Synthetic embryos create an ethical catch-22

The writer is a science commentator

Egg plus sperm equals embryo. It is hard to think of a more basic rule in biology. Still, rethink it we must. Last week, at a stem cell conference in Massachusetts, researchers revealed they had created “synthetic” human embryos using neither eggs nor sperm. These structures, more correctly called embryo models, were instead grown from single living stem cells, which were derived from a real human embryo. It was not a one-off achievement: another team created an embryo model with a heartbeat.

The apparent breakthroughs — yet to be published in peer-reviewed journals — are intended to shed light on infertility, pregnancy loss and birth defects. But they also raise moral and legal concerns. Science, and society more widely, now needs to consider how closely these lab-cultivated ersatz embryos, essentially tapestries of tissue, approximate to the real thing. An open discussion — along with updated regulation and careful consideration of how such work might be commercialised — will encourage public support for valuable research that could lead to treatments. 

About one in five pregnancies ends in miscarriage. Yet science affords surprisingly little insight into the reasons, partly because studying embryos in vivo is difficult. The alternative is to scrutinise embryo development in the lab, including using leftover embryos donated by IVF patients. The research use of human embryos is governed by strict laws that bow to a developmental timeline.

After fertilisation, the cells divide for about four days before tightening into a blastocyst. After that comes implantation in the womb, signalling the start of pregnancy. By day 14, the embryo undergoes “gastrulation”, when the body pattern begins to take shape and distinct cell lines materialise. One hallmark is the “primitive streak”, a groove that appears as bilateral symmetry develops.

Broadly, in the UK and in many other countries, human embryos cannot be cultivated beyond day 14. This means the exact scientific detail of what happens afterwards — including how the embryo self-organises into different tissue types — remains a mystery. Animal embryos, which can be nurtured for longer, are of limited relevance.

That is where “stem-cell-based embryo models” come in. A team led by Professor Magdalena Żernicka-Goetz, who works at both Cambridge university in the UK and the California Institute of Technology, isolated an embryonic stem cell from a human embryo and coaxed the proliferating cells to self-assemble into an embryo-like structure to just beyond day 14. Żernicka-Goetz and two other authors are named as inventors on a relevant patent; another group, led by Jacob Hanna at the Weizmann Institute of Science in Israel, published a similar preprint on the same day.

A rival team at Cambridge university’s Gurdon Institute, describing as-yet unpublished work, said it had developed a synthetic embryo to the stage at which a heartbeat could be detected, though it was deliberately engineered to lack tissues critical to further development.

Why does this matter? In many countries, synthetic embryos do not meet the formal definition of an embryo (though the use of embryonic stem cells is still regulated). Instead, they are regarded more akin to lab-grown human tissue, which is regulated more liberally. But the quest for biological authenticity sets up a catch-22: the more similar an embryo model, the more scientifically useful it becomes — but also the more ethically problematic. 

Synthetic embryos can also be created using reprogrammed adult stem cells, which avoids some restrictions. But whichever technique is used, this science is now outpacing our ability to regulate it — and it is not unreasonable to worry about what an unscrupulous scientist might try. 

UK law prevents synthetic embryos being used to create babies but researchers are already testing the principle on animals. Scientists in China have implanted monkey embryo models in female monkeys, though the pregnancies spontaneously aborted soon after. Such pregnancies might be inherently doomed to failure; alternatively, technical improvements could make them viable.

If the latter, scientists must be vigilant — self-regulation did not prevent the calamity of gene-edited human babies in China. Cambridge university, an epicentre of this novel research, is sensibly consulting on a governance framework but the issue of synthetic embryos is bigger than one campus. Much scientific good and human happiness can come of this exciting research into pregnancy loss, as long as we can head off the harms.