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
Film & TV
5 min read

The death of Hollywood

Out of the ashes, new stories will rise

Theodore is author of the historical fiction series The Wanderer Chronicles.

Studio executive's react.
Seth Rogan's The Studio, a Hollywood satire.
Apple TV.

There is no more obvious sign of the ailing of the Hollywood behemoth (if not to say, its actual death) than the utter failure of Disney’s latest live-action re-release of Snow White

According to Forbes, Disney’s total investment in the movie, including production and marketing, likely exceeded $350mn. To break even, it would have needed to take around $500mn gross at the box office, after distribution and movie theatre cuts. To date it has made just under $200million. 

If nothing else, that is a tremendous waste of money. But the essential problem seems to have been that the movie’s creators were trying to bend themselves (and the story) into pretzel-shaped contortions to satisfy the various demanding (and contradictory) ideological axioms of LalaLand. The result? Not only do they fail on their own terms: a movie about a young princess finding her inner girl power and leading an oppressed people to overthrow a tyrannical autocrat ends by setting up a new regime under one unchallengeable and all powerful ruler: a system of “Snow-White Supremacy”. It also fails on the archetypal axioms of story. There’s a reason why parents still read to their children the traditional version of Snow White, which scholars believe to be so long-living and so “true” that its roots seem traceable as far back as Ancient Greece. Modern storytellers mess with that long lineage of audience appeal at their peril; as no doubt several Disney executives have now found to their cost. 

Last month the veteran Hollywood screenwriter and novelist Andrew Klavan concluded, after watching the last annual offering of glamour-slick virtue signalling that is the Oscars, that Hollywood is indeed a dying beast. He argued that the collective movie-making culture has become so captive to a certain ideological mindset that it has prioritised that over the more basic and primary objective of telling stories. When ideology overrides the essence of storytelling - delivering stories reflective of life as it actually is and as we find it - then the art suffers and audiences instinctively turn away.  

Why? Because we all come to stories to find truth (even if it is dressed up in the “lie” of fiction). The problem with the ideological mindset approach to storytelling is not that it does not start with good intentions (let’s say a value like “compassion”); but that it drives towards and ends with outcomes very far from life as we know it to be. So, for example, compassion for allowing female-identifying men into women’s sport ends up with Olympic crowds applauding a man punching various women in the face to earn himself a gold medal. Or well-intentioned young people marching throughout the cities of Europe in support of terror groups who behead babies. There is a cognitive dissonance between the makers of movies imbibing and propagating this sort of mindset and their audience of millions. 

No wonder those audiences are tuning out. Because the central thing that people want from art are good stories. Good stories make us nod and say: yep, life is like that - however far-fetched the premise or the setting may be. Bad stories make us feel like someone has tried to sell us a lie. They are “phoney” - and at a gut level, we know it. 

So, if Hollywood’s time in the limelight (and the pay dirt) may be running out, where should we look for a new resurgence (dare we say, resurrection?) in the art of storytelling? 

“Two are better than one because they have a good reward for their toil.” Collaboration seems to produce the goods.

It would be foolhardy to come down too hard on an answer to that question, since ultimately stories can and have come from anywhere. But if I had to lay down money on the kind of environment out of which any resurgence in the storytelling industry (whether of the moving image or the written word) will come, I would be betting on some sort of life-affirming, collaborative, creative network or community based around the foundational values of truth, goodness and beauty, and motivated by a shared desire to see the renewal and revitalisation of  Western culture everywhere.  

Such networks have been springing up with the ubiquity and rapidity of mushroom colonies all over the West, particularly in the US and across Europe. 

 Angel Studios has emerged as one of the more front-footed of these. This is a US-based media company that produces and distributes films and TV series with inspirational and faith-based themes: projects like The Chosen - the globe-conquering pay-it-forward re-telling of the Four Gospels - and Sound of Freedom, the latter grossing over $250million worldwide. (Disney take note.) 

While Angel’s content may have arisen out of niche audience demand (it was founded as a successor to the VidAngel app that sourced child- and faith-friendly content), other collaborative networks exist with a broader mission for cultural renewal. The Everything Network is one such example. A UK-based Christian network of leaders across multiple fields of society, it operates from the principle that, for centuries, society has benefitted from the way Christianity has contributed to the whole of life: from the art we create, to the laws we make, and the way we care for those in need. If God cares about everything, then the invitation persists for us to work towards the renewal of all things. 

This includes the stories we tell. Hence, under one aegis, authors, poets, or screenwriters are connected with financial backers, producers, directors, animators, marketeers and so on. Implicit within the network’s mission is a recognition that stories have the power not just to entertain, but to change the world. For good and for bad.  

Just look at the Bible. 

At a more modest level, creative networks are coming together all over the West: in churches, across the broader arts and entertainment landscape and so on, in part as support communities for people working in those industries, but also as incubators for collaborative output. Some are more ambitious than others. And many are proving the truth of the proverb: “Two are better than one because they have a good reward for their toil.” Collaboration seems to produce the goods. 

So, if truth, beauty and goodness are the weapons on the battlefield of imagination, and the soul of the world is the prize, perhaps these emerging creative networks are the divisions, the battalions, the platoons deployed along the front line. Time will tell which are most effective. 

What is certain is that, long after Hollywood’s spell over us all is broken, humans are still going to want to hear good stories. Stories that tell us something meaningful and true about life as it appears before us.  

I’ll have my bucket of popcorn ready just in case.

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