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
Assisted dying
Culture
Politics
5 min read

Assisted dying and the cult of kindness 

I witnessed an assisted death. We need to be honest in the debate about it.
A tableau shows minature figures of two people, one sitting on a life size syringe and the other stands
Etactics Inc on Unsplash.

The Assisted Dying Bill is likely to be passed into law this autumn, the government having promised to ‘rush it through’. The debate will invariably be conducted in a fog of euphemistic language in which ‘compassion’ and ‘dignity’ will feature heavily on both sides, while the main point is likely to be missed: the legalisation of euthanasia or AD, marks a tectonic shift from a Christian to a post-Christian society and should be a wake-up moment for dozing Christians. 

I was recently present when my aunt, an artist who had become a Canadian citizen, died by euthanasia in her own home while in the very early stages of motor neurone disease. She was 72, divorced, living independently, fully mobile (although she had lost the use of one arm) and was laughing and joking up to the moments before the doctor (or ‘The Killer’ as her son called him) injected the first dose of the lethal cocktail. It happened at 7pm on a Tuesday evening. She had made the phone call requesting her death at 3pm the previous Sunday – yes, a Sunday. Service of a kind our NHS can only dream of. 

As a reluctant witness to what I consider a murder-suicide, I was nevertheless beguiled by the relatively clean ending (although there was some disturbing gurgling that apparently occurs as a result of the lungs filling with fluid) to a life that was about to become very difficult. Her two older siblings, including my mother, are each currently several years into slow deaths from combined Parkinson’s and dementia. 

I am an almost daily visitor and a secondary carer to my mother, and while she is mute, benign and seemingly contented, the toll on my stepfather and on me is enormous. I often pray for it all to be over – it’s an endless grind and her former self would be utterly horrified to see herself this way! – and yet, as a Christian, I have to see purpose in it. One thing it certainly does do, is force carers to be selfless and compassionate in the strict sense of the word, which is ‘to suffer with’. 

Her decision to die was the ultimate consumer choice – she availed herself of a service that promised to free her from her ailing body as quickly and comfortably as possible.

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My aunt didn’t want the trial of becoming ill and dependent, and the Canadian government gave her an opt-out which she grabbed the instant she received her diagnosis. Confirmation by two doctors that she was terminally ill and of sound mind – almost a trifling formality – got her immediate approval. She was, to use her kind of language, ‘out of here’ a mere three months later. 

How could she have been so cavalier and determined to die, despite the protests of her son, nephew and granddaughters? She was, in hindsight, a perfectly minted product of the 1960s who believed above all in doing her own thing - whatever felt right. Such notions were anathema to her Christian parents and their dutiful wartime generation but are now the norm.  

Like many who came of age to the sound of the Beatles, she toured the spiritual supermarket and picked out the nice bits from Christian, pagan and Eastern religions – predominantly those that allow you to think that life is about ‘being in tune’ or feeling good about yourself. This did most definitely not include becoming immobile and having strangers change her nappy. She believed in an afterlife, ‘love’, aliens and reincarnation but definitely not in judgement or consequences for her suicide. 

Her decision to die was the ultimate consumer choice – she availed herself of a service that promised to free her from her ailing body as quickly and comfortably as possible, with the added bonus of leaving her assets to her family. 

The truth, as the Canadian experience demonstrates, is that AD is not a slippery slope but a cliff edge.

Polls in Canada and the UK show that the vast majority would consider this a win all round. According to Opinium, 75 per cent of British adults support AD. In political terms this a ‘bridge issue’ almost without comparison, uniting 78 per cent of Conservatives with 77 per cent of Labour supporters, yet no issue should more starkly dramatise the unbridgeable chasm between Christian and secular world views. 

The sharpness of this divide has, however, been successfully obscured by the insidious (and to my mind, diabolical) Cult of Kindness that has inveigled itself into both secular and Christian space. Imitating Christian virtues, it subverts them by subtly perverting language - by using ‘compassion’ when what is meant is ‘convenience’, for example – and by making ‘happiness’ rather than self-sacrifice the highest good. This leads both sides into dishonesty and self-delusion. 
 
The biggest pro-AD lie is that it is merely an escape route for the tiny few facing the most intolerable suffering with no additional consequences. The truth, as the Canadian experience demonstrates, is that AD is not a slippery slope but a cliff edge. It is now the fifth most common cause of death and climbing by 30 per cent each year. Every seriously ill Canadian now feels some pressure to address the option. Cases of people choosing AD out of despair, depression or at the suggestion of a lazy or uncaring State official are already numerous. Those who have signed an advance consent waiver setting a date for their euthanasia in the event of their mentally incapacity, are now being terminated. In some cases, the demented refuse to cooperate and are euthanised under forced sedation. The State is already saving money and families are saving their inheritances. Life itself has been downgraded. 

The Christian side indulges in even bigger untruths. Windy episcopal speeches about advances in palliative care avoid the hard fact that denying AD involves many suffering prolonged and painful deaths while family finances are destroyed and carers worn down to a husk. The pill can’t be sugared: thou shalt not kill is absolute, not an invitation for an ethical discussion. The point is so fundamental that to avoid it and be drawn into discussing the minutiae of legislation is a betrayal of the faith. 

Christians won’t save the secular world from AD and its consequences, but the current debate is an opportunity for honesty and for Christians to save themselves from the delusion that the true virtue of compassion can be inverted to justify killing.  

The Christian religion began with an agonising death of a kind which its scriptures exhorts its followers not to fear. It’s a tough message: God doesn’t promise the comfort we would like in this life. We do have the means and the duty to alleviate much suffering, but death as a consumer choice is simply off the table.