Explainer
Biology
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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
Creed
Death & life
Monsters
Paganism
5 min read

Will the owner of ‘Halloween’ please come and collect it?

A mutant festival of saints, spirits, and supermarket costumes resists belonging to anyone
A witch, a priest and a druid stand in a store and look quizzically towards a halloween pumpkin
Nick Jones, Midjourney.ai

The trouble with modern Halloween is that it’s hard to say who it really belongs to. Our contemporary public holiday – 31 October, when people dress up as skeletons, light jack-o-lanterns, and go ‘trick-or-treating’ – has a few prospective owners.  

Perhaps Christians could claim it. The term “Halloween” is a shortening of ‘All Hallow’s Eve’, which is the day before All Saint’s Day (1 November) in the Church calendar.  

But this doesn’t fit with a few things. Don’t Christians dislike all that dressing up as evil spirits, and summoning up misrule and revelry? Instead, the case is made for a pagan ownership of Halloween: it was all due to a Celtic festival called Samhain (pronounced ‘sow-in’). This was a day for appeasing evil spirits, contacting the dead, and acts of mischief – all better fits for modern Halloween, surely? 

Sadly, we just don’t know enough about Samhain to say. We only have evidence about it from centuries after the Christian era, and in limited scraps like: “Samhain, when the summer goes to its rest”. It is unlikely the Christians invented this, to be sure – but none of the data tells us how it was celebrated.  

In fact, there is no evidence at all that All Saints Day was a churchy attempt to ‘take over’ a pre-existing pagan festival. From the get-go, Christians commemorated their dead on the basis that they were still alive in heaven, and able to bring prayers to God. A quick peek at the Book of Revelation (the final book of the Bible) gives a behind-the-curtain look: “and the smoke of the incense, with the prayers of the saints, rose before God from the hand of the angel”.  

Over time, it became more official which ‘holy ones’, or saints, should be honoured at which times. This was not about making dead Christians into gods, though. A famous theologian called St Augustine explains the proper view of the early Christians as they kept hold of bones and clothing from their dead: “We do not build temples, and ordain priests, rites, and sacrifices for these same martyrs; for they are not our gods, but their God is our God”.  

Gradually, a date was set to celebrate all those great men and women in heaven – from this came All Saints, or All Hallows Day. A tradition in northern Europe set this on the 1 November: “As a jewel worn on the brow sparkles time and again, so November at its beginning is resplendent with the praise given to all the saints” reports an English calendar from around 800AD.  

It is all well and good celebrating those who have made it to heaven. But what about the majority of Christians? Those who had died unrepentant and lukewarm – what on earth could be done for them? Here came another separate development: offering prayers and worship on behalf of those who had died as forgiven sinners, but who were still, if you like, serving their time for their bad choices.  

It gradually became the norm to tack that practice onto the pre-existing All Saints Day, so that the souls of regular Joes could have powerful heavenly intercessors close by. And so, All Souls Day became an established part of the Church’s year too, falling on 2 November.  

 

But here’s the twist. This season of ‘Hallowtide’ (All Saints and All Souls together) carried on for centuries, until England suddenly and violently abandoned it all in the sixteenth century. Seemingly overnight, the Reformations of the Tudor monarchs ended All Souls Day by scrapping all mention of a purgatory for the dead, and attempts to pray for them there. All Saints Day limped on in the new Established Religion as a remembrance of Christian exemplars – but they were not to be thought of as in radio contact from heaven anymore.  

Some people tried to carry on as usual, in illicit gatherings on hilltops, where they would burn straw, and gather to ask for help from great saints and pray for loved ones. But the majority followed the new religious settlement and tried to forge new communal rituals as best they could. The night still had a ‘supernatural’ afterglow thanks to centuries of the now-absent All Saints and All Souls. 

Then, in the nineteenth century, there was a comeback. Irish immigration to the USA and Great Britain plonked a fully formed Hallowtide into English-speaking culture again. It took like a duck to water. Perhaps this was to be expected. Here was a civilisation which had been rapidly deprived of its ordinary way of expressing connection to their deceased loved ones, as well as a sense of protection from heavenly guardians. They were clearly starving for some way to communicate feelings about ‘the beyond’, and to find hope in the darkening, colder days.  

‘Halloween’, really a modern döppleganger of All Hallow’s Eve, quickly became a popular national custom – a world custom, indeed, due to US influence. It took from Christianity that otherwordly atmosphere – but it did not jettison any of the customs that had arisen since the Reformation, and which were themselves continuations of folky responses to the coming of Winter; Samhain is almost certainly a part of that background here, even if it is not a direct connection, as we have seen. 

This Halloween mystery has a twist, then. Here is really a mutant of a festival that belongs to no one in particular - and that is the point. One could really call it one of modern pluralistic society’s great achievements. It has taken over management of this eerie season from the church, and arguably made a successful shared custom out of it. On the other hand, it is arguably consumeristic, tacky and frequently immoral: it was only a few years ago that supermarket costumes allowing people to dress as ‘mentally ill’ showcased this shallowness. 

So, as a Christian, I have some regrets that Christianity does not really ‘own’ modern Halloween, anymore. Because the original All Hallows, as well as All Souls, seem to me to be a historic high point of confidence about our human fate. Here was a whole civilisation that seemed to announce to itself, every November, that death, human wickedness, and the Devil, were not in charge here – those who had died in Christ were now more fully alive; that no one is so beyond hope that they are not worth praying for. The darkening nights and colder air must have seemed less daunting to them.  

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