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Biology
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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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Article
Belief
Culture
Film & TV
Identity
5 min read

Wednesday works wonders bringing the outsiders in

Tim Burton’s echoes of C.S. Lewis

Lauren writes on faith, community, and anything else that compels her to open the Notes app. 

Wednesday Adams scowls while Enid smiles.
Wednesday and Enid.

There’s something delightfully ironic about the mainstream success of Wednesday – Netflix’s Addams Family spin-off directed by Tim Burton. With its whimsy gothic aesthetic, star-studded cast and viral TikTok dance to boot, the first season was a highly bingeable hit in 2022. This summer, the split-release of season two scored over 50 million streams in its first five days. But beyond its cult-like reception lies something deeper: a collective reckoning with identity, acceptance and the desire to belong. 

Jenna Ortega’s Wednesday Addams is an outsider among outsiders. Upon returning to Nevermore Academy – a supernatural boarding school meant to be a haven for ‘freaks, monsters and outcasts’ – she finds herself more alienated than ever. Don’t feel sorry for her: she’s difficult, destructive and I’m not sure I’d want to share a dorm with her (or her pet disembodied hand, Thing.) But that’s why we love her so much. 

Wednesday ‘taps into that sense of not quite fitting in that everyone has,’ praised Marina Hyde on her The Rest is Entertainment podcast. ‘We all feel like we’re the kind of excluded weird mad kid from Burbank, as he [Burton] was growing up.’ 

C.S. Lewis termed the phenomena of not quite fitting in as the ‘Inner Ring’ – the unwritten systems of belonging that permeate all areas of life, from early youth into old age. It can neither be fully defined nor totally avoided. Lewis suggests that all people, at some point or another, experience this ‘desire to be inside the local Ring and the terror of being left outside.’ Ultimately, he warns, this pursuit of surface-level or self-furthering belonging ‘will break your hearts unless you break it.’ 

Lewis, one of Christianity’s most profound cultural influencers, was stirring a deeper call among his fellows Christians: to remember that the gospel is not just good news for those sitting comfortably in the pews – it’s good news for those outside. It’s good news for those searching for belonging in a world that prizes conformity and feasts on exclusivity. 

Tim Burton’s genius lies in his ability to reach out, subverting the mainstream and dismantling the Inner Ring, seemingly with ease. Everyone’s an outsider, so no one is an outsider. As in Edward Scissorhands or Jack Skellington from The Nightmare before Christmas, Burton’s decision to not only tolerate but to celebrate the outcast bridges the gap between the socially excluded and socially accepted. 

The sense of belonging that Burton creates doesn’t feel twee, manufactured or forced. It isn’t the sort of embrace that comes under strait-laced conditions, either. He cultivates spaces where the strange, the sad and the misunderstood become protagonists, empowered to tell their own story. He boldly platforms that which is different, unwilling to conform or compromise. Even the visual language of his work is distinct and unashamed, and his trademark scribbled twists and turns that creep into set designs, costumes and title sequences. 

In Wednesday, this contrast is emphasised by a window that is half-spiderweb, half-kaleidoscope, dividing the room that Wednesday shares with Enid, the optimistic and bubbly roommate. They’re an extreme black-cat, golden-retriever pairing who have little in common, except for feeling that they don’t fit in. 

Their desire for belonging and acceptance looks different. Enid cares very much about how others view her, whereas Wednesday’s cold defiance masks her vulnerability to be seen, known and accepted. This symbolic shared space, and the friendship that is imposed upon Wednesday by Enid, signals a deeper truth: belonging is not found in sameness, but in recognising what connects us and how we can honour one another in spite and because of our differences. 

The subversive nature of Burton’s imagined universe holds a dim mirror to the liberating reality of God’s Kingdom.

While Burton elevates the outsider, his worlds often remain solitary and cut-off. But the Church, at its best, offers not just visibility but the embrace of fellowship. Jesus consistently chose people on the margins – lepers, tax collectors, women – and invite them into relationship. The gospel accounts for him taking less efficient travelling routes seemingly to encounter the lonely, the sick and the despised, to share news of their belonging to God, whose love for them was so strong that he would dwell not only among them, but within them through his Spirit. 

The culture of the early church was informed by Jesus’ example, and their meetings were a mosaic of cultural, ethnic and social diversity, brimming with unlikely partnerships and clashes of custom. Paul reaffirmed the concept that all are ‘one in Jesus Christ’ in his letter to the church in Galatia, declaring that ‘there is neither Jew nor Gentile, neither slave nor free, nor is there male and female.’ This is not a call to erasure, but to radical inclusion. Rather than everyone being an outsider, as in Burton’s world, everyone is an insider in the Kingdom of God. 

Perhaps it isn’t about whether Tim Burton or the Church has done more for outsiders, outliers and outcasts, but to invite personal challenge: Am I willing to get used to different? To disturb my norms, routines and expectations in the name of mutual inconvenience? To embrace a little mess and chaos for the sake of greater unity? 

The subversive nature of Burton’s imagined universe holds a dim mirror to the liberating reality of God’s Kingdom, where the last are first, the poor receive a rich inheritance, and the margins become the centre. Where Burton’s audience may find solace in shared strangeness, the gospel offers something greater: a home not built on similarities and commonalities, but on divine welcome and spacious grace. And an unlimited set of keys to welcome others to their room, too. 

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