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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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5 min read

I disobeyed Disney’s command to 'celebrate happy’

You don’t have to live your best life

Natalie produces and narrates The Seen & Unseen Aloud podcast. She's an Anglican minister and a trained actor.

A family pose for a picture at Disneyland
Disneyland.

I’ve just got back from a wonderful family holiday in California. And, of course, we couldn’t take our teenage daughters to California and not go to Disneyland.  

This year marks the seventieth anniversary of Disneyland, the Californian theme park conceived and built by Walt Disney, which opened in 1955. We forget now that this was a revolutionary concept in its time and wonderfully founded on the wholesome notion of creating a place where families could immerse themselves in an imaginative world; where parents and children could play and have fun together. In our screen-obsessed, individualist, loneliness-epidemic age, that continues to be a very good idea. 

We spent two days at Disneyland which proved enough time for me to have a chat and selfie with Iron Man; become a Space Ranger firing lasers alongside Buzz Lightyear; go on a turbulent adventure through a dangerous lost temple with Indiana Jones; and even join the Rise of the Resistance to be chased by some mean-looking Storm Troopers. Good times. 

However, a point of friction for me, ironically, was the theme for Disneyland's 70th anniversary celebration: "Celebrate Happy".   

I think Disneyland is great. A place designed for families and friends to have fun together absolutely gets my jaunty thumbs up. But I got increasingly annoyed by being told I should be happy all the time. Apart from anything else, the motto was clearly coined by someone who has never experienced the greatest irony of all: Disney Leg.  

Disney Leg (grown-up name Cutaneous Vasculitis, also experienced when playing golf) is a form of small blood vessel inflammation resulting swelling, a purplish rash, burning sensation and itching caused by walking or standing for hours at a time in high temperatures. It occurs most commonly in women in their late 40s or early 50s. I was one such woman. And I can tell you for nothing that Disney Leg is no celebrator of happy.  

Disney leg may have made me more Eeyore than Tigger, but my Disney experience was also framed by reading Kate Bowler’s wonderful book, Everything Happens for a Reason: And Other Lies I've Loved. I love Kate Bowler. I want her to be my best friend, forever. I want to be her when I grow up.  

I first met her when I listened in to the Seen & Unseen Live that featured her in conversation with Graham Tomlin. She introduces herself saying, “I’m Kate. I’m a Duke professor, podcaster and author with a single mission: giving you a little more permission to admit that you’re not always ‘living your best life’. After years of being told I was incurable, I was declared cancer-free. But there’s no going back. I am forever changed by what I discovered: life is so beautiful and life is so hard.”  

For everyone.” Kate is leading her own Rise of Resistance as she resists the tyranny of the wide and pervasive culture of extreme positivity that could also be summed up as “celebrate happy”.  

If my life is a failure because I’m not happy all the time, then how do I find the courage and hope that I need when faced with suffering or challenge? 

If Kate had been there, she wouldn’t have insisted that I celebrate happy, she would have found some shade and a bucket of iced water for me to immerse my Disney ankles in. She would have listened to me describe my discomfort with compassion and empathy such that I would then also feel able to tell her about how much I was enjoying myself. 

You see, I believe that the way towards “happy” isn’t through denial of suffering. It can’t be. We all know that life can be unbearably hard as well as achingly funny. To deny one is to negate the reality of the other. And to make “happy” our life goal is to exclude so much else that is beautiful in its complexity. If my life is a failure because I’m not happy all the time, then how do I find the courage and hope that I need when faced with suffering or challenge? And suffering and challenge are an everyday part of life that we simply cannot choose to ignore. The unpaid bills, the cancer diagnosis, the broken relationship - these things don’t go away or hurt less when I insist that I’m living my best life. 

Some of the best times of my life have occurred at exactly the moment when life has been hardest. Because that’s when I’ve had to acknowledge that I’m not in control of everything; that there is something, Someone, bigger and more powerful and more glorious than anything this world can offer me. If I insist on making happiness my god, I might easily miss out on the God who loved me so much he was prepared to suffer and die for me. My best life is found not in “happiness” but in the truth of God’s sacrificial love for me. 

I don’t mean to denigrate Disney at all. I think the Disney DNA of fun and a warm welcome give the rest of us much to learn from. Did you know that the people who walk around Disneyland dressed up as the famous Disney characters are highly trained, including the golden rule: when a child hugs you, you don’t let go until they do. Isn’t that beautiful? (I wonder how that would play out if I insisted on that in my church?)  But I do want to take the focus off the demand to “celebrate happy” and be free to celebrate the wider experience of life as well. 

What I took from my Disney/Kate Bowler sandwich is that the best of life comes from embracing the highs and lows; being honest about and unafraid of mixed feelings.  

Life is, as Ronan Keating once said, a rollercoster, just got to ride it. But also, I would add, life is getting fed up in the queue to get on the ride. Life is also feeling too hot or tired and needing to sit down. Life is also looking at your photos afterwards and realising that Tinkerbell has photobombed you. And I believe that all of that is to be celebrated, along with the happy. 

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