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Influencing PolicySanger Life

Claims of genome edited babies shock the world

By: Sarion Bowers, Policy Lead at the Wellcome Sanger Institute
Date: 06.12.18

The build up to the Second Genome Editing Summit in Hong Kong was a fairly routine affair. There was little to draw attention to the impending gathering of people from across the world to discuss the important and technically complex topic of altering the human genome. But the day before the summit began, there was a moment of drama as it was announced the Chinese Academy of Sciences, one of the co-organisers of the first summit in Washington two years earlier, had dropped out months before. The news created ripples and was sufficient to pique the interest of a few journalists. It seemed like this might be one of the bigger stories of the summit. Within hours the story was lost in history-changing news that a Chinese scientist, He Jiankui, had edited the genomes of embryos and implanted them, resulting in the birth of twins. Global shock and condemnation were immediate.

Scientists and clinicians have previously treated a small number of patients using genome editing, but in these cases the changes were made in cells that would not be passed on to the next generation, and only in one type of tissue, usually blood or lungs. In some of the cases, the cells containing the changes died out as the person’s own, unaltered cells took back over. What He Jiankui had done was completely different. By editing embryos, the changes made will be passed on to the next generation. Every cell in these babies’ bodies will contain the changed genome. It was also illegal in many countries including the UK and the EU.

As news of the edited babies spread, more details emerged, but so did conflicting accounts of what had happened. It quickly became clear that He had chosen to edit healthy embryos that were part of an otherwise routine IVF treatment. He had altered a gene known as CCR5.

HIV immunity?

Naturally occurring variations in CCR5 are known to make individuals more resistant to HIV infection, but the full function of CCR5 is not known.  There is also evidence that the same variation that makes an individual immune to HIV makes them more susceptible to West Niles Virus. These are complex systems and because He had edited it in the embryo, every tissue carries the change in CCR5. If the CCR5 gene has a function outside the immune system, those body functions will be affected too.

Hot on the heels of the news that He had edited healthy embryos came news that the editing had “worked” in one twin, but had only partially worked in the other twin. This second twin had one altered copy of the CCR5 gene and one original copy. He had chosen to implant this embryo anyway, despite the fact that partial editing means the baby probably won’t have immunity against HIV infection – He’s justification for the editing in the first place.

Next followed the hospital He worked at denying all knowledge of the project and denouncing the work. Questions quickly followed about the oversight and ethics approvals for the research, the answers to which seemed only to create more questions. None of the work had been peer reviewed and little data was available to verify He’s claims.

The Summit

Meanwhile, the Summit, which hadn’t begun when the news story broke, was now opening with a bang. More importantly, He was one of the delegates. As experts on different aspects of genome editing were taking to the stage, the news of He’s work was making headlines around the world. Journalists were descending on the venue, and organisations and individuals were putting out statements largely denouncing the work.

In a frenzy of media attention, less than 48 hours after his announcement, He joined a panel discussion with scientific heavyweights including Kathy Niakan, the first scientist in the UK to get permission to edit embryos for research purposes. The panel discussion had always been part of the agenda, but now had an entirely new significance.

The fact that He joined the group and stood up on the stage to talk about his work is worth reflecting on. In the aftermath of his news, which he suggested had been unintentionally leaked, sensationalist headlines and statements condemned not only the science but also the scientist, sometimes in the most heated of terms.

Most scientists are unused to media attention and many will actively shun it, but He stood up. He presented his work and answered questions from the panel, the audience and the assembled press. His answers were not particularly reassuring; his participants were recruited in a manner unlikely to be considered ethical in many countries. His reasoning for choosing CCR5 was flimsy and his view that his work was ethical and in compliance with good practice was in stark contrast to the views of much of the world and the audience directly in front of him. But at the same time, He was there.

There is probably little to defend in what He did. The line between pioneer and villain is vanishingly faint at the best of times. Whether someone is deemed a visionary or a cowboy has more to do with popular opinion and the outcome than their motivations or the precautions they took. He has leapt ahead with a technology we do not fully understand and the consequences for the twins could be severe indeed. The justification of providing HIV immunity, when HIV transmission to embryos is preventable and the disease has management strategies, is weak. Editing healthy embryos seems indefensible. But, the worst thing we could do now is drive scientists like He underground.

Genome editing – when, not if

Scientists, regulators and policy makers have known for a long time that it was a case of when, not if, an embryo would be edited. We should use this moment to learn what we can, we should ensure these babies do not disappear, left to an uncertain fate. It may be unpalatable to many, but it is imperative that we engage with He. Not least to know what was done and how he got so far unchecked, so we can all learn lessons from this incident. He did not operate in a vacuum, and there are a lot of questions that need to be answered, many of which will start with his account.

Scientists are often driven by a combination of wanting to make a difference and wanting to be first. Keeping scientists in the fold is one of the most important ways scientists can regulate themselves, particularly where legislation doesn’t. He has said his desire was to tackle a health crisis in China – to make a difference with a challenging issue. It is probably easy to dismiss He as an unregulated outlier, but the drivers of stigma relating to a health status, desperation for a family, and lack of access to health care are universal problems. If we fail to tackle these global issues, genome editing of embryos may be an attractive option to the desperate and the vulnerable.

The future

The organising committee of the Second Genome Editing Summit has released a statement, reiterating their view that genome editing in a way that is inherited should not be allowed at this time. They also reiterated the need for countries to engage in public discussion and debate on genome editing. He has shown that genome editing of embryos is a real consideration, but he has also shown us that the global science community is together in its opposition to editing of embryos at this time. Although undoubtedly unintentional, He has also offered us a meaningful starting point for that public conversation – which might ultimately be the most important thing that comes from this.

About the Author

Sarion Bowers is Policy Lead at the Sanger Institute

Human Embryo Editing: science fiction or science fact?
Influencing PolicySanger Life

Human Embryo Editing: science fiction or science fact?

By: Anna Middleton, Head of the Society and Ethics research group at the Wellcome Genome Campus Connecting Science
Date: 29.11.18

“As scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis”

2015 Organizing Committee of the First International Summit on Human Genome Editing

And here we are at the end of 2018, ‘revisiting’ this for real. I’m writing this while sitting in the audience in Hong Kong at the Second International Summit on Human Genome Editing, funded by the Royal Society, National Academy of Sciences, National Academy of Medicine and the University of Hong Kong. As an invited presenter on the public responses to genomics I’m excited to be sitting amongst global representatives from science, medicine and ethics.

The first thing that strikes me is the overwhelming presence of media in the auditorium, all excited by the announcement yesterday of the ‘first’ edited embryos to have been born, apparently delivered a few weeks ago.  The veracity of this is still very much a topic of debate across the media and scientific establishment.  There are many gaps and unusual elements to the announcement that call for caution and further detail.  But in the busy coffee breaks, the chat focuses on the ‘disbelief and horror’, and ‘how did he manage to do this without ethical regulation?’ There is concern in the air about the ‘ease’ with which the scientist could persuade a series of patients undergoing IVF to allow him to edit their healthy embryos. Prof He Jiankui, an associate professor at a Shenzhen university (https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684) claims to have edited a single gene that may offer some level of protection against future HIV infection.

The editing of embryos with intention of implantation and pregnancy, is illegal in many countries including the UK, all of the EU and the US.  A change in the law is not going to happen any time soon, but I guess that may give time for the scientific research and ethical enquiry to reach some level of consensus on what could and should be offered.

What seems to be generally agreed amongst the audience of delegates at this Summit is that the science just isn’t there yet to guarantee that there would be no downstream effects of editing one gene and either inadvertently editing another at the same time, or causing a disruption of an unexpected pathway leading to the creation of disease. So, what cannot be guaranteed is that these newly edited children won’t be susceptible to other serious health problems. We are reassured by Prof He that he will cover the medical bills for these children up to the age of 18.

Such reassurance on medical bills doesn’t really cover all of the implications and issues that Prof He’s announcement presents. The Nuffield Council on Bioethics previously reported in ‘Genome Editing and human reproduction report’ (July 2018): ‘We can, indeed, envisage circumstances in which heritable genome editing interventions SHOULD be permitted’. But the caveat was that such a possibility would only come after appropriate public debate.

At the Summit, one of the leaders in the field,  Prof George Daley, from Harvard Medical School reassured his audience that the current ‘mishap’ should not put us off striving for delivering the best science together with ethical frameworks to offer oversight of embryo editing. He asserts: ‘we need a well-defined translational pathway’ so that in the future we could offer embryo editing clinically for those that need it.

The science and the ethics of these issues have a long way to go. But already Prof He’s claim is opening up another level of debate.

Prof Daley was also asked about  ‘other clinical pathways that could be used instead of embryo editing, what about pre-implantation genetic diagnosis?’ He replied that he envisions in the future that embryo editing will be easier than PGD; and editing of gametes before fertilisation will become a reality, thus both of these may become the treatment of choice.

So there we have it. At this Summit on Genome Editing, we appear to be heading towards a future where editing of embryos in clinical practice to patients and families is technically possible. At the Summit we hear impassioned calls from patient groups, for example, the Sickle Cell Disease Community who are embracing genome editing, primarily in somatic testing, but they were not ruling out work in embryos.

There are repeated calls from the audience for ‘consensus’ and ‘acceptability’ from the public. These calls are fleetingly mentioned without real thought or understanding of just how hard this is to do. With an average reading age of 10 in the UK and 85 per cent of people having never heard of the word ‘genome’ before, we have a long way to go to socialise this enough to enable meaningful debate.  That’s not to say we shouldn’t do it, we absolutely should, but instead of just imagining this happens by osmosis, we should adequately value, resource and support the communication research to enable this to happen appropriately.

The summit organisers have put out a statement on the issue, which concludes that, currently “the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing.”

The question of if this is fact or fiction will become clear in coming days and weeks. What is clear is that there is an urgent need for the community to reach some conclusions on the issues raised. And the clock is ticking.

About the Author

Anna Middleton is Head of the Society and Ethics research group at the Wellcome Genome Campus Connecting Science