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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Article
Culture
Sport
Trauma
5 min read

Scottie Scheffler has a lesson for this summer's fading sports teams

The Open Champion's musings speak to the demise of Welsh Rugby and West Indian cricket

Graham is the Director of the Centre for Cultural Witness and a former Bishop of Kensington.

A cricket batsman surrounded by opposition players leaves the crease.
A West Indies Batsman leaves the crease.
xcom/windiescricket.

This past week, while England were beating India at Lords in a nail-biting, high-quality Test match which was in the balance until the very last ball, on the other side of the world in Jamaica, something tragic was unfolding. The West Indies were bowled out for the paltry sum of 27 runs against the fearsome Australian bowling attack, the second lowest total of any team in around 150 years of Test cricket. 

Why tragic? People of my age remember the 1970s and 80s West Indies as one of the best cricket teams in the world. Superb bowlers such as Malcolm Marshall, Curtly Ambrose, Michael Holding and Joel Garner terrorised batsmen from Adelaide to Antigua, from Cape Town to Christchurch. They hurled down cricket balls at a frightening speed, whizzing past the heads of batsman who didn't even have the security of a helmet. At the other end, a succession of brilliant batsman like Viv Richards, Gordon Greenidge, Clive Lloyd and Alvin Kallicharan scored hundred after hundred, as together they made-up one of the greatest teams in the history of Test cricket.  

Since then, a sorry mess of dried-up funding, poor governance, neglect of grassroots cricket, and the competition of other sports such as athletics or basketball, has seen the standard of West Indian cricket decline dramatically, especially at the most complex form of the game - international 5-day Tests. So, the 27 was not a huge surprise. Something catastrophic like that was bound to happen one day.  

In those same 1970s, Wales boasted one of the best rugby teams in the world. Gareth Edwards, Barry John, JPR Williams and Phil Bennett were at the heart of a dazzling and brilliant team. Rugby is Wales's national sport, yet in recent years a similar story of incompetent governance, lack of funding, and an inefficient regional structure has led to its dramatic decline, and a harrowing 18-match losing streak, which finally came to an end with a narrow victory over Japan, hardly one of the world's greatest teams. Last year's Six Nations ended with an embarrassing 68-14 home defeat against the team they hate to lose to - England. The current Lions team contains no Welshmen at all - the first time since 1896.

Then there is the demise of Manchester United. “We’ve seen it all. We’ve won the lot. We’re Man United and we’re never going to stop” sing United fans at most games. All very grand, but these days they don't win anything. The great triumphs were back in the 1960s, and then the 90s and 2000s under the great Sir Alex Ferguson. After a takeover by the incompetent Glazer family, who have increased sponsorship revenue but leeched billions out of the club, and seem incapable of running a global football institution, United have declined dramatically, ending up 15th in the league last season, and with a failure to recruit new players this summer, look destined to do even worse next season. 

The fall of such sporting giants often elicits a strong dose of Schadenfreude in opposition fans. I was moaning about the fortunes of Man United to a Chelsea-supporting friend recently. He had zero sympathy. 

And yet there is something tragic about lost sporting glory. Watching the current West Indies, Wales and Man United teams getting beaten by mediocre opposition brings a heavy sense of sadness - even if you're not Welsh or West Indian. Like King Lear, reduced to wandering around a ‘blasted heath’ like a madman, Icarus falling to the sea after over-reaching, or Sisyphus, once a king, yet incurring the wrath of the gods and now condemned to eternally rolling a stone up a hill only for it to fall down the other side (sounds just like Man United’s recent seasons), these teams’ current manifestations can’t escape the glory that was once theirs but is no longer.  

Fading sports teams are our contemporary memento mori

“How the mighty are fallen.” The phrase comes from the Old Testament - when the young warrior David mourned for the slain King Saul. Reflecting on lost human glory was in the past thought to be a valuable thing. Churches up and down the country have effigies of dead local grandees, lying in stone with hands clasped in prayer, as a reminder that human glory fades, death comes to us all, that our wealth will be handed on to others, and the things we are most proud of most likely forgotten. 

Scottie Scheffler, the world' No 1 golfer and who just won the British Open recently spoke about winning a gold tournament, having a brief sense of euphoria, which then vanishes within a few minutes as life returns to normal. He wondered aloud whether it was all worth it: “There are a lot of people that make it to what they thought was going to fulfil them in life, and you get there, you get to number one in the world, and they're like, 'what's the point?'” 

Scheffler has made no secret of his Christian faith. It presumably lies behind his comments that golf can’t give what he called “fulfilment in the deepest places of your heart". And maybe that is the ultimate lesson of these teams that were once great and are no more - a reminder that sport can be a source of great joy and achievement, but ultimately is unable to satisfy our deepest longings, because its glory is fleeting.  

Fading sports teams are our contemporary memento mori. As humans we somehow yearn for something permanent, unshakeable, eternal, what our forebears found in God, but we moderns struggle to find anywhere. Wordsworth’s classic questions: “Whither is fled the visionary gleam? Where is it now, the glory and the dream?” are echoed in the demise of sporting greatness, and the existential musings of Scottie Scheffler. 

One day, every sportsman or woman, every team - in fact, every one of us - will experience what the West Indies, Wales and Man United experience right now. The flower fades and the grass withers. And perhaps in that moment of lost fame, we will find the wisdom to seek more lasting things than sporting glory. 

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