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
Books
Culture
Morality
Sin
7 min read

After the Salt Path revelations I’m liking it even more

We edit our own reality by the stories we tell ourselves

Roger is a Baptist minister, author and Senior Research Fellow at Spurgeon’s College in London. 

A newspaper front page shows its title and a falling sea bird
How The Observer broke the story.

The Observer held nothing back in its exposé headline:

“The real Salt Path: how a blockbuster book and film were spun from lies, deceit and desperation”

The truth behind the summer’s feel-good movie and the reputation of author Raynor Winn lie in tatters, shredded by the revelations unearthed by relentless investigative journalism.

The uplifting story of how a couple face financial ruin, homelessness and a terminal illness by walking the South West Coast Path has been an inspiration for many who’ve either read the book or seen the film, or both. The story works because it reflects back to us the life we know, the lives we live. And when you add the seaside of Somerset, Devon, Cornwall and Dorset, what’s not to love?

But now it needs to be seen in an altogether different light.

The article beneath the headline was thoroughly researched, carefully constructed and uncompromising in the allegations implied by the discoveries, observations and commentary of its narrative.

“… not her real name”

“… she was a thief … embezzled the money”

“… arrested and interviewed by the police”

“… five county court judgements”

“… they owned land in France”

“… nine neurologists … were sceptical”

Point by point the back story of the Salt Path is pulled apart.

First, Raynor and Moth Winn are not the “real”, “legal” names of Sally and Tim Walker.

Second, The Observer uncovered that the couple had money troubles for reasons other than the failed business investment they had claimed. Rather, as a part-time bookkeeper for an estate agent and property surveyor, Sally was accused of syphoning off £64,000 from the company’s accounts. Concerning which, it was reported that she was arrested and interviewed by the police.

Third, it was mounting debts from settling the matter with her former employer, alongside other debts, that actually led to the repossession of their home and their resulting homelessness. Not the failed business venture.

Fourth, they weren’t actually homeless as they owned a property in France, near Bordeaux. While it was in a state of disrepair and not habitable, they had previously stayed on site in a caravan.

And then finally, in a revelation that undermined the very heart of the story of their journey together, medical experts observed that it was extremely doubtful that Moth had suffered from corticobasal degeneration (CBD) for 18 years. The journalist had consulted nine neurologists, and this was the reported consensus. Not only were Moth’s presenting symptoms not what were expected, the normal life expectancy with the condition was tragically short at six to eight years.

Pulling the various strands of its investigation together The Observer thumps the tub about the importance of ‘truth’. It is not acceptable to be mis-sold an idea of truth where important passages of the book are invented. There are both “… sins of omission and commission”:

“The story, no doubt, has elements of truth, but it also misrepresents who they were, how they started out on their journey and the financial circumstances that provided the backdrop.”

However, life is complicated and there are always two sides to a story.

In a response posted to her website Raynor Winn answers each of the accusations in turn. Amid the storm of vitriol and threat unleashed online by the article, she protests that, “… [it] is grotesquely unfair, highly misleading and seeks to systematically pick apart my life.”

Most distressing has been how Moth has been traumatised by the suggestion his diagnosis was made up. Along with her online statement Winn has posted appropriately redacted letters from the neurologists treating Moth that confirm his diagnosis and the narrative of the book.

As for the charges of embezzlement, she does concede that there were difficulties with a former employer. Allegations were made to the police, and she was questioned about them. However, no charges were brought, and a settlement was reached that included her paying back money on a “non-admissions basis”.

“Any mistakes I made during the years in that office, I deeply regret, and I am truly sorry.” Raynor Winn

This, however, was not the failed business deal that lay behind their financial difficulties and which triggered their homelessness and the Salt Path story.

Winn reports that the property in France is an “uninhabitable ruin in a bramble patch” with its own, unrelated, back story. When they did explore selling it at the height of their difficulties, a local French agent valued it as virtually worthless and saw marketing it as pointless.

Ultimately, they chose not to declare themselves bankrupt and simply wipe out their debts. Rather, they made an agreement with their creditors for minimal repayments. The success of the book has enabled all their debts to be cleared.

Which leaves the implicit accusation of not being who they said they were, of hiding behind pseudonyms and not owning their “real”, “legal” names. She explains that the reasons Sally Ann and Tim Walker are Raynor and Moth Winn is really quite straightforward.

In the early years of their relationship she told Moth how much she disliked being called Sally Ann and would have preferred the family name, Raynor. Moth called her Ray from that point on. Winn is her maiden name. As for Moth, well his name is Timothy, get it? Friends and family use the names interchangeably, Sal/Ray, Tim/Moth.

Having read the book and seen the film earlier this summer I was particularly taken with The Salt Path. The humanity of their story, the journey they’d been on and the insights to a life well-lived that it offered.

Goodness, which one of us has never made a mistake, a bad call, or a wrong choice, “through weakness, through ignorance or through our own deliberate fault”?

When The Observer’s bombshell broke my heart fell. Moral high horses were being mounted and outrage expressed. Raynor Winn was being cancelled, literally cancelled.

She pulled out of her forthcoming Saltlines tour, which would have seen her perform readings from her books alongside the music of the Gigspanner Big Band during a string of UK dates. There were also calls for Penguin to cancel her next book, On Winter Hill, set for publication in October.

But do you know what? On reflection, after the revelations about the Salt Path story I’m liking it even more. And for exactly the same reasons I liked it before. Because it reflects back to us the life we know, the lives we live.

For a start, life is messy. Sometimes it’s even murky, full of misunderstanding, misinterpretation and constructed narratives. Goodness, which one of us has never made a mistake, a bad call, or a wrong choice, “through weakness, through ignorance or through our own deliberate fault”? Skeletons and cupboards come to mind.

Then, on the back of that, we all fashion the story of our lives. Whether it’s curating our online presence with the images we post to social media, or the anecdotes we share and the face we present to those who are part of our day-to-day lives. The pull is always towards a version that shows us in the best light.

In fact, it can even go right down to the stories we tell about ourselves, to ourselves. The interpretation of what has happened to us and why. Interpreting how much of our experience is down to what has been done to us or is the fruit of our own responsibility.

Now, I may not want to go as far as University of Sussex Professor of Neuroscience, Anil Seth, whose books, articles and Ted Talks see us living in a kind of ‘controlled hallucination’. An interpreted version of reality constructed and calibrated by our brains out of our experience. But there is no doubt in my mind that we edit our own version of reality by the stories we tell ourselves and each other.

This is how things are. This is what it means to be human. Some bits are edited in, others edited out. Some experiences we can interpret in one way, while others might view them very differently from where they stand.

When we feel the temptation to write someone off because of what they’ve done we do well to reflect on our own experience. Then we may well be grateful that we haven’t been cancelled because of our past indiscretions.  As the old saying goes, “There, but for the grace of God, go I.”

I’m reminded of how Jesus handled himself is such circumstances. When a self-righteous crowd were swiftly wanting to rush to judgement on a woman’s flawed sexual choices, Jesus encouraged those who were without fault to be the first to act. Slowly they all realised what he was saying and backeddown.

For myself, I have always found the prayer of confession to be profoundly helpful. It keeps us grounded in the reality of our own experience and should caution us about cancelling others and writing them off.

Almighty God, our heavenly Father,

we have sinned against you

and against our neighbour

in thought and word and deed,

through negligence, through weakness,

through our own deliberate fault.

We are truly sorry

and repent of all our sins.

For the sake of your Son Jesus Christ,

who died for us,

forgive us all that is past

and grant that we may serve you in newness of life

to the glory of your name.

Amen.

For our skeletons there is forgiveness.

For what lies ahead, we have the possibilities of starting over.

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