Considerations for the governance of gene drive organisms

ABSTRACT

Governance is a broader and more flexible concept than statute-driven regulations as it incorporates components outside the latter’s remit. Considerations of governance are critical in the development of emerging biotechnologies such as gene drive organisms. These have been proposed or are being developed to address public and environmental health issues not addressed easily by conventional means. Here, we consider how the concept of governance differs from statute-driven regulation with reference to the role each may play in the development of gene drive organisms. First, we discuss existing statute-based regulatory systems. Second, we consider whether novel risks or different concerns derive from gene drive organisms, concentrating on characteristics that contribute to public health or environmental risk and uncertainties that may affect risk perceptions. Third, we consider public engagement, outlining how existing statute-driven regulatory systems and other governance mechanisms may provide opportunities for constructive interactions. Finally, we provide some observations that may help address science- and values-based concerns in a governance space larger than that of statute-driven regulatory systems.

KEYWORDS:

• Gene drives
• governance
• regulation
• risk
• risk management
• public engagement

Notes

¹ Prior to 2015, what is now known as the US National Academies of Science, Engineering, and Medicine (NASEM) existed as separate bodies: the National Academy of Sciences (NAS) and National Research Council (NRC), the National Academy of Engineering (NAE), and the Institute of Medicine (IOM). Citations listed in this paper reflect the status of the institutions at the time of publications were issued.

² An early modern attempt at characterizing the Goldilocks fulcrum addressed potential outcomes of recombinant DNA (rDNA) research, and resulted in a voluntary moratorium on research until such risks could be discussed among the scientific community. The Asilomar meeting held in 1975, recommended that a Recombinant DNA Advisory Committee (RAC) be formed to provide guidelines for safety under the auspices of the National Institutes of Health (NIH). The resulting NIH Guidelines for Research Involving Recombinant DNA Molecules has been updated several times, and still pertains to contained research involving genomes intentionally altered using modern molecular biology. The most recent version is the 2016 NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules https://osp.od.nih.gov/wp-content/uploads/2013/06/NIH_Guidelines.pdf, and does not expressly address gene drive organisms. A recent workshop (July 2017 https://osp.od.nih.gov/event/nih-guidelines-honoring-the-past-charting-the-future/?instance_id=39 examined the current biosafety oversight framework, and discussed its future direction for the emergence of new technologies and their products, expressly including gene drives.

³ The AAS salmon is the triploid, all female Atlantic salmon that is intended for the production of food. At the time of the US approval, it was to be bred from a fertile diploid genetically engineered parent and a wild type Atlantic salmon on Prince Edward Island, Canada. After being processed to produce an all-female triploid population, eyed eggs were to be air-shipped to Panama, where they would be raised to market weight in land-based grow out tanks (not ocean nets). Fish would be harvested on site, processed at a nearby facility, and the resulting gutted fish, steaks, or fillets would be air-shipped for sale in the US. Following the US approval, AquaBounty petitioned the Canadian Government to extend their Canadian breeding facilities to include a grow-out facility (also in land-based tanks); this was approved.in the summer of 2017 http://aquabounty.com/aquabounty-expansion/. A subsequent approval of a supplemental application to raise fish in the US was made in 2018 https://www.fda.gov/downloads/animalveterinary/developmentapprovalprocess/geneticengineering/geneticallyengineeredanimals/ucm605681.pdf although there is still a Congressional prohibition against importation of the fish.

⁴ For the purposes of this article, ‘modern molecular biotechnology’ encompasses techniques or procedures, such as in vitro interventions, to study the underlying science governing life processes, or to alter organisms or their derivatives in order to make or modify products or processes for specific uses. We note that this definition has been made for the purposes of this article, and has no formal regulatory or policy status of which we are aware. It is a modification of the UN Convention on Biological Diversity (article 2) definition of biotechnology. https://www.cbd.int/convention/articles/default.shtml?a=cbd-02 (accessed 10/10/2017).

⁵ In the United States, regulatory agencies are careful to use the term ‘genetically engineered’ to refer to organisms that have had their genomes intentionally altered using modern biotechnology, as it is the opinion of the science-based regulatory agencies that with the exception of a small number of wild sources (e.g. berries, nuts, seaweed, game) all agriculturally important species have been genetically modified by selective breeding or other means. Others use the term ‘genetically modified’ to describe organisms that have been genetically engineered. In this document, the term ‘genetically engineered’ will be used unless specifically citing another document in which the latter is used. At the time of this writing, there is significant discussion concerning whether organisms that have had their genomes edited in particular ways (i.e. what is referred to as ‘allele transfer’) fit the terms genetically engineered, genetically modified, or are a class unto themselves for regulatory purposes.

⁶ The US EPA defines an ecological risk assessment as the process for evaluating how likely it is that the environment may be impacted as a result of exposure to one or more environmental stressors such as chemicals, land change, disease, invasive species, and climate change, and includes four stages: planning and scoping; problem formulation; analysis; and risk characterization.

⁷ Durability can be thought of as the phenotypic stability of a gene drive organism over time.

⁸ Ae. aegypti has a very large and highly repetitive genome; attempts to produce a genomic map in which contiguous DNA sequences are anchored to a physical chromosome have proven to be problematic. This report claims to have overcome many of these obstacles to anchor the genome to the three Ae. aegypti chromosomes.

One edit didn’t seem to make it in, and that may be an issue on my part. The text for Footnote H currently reads

Ae. aegypti has a very large and highly repetitive genome; attempts to produce a genomic map in which contiguous DNA sequences are anchored to a physical chromosome have proven to be problematic. The authors report they have overcome many of these obstacles to anchor the genome to the three Ae. aegypti chromosomes.

⁹ Although the 2014 Guidance Framework does not explicitly address mosquitos with gene drives, many of the issues raised by GM mosquitoes are very closely related. The VCAG is currently completing a similar Guidance Framework specifically addressing mosquitos with gene drives, anticipated to be issued in early 2018 (personal communication with FNIH).