Past Activities 2017-2018

Dear Forum,

My name is Dr. Doug Herrin. I previously worked on life sciences policy at Department of State and White House. Now I am a medical doctor at Yale University. It is a pleasure to participate in this conversation.

Discussions on synthetic biology (and gene drives, CRISPR, etc) has implications for all living organisms. Regulations surrounding these technologies would impact not only plants, insects, and nonhuman animals but also innovations in human health care, food security, and microbial life.

Historically it seems this forum has briefly discussed health implications, but has not included a robust and regular conversation on public health or human health perspective. The full and proven applications of synthetic biology and gene editing technologies could reasonably lead to life-saving interventions and reduce the effect of disease through somatic and germ line mutations; granted, there is cost-benefit to any new medication or procedure. Lives could be saved through the role of gene drives in reducing the transmission of mosquito diseases, gene editing that modifies host responses against infectious (HIV) and immunological diseases, and combating cancer and genetic diseases. Platform technologies have a high likelihood of leading to R&D breakthroughs (vaccines, medications, therapies, etc) with a likely substantial impact on the bioeconomy and entrepreneurial/business ecosystems.

There would likely be unintended consequences for human health if the topic of public health and human health are not fully discussed in regards to the CBD and the 3 priorities, even more so if regulations and laws are codified and designed without the foresight of a public health and medical perspective. The effect of these technologies on the environment and human species is difficult to predict and premature. In this context, there is a responsibility to create a regulatory structure where innovation thrives and discovery is not impeded. Evidence must drive policy discussion and our regulatory structures should be proportional to the risks that are based in evidence. I would further argue that whatever regulatory systems are developed for synthetic biology, the most minimal regulations should be set up to promote a reasonable level of safety, especially when and if there is an absence of evidence that implementing this technology causes harm.

Thank you,
Doug

Dear Colleagues:

I am Kent Redford with a background in conservation and an interest in the intersection of synthetic biology and conservation practice.
Thank you to all who have contributed - it is a rich discussion.

I would like to enter with a couple of points:

1) when we think about possible outcomes of synbio interventions it is important to compare those possible outcomes to what would happen/is happening in the absence of the intervention (counter-factual). This perspective allows to see that the status of much of biodiversity in all its attributes and components is decreasing steadily - any given intervention may either accelerate or decrease that trend. But preventing interventions will not, in and of itself, make things better.

2) it might be useful to consider potential synbio impacts, both negative and positive, as either direct or indirect. Considering negative impacts, direct negative impacts could be generated by loss of genetic diversity and indirect negative impacts by loss of ecosystems through placement of algal raceways. Considering positive impacts, direct positive impacts could include controlling invasive disease threatening endangered species whereas indirect positive impacts could be through increased food production allowing for less land under agriculture and therefore available for restoration of natural habitat.

Thank you for the opportunity to contribute.

Kent

See More from bch@cbd.int

Kent Redford
Archipelago Consulting
Portland, ME 04112, USA

Cell: ++ 914-263-6163
Skype: Kent.H.Redford
redfordkh@gmail.com

Dear Members
At the end of first week, we moved from mosquitoes to CRISPR. Now we may try to list the points for topic 1 agreed by all members so far. Hence, we may enlist the gaps to discuss in the forthcoming days..
As I understood from the discussion (members may please change where they differ in their views, I’m just trying to list)
1. Synthetic biology is highly appreciable in confined research environments and should be encouraged with stringent regulations when and where required
2. Vector control is permitted (provided it’s not eradicating the species as a whole) and its impact analyses on biodiversity, food chain in its local ecology should be studied in detail over a period of time with periodic intervals
3. Cases of GMO’s release towards protecting the environment viz., clearing the oil spillage in water bodies, Geography based research may be permitted only if they are protecting the environment (more discussion in this subject area is needed)
4. Release of crops with sterility genes and resistance marker genes are to be stopped / or prevented. GMOs may be released in the environment on confirmation that they don’t contain any such genes (may be removed using any other technique)
5. Release of herbicide tolerance or tolerance to any other chemical in food crops should be restricted (as there may be carryover of harmful chemicals in food products)
6. Synthetic biology and its products are highly beneficial molecular farming, in processing industries, fuels etc.. as the deliverable is not a GMO?. Only the product reaches the consumer.
We are yet to discuss
1. Contribution of synthetic biology at its impact on climate change related issues and biodiversity
2. Gene delivery systems in human health and related research
3. There are new areas of research in which synthetic biology intervention is needed to concentrate more viz., neurodegenerative diseases, retinitis pigmentosa, cancer research and handling of human pathogens for research in relation to biodiversity (of natural alleles)
4. Members may recommend eradicating pathogens rather than vectors in all possible cases (may exclude Malaria for time being).
In my opinion we are yet to cover three major subjects.. 1.Medicine, 2. Agriculture and 3. Microbiology as they directly impact on both human and environment.

thanks

Hi and thank you everyone.

My name is Arinze Okoli, I am a research scientist with GenØk, the Norwegian centre for Biosafety, Tromsø.

With reference to [#8517] the yet uncovered areas of Microbiology & Medicine, I´ll like to pick up the thread of [#8495]  on application of SynBio, in particular the techniques of CRISPR and chemical DNA synthesis on viruses.

Christoph Then in post [#8495] has already called attention to the topical issue of resurrection of extinct viruses using chemical DNA synthesis, and I agree it is a topic worthy of discussion in this group. Chemical DNA synthesis is also currently widely being experimented in viral mutagenesis, development of vaccines and gene therapy vectors, a platform popularly referred to as SAVE (synthetic attenuated virus engineering). Although several of such developments are still at pre-clinical trials stage, it is envisaged that the elevation to clinical trial last year of CRISPR-modified cells in oncotherapy (http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988) may see several of such developments approved for clinical trials. 

It is note worthy that in clinical trials of medicinal products, volunteers may not be restricted to the hospital; therefore, they interact with the community: families members, friends and work colleagues. This increases the chances of introduction of the GE product into the environment. When the GE product contains or consists of live and replication competent virus(s) the biosafety implications also for the ecosystem and biodiversity becomes even more far reaching.

In this forum the inadvertent release of products of GE appears to receive lesser focus than the intentional release of same products. With medicinal and microbiological products, clinical trial is already a release (intentional) into the environment; unintentional release can (and do) occur during experimental (in the laboratory) and pre-clinical trials (using animal models). it is also worth noting that GE medicinal products (in contrasts to GE Agricultural products) can receive accelerated approvals (the case of Ebola therapeutic products and several oncolytic products and products for treatment of congenital diseases). Thus, calling for stringent measures at this early stages of SynBio.

Based on experiences with GM medicinal products, I conclude, by highlighting ( and in support of post [#8498] by Ms Sarah Agapito, the lack of dedicated biosafety research in this area. It is also pertinent, as many posts in the forum have already emphasized, to assess whether the current risk assessment tools, which are designed for GM, are robust enough for the assessment of GE products.

I would like to react to post [#8561] on clinical trials with medicinal products containing GMO. Besides working on synthetic biology, I also do environmental risk assessments for GMO used in clinical trials and would like to share my views on the risk assessment process.
Before a GMO will be used in a clinical trial, it will have to be tested in contained use both in vitro (e.g. in a cell line) and in vivo (pre-clinical studies in animals). These contained use experiments do not differ from any other laboratory work effectuated in contained use and are usually done in a BSL-1 or -2 facility as the GMO used for clinical trials are mostly non-pathogenic.
Then, many GMO used in clinical trials are not actually released into the environment. These GMO are administered to patients and are either unable to replicate (e.g. replication-deficient recombinant viruses), are not shed (e.g. cells) or cannot survive over long periods of time in the environment (e.g. enveloped viral particles). These GMO are therefore regarded as having a negligible environmental risk and not to have an effect on biodiversity. Clinical trials that are currently about to start with CRISPR-modified cells therefore do not have any special effect on biodiversity, even if they will have an effect (positive or negative) on the patient treated with them.
If a replication-competent virus is used in a clinical trial, studies on biodistribution and shedding of the virus will be conducted in the pre-clinical phase and usually attenuated viruses with a reduced replication capacity or the potential to only replicate in a specific cell type (e.g. a cancer cell) will be used. Still, if considered necessary, study patients treated with a replication-competent virus can be quarantined in the study hospital. To my knowledge, however, no transmission of GMO to medicinal personnel or close contacts via shedding has been observed so far, when patients were administered with a replication-competent virus and did not have to remain in quarantine (see Imlygic as an example, an oncolytic herpesvirus that has gained marketing authorization in the EU and the US).
Furthermore, GMO used in clinical trials can also be an example for an application where risks and benefits are addressed. While a clinical trial with a GMO can bear risks for the patient, the benefit of a potential long-term clinical response in a patient with poor prognosis under standard therapy may outweigh those risks.
I therefore think that
1) a more stringent risk assessment for medicinal products containing GMO is not necessary and
2) the intentional release of GMO in the scope of clinical trials does not necessitate more stringent regulation on synthetic biology.