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
Art
Character
Culture
Faith
5 min read

Inside the minds of Siena’s finest artists

To exhibit art from a golden age, it first needs to survive.

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

A split wooden sculpted head stands in an exhibition.
Lando di Pietro's carving from 1388.

Curating an art exhibition about the emergence of recognisably life like painting and sculpture, pre-supposes just one thing. That the once innovative and venerated art works survive to today, even if shorn of their original, usually religious, settings. Those that made it to the National Gallery’s Siena: The Rise of Painting 1300-1350 have some tales to tell. That give us insight into their creators and their beliefs. 

A cracked skull is sadly not an unusual find in the aftermath of an explosion. But the head discovered in the rubble of a Siena church following a World War Two Allied bombing raid in 1944 was remarkable. Almost life-sized, made of walnut and depicting Christ’s face, the carving had originally been part of the figure on a crucifix, but now severed from its body, the head was almost sheered in two. From this destruction spilled more secrets.  

Hidden inside the skull, its creator Lando di Pietro inserted parchment with personal prayers. What little documentation we have about 14th century artists is usually public: contracts, lawsuits and wills, but these two scraps of writing represented Pietro’s personal faith. He dramatically asserted himself as the creator of the work: 

“Lord God made it possible for Lando di Pietro of Siena to sculpt this cross from wood in the likeness of the true Jesus Christ to recall for people the Passion of Jesus Christ…have mercy on all generations”  

And Lando also prayed for good health and for the world. 

The fragment of a crucifix dating from 1338, is the only surviving example of wooden sculpture by this renowned goldsmith and architect, one of the Trecento creators on display at Siena: The Rise of Painting 1300-1350. In the hothouse of creativity that was the Tuscan town in the first half of the 14th century, goldsmiths collaborated with sculptors and painters, and the images they collectively created inspired manuscript illuminators, whose works, passing through many hands, went on to inspire other artists. 

Siena’s position on the Via Francigena, the major pilgrim route between northern Europe and Rome, ensured the city’s artistic innovations spread to Britain and eastern Europe and beyond. And Sienese painter Simone Martini’s patronage by cardinals and members of the Papal curia in the Pope’s court at Avignon, showcased the techniques, materials and styles of Siena to influential church leaders and royal courts throughout the Catholic communion. Interconnected through marriage and diplomacy, the courts of northern Europe would have diffused Sienese style through the exchange of gifts, and hosting and commissioning peripatetic artists from the city. 

The portability of devotional objects also spread the developments of Siena’s more naturalistic and emotional style, way beyond the city’s boundaries. 

Decorative crosiers would have been in motion during processions, and the sculptural decoration contained in their curved tops were viewed in the round. On the Master of San Galgano Crosier, about 1315-20, the cast figure of the saint kneels in front of his makeshift cross. St Galgano’s praying hands and bent elbows form a perfect line with the sheathed sword, that the twelfth century knight miraculously drove into a rock. The Abbey of San Galgano grew up near the site of the miracle, and the intricately decorated reliquary containing the saint’s head is faithfully reproduced in enamel at the top of the staff.    

Simone Martini’s Orsini Polyptych, dating from around 1310, can be understood as a freestanding, miniature, double sided altarpiece, depicting a silent Annunciation on one side, and a tumultuous Passion cycle on the other. The polyptych’s probable patron, Cardinal Napoleone Orsini is portrayed at the foot of the cross in the Deposition. Fully closed for transportation, the eight panels resemble a block of marble encased in gold. With the outer wings closed, the marble ‘covers’ become a setting for an Annunciation diptych. Fully opened, the panels tell the Passion, story Christ’s torture and death.  

Originally the panels were likely hinged together, so the work could fold like a concertina. After a period at the Papal curio in Avignon, the panels were separated centuries ago. Seeing the panels individually lost the tangibility of the object’s manipulation of space, through folding and portability. Seeing them united in the National Gallery for the first time in centuries is incredibly moving. 

An early fifteenth century French prayer book The Belles Heures of Jean de France, Duc de Berry, has a Lamentation scene sharing many motifs with the Orsini Polyptych, including the woman tearing at her hair, Saint John the Evangelist covering his eyes, and the back view of Mary Magdalene crouching over Christ’s feet. Within a hundred years, the Sienese emphasis on human emotion and portraying figures in recognisably three-dimensional space, had rippled out to other art forms and other countries.  

One of Britain’s medieval treasures, the Wilton Diptych, commissioned by Richard II about a decade earlier than Berry book of hours, also reveals the influence of Siena: from the king’s animated pose kneeling before the Virgin and Child, to the egg tempera paint, and gold leaf sgraffito, where the surface is scratched away to depict sumptuous textiles. 

In an exhibition full of showstoppers, the unification of the back predella (altarpiece base) of Duccio’s Maestra altarpiece is a standout moment. Installed in Siena Cathedral in 1311, Maestra has the oldest surviving narrative predella. On the front, depicting the Virgin Mary at the centre of a heavenly court, the painter had included his signature and a prayer. 

“Holy Mother of God, bring peace to Siena, and bring life to Duccio who painted you like this.”  

While the front image of the heavenly court would have been viewed from afar, the congregation could move close to the back predella and view a sequence of panels on Christ’s teaching and miracles as they prayed.  

In 1771 the Maestra was sawn in half, and the predella dismantled. Its individual scenes were dismantled and displayed, and then sold, separately. The eight surviving panels are reunited in the National Gallery for the first time in 250 years. 

The Black Death struck Siena in 1348, killing up to half its population, including many artists. Over centuries, plague, war, differences of religious doctrine, and fashion for Grand Tour mementoes, saw objects dismembered and repurposed. Yet the emotional resonance of maternal love seen in Ambrogio Lorenzetti’s Madonna del Latte, c.1325 or the humanising family drama of Simone’s last surviving work, Christ Discovered in the Temple, 1342, could never be undone. Art grounded in human emotions and human perceptions of the spaces around us, was here to stay, 

The wartime work of the Monuments, Fine Arts, and Archives (MFAA) unit in preserving treasures such as the Head of Christ found in the ruins of the Basilica di San Bernadino all’Osservanza, was dramatised in George Clooney’s 2014 film Monuments Men. Creativity’s boundless resistance to the forces of destruction will always be box office.  

  

Siena: The Rise of Painting 1300 -1350 National Gallery, until 22 June. 

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