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
Community
Culture
Nationalism
Politics
5 min read

Nationality can never unite a nation

For countless people, it’s a complicated thing.

Graham is the Director of the Centre for Cultural Witness and a former Bishop of Kensington.

A montage of two conversation participants side-by-side.
Fraser Nelson and Konstantin Kisin.
Triggernometry.

What does it mean to be English? A debate has broken out on this thorny question, sparked by a conversation between Konstantin Kisin and Fraser Nelson, where Kisin, a British-Russian social commentator suggested Rishi Sunak, as a ‘brown Hindu’, was British but not English, and Nelson (a Scot) said that it was simple – if you’re born and bred in England, you’re English. End of story.  

The video on YouTube got 4 million views. Since then, Suella Braverman has weighed in with her instinct that despite being born and raised in England, she will never be truly English. The debate has generated more heat them light over these past weeks – just read the comments after Nelson-Kisin YouTube video to get the gist.  

Now this is something I've thought about all my life, as it's been a bit of an issue for me.  

I was born in England, have lived most of my life in England, my dad was English, I speak with an English accent, and love it when England beat the Aussies at cricket.  

However, my mum was Irish. She was born and grew up in Limerick, met my dad in Dublin after he had moved to Ireland to train to be a Baptist minister. I never knew my father's family, as his parents had both died before I was born. So, the only family I knew in my childhood were Irish. Family summer holidays were spent in Dublin or most often in County Clare in the wild west of Ireland. Growing up, I felt at home in Bristol where we lived, with my English friends, supporting the mighty Bristol City at Ashton Gate. Yet the place where I felt most secure and rooted, at home in a different way, surrounded by grandparents, aunts, uncles, cousins and people who had known my family for generations, was Ireland.  

While my dad liked football, and we cheered when England won the World Cup in 1966, my mum was a big rugby supporter. So when it came to the Six Nations (or Five Nations as it was in those days) there was no question of who we followed, driving to Cardiff Arms Park or Twickenham, festooned in green scarves, cheering on the boys in green. I still do support Ireland, rooting for Peter O’Mahony and Caelan Doris as well as players in the team less Irish (at least by descent) than me, like New Zealanders James Lowe and Jamison Gibson-Park, the Australian Finlay Bealham, or the very un-Irish sounding, yet hero of the nation, Bundee Aki.  

Of course, my story is far from unique. The Irish diaspora is everywhere. Irish people for centuries have left Ireland to find jobs, to see the world, or like my mum, following a spouse to different shores. There are loads of us, part-Irish, living in England, caught in our nationality somewhere in the middle of the Irish sea. 

So am I English? Or am I Irish? I have held both passports, long before Brexit. I can sing God Save the Queen and Amhrán na bhFiann. The truth is that I'm a bit of both. Sometimes my Englishness comes to the fore, sometimes my Irishness. I remember being at school in the 1970s during the IRA bombing campaign and getting abuse and graffiti on my school locker for being Irish, then spending holidays in Ireland and being teased for sounding English. Such is the fate of the half-breed.  

So for me, and for countless other people who have a mixed heritage, nationality is a complicated thing.  

When nationality becomes the primary location of a person's reason for being, that's when it can become dangerous. 

There are many different factors involved in a person's national allegiance: where they were born, where they grew up, where their parents or ancestors came from, where they decide to settle later in life. It can also be affected by emotions as varied as gratitude for a welcome received or resentment for rejection. Centuries ago, when people didn't travel much, and most didn't travel far from the place where they and their parents were born, the nation states that emerged in Europe and across the world out of the great empires of earlier times were relatively stable entities and could claim a degree of settled character, and a claim to loyalty. The twentieth century, with two world wars fought largely over nationality and race showed us the dark side of absolute loyalty to country or ethnic origins. 

In today's hyper-mobile world, and especially in the UK, which is a magnet for people all over the world, there are probably very few people with simple, pure national heritage. Most of us have some migrant blood in our veins, stemming from some ancestors who moved from their home at some point in the past, seeking a better, or a different life elsewhere.  

Being nationalistic or patriotic by supporting a sports team, learning a language, or being proud of one's origins is a good thing. Life would be a lot poorer without the possibility of rooting for your national team, taking pride in your national culture or history, feeling rooted in a particular place on this good earth. We were made to put down roots in a place, to care for it and take pride in it.  

Yet nationality is too fluid and imprecise a concept to provide a firm sense of identity. When it becomes the primary location of a person's reason for being, that's when it can become dangerous. That's when we begin to fight wars over national sovereignty, identity and superiority.  

Nationality can never become a strong enough centre to unite a people. It’s why the debate on ‘British values’ never quite lands. Even if we could decide what they are, is the implication that they are better than other values? And if they are does that give us the right to feel superior to other nations who don’t share them? And even if we could identify them, I imagine the French, the Germans or the Swedes would probably recognise a lot of them and claim them as their own.  

To have a firm sense of identity, a centre around which to gather, requires a stronger and more unshakable foundation. I may be part English, part Irish, but I am wholly a child of God. Even more deeply rooted than my Irish mother and English father, the place of my birth or my family roots, lies my identity as someone whose true origin comes not from them but from the God who made me, continues to love me, and will hold me until my dying day and beyond. And unlike national identity, this identity can be true of anyone, therefore it’s not something I can ever use as a badge of superiority over anyone else.  

That is who I am. Nothing can disturb or change it. And only something like that – something unshakable, independent of our changeable feelings and shifting allegiances can provide a firm basis for belonging and cohesion.  

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