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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
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7 min read

What my film about the prodigal son really means

Our relentless focus on productivity devalues the things that make us human

Emily is designer and animator at the Theos think tank.

An animated man runs through a jungle.
In Sync with the Sun.
Theos.

Watch now

In his 2021 book 4,000 weeks: Time Management for Mortals, Oliver Burkeman observes that an obsession with productivity doesn’t give us more control over our lives, ‘instead, life accelerates, and everyone grows more impatient. It’s somehow vastly more aggravating to wait two minutes for the microwave than two hours for the oven - or ten seconds for a slow-loading web page versus three days to receive the same information by post.’ 

With technologies like artificial intelligence rapidly accelerating our lives, this constant demand to squeeze more into our time is not only limited to the mundane tasks that we have to do and wish we didn’t. It seeps into what we want to do and indeed must do in order to flourish: creating art, spending time in community, and caring for others. The problem is that these things cannot be measured in productivity metrics because they inherently do not function in that way. How do you measure how ‘productive’ a conversation is? Or a work of art? Artists such as Vincent Van Gogh or Emily Dickinson didn’t see their influence in their own lifetime. 

The more we measure our lives in productivity metrics, the more we devalue the things that make us human, ultimately making our lives and the world around us increasingly artificial. This is the basis of my recent film, In Sync with the Sun, which is a short animation about the rhythms of activity and rest that are written into our world, and what happens when an obsession with productivity takes over.  

I wrote the initial script for the film after a period of burnout. I was fully in the “make the most of every second” mindset, which left me feeling exhausted and confused about where my value resides. In response, I began researching the sleep-cycles of various animals and I was liberated by surprising details such as the fact that lions, which we see as mighty and majestic animals, sleep for around 21 hours a day. Even creatures like jellyfish, which don’t even have brains as far as we know, still have cycles of rest. Every living thing thrives in these rhythms of activity and rest, even down to plants and minuscule organisms. Our whole world is built on this pattern, in sync with the sun. Yet for us humans, our rhythms have been broken by technology, leaving us confused about our limitations and what we should do with our short lives.  

The film begins in nature, deep in the jungle where some leopards are sleeping. But the tranquility is abruptly interrupted by the voice-over declaring, “the war against sleep began when artificial broke into the night.” Brilliant white light breaks up the deep blues and purples on screen, until the screen is filled with blinding white. I wanted it to feel like that moment you peer at your phone in the middle of the night - the pain of your pupils trying to adjust. If you think about it, for 99.9 per cent of human history, our eyes would have never had to do that - until now.  

Artificial light wasn’t powerful enough to change that. Instead, it’s given us an unquenchable guilt about how we use our time. 

With his invention of the light bulb, Thomas Edison was determined to banish the night, and the limitations it enforced on us. Edison was known for being fiercely obsessed with productivity and, as a result, was an anti-sleep warrior who believed,

“There is really no reason why men should go to bed at all.”

As someone living a century on, I find it baffling to imagine that humans should eradicate sleep entirely. Perhaps because just 100 years later we are seeing the results that sleep-loss and over-working can have on our physical health and wellbeing. Maybe we cannot supersede nature after all, since we are an embedded part of it. It seems that “Sabbath" rest is written into our world and into our humanity. Artificial light wasn’t powerful enough to change that. Instead, it’s given us an unquenchable guilt about how we use our time. Now we decide when the day ends, so whoever can rest the least wins. 

The battle is still raging; incandescent bulbs only set aflame that root desire to be increasingly productive. The hamster wheel is spinning uncontrollably, and we must keep up. So, what do we do? The attempt to remove the limitations outside of us has revealed that they are in fact inside of us too. Therefore, the only way to keep up is to remove the human from the hamster wheel altogether. The failure of artificial light leads to the birth of artificial minds.  

 As a creative, this is what frustrates me most about artificial intelligence; that it is mostly being driven by this quest to bring everything under the reign of productivity. It goes without saying that this is greatly needed in some areas of society. Just like artificial light, it can and will do a lot of good in the world. However, when the obsession with productivity is prioritised over human flourishing, that’s when we know there is a big problem with how we view our lives.  

Thinking back to the examples of Van Gogh and Emily Dickinson; what is lost when we don’t allow space for artists, carers, mothers, or any skilled role that requires an element of patience? For me personally, I can’t force creative inspiration, instead it comes at me, often at times when I’m not looking for it. Similarly, sometimes that inspiration leads directly to an instant idea, but most often it’s a vague idea I jot down to which later life experiences and opportunities then build onto, forming it into something bigger and more in-depth. This could be compared to a role or situation that requires relationship building. Sometimes there are moments of instant bonding and “productive” progress in relationships, but it’s often more complex where external experiences or changes, which are outside of our control, may unexpectedly deepen understanding between people after long periods of frustration. 

In my animation, I used the metaphor of a butterfly to illustrate this sentiment. After the character realises he is not made for a life of relentless productivity, he steps out of the black and white skyscraper into the lush wilderness. A butterfly lands on his productivity badge and the voice over says, “You’re not a machine.” I imagine the Creator saying this to the loved creation. Creatures like butterflies seem completely unproductive to our human standards. They take weeks to form in the chrysalis and exist in the world for less time than that. Yet they are a source of wonder and beauty for anyone who has the privilege of seeing one up close. A reminder that nature is not in a rush. Where AI is concerned, however, speed and profit are the focus of desire. But looking at the world around us - that we are a part of - it’s clear that not everything can or should be valued by these limiting metrics alone. 

The overarching narrative of In Sync with the Sun is loosely inspired by the biblical story of the prodigal son. The main character has travelled far away from his home in pursuit of success, and he eventually realises that this master does not love him. At the end he comes home again, finding connection in community and in the good rhythm of productivity and rest that he came from. I wanted the film to address the issues that an unhealthy obsession with productivity can cause, and instead evoke a desire to accept and live more in sync with the boundaries and rhythms that are embedded in the natural world we are a part of.  

The film ends with the line, “The only thing that can stay awake is not awake at all.” In the midst of the changing world of AI, humans might be tempted to measure our productivity levels in comparison to these machines. However, technologies always raise the productivity bar higher and higher, and one day we need to accept that we simply aren’t going to be able to reach it. We don’t sit apart from nature like technology does, so let’s stop resenting that, and instead celebrate it. To quote Oliver Burkeman again,  

“the more you confront the facts of finitude instead - and work with them, rather than against them - the more productive, meaningful and joyful life becomes.” 

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