Controversial world first genetic modification of human embryos
23 April 2015
Urgent demands for debate on the ethics of human germline gene editing and an international moratorium on using the CRSPR-Cas9 technique for this purpose have been sharply underlined by the news that Chinese researchers have already used the technique.
Testing in human embryos
A team led by Junjiu Huang of Sun Yat-sen University in Guangzhou have reported on attempts to replace the beta-globin (HBB) gene in human embryos; mutations in this gene cause the disease β-thalassaemia. The research was reportedly rejected for publication by the prestigious journals Science and Nature , on ethical grounds, but accepted by the journal Protein & Cell.
The CRISPR-Cas9 technique for gene editing has made the technical prospect of the therapeutic treatment of human embryos to repair disease-causing mutations much more likely – although perhaps not as close to potential clinical reality as postulated, since the Chinese group report serious problems.
A stern warning for clinical application
Testing a total of 54 embryos from the 86 originally treated, the researchers found that the initial stage of the gene editing process (excising the HBB gene) had been successful in only 38, and the replacement HBB gene introduced successfully in only a minority of instances, resulting in mosaic embryos with a mixture of original and replacement versions of the gene.
They also observed ‘off-target mutations’ – genetic changes in unexpected parts of the embryo genomes – at much higher rates than previously observed in experiments using the technique in adult human cells or mouse embryos. Such mutations could of course have severely detrimental effects on the embryo.
The researchers conclude that their finding ‘highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform’ before clinical use, and plan to develop new strategies to reduce the incidence of the unintended, off-target mutations. George Daley of Harvard Medical School in Boston went further, telling Nature News that the study "should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes".
Intensifying ethical debate
Practical considerations aside, the ethical debate over the genetic modification of human embryos is inevitably set to intensify following this latest news. The research did use 'non-viable' embryos that had been fertilised by two sperm during in vitro fertilisation procedure. Such embryos can divide and develop to a limited extent only, and could not ever give rise to a human fetus. This may have limited ethical criticism of the research to some extent, but of course it also limits knowledge about what findings in normal, healthy human embryos might have been. Other Chinese groups are also thought to be working on human embryonic gene editing.
Thus far, calls for ethical and moral debate have been led by scientists concerned about the potential negative impact on less controversial research (such as therapeutic gene editing applications for human adults with severe genetic disease)that could result from public backlash against human embryo modification. We can now expect wider groups including ethical experts to weigh into the debate; the UK Nuffield Council on Bioethics announced plans earlier this month to consider the ethical issues surrounding gene editing, and no doubt similar bodies world-wide are doing the same thing.
Posing the essential questions
In some senses, the news is a reprieve; evidence that gene editing is not all but clinic-ready for human embryos, so that despite the rapid and widespread uptake and use of the technique, there is still time for international discussion and decision-making. Ultimately, the issues boil down to the question of how far we are prepared to go in order to pursue the dream of therapeutic modification of humans.
Is experimentation with embryonic modification justified by this goal, or is it always ethically unacceptable? What might the results of progression in this field be, for good or ill, and do we want to find out? Should it prove that the appetite for therapeutic benefits outweighs the concerns, what will the political and legal ramifications be, and conversely, how would any international moratorium against the practice be maintained and enforced now that it is at least theoretically feasible?
The latest scientific news means that the need to work towards answers to these and many other questions relating to the genetic modification of human embryos has effectively progressed from urgent to imperative.