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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Essay
Culture
Doubt
Music
Psychology
9 min read

What happens when perfect plans are outsmarted by the world?

There may be delight hiding in the doom.
Two people sit and stand next to a grand piano on a stage.
Striking the wrong note.
Polyfilm.

If I’ve learned anything at all from decades working with businesses, it’s that they love an acronym. For a while the acronym we loved was VUCA. Not a nuclear jet nor a foot wart, VUCA emerged from the leadership theories of Warren Bennis and Burt Nanus to reflect the Volatility, Uncertainty, Complexity and Ambiguity of contemporary leadership. Nothing gets a roomful of executives nodding sagely than the observation that we live in a VUCA world. For a while it felt almost sacrilegious not to evoke VUCA at some point when training leaders. It was comforting to tell people who were supposed to be shaping the world that everything was, well… a bit nuts. 

But in the last few years VUCA has lost its shine. Things have started to get too crazy, a bit too VUCA for anyone’s liking. The wars, the plagues, the natural disasters, the political upheaval, the shaking of old certainties- it’s all gone a bit super-VUCA. The acronym that once reassured us that the world tends to resist our perfect plans has been outsmarted by the world it once captured. What are we to call this permacrisis, this omnishambles, this SNAFU, when super-mega-hyper-VUCA just sounds stupid? A new acronym was needed. Enter stage left- BANI, the invention of futurologist Jamias Cascio to designate the way things are now: Brittle, Anxious, Non-Linear, Incomprehensible. We’ve had a romantic breakup with the world- you’re not like it used to be, you used to be fun, you’ve changed!  

In March, Seen & Unseen celebrates its second anniversary. We are two years old. Old enough to appreciate a birthday cake, too young not to burn our fingers on the candles. I’ve been writing for the site since the beginning and to this day feel surprised that this quirky mishmash of a brainfart I keep writing is still accepted for publication each month. Either the folks at Seen& Unseen are pathologically kind to their own detriment, or my monthly missive of misery is not quite as off the wall as I fear it might be.  

When I look at the world, I feel like we’re in a football match with no referee. I keep shouting foul and looking for someone to blow the whistle. It feels like the Tower of Babel. Even the technologies we thought would unify us have made us incomprehensible to one another. Like the scene in That Hideous Strength (the third book in C.S. Lewis’ Cosmic Trilogy) where a roomful of people is magically befuddled. They can no longer understand each other, and anyone who rises to take charge of the situation speaks gibberish that only adds volume to the babble. We don’t need any more opinions. We certainly don’t need any more people with misplaced certainty they have the answer. 

To be honest, I’ve just run out of ideas. I’m confused, baffled, clueless. But what embarrasses me most is not my helplessness, it’s my hope. For some reason, in jarring contrast to the circumstances, I can’t shake off the sense that ultimately all this will make sense, that breakdowns lead to breakthroughs. We’re in the unbearable part of the story where everything goes wrong, but if we put the book down now, we’ll think that was the end of it, when it was really just the set up. Pretty much everything I’ve written for Seen & Unseen over the last two years equates to: grief, this looks bad, but maybe there is more to it than it appears. 

There is another anniversary being celebrated this year. This January marked the fiftieth year of a musical event so remarkable that a new dramatization of it premiered at the Berlin Film Festival to mark the occasion – the recording of The Köln Concert. (Watch the trailer of Köln 75.) If we are looking for a story of how beauty emerges from disaster, this one is worth telling. The event was organised by eighteen-year-old Vera Brandes, at that time the youngest concert promoter in Germany. She booked the Cologne Opera House, but given that it was a jazz concert, it was scheduled to begin at 11:30pm following an opera performance earlier that evening.  

The performer, jazz pianist, Keith Garrett travelled to the concert from Zurich. But rather than flying, he sold his ticket for cash and opted to make the 350-mile trip north with his producer Manfred Eicher in a Renault 4. He had not slept well for several nights and arrived late afternoon in pain, wearing a back brace, only to discover that the opera house had messed up. The Bösendorfer 290 Imperial concert grand piano he had requested had been replaced by a much smaller Bösendorfer baby grand the staff had found backstage. The piano was intended for rehearsals only, in poor condition, out of tune, with broken keys and pedals. It was unplayable. Jarrett tried it briefly and refused to perform. But Vera Brandes had sold 1,400 tickets for the evening. So, while he headed out to eat, she promised to get him the piano he required. 

But it was not to be. The piano tuner who arrived to fix the baby grand tells her a replacement is impossible. It was January in Northern Germany, the weather was wet and cold, and any grand piano transported in those conditions without specialist equipment would be damaged irreparably. They had to stick with the piano they had. Keith Jarrett’s meal didn’t go well either. There was a mix up at the restaurant and their food arrived late. They barely had chance to eat anything before returning to the venue. And when Garratt saw the tiny defective Bösendorfer still on the stage, he again refused to play, only changing his mind because Eicher’s sound-engineers were set up to record.  

So the concert begins. A reluctant pianist – tired, hungry and in pain – sits at a ruined piano, and records the bestselling piano solo album and bestselling jazz album. Ever. He improvises for over an hour. Starting tentatively, exploring the contours, befriending the limitations of his damaged instrument – learning its capabilities as he plays. But soon Jarrett is whooping, yelling and humming with delight as he extracts beauty from the brokenness. The limited register forces him to play differently. The disconnected pedals become percussion. By the time he reaches the encore, the joy of his playing is irrepressible – it sends shivers down the spine. And when he finishes, the applause goes on. Forever.  

Jarrett pulled off an impossible feat and sealed his reputation as one of the greatest pianists of his generation. And I take heart from the event, because when I face the world, I sometimes imagine I feel like he did facing that piano. Tired and pained and doubtful any good will come of playing. Can I order a new world, please? One more to my liking. One less likely to hurt. Yet I can’t quite shake off the intuition that there may be delight hiding in the doom, a treasure only unearthed by those willing to play. 

I am drawn to Job. He is a hero to all those who are sick of the answers of others but have no answers themselves. 

This year I celebrate my own anniversary. I was born seven months after that fateful night in Cologne, in the equally salubrious town of Birkenhead. This is my fiftieth year too. The 3:15pm of life: too early to clock off, too late to start anything new. If living is a race between maturity and senility – gaining the wisdom to live before losing our marbles – then I’m odds-on for a photo finish. The evidence accumulates daily that I am likely to live longer than most of my vocabulary.  

Jung held a positive view of old age. He viewed it as the time for religion to ripen. And I can’t help agreeing with him. The older I get the closer God seems. As muscle mass thins the spirit deepens. Outwardly I’m fading away, inwardly I am being renewed day by day. This undoubtedly underlies my hope of beauty arising from our brokenness. In some small and barely noticeable way it is already happening in me. And I know I’m not alone in that.  

Jung also wrote about Job- the Hebrew epic of suffering and restoration. Job’s life is like one of those old blues songs. He loses his wife, his kids, his home, his health. He’s left broken, infested with sores and sitting in the dust. If you’ve been in a situation like that, you’ll know that even the most well-meaning friends can respond with surprising incompetence. Job’s friends are no different. They are true believers in Just-World Theory, the universal human tendency to assume that if bad things happen to us we must deserve them, we must have been bad. They live in a world ultimately governed by the kind of instant karma that causes car crashes on YouTube, and they’re keen to teach Job the way the world really is.  

But Job resists them at every turn. He may have a proverbial reputation for patience, but he is anything but patient. I used to think this was a story about a man defending his innocence, but it’s much more than that. It’s the story of a man who goes through a breakup with God. He once lived a life of goodness, abundance, and gratitude in which he knew God as attentive and lovingly present. His friends are not just arguing that he’s being punished for some undisclosed sin, but that he’d always been wrong about God. He’d never known God- not really. The God they knew was volatile, capricious, arbitrary, vicious - like a rescue dog, you never quite knew when he would turn. And Job’s suffering was the proof of it. 

The problem for Job is that he has no clue why he is suffering, but he will not let his friends obliterate the history he has shared with heaven. He knows God to be utterly faithful, constantly present, sublimely attuned, hugging the contours of his life as the sea hugs the shore. He wants nothing to do with a fickle god who falls asleep on the job or flounces off the first time we let him down. He rejects the here-again gone-again god of his friends. Sometimes, to know God, we need to reject those who claim to speak for God.  

The weird thing in Job’s story is that eventually God shows up. Over the course of the narrative, he has asked God 122 questions, and God responds with 61 of his own. The questions are rhetorical- they point to all the places God is present that Job isn’t, all the things that God knows that Job doesn’t, all the things God has done that Job hasn’t. And by the end, Job is satisfied, his friends are dismissed, and his life is restored. God is as Job expected, intimately present but ultimately mysterious. He was right to reject the obtuse certainties of his friends and face the pain of the world with a cultivated sense of unknowing. 

When I ponder how best to bring beauty out of a BANI world, how best to play its brokenness like Jarret played his Bösendorfer, I am drawn to Job. He is a hero to all those who are sick of the answers of others but have no answers themselves. He is also a hero to those who, despite all evidence to the contrary, cannot smother their hope. Those who discern the leavening yeast sown in the hearts of humans across the planet; too inconspicuous to make the news, but destined to rise when the time is right.

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Watch the Köln 75 trailer