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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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5 min read

This is why we must go down to the sea

Stepping off the shore restores more than our sanity

Paul is a pioneer minister, writer and researcher based in Poole, Dorset.

A sunset over an island casts golden light on the sea and a beach.
An Argyll beach.
Nick Jones.

It’s that time of year again. Much of Britain has been enjoying (or possibly enduring) a heatwave, the summer holidays are approaching, and our thoughts naturally turn toward an escape from our ordinary, often urban, landlocked, lives. And for many of us that escape will be to the sea. It’s true, we really do like to be beside the seaside. As a nation our souls seem to suffer from an annual experience like that described in John Masefield’s poem Sea-Fever as we head coastwards muttering ‘I must go down to the sea again...’  

We want to holiday by the sea – as the market for second homes in places like Cornwall will confirm. We also want to live permanently by the sea, or at the very least by the water. Some experts estimate that properties by the water have an average increased value of around 48 per cent. Water sells. It does so perhaps because proximity to it provides something of a mental escape from the overwhelming rigidity and linearity of our predominantly urban environments.  

Iain MacGilchrist has argued that our modern lives suffer from the triumph of the left-brain hemisphere’s attention to the world. This is a focussed attention that is all about controlling and getting. It leads to the creation of a self-contained and ordered world with little attention to context. And so little attention to the natural, complex, fluid reality of creation. MacGilchrist goes on to correlate the rise in a variety of mental illnesses characterised by what he calls ‘right hemisphere deficits’ with industrialisation and the development of our culture of modernity.  

In his book Blue Mind Wallace Nichols explores the evidence for the positive effect of water on the brain. He highlights how a proximity to water can heal, restore, give us a sense of connection and promote calm. He argues that water can shift our minds into what he calls ‘drift’, the kind of mental attention which generates calm. Being with, on, better still in water, is undoubtedly good for us. No wonder we are drawn to it.  

Yet at the same time water, and particularly the sea, has been a source of terror. A no-go area ‘where there be dragons’, OK, lobsters for sure, probably sharks, and whales like Moby Dick. The sea remains one of the last places of mystery, an unfathomed, unfathomable place of endless dark water. We know more about the far reaches of the universe than we do about the truly deep ocean. Mythical creatures of the deep, whether Nessie, or one of various giant specimens hauled unsuspectingly from the ocean, continue to populate the diminishing space of our wonder and fear of the unknown.  

So whilst elucidating the psychological benefits of water is certainly helpful, it’s all a bit…tame. Is it just another way of humans turning the wild and numinous into something we now think we understand? Something we can now control and apply in our lives for our own benefit and comfort? Have we demystified the sea? Reducing its mysteries to little more than a balm for our troubled modern minds? A lure for our attention and our debt in an overheated housing market? 

In the Christian tradition the sea is a place of profound paradox. Creation begins with God’s Spirit hovering over the water. However, the Hebrew scriptures also present the sea as a place of God’s absence. The sea is the place of monsters and mystery, and death. It’s also the place of perhaps the most famous whale in all literature. The whale that swallows the hapless Jonah. Jonah’s story expresses the deep paradox of the sea as a place of death and yet also a place of divine encounter. It is in the depths of the sea, and the digestive system of the whale, that Jonah’s epiphany takes place and his journey starts anew. 

Stories of Jesus also deal with this paradox of wildness and encounter in the chaos of the sea. In the story of the calming of the storm the wild threat of the sea is not rendered as simply something to be avoided. Jesus is not a fixer making all daily dangers obsolete. Rather the story says that it is precisely in such moments of wildness, fury and terror that his powerful presence can be encountered.  

To step off the shore and into the sea is to enter the possibility of the death and (paradoxically) the real possibility of deeper life.

It’s for these reasons perhaps that, John Good, a friend of mine, has formed a Christian community that’s based around encounter with the sea. Located as it is in an area almost surrounded by the sea, it started as a social enterprise helping people access the water who otherwise lacked the equipment or resource to do so. Pretty soon it became clear that this was transformational for people. Enabling families otherwise excluded from a life-giving resource to enjoy it as much as anyone else was powerful. One person referred to the experience by saying that on that day the sea had been ‘her saviour.’ Ocean Church began with a gathering on three large, tethered paddleboards some metres offshore. They now run retreats and pilgrimages on the sea, practice centering prayer (a form of Christian meditation or contemplative prayer) on the sea and continue to explore what it means to meet God on the water.  

We yearn for the sea, and the water, for more than a balm for the mind. The sea remains that place, in our mechanised, technological world with its constant lure of control and mastery, where an immersion in dangerous mystery can still be experienced. To step off the shore and into the sea is to enter the possibility of the death and (paradoxically) the real possibility of deeper life. To be held buoyant by the sea and look to the horizon is to get it touch with our finitude in the context of the vastness of the seas. It is to engage with our utter dependency on the creation which we inhabit and to connect with the presence that holds that creation together.  

To step into the sea is even therefore a step of faith. A step in the direction of our own vulnerability. A brave step away from the world in which our technology, our algorithms, our machines and our skyscrapers dupe us into a faith in our own control, our own supremacy. A step into the depths. ‘Deep calls to deep’ says the psalmist as ‘all your waves and breakers have swept over me.’ As many of us step into the sea this summer it may certainly be a step toward a restored sanity, but it might also be a step toward a restored soul.   

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