopted for BS - LMOs means ´any living organism that possesses a novel combination of genetic material through the use of MODERN BIOTECHNOLOGY.’

FOR THE SPECIFICITIES OF BS already discussed by many participants I propose the inclusion of one more application in the definition of the term MODERN BIOTECHNOLOGY in the context of Cartagena Protocol. In this case we could include that the ´Modern biotechnology´ means also the application of ´the genomic reconstruction (or ´de novo´design/ or redesign / or engineering) with chemically synthesized genetic material´  (together with other applications definied in the Art. 3, item (i) of Cartagena Protocol).  

In this sense it´s possible to capture the regulations and the experience we already have with LMOs, using a broad concept that is already agreed upon and we could avoid all the effort of duplicating the work. Also is important to mention that the case-by-case nature of the risk assessment framework allows the risk assessor to evaluate specific risk hypothesis associated with the specific organism.

Thank you.

Best regards,
Luciana / Ministry of Agriculture - Brazil
posted on 2015-05-06 15:18 UTC by Ms. Luciana Ambrozevicius, Brazil
This is a reply to 7062 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7078]
Dear Colleagues,
My name is Lázaro Regalado
In general terms I think that the way suggested by Luciana  (Ministry of Agriculture of Brazil) [#7062] is reasonable and practical as a point of departure , as said previously [#7045] the broad spectrum of proposal should lead to find a common ground and hopefully we’ll fulfill our mandate.
Best regards,
Dr Lázaro Regalado
National Center of Biosafety, Cuban Ministry of Science Technology and Environment
posted on 2015-05-07 04:32 UTC by Mr. Lazaro Regalado, Cuba
This is a reply to 7058 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7079]
Following Dr. Ryo Kohsaka (# 7059) instruction to be brief,  and in an attempt to move forward,  I express my support for the definition proposed by Dr. Michael Paton (#7058) who quotes the definition “attempted” by EU scientific communities.

From this “attempt” and from our own discussions, it is clear that given the emerging nature of synthetic biology and the divergence of stakeholders in this group, reaching consensus on a definition,  will not be an easy task.

I would also like to support Dr. Louise Horsefall who requests that unsubstantiated statements such as # 7043 (Mr. Bass) do not go unquestioned.
posted on 2015-05-07 04:41 UTC by Dr. Maria Mercedes Roca, CIBIOGEM, Mexico
This is a reply to 7079 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7080]
Dear all:

After the first intervention, I kept rather watching on the direction of the discussion. I shall be brief as Dr. Kosaka (# 7059) and Dra. Maria Mercedes [#7079]commented.
Certainly, there are different views on how to define the synthetic biology, and we could indulge in science, and it is not easy task to conclude. Also many different participants, some are new to CBD forum, and some have previous experience such at RA&RM on biosafety under CPB, threw would be different approach and consideration in this forum. Yet, the focus shall be made to define synthetic biology, in association with the CBD, and a broader concept to cover all possibilities of inclusion for SynBio subjects, may not fit with the CBD goals.

Regards,

Kazuo Watanabe
University of Tsukuba
posted on 2015-05-07 05:04 UTC by Mr. Kazuo Watanabe, Japan
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7102]
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.

The question of coming to an operational definition of synthetic biology, comprising inclusion and exclusion criteria, seems develishly complicated. For me there are a number of important basic fundamental aspects:
o 'Synthetic biology' is for a large part conceptual and abstract in nature, which makes a precise and legally sustainable definition all the more elusive.
o In my opinion the essence of the concept of synthetic biology is that it provides a different perspective on biological systems; loosely phrased it looks upon biological systems as a chemically coded systematics (language, circuits, systems, devices) that can be recoded and redesigned and, eventually, coded and designed from scratch. That is, we now have a set of conceptual building blocks that allows us to (re)code and (re)design self-assembling and self-replicating (or induced-replicating) systems that can be put to use for our benefit.
o In my opinion the essence of synbio therefore is that it changes our perspective and the way we look at 'things' and the way we define them. That is, it is not so much the tools, instruments and scientific principles that are used in synbio that are essentially different, it is what we think we can do, build and achieve with those instruments. 
o Consequently, from this perspective much of what we already do within the field of GM, is an integral part of synthetic biology. 

For the sake of discussion (as this is a discussion platform) I am proposing to rethink the actual need for an operational definition of synbio.
o First of all, there are ample (conceptual) definitions available, of which the SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks) proposal is broadly applicable and favored by us. As a general principle synthetic biology should not be seen as separate from GM. Rather GM is to be seen as a subset of synbio; the SCENIHR definition is in full accordance with this principle.
o The question is where the need for further operationalization comes into the discussion.
o One of the proposed reasons is that we need this to assess the possible effects (either beneficial or adverse) in its broadest possible sense (health, environment, social, economic, legal). 
From my perspective it is neither fruitful nor logical to make use of a top-down definition. It will be the final products that will have the impact you want to assess, and not the development platform of synbio as such. Focus should therefore be on the 'product space' - which can either be living (as in self-organizing and self/induced replicating) or non-living.
o It seems that many of the unresolved issues related to the 'synbio definition' are not so much intrinsically connected to the concept of synthetic biology but much more to the definitions of underlying aspects like 'genetic resource'. Focus should be on clarification on the interpretation and definition of these terms, and not on 'synthetic biology' as a systematics.

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

Respectfully,

Jaco Westra
posted on 2015-05-08 11:26 UTC by Mr. Jaco Westra, Netherlands
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7110]
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 have been following the discussion and since there already are so many comments, I will try to state the comments I can agree with.

First of all, I agree with many of the conceptual definitions concentrating on computer-aided engineering and design, standardization, construction and redesign that have been posted by (for example) Ossama AbdelKawy, José Leonardo Bocanegra Silva or Mart Loog. However, in a practical approach, these definitions cannot distinguish synthetic biology from genetic engineering. For the moment, I do not think this differentiation is necessary and agree with many of my predecessors that products of synthetic biology are covered under the LMO definition in the Cartagena protocol as well as in national guidelines on genetically modified organisms.

As a risk assessor on genetic engineering, however, I think we should find a possibility to define organisms of synthetic biology that do not fall under the LMO definition. This definition could be the one of Steven Evans who proposes that an organism of synthetic biology ´can no longer exchange information or transcribe/translate information with its originating species strain or any other 'natural' species.´ This definition would include organisms with xeno nucleic acids currently developed as these organisms can still exchange information with their originating species. I do not think that we should define certain techniques as a criterion for synthetic biology, because an organism will not have a different risk for biodiversity depending on the technique used to create is, if the modification is the same. Therefore, I agree to Paul Freemont that we should not use a list as broad as the one by Jim Thomas that contains many standard molecular biology techniques currently used in genetic engineering that cannot be used as a defining criterion for synthetic biology. Like Maria Mercedes Roca I hope that this discussion will not restart the unscientific debate around genetic engineering, because I think it is neither the topic nor will it help us find a definition of synthetic biology.

Best regards,
Swantje Strassheim
posted on 2015-05-08 16:10 UTC by Ms. Swantje Strassheim, Germany
This is a reply to 7110 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7112]
Dear Participants,

My name is Theresa Good and I am a program officer at the USA National Science Foundation (NSF) with responsibility of funding projects in the area of synthetic biology.

I agree with many of the comments that have been posted about the operational definition of synthetic biology.  From the perspective of an agency which funds basic and applied research in this area, we take a broad view of synthetic biology as part of a spectrum of activities in advanced biotechnology that include genetic engineering and metabolic engineering.  In general, we think of synthetic biology as an approach with brings in ideas of design from other disciplines outside of biology, as well as modularity, reusability, and other features that accelerate the development of modified organisms (or DNA). 

In the context of identifying risk to biological diversity, the environmental risks of an organism produced via synthetic biology, genetic engineering or metabolic engineering seem to be indistinguishable.  That is to say, that the environmental risk of the organism or material is not dependent upon the way that they are produced, but instead on the way that they are used. 

In evaluating research projects to be funded, at NSF, we would evaluate the environmental risks and safety of all projects produced via applied biotechnology in the same way, and would not distinguish risks associated with synthetic biology from genetic engineering or other technologies designed to modify an organism.
posted on 2015-05-08 16:44 UTC by Ms. Theresa Good, United States of America
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7119]
I appreciate the opportunity to comment on this Forum. I am Dr. Maria Fedorova from DuPont Pioneer representing CropLife International. My educational background is in molecular genetics and for almost two decades I conducted research in plant molecular biology.  For the past 10 years I have been involved in biotechnology regulatory affairs, in particular coordinating characterization and safety studies on genetically modified crops. 

By reading posted comments, it looks to me that it will be challenging to develop a consensus definition which is agreed upon by everybody. And further, to identify a set of inclusion and exclusion criteria that would not become obsolete in a relatively short term due to next scientific breakthroughs. Instead, I propose that we ask ourselves why do we need to strive for a formal definition, what purpose would it fit? 

Calling an organism a product  of ‘synthetic biology’ does not make it a priori any meaningfully different or inherently risky. I fully agree with several Forum experts who expressed that any potential biosafety risks or benefits are embedded in the characteristics of the organism itself, and not in the name of the process or the set of tools used to produce it. 
 
The bottom line,  and as also expressed by a number of participants, if a living organism is produced using the recombinant nucleic acid technology and contains a novel combination of genetic material (whether of a natural or an artificial origin), it will be effectively an LMO and as such, covered by the Cartagena protocol.  A potential new category might be needed in future for completely de-novo created organisms, however at this moment such discussion is premature.
posted on 2015-05-08 20:02 UTC by Ms. Maria Fedorova, DuPont Pioneer
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7121]
Once again many thanks for the opportunity to participate in and observe this discussion. Reviewing the comments  so far there appear to be some proposals that strike me as of concern and i would like to share the following observations.

1. Calling a spade a spade..

The first is a proposal expressed in several places to massively limit the definition of synthetic biology to only  apply the term synthetic biology when something is ‘truly novel’  ,’ only using non-canonical nucleotides’, only where the engineered systems are so artificial that they ‘cannot exchange with nature’, or where the elements are not “natural” (where apparently synthetic DNA/RNA is regarded as  ‘natural’ by those putting forward this view). In effect what these suggestions propose is to very narrowly define synthetic biology as  synonymous with xenobiology.

In my view to take this narrowing approach is to deliberately (and bizarrely) ignore the reality of what is commonly described as Synthetic Biology and the actual real world work of most people and companies who self-describe as  Synthetic Biologists. To try to re-cast Syn Bio as ‘just xenobiology’ is to willfully put aside an extensive and overwhelming existing literature and common understanding on Synthetic Biology, including the findings of the CBD’s own extensively peer-reviewed technical series onb this topic, the investigations of several regional commission processes (e.g. The Presidential Commission on Bioethics, The European Group on Ethics etc. Its to ignore the reality of how that term gets used for funding, by professional organizations and by commercial companies who apply these technologies under the term ‘synthetic biology’, meet at “synthetic biology’ conferences, jamborees, give pitches to venture capitalists to join ‘syn Bio accelerator programs etc’.. All of that is what is commonly understood as Synthetic Biology. This is why i pointed to the scientometric studies of Oldham, Joly and others - it is possible to empirically describe the terrain of synthetic biology.

In English we have an expression that “you should call a spade, a spade” which means you should be straightforward and honest about what a thing is and not pretend its something else because you have another agenda. In my view the CBD should also honestly use the term Synthetic Biology  in line with how the term is commonly used in order to better describe actually what it really is, not what it would be strategically useful to describe within the exigencies of biosafety assessment  processes.

After all when the COP requests a definition, why wouldn’t we respond by calling a spade a spade?The underlying assumption of those arguing for narrowing the definition towards xenobiology appears to be (generously) that the only purpose of crafting a definition is to carve out a new area for biosafety assessment and that we wouldn’t want to have a definition that overlaps with existing definitions of an ‘LMO’. (why not?) This view of the operational purpose of a definition seems singularly  obsessed with use of a definition for biosafety assessment under a Cartagena framework This viewpoint implicitly fails to acknowledge that there will be many other aspects (beyond biosafety assessment) that an agreed definition will be put to and indeed that there are other reasons for an operational definition and other areas urgently requiring oversight (e.g. assessing and managing societal impacts and risks arising, the indirect impacts on biodiversity and sustainable use, questions of ‘digital biopiracy’, proposed changes in conservation practice etc).

Less generously one might note that  the effect of confining the definition of syn bio for international oversight purposes to only  the most speculative and least commercialised corner of synthetic biology activity  (that is xenobiology) will be to have the least disruption on the actual  industrial enterprise of synthetic biology and least likely to upset investment and fundraising. If Syn  Bio is successfully framed this narrowly at the CBD then a company can still go to governments and the markets for funds for say metabolic engineering projects  while claiming to be doing ‘synthetic biology’ but when the government then comes along wanting to oversee the same  ‘synthetic biology’ the company can say they are doing no such thing because they are not using xenobiological molecules.

2. Not losing sight of ‘techniques’

The second proposal that i have trouble with is the suggestion to ignore aspects of intention or technique in crafting a definition and only define according to the composition of a final syn bio product. As Helmut Gaugitsch points out this process-based vs. product-based debate has a long and predictable history in the GMO debate and it would be tedious for those ideological dynamics to re-emerge here.

In truth the question of intention is significant for defining Synthetic Biology (since this is a field driven by a set of unusual assumptions and intentions - e.g. to make biology engineerable), it is unquestionably a field that is utilizing a broader basket of techniques and tools than ‘classical genetic engineering’ or recombinant DNA (that is a measurable variable) and we know that changes in technique can both alter risk profiles as well as have significant economic, social, political, cultural , ethical etc implications ands so cannot just be conveniently airbrushed out of the picture to try to dampen societal controversy. Its also true that ‘product’ can in some situations be another measurable variable but viewed alone can equally hide differences (e.g. a Syn bio vanillin is arguably indistinguishable from other vanillins but whether its made from lignin, farmed vanilla beans or monoculture sugar in vats of engineered microbes makes a huge different on the footprint of that specific flavor - so technique matters - and it matters to biodiversity.

In fact the COP of the CBD has already chosen to repeatedly define synthetic Biology in relation to techniques and determined that technique matters. Paragraph 3a of decision XII/24 requests states to establish, or have in place, effective risk assessment and management procedures and/or regulatory systems to regulate environmental release of any organisms, components or products resulting from synthetic biology TECHNIQUES, 3b refers to  “organisms resulting from synthetic biology techniques’, 3d requires “scientific assessments concerning organisms, components and products resulting from synthetic biology techniques” and so on. Decision X11/24 actually refers to ‘synthetic biology techniques 8 times’ - and appropriately so.

I once again reiterate my suggestion that a definition, to be useful, should be drafted to triangulate between these 3 elements of the intent, techniques and products of synthetic biology. ideally with a living list of hallmarks to help.

3. Open discussion

The third suggestion that I found disturbing was an expressed sentiment by some participants that it is not acceptable to consider “ the possible socio-economic impact, fair and equitable sharing of benefits across national boundaries, the role of indigenous communities, centers of origin and other such topics”  (Maria Mercedes Roca) when considering the implications of crafting a definition. It was expressed  that to do so would be “tortuous and unscientific” and that discussions of this group “may lose scientific rigor”. Once again the assumption here seems to be that that a definition-building exercise is only aimed towards narrow, strictly ’scientific’ ends (such as a technical biosafety risk assesment).

This is wrong. In fact the request to the Open Forum and to the AHTEG that came from COP explicitly asked for “representation of indigenous and local communities and all relevant stakeholders”, asked that the group Identify the potential benefits and risks of organisms, components and products arising from synthetic biology techniques to the conservation and sustainable use of biodiversity and related human health and socioeconomic impacts relevant to the mandate of the Convention and its Protocols” and indeed the decision  XII/24 urged parties (and therefore one would assume this forum) to take into account “other issues such as food security and socioeconomic considerations with, where appropriate, the full participation of indigenous and local communities”  and to “and to promote interdisciplinary research that includes related socioeconomic considerations;” As this forum goes forward i would urge fellow participants not to attempt to narrow the scope of acceptable discourse only to technical/scientific discussions. If that happens we would not be fulfilling our mandate.

4. On the necessity of definitions

A few comments (e.g. Jacob westra) argued that “ there is no actual need” for an operational definition or that it would be “counterproductive” to develop a definition (Genya Dana - USA).

I would strongly agree with Hilary Sutcliffe and others (e.g. Lazaro Regaldo) that a definition is essential.  “Not least because someone will impose one whether you like it or not, which may or may not be satisfactory.”  In any case the 193 nations of the COP have requested that this process develop an operational definition. That may be inconvenient for some but it is a clear international agreed decision.

I look forward to the rest of our discussions in the weeks ahead.

Best Wishes
Jim Thomas
ETC Group. (Canada)
posted on 2015-05-09 02:52 UTC by Mr. Jim Thomas, ETC Group
This is a reply to 7121 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7130]
Dear Participants and the Chair on this on line forum,

Thank you for all because I realize there are many different thoughts and opinion about this topics and I learnt too much from many comments in this discussion.

When I look at the posted comments, the definition of term "organisms" may be taken a mutual consensus in the Parties as the same meanings as the LMO of Cartagena Protocol.  But regarding the definition of synthetic biology, it seems that the outlet of our discussion have not been determined yet.

I would like you to be back to Dr. Paul Freeman's comment [#4814].  In the first parts of his comments, he introduced us an excellent explanation about what the synthetic biology is and the relationship (overlaps) between modern biology and synthetic biology.   I have no objection about his explanation because I believe the explanation would be cover with the scope of current existing synthetic biology.  He also stated in the comment[#4036] that “I think by defining synthetic biology in the broadest possible terms that encompass all development in molecular and cellular biology, genomics, bioinformatics, developmental biology etc is very confusing and is based upon researchers using the term to enhance their published work.”.

I completely agree with his statements.  The mainstream of this discussion must be whether the new emerging issue “Synthetic biology”, which needs some new regulation systems, is identified and separated from the historical technology “Modern Biotechnology” or not.  The proposed definition of synthetic biology by EU scientific committees does not work for both identification of synthetic biology and separation from “modern biotechnology”.  I think Dr. Paul Freeman's explanation itself is fit for the definition of synthetic biology. 

In addition, the “operational” definition should be more specific and clear one, including the identification of the synthetic biology and separation from historical technology, for further discussion in this online forum.  In that point, as I stated a comments in Topics 2 [#6935], we had better moving to the discussion focusing of “Products” derived from synthetic biology.

As Mr. the Helmut Gaugitsch’s [#6935] answered my questions in my comments [#6935], there are two kinds of concepts about the “Products”, reproducible entities(such as LMO’s) and materials derived from synthetic biology.  However, the latter “Products” might be difficult to make risk assessment on product basis because there would be no genetic materials in the latter products.  I do not agree with the procedure, process-based assessment.  The target for risk assessment must be product-based method.

The above is my current thought regarding Topics 3.  
I look forward to other comments and counterarguments about my thought.

Hideyuki
posted on 2015-05-10 07:23 UTC by Mr. HIDEYUKI SHIRAE, Japan
This is a reply to 7121 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7131]
Dear Colleagues,
My name is Lázaro Regalado
First of all I would like to thank our moderator Mart Loog for conducting us as well as the comments and views expressed by all participants in this forum.
So far, more than 60 interventions on topic 3 have been posted; In this regard I would like to draw the attention to the post [#7121] from Jim Thomas:
He analyses critically some approaches and makes sense: about the scope of the term SB, “the possible socio-economic impact, fair and equitable sharing of benefits across national boundaries, the role of indigenous communities, centers of origin and other such topics”, ¨Decision XII/24 in connection with ¨ actually refers to ‘synthetic biology techniques 8 times’ - and appropriately so¨ and  on the necessity of definitions.
If we take a look at the decision mentioned above and If we take into consideration that there are many definitions suggested some of them the same proposed by different participants, then we can’t ignore this fact.
My suggestion to examine and evaluate the related document sent by Bolivia in response to notification inviting the submission of information on synthetic biology (SCBD/BS/CG/MPM/DA/84279)
Another point of view expressed:
¨It is clear to us that the profit motive does not necessarily work to support the goal of the preservation of biological diversity or the fair sharing of costs and benefits between developed and developing countries…..¨ Matthew Legge

Respectfully,
Dr Lázaro Regalado
National Center of Biosafety, Ministry of Science, Technology and Environment. Cuba.
posted on 2015-05-10 08:00 UTC by Mr. Lazaro Regalado, Cuba
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7132]
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.

There is some consensus in this discussion that a broad definition of synthetic biology is needed so that it remains applicable to future technological advances. Only a broad definition can apply, given that synthetic biology is a general term encompassing a range of tools and technologies and multiple disciplines, and that it represents a continuum of advancements in these disciplines. Some participants have proposed that specific techniques should be included in a definition, however this restricts the definition to known techniques, namely those of the past and emerging in the present. For the same reasons, any inclusion and exclusion criteria should not be strictly defined, and these should focus on the characteristics of the organisms created.

There is also some consensus in all of the topics (1-3) currently under discussion that organisms developed using synthetic biology approaches are LMOs within the scope of the Cartagena Protocol definition (but not all LMOs are necessarily products of synthetic biology). In my post under Topic 2, I drew the conclusion that the living products of synthetic biology fall within the Protocol’s definition of LMO.

The following definition, which draws from the proposals of many other participants in this discussion, is proposed: Synthetic biology is a multidisciplinary approach for the design and engineering of biological systems.
This definition focuses on the various tools and technologies that may be used in a particular synthetic biology application, with the term ‘approach’ used to represent these.

In regard to inclusion and exclusion criteria, guidance is already provided in the language of the Convention and the Cartagena Protocol, and these should be determined according to the characteristics of the biological system created by the synthetic biology approach. By definition, an LMO must be ‘living’, and it must contain a ‘novel combination of genetic material’ as a result of the application of ‘modern biotechnology’. These three criteria appear to only expressly exclude non-living entities created by synthetic biology approaches. Furthermore, the Protocol broadly defines ‘living organism’ as one that is ‘capable of transferring or replicating genetic material’, and the Convention defines ‘genetic material’ as including nucleic acids from ‘plant, animal, microbial or other origin’. It has been suggested that certain organisms created using synthetic biology approaches may be differentiated from LMOs by their ‘de novo’ creation, or that ‘LMO’ as defined by the Protocol does not extend to xeno-systems, however these definitions indicate that such organisms/systems may not be excluded from the Protocol’s scope.

As I noted in my post under Topic 2, the Protocol already envisions case-by-case assessment of LMOs, and its provisions remain applicable to LMOs created using synthetic biology approaches.

Best regards,
Felicity Keiper
Bayer CropScience
posted on 2015-05-10 08:37 UTC by Ms. Felicity Keiper, Bayer CropScience
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7136]
Dear all, my apologies for coming to this discussion so late. I am Dr Michele Garfinkel. I manage the Science Policy Programme at EMBO (European Molecular Biology Organization). I have been working on issues in synthetic biology for over a decade and am interested to see both how much the discussions have changed, and in some cases how much they have not! I look forward to the continuing forums to see how they develop and to being able to participate more fully.

The one point I would make for now, in the context of discussions that have been going on for many years now: If we will insist on a definition of synthetic biology for regulatory or functional reasons then we could think about starting with a minimal definition, and then adding in elements that are inescapably synthetic biology and not just emerging biotechnologies; in other words, what is the incremental difference between synthetic biology and all biotechnology that makes it uniquely identifiable?

I would note that, just for example, an argument could be made that Crispr is the opposite of synthetic biology: it is extremely precise, its great value is in the possibility of making just a few very specific modifications per genome. There are many concerns about Crispr, those concerns may or may not overlap with synthetic biology in terms of safety or ethics or environmental impacts including biodiversity, it may be used as a tool along with synthetic biology, but Crispr is not itself synthetic biology. On the other hand, conventional breeding by even the most straightforward definition can be considered to contain elements of "synthesis", of some sort. Again, there may be concerns that overlap with synthetic biology, but by working toward defining those characteristics unique to synthetic biology, we will then be able to also point out where there may be overlaps with other biotechnologies of concern, a useful exercise in thinking about environmental and other societal outcomes.
(edited on 2015-05-10 12:38 UTC by Ms. Michele Garfinkel)
posted on 2015-05-10 12:36 UTC by Ms. Michele Garfinkel, EMBO
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7138]
Dear the Forum Participants,

I am Kazuyuki SUWABE, in charge of environmental risk assessment of LMOs in the Japan Ministry of Agriculture, Forestry and Fisheries (MAFF).
I thank Dr. Mart Loog for chairing this online discussion and thanks also participants for many contributions which I have learnt a lot.

As many pointed, I fully agree that this is a great challenge for us to think of an operational definition of Synthetic biology. I think the synthetic biology is convergence of techniques to create organisms which has not been achieved by existing techniques (I do not mean to propose this as my definition). Novelty, artificiality (synthesis), inter disciplines seem some of key features for me.

It is always exciting to read insights in comments and proposals but at the same time I am concerned with some proposed definitions as Dr. Garninkel mentioned [#7136]. Some proposals are not clear enough and seem to cover organisms which are obtained not only by modern biotechnology (LMOs) but also by old biotechnology e.g. chemically-induced or gamma-irradiation-induced mutational variants.

I understand in this topic we should not discuss which to be subject to regulations or not and do know this task is not easy; but at least a definition of synthetic should not include what have been used for many years e.g. organisms developed through traditional breeding techniques.
If it does not have clear distinction, it will bring us confusion when we use it.

I will be happy if my comment can contribute to this discussion and help it move forward.

Best Regards,
Kazuyuki SUWABE, MAFF, Japan
posted on 2015-05-10 15:49 UTC by Mr. Kazuyuki SUWABE, Japan
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7142]
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 will not go into trying to define synthetic biology, much has already been said by those who have  long-lasting experience. But what I do want to add to this discussion in particular is that I do not see it as a good strategy to limit the definition to "xenobiology". As said by many in the three discussions going on, practically all products arising fall into the definitions already set by the Cartagena Protocol relating LMO and Modern Biotechnology definitions.
I applaud the level and intensity of the discussions, these topics are crosscutting between the different legal instruments (CBD, PC, PNKL, PN) and need to be visualized transversally.
Kind regards!
Francisca
posted on 2015-05-10 17:36 UTC by Ms. Francisca Acevedo, Mexico
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7143]
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.

Synthetic biology is not a monolithic bloc, it is diverse and on the move. The general subfields are well described. However the large diversity of the disciplinary backgrounds of the scientists contributes not only to the structuring of the field but is also framing the individual research agendas to a great extent. In addition during the short time of its existence, synthetic biology has not only grown substantially and moved on at the methodological level, but also broadly expanded its scope. Thus synthetic biology is very divers and constantly advancing. It is best characterized by a mosaic like picture with the engineering approach as a unifier. That makes societal evaluation of synthetic biology a challenging task and prone to misunderstandings. Confusions arise not only on the level of what part of synthetic biology the discussion is on, but also on the level of the underlying concepts in use. For this reason it is important

to frame an operational definition specifically for the context it is needed for.

Therefore for an operational definition of synthetic biology in the context of the relations of synthetic biology to biological diversity two attributes are needed:

1. The definition needs to be wide enough to capture all current (and upcoming) applications that might be important to biological diversity.

2. To give the wide scope and the heterogeneity of synthetic biology justice a very general definition needs to be framed with specific inclusion and exclusion criteria that are relevant.

For the identification of inclusion and exclusion criteria, it is suggested to focus on characteristic features of synthetic biology that are relevant for biodiversity. Here features that are new to synthetic biology when compared to genetic engineering are suggested (and I discuss them in more detail in the second topic of the online forum):

- In comparison to genetic engineering, organisms produced by synthetic biology are characterized by a much larger depth of intervention into the organism.
- 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. 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.
- Orthogonality, that is caused by the xenobiological approach

Organisms that exhibit one of the above mentioned features should therefore be included in the definition.

Best regards,
Margret Engelhard
posted on 2015-05-10 17:41 UTC by Ms. Margret Engelhard, Germany
This is a reply to 7143 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7147]
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 “Operational definition of synthetic biology, comprising inclusion and exclusion criteria”, lot of elements have been debated here.

All players of Synthetic Biology (SB) know for a fact that there is no consensual definition for it, even we have to accept that clear definitions are the necessary foundations for any science. We live with this paradox. For example, the more inclusive the definition is (like Jim Thomas' convincing one ) the less exclusion criteria it tends to have, which is nonetheless a problem.

Before trying to solve this issue, one must try to understand its origins. One of them is that so many players label their research with this trendy “SB” tag, that it's hard to find unity in all the field, not for scientific and definitional reasons, but because there is a marketing added-value, far for science, in joining the field. Based on this consideration, we should deserve more energy to decipher actual original and creative SB research, from classic biotech opportunisticly labelled SB research, than to look for an elusive definition that encompasses them all.

And additional challenge comes from the very fact that SB deals by definition with blurring the frontier between “natural” and “artificial” (whether it relates to organisms or their bioproducts). As such it challenges the very notion of “category” in biology, which leads everyone to a conundrum when trying to define operational exclusion criteria. To my opinion, a pragmatic definition of SB would be any “experimental attempts to explore new directions with modified organisms or proto-organisms (i.e. protocells)”. It might be vague and non-operational, but precisely, its vagueness accurately depicts, to my mind, the humility we biologists should manifest in recognizing that we fail to have a consensual definition, with exclusion criteria, of biological life itself.

My last consideration relates to the objectives of such an operational definition, an issue that deserve intensive care. What is operational for an lawyer specialized in IP may not be as operational of a public reseacher. For me, operational defintions of Synthetic Biology must (1) preserve freedom or research (2) pay attention to science-based societal concerns (3) preserve as much as possible the status of biological organisms as public goods, how modifed they can be by man-made interventions.

Best
Thomas
(edited on 2015-05-10 18:38 UTC by Mr. Thomas Heams)
posted on 2015-05-10 18:37 UTC by Mr. Thomas Heams, AgroParisTech
This is a reply to 6762 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7152]
A sufficiently broad definition should be used to ensure that relevant applications are not missed. This definition can also be applied to LMOs but should necessarily go above and beyond. For example:

“Synthetic Biology is using technical processes that are interfering with genetic information and the biological characteristics of cells and organisms and that are not governed by the natural gene regulation. It uses isolated biological active compounds that are prepared outside the organisms. It provides products, compounds and organisms that are biological active, might be able to reproduce and may have no natural template.” 

If applied in practice such a definition allows for example a distinction between breeding processes, random mutagenesis and directed evolutionary processes on the one hand, and genome editing, gene synthesis, new cellular or cell free systems, targeted DNA replacement and DNA alteration on the other hand.
posted on 2015-05-10 19:10 UTC by Mr. Christoph Then, Testbiotech
This is a reply to 7136 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7157]
Thank you for the opportunity to participate in this discussion on an operational definition. I also apologise for coming so late to the discussion. My name is Dr. Paul Oldham and I run a small analytics company and am a Visiting Senior Fellow at the United Nations University Institute for the Advanced Study of Sustainability (UNU-IAS). I was the lead author of a 2012 PLOS One article that used scientometrics to map the scientific landscape for synthetic biology as a contribution to thinking about the implications of this emerging field for the objectives of the Convention(http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034368). I have followed the discussions on syn bio at the COP and continue to monitor the scientific literature and patent data on this topic.
On the question of an operational definition, my view is that synthetic biology is a rallying flag for researchers who describe their work in the scientific literature as “synthetic biology” or synonyms such as “synthetic genomics”. One of the reasons that synthetic biology is difficult to capture with precision is that it involves a combination of convergences and overlaps with well established fields, such as genetic engineering, protein engineering or systems biology, while at the same time it also involves novel approaches resulting from the combination of different disciplines. This can (as we see from the 35 definitions + 1 from the EC scientific committees) make it difficult to be specific about synthetic biology. Another aspect of this issue is that there are contestations within the field about what synthetic biology is or isn’t with some more likely to focus on engineering while others might prefer to focus on basic biology (such as the literature on the origin of life). Contestations about what a new field ‘really’ is, or isn’t, in part reflect jockeying for position within the field but also reflect the fact that the field is emerging from combinations of different disciplines.
This is relevant to two aspects of the present discussion. First, the old vs. new discussion. In this case it is right, as Paul Freemont has highlighted, that some aspects of synthetic biology are not new in so far that synthetic biology uses standard methods and techniques. However, the combination of different methods and techniques in new ways may result in novelty. In short, it is not simply a matter of the age of a particular method or technique but the combination or recombination of methods and techniques in new ways that is important. A second difficulty with old vs. new is that proponents of an emerging area of research are more likely to emphasise that their work is old, and nothing different to what has gone before, when confronted by the possibility of unwanted regulation while they will emphasise novelty and the new when pursuing funding or investment. This is understandable. However, I think participants in the AHTEG and the COP itself should be wary of such tendencies. In particular I think there is an important role for independent empirical evidence in promoting democratic deliberation on this topic to inform decision-making.
As we emphasised in our previous work, and as Todd Kuiken has rightly pointed out in his very useful contribution on products, when confronted by possible regulation participants in an emerging field may choose to start calling it something else. For example, our scientometric work suggests that metabolic engineering would be a good alternative label in the case of synthetic biology. Furthermore, our work also suggested that as researchers coalesce around synthetic biology it is also starting to diversify into sub-fields such as “plant synthetic biology” or “mammalian synthetic biology”. In short, the object of policy attention may shift and change over time. As others have pointed out, it is important to capture the evolutionary and shifting nature of this emerging field at the level of the operational definition.
A second aspect to contestations about the definition of this emerging field relates to process vs. product distinctions. In line with the observations above, I agree with Helmut Gaugitsch that the process is likely to be as important as the product and that both need to be taken into consideration rather than creating an artificial separation. 
I would also echo the concerns that have been expressed about efforts to limit synthetic biology to LMOs as defined in the Biosafety Protocol… for the straightforward reason that synthetic biology is not, in my understanding, concerned simply with the actual or potential transboundary transfer of LMOs (the scope of the Protocol), but also involves the broader transfer of components and designs in electronic form. That is, it involves the dissemination of biological parts and designs that may be used in multiple countries to assemble parts and, in the longer term, organisms in situ.  The most obvious examples of this would be biobricks (http://biobricks.org). In short, we need also to consider transfers of bioinformation in synthetic biology. 
I also think that debates under the Convention are not simply about risk and risk assessment. In my view efforts to reduce the debate to risk assessment close off other fruitful avenues for debate and possible action. For example, as Thomas Hearns has noted, the principle of scientific freedom is an important one (for example in the Human Rights Covenants). In the context of the Convention this also allows us to ask the question: “what does a professional synthetic biologist look like” in terms of professional training in responsibilities towards the environment. In terms of an operational definition there is a need to recognise, and perhaps influence, the aspirations and orientations of the field with respect to environmental responsibilities.
Finally, Jim Thomas has mentioned scientometrics. In our work on the topic we identified 36,000 words and phrases in 1,255 publications on synthetic biology which we narrowed down to 355 terms that captured the majority of publications. I am presently updating this to 2014 with a dataset of over 2,000 publications. The point is that it should be possible to identify the key methods and techniques, components, organisms and products of synthetic biology through considered and careful analysis of the literature. This could then serve as a clear (and testable) foundation for developing inclusion and exclusion criteria in a transparent way without relying exclusively on opinions.
In closing, and since we were invited to contribute to an operational definition, I would offer the following idea based on the above.

“Synthetic biology is an emerging area of research and development involving novel combinations of methods, techniques and practices drawn from a range of disciplines directed to understanding, designing and engineering biological components, organisms and products.”

The potential utility of this construction is that it uses the language familiar to the COP (research and development - to mean non-commercial and commercial research). Reference to combinations reflects the overlaps and convergences between disciplines. Reference to understanding, design and engineering reflect key aspects of research in the field. Finally, references to components, organisms and products uses the language agreed by the COP (on two occasions) signalling emerging shared understanding between Parties. This operational definition is quite broad but deliberately seeks to focus on novelty (combinations of methods) and to permit the development of inclusion/exclusion criteria on components, organisms and products without specifying them in the definition itself.
With apologies if this has been rather longer than intended and for the lateness of the contribution.
posted on 2015-05-10 20:27 UTC by Mr. Paul Oldham, One World Analytics
This is a reply to 7157 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7161]
Dear colleagues,

I have read with great interest the fascinating exchanges under topics 1, 2 and 3.

Following the request of the Secretariat to be brief, hereby some bullet points in reaction to topic 3: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria”:

• In line with the comments by Ray Layton, Katsiaryna Sidarenka and others: for a meaningful about SynBio in on line debates, AHTEG meetings and the COP, we need to know what we mean by Synbio.
• While a legal definition will be difficult and not necessary at this point in time, having a clear  and – at this stage – not too detailed operational definition is important
• I support Boet Glandorf and others who suggested as working or operational definition the definition of the European SCENIHR.
• I fully endorse Hector Quemada’s point that defining Synthetic Biology is not merely an academic exercise, but to determine whether Synthetic Biology is objectively unique from other already-existing areas, and whether the outcomes of this research and development require new approaches to regulation. 
• In line with the points by Jaco Westra, I share Gerd Winter’s doubts whether it is wise to use the term “synthetic biology” as one that defines the scope of a regulation in the field.
• I agree with Hans Bergmans, Nikolay Tzvetkov, Luciana Ambrozevicius and others that organisms developed using synthetic biology approaches are LMOs within the scope of the Cartagena Protocol definition
• I agree with Helmut Gaugitsch that it will be counterproductive to revamp the old “process vs product” debate, because the definition of the Cartagena Protocol requires for an LMO that it 1) possesses novel genetic combinations, that 2) is obtained through the use of modern biotechnology. These ‘regulatory triggers’ should of course not be confused with the fact that any potential biosafety risks or benefits are embedded in the characteristics of the resulting organism itself, and not in the name of the process or the set of tools used to produce it.


Best regards

Piet van der Meer
posted on 2015-05-10 22:56 UTC by Mr. Piet van der Meer, Ghent University, Free University of Brussels, Belgium, PRRI
This is a reply to 7157 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7163]
Dear Secretariat, moderator and colleagues.

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 are coming to the end of our first discussions and many useful and constructive comments have been posted. We would like to say just a few words on the subject of an operational definition of SynBio. As has been pointed out by others, this is a fast evolving field and definitions may be outdated quickly. However, in order to focus and continue our discussions, we need an operational definition. This definition can be revisited and updated at any time. Three Scientific Committees of the EU Commission have provided an operational definition (see comments by Boet Glandorf, Helmut Gaugitsch and Michael Paton) which could provide a good starting point for our deliberations. Moreover, we agree with Francisca Acevedo - the definition should not be restricted to xenobiology.

Looking forward to our future discussions,

Marja Ruohonen-Lehto and Katileena Lohtander-Buckbee
posted on 2015-05-10 23:17 UTC by Ms. Marja Ruohonen-Lehto, Finland
This is a reply to 7138 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7165]
Dear all and Mr. Suwabe-san:


As Mr. Suwabe [7138] san Pointed out and I also had stated, the current discussion shall be focused on up coming issues, not the technology already used and proven generally regarded as acceptable with respect to the biodiversity conservation under CBD context. Also although we have science base discussion, yet the discussion focus shall be on synbio and  biodiversity, and it shall not be expanded to cover all likely topics on sunbio if it does not touch with CBD.


regards,
Kazuo Watanabe
University of Tsukuba
posted on 2015-05-10 23:55 UTC by Mr. Kazuo Watanabe, Japan
This is a reply to 7161 RE: Opening of the discussion: “Operational definition of synthetic biology, comprising inclusion and exclusion criteria” [#7166]
Dear All and Dr. Piet van der Meer:

Piet van der Meer  [#7161]:Thank you for summarizing the current intervention. The comments also summarize, what I meant in #7165, and this forum is not purely academic / scientific expertise. It is under CBD to make common understanding to deal with CBD mission.

Especially, I agree with Hans Bergmans, Nikolay Tzvetkov, Luciana Ambrozevicius followed by Piet van der Meer on the association between the current synthetic biology, and LMOs that are within the scope of the Cartagena Protocol definition.

regards,
Kazuo Watanabe
University of Tsukuba
Japan
posted on 2015-05-11 00:11 UTC by Mr. Kazuo Watanabe, Japan