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
Attention
Culture
Weirdness
Wildness
6 min read

Take a walk: the world is weirder than you think it is

Psychogeography and the dark alleyways of the mind.

Mockingbird connects the Christian faith with the realities of everyday life.

A backlit person at twilight holds a hand out towards the camera, holding some fairly lights
Riccardo Annandale on Unsplash.

This article, by Blake Collier, first appeared in Mockingbird. Published by kind permission. 

 

Entre chien et loup. 

The phrase literally means “between dog and wolf” and has most immanently been used to describe the twilight hour where day and night intermingle before night fully takes hold. 

Jean Pruvost, a linguist who has studied the expression, gave some background on ‘entre chien et loup.’ He says it comes from a Latin phrase, intra hora vespertina inter canem et lupum, that dates back to at least the seventh century. And it refers to the time when the daylight dims and you could mistake a dog for a wolf. 

One could imagine before the advent of electricity and modern public lighting how ambiguous this time of day could be as the landscapes around your small village were being consumed by the darkness — the human eye not fully able to calibrate fully for day or for night, hence the inability to distinguish between a friendly pet and a looming threat. 

This is what is popularly known as liminal space in our current epoch. This liminality is always present, however, not just at dusk. As we move through the worlds we inhabit, whether natural or built, we are constantly finding ourselves within transition or transformation. Psychogeography is a broader term that is often used to investigate the liminal movement of bodies through space. In its most simplistic form, it is how our mind interacts with and processes the physical landscapes that we inhabit and how those landscapes affect our mind. The actual history of the term is much more complicated — honestly, convoluted — however at its core it is scratching at the nebulosity of things like entre chien et loup

At the outskirts of a city or town, one begins to see the fraying of the edges, those areas where we have yet to fully enact our illusory control over the land.

About seven or eight years ago at the height of my running prowess, I got up one Friday morning very early and started a ten-mile run I had planned around nearly the full border of my hometown of Canyon, Texas. I did not know if I would make it the whole way, but the intent was there and the map was set. However, something interesting happened as I began plodding down my route. Those lines that show up on our maps often engender varying qualities of trails. Most of the time I was hitting asphalt and sidewalks, but when you are following a broad circle around a town, it’s not uncommon to find ambiguous stretches between incorporated and unincorporated parts of the town. Somewhere within the first mile or two, one of the “roads” I had included on my path ended up being nothing more than a worn trail through prairieland behind a group of houses. 

I bring this story up because, though I did not know it then, I was enacting a psychogeographic practice. Iain Sinclair, who is probably one of the most well-known proponents of modern psychogeography, walked the M25 around London in seven different treks over a time period. The M25 is a 125-mile loop around London and is considered one of the busiest highways in the world. As he ambled along the highway — sometimes on asphalt, sometime “around” the trace of the highway — he would take note of what he saw, and he eventually wrote the book London Orbital. This practice allowed him to see London in a new way because at the outskirts of a city or town, one begins to see the fraying of the edges, those areas where we have yet to fully enact our illusory control over the land. They have neither been captured by urban sprawl nor have they been renovated and gentrified. These lacunae are ambiguous regions between the built and unbuilt (or decayed). Once again, we are placing ourselves intentionally into places where we attend to the ley lines which connect the physical markers to the perceived or imagined topographies of the places where we exist. 

To put it bluntly, being intentionally attentive to surroundings can trigger investigations into the seen and unseen powers that hole up in our built environments and the natural world that pushes back against it. 

The path through the prairieland I spoke of earlier ended at a concrete curb and a recently repaved residential street that ran right next to a Catholic church, almost like the church was posting itself on the fringes of the town to warn of impending threat, or perhaps giving a welcome sight to a weary traveler. I suppose it depends on how you look at it. 

Yet it is exactly this work of attending to where we live and reacquainting ourselves with it that is, I believe, at the heart of this purposeful ambulation through space. Our lives fall into banality most of the time. We take everything for granted and we see our lived environment through that myopic lens. But take a walk on the outskirts of where you live, without a phone or music or any other technological mediation, and just look around the space and pay attention to how it embroils your emotions. I can nearly guarantee that you will find the place you live is much weirder than you thought it was, and you might even learn a thing or two about what your place values. I knew that Catholic church was in that general area of that path, but I didn’t realize how that path would empty me out before its hallowed presence. 

However, as I thought about it, it made sense that in this community the Catholic church would be found on the edges of the town. There are somewhere around ten other churches in a town of about 17,000 all of which are Protestant. However, if you go just ten or eleven miles west to the town of Umbarger, the roles are reversed. There is still one Catholic church, but as far as I know no Protestant churches. Merlin Coverley, in his book tracing the history of psychogeography, finds that “contemporary psychogeography as closely resembles a form of local history as it does a geographical exploration.” One could take the observations from their ambulation and dig into their place’s past to see why this might be the case. However, this is very much the chien of this psychological study of environment.  

What about the loup? Psychogeography has always had connections to the occult and the weird. Coverley continues later in his book, 

“Here, then, we find all the features ascribed to psychogeography today: the mental traveler who remakes the city in accordance with his own imagination is allied to the urban wanderer who drifts through the city streets; the political radicalism that seeks to overthrow the established order of the day is tempered by the awareness of the city as eternal and unchanging; and the use of occult symbolism reflects the precedence given to the subjective and the anti-rational over more systematic modes of thought.” 

All of this is to say that what we might find out about the place we live in when we give ourselves to its fringes and walk its shores might have a darker tone which implicates local politics and powers. Perhaps we will even find ourselves confronted by a metamorphosis which changes the very way we live, work, and move in these places. 

Sinclair’s earlier work Lud Heat in 1975 set out to remap London by way of connecting London’s churches built by eighteenth-century architect Nicholas Hawksmoor and their odd loci to numerous prominent murders like the Radcliffe Highway Murders and those by Jack the Ripper. There is a thread that ties some of the imagery Hawksmoor used in his churches to ancient Pagan symbolism. To put it bluntly, being intentionally attentive to surroundings can trigger investigations into the seen and unseen powers that hole up in our built environments and the natural world that pushes back against it. 

If nothing else, this study of the ambiguous transgressions between mind and place helps us bring a new profundity to our existence. It psychologically brings us back to a place where our intellectual, physical, and technological prowess cannot protect us from the hairs that stand on the back of our necks. Because everything, if attended to perceptively, can be seen as a dog or a wolf. And that should give us great pause in the everyday grind of our lives.