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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Review
Books
Culture
Language
Romance
6 min read

Jane Austen‘s most excellent fan club

The very fine authors who draw inspiration from Jane.

Beatrice writes on literature, religion, the arts, and the family. Her published work can be found here

A book cover with a handwritten title that reads: Jane Austen volume the first
Paolo Chiabrando on Unsplash.

250 years after Jane Austen’s birth, her stories are still an incredibly significant part of our culture. The annual Jane Austen Festival in Bath is gearing up to be bigger than ever; Winchester Cathedral is set to unveil a new statue of Austen later this year; and – perhaps most controversially – Netflix has announced yet another adaptation of Pride and Prejudice.  

Historically, there’s been an overwhelming focus on two elements of Austen’s writing: the Regency setting, and the romance plots. There’s nothing inherently wrong with enjoying these two aspects of her novels. I know I do. But this comes at the risk of underestimating the richness of Austen’s literary legacy. The internet is littered with listicles and blog posts in the format of ‘What to Read Next If You Love Jane Austen.’ Some of these lists will point you to other nineteenth-century literary classics. Others will home in on the romance element, recommending Helen Fielding’s wildly successful Bridget Jones’s Diary, Georgette Heyer’s Regency romances, or even Julia Quinn’s Bridgerton series.  

I’d like to share with you an alternative and more eclectic list of books that I’ve fallen in love with as a lifelong Austen fan. Only one of these books is set in the Regency era; some have a romance as a major part of the plot, others don’t; some share Austen’s realistic writing style, one borders on magical realism. But I think each of these novels or authors brings out a fascinating and often overlooked aspect of Austen’s literary inheritance.  

Anne Brontë’s The Tenant of Wildfell Hall (1848) 

Austen is regularly compared to Charlotte Brontë, who famously wrote Jane Eyre, but I think her younger sister Anne is a fairer comparison. Writing only a few decades after Austen’s death in 1817, Brontë’s style is closer to Austen’s realism than to her own sister Charlotte’s use of gothic tropes and supernatural themes. Like Austen, in The Tenant of Wildfell Hall – as well as in her other novel, Agnes Grey – she focuses on simple language and engaging dialogue. Austen and Brontë also share a deep concern for female education. In several of her novels, notably Pride and Prejudice and Emma, Austen critiques the reality that many young women from middle-class and upper-class families were being taught to value ‘accomplishments’ like dancing and singing over any other form of education, with the aim of attracting a rich husband. Similarly, in The Tenant of Wildfell Hall Brontë’s heroine Helen criticises society’s belief that boys and girls should be educated differently, with boys being taught about the dangers and vices of the world, and girls being kept in ignorance of them. Helen thinks that this attitude makes girls more vulnerable to suffering and disappointment; I suspect Austen would have agreed. 

Barbara Pym’s Excellent Women (1952) 

Now somewhat forgotten, many of Pym’s stories are considered ‘novels of manners’, that is, novels that detail the costumes and values of a particular sphere of society at a particular time in history: in Austen’s case, the middle and upper classes in Regency England; in Pym’s case, the parishioners of a typical Anglican community in post-World War II London. Like Austen, Pym’s writing style is incredibly witty, and both writers favour everyday stories about ordinary people. In fact, Pym took the title Excellent Women from a phrase used by Austen in her unfinished novel Sanditon. These so-called ‘excellent women’ perform seemingly unheroic, small duties for others, the kind that may well go unnoticed, but which are often indispensable in small communities. In Pym’s novel, the first-person narrator, Mildred Lathbury, spends her life between working at a charitable organisation and helping and helping the priest at her local Anglican church. Mildred’s work is often taken for granted, much like the heroine of Austen’s Persuasion, Anne Eliot, whose family are remarkably ungrateful for all the ways in which she eases their burdens. Novels like Pym’s rightly celebrate the quiet bravery of the women who devote their lives to serving others.  

P. D. James’ Death Comes to Pemberley (2011) 

Detective fiction is not the first thing that crosses my mind when I think about Jane Austen. And yet, in a 1998 talk to the Jane Austen Society titled ‘Emma Considered as a Detective Story’, novelist P. D. James made a compelling case that Austen should be considered a precursor to the genre. James argued that a detective novel isn’t defined by the discovery of a murder (nobody dies in Dorothy Sayers’ acclaimed Gaudy Night, for example), but by the unveiling of a mystery. In Emma, Austen scatters clues for us readers along the way but withholds enough information as to keep us – and Emma herself – in the dark. When it’s revealed that Jane Fairfax and Frank Churchill have been lying to hide their secret engagement for the entirety of the novel’s timeline, Emma realises how much she’s been deceived, and it’s this theme of deception that really links Austen’s novel to the detective genre. Yeas after her talk, James ended up writing a detective fiction sequel to a different Austen novel, Pride and Prejudice. Death Comes to Pemberley takes place six years after Elizabeth Bennet and Mr. Darcy’s wedding. A man is found dead on the grounds of Pemberley and Mr. Wickham is the prime suspect. I won’t say any more. It’s my favourite retelling of an Austen novel. 

Kazuo Ishiguro’s The Buried Giant (2015) 

The Buried Giant tells the tale of a Briton couple, Axl and Beatrice, as they set out on a quest to find their long-lost son in a post-Arthurian England where people struggle with the loss of long-term memories. Ishiguro blends a very realistic portrayal of the relationship between a married couple with magical elements such as the presence of a dragon whose breath causes forgetfulness. On paper, this is also not an obvious recommendation, yet memory is a crucial theme for Austen. Persuasion is centred around Anne Eliot’s memories of her broken engagement to Captain Wentworth, which simultaneously bring her happiness and suffering. Mansfield Park’s heroine, Fanny Price, has an equally complex relationship with her past. She often she misses her childhood home, yet part of her is glad that she was taken to be raised by the Bertram family at Mansfield Park, a place which she loves in spite of painful memories of being mistreated by her Aunt Norris. Fanny thinks of memory as the most wonderful faculty of human nature, as it can be at times incredibly ‘retentive’, at others ‘bewildered’ and beyond our control. Ishiguro would surely agree, as that’s precisely what The Buried Giant is about: the ways in which memory can both fail us and yet give us hope, recall suffering and yet brings us closer to those we love. 

 It’s hard to overestimate Austen’s impact on the literary world. And while she’s sparked a revival in literature set in the Regency era, it’s also fascinating to see how she’s influenced writers working in seemingly very different genres from her. Anne Brontë’s novels may be darker in tone, but they show very similar concerns to Austen’s, especially when it comes to virtue and education. Barbara Pym wrote Excellent Women over a century after Austen’s death, yet shared Austen’s interest in highlighting the joys and sorrows of ordinary life. P. D. James found inspiration in Austen despite her own background being in detective fiction. And Ishiguro, despite writing novels ranging from dystopian science fiction to magical realism, has mentioned Austen as an inspiration.  

If you’ve already read all of Austen’s novels, read them again – no one writes quite like her. But once you’ve reread them all, why not try one of these novels next? They may illuminate a side of Austen’s writing that you’ve missed before. 

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