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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Explainer
Christmas culture
Culture
Middle East
7 min read

The mysterious Magi: outsiders, outlandish, Uyghur?

Many claimed the Wise Men, wherever the story was heard.

Benjamin is a DPhil student in the Faculty of History at the University of Oxford. He is researching the experience of Christian communities in medieval Central Asia.

Silhouttes of three wise men approach the Virgin and Child, painted on stone.
The Magi, Catacombs of Priscilla, 250AD.
Public Domain.

Our nativities are full of familiar figures. Mary and the angel Gabriel, Joseph and the landlords of Bethlehem (of varying hospitality), the shepherds above the town and the heavenly host. Finally, there come the three gift-bearers. While familiar, these perhaps remain the most mysterious guests at the manger. Are they three kings? ‘Wise men’? ‘Magi’? What indeed is a ‘magi’?  

Most of the features of our nativity come from the first two chapters of Luke’s gospel, but the magi (along with their counterpart, King Herod) are the primary contribution of Matthew’s gospel, appearing in the second chapter. The word used in Matthew is magi (magoi), a term that was often used for the priests of the Persian religion, today known as Zoroastrianism but in Antiquity known to outsiders simply as ‘magianism’.  However, in the gospel it is perhaps intended to carry less specific meaning, instead indicating more broadly those learned in esoteric knowledge, hence our common translation of ‘wise men’. We might be reminded of the class of experts who Nebuchadnezzar summoned to help interpret his dreams, over whom he promoted Daniel to be chief. These were people both knowledgeable and practiced in observing the patterns of nature, experts in hidden knowledge and science, propitiating and interpreting the divine, ‘magic’, alchemy, and astrology. Indeed, this is where we get our word magic from. It is someone of this kind who is intended by the other use of ‘magic’ in the New Testament, when in the book of Acts Simon the ‘magi’, having believed and been baptised, asks to buy the power of the Holy Spirit from Peter and John. Whichever definition is intended in Matthew, these are unexpected guests in Bethlehem.  

We learn very little further about them besides that they came from ‘the east’, to which they return as mysteriously as they arrived. Might they perhaps have been from one of the neighbouring eastern states that lay just outside the borders of the Roman Empire, such as Osroene, Adiabene, or Armenia, or even from the great Persian Parthian Empire? Parthia and its provinces were named specifically in the Book of Acts, but Matthew’s is a far more ambiguous reference. Indeed, many scholars would question the historicity of the episode of the magi’s visit, seemingly unrooted in time and place in contrast to the historical and geographical grounding of the rest of the gospels, and so clearly serving as a fulfilment of prophecy about the messiah. The old song of Psalm 72 says: “May the kings of Tarshish and of distant shores bring tribute to him. May the kings of Sheba and Seba present him gifts. May all kings bow down to him and all nations serve him.” Elswhere the book of Isaiah records: “The nations will come to your light, Kings to the brightness of your dawn… young camels will come bearing gold and incense, proclaiming the praise of the Lord.” When you see the gift-bearing magi represented as camel-riding kings on your Christmas cards, they are being shown as the fulfilment of these prophecies.  

Christians in medieval Europe were dimly aware of just how widespread Christianity was, and they represented this in their stories about the magi.

What is crucially important in their role as prophecy-fulfillers is that they are gentiles. Indeed, they are the first of those outside of God’s chosen people to recognise the Messiah. While Luke shows Jesus announced to the poor and humble among the Jews, rather than the priestly or royal, Matthew shows him recognised by the gentiles, the first trickle of a mighty torrent prophesied throughout the Old Testament: “All the nations you have made will come and worship before you, Lord,” sings the Psalmist. “In the last days the mountain of the Lord’s temple will be established… and all nations will stream to it,” records Isaiah once more. This is echoed also in Micah, the book quoted in Matthew by the chief priests to the magi: “The mountain of the Lord’s temple will be established, and many nations will come and say – let us go up to the mountain of the Lord.” These were outlandish claims and the magi represented the outlandish start of their fulfilment.  

Nevertheless, the magi in Matthew don’t float entirely untethered from historical reality, as they act out a story within the solidly historical setting of Herod’s final paranoia. His anxiety about the title ‘king of the Jews’, and his desperate massacre of the innocents both fit with what we know of his last days. For Herod, an Idumean (or Edomite), his questionable Jewishness had been a source of anxiety throughout his life, and he had become deeply unpopular by the end of his life, perceived as far too close to the Romans. Some scholars have suggested that Herod would have found fewer than a dozen infant boys around Bethlehem, as such it is unsurprising that his order is otherwise absent from the historical record. One of the few authors to cover this place and time was Josephus but writing almost a century later, he is much hazier on this period. He does, however, note that at this time Herod’s paranoia had driven him to kill three of his own sons, including his heir, historically much more significant and shocking. Josephus also claims, that on his deathbed Herod gave orders to have all the principal men of the entire Jewish nation killed when he died, to increase the mourning of the people, orders which were not carried out. 

That one day people of all nations and tongues would come to worship the God of Israel is one of the more outlandish claims recorded in the Old Testament. Even for early Christians, who were more actively seeking its fulfilment, it must have remained somewhat unimaginable, given they were still a minority in a corner of the Roman and Persian Empires who knew very well that human societies stretched on beyond their known horizons. By the Middle Ages, it was appearing a lot less outlandish. There were now Christians as far flung as Iceland, China, and Ethiopia. Christians in medieval Europe were dimly aware of just how widespread Christianity was, and they represented this in their stories about the magi. They imagined them as three kings (echoing prophecy and expounding scripture) from the three ‘petals’ of the world which connected at Jerusalem, representatives of the many gentile nations who would embrace the gospel. One for Europe, one for Asia, one for Africa; even in medieval Europe the church was understood as encompassing all three, and the magi were the first indication that it would.   

In Asia, ‘east’ of Jerusalem, the magi assumed different significance. Whether in Persia or China, claims were frequently made that the magi had come from their own place or people. Among the Christians of Mesopotamia (covering present-day Iraq and parts of Syria and Turkey), where Christianity had first arrived under the Parthian Empire, various legends were written about them in Syriac (a dialect of Aramaic). Here they often numbered twelve and were claimed as the founders of various churches and villages. Further east, and later, in the thirteenth century, an Armenian Christian lord, Smbat Sparapet, recorded in a letter that, while travelling across the Mongol Empire and visiting Christians in Central Asia and China, he had noticed they all decorated their churches with images of the magi. He recorded that the magi were believed to have originally come from China, from the region corresponding to present-day Gansu province. His brother, the Armenian king of Cilicia (south-east Turkey), who later made the same journey alternatively recorded that the magi had rather come from among the Uyghurs.  

The Turfan Oasis, lying to the north of the great Taklamakan desert in today’s Xinjiang province in China, also known as the Uyghur Autonomous Region, was home to a community of Uyghur Christians between at least the eighth to fourteenth centuries. One of the few surviving indications of their presence is a large collection of fragmentary manuscripts, preserved by the dry desert conditions. Among these is a unique legend concerning the magi, originally written in Syriac, but here translated into Uyghur. It preserves the account from Matthew but with some additions. For instance, the identification of the magi with the Zoroastrian priesthood is made explicit, probably owing to the original Syriac authors’ own familiarity living among the ‘magians’ of Mesopotamia. Most striking of all though is the word choice of the Uyghur translator. Approaching the infant Jesus, the magi hail him as ‘Khan Messiah, the son of Tengri.’ The magi’s royal gift of gold recognises Jesus as ‘khan’, a straightforward translation of ‘lord’ but one which carries local cultural resonance. Tengri, however, was the high God of the Uyghurs and Mongols. He was the creator, present everywhere, but associated particularly with the heavens. To see Tengri in Jesus was to see the mighty God who forged their own sky and steppe come to earth as infant and man.  

The popular legend that the magi had come from among the Uyghurs, which perhaps motivated this translation, connected their immediate reality to the distant settings of the gospel stories. Like the legends of the medieval west, this too served to communicate the truth that in the recognition of Jesus by the first gentiles, the magi, could be seen the start of the gospel’s journey to all gentiles, all nations, tongues, and petals.  

This Christmas, when you see the magi on your cards and in your nativity scenes, or you sing carols about three kings, think about the deep traditions that have formed these images, representations of prophecies fulfilled in Jesus, of the inclusion in the kingdom of all nations and of you too. 

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