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
Music
Sin
Suffering
5 min read

The holy or the broken: Hallelujah at 40

What’s the magic sauce Leonard Cohen mixed into his masterpiece?

Belle is the staff writer at Seen & Unseen and co-host of its Re-enchanting podcast.

A black and white photo shows, singer Leonard Cohen to the right hand side, eyes closed and head inclined slightly upwards.
Leonard Cohen, 2008
Rama, CC BY-SA 2.0 FR, via Wikimedia Commons

It’s summer 1984 – Richard Branson has just launched Virgin Airways, the Soviet Union have boycotted the Olympic games, the miner’s strike is still raging on, and Footloose is pretty much the only thing you can watch in the cinema.  

Amidst it all, happening miles under the cultural radar, a songwriter of astronomical talent and middling success walks into a pokey studio in New York. He’s clutching a battered notebook which contains eighty verses of a song that he’s been writing and re-writing for multiple years. A song that has been driving him to utter madness, residing tormentedly in his mind. The metre is running in the recording studio, so the eighty verses are promptly whittled down to just four and the song is finally wrestled into existence.  

A barely noticed existence, that is.  

Those four chosen verses, the ones lucky enough to have escaped the confines of the notebook, continue to dwell in obscurity for a while yet. This seemingly cursed song is housed in an album that the record company have refused, claiming it to be of no real commercial value. Subsequently, it will enjoy a tiny release in Canada in December 1984, but nowhere else. It is, to sum up, profoundly ignored.  

Now, let’s fast-forward exactly forty years. 

That obscure, over-looked and under-estimated, little song has been covered by more than three-hundred artists, including Bob Dylan, Jeff Buckley, and Lou Reed. Its lyrics have been dissected and studied by the likes of Bono and Salman Rushdie. It’s a movie soundtrack favourite, a talent show staple, and a part of the furniture at weddings and funerals the world over. Books have been written about it, documentaries made about it. I don’t think it’s a major exaggeration to say that it’s in the cultural air we breathe. 

 A song that once had its maestro banging his head against the floor in frustration, now belongs to us all. Can you hazard a guess at which song this may be the origin story of? I can give you a hint, if you’d like? It goes like this, the fourth, the fifth, the minor falls and the major lifts… 

You’ve got it.  

This humble tale is the story of ‘the baffled king composing Hallelujah’

Generation after generation finds itself notably and profoundly moved by this song. We treasure it, we value it, we let far too many people cover it (looking at you, Justin Timberlake).  

So, I guess I’m wondering - why?  

It’s one of those odd questions to which everyone, and no-one, has the answer. And it’s not that I don’t recognise the outright genius of Leonard Cohen and accredit the success to his mastery, I do. But, apparently, not even Cohen himself fully understood why this song has become such a phenomenon. Its success is an oddity, really. So, we have every right to ask ourselves - what’s the magic sauce that’s mixed into this song?  

Cohen... makes a bee line for the deep stuff, the uncomfortable stuff, the stuff we keep hidden – and plants the word ‘hallelujah’ in there.

It opens with Cohen telling the biblical story of King David, who played the harp so beautifully it had a kind of mystical effect – it supernaturally calmed the spirit of the dangerously erratic Israelite king, Saul. David, who himself would go on to become the ruler of Israel, is the ‘baffled king’ about whom and to whom Cohen appears to sing. As Alan Bright notes, 

‘He (Cohen) has placed us in a time of ancient legend, and peeled back the spiritual power of music and art to reveal the concrete components, reducing even literal musical royalty to the role of simple craftsman.’ 

The second verse mingles two further biblical stories together – that of (afore-mentioned) King David and Bathsheba, and Samson and Delilah. Both stories, both men, are brought to despair by abuses of power, moral failure, violence, and death. Their lives are truly toppled by their own brokenness and their own breaking-things-ness. To borrow a phrase from Francis Spufford, their stories act as a signpost for the ‘human propensity to f*** things up’. 

These verses are so particular in their subject matter yet so universal in their resonance. Most people have a vague-at-best understanding of the biblical stories its lyrics are alluding to, but a precise-to-the-point-of-painful understanding of the way that old ‘human propensity’ can have its way.  

And here is Leonard Cohen, using such despair and brokenness to house a sacred cry. Here’s Leonard Cohen, placing his finger on our vulnerability and telling us that it’s right there – right in the place of pain and shame – where we can engage with the divine. Here’s Leonard Cohen, telling us that if the God of the Bible exists, he can handle the very worst of us.  

This song, whether we know it or not, steels past our defences. It makes a bee-line for the deep stuff, the uncomfortable stuff, the stuff we keep hidden – and it plants the word ‘hallelujah’ in there. It tells us that brokenness is inevitable, but it can be made holy. Isn’t that our deepest desire? To know that we’re not too far gone? To be told that we’ll fail, all the time, but never one time too many? 

I think, if you were to put that message in any context less real and raw, we’d be suspicious of it. If this song was less gritty, it would have stayed ignored. But it’s just messy enough to have us trust it, Cohen just about honest enough for us to believe him when he tells us that he ‘didn’t come to fool’ us.  

So, long may it continue. Long may it sneak past our emotional barricades and wreak havoc in our guarded hearts. Long may the four-minute-long weep-a-thon reign (just, not Justin Timberlake’s version, I beg).