(1) The implications of regulatory variation for HGE between countries

Overview of regulatory conditions: Our documentary research has produced comparative insights into recent regulatory developments for HGE, including an in-depth study of the regulatory situation of this technology field in China, and the implications of these developments for stakeholders in the UK. At present, a highly diversified regulatory environment exists for HGE and the reliable implementation of regulatory rules is not a given. Far-reaching changes can be expected as the technology progresses.

Emerging regulatory and policy challenges: data from the interviews and workshop have generated new understandings of the challenges that are likely to arise from international regulatory variation, from the perspective of UK stakeholders. Project participants expected that: (i) some countries would not be able or willing to implement consistent regulatory standards for HGE; (ii) regulatory variation could lead to the surfacing of rogue clinics and premature applications; (iii) there would be a domino effect in which countries that initially rejected germ line gene editing would gradually embrace permissive regulations; (iv) the emergence of non-therapeutic and genetic enhancement applications that involve heritable gene editing will be difficult to stop at a global level and be a likely consequence as the technology progresses; (v) an international medical market for HGE could emerge that makes strategic use of regulatory differences; (vi) clinics and corporations in permissively regulated countries will try to attract patients from countries in which HGE was prohibited; (vi) that UK researchers, clinicians and fertility corporations would seek opportunities for research and profit making overseas, as long as HGE was prohibited in the UK.

(2) Challenges to the governance of shared global risks of HGE

The project has developed a series of critical insights into two types of global risks that have so far received insufficient attention in the literature: (i) the emergence of germ line gene therapy tourism, and (ii) the surfacing of “rogue” IVF clinics that would offer reproductive gene editing for non-therapeutic and enhancement purposes.

Germ Line Gene Therapy Tourism: A widespread assumption among participants was that once HGE was available in some parts of the world, patients from countries in which the technology was banned would travel to countries where HGE was permitted or available in a legal grey area. Various ethical and regulatory challenges were associated with this possible development: (i) that embryos, fetuses, newly born children and their future descendents would be subjected to unacceptable health risks; (ii) that patients would be lured to pay for premature or irresponsible HGE applications as the result of deceptive advertising, (iii) that overseas clinical applications would be provided outside of a systematic research framework, without reliable peer review, and independent of the oversight of drug regulatory or other government authorities; (iv) that potential adverse reactions or problems such as increased miscarriage rates were likely to be kept secret and not to be shared with the scientific community; (v) that the NHS would be forced to pay for the treatment and care of patients who experienced adverse effects from reproductive gene editing in overseas clinics.

Reproductive Gene Editing in illegal and "rogue" IVF clinics: The surfacing of ‘”rogue” clinics was seen as particularly likely in countries with not yet fully formed, leniently enforced or no regulatory infrastructures for HGE. Participants identified the following challenges related to the surfacing of rogue clinics: (i) the risk that unscrupulous clinicians would exploit the desire of parents who were desperate to have a child without a genetic disease or other health problems; (ii) the possibility that rogue clinics would start to introduce non-medical and enhancement-oriented forms of reproductive gene editing, (iii) that these clinics would provide insufficient information on the methods and treatment protocols they use; (iv) that rogue clinics offer clinical services that are based on insufficient forms of preclinical and/or clinical evidence; (iv) sell potential “snake oil” interventions, which would not involve gene editing at all, despite the fact that they were sold and advertised as such. Project participants saw it as a central priority to protect patients from these irresponsible applications (see policy options below).

(3) Contributing to ethically robust international research and corporate collaborations in the HGE field

The project has produced policy relevant data related to two aspects of the internationalization of HGE clinical research and applications: (i) the possibility that UK researchers and corporations provide HGE treatments in permissively regulated countries to avoid regulatory restrictions in the UK, and (ii) the involvement of UK researchers in overseas clinical research studies.

UK researchers and corporations operating abroad to avoid regulatory restrictions in the UK: Several participants expected that it was likely that UK researchers, clinicians and fertility companies would seek opportunities to provide and commercialize HGE applications overseas, especially as long as HGE was not permitted in the UK. There was widespread consensus that if these clinical applications are not part of a systematic and formally approved clinical study this was bad practice, which should be addressed and prevented by UK government bodies, research councils and scientific and medical organizations. Participants expressed concerns that the operation of UK researchers and corporations in more permissively regulated countries could (i) harm the scientific status of the UK, (ii) subject UK patients seeking services from UK companies operating abroad to legal uncertainties, (iii) prevent progress for the clinical translation of HGE by striving for the generation of fast profit instead of robust research data.

These concerns notwithstanding, some participants also supported the operation of UK researchers and fertility companies in more permissive countries, at least if these collaborations would enable patients to access potentially beneficial interventions for severe genetic disorders that are not yet available in the UK. Two central reasons were cited to support this perspective: (i) inaction is a violation of patients rights and ignores patient suffering; (ii) acknowledging reproductive freedom is especially important in light of the burden and inevitability of serious genetic diseases, and the instinctive and intuitive desire of parents to have an unaffected child.

The involvement of UK researchers in science-driven overseas clinical research studies: Participants saw involvement of UK researchers and clinicians in overseas HGE trials as acceptable, as long as these interventions were provided as part of a systematic, science-driven clinical study format that was formally approved by a government agency and conducted in line with international guidelines. As a set of minimum criteria for involvement in international HGE trials participants suggested the following yardsticks: (i) open and transparent treatment protocols; (ii) independent ethical review; (iii) approval by a national-level government agency; (iv) clinical applications must be based on sufficient preclinical evidence on safety and efficacy; (v) follow from a convincing medical rationale that justifies the interventions; and (vi) be conducted only in an international dialogue and under systematic, independent peer review.

(4) Generated policy options to address identified challenges

Based on the methodological approach of forward engagement (as developed by Fuerth 2012), which aims to identify challenges that arise from new technologies as well as possibilities for adaptation and governance as far in advance as possible, the project also aimed to generate potential policy options through which identified challenges can be addressed.

In the context of interviews and workshop, participants developed the following seven policy options:

1. Proactive regulation: the option that the UK should change current legislation to permit clinical HGE research and applications before other countries, to set an example to the world on how to regulate clinical research and practice in this whole area.
2. International guidelines: all participants agreed that the development of international guidelines for HGE clinical research and applications was essential. But it was also acknowledged that (i) these guidelines would not be legally enforceable, (ii) a complete global consensus on how to regulate this field will be impossible to achieve, and (iii) that international standards will not reach all stakeholders in this field.
3. Public education: as a means to prevent patients from seeking risky and premature HGE applications overseas, by informing them about (i) the recent stage in the preclinical and/or clinical development of HGL interventions, (ii) possible adverse effects and risks, and (iii) to alert them of deceptive marketing and advertisement strategies. This could also involve: (i) the identification and public criticism of so-called “rogue” clinics; (ii) the publicizing of cases that led to clinical adverse effects, (iii) the provision of assessment criteria on which basis patients can make informed decisions. Patient organizations, government bodies and scientific associations should play a crucial role in achieving these aims.
4. Scientific sanctions: the development of sanction for UK researchers who engage in irresponsible research and commercial practices abroad, that take place outside of a systematic research framework and that violate UK norms. Such sanctions could include: (i) exclusion of researchers from professional societies; (ii) prevent researchers from access to funding; (iii) prevent publications in top journals; (iv) publishing cases of fraud, (v) put pressure on overseas clinics that collaborate with “irresponsible” UK researchers and corporations, by clarifying that they operate outside of internationally acknowledged norms.
5. Adjust advertisement regulation: the option to change UK advertisement law to enable the prosecution of false advertisement of medical services that are offered by UK companies outside UK jurisdiction. Problematic advertisement strategies of UK companies abroad should be criticized and publicized.
6. Scientific diplomacy: the option that UK government bodies take an active role in (i) liaising with governments in countries where UK companies offer controversial HGE therapies, and (ii) discouraging companies to go abroad with interventions that are not approved in the UK.
7. More inclusive and international forms of public deliberation: public viewpoints on the potential uses of HGE are currently under-represented in policy debates. To ensure the development of regulatory options that correspond to the needs and perceptions of patients and laypeople, more inclusive and international forms and forums of public deliberation will be required.

Publications:

Journal Articles:

Rosemann, A. et al. (under review) Heritable human gene editing: Opportunities and limitations of international guidelines. (Under review at Bioethics).

Rosemann, A., Balen, A., Nerlich, B., Hauskeller, C., Sleeboom-Faulkner, M., Hartley, S., X.Q. Zhang and N. Lee (2019). Heritable human gene editing in global perspective: national and international policy challenges. Hastings Centre Report, 49(3), 31-42.

Jiang, L. and A. Rosemann (2018). Human embryo gene editing in China: the uncertain legal status of the embryo, Biosocieties, Doi.org/10.1057/s41292-018-0116-1

Rosemann, A., L. Jiang and X.Q. Zhang (2017). Human Germ Line Gene Editing: Why comparative, cross-national studies on public viewpoints are important. Anthropology, DOI: 10.4172/2332-0915.1000175

Blog Posts:

Nerlich, B. and A. Rosemann (2019). Towards a global dialogue about heritable germline editing: Mapping needs and challenges. BioMed Central – On Society Blog (July 2019).

Rosemann, A. and B. Nerlich (2019). Heritable Germline Editing: National and International Governance Challenges and Policy Options. Making Science Public Blog (forthcoming July 2019).

Background Briefing Paper

Rosemann, A., Jiang, L. and X.Q. Zhang (2018). The Regulatory and Legal Situation of Human Embryo, Gamete and Germ Line Gene Editing Research and Clinical Applications in the People’s Republic of China. Background Paper. Nuffield Council of Bioethics.

Project reports:

Rosemann, A. (2017a) Germ Line Gene Editing in Global Context: Final Project Report. (Distributed to all project participants and relevant stakeholders).

Rosemann, A. (2017b) 'Germ Line Gene Editing in Global Context: Challenges and Needs from a UK Perspective'. Report for the Nuffield Council on Bioethics's Working Party: “Genome Editing in Human Reproduction.”

Digital Resources:

Video Interviews on YouTube Channel 'Heritable Gene Editing in Global Context': https://www.youtube.com/channel/UCxfGTwkCAEu_49EPy7Yg3bQ/videos

EuroStemCell (2017). A Digital Gateway: Regenerative Medicine in Society. EuroStemCell Website: http://www.eurostemcell.org; Co-production Achim Rosemann with Jan Barfoot, Adam Price-Evans, Ryan Lewis, Anna Couturier, and Clare Blackburn.

Conference panels:

Society for the Social Study of Science, 42. Annual Meeting, Boston. Panel organizer and chair. ‘Gene Editing and the Challenge of Public Engagement: Local and Global Perspectives’, Aug 2017.

Conference Presentations and Invited Lectures:

(2018) Heritable Genome Editing in Humans: Discussing the Limitations of International Guidelines. Conference: Health, Culture and the Human Body, 4 October 2018, Istanbul University. (A. Rosemann and Christine Hauskeller)

(2017b) Human Germ Line Gene Editing in Global Context: Regulatory challenges and needs. 42d 4S Annual Meeting, Boston, USA, August 30, 2017.

(2017c) The Genetic Modification of Human Life. Invited Lecture. University of Warwick, November 30, 2017.

(2017d) Genetics and Ethnicity. Invited Lecture at interdisciplinary module: Genetics, Science and Society, University of Warwick, March 9, 2017.