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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Review
Books
Culture
Film & TV
Purpose
8 min read

You may never take the Salt Path but here's why the tale makes sense

Kindness runs deep in the architecture of reality.

Roger is a Baptist minister, author and Senior Research Fellow at Spurgeon’s College in London. 

A hiking couple sit on the grass next to a pack.
Gillian Anderson and Jason Isaacs.
BBC Films.

The Salt Path is a phenomenon.  

An internationally best-selling book and now a movie starring Gillian Anderson and Jason Isaacs. How is it that a memoir of a middle-aged couple walking the South West Coast Path from Somerset to Dorset, via Land’s End, has had such an impact? 

Well, it’s because it resonates. It rings true. It’s about life as we know it, even if we haven’t hiked the 630 miles of the path from start to finish. A journey that is also, incidentally, the equivalent of climbing Mt Everest four times over. 

In the events leading up to their walk Raynor (Ray) and Moth Winn are dealt a series of body blows. They’re left bankrupt and homeless empty-nesters, struggling to come to terms with Moth’s deteriorating health.  

It was just as the bailiffs were seeking to gain access to their farm and take possession of it that Ray spotted an old book, 500 Hundred Mile Walkies, and took inspiration. 

‘We could just walk.’ 

And that’s what they did. 

So, what are the truths about life and our human experience that this story opens up for us? 

Life is precarious  

Bad stuff happens. Sometimes we bring it on ourselves, the consequence of wrong or ill-judged decisions. Other times it is thoroughly undeserved. Life turns around and bites us, hard. We’re left with our heads numb and spinning round with the persistent but unanswered question, ‘why me?’ 

For the Winns, an investment in the business of a trusted, life-long friend failed. The deal he structured left them responsible for the debts of his company. The end of a prolonged legal battle meant they lost everything, their farm, their home, their business, and the life-long friend. 

The same week also found them in a hospital in Liverpool getting the diagnosis for Moth’s chronic shoulder pain. It was not the suspected nerve damage, but rather the fatal neurological condition corticobasal degeneration. CBD. A diagnosis that was untreatable and only finally confirmed postmortem. 

Whether it’s the South West Coast Path or the familiar details of our own life, we can never fully anticipate tomorrow. We do not know what lies behind the next headland or what unwelcome surprises life may spring on us. No, we need to live in the moment. It’s pointless worrying about tomorrow and we ought to let it worry about itself. We can only live in today. As Ray reflected towards the end of their time on the path: 

“This second in the millions of seconds was the only one, the only one that we could live in.” 

Who am I, really? 

Early in the book Ray recalls: 

“I once heard a lecture by Stephen Hawking, when he said, ‘It’s the past that tells us who we are. Without it we lose our identity.’ Perhaps I was trying to lose my identity, so I could invent a new one.” 

Who are we when everything is stripped away? What defines us? Homeless and jobless, questions about where we’re from and what we do are not only awkward, they also create an existential void.  

Often mistaken for tramps, Ray and Moth noticed people treating them differently. Some quietly moved away, others were more forthright, “disgusting!” But the judgement of others does not define who we are. Yet, who actually were they in this new world of theirs?  

And then there’s the impact of failing health. Each stage of deterioration promising to erode what can be physically done and requiring a redefinition until there is nothing left at all.  

Yet identity is deeper than that. It is at the core of who we are, at the very heart of us. It is the sum of our experiences and choices, our successes and failures, of what we have gladly embraced and that which life has unexpectedly thrown at us. We are unique individuals with intrinsic value, worth and dignity. People who love and are loved. 

At the end of the path Ray muses: 

“Most people go through their whole lives without answering their own questions: What am I, who do I have within me? The big stuff. What a waste.” 

I guess that’s one of the attractions of making space to walk. To lose the distractions and busyness of our over-complicated lives for self-discovery to break in. 

One step at a time 

How do you get your head around walking 630 miles? How can you appreciate the demands of climbing unknown hills and cliffs and navigating their gullies and ravines.  

On top of the terrain there’s the notorious English weather to negotiate. With little money and only a tent for respite: when it rains you get wet and stay wet, when it’s cold, you shiver and put on as many layers as you can. Even in August it can be challenging. 

Walk, eat, sleep, repeat. 

Sometimes the only thing to do is put one foot in front of the other.  

“Each step had its own resonance, its moment of power or failure. That step, and the next and the next and the next, was the reason and the future. … each day survived a reason to live through the next.” 

There is always agency. There is always the opportunity to choose today which path to travel and which attitude to serve. To give in or go on, to be a defeatist or hopeful, complaining or generous, those choices are always there, even when they’re limited. Even in the wake of unfair decisions and unexpected tragedy, we choose today the way we take. And sometimes that’s all we can muster. 

The kindness of strangers 

Ray and Moth’s story is littered with moments of kindness and warmth. From the lovelorn waitress who sneaks them the day’s leftover pasties to the generosity of a hippie commune there is a recurring theme that echoes an underlying goodness in the nature of people. And often it is those with the least who prove to be the most open-handed and thoughtful. 

On more than one occasion the Winn’s themselves share from their own meagre supply of food, especially their precious fudge bars, with those in a more uncertain state than their own. On another occasion they step into a tense and potentially violent situation with a young woman, Sealy, the subject of an abusive relationship. They offer her company and a way out, ultimately paying for her £5 bus journey to get away to family. 

There is something heartwarming about kindness, something elevating. Both the giver and the receiver feel encouraged, lighter, happier. The abiding truth continues to stand the test of time that it is ‘better to give than to receive’.  

Strangely, watching these scenes play out in my local Showcase Cinema was an uplifting and inspiring experience. You can never predict or properly anticipate when a tear will unexpectedly present itself to the corner of your eye. I suspect that kindness runs more deeply in the nature of things than we comprehend. It is part of the deep architecture of reality.

Love and relationship in tough times 

When it comes down to it, The Salt Path is about Ray’s relationship with Moth. How they face an unimaginably difficult set of circumstances and find a way through together. This is a profoundly hopeful story. And from it we can draw hope too. 

There was nothing religious about what they were doing, “It’s not a pilgrimage. Is it?”  

At one level it is purely a response to desperation. But in the midst of it all they have each other. Thirty-two years together, having begun their relationship when Ray was 18, they are still deeply in love. They epitomise the values enshrined in the marriage vows. 

“… to have and to hold from this day forward, for better for worse, for richer for poorer, in sickness and in health, to love and to cherish, till death us do part …” 

This is not slushy sentimentality but rather love that proves itself in the face of the onslaught of ‘worse … poorer … sickness … death’. 

The conclusion of their journey led Ray to a realisation: “I was home, there was nothing left to search for, he was my home.” As the ancient poet wrote: 

“Set me as a seal upon your heart,  

as a seal upon your arm; 

for love is strong as death, 

passion fierce as the grave. 

Its flashes are flashes of fire, 

a raging flame. 

 

Many waters cannot quench love, 

neither can floods drown it. 

If one offered for love 

all the wealth of one's house, 

it would be utterly scorned.” 

(Song of Solomon) 

That’s it then. The book and the movie work because they reflect back to us the life we know, the lives we live. Yes, they’re in high relief in the choices that Ray and Moth take, but that clarifies things for us. Most of us won’t ever find ourselves in the position they were in, but we can empathise. Most of us would never think to do what they did even if we were. But for all that, we see, we understand and it makes sense. 

If you get a chance to see the film, then do. Gillian Anderson and Jeremy Isaacs are exceptionally good in their understated performances. The visual experience of the South West coast is everything you would expect it to be, sounding as majestic and immersive as if you were there. A real treat. 

For me, the most poignant and telling moment of the story happens at Lyme Regis. Moth says: 

“When it does come, the end, I want you to have me cremated. …keep me in a box somewhere, then when you die the kids can put you in, give us a shake and send us on our way … They can let us go on the coast, in the wind, and we’ll find the horizon together.” 

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