POSTED ON BEHALF OF CASPER LINNESTAD
Dear Forum participants,
Once again I would like to thank you all for your enthusiastic contributions to the forum. There were over 200 comments posted by 94 participants from 33 Parties, 1 non-Party and 36 organisations.
The views shared covered a very wide range of issues some of which were not directly related to the topic of the discussion. As such, I will attempt to focus this summary primarily on those comments that were directly relevant to the topic, “Review recent technological developments within the field of synthetic biology to assess if the developments could lead to impacts on biodiversity and the three objectives of the Convention, including unexpected and significant impacts”, including potential positive and negative impacts.
The following is an attempt to include all points raised, however due to the large volume of interventions, I apologise in advance if I have missed anything.
1) What are the potential impacts, including unexpected and significant adverse effects, of the most recent technological developments in synthetic biology on biodiversity and the three objectives of the Convention?
Potential negative impacts:
Several of the negative impacts listed by participants were similar to those previously listed in past discussions and meetings held by the CBD on synthetic biology. The updated input was nevertheless very welcome also in this round of our online discussion. This included risks arising from horizontal gene transfer leading to alterations in genetic biodiversity and a spread of undesirable phenotypes, effects on non-target organisms, invasiveness resulting from increased fitness, amongst other things. There were also concerns regarding the use of organisms resulting from synthetic biology for the generation of biofuel and bioenergy where by the increased demand for biomass may lead to the establishment of plantations in former forests, harvesting natural grasslands, pressures on deserts and wetlands. In addition the increased agricultural practices may result in a decline in soil fertility and structure. There was also some mention of the potential negative impacts on implementing access and benefit sharing arrangements due to a decrease in barriers to ‘digital biopiracy’.
Not surprisingly, the CRISPR/Cas9 system was heavily discussed, particularly in the context of mosquito population control, and how such a technology could lead to unexpected outcomes due to off-target effects such as unexpected and unpredictable changes in the genomes and thus in the phenotype of an organism and its descendants. Participants also elaborated that while organisms may experience mutations that occur naturally and spontaneously, there are natural mechanisms within the organism that have evolved to provide tight regulatory checks, such as epigenetic regulation, of such mutations. Artificial genetic modification, however, is designed to override such regulation. Therefore, claimed some participants, organisms containing such modifications should be considered experimental and, given the precautionary principal, not considered as ready for commercialisation or ecological release.
There was also some discussion on biosafety considerations related to organisms resulting from synthetic biology that are currently under development or in use within contained environments that may be accidentally or unintentionally released into the environment. This was of particular concern in the context of organisms containing gene drive systems. This issue was presented in the context of whether or not the research on organisms designed to contain gene drives should be carried out in facilities that are at BSL3 or 4 in order to ensure that there is a minimal risk of such organisms getting released into the environment.
There were also some concerns raised regarding the potential legal gaps that may be raised in the context of applying the Nagoya Protocol to the fair and equitable sharing of genetic resources on which synthetic biology applications are reliant.
Potential positive impacts:
In expressing their views on the potential benefits of synthetic biology, participants listed a number of applications where synthetic biology technologies are beneficial, including public health/medicine, agriculture, industrial uses, species conservation, environmental remediation, and invasive species control. They also stressed that many of the potential negative impacts are unfounded concerns that have been faced with the introduction on LMOs in the past and represent speculative apprehensions that have not materialised since. Furthermore, they also stressed that the techniques that are commonly used under the umbrella term that is “synthetic biology” are simply an extension of methods that are considered modern biotechnology and as such they can be dealt with similarly.
Participants also listed that some of the benefits imparted, based on past experience, included a reduction in soil erosion, decreasing fuel and chemical pesticide use, increasing disease and pest-resistance within plants, increasing on-farm insect biodiversity, raising crop product quality, and improving farm productivity and farmer income. Furthermore it was also noted that that replacing natural products with synthetic ones could reduce pressure on natural habitats.
They also noted that some of the potential negative effects are also not unique to synthetic biology but rather are issues that are common to the introduction of new technology in general, be it through products derived through synthetic biology, other novel manufacturing processes, or more traditional routes such as non-biological chemical synthesis and product substitution/replacement.
Participants also pointed out that any perceived gaps in knowledge that may arise out of the potential adverse effects would only be filled through encouraging research in those areas and that any effort to discourage or suppress such research will only serve to prevent such knowledge from being obtained. Furthermore, in elaborating on the supposed off target effects that accompany CRISPR/Cas9, some participants indicated that the literature on the topic is inconclusive and that even in the event that off target mutations do occur that this is analogous to mutations that could occur naturally spontaneously in an organism. Participants also stressed that not all changes in DNA would lead to an effect on the functioning or characteristics of an organism. Furthermore, in light of the frameworks that are already in place in the context of the Cartagena Protocol there is probably no need for new or unique regulations or provisions and that if new regulations are put in place they have to be evidence-based and proportionate to risk.
2) What research and cooperation activities are being conducted on the possible benefits and potential adverse effects of organisms, components and products of synthetic biology on biodiversity to fill knowledge gaps and identify how those effects relate to the objectives of the Convention and its Protocols?
Several Participants shared a number of research and cooperation activities that have been taking place in the context of synthetic biology. Below is a selection of some of the research activities that were mentioned during the discussion and have a direct link to identifying potential benefits and adverse effects of organisms, components and products of synthetic biology:
• A number of new gene editing tools have been developed for research purposes with the view to reducing the off-target effects from CRISPR such as:
a) New CRISPR associated proteins that can operate similar to the Cas9 system including Cpf1 as well as a mini-Cas9 system from Staphylococcus aureus;
b) New bacterial genome editing system that combines a yeast based system with CRISPR-Cas9;
c) Natronobacterium gregoryi Argonaute (NgAgo) as a DNA guided endonuclease for gene editing that would be a different approach from CRISPR/TALENS/ZFN etc.;
d) The use of Lambda Red to edit bacterial genomes.
• Further to the research and development of gene editing tools, research is also being carried out regarding the possible off-target effects that may be caused by CRISPR, including the work of Schafer et al (https://www.nature.com/nmeth/journal/v14/n6/full/nmeth.4293.html
) Wilson et. al, (http://www.biorxiv.org/content/biorxiv/early/2017/06/21/153338.full.pdf
) and Chen et. al. (http://www.biorxiv.org/content/early/2017/07/06/160036
• The Dutch National Institute for Public Health and the Environment (RIVM) commissioned four reports which describe experience gained with environmental risk assessment of LMOs and new developments in white, green and red biotechnology. These can be found at: http://www.stw.nl/nl/content/biotechnology-and-safety
. Based on these reports a call for research into the safety aspects of these new developments in modern biotechnology - including synthetic biology - was released last year.
• The RIVM also issued a policy report on gene drives resulting in adjustment of the Dutch legislation for working with gene drives in contained use facilities (http://www.rivm.nl/Documenten_en_publicaties/Wetenschappelijk/Rapporten/2016/februari/Gene_drives_Policy_report
). Furthermore, RIVM is working on aspects of risk assessment for contained use of gene drives in cooperation with several European partners.
• RIVM is also conducting research on the potential impact of new technological developments of modern biotechnology on risk assessment methodology. A policy report is expected towards the end of 2017.
• The Commission of Genetic Modification, together with the Health Council of the Netherlands, published in 2016 a report that describes major new developments and applications in biotechnology and possible stumbling blocks and (ethical and societal) dilemmas which arise from these developments and trends. This trend analysis can be found at http://www.cogem.net/index.cfm/en/publications/publication/trend-analysis-biotechnology-2016
• Research on Golden Rice demonstrating that when the modified plant with the Indian variety Swarna unexpected gene disruption occurred, which lead to extensive disturbance in their growth. The new gene constructs interfered with the non-modified plant’s own gene for producing growth hormones, and the additional gene constructs were not, as intended, active solely in the kernels, but also in the leaves. (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169600
• The German Federal Office of Consumer Protection and Food Safety (CCBS) has been monitoring the effects of synthetic biology since 2009. In its first report on monitoring of synthetic biology that was released in 2012, CCBS concluded that all organisms created with the help of synthetic biology so far are GMO and their risks can be assessed under existing regulations and using existing methodologies. The next report is expected for the end of 2017 and it is expected to come to the same conclusions as the 2012 report.
• Research being carried out under the ISO/TC 276 Biotechnology standards that are being developed by the International Organization for Standardization (ISO), which can be found at https://www.iso.org/committee/4514241/x/catalogue/p/0/u/1/w/0/d/0
• Several programs have been developed by The Defense Advanced Research Projects Agency (DARPA) in the USA has developed five programs that demonstrate the growing complexity of synthetic biology under development that could have a direct impact on the objectives of the convention. These are: “Living Foundries”, “Biological Robustness in Complex Settings”, “Safe Genes”, “Insect Allies” and “Ecological niche-preference engineering”. Additional information about these programmes can be found at http://www.darpa.mil/about-us/about-darpa
• A small pilot project was started by GenØk on plasticity of plant cells that have been genome edited, and how they can cope with such interventions, focusing on CRISPR off-target activity (available at http://genok.no/the-synplast-project/
3) Are there other recent technological developments that have taken place within the field of synthetic biology that need to be considered in this discussion?
Several participants indicated that there are no other recent technological developments that have taken place within the field of synthetic biology that need to be considered. On the other hand, other participants disagreed and pointed to the need for further research in the field of synthetic biology in order to determine whether there are any recent issues that warrant caution. Below is a selection of specific technological developments that have taken place within the field of synthetic biology that were mentioned during the discussion:
• The applications of recent synthetic biology techniques expand the possible range of host organisms to all living beings which is far beyond the range of organisms that were successfully modified through the more traditional modern biotechnology tools.
• Many applications of synthetic biology, including those using modified microorganisms, will no longer be under contained use as they are intended to be introduced into the environment.
• The application of “big data”, machine learning, artificial intelligence and robotics with a view to constructing genomes, which are expected to enable rapid and automatic prototyping of highly novel organisms.
• The development and application of external genome regulation methods, such as RNA interference in the form of sprays to control pests or influence plant characteristics.
• The application of CRISPR/Cas-based gene drives in organisms, especially in insects, and the need to thoroughly consider the potential benefits and risks at the ecosystem level.
• The increased accessibility of the biotech tools, such as CRISPR kits, to the DIY community and the public at large outside of formal laboratory facilities.
• The use of modified algae production for the production of chemical substances poses a need for relatively “open” production ponds/facilities, due to the need for sunlight, which requires well designed either physical or biological safety and containment measures.
• Whole cell sensor development is being more actively pursued and given that such sensors may be used either inside or outside laboratory facilities, it would therefore require well designed containment strategies.
• The development of cell free systems would require the development of new and appropriate risk assessment methodologies.
• Addressing the ever-increasing speed of development within the field of biotechnology given that new biotechnology tools combined with automated laboratories DNA-circuitry design tools and bioinformatics may lead to the production of more modified organisms faster than their risk can be assessed.
• The emerging field of ‘Molecular Communication’ which is the application of information theory to molecular processes where communication signals, such as those used between organisms, are physically encoded in molecules.
• The development of tools to enable the simultaneous targeting of multiple sites, or multiplexing, within a genome at once, often with just one construct/vector using nucleases such as CRISPR/Cas9 or PTG/Cas9, amongst others.
Finally, a few other considerations were raised that, while very useful, were not directly relevant to the scope of the discussion. These considerations focused primarily on the operational definition of synthetic biology and the appropriateness of current risk assessment methodologies for LMOs.
With regards to the views shared concerning the definition, I would like to remind participants that the COP considered the definition that was produced as an outcome of the work of the AHTEG as a useful starting point for the purpose of facilitating scientific and technical deliberations under the Convention and its Protocols (CBD/COP/DEC/XIII/17). I am confident that we will be able to work within the scope of the COP decision on this matter and move forward in the context of this definition to facilitate the focusing on the discussion topics at hand.
With regards to the points raised on the appropriateness of current risk assessment methodologies when managing organisms resulting from synthetic biology there will be a future discussion on this issue and therefore the comments on this topic were not included here.
I thank you all for your kind attention and all of the hard work you have put into providing views to facilitate to work of the upcoming meeting of the AHTEG.