Last week scientists from round the world gathered in Washington DC for an international summit on human gene editing to discuss not only scientific breakthroughs, but also ethics and governance issues.
The science behind gene editing
Gene editing represents a recent leap forward in the capacity to reliably introduce precise genetic modifications to genomic DNA, thanks to a range of related techniques (zinc finger nucleases; transcription activator-like endonucleases or TALENs; and the CRISPR-Cas9 system) that harness genetically engineered bacterial enzymes to recognise and cut specific DNA sequences.
CRISPR in particular has effectively made accurate gene editing a practical reality for many researchers, and improvements continue to emerge; last week scientists from the Broad Institute reported that a new, enhanced eSpCas9 enzyme dramatically reduces ‘off-target editing’ – unintended cuts in DNA – and will be made available to other researchers.
Medical applications of gene editing
There are two major areas of medical application for gene editing technology. The first is gene therapy, introducing ‘healthy’ genes into a patient with defective or absent genes. For example, it was recently used to cure (or at least suppress) otherwise intractable cancer in a baby. The second and more controversial use is for germline (heritable) gene editing to correct defective or missing genes associated with severe disease – permanently, because offspring of the individual who underwent gene therapy as a fetus would inherit the altered gene.
Gene editing has other clinical benefits, making it easy to create cells and model organisms that mimic disease states – a huge boost for medical research. Combined with stem cell technology it also offers new potential to regenerative medicine, creating healthy new tissues to replace those that are diseased – possibly also combining two ethical dilemmas in one, if human embryonic stem cells are used.
There are two main barriers to general medical applications of gene editing. The first is safety; the risk of introducing off-target changes to the DNA that could have harmful effects – such as inducing cancer, as seen in the past when gene therapy vectors have inserted in the wrong place in the genome. However, with further refinements to improve and ascertain safety, the technique may become suitable for gene therapy for an expanding range of conditions.
Debating the ethical issues
The second major barrier applies only to germline gene editing. Many consider that introducing changes to the human germline crosses an ethical line – whether for moral reasons, safety concerns for future generations, or various other reasons.
Things have changed since the first international conference recommended an absolute moratorium on human germline genetic modification: researchers in China have reported the use of CRISPR to modify human embryos, albeit non-viable ones. They found alarming effects: a very low success rate and off-target edits. However, given the pace of development, it is reasonable to suppose that improvements in the techniques could render these basic efficacy issues redundant in time. Assuming that it is technically feasible to edit the human genome of a fetus, should we, and under what circumstances? These were the issues under consideration at the Washington conference last week.
Debate was reportedly wide ranging. To some, given the severity of some human genetic diseases, it would be unethical not to use gene editing to eliminate them. Others felt that the risks to future generations outweighed the benefits, especially given the capacity to use prenatal genetic diagnosis (PGD) to screen out affected embryos as part of the IVF process, whereas some contended that it was more inherently ethical to edit affected embryos than to identify and discard them.
Looking beyond applications for severe disease, some considered future pressures to use gene editing for milder forms of disease…and thence to the dreaded ‘designer babies’ scenario, making modifications to enhance beauty, or sporting prowess, or intelligence. At present this is largely nonsense – such traits are multifactorial, and their complex genetic influences are far from understood. But then, we do seek to unravel the full mysteries of the genome, so it is not so ridiculous to suppose that one day we might succeed.
To be continued…
Perhaps unsurprisingly given the number of CRISPR experts present, a statement from the meeting concluded against any form of international moratorium and gave a strong endorsement of gene editing of human embryos, eggs or sperm cells for basic research – but said that creating live babies from gene edited cells through IVF or embryos through implantation was ‘irresponsible’ because of safety concerns and the lack of societal consensus on whether it was ethical or not.
There were calls for proper regulatory oversight of the field. They also thought that ‘the clinical use of germline editing should be revisited on a regular basis’ as both science and societal views ‘evolve’.
These debates will not go away any time soon. In scientific terms, the genie is out of the bottle, and we can reasonably expect to see not only further improvements in the technique, but also wider applications. Some of these will inevitably push the boundaries of acceptability. Whether it is possible to come to an international consensus on fundamental ethical boundaries is uncertain, but individual countries will have to make their own decisions - and probably be prepared to revisit them over time.
This is a challenge for whole societies, not just scientists and bioethicists. They, as experts, can sensibly set out the risks and the issues – but ultimately, it should be for all of us to reach a consensus on the acceptable uses of human gene editing.