Explainer
Biology
Culture
Ethics
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
Culture
Easter
Romance
Theatre
6 min read

Hadestown hints at so much more

The subterranean stage hit resonates deeply.

Freya is a curate at St Mary's Church, Islington.

A theatrical staging shows a couple seperated by a man standing between them.
Eurydice and Orpheus separated.
Hadestown.com

Hadestown – a folk jazz opera interpretation of the tragedy of Orpheus and Eurydice – is currently flourishing in London’s West End. Like the myth upon which it is based, Anaïs Mitchell’s opus has had many iterations. I had been listening to these songs for a decade by the time I saw the stage show. As a Christian priest, I am used to relating all myths, narratives, and fables to the story of Christianity. And yet, it was not until I saw Hadestown performed that the resonance with the Christian “myth” hit me all at once.  

In the myth (and the musical), a hero goes down to the underworld to retrieve his beloved from Hades, god of the dead. On Holy Saturday (the day between Good Friday and Resurrection Sunday), the church celebrates Christ’s descent to the dead and his freeing of imprisoned souls. This tradition is commonly known as the Harrowing of Hell. Art imagining this victory often depicts Jesus standing atop hell’s gates, ripped off their hinges, as he plunders the realm of a bound figure. Icons have Christ encircled in ripples of light as if he’s burst through the very walls of time and space to snatch his people from Death’s clutches. In some portrayals, he is pulling Adam and Eve – the original symbols of the rift in the God-humanity relationship – from their graves. The Harrowing of Hell receives more emphasis in Catholic and Orthodox traditions, but all Christians share some concept of Christ as rescuer, saviour, liberator.  

In the mythical world of Hadestown, something is broken. The seasons have collapsed, resources are scarce. Trouble in the underworld is causing everything to be off kilter in the overworld (not an uncommon concept in ancient thought). A contemporary audience can certainly relate to references to rising seas and widespread famine, as well as to the futility and despair permeating everyone’s inner monologue. The question the show poses is: can anyone break this cycle? Is there someone who could restore a broken relationship, rescue a soul back from the underworld…even make Spring come again?  

Humanity’s potential champion is Orpheus, a young man blessed with a supernatural gift for poetry and music. He is composing a melody “to fix what’s wrong”. When the song is finally sung, “Spring will come again” – the world will come “back into tune”, and “all the flowers will bloom”.  

The foil to Orpheus’s optimism is Eurydice, his lover. In this version, she is not killed but leaves for the underground realm of Hadestown, seeking food and shelter. I was moved afresh by her lament (‘Flowers’), sung in the depths of Hadestown’s mines, as Eurydice, like the prodigal son from St Luke’s story, realises what a mistake she has made. Hadestown’s inhabitants, it transpires, are not just trapped by the city walls – they are spiritually captive, indentured to Hades and his vision: eternal industry; perpetual war. Eurydice can no longer remember her beloved’s name, but she can remember that he could make flowers bloom in winter. She sings a petition for him to come and find her “lying in the bed [she] made.” 

We the audience know all along that Orpheus is coming, thanks to the song in the preceding act (‘Wait For Me’). Upon learning where Eurydice is, he undertakes the perilous descent to the underworld, all the while repeating “wait for me, I’m coming”. In a breathtaking moment of set design, the walls of Hadestown move aside in response to the beauty of Orpheus’s song. Eurydice’s prayer is answered by his sudden appearance, and his poignant invitation: “come home with me”.  

After the bows, the cast toast to the Orpheuses of the world, who show us things as they could be.

Orpheus is soon confronted, however, with the ugly reality of Hadestown. Eurydice has already signed her life away. Beaten and defeated, his innocent worldview shattered, Orpheus sings over and over “is it true?”. He is asking something more fundamental than if what is happening around him is real. He is demanding if this, the world that is, is the world that should be. Should we let the truth belong to those who “load the dice”, he asks?  

Hadestown’s walls take pity on Orpheus as they did before, echoing his song through the mines, where the workers – millions of other Eurydices – take up his song. The Dead-to-the-world realise they have been deceived, and remember who they were. And their faith starts to grow – that if Orpheus can walk out of Hades, then they can too. They want freedom.  

Persephone, Hades’ estranged queen, is won over by Orpheus. But Hades understands the truth about love: one flower starts a Spring. The fall of a kingdom begins with a crack in the wall. Unwilling to kill Orpheus because of Persephone, Hades instead sets up the famous tragic terms: if Orpheus can walk all the way to the surface without looking back to check Eurydice is behind him, freedom is theirs. It is a test Orpheus is doomed to fail, thanks to his experience in Hadestown. The mentality of the underworld has come to live in Orpheus’s head, and so “the path to paradise” becomes “the road to ruin”, and the story meets its inevitable end.  

And yet Orpheus does not fail as completely as he thinks. His musical gift has reconciled Persephone and Hades, and this has brought Spring to the world again. After the bows, the cast toast to the Orpheuses of the world, who show us things as they could be, and leave us with the responsibility to keep singing despite the circumstances, to reject despair, to hold on to that vision of every captive soul walking out of Hell. 

Myths tell us what we collectively fear and desire. Contemporary retellings show us how these longings have changed – or not. In what C.S. Lewis called the “true myth” of Christ, we see the fulfilment of Hadestown’s hopeful vision.  An early modern hymn describes Christ like Hadestown’s Orpheus – his presence “sees December turn’d to May”, making all the ground of the expectant “under-earth” turn to flowers. He is the one who has walked “the road that no one ever walked before”. The one who didn’t need to persuade the gods to empathise with him, because he was God. The one who was the perfect advocate for humankind, because he was human. Divinity without caprice, love without finitude: the one who experienced fear, temptation, ridicule – and yet did not turn back from the task. A peasant living under occupation: “this poor boy brought the world back into tune”.  

I was fortunate enough to see Melanie La Barrie in one of her final performances as Hadestown’s Hermes. Her voice gives the divine storyteller a godparental authority: La Barrie’s Hermes doesn’t so much narrate the story as prophesies it. At the inescapable end of the play, Hermes stands looking down like a graveside mourner, searching for the words to reignite the company. Hermes seems to have a divine vocation to keep telling the tale “regardless of how it ends” until it changes. This act is presented to us as faith, hope, resistance. In this new reality, where Spring has returned and the cosmic order has shifted, the tale might turn out differently upon the next telling, and so Hermes strikes up the band once more.  

Every year we sing the sad song again. The betrayal, the trial, the burial: the body in the tomb; the disciples in hiding. For so many, the-world-as-it-is feels like an endless Holy Saturday. The tradition of the Harrowing of Hell whispers to us to hold steady, because the rescuer is coming. “The darkest hour of the darkest night comes right before the dawn”, and a crack is appearing in the wall. 

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