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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Article
Culture
Easter
Sport
4 min read

Rory McIlroy’s pilgrim’s progress

The golfer’s relief at finally laying his burden down.

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

A golf clutches his face after winning a competition
McIlroy's moment at the Masters.
Simon Bruty/Augusta National.

It's Sunday evening. Along with most golf fans, I'm still up around 1 am, gripped by the drama unfolding on the famous course at Augusta, Georgia. Despite being one of the world’s best golfers, for the past eleven years, Rory McIlroy has been carrying around three big burdens. One, he has never won the Masters, one of golf’s iconic competitions. Two, he last won a ‘major’ eleven years ago and inexplicably has kept missing out on winning golf’s biggest tournaments. Three, there is the ‘career grand slam’ – winning all four ‘majors’ (of which the Masters is one) – something only five golfers in the history of the game have done before, none of them European. Rory has won three of them, but this one – The Masters - has always eluded him. 

After four agonising days, with his fortunes switching this way and that like a drunk driver careering down a road, Rory stands over a four-foot putt on the final play-off hole, one that even average amateur golfers like me would expect to make. Heart pounding, he nudges the ball forward. As it rolls into the white-ringed hole, his knees crumple, shoulders shake, as tears of relief and joy pour down his face. You can almost see all three burdens roll away in that moment. As he put in in a post-round interview: “This is a massive weight that's been lifted off my back.” 

As a self-confessed fan of Rory, who seems genuinely humble and likeable, with a golf swing as smooth as butter, I punch the air, probably like most golf fans around the world. Watching the post-round interviews, you can sense his elation and liberation. As Scottie Scheffler, last year’s winner, clothes him in the coveted green jacket, awarded to all winners of the tournament, Rory cannot stop grinning, wandering around the Champions’ Locker Room, which he has had no right to enter until this point, like a kid in a sweet shop.  

Now I’m sure the golf committee at Augusta National never thought for a moment they were drawing on rich religious imagery for their award ceremony and the emotions generated in winning their tournament, but Rory’s relief made me look up a moment in John Bunyan’s Pilgrim’s Progress. The parallels in this old tale of Puritan faith were even more striking than I expected.  

In Bunyan’s dream-story, the main character, Christian, having been through years of tests, trials, ups and downs, reaches the climax of the tale as he reaches Calvary, the place where the cross of Jesus Christ stood: 

Just as Christian came up to the cross, his burden loosed from off his shoulders, and fell from off his back, and began to tumble; and so continued to do till it came to the mouth of the sepulchre, where it fell in, and I saw it no more. 

Then there was the tearful joy and relief:  

Then was Christian glad and lightsome. He looked therefore, and looked again, even till the springs that were in his head sent the waters down his cheeks. 

There was even the celestial equivalent of the green jacket. Three angels appear, and one of them: 

…stripped him of his rags, and clothed him with a change of raiment. And unto him he said, Behold, I have caused thine iniquity to pass from thee, and I will clothe thee with change of raiment.  

Burdens rolled away, tears of joy, dressed in new clothing. It’s all there.  

Yet this comparison tells of a difference. 

Bunyan’s relief was about forgiveness. Rory McIlroy’s came from winning a game of golf. His Twitter / X self-designation delightfully used to read: “I hit a little white ball around a field sometimes.” (It now reads ‘Grand Slam Winner’ - not so good in my humble opinion). 

The lessons drawn were all about persevering, persistence, getting there in the end. Looking across at his young daughter Poppy, Rory said:  

‘Never, ever give up on your dreams. Keep coming back, keep working hard, and if you put your mind to it, you can do anything.’ 

Yet of course there was nothing inevitable about his victory. It could so easily have gone the other way. His putt might have slid past the hole, Justin Rose, his play-off opponent might have sunk his, and Rory might never have won the Masters, never won the Grand Slam. That is the nature of sport. However strong your dreams, however good your skills, winning is never guaranteed. Not everyone’s dreams come true. It's simply not true that “if you put your mind to it, you can do anything.”  Ask Justin Rose.

Bunyan’s relief is something completely different. It's not the relief of having achieved something. It's the relief of receiving something - a totally undeserved gift - more like a prisoner receiving news of an unexpected release, or someone owing huge debts receiving a windfall which enables her not only to pay off the debts but to live comfortably in the future. 

The relief of the winner who finally achieves their dream is wonderful to watch. But for those whose dreams don't get fulfilled, for the likes of Justin Rose, who at age 44 seems destined never to win it, that kind of joy remains tantalisingly out of reach. 

Christian’s tears of happiness are not the tears of the winner but of the loser. They are for those whose dreams never come true as well as those whose do. They are for those who fall short yet are given the gift of forgiveness, peace and hope. They are - potentially at least - for all of us, winners or losers.  

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