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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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Why we should mourn the death of the semi-colon

In our busy, frenetic lives, we need that small pause more than ever.

Paul is a pioneer minister, writer and researcher based in Poole, Dorset.

A woman stands across a busy roads, looking up from her phone in a sad way.
Su San Lee on Unsplash.

In the morning news; a headline about the decline of a species. Thankfully not a rare rhino or butterfly this time. It’s a punctuation mark. The semi-colon is an increasingly endangered creature. According to recent research it has declined in use by 50 per cent in the past two decades. This on top of a 70 per cent slide in usage between 1800 and 2000. Further research suggests that 67 per cent of students rarely use it and over 50 per cent wouldn’t know how to anyway. 

I’m kind of indifferent on the merits or otherwise of the semi-colon. But I at least appreciate the option. So, its value feels worth defending. Who knows what unintended consequences in the ecology of language might occur if we lost it all together?  

The semi-colon was invented in the 15th century by a scholar and printer Aldus Pius Manutius the Elder (whose name might have benefited from a semicolon itself). A hybrid between a comma and a colon, the semi-colon invites a pause; it’s a moment to breathe. And it opens enough space to reflect on what might be being said between what went before and what comes after. It signals a kind of meaning in the gap. It creates a hint of resonance beyond the plain meaning of the words of a sentence.  

Despite its enthusiastic use by the likes of no less than Jane Austen and Charles Dickens it has certainly come in for some stick over the years. Kurt Vonnegut famously said of semi-colons ‘all they do is show you’ve been to college.’  Who knew two marks on a page could signal such elitism? The semi-colon says, ‘you're trying too hard’. Or it might just say, ‘why did you do that?’, since so many people fail to understand what it represents. Novelist John Irvine reckoned readers ‘think the author has killed a fruit fly directly above a comma’. 

So what is killing off the semi-colon? Well, if the statistics above are to be believed it could be as simple as a decreasing understanding on how to use it. Though of course there are feedback loops here. We learn grammar and punctuation as much by reading as by being taught. Others point the finger at the breathless world of social media. As more and more of our communication is constrained by space and time, the semi-colon’s quiet request for a pause for consideration is being largely ignored.  

We need semi-colons if our lives are to be more than just an incessant flow of connected moments .

If this is the case then the semi-colon is another species within a kind of mass extinction which is the result of the great acceleration of our age, alongside the coffee break, lunch break, walk round the block and long stare out of the window. These are simply things that we don’t have time for anymore; we wonder if they had any value in the first place. The semi-colon is largely being replaced by the dash. Which is pretty ironic when you think about it.  

Perhaps concern over the loss of this little mark is in an awareness that it’s a kind of canary in the gold mine of our culture of acceleration. The loss of the semi-colon is a sign of the loss of something far more significant: the rhythms and cadences of our lives that afford pause, reflection; that open up the kind of spaces where creativity; meaning; imagination; spirituality happen. 

The semi-colon reminds me, strangely, of the Hebrew psalms. The monastic tradition includes regular communal singing (or saying) of the psalms. Typically, these poems, which formed such a key part of Hebrew worship, work on the basis of what is known as parallelism. Essentially each thought in a psalm is composed as a sentence in two lines. The two halves of these sentences are parallel, in the sense that they both make statements about the same thing. Sometimes these statements say the same thing differently. Sometimes one half of the sentence builds on another. There are endless creative ways in which the psalmists use this simple device.  

When psalms are used in prayer or worship parallelism is often observed by introducing a pause at the end of the first half of the sentence. It's an odd tradition if you are not used to it. An established monastic community naturally feels the length of pause together. Visitors to a service in a monastery often end up coming in early.  

Yet, with time you begin to realise these pauses are a wonderful thing. The pauses create a rhythm and time signature that invites reflection. The pause says ‘take your time, there’s a lot of meaning here in all these similes and metaphors, what might they mean to you?’ Perhaps even ‘what, in this moment to breathe, might God be saying to you?’ 

There’s a feeling for so many of us that life is starting to feel a bit like the final chapter of James Joyces’ Ulysses: devoid of punctuation. We need semi-colons if our lives are to be more than just an incessant flow of connected moments. And we need to learn how to use them. We need practices that make space for the undervalued attributes of reflection, daydreaming, prayer. In that sense saying the psalms may be a practice worth giving time to. 

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