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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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I’m not sure Christopher Nolan has actually read The Odyssey

The director has drunk the Kool-aid of modernity, and done so deeply
the head of a classical statue looks up amid embers around it.
The odyssey poster.
Universal Studios.

Greek myths are full of hubris. Full of it. I feel like ‘hubris’ isn’t a word you hear very often anymore. It means excessive pride or self-confidence that leads to a downfall, in case you were wondering. “Boris Johnson’s hubristic underestimation of the effects of ‘Partygate’ was the final nail in his political coffin,” we might say.  

In one myth, Icarus is imprisoned, but given wings held together by wax in aid of his escape. He is warned not to fly too close to the sun, because the heat will melt the wax. Guess what he does? Yep! Flies too close to the sun. The wings melt and he falls to his death. Hubris

Another myth tells the story of Prometheus. No, not the slightly underrated Alien prequel. (That’s right, I said underrated, but that’s another article for another day). Prometheus defies the Greek gods by stealing fire and giving it to humans. As punishment, Zeus ties Prometheus to a rock and has an eagle eat his liver, only for it to grow back overnight so the eagle can come back the next day and start again. Hubris. 

Greek myths are full of hubris. Full of it. 

And so, this is why I find the new poster for Christopher Nolan’s upcoming adaptation of Greek epic The Odyssey so … bizarre. But then I’ve been nervous about Nolan’s adaptation since it was announced. Nolan is a wonderful filmmaker, but he’s also deeply naturalistic in the messages he conveys. By this, I mean that all his films suggest that nature – the physical, material world of atoms and things – is all there is. Even when he has opportunity to explore themes of the mystical, or magical, or the supernatural, he only does so when a purely ‘natural’ explanation for such things is possible.  

For example, in The Prestige (and HUGE spoilers for the film here: it’s incredible, please watch it if you haven’t), Nolan tells the story of two rival magicians, played by Hugh Jackman and Christian Bale. Robert Angier (Jackman) is trying to work out Alfred Borden’s (Bale) teleportation trick. The secret? (Seriously: big, big spoilers here). Science. Nikola Tesla has invented a device that can clone someone but send the clone to a different location. The trick – the mysterious MacGuffin at the film’s heart – has a natural, scientific explanation. Magic isn’t real and you’re a fool if you think otherwise. 

Perhaps this is also why Nolan directed the wonderful Dark Knight trilogy. After all, Batman’s superpower is just wealth: it’s entirely naturalistic, with nothing that can’t fit into a scientific way of understanding the world. Or we could point towards the science fiction that underwrites Inception, Interstellar, and Tenet. For a filmmaker so gifted at tension and intrigue, he has surprisingly little truck with mystique, mystery, and the divine. But this is a problem when it comes to The Odyssey. A huge problem.  

Let’s return to that poster I mentioned earlier. It shows the head of a classical Greek statue, flames ember underneath it. The caption? Defy the Gods. And it’s at this point I start to wonder if Nolan has actually read The Odyssey. Because The Odyssey takes questions of divinity and their authority very, very seriously. Like many Greek myths and poems, the message of The Odyssey isn’t ‘defy the Gods’. No: it’s ‘trying to defy the gods is an unbelievably stupid, futile, and dangerous thing to do’. Nolan would seemingly have us raze Mount Olympus to the ground.  

Look, all we have is a poster so far. Nolan might prove me wrong. But we shouldn’t be surprised if Nolan reworks The Odyssey in such a way that ‘defy the Gods’ becomes its central message. Because Nolan is a quintessentially modern filmmaker.  

In a 1965 book called Freud and Philosophy, French philosopher Paul Ricœur described the modern period as dominated by a climate of suspicion or scepticism. Within this ‘climate of thought’, the straightforward understandings of things are actually deceptive, instead hiding hidden, deeper, and ‘truer’ meanings. He described Sigmund Freud, Friedrich Nietzsche, and Karl Mark as the ‘masters of suspicion.’ And so the world around us is to be approached suspiciously, to uncover the ‘truer’ meanings about our subconscious (so Freud), our false, religiously imposed morals (so Nietzsche), or our exploitative economic systems (so Marx). 

Each of Ricœur’s ‘masters of suspicion’ might be mapped on to one of the villains in Nolan’s Dark Knight trilogy. Liam Neeson is Ra’s al Ghul, a Freud-like figure who helps Bruce Wayne navigate the psychological effects of his parents’ murders in childhood. Heath Ledger’s mesmeric Joker is Nietzsche’s stand-in, exposing our misguided systems and structures of ethics, tethered to a religious framework we no longer hold to. Tom Hardy’s Bane is Marx, freeing Gotham’s proletariat from the economic structures that oppress them so. 

It's not a perfect fit, but I think there’s more than enough evidence to say that Nolan has drunk the Kool-aid of modernity, and he has drunk so very deeply. And this would be fine – absolutely fine – if he wasn’t planning to adapt The Odyssey. Because, as a quintessentially modern filmmaker, Nolan’s work emerges out of and celebrates a culture wherein ‘defy the gods’ is a slogan that can only be heard as heroic, courageous, and noble, rather than dumb and futile, as The Odyssey would stress to us. 

Defying divinity is not heroic. The Odyssey knows this and knows it well. Defying the gods never ends well for humans stupid enough to try in Homer’s work. Our modern sensibilities encourage us to be suspicious of institutionalised power, especially when that power takes a religious shape. We are predisposed to imagine that invocations of the divine are nothing more than thinly-veiled power-grabs. And sometimes they are. But The Odyssey is right to say that divinity itself is not to be trifled with. Renounce your creator at your peril. 

Like all his other films, Nolan’s The Odyssey is likely to be tense, wrought, and cinematographically immaculate. But also like his other films, I worry it will be deeply naturalistic in the way it handles the inescapably divine and supernatural elements present in Homer’s epic. The Odyssey has an important message for our increasingly hubristic society. I just worry that Nolan’s not the man to convey it as it deserves. 

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