Gene editing aims to modify the genetic sequence at a precise genomic location. Recent breakthroughs in gene editing techniques such as the clustered regularly interspaced short palindromic repeats (CRISPR) system have ushered in a new era for gene editing and health innovation. The purpose of the Expert Meeting (6-7 July 2017, Federal Ministry of Education and Research, Berlin, Germany) was to explore the core scientific, legal, regulatory and societal challenges facing the responsible development and use of gene editing in somatic cells for advanced therapies. Experts noted that the trajectory of gene editing in research and development and the uptake of future therapies in the clinical setting remain unclear due to uncertainties in the scientific, regulatory, and economic landscapes. Many policy issues are also raised in the context of other emerging technologies. Governance must cope with a moving technical frontier and some level of uncertainty around risks and benefits.
Key findings and policy messages from the Expert Meeting:
A clear technical breakthrough. Though evidence is still accumulating on the precision of gene editing techniques, CRISPR/Cas9-mediated gene editing is a major technological breakthrough with great potential for advanced cell and gene therapies. To help clarify the issue of off-target effects, a comprehensive and standardised battery of assays for measuring the outcomes of gene editing should be considered.
Governance issues similar to other emerging technologies. Techniques and applications in gene editing are still emerging. Despite the great attention to gene editing in the public sphere, many policy issues in gene editing for advanced cell and gene therapies are also raised in the context of other emerging technologies, e.g., governance must cope with a moving technical frontier and some level of uncertainty around risks and benefits.
Degree of public concern distinguishes gene editing. One potential distinguishing characteristic of gene editing is the degree of public interest and concern. This likely stems from the potential use of the technology not within the current context of somatic therapies, but in the context of human germline modification.
Learning from gene editing as a case. As policies and institutional capacities are developed around the use of gene editing, these could serve as a model for policies in other areas of advanced therapies and emerging technologies for health. Gene editing might afford societies a chance to develop new frameworks for upstream engagement.
Being systematic about public engagement. The degree of public concern and interest in gene editing underscores the need for public engagement at an early stage in the process of research and development. Engagement processes must be balanced, and stakeholders should be wary of “overselling” the technology. A central lesson of systematic work on public engagement is that openness, transparency and participation are key. It is more appropriate to talk about different “publics” that need to be engaged in different contexts than a single “public”.
There remains a significant need for developing and sharing successful strategies for integrating public engagement in research and development. Many countries and stakeholders struggle with putting public engagement into practice, seeking better models for increasing public engagement at an early stage and integrating findings into policy. Governance frameworks under the rubric of “Responsible Research and Innovation” are seeking to address this issue in a more systematic way by bringing together an array of mechanisms into toolkits and usable resources.
Effectiveness of existing regulations. Human somatic cell gene editing technologies are regulated in many jurisdictions. Stakeholders could discuss how effective the existing regulatory regimes are for dealing with current, and future, applications.
Meeting challenges for regulatory science. Many jurisdictions have usable regulatory frameworks for protecting health and ensuring safety of advanced cell and gene therapies. However, the small size of patient pools makes generating the necessary knowledge base quite difficult without extensive institutional cooperation or larger aggregating centres. Some jurisdictions are better set up than others in meeting this challenge. Furthermore, animal models may be less useful in the context of advanced cell and gene therapies than in the testing of pharmaceuticals, placing more emphasis on well-designed clinical trials. More use of post-marketing studies and real-world evidence might offer new approaches.
Platform technology. The regulation of CRISPR might be especially difficult because it is a platform technology that can be employed across multiple fields. Multiple agencies may be charged with setting regulation standards, and levels of societal concern may vary across contexts.
Communication between regulators and developers. Greater communication between the industry/ research community and regulators has the potential to improve clarity in the regulatory process and render the system more efficient and predictable. Guidance documents could help engagement as products near regulatory milestones. • Trust and trust-worthiness at the institutional level. More policy attention could focus on how research institutions build trust and trust-worthiness, including the development of transparent governance with broader participation.
Regulatory cooperation. Discussion around regulatory cooperation among relevant national agencies is ongoing in a number of fora. These discussions should be continued, deepened, and made more inclusive in order to find avenues for facilitating commercialisation and diffusion of therapies across countries.
Innovation and the Public Good
Opening innovation. Identify and analyse possible issues in the existing intellectual property system and discuss options to address possible challenges in the context of health innovation. Future work around open innovation could be built around public research for the public good. Policies should seek to foster collaboration between public and private stakeholders, and between agencies.
The goal of public benefit. Ultimately, the degree of public benefit should be the aim of public policy in this arena, but clear policy choices will not always follow from this mandate. Actors should think beyond just health to a holistic approach that includes the innovation system, increased research leadership, and the just distribution of benefit. Patients, the broader public, and the innovation system itself are all cited as considerations. As a result, stakeholders should discuss shortand long-term policy options to implement emerging technologies into clinics: how to implement a system of continuous assessment of public health impact along the innovation trajectory; how to realise public benefit of gene editing; what reimbursement models may help the uptake of advanced therapies?