Science marches on: key scientific developments in embryo research

'Science marches on' was the third session of the Progress Educational Trust's 2018 Annual Conference 'Make Do or Amend: Should We Update UK Fertility and Embryo Law?'. The session focused on the key scientific developments within embryo research, asking: where are we now, what can we learn from past battles and, most importantly, where are we going?

The first speaker, Dr Kathy Niakan, group leader of the Francis Crick Institute's human embryo and stem cell laboratory, is the first researcher licensed by the Human Fertilisation and Embryology Authority (HFEA) to edit the genomes of human embryos. Dr Niakan began by describing just how little we know of our own early development – how do the first emerging cells in human embryos function? What are the critical genes involved in this process?

Dr Niakan is using genome editing to peer into the human embryo's first days to answer fundamental questions about our biology. For example, the gene OCT4 is known to be important for embryo development. Dr Niakan used genome editing to eliminate production of OCT4in human embryos and found the embryos were much less likely to successfully form into blastocysts than control-treated embryos (see BioNews 919).

An unexpected finding was the differing role of OCT4 in mouse and human embryos, with the data suggesting that the gene is needed earlier in human development than in mice. This fundamental difference between species showed that even after 20 years of studying the gene there are still surprises.

Dr Niakan ended her talk with a caveat – there are still many unknowns around genome editing human embryos and further fundamental research is sorely needed.

The second speaker, Dr Evan Harris, former Liberal Democrat MP for Oxford West and Abingdon, was a member of the public bill committee that scrutinised the Human Fertilisation and Embryology Act 2008 before it became law. Dr Harris spoke of human admixed embryos and what happened in the run-up to the 2008 decision to license their creation and use for research purposes. He helped coordinate a public and parliamentary cross-party campaign to lift the ban on such embryos.

On the initial decision in 2006 to ban human admixed embryos, Dr Harris said: 'When government was faced with something difficult, they tended to take the safe approach... But this isn't safe for the patients who may benefit from the research.'

His talk was peppered with news articles from the time – including the memorable 'Meet Dr Death' article about him in the Daily Mail, which depicted the pushback from certain groups. Over the years, the public mood has changed and with it, the media – from Dr Death and 'nightmare planet of the apes scenarios' to more measured and balanced stories.

His take-home message was that he thinks the cultural climate has moved and we will no longer 'have to fight on every issue'. Our approach should be optimistic – we should be calling for proactive regulation now. Dr Harris ended his talk: 'Things have changed, and we should welcome it.'

The third speaker, Dr Andy Greenfield is the principal investigator and programme leader in mammalian sexual development at the Medical Research Council's Harwell research centre. The title of his talk - 'I see the boys of summer: sex, embryos and the meaning of life' - referred to a poem by Dylan Thomas, based on the sight of several middle-aged men going for a swim 'in their ruin'. In Dr Greenfield's words: 'Is the HFE Act a boy of summer in its ruin? I think that's probably not true – but it's pressing against the swimsuit in various places... uncomfortably so.'

Dr Greenfield focused on the 14-day limit on maintaining human embryos in culture and whether this should be extended, a task he compared to 'dancing through a minefield blindfolded'.

The talk centred around a thought experiment discussing a hypothetical twin earth, or 'Twearth'. This is a planet much like our own, except that you can culture embryos for 21 days. So, what are scientists doing on Twearth, considering they can grow embryos for longer? According to Dr Greenfield, they have robust and reliable protocols to culture embryos to 19-20 days. They can examine gastrulation and primordial germ cells among other things. They are better at differentiating pluripotent stem cells and, importantly, all this knowledge has been translated into the clinic.

Dr Greenfield then asked what are the ethical or moral implications of this? Has anything gone wrong on Twearth? He concluded that it's hard to identify any additional 'wrongdoing' than compared to Earth, with no obvious moral transgression between research at 14 and at 21 days.

'These limits are not moral bright lines – they are regulatory,' said Dr Greenfield. With this, he suggested that we would benefit from extending 14-day rule, but this came with a warning.

To revisit this limit, we would need a 'Warnock committee of the 21st century'. The 14-day limit is derived from a number of arguments – ethical, theological, psychological, sociological and scientific. Dr Greenfield asked: 'If we disentangle and deconstruct this amalgam of arguments, will we get something better? There's a risk we could get something worse.'

He ended his talk with a call to action – to 'make the change' but do the lobbying 'carefully and cautiously' to prevent regression of the limit.

At this stage, the chair of the session, Dr Roger Highfield, director of external affairs at the Science Museum Group, took questions from the audience.

On whether the law limited Dr Niakan's research into genome editing, she stated that the law at the moment allowed her to do the work she focused on. She discussed the benefit of the law clearly setting out boundaries for these studies. Importantly, it was a law already in place before CRISPR/Cas9 genome editing technology came along.

There was great interest in what we could learn from the campaign for licensing hybrid embryos. What led to the change in the cultural climate? Rather than a particular argument, Dr Harris suggested the essential factor was to 'organise', putting scientists and patients directly in front of parliament and the media to show both sides of the story, as well as finding allies in government.

One of the final questions addressed the elephant in the room - Dr He Jiankui and the genome-edited twin babies (see BioNews 977). Dr Niakan said that if his claims were true, this was 'human experimentation of the worst kind'.

Dr He, at the Southern University of Science and Technology in Shenzhen, China, claimed in November to have created the first babies following the genome-editing of human embryos. Dr He and his colleagues used CRISPR/Cas9 genome editing to remove a gene called CCR5 with the goal of conferring HIV resistance.

There was 'clearly no unmet clinical need', said Dr Niakan. From the data she had seen, the mutation incurred is not one that has been seen before in humans, she added. And there were major issues around consent and coercion with Dr He 'paying out of his own pocket for IVF'. Dr He allegedly failed to tell his institution; he contravened the global consensus on genome editing embryos; and the experiment was based on a flawed pre-clinical study and done in secrecy, she said.

'And these are just some of the issues,' Dr Niakan finished.

PET would like to thank the sponsor of this session, the Anne McLaren Memorial Trust Fund, and the other sponsors of its conference - the Edwards and Steptoe Research Trust Fund, the European Society of Human Reproduction and Embryology, JMW Solicitors, Ferring Pharmaceuticals, the European Sperm Bank, the London Women's Clinic, Vitrolife and the Institute of Medical Ethics.