Arguments over who whether limits should be placed on the use of modern genetic modification techniques (and if so, what, and who should decide?) are accompanying intense ethical and related discussions.
When genetic engineering first came on the scene, it provoked serious debate about the limits that could and should be place on its applications. A pivotal 1975 Asilomar International Congress on Recombinant DNA Molecules held in California brought together scientists, clinicians and other experts to debate the appropriate use of genetic modification; great benefits were expected from its use, but the need to create ethical boundaries for use were agreed on. Forty years on, the technical breakthrough that has made CRISPR-Cas9 and related nuclease-based genome editing techniques possible – allowing hitherto unprecedented ease and relative accuracy of genome modification – has prompted calls for a fresh review of the ethical boundaries of clinical application.
Scientists first brought the issue to public attention with calls for an international moratorium on human germline (heritable) genome engineering. Part of their concern was that fears of such applications could skew public debate and effectively hinder the clinical use of the technique for therapeutic (gene therapy) applications in children and adults. Such fears may have been well-founded; certainly, the big benefit of the original Asilomar conference was that it boosted public confidence that research for human health benefit could proceed apace without the constant risk of unethical use.
Now the startling speed with which genome editing techniques have emerged has heralded the urgent need for fresh reconsideration of what is possible, and what is desirable. But just who should decide?
In the US there have been calls for political and legal input to the debate. Last month a subcommittee of the US House Committee on Space, Science and Technology held a hearing on the topic, with expert ‘witnesses’ including pioneer Jennifer Doudna – herself embroiled in a high-value intellectual property battle over patent rights.
Meanwhile, Nature reports that the latest development is a bill relating to funding of the US regulator the Food and Drug Agency (FDA) that would prohibit using public funds to evaluate applications for clinical trials involving genetically modified human embryos. Previously, a legal instrument (the Dickey–Wicker Amendment) has been used to block human embryo research, but the FDA has not been involved before.
Biomedical bodies the National Academy of Sciences and National Academy of Medicine are said to be developing guidelines for the use of genome editing, based on consideration of ethical, legal and social issues. A summit is to be held later this year, and a multi-disciplinary international committee convened. The FDA funding bill is also said to call for the FDA to appoint an independent expert panel to evaluate this report.
The UK perspective
What position the UK will take remains uncertain. The country has proved liberal in being set to become the first country to permit the creation of ‘three-person’ embryos to avoid the transmission of serious forms of mitochondrial disease, a form of germ-line modification, albeit one that directly affects only mitochondrial DNA.
Earlier this year the Nuffield Council on Bioethics held an expert workshop to consider ethical and regulatory challenges posed by rapid scientific advances in genome editing in April this year, with a view to shaping future work in this area.
The report from this workshop is now available; it examines plant, animal and human applications of the technology but unsurprisingly, the most contentious were felt by participants to be those relating to humans and of these – again, as might have been expected – heritable or germ-line genetic modifications raised the most complex concerns. Overall, the workshop felt that the use of genome editing for gene therapy might become more common with relative speed, alongside increased use of prenatal genetic diagnosis (PGD) facilitated by next-generation DNA sequencing, to identify and exclude affected embryos from in vitro fertilisation. However, the proliferation of successful gene therapies might in itself raise expectations for treatments to eliminate serious disease linked genetic mutations from the germ-line.
High time to talk
Naturally, the future is uncertain, and certainly the science is arguably not yet ready for human genome modification – not that this precludes experimentation. Safety issues would precede the more nuanced ethical issues – but one thing is clear: the conversations that are beginning are important, and timely. It is necessary to envisage possible future scenarios in order to shape the legal, regulatory and social environments so that technological possibilities can be put to work in a manner largely acceptable to the society. As with mitochondrial transfer, however, the difficulty of comprehending the ingenious science, limitations and potential for non-experts is a barrier to effective discussion. But breaching that barrier is surely essential, unless we are willing to leave ethical decision-making solely in the hands of the scientific pioneers.