Human Germline Genome Editing – Genetics bodies weigh in on debate with position paper

In an article published in American Journal of Human Genetics on 3 August 2017, an international group of 11 organisations with genetics expertise has issued a joint position statement, setting out 3 key positions on the question of human germline genome editing:

• At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy.

• Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research.

• Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

This serendipitously timed statement comes on the heels a paper in Nature reporting the first gene editing of human embryos in the US and which has drawn the attention of the wider mainstream media and reignited the public debate as to the desirability, feasibility and ethics of editing the human genome in an inheritable way.

Whilst debates about the ethics of gene editing (both somatic and germline) go back decades, human germline genome editing was never technically possible before the CRISPR/Cas9 system. Germline cell editing poses significantly more concerning ethical and regulatory issues than somatic cell editing; the latter will only result in uninheritable changes to the genome of a population of cells in the particular individual treated, whilst the former involves genetic changes that will be passed down, for better or worse, to the individual’s offspring.

The ASHG position paper

The working group considered that ethical issues around for germline genome editing largely fall into two broad categories – those arising from its potential failure and those arising from its success. Failure exposes individuals to a variety of health consequences, both known and unknown, while success could lead to societal concerns about eugenics, social justice and equal access to medical technologies.

The 11 organisations acknowledged numerous ethical issues arising from human germline genome editing, including:

• exposing individuals to potentially harmful health consequences, since the magnitude of the potential risks of off-target or unintended consequences are yet to be determined;
• the risk that if highly restrictive policies are placed on the conduct and public funding of basic research in the field, this could push research out of the public eye and public interest – to private funders or overseas, in settings with potentially limited transparency and oversight. This could result in the degradation or omission of mechanisms that ensure that research is subject to ethical and peer oversight mechanisms, such as through ethics board approval, data sharing, peer review and dissemination of research resources (in this connection it should be noted that China is a good example of a jurisdiction where there is very strong government investment in biotech, including CRISPR, and less regulatory standards than in the West. This combination of factors seems to be fuelling the pace of research there (many CRISPR “firsts” have come in China – e.g. first CRISPR clinical trial in humans; first CRISPR editing of human embryos), but potentially at the risk of less rigorous, well controlled science being conducted (e.g. the recent retraction of the NgAgo paper);
• the de facto inability of future individuals the subject of genetic editing to consent to that editing;
• concerns around the boundaries of eugenic use of gene editing technology, which the groups acknowledged “could be used to reinforce prejudice and narrow definitions of normalcy in our societies”; and
• ensuring the gene editing technologies do not worsen existing or create new inequalities within and between societies, noting: “Unequal access and cultural differences affecting uptake could create large differences in the relative incidence of a given condition by region, ethnic group, or socioeconomic status. Genetic disease, once a universal common denominator, could instead become an artifact of class, geographic location, and culture.” A dangerous consequence of such inequality could be that “reduced incidence and reduced sense of shared risk could affect the resources available to individuals and families dealing with genetic conditions.”

Having outlined its consensus positions and justifications therefor, the working group concludes that “Many scientific, medical, and ethical questions remain around the potential for human germline genome editing. ASHG supports somatic genome editing and preclinical (in vitro human and animal) germline genome research but feels strongly that it is premature to consider human germline genome editing in any translational manner at this time. We encourage ethical and social consideration in tandem with basic science research in the upcoming years”.

This appears a reasonable position largely in line with previous recommendations from a number of major national and international groups surveyed by the working group. It balances the need to encourage further basic research and validation with strong awareness of the ethical and societal implications of human germline genome editing, setting a high bar before such technology should be translated to the clinic. No doubt, however, the debate will continue, particularly in respect of public funding for such work. For example, whether the US (which currently does not allow public funding of the use of gene editing technology in human embryos) will maintain their stance in the face of international competition and potential loss of talent and investment remains to be seen.

For more information about the science of CRISPR, its wide range of applications in life sciences and beyond, and latest developments in the field, please see Allen & Overy’s dedicated CRISPR microsite.

This is an abridged version of a more detailed article on the ASHG working group's position paper, available here.

This post was originally co-authored by Daniel Lim.