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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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Column
Comment
Ethics
Football
Politics
5 min read

PSG’s win signals politics over purpose – other institutions take note

When church and football feign neutrality, politics can ride roughshod
A footballer holds up the European cup, behind him fans are jubillant.
PSG fans celeberate.
PSG.TV.

There’s a new name on the Champions League trophy.  

In the most one-sided final in the competition’s history, Paris Saint-Germain trounced Inter Milan 5-0 to lift Europe’s most prestigious club trophy for the first time in their history. 

But this is not the PSG of recent years. Gone are the Galacticos: no Messi, no Neymar, no Mbappe. Where previously PSG resembled a 13-year-old boy’s attempt to win Football Manager by just buying all the best players, this year’s team looks like … well, a team. 

And what a team. Vitinha is metronomic in midfield. The game is played at his pace. He is the jazz instructor in Whiplash. “Not my tempo,” he says, over and over again, until reality bends to his will. Hakimi and Mendes are boundless balls of energy as the two wing-backs. They always threaten and it is no surprise that Hakimi gets the first goal. 

And then there are the forwards. 19-year-old Désiré Doué somehow looks the consummate professional at such a young age. Ousmane Dembélé has a quiet night by his standards, but the Barcelona reject looks born to play for this team. Khvicha Kvaratskhelia is the kind of footballer you imagine yourself as when playing on school playgrounds. So unorthodox, but simply irresistible. The ultimate jumpers-for-goalposts footballer. He may well be the closest thing football has to a personification of what the sport is all about. He is joy and flare masquerading as a 24-year-old Georgian lad. 

At the helm of it all is Luis Enrique. Enrique’s teams are aggressive, fluid, and intelligent. “They pass forward with spite” Steven Gerrard says during the TV coverage of the match. What a line.  

In 2019, Enrique lost his youngest daughter Xana to bone cancer, aged just nine. To hear him talk about his loss is heartbreaking. At full-time the PSG fans unveil a picture of Xana with her dad in a genuinely tender moment of compassion and humanity. 

All this is to say that, wherever you look, this incarnation of PSG is a deeply, deeply likeable one.  

But then, that’s the point, isn’t it? 

PSG were taken over by Qatar Sports Investments in 2011. Qatar’s near 15-year involvement with the club has led to eye-watering sums of money being spent with the stated aim of winning the Champions League. In 2017, they sign Neymar from Barcelona, meeting the €222 million release clause in his contract. A fee so deliberately high no-one would ever meet it. A fee still unsurpassed eight years on.  

While the age of the superstars may be over at PSG, they still have European football’s highest wage budget by some distance (an impressive feat when you remember that Real Madrid exist). Their Georgian talisman Kvaratskhelia only moved to the club in January for a reported €70m. Hardly loose change. 

Paris Saint-Germain is a Qatari ‘sportswashing’ project. An attempt to make a political regime palatable to European sensibilities by assembling a football team that is deeply, deeply likeable.  

And it certainly seems to be working. Rio Ferdinand, on co-commentary for the final, declared that a PSG victory would be ‘good for football’. So did Jason Burt, chief football correspondent for The Telegraph in an article that unironically has a subtitle starting “They may be funded by a nation state but …”. 

This is why I find it so disingenuous when people demand we ‘keep politics out of football’. (And anyway, what people often mean here is that they’d like to keep left-wing politics out of football, like the ‘take a knee’ or ‘rainbow laces’ campaigns). Politics is already in football and has been for quite some time now. If you haven’t spotted it, you simply haven’t been paying attention. 

I like Luis Enrique. I adore Vitinha. Kvaratskhelia makes me misty-eyed about the very nature of football. But PSG winning the Champions League is bad for football, because it’s a political victory before it’s a sporting one

PSG’s triumph is a timely reminder to the Church that it must remember the political nature of the call placed upon its very existence.

As is so often the case, football and religion find parallels in one another. For the Church, too, all too frequently finds itself as a political football. Debate continues about the place of Church of England Bishops in the House of Lords with only 33 per cent of Britons keen for religious leaders to express political opinions.  

But while this would certainly make the Church’s life easier, it’s simply not an option available to it. 

‘Gospel’ is not a Christian term. Not originally. It was a term used to describe an announcement or decree made about the Roman Emperor, a practice the Romans adopted from the Greeks before them. It is, in other words, an intractably political term. It is the ‘party-political broadcast’ of the ancient world.  

In hijacking the term ‘Gospel’ as a description for Jesus’ life and teaching, the early Church announces itself as an irrevocably political entity from its very beginnings. A body of people called to proclaim a political message. Or, at least, a message with significant political implications. Christ is king; Caesar is not.  

This does not mean that the Church is inherently left- or right-leaning. The Church is far older than this simplistic understanding of politics and will surely outlive it, too. But it does mean that the Church has a stake in the politics of the day; that it cannot be politically disinterested without simultaneously compromising something of its most fundamental identity.  

PSG’s Champions League win is not the first by a nation-backed club. Manchester City – principally owned by Vice President of the United Arab Emirates Sheikh Mansour bin Zayed Al Nahyan – won the Champions League in 2023 (also beating Inter Milan in the final; bless them). Depending on what we make of Roman Abramovich’s connections to the Russian state, it’s also worth noting Chelsea’s wins in 2012 and 2021, too. 

But PSG’s win – and the emphatic nature of it over one of the ‘old guards’ of club football – feels like a watershed moment for the sport. It is the culmination of the past 20-or-so years of both football’s internal politics, and the external politics acting upon it. It is a worrying statement of intent of its direction of travel, too.  

When Christianity and football feign political neutrality, they simply invite the dominant politics of the day to ride roughshod over them. Insidious politics will always fill any vacuum available to it. PSG’s triumph is a timely reminder to the Church that it must remember the political nature of the call placed upon its very existence. Otherwise it will find itself a mouthpiece for a kingdom to which it does not belong.  

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