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9 min read

Ethics needs to catch-up with genetic innovation

Are we morally obliged to genetically edit?

John is Professor Emeritus of Cell and Molecular Biology at the University of Exeter.

An artistic visualisation of a DNA strand growing flowers from it.
Artist Nidia Dias visualises how AI could assist genomic studies.
Google Deepmind via Unsplash.

It makes me feel very old when I realise that Louise Brown, the first baby to be born via in vitro fertilisation (IVF), will be 47 years old on July 25th this year. Since her birth in 1978, over 10 million IVF-conceived babies have been born worldwide, of whom about 400,000 have been in the UK. Over that period, success rates have increased such that in some clinics, about 50 per cent of IVF cycles lead to a live birth. At the same time, there have also been significant advances in genetics, genomics and stem cell biology all of which, in relation to human embryos, raise interesting and sometimes challenging ethical issues. 

I start with a question: what is the ‘moral status’ of the early human embryo? Whether the embryo arises by normal fertilisation after sexual intercourse or by IVF, there is a phase of a few days during which the embryo is undergoing the earliest stages of development but has not yet implanted into the wall of the uterus; the prospective mother is not yet pregnant. In UK law, based on the Human Fertilisation and Embryology Act (1990), these early embryos are not regarded as human persons but nevertheless should be treated with some respect. Nevertheless, there are some who oppose this view and believe that from the ‘moment of conception’ (there actually isn’t such a thing – fertilisation takes several hours) embryos should be treated as persons. In ‘conventional’ IVF this debate is especially relevant to the spare embryos that are generated during each IVF cycle and which are stored, deep-frozen, in increasing numbers for possible use in the future.  

A further dimension was added to this area of debate when it became possible to test IVF embryos for the presence of genetic mutations that cause disease. This process is called pre-implantation genetic diagnosis and enables prospective parents who are at known risk of passing on a deleterious mutation to avoid having a child who possesses that mutation. But what about the embryos that are rejected? They are usually discarded or destroyed but some are used in research. However, those who hold a very conservative view of the status of the early embryo will ask what right we have to discard/destroy an embryo because it has the ‘wrong genes’. And even for the many who hold a less conservative view, there are still several questions which remain, including ‘which genetic variants we should be allowed to select against?; should we allow positive selection for genes known to promote health in some way?’; should we allow selection for non-therapeutic reasons, for example, sporting prowess?’ These questions will not go away and there are already indications that non-therapeutic selection is being offered in a small number of countries. 

Genetic modification 

This leads us on to think about altering human genes. Initially, the issue was genetic modification (GM) which in general involves adding genes. GM techniques have been used very successfully in curing several conditions, including congenital severe immune deficiency and as part of treatment programmes for certain very difficult childhood cancers. One key feature of these examples is that the genetic change is not passed on to the next generation – it just involves the body of someone who has already been born. Thus, we call them somatic genetic changes (from the Greek, sōmatikos, meaning ‘of the body’).  

Genetic modification which is passed on to the next generation is called germline GM which means that the genetic change must get into the ‘germ cells’, i.e., the sperm or egg. Currently, the only feasible way of doing this is to carry out the genetic modification on the very early embryo. At present however, with just one very specific exception, GM of human embryos is forbidden in all the countries where it would be possible to do it. There is firstly the question of deciding whether it is right to change the genetic makeup of a future human being in such a way that the change is passed to succeeding generations. Secondly, there are concerns about the long-term safety of the procedure. Although it would involve adding specific genes with known effects, the complexity of genetic regulation and gene interactions during human development means that scientist are concerned about the risks of unforeseen effects. And thirdly, germline GM emphasises dramatically the possibility of using GM for enhancement rather than for medical reasons.  

Genome editing 

This leads us to think about genome editing. In 2011, it was shown that a bacterial system which edits the genomes of invading viruses could also work in other organisms This opened up a large array of applications in research, agriculture and medicine. However, the ethical issues raised by genome editing are, in essence, the same as raised by GM and so there is still a universal prohibition of using the technique with human embryos: germline genome editing is forbidden. Despite this, a Chinese medical scientist, He Jiankui, announced in 2018 that he had edited the genomes of several embryos, making them resistant to HIV; two babies with edited genomes had already been born while several more were on the way. The announcement caused outrage across the world, including in China itself. He Jiankui was removed from his job and then, after a trial, was imprisoned for three years; his two colleagues who collaborated in this work received shorter sentences. 

At present the universal prohibition of human germline genome editing remains in place. However, the discussion has been re-opened in a paper by an Anglo-Australian group.  They suggest that we need to develop heritable (i.e. germline) polygenic genome editing in order to reduce significantly an individual's risk of developing degenerative diseases. These includecoronary artery disease, Alzheimer’s disease, major depressive disorder, diabetes and schizophrenia. I note in passing that one of the authors is Julian Savulescu at Oxford who is already well-known for his view that parents who are able to do so, are ‘morally obliged’ to seek to have genetically enhanced children, whether by PGD, GM or genome editing. The use of polygenic editing, which would, in all likelihood, be available only to the (wealthy) few, fits in well with his overall ethical position. Needless to say, the paper, published in the prestigious journal Nature, attracted a lot of attention in the world of medical genetics. It was not however, universally welcomed – far from it. Another international group of medical scientists and ethicists has stated that ‘Human embryo editing against disease is unsafe and unproven …’ and even go as far as to suggest that the technology is ‘… going to be taken up by people who are pushing a eugenics agenda …’ remain very pertinent. 

Harder still and harder 

I have no doubt that amongst different reader there will be a range of opinions about the topics discussed so far. For anyone who is Christian (or indeed an adherent of almost any religious faith), one of the difficulties is that modern science, technology and medicine have thrown up ethical questions that could not have even been dreamed of by the writers of the Bible (or of other religious texts). We just have to use our wisdom, knowledge and general moral compass (and for some, prayer) to try to reach a decision. And if what I have already written makes that difficult, some recent developments multiply that difficulty still more.  

In the early years of this century, scientists developed methods of transforming a range of human cells into ‘pluripotent’ stem cells, i.e., cells capable of growing into a wide range of cell types. It also became possible to get both induced stem cells and natural stem cells to develop into functional differentiated cells corresponding to specific body tissues. This has huge potential for repairing damaged organs. However, other applications are potentially much more controversial. In 2023, Cambridge scientists reported that they had used stem cells to create synthetic mouse embryos which progressed at least as far as brain and heart formation within the normal pattern of mouse embryo development. 

At about the same time, the Cambridge group used individual human embryonic stem cells (from the blastocyst stage of embryonic development), to ‘grow’ early human embryos in the lab. There is no intention to use these embryos to start a pregnancy – indeed, it would be illegal to do so – but instead to study a period of embryo development which is not permitted with ‘real’ human embryos (research must not continue past 14 days of development). But how should we regard synthetic embryos? What is their moral status? For those who hold a conservative view of the normal human embryo (see earlier), should we regard these synthetic embryos as persons? Neither does the law help us. The legal frameworks covering in vitro fertilisation and early embryos (Human Fertilisation and Embryology Acts, 1990, 2008) do not cover artificial embryos – they were unknown at the times the legislation was drawn up. Indeed, synthetic embryos/embryo models are, in law, not actually embryos, however much they look like/behave like early embryos. Earlier this month, the Human Fertilisation and Embryology Authority (HFEA) discussed these developments with a view to recommending new legislation, but this will not dispel an unease felt by some people, including the science correspondent of The Daily Telegraph, who wrote that this research is irresponsible.  

But there is more. In addition to synthetic embryos, the HFEA also discussed, the possible use of gametes – eggs and sperm – grown from somatic stem cells (e.g., from skin) in the lab. Some authors have suggested that the production of gametes in vitro is the ‘Holy Grail’ of fertility research. I am not so sure about that but it is clear that a lot of effort is going into this research. Success so far is limited to the birth of several baby mice, ‘conceived’ via lab-grown eggs and normal sperm. Nevertheless, it is predicted that lab-grown human eggs and sperm will be available within a decade. Indeed, several clinicians have suggested that these ‘IVGs’ (in vitro gametes) seem destined to become “a routine part of clinical practice”.  

The lab-grown gametes would be used in otherwise normal IVF procedures, the only novelty being the ‘history’ of the eggs and/or sperm. Clinicians have suggested that this could help couples in which one or both were unable to produce the relevant gamete, but who still wanted to have children. In this application, the use of IVGs poses no new ethical questions although we may be concerned about the possibility of the gametes carrying new genetic mutations. However, some of the more wide-ranging scenarios do at the least make us to stop and think. For example, it would be possible for a same-sex couple to have a child with both of them being a genetic parent (obviously for males, this would also involve a surrogate mother). More extremely, a person could have a child of which he or she was actually, in strictly genetic terms, both the ‘father’ and the ‘mother’. What are we to make of this? Where are our limits?  

Dr Christopher Wild, former director of International Agency for Research on Cancer, explores in depth many of the developments and issue I outlined above. His article on why a theology of embryos is needed, is clear, well-written, helpful and thought-provoking. 

 

This article is based on a longer blog post with full footnotes.  

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Truth and Trust
6 min read

The BBC and the Church of England: two giants, one crisis of trust

Will honourable resignations save the BBC—or anyone?
TIm Davie, sits in an interview in front of screens showing facts about the BBC
Tim Davie, former BBC boss.
BBC.

Sometimes it seems like the BBC is never out of its own headlines. Just as one crisis is finally overcome, another erupts. This year alone we’ve seen outcry over a documentary on Gaza and the Glastonbury fiasco. Now, the broadcaster’s director general Tim Davie and head of news Deborah Turness have resigned over the latest scandal. A leaked internal dossier concluded a Panorama documentary on Donald Trump had misleadingly edited a speech he made on 6 January (it also raised questions over the BBC’s LGBT coverage and its Arabic language service).  

Both Davie and Turness have insisted that the corporation is not biased in its coverage, even if mistakes had been made by its journalists and editors. But both found the pressure too much to bear. Speaking outside the BBC’s London HQ, Turness said:  

“I stepped down over the weekend because the buck stops with me. But I'd like to make one thing very clear, BBC News is not institutionally biased. That's why it's the world's most trusted news provider." 

She was right to identify trust as key. Can we trust the BBC to tell us what is going on in the world fairly and accurately, if it makes mistakes like these? Can we trust the individuals within the broadcaster to report the news impartially, regardless of their personal views? Indeed, can we trust those currently condemning the BBC to be acting in good faith, and not motivated by political hostility or commercial rivalry?  

According to research by the Reuters Institute for the Study of Journalism, the BBC is the most trusted news brand in Britain, with 60 per cent of people saying they have faith in its output. Some of its newspaper antagonists can muster barely a third of that trust score. An Ofcom survey from 2019 found an impressive 83 per cent of viewers of the BBC’s TV news output trusted it to be accurate. 

But trust in the media overall is slipping away in Britain. A decade ago, 51 per cent of people told the Reuters Institute they trusted the news in general; a Brexit referendum, Covid pandemic and ten years of political turmoil later, that figure is just 35 per cent.  

Trust in the BBC is one of its most precious commodities, part of what helps it stand out both in Britain and globally. This is why Davie and Turness decided to fall on their swords, despite nobody suggesting they had personally done much wrong. It has to preserve the trust of its audience at all costs and the price to pay has historically been that when someone messes up, the people at the top resign. We saw the same back in 2012 when the then director general George Entwhistle quit after just 54 days in the role after the BBC got sucked into the Jimmy Savile abuse scandal. In 2004, both the director general and chair of the BBC’s board had to resign in the wake of the suicide of Iraq War whistleblower David Kelly. 

This – the regular spectacle of the ‘honourable’ resignation – is an increasing rarity in other parts of public life. In our post-truth post-shame political environment, it is more common for politicians to brazen out scandal and disgrace, and rarer for their party institutions to insist leaders fall on their swords. We lost count of how many scandals Boris Johnson survived as prime minister before he was finally felled by Partygate in 2022. Across the pond, Donald Trump has effectively rendered himself uncancellable by capturing the Republican Party and much of the US media ecosystem, despite corruption and growing authoritarianism. As the Guardian columnist Marina Hyde put it, “The BBC is the last place anyone still resigns from.”  

And yet. There is an interesting counter-example from another storied British public institution battling to maintain relevance in the 21st century and wracked by scandal and division: the Church of England. Just a year ago it too suffered the ignominy of seeing its leader resign in disgrace. Justin Welby was forced to quit as Archbishop of Canterbury after he was criticised in an official review over John Smyth, one of the most prolific abusers in the church’s history.  

Welby painted his resignation in similar terms: an honourable act of falling on his sword to take responsibility for the institution’s broader failings. In his cloth-eared valedictory speech in the House of Lords, the outgoing Archbishop told his fellow peers that “there comes a time, if you are technically leading a particular institution, when the shame of what has gone wrong, whether one is personally responsible or not, must require a head to roll.” And in this particular case, there was only “one head that rolls well enough”, Welby added; his own.  

But did this supposedly principled act of resignation rebuild trust? Not really. In fact, it may have done the opposite and further damaged the public’s trust in its national church. Welby initially hesitated and refused to resign after the damning Smyth report was first published, only agreeing to go after a weekend of simmering outrage. The vibe was less 'honourable man falling on his sword' and more 'leader convinced they’d done little wrong reluctantly forced out against their will'.  

And yet with the passing of time, his resignation has become mired in regret. Growing numbers of both bishops and others in the church have questioned just how liable he really was for the failure to stop Smyth’s abuse, and how robust the Makin report’s conclusions are. There is an increasing sense Welby was forced out in a rush to find a scapegoat, any scapegoat, to stem the bleeding and show that the church was taking it seriously.  

His successful defenestration has radicalised the more hardline elements of the abuse survivor movement, encouraging them to try to topple their other despised enemies within the church hierarchy. Bishops now fear they will be next on the chopping block, regardless of their culpability; unsurprisingly this does not engender greater trust. In fact, many observers would suggest trust between the bishops and those in the pulpits and pews has never been lower in modern times. The tortured attempt to introduce blessings for gay couples has poisoned the well further, contributing to the system for appointing new bishops to begin to break down. Somehow, both the liberal and the conservative wings of the Church feel equally betrayed by the bishops’ actions during the gay blessings saga.  

Trust is slowly earned, and quick to drain away. Even doing the honourable thing and resigning is no longer a surefire route to restore trust in our public institutions. Just as with Welby, it is likely these BBC resignations will not rebuild confidence in our national broadcaster. Instead, they may well further encourage the right-wing press and demagogues like Trump to scream “fake news” and hector impartial news outlets further. The resignations also tell the ordinary viewer and listener the accusations of bias must be true – otherwise why would these bigwigs have to stand down? 

There are no easy lessons to read across from the Church of England’s battle to regain trust to the BBC. For years now bishops have been urging clergy and lay people to try to trust them once more, to put aside defensiveness and hostility and work together in vulnerable collaboration. And things have mostly only got worse. Trust cannot be willed back into existence, nor will it return through the bloodletting of high-profile ‘honourable’ resignations.  

In fact, there’s a deeper problem which goes much further than the BBC or the Church of England. A deeper crisis of trust in society at large. For 25 years the Edelman Trust Barometer has been measuring societies around the world, and of 28 nations polled last year the UK’s average trust score was rock bottom: just 39 per cent of people on average said they trusted businesses, the government, or the media. In fact, almost everywhere people are running low on trust. Fears that government leaders and media elites purposely lie to us are at an all-time high. Until we can find ways to rebuild the ties that bind us, as individuals and communities, it is hard to see how the large institutions that used to shape British civic life – whether that is the BBC, the Church or parliament – can regain the public’s trust, resignations or no resignations.

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