Human embryos genetically modified - but is it ethical?

In a controversial case of CRISPR/Cas9 gene editing, Chinese scientists are claiming to have genetically modified human embryos for the very first time. The study has made headlines around the world, with some scientists praising the possibilities of the technique while others questioned the surrounding safety and ethical issues.

The research team, led by Junjiu Huang of Sun Yat-sen University, attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder. They undertook CRISPR/Cas9 gene editing to replace the defective gene with a healthy one and published their results in the journal Protein & Cell.

The team obtained 86 ‘non-viable’ embryos (ie, embryos which cannot result in a live birth) from local fertility clinics. All were injected, 71 survived and 54 were genetically tested. The results revealed that 28 of these were successfully spliced and that a fraction of those contained the replacement genetic material.

Analysis also revealed a number of “off-target” mutations acting in other areas of the genome, described by the researchers as “similar to what was observed in human cancer cells”. The researchers concluded that “clinical applications of the CRISPR/Cas9 system may be premature at this stage”, citing the need to “more comprehensively understand the mechanisms of CRISPR/Cas9-mediated genome editing in human cells”.

But some groups wonder whether the experiments should have been conducted in the first place, with public interest group the Center for Genetics and Society (CGS) calling for a halt to experiments aimed at the creation of genetically modified human beings. The organisation notes that the use of germline modification (genetic changes that will be inherited by all subsequent generations) to create a human being is prohibited by more than 40 countries and several international human rights treaties due to safety and social concerns. In Australia, research on human embryos is heavily restricted.

“The medical risks and social dangers of human germline modification cannot be overstated,” said CGS Executive Director Dr Marcy Darnovsky. He claimed not only that Huang’s paper demonstrates “the enormous safety risks” involved in creating a genetically modified human, but that even successful genetic modification could “lead to new forms of inequality, discrimination and societal conflict”.

Professor Shirley Hodgson from St George’s University of London described the work as “a significant departure from currently accepted research practice” due to the fact that “any manipulation of the germline of human embryos is potentially heritable”. She said there are “obvious concerns about the heritability of genetic alterations induced and the way in which such research could [eventually] spread from work on ‘non-viable’ embryos to work on viable ones”.

Ironically, the use of non-viable embryos to avoid ethics issues may have contributed to the experiment’s less-than-successful results. The embryos in question resulted from eggs fertilised by two sperm - which, according to ARC Senior Research Associate Dr Mel McDowall, “would be deemed ‘unhealthy’ or compromised by an embryologist”. The Francis Crick Institute’s Professor Robin Lovell Badge continued, saying “It is possible that the DNA repair mechanisms that are more likely to lead to errors have been activated in such abnormal embryos, as these struggle to cope with an abnormal genetic complement.”

Others have taken a more optimistic view of the potential for gene editing to repair genetic mutations. Associate Professor Peter Illingworth, the medical director at IVF Australia, noted that it is “normal practice to test embryos from people who carry genes for serious disorders such as β-thalassaemia” - the capacity to change the embryos to get rid of the disorder would thus be “an enormous step forward”. And while he acknowledged that more research is needed to assess the feasibility, safety and ethics of the technology, Associate Professor Illingworth is unopposed to its future use to treat serious genetic conditions such as β-thalassaemia.

Dr Dusko Ilic, from King’s College London, added that current preimplantation genetic diagnosis (PGD) technology is already enabling doctors to determine which embryos carry mutations for several hundred monogenetic inheritable diseases. He stated, “If and when one day genome editing in embryos becomes a successful and safe technology, the couples who were so unlucky as to not have even a single healthy embryo will have an opportunity to have a healthy child.”

While discussion continues around the rest of the world, Huang’s team has said it will persist in its gene-editing efforts - as will at least four other groups in China. It is clear that this area of research will face more hurdles than most, but, should it continue, its eventual impact on society could be extraordinary.