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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Column
Books
Culture
Music
Space
6 min read

Magnificent or mundane: how do you react to the overview effect?

Creators of a book, an album and a game, can’t agree.
A small white space capsule orbits around the earth.
A SpaceX Dragon capsule orbits above Earth.
NASA.

As I write this, two Nasa astronauts – Suni Williams and Butch Wilmore (possibly the most USA-sounding name imaginable) – are preparing to leave the International Space Station to return to Earth. They were supposed to stay on the space station for eight days, but a technical problem with their spacecraft meant they’ve been stranded in space for nine months.  

Nine. Months.  

It sounds like the premise for a horror film. Two stranded astronauts slowly descend into madness as they become increasingly isolated and cut off from humanity. Written and directed by M. Night Shyamalan, probably. 

That’s a lot of time to be stuck orbiting Earth, gazing at the pale blue dot, contemplating our little corner of the universe. There’s a phenomenon called the overview effect: a shift in thinking astronauts go through when they see Earth from space. Putting the planet into the wider context of the entire cosmos leads observers to rethink humanity’s place in the universe, and what it means to be human.  I imagine Suni and Butch have had quite a bit of time to do just that in recent months.  

And the overview effect is currently having a bit of a moment in wider culture, too.  

If you went into any bookshop in the weeks before Christmas, you likely saw stacks of Samantha Harvey’s novel Orbital. It tells the story – although there’s not much by way of traditional ‘story’ in Orbital – of six astronauts on the International Space Station, pondering the nature of humanity from their lofty vantage point. 

Having won the booker prize, booksellers were keen to encourage readers to buy Oribtal. Praised by the Booker Prize judges for its “beauty and ambition”, I was looking forward to reading it, when I could. (And, let’s be honest, it’s a short book, which probably helped sales. Who has the time to read Ulysses or Infinite Jest in between school runs and weekly shops?) 

When I finally read it in January, I was left disappointed. I found a surprising lack of humanity in Orbital. With the exception of one astronaut – who spends her time mourning her recently deceased mother some 250 miles up in the sky – the characters feel somewhat paper thin; barely human. As the story meanders from person to person, never really settling on one character long enough to really develop them, it feels a bit … insubstantial?  

Maybe it’s a victim of its own hype. Maybe the not-quite-humanness of the astronauts and the listless quality of the narrative are intentional, designed to capture the ungrounded nature of life in space in both form and content. Maybe that’s being generous. Either way, I was left closing the book and shrugging my shoulders. If Orbital was supposed to offer a glimpse into that overview effect, it left me nonplussed. 

By coincidence, Steven Wilson has just released his eighth solo album: The Overview. Who is Steven Wilson, you ask? Only “probably the most successful British artist you've never heard of” according to The Daily Telegraph. With Wilson’s album currently sitting at #1 in the UK album charts, it doesn’t seem an unwarranted title.  

In The Overview, Wilson explores the overview effect across just two lengthy pieces of music. In the first, Wilson contrasts the mundanities of life on Earth with the chaos of space, calling us to attend to miracle that is humanity, thanks to lyrics written by the annoyingly talented Andy Partridge of XTC: 

“And there in an ordinary street  

A car isn't where it would normally be  

The driver in tears, about his payment arrears 

 Still, nobody hears whеn a sun disappears in a galaxy afar.” 

With Partridge’s help, Wilson manages to capture that humanity so sorely lacking in Orbital. Amid a sea of seemingly barren space, there is life here on this small, pokey planet, and the dramas and stresses of a man fretting about his debts don’t seem out of place, even when compared to the implosion of a star on the other side of the universe.  

All this makes a recent interview with Wilson all the more odd.  

When speaking about the overview effect, Wilson says “Your life is futile, it’s meaningless – and isn’t that a wonderful thing?” before doubling down: “And I do mean that. We spend so much of our time anxious, stressed, worried about things that sometimes we just need an injection of perspective.” 

For Wilson, this perspective – this overview effect – is liberating. It allows to stop navel-gazing, to pick our heads up and to realise our freedom to do whatever we want. After all, everything’s just matter in varying different arrangements:  

“The clouds have no history 

And the sea feels no sorrow 

The oxygen recycled 

And the atoms are just borrowed,”  

At the climax of the album’s second epic, Wilson sings – with more glee than it warrants –  

“There's no reason for anything  

 Just a beautiful infinity 

 No design and no onе at the wheel.” 

 Cheery stuff. 

It's easy to see why, in the same interview, Wilson rails against the concept of religion: “Religion is a classic manifestation of cosmic vertigo … To even understand even the very simplest, most basic facts about space, should be enough to disabuse anyone of the notion of God. But apparently it doesn’t.” 

It all sounds a bit like an angsty teenager encountering the New Atheists for the first time. And this edge to Wilson’s work jars uncomfortably with the humanitarian streak that runs through his music. Wilson wants (rightly) to celebrate the mundane, the ordinary, and the human. And simultaneously wants to tell us that we’re just … stuff. Just atoms arranged in one way or another. Wilson pays lip-service to the humanity missing from Orbital, but it’s superficial.  

And all this reminds me of my favourite video game ever: 2019’s The Outer Wilds. (Not to be confused with 2019’s also-space-based-but-decidedly-mediocre The Outer Worlds). In The Outer Wilds, you play as an alien with a ramshackle spaceship who sets off to explore their solar system. Except every 22 minutes, the sun explodes. When it does, you wake up on your home planet and start again. 

You use these 22-minute loops to explore the solar system, flying manually from planet to planet, and exploring every nook and cranny of them in the process. You see awe-inspiring sights and are confronting with the absolute otherness and horror of the vastness of space.  

And yet. As you explore, you come across notes left by long-forgotten civilizations. Mundane lists and frustrated exchanges between colleagues. You come across life, in other words, even if you don’t meet many other actual people. I can’t say much more than this without ruining the game: The Outer Wilds depends on your real-world knowledge to progress, and so, the more I tell you, the more I ruin.  

But, suffice it to say that this is exactly what is missing from Harvey and Wilson’s work. While they both ostensibly want to remind us of the value and the miracle of humanity, both leave me feeling cold. Both leave me with the impression that life is little more than atoms arranged one way and not the other. Just stuff.  

But in The Outer Wilds, the sun’s implosion – and all that is lost with it – is a genuine heartbreak every single time. I think about all the stories I’ve read, and the people I’ve met, and how it’s all about to be lost as a bright supernova washes over me. And then I wake up again at the start of the cycle, relieved that all is not lost.  

If you can, you should play The Outer Wilds. It’s beautiful. Really, really beautiful. More so than Orbital or The Overview. Our place in the universe can be overwhelming; we’re small, and the universe is strange and scary. But we’re not just insignificant stuff. Our stories and the people we share them with matter. And Outer Wilds captures this tension impeccably. Only it captures life’s miraculous nature in the way it deserves. 

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