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
Death & life
Digital
Easter
4 min read

Do you have a right to be remembered?

Our desire to be in control might not survive our demise.

Jack is a graduate of Peterhouse, University of Cambridge and Blackfriars, University of Oxford. He writes, and also works in local government.

A composite show a smiling woman next to a small illustrate of someone walking off into the distance.
Kristyna Squared.one on Unsplash .

“Madam, those that are about to die salute you.”  

Words attributed to Roman captives and criminals fated to die before the emperor, were used (ironically) by Councillor Kieron Mallon at the last Council meeting of this term of Oxfordshire County Council last week. ‘Madam’ was the Council’s Chair, wishing everyone well. Elections are on the way. 

Easter is also on the way, and in the period leading up to the commemoration of the resurrection of Christ from the dead, nearly 2,000 years ago, Christians are invited to think about their own mortality. ‘Remember that you are dust, and to dust you will return’ were words my priest intoned to me as he marked a cross with ashes on my forehead on 5 March, Ash Wednesday. 

Ash already emblemizes a belief in rebirth, even before the power of the story of the Christ’s resurrection is considered. I for one felt immensely hopeful on Ash Wednesday this year. Having just secured a new place to call home, and one year into my job as Democratic Services Officer to Oxfordshire County Council, looking after the likes of Councillor Mallon, life felt pretty swell. 

My priest and I spoke about the ways in which death and hope are joined at the hip. The ancient Greeks believed that a phoenix obtains new life by rising from the ashes of the one before it. So do we. I have found myself, so far this year, visiting people and places I strongly associate with former lives, from friends I lived with as an undergraduate to a town I went on holiday as a child to the beach where my late Granny’s ashes were scattered. ‘Ashes to ashes, dust to dust.’ 

More specifically, the Christian believes that ‘whoever loses their life for [Christ’s] sake will find it’, in the sense that true self-discovery arises when we let go of the ego, when we allow ourselves to be changed. Thinking about mortality, therefore, changes life, in so far as we are better equipped to surrender and salute the Saviour. That worldview has shaped public servants in years gone-by. 

An overwhelming majority of people in the course of human history have been forgotten.

I recently heard Dr Ian McGilchrist, the psychiatrist, describe the desire to control everything in life as the ‘besetting sin’ of the age in which we live. The desire to be remembered, rather than reborn, captures it better in my mind. Mankind has always wanted to remain in control. Souls will always be reluctant to surrender. However, what we have now is a world in which people feel uniquely entitled to make impact. 

People feel that they have a right to be remembered, but it is not so. An overwhelming majority of people in the course of human history have been forgotten. Moreover, the past can be especially compelling when we have a window into a world in which people did not necessarily expect to make any kind of worldly impact whatsoever. Theirs was a happier place. 

The twentieth century was described by Philip Rieff in 1966 in terms of the ‘Triumph of the Therapeutic’. He wrote, ‘Religious man was born to be saved’, but ‘psychological man is born to be pleased.’ ‘Psychological man may be going nowhere, but he aims to achieve a certain speed and certainty in going’. Therapy enables that objective. But therapy to what end? 

Counselling can be construed as a device to regain control. The counselled, if fixed, can go about trying to change the world, trying to make an impact, resuming the rather pleasing but never-ending mission to be remembered. For anyone of a religious sensibility, however, that is not the objective. Rather, new life is given only for the whole resurrection story in our own lives to be repeated. 

Around the time that Rieff wrote his book, the historian Herbert Butterfield, a Christian, wrote this. ‘Those who lived when the world was static – when the silhouette of the ploughman against the horizon hardly changed in the passage of a thousand years – may have something to teach us, who only know a breathless, rapidly changing world and who seem to be having to pluck what we can from life while running at full speed.’ 

Social media has surely exacerbated this condition because it connects us to others at the cost of contemplation about what life – and death – really entails. It is a place where we try to evidence to others the impact we are having, where we write our own eulogies and our own epitaphs and have access to the whole world whom we expect to read the same. 

Life changes to a much greater extent these days, in this place, than it did for the ploughman in the passage of a thousand years, or captives and criminals in the Roman world, including Jesus Christ who was identified as one such. However, if we can somehow create conditions to focus less on having impact in and on a volatile world, and being someone who ought to be remembered, we will find that we have more hope. 

In turn, we will change the world for the better, but despite ourselves, and for me that is what this period leading up to Easter is all about. We may find that others who are about to die salute us too, for the good deeds we have done that may well be forgot. 

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