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
Character
Culture
Idolatry
Psychology
6 min read

We need a sense of shame - but need mercy even more

Shame may be necessary, but only if it can be defeated

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

Frankstein stares our from his covered face.
Jacob Elordi plays Frankenstein's monster
Netflix.

I’ve been thinking about the nature of shame a lot recently. Both professionally and personally, it’s a topic that is demanding my attention. It’s following me around, insisting that I look it in the eye, shoving and nudging me – taunting and tempting me to finally snap and wrestle it to the ground. I guess that is the very nature of shame, isn’t it? It’s always so stubbornly there.  

I’ve also noticed that it seems to have elbowed its way into cultural conversations; it’s been putting a real PR shift in, seeking rehabilitation in public discourse.  

The actor, Jacob Elordi, was recently interviewed by the Wall Street Journal. Kind of interesting, kind of not. The sliver of it that really caught my attention was when the interviewer asked Jacob,  

‘What’s one lost art that you wish would come back in style?’  

To which Elordi replied,  

‘The art of shame. I wish people could experience shame a little heavier’.  

Gosh.  

It makes sense that this was Jacob’s answer; the interview was conducted to promote Frankenstein, Guillermo Del Toro’s new movie in which Jacob Elordi plays Frankenstein’s monster. So, I get it. He’s been consumed with what components make up a monster, endeavouring to literally turn himself into one. He’s been ruminating on the recipe of evil, and perhaps he’s found one key ingredient – shamelessness. Maybe Jacob, having dwelt on such, has subsequently looked out at the not-so-fictional ‘monsters’ wreaking havoc and has diagnosed the same thing, a distinct lack of shame.  

It's a solid thesis.  

It reminded me of another recent interview, this one with the acclaimed author, Zadie Smith. She said,  

‘Shame gets a bad rap these days. I think it’s quite a useful emotion, corrective on certain kinds of behaviour… I assume people – including myself – are just deeply, deeply flawed. And so, shame is usually quite appropriate on a day-to-day level… shame is a kind of productive thing to create change. I guess I do believe that. I know it’s definitely a Christian emotion, that’s why it’s so out of fashion. But I always thought it quite productive in the gospels, that idea that you assume that you are entirely in sin. I always assume that.’  

I half agree with both Jacob and Zadie. In a way, I’d be a fool not to. Not to mention, proof of their thesis. 

I cannot deny that I am, as Zadie points out, deeply, deeply flawed. There is a crack in everything I do, a fracture in all my best intentions. And yours, too, I’m afraid (but I have a feeling you know that). There is a brokenness to us, a breaking-things-ness. To each and every one of us, ‘hurt’ is both an adjective and a verb – something we feel and something we do. The things I want to do, I never manage. The things I don’t want to do, I seem to manage every day. I am falling short, missing the mark – I am so fallibly human.  

To acknowledge such is not only obvious, nor is it simply ‘useful’, as Zadie suggests. It’s inherently spiritual, it’s paradigmatic. 

Last summer, I hosted an event at which Francis Spufford, one of my most cherished wordsmiths, playfully quipped, ‘I’ve heard original sin (the notion that we are, as Zadie notes ‘entirely in sin’) described as one of the few theological propositions which you can actually confirm with the naked eye’. ‘Sin’, Tyler Staton similarly writes, ‘is simultaneously the most controversial idea in Christianity and the one most universally agreed upon’.  

There’s something deeply wrong with the world. We all know that.  

Which, presumably, is what Jacob Elordi is getting at – he’s observing bad people not feeling bad enough about the bad that they do, or worse still, the bad that they are. A healthy dose of shame is the medicine that this world needs, he suggests. 

Oh Jacob, I sympathise with that. The thing is, I have a hunch that the presence of shame makes as many monsters as the absence of it.  

And Zadie, I wonder if shame births as much destruction as it does ‘correction’.  

While I agree with you both that, in a world as broken as ours, shame needs to exist in some form or another, it also needs an antidote. It’s a dangerous substance; toxic and destructive. Don’t let it fool you, don’t be over-generous to it – shame may (in its most moderate and appropriate forms) be an acknowledgment of the disease, but it is not the medicine. It could only ever be ‘useful’ if it is, ultimately, defeatable.  

At least, that’s my – admittedly very Christian – conviction. That’s my take. I can’t pretend that it’s not as theological as it is sociological in its underpinnings. 

I’m relatively new to the liturgical aspects of my own faith tradition (that is, the formalised scripts, actions and rituals that have long fuelled religious experience) , so I have the pleasure of not being numb to them. When I read the ancient words of ancient prayers, they shoot right through me, particularly these ones:  

‘Almighty God, our heavenly Father, we have sinned against you and against our neighbour in thought and word and deed, through negligence, through weakness, through our own deliberate fault...’ 

Ouch.  

As I read those words, week in and week out, my brain creates a helpful montage for me – whirring through the countless ways in which I have failed – in what I think, what I say, what I do. I’m confronted with the ways that my breaking-things-ness has leaked out of me through my negligence, it’s spilled out of my weakness, the force of it directed at others through my own deliberate fault.  

Oh yes, I’m well acquainted with the emotion of shame.  

But the only thing productive/appropriate/corrective about falling on my face in shame, is that there is a mercy that can scoop me up. It’s not hopeless, you see? There’s a mend-ability. There’s an antidote to shame; there’s a balm for its burn. There’s a bewildering love that banishes shame from within me – there’s a rescue route from its toxic spiral.  

The moment that shame is acknowledged, its presence verbalised, its power felt – is the very moment it needs to be neutralised. It cannot fester, it cannot be afforded the loudest, nor the last, say.  

And so, to Jacob Elordi’s interesting wish – that ‘people could experience shame a little heavier’, and to Zadie Smith’s fascinating thesis that ‘shame is a kind of productive thing to create change’- I hear you. I see what you’re getting at. But I can only ever wish people to experience the heaviness of shame if it means that they are more sensitive to the feeling of it being undeservedly lifted off them. That’s where change happens. That’s the medicine.  

So, Jacob and Zadie, let’s agree to half-agree on this one, shall we?  

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