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
Generosity
Virtues
6 min read

We need to rescue volunteering

Our use of the word now reflects unwanted obligations, rather than a deep desire to serve.

Juila is a writer and social justice advocate. 

Two small lifeboats raft together on a river rescue.
Lifeboats on the River Thames.
x.com/rnli_teddington

It’s a hot summer evening and there are 30 of us sweating in our dry suits. Tuesdays usually mean lifeboat training, but this night is a little different. An intermission from the usual intensity of a team-building exercise: racing two lifeboats across the river Thames. Allocated into teams of two rowing in a knockout tournament, we are going to be here for a while. Our cheers provide the soundtrack for the BBC radio crew recording a programme on volunteering. The mood is convivial; the competition is fierce. None of us have to be here; all of us choose to be. We are a lifeboat crew, and we are all volunteers.  

Around 25 million people in the UK do some form of volunteering. And they are celebrated during Volunteers’ Week, which has been running for 41 years. The benefits are well documented these days. The mental and physical health boost. A sense of purpose. The chance to learn new skills. A route to forging connections with other people. 

Despite this, though, the number of people volunteering has been on a twenty-year decline. One in three organisations are struggling to retain volunteers, in part due to the cost-of-living crisis making people’s time and capacity more precious than ever.  

Beyond that, our use of the word seems to have shifted to reflect unwanted obligations, rather than a deeply held desire to serve. ‘I suppose I better volunteer to put out the chairs’ we might pronounce with the deathly weight of Katniss Everdeen’s ‘I volunteer as tribute,’ glancing to the left and the right in case anyone saves us from the undesirable task. It seems the very idea of volunteering needs rescue.  

It wasn’t on my radar to be lifeboat crew, but an unexpected new job in an unfamiliar London suburb unlocked this possibility. When I considered ‘Why wouldn’t I?’, I couldn’t find a strong reason. So, one autumn evening I trekked down for my first Tuesday night at Teddington lifeboat station. It was time to fill in the paperwork: I was officially a volunteer. 

Over the months that followed, I found myself wondering why other people gave their time, energy and skills to complete the nearly 50 training modules and to be available 24/7 when someone on the water was in need. I hungered for people’s stories, to know why they kept answering the call when their beds were warm and the night was unknown. So, over the four years that I was on the crew, I asked them. I spoke with teachers and students, company directors and full-time parents. I heard stories of multiple generations on a crew, their family’s blood running orange and blue. One woman spoke of overcoming her fear of heights to scale the side of a boat; another had an unexpected tale of a dolphin attack. Each time, I had the same question: why do you do it? 

And I was struck by the fact that none of them gave an answer that fully added up. They could name parts of it: care for people, teamwork, a love of the sea. Sometimes of the reasons they started (‘Dad did it’) were not why they stayed on (‘I could make a palpable difference’). I didn’t meet anyone who didn’t enjoy being on the water. Play and peril can co-exist – and we need to have moments of joy along the way if we’re going to be in it for the long haul. But in each case, the answers always seemed to come up a little short. If I was looking for something neat and complete, I wasn’t finding it.  

This is, perhaps, the difference between volunteering and having a hobby. At some point, volunteering will cost you something. 

Back on the river, the knockout races are suddenly interrupted. A call from the coastguard: there’s a person in difficulty in the river. The mood switch is instantaneous; the action swings from contesting to collaborating to get a boat headed upstream as fast as possible. Somewhere, someone is having a very bad day. This is what we exist for.  

The RNLI was born out of a need. In the early nineteenth century, nearly 2,000 ships – and their crews – were being wrecked on British and Irish coasts every year. Sir William Hillary saw this loss firsthand from his home on the Isle of Man, joining with others to rescue as many as possible – but it wasn’t enough. People continued to perish. So, he rallied other activists and philanthropists, and in a London pub, the charity now called the Royal National Lifeboat Institution was formed. Hillary’s motto, 'with courage, nothing is impossible’, can still be found adorning lifeboat stations around the country. 

None of the lifeboat crew members that I met seemed to think of themselves as anything but ordinary. They were full of admiration in the stories of fellow crew mates, but saw themselves as entirely human, naming everyday needs and familiar comforts. Writing about courage, Andrew Davison recognised that, 

 ‘The willingness of a courageous person to forgo ease, safety, the comforts of home, and even to risk life and limb, does not spring from hatred of any of those things’.  

This is, perhaps, the difference between volunteering and having a hobby (also commendable for its health benefits, sense of purpose, opportunities for connection). At some point, volunteering will cost you something. That sacrifice is needed demonstrates the level of care; otherwise, it’s simply another act of self-actualisation in the service of the volunteer themselves. 

It’s dark on the river and the boat crew is still out. The BBC’s team has packed up for the evening. We have tidied the station, no evidence of the antics of hours earlier. We depart. Close to midnight, those of us who can, return. We bring the boat in from the water, and make it ready for the next call, which will inevitably come. One less job for those who’ve been on duty all evening. It’s the least we can do.  

In the origins of the term is a spirit of offering. The Latin voluntaries carries a sense of ‘to give of one’s free will’. This, perhaps, is where we’ve lost our way with the whole idea. For there to be a sense of duress in volunteering is to strip the generous act of its power. Where there is obligation on one side and self-interest on the other, we can find the middle ground marked by devotion, by having chosen to serve and therefore having the commitment to see it through. This is the invitation that volunteering can offer us, and that I glimpsed from people who had been volunteering on the lifeboats for decades.   

Writing to the sea-faring city of Ephesus in ancient Greece, the church leader Paul encouraged people to ‘submit to one another’, which is another way of saying sacrificially help each other. In smaller coastal communities, a lifeboat crew might be called out to save a family member. In London, a city of millions, it will always be a stranger. But either way the decision was the same: to show up. The reasons why we do it don’t always add up. There are flavours of compassion, of wanting to be useful, to be part of something bigger. But there seems to be something else as well. A dedication to meeting a need. Put another way, we might call it love. 

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