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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Column
Culture
Football
Leading
Sport
7 min read

Referees and stupidity

What one referee’s foul-mouthed rant tells us about the nature of sport, and authority.
A striker is about kick a football towards a goal, a red beach ball sits between him and the goalkeeper.
Darren Bent and the beach ball goal.
Sky.

Picture the scene: 

You have a monthly column writing about football from a Christian perspective. You’ve just finished this month’s piece and are about to send it off to your editor.

Before you do, you go to make a coffee. You open Twitter, only to find your timeline filled with videos of a Premier League referee openly slagging off a Premier League club and manager in some of the most obscene ways imaginable. You sigh, trudge back to your laptop, and begin re-writing your column.  

Deary, deary me.  

It is difficult to even begin quantifying the amount of trouble Premier League referee David Coote is in, following the emergence of videos in which he (allegedly?!) calls Liverpool Football Club “s***” and former manager Jürgen Klopp a “German c***”. It’s not clear when the video was filmed but given Coote (allegedly?!) mocks social distancing regulations, it may well be from a few years back.  

There is also a second video in which Coote says: “just to be clear, that f***ing last video can’t go anywhere. Seriously.” The person next to him chimes in: “He’s a premier league referee. Let’s not … let’s not ruin his career,” seeming to confirm that Coote is the person in the video. This second person then goes on to say: “let’s face it: we’re good blokes” seemingly oblivious to having said in the previous video: “Liverpool are all f***ing b******s, and we hate scousers.”  

The marks perhaps a new low point in the relationship (if that’s not too generous a term) between fans and referees. I talked last month about the prominence of conspiracy theories amongst (some) football fans; we might forgive some Liverpool fans for thinking this particular referee had it in for them … 

My wife and I were at Anfield last Saturday for Liverpool vs Aston Villa. David Coote was the referee. We’re lucky enough to sit in the front row at Anfield, and David Coote and his linesmen were warming up directly in front of us. Even before kick-off, some people in the crowd were making sure Coote knew what they thought of him.  

In the first half, Villa winger Leon Bailey brought down Mo Salah as he was seemingly through on goal. Normally this would be a red-card offense for denial of a goal-scoring opportunity; in this instance there was not even a foul awarded. It’s safe to say that the people sat near us think even less of David Coote than David Coote thinks of Jürgen Klopp.  

In the grand scheme of things, David Coote will be fine. He’ll probably end up as a pundit somewhere, earning more than he does currently for telling viewers why any given refereeing decision in any given match was the right one.  

According to a statement by PGMOL (the body responsible for Premier League officiating), Coote has been “suspended with immediate effect pending a full investigation.” But you never know, if any institution can contrive to find a way for someone to keep their job after this, it’s PGMOL. He might be back not-brandishing red cards straight after the current international break. In April 2023, assistant referee Constantine Hatzidakis was caught – on camera – allegedly elbowing Liverpool full-back Andrew Robertson in the face. After a PGMOL investigation, he was cleared of any wrongdoing.   

But for some Liverpool fans the leaking of this video is nothing other than vindication. “We knew he [and, by extension, other refs] were corrupt. This is just proof!” 

But this is, I fear, only bad news for the sport. There is already a widespread ‘us and them’ mentality when it comes to the footballing establishment. It often feels as though football happens despite referees, not because of them. 

The footballing media don’t help this. Most post-match analysis now centres on the referees. Did they make the right decision? Should that person have been sent off? Were there too many yellow cards? Were there not enough yellow cards? 

I am, frankly, bored of talking about referees. I watch football to see Mo Salah be the best player in the world, or to see Virgil Van Dijk be the most imperious human being that’s ever walked on the earth. Not to see some wannabe police officer have a power trip. Look, I wouldn’t want to be a ref. They’re subject to horrific abuse, both in person and online. And yet, the increasing centrality of referees and refereeing to football discourse is unhealthy for the sport.  

Only those secure in their authority and competence can operate with the vulnerability necessary to have that authority and competence questioned. 

The breathtakingly arrogant assumption of authority that oozes from every fibre of Coote’s being in the videos is, I think, somewhat indicative of the way authority has been wielded in this country in recent years.  

Such heavy-handed wielding of authority – whether it’s Boris Johnson’s incessant disbelief that anyone would have the gall to question his decision to party during lockdown, or the apparent ease with which David Coote seems to imagine himself the most important person on the football pitch – all ultimately stem, I think, from insecurity.  

We have just seen the re-election of convicted felon Donald Trump as President of the United States of America. What a sentence that is.  

Perhaps more than anyone else, Trump typifies the desperate kind of insecure man who craves authority. A man of deeply fragile ego, Trump’s attempted coup of January 6th 2021 – for what else can we say it was? – was the violent manifestation of an infant’s inarticulate magpie mentality, denied their most recent ‘shiny thing’. 

A toddler with nuclear codes. 

Only those secure in their authority and competence can operate with the vulnerability necessary to have that authority and competence questioned. In a move straight out of the Johnson/Trump playbook, Coote initially denied the videos were real, and then claimed not to remember their content, as thought that in any way served as mitigation. (Imagine: “Yes, your honour, that video certainly does show me killing the victim, but I can't remember doing so!”) 

This is not a man whose authority is based on vulnerability or transparency. 

Sadly, our politicians seem increasingly unwilling to display such vulnerability, and so do our referees. The latter might seem less important than the former, but they both speak to a broader culture of insecurity that leads the authority being wielded by the unfit.  

And sport is uniquely placed to combat such insecure seriousness of authority. Because sport is, ultimately, really, really stupid.  

In 2009, a Liverpool fan threw a beach ball onto the pitch in a match against Sunderland. As Sunderland striker Darren Bent took a shot, it ricocheted off the beach ball sending it one way, while the football went another. Liverpool keeper Pepe Reina dived after the beach ball, leaving the football to cross the line for a goal.  

Sunderland won 1-0.  

It was an unbelievably stupid moment. It was the pinnacle of sport as far as I’m concerned; exactly the kind of stupid nonsense I watch sport for.  

I want my stupid sport back. The kind of stupid sport that people don’t feel strongly enough about to record videos as unbelievably arrogant as Coote’s. All sport is a gift from God, football included. It is simply a gift to be enjoyed; nothing more, nothing less. It is profoundly unserious in this respect. 

There’s an episode of The Simpsons I think about a lot. Lots of advertising billboards come to life and begin harassing the residents of Springfield. The solution? Just don’t look. The billboards thrive on the attention; it’s what keeps them alive. Without it, they die.  

Men like David Coote, Boris Johnson, and Donald Trump thrive on authority; on being taken seriously. They are human billboards, advertising nothing but themselves. This makes them immensely unsuited to the very authority they crave. 

Coote might have said “that f***ing last video can’t go anywhere. Seriously.” But the very fact that he recorded it in the first place, that he voiced such thoughts in the first place, displays exactly the kind of insecurity and temperament of character that leads to people absolutely buckling under the weight of authority. 

What is football to learn from the David Coote incident? Just don’t look. The endless, austere-faced analysis of the minutiae of refereeing leads only to a culture that attracts people like Coote to the job in the first place. The sooner we stop talking football so seriously, the sooner we will be rid of the Very Serious MenTM ruining the sport.  

Indeed, ‘looking’ at the world’s Boris Johnsons and Donald Trumps – them and the people that prop them up, like failed-author-cum-politician Nadine Dorries, or the inexplicably daft Elon Musk – is to give them precisely what they want: attention. They are attention black holes; you do not reason with black holes, and no good can come from playing around with them. 

No, only Pepe Reina’s beach ball can save us from the David Cootes of this world.