Genetically modified embryos: a panacea for mankind – or a crime against scientific ethics?

The research published from China this week has provoked a feverish bout of soul-searching - Steve Connor reports expert opinion is divided

Genetically modified embryos are a divisive issue among scientists (Getty Images)

The announcement that Chinese scientists have attempted to genetically engineer human embryos took much of the world by surprise, but for those familiar with the latest gene-editing technology it was a long-anticipated inevitability.

Researchers in China not only revealed that they attempted to modify the genes of “spare” embryos deemed unsuitable for IVF treatment – the first such attempt anywhere in the world – they had done so on an almost industrial scale, involving 86 “non-viable” embryos donated by a nearby fertility clinic.

The study came to public light after it was published in a rather obscure online science journal called Protein & Cell, set up in China to publish peer-reviewed science that cannot find a home in more prestigious international journals such as Nature and Science.

In fact, according to a news report in Nature, the lead author of the paper, Junjiu Huang of Sun Yat-sen University in Guangzhou, had submitted the scientific paper to both journals but had been rejected in part because of ethical objections – and possibly because of uncertainties over the provenance of the embryos used.

Ever since genome-editing technology Crispr/Cas9 emerged a couple of years ago, scientists had been predicting that it wouldn’t be long before it was used to correct defects in the genes of humans, including those in the “germline” cells of sperm, eggs and embryos, which are passed down the generations.

In short, Crispr promises to eliminate many inherited diseases for good from affected families, but some scientists in Britain were appalled by the Chinese research, arguing that it overstepped the ethical boundary separating good scientific practice from badly-conceived experimentation of dubious ethical standard.

“This is a significant departure from currently accepted research practice. This is because any manipulation of the germline of human embryos is potentially heritable,” said Shirley Hodgson, professor of cancer genetics at St George’s University of London.

There had been rumours circulating for some weeks that there were at least four different groups in China attempting to engineer the human germline of eggs and embryos with Crispr/Cas9.

Nevertheless, it still shocked many scientists, including Ewan Birney of the European Bioinformatics Institute. “I am concerned by this study. Using the gene-editing technology Crispr/Cas9 in human embryos is unacceptable in the UK ethical framework,” Dr Birney said.

China is not the only country where scientists are beginning to think the “unthinkable” of tinkering with the genes of eggs, sperm and embryos, to bring about germline genetic modification that would be inherited by each subsequent generation within a family affected by inherited diseases.

In March, for instance, a journalist writing for MIT Technology Review revealed that scientists working at the Harvard Medical School had attempted to use the Crispr technique on human ovarian tissue, which could have included human egg cells – although the work had not advanced to the stage of being ready for a scientific publication.

Crispr has astonished scientists by the simplicity and accuracy at which it can “cut and paste” the building blocks of DNA at precise points on the chromosomes, rather like a spell-checker being able to find, correct or delete a single misspelt word in a 46-volume encyclopaedia. It has already worked well on adult (non germline) human cells, as well as animal cells and embryos.

Dr Huang told Nature the 86 embryos in his experiment had all been fertilised abnormally by two sperm cells, which would have given them three sets of chromosomes rather than the normal two of a healthy, fertilised egg. These embryos were therefore “non viable” and could not have developed into a foetus even if they had been transplanted into the womb – and he emphasised there was never any intention of this.

The study revealed that each embryo had been injected with the Crispr enzyme complex at the single-cell stage, soon after fertilisation. After 48 hours, when the embryos had developed to the 8-cell stage, their chromosomes were analysed to see whether Crispr had been successful at modifying a defective blood-protein gene responsible for beta-thalassaemia.

The Chinese team reported that 71 embryos survived the experiment and 54 of them had been genetically tested. Of these, 28 embryos had the blood gene “spliced” but only a fraction of those contained the replacement genetic material. More disturbing was the discovery of “off target” effects, when the Crispr complex changed something at the wrong position on the DNA molecule. This could have created new genetic problems for the embryo – if implanted into a womb.

The results were disappointing. However, Crispr in the hands of other scientists has produced remarkably few off-target effects, and it is possible the poor accuracy seen in the Chinese study may have been the result of using defective “triploid” embryos with three sets of chromosomes. “The authors used abnormally fertilised embryos, presumably because they did not want to be accused of using embryos that could undergo development to term if implanted,” said Professor Robin Lovell-Badge of the Crick Institute in London.

“It is possible that the DNA repair mechanisms that are more likely to lead to errors have been activated in such abnormal embryos,” he said.

Other studies have shown Crispr to be such a powerful tool for gene editing that it has led some experts to suggest a global moratorium on experimenting with human germline cells until the ethics of what some see as the technological path to “designer babies” have been publicly debated.

“I disagree with a moratorium... indeed I am fully supportive of research being carried out on early human embryos in the lab, especially on embryos that are not required for reproduction and would otherwise be discarded,” Professor Lovell-Badge said.

Dusko Ilic, a stem cell researcher at King’s College London, agreed: “If the technology exists, scientists will continue doing such experiments and eventually, one day, repair of mutation-causing genetic diseases can become a reality,” he said.