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.  

Join with us - Behind the Seen

Seen & Unseen is free for everyone and is made possible through the generosity of our amazing community of supporters.

If you’re enjoying Seen & Unseen, would you consider making a gift towards our work?

Alongside other benefits (book discounts etc.), you’ll receive an extra fortnightly email from me sharing what I’m reading and my reflections on the ideas that are shaping our times.

Graham Tomlin

Editor-in-Chief

Review
Art
Culture
Royalty
Weirdness
5 min read

From witchcraft to statecraft: inside the mind of King James

A new exhibition examines art the monarch commissioned and inspired

Susan is a writer specialising in visual arts and contributes to Art Quarterly, The Tablet, Church Times and Discover Britain.

A portrait of King James VI, his eyes fix the viewer.
King James, by an unknown artist.
National Galleries of Scotland.

James IV and I devoted his twenties to trying to rid his kingdom of witchcraft. And 400 years after his death, witches continue to cast a long shadow over his reign. While James’ beliefs on evil developed and refined over his 58-year reign, his reputation as solely a torture and femicide perpetrator remains stubbornly hard to shift. For many, identification with the abused, marginalised- yet- magical trumps all other historical considerations. 

In the exhibition World of James VI and I, the National Gallery of Scotland presents a more rounded picture of the cradle king, who gained the throne of Scotland at 13 months old and became the first joint monarch of Scotland and England in 1603, on the death of Elizabeth I. The beginning of James’ reign in England saw the first productions of Shakespeare’s Macbeth, King Lear and The Tempest. Inigo Jones’ appointment as Surveyor of the King’s Work introduced the classical architecture of Rome to the country, designing The Queen’s House in Greenwich and the Banqueting House at Whitehall. 

The painted ceiling of the Banqueting House by Peter Paul Rubens provides insight into James’ preoccupations. Commissioned by James in 1621, the tennis court sized series was installed in 1636 becoming a memorial to the late King. In The Apotheosis of James I, the King is depicted ascending into heaven on a giant eagle belonging to Jupiter, ruler of the Roman gods. The winged figure of Victory, together with a figure representing Great Britain hold a laurel wreath above the King’s head, in exchange for his earthly crown. Parallels between the King and divine power are explicit, underlined by the figure of Religion holding the freshly translated Bible showing the first words of St John’s gospel ‘In the beginning’ (was the Word). In a side panel to The Union of the Crowns, where the King is presented in a Biblical setting, Minerva, goddess of wisdom is stamping on Ignorance, represented by an old woman, naked and floored. 

Rubens’ identification of an old woman as low status and powerless did not come out of thin air. In the social hierarchy of seventeenth century northern Europe, most ordinary people had few rights and women had next to none, entitled only to the legal protection of their husband’s rank. But lack of rights did not prevent women from influencing their communities’ moral tone. The victims of the infamous East Berwick witch trials in 1590-92 and Pendle witch trials in 1612, first came to the attention of authority through accusations and feuds within their own communities. 

Daemonologie, published in Edinburgh in 1597, was written following James perceived experiences of witchcraft when storms imperilled his voyage from Denmark to Scotland, returning with his new 15-year-old bride Anne. It is believed the King was involved in interrogations of witchcraft suspects in East Berwick, authorising their torture and execution. One suspect’s ability to recount a conversation from the royal bridal chamber, convinced James the accused were the tools of diabolical powers intent on killing the royal couple. Beliefs around women’s inherent weakness, positioned them as easier prey for malevolent forces:  

‘sexe is frailer than man is, so is easier to be intrapped in these grosse snares of the Devill’ 

In later life James became more sceptical about claims of witchcraft and demonic possession, and searched for evidence to discount what was only the work of fantasy and attention-seeking. 

But the King’s family history and tumultuous times he lived through, made the road to discernment a long and winding one. James last saw his mother, Mary Queen of Scots as an 11-month-old infant. His father Lord Darnley was killed in a mysterious explosion, possibly arranged by his own wife. Mary was imprisoned in England by Elizabeth I and executed in 1587 at Fotheringhay Castle in Northamptonshire. In the lead up to his marriage James lamented that as a child he was ‘alone, without father, mother, brother or sister.’ 

The normalcy of removing troublesome relatives is illustrated by a 1605 portrait of Lady Arabella Stuart, attributed to Robert Peake the Elder. The King’s cousin died in the Tower in 1615, where James had her imprisoned, in case her marriage to William Seymour gave her too strong a claim on the throne. 

Today’s witches on Etsy may feel they are reclaiming a lineage of folk wisdom and reparation for past wrongs. But willingly stepping into the scapegoat role...  has no historical precedent.

Death also stalked James and Anne’s family, with only two out of their seven children surviving into adulthood. Their eldest son and heir Prince Henry Frederick died aged 18, and was mourned throughout Europe in the decades that followed the death in 1612, as he was seen as the great hope of the continent’s future.  

The World of King James VI and I is full of visual meditations on death. On entering visitors are greeted with Livinius de Vogalaare’s The Memorial of Lord Darnley, 1567, a substantial canvas, with a crowned, grey-robed infant James, kneeling before his father’s coffin. Darnley’s effigy with hands in prayer lies on top the casket, unicorns either side of his head. An engraving of Prince Henry Frederick’s Hearse, 1640 copy from 1612 original, shows the richly decorated hearse, complete with a wax effigy dressed in the prince’s clothes, which was accompanied by 2000 mourners as it made its way to Westminster Abbey. Eighteenth century artist James Mynde’s engraving The Mausoleum of James VI and I, illustrates the Jacobean era’s fondness for lavishly dressed effigies of the deceased, surrounded by figures of classical deities. 

Charm stones, believed to cure sickness in people and animals, formed part of James’ cosmology, together with the new translation of the Bible he commissioned, intended to sound beautiful for this age of oracy. James advocated for Protestantism and the reformation, while being in regular communication with the Papacy. He also brought a more English style of worship to the independent-minded Scottish kirk, insisting they used chalices and altar cloths. The monarch was devout, yet flexible, in his Christian beliefs. 

A simple reading of the Jacobean court is not possible. It was a place of ritualised gift-giving, with ciphered and initialled jewels indicating who was in or out of favour, whose power was rising, and whose power was waning. James believed he was sent by God to rule and protect his people, and felt justified in extinguishing anyone or anything threatening his divine project. Self -proclaimed, or community-nominated witches provided useful scapegoats for discontent around James’ rule, underlined in 1605 by the Gunpowder Plot. 

Today’s witches on Etsy may feel they are reclaiming a lineage of folk wisdom and reparation for past wrongs. But willingly stepping into the scapegoat role and presenting a blank screen for the dark projections of the powerful, has no historical precedent for bringing liberty or social transformation. Cos-playing the historically marginalised will not make things better for today’s excluded and underserved, but focusing on down to earth, earthly political and economic power will. 

 

The World of James I and VI, National Galleries of Scotland, until 14 September.