Ethics of making human blastocysts in a lab

The findings of two papers released today in the journal Nature by two separate research groups – one mainly Australian – show that when it comes to ethics, science and the law, nothing stands still for long.

Both research groups have made significant advances in the field of early human development by generating early human embryo-like (blastocysts) structures from cells in a dish, opening up a new level of scientific research.

Twenty-four years ago, the world woke to the news that it was possible to successfully clone an animal. In February 1997, Ian Wilmut and his research team at the Roslin Institute, UK, announced in Nature that they’d successfully cloned a sheep they called Dolly, born in July 1996. 

The news raised the possibility that cloning a human may become technically feasible, resulting in intense political and ethical debate around issues such as how human embryos can be created; what forms of human reproduction are acceptable; and what research uses of human embryos should be allowed. 

Governments acted swiftly, with three Australian states (Victoria, South Australia and Western Australia) enacting legislation purporting to ban human reproductive cloning, and to regulate research on human embryos. In 2002, the Australian Parliament enacted legislation that prohibited both therapeutic and reproductive embryonic cloning.

In 2006, a surprise conscience vote from parliamentarians – opposed by then-Prime Minister John Howard – amended the law to legalise human somatic cell nuclear transfer, when DNA is taken from a mature cell and used to fertilise an egg. This method allows the creation of embryos, from which stem cells can later be derived.

The research covered in one of today’s new papers, led by Monash University’s Professor Jose Polo, has managed, for the first time, to generate a model human blastocyst – the tiny ball of cells that will become an embryo and, potentially and if allowed, a human – out of skin cells.

Polo’s team call their new creations iBlastoids. 

Through the use of stem cells and related reprogramming technology, Polo and his team say the iBlastoids show a new way to study how the cells at this very early stage of development interact, potentially leading to improvements in infertility treatments and ways to prevent miscarriages. 

But, as deputy director of the University of Melbourne’s Centre for Stem Cell Systems Professor Megan Munsie points out, when it comes to the ethics governing this research, we have yet to establish consensus – or even clear guidelines.

“Because these are not the same as a sperm-egg embryo, we should be having a conversation around whether blastocyst structures should be governed by the same ethical considerations,” she says.

“While these models are similar, they should not be considered equivalent to human embryos created in an IVF lab. This distinction is important. Ethical and legal considerations are different. How and when they are used in research is likely to be different.” 

Scientifically, and therefore ethically, we are in new territory. Until now, early-stage embryos have only been developed from mouse cells, and ethical guidelines have reflected that research. 

Currently, stem-cell scientists have to abide by the 14-day rule, which outlaws research on pure human embryos over two weeks old. It is encoded in laws in at least 12 countries, including the US, UK, Australia and New Zealand.

First proposed in 1979 by the Ethics Advisory Board of the US Department of Health, Education, and Welfare to account for the emergence of IVF, the 14-day rule was officially endorsed five years later by the UK’s Warnock committee, which was established to inquire into the technologies of  in-vitro fertilisation and embryology. 

The 14-day rule is centred on the notion that by day 15, the embryo can split into twins and enter a point where its biological individuation is assured. It’s also the time when we see the earliest development of the human’s nervous system (spinal cord and the brain), at which point many scientists believe there is risk of the embryo suffering pain. 

However, legal scholar Dr Patrick Foong, from Western Sydney University, who has written extensively on the topic, says it’s impossible to know if an embryo can feel any pain at such an early stage. 

“I don’t think even scientists know when exactly this happens,” he says. “We know that as the embryo starts to develop, there is a greater risk of pain, but the current 14-day limit is an arbitrary compromise between gaining utilitarian benefit of scientific research, and alleviating public concern.” 

While ethical debates about the impact of new scientific discoveries aren’t new, embryonic research has particular resonance in the wider community. For many, the thought that an embryo – even a model of one – can feel pain is enough to convince them to abandon all experiments; for others, the answer is not so clear cut. 

“The question of when exactly embryos become sufficiently sentient to feel pain is controversial, though it is certainly not something like 14 days,” says moral philosopher Dr Russell Blackford.

“You’ll see claims more of the order of 25 or 30 weeks from various sources that look into how far the brain has developed, what sort of responsiveness the embryo seems to display and so on. 

“The 14-day limit really has nothing to do with a threshold of sentience; it is about when the embryo becomes a unique biological entity that can no longer split and can be fully implanted in the womb.”

Blackford – who also lectures in human and social sciences at the University of Newcastle – says it is ethically and morally impossible to arrive at the “right” answer, and that it all depends on what you prioritise as a person. 

“If you believe, for example, that there is an absolute moral restriction on taking innocent human life, you will not think this can be outweighed by the possibility of scientific and medical advances,” he explains. “But if your view of morality is based more on consequentialist and utilitarian considerations, you might come to a very different conclusion.”

Munsie says that the legal definition of an embryo is different to that of what the average person may think – and that people often conflate a foetus and embryo to mean the same thing. 

“In the community, there remains confusion around what is an embryo, and what is a foetus,” she says. “In previous debates the term ‘baby farming’ has been used, and I’d hate to think that people think that is what this research on blastoids involves.”

So if iBlastoids are not an early-stage embryo but a very close copy, should they be treated as such? The International Society for Stem Cell Research (ISSCR), based in Illinois, US, confirms it expects to release an update to the guidelines for stem cell research and clinical translation later this year related to stem cell-based embryo models and their use in research, as well as positions on research using human embryos.

Yet the ethical debate, and in particular discussions about the grey area surrounding the personhood of artificial or even “natural” (sperm-egg) embryos, is an essential part of Western democracies, which want to ensure that high moral and ethical standards are enshrined in law. 

Foong says that couples with surplus embryos already donate them to research, with many of these embryos kept in storage for as long as five years (after which they’re usually destroyed). If we are to find out more about early-stage human development, studying the embryo – or even perhaps early-stage embryo models – could be key to finding out more about what causes miscarriages and infertility, he says.

“It’s important that we have checks and balances in this field, as independent oversight provides comfort to the wider community,” Munsie says. “It may well be that some people opposed to human embryos may find this research more acceptable.

“There is tension between what a human embryo is and what people think it is, which is all the more reason to talk about those grey zones and give people an opportunity to have their say. We need to take this very seriously.”