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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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10 min read

Wanted, not wasted: the older brother who couldn’t lead

In Peaky Blinders and House of Guinness, Steven Knight shows being needed—not being perfect—transforms

Will Fagan serves as a minister in the Episcopal Church in Birmingham, Alabama.

Dressed in Victorian clothes, two brothers raise their arms together.
Anthony Boyle and Louis Partridge in House of Guinness.
Netflix.

If you’ve watched House of Guinness recently, you’ll find show creator Steven Knight return to familiar territory: masterfully exploring complex dynamics between brothers, family legacy, and ambition – captivating themes he previously explored in his ever-popular Peaky Blinders. In the respective dramas, we find both older brothers struggling to fit into roles and living with the weight that often accompanies that struggle.  

In societal terms, we are not unfamiliar with the oldest son’s placement as the first in line of dynastic succession and head of the family. The Prince of Wales will succeed his father as King; Prince George will succeed his father and so on.  

This dynamic plays out, of course, in common lives as well. Throughout history, the oldest son, as a rule, inherited the family home, the landholdings, and the family business (even if its legal standing was murky at best): Santino became the Don (The Godfather, 1972), Josh Kroenke and Tony Kahn essentially run their respective fathers’ Premiership football clubs, and at some point in your family line, I bet a great uncle took over his father’s blacksmith shop, leaving his younger brother – your direct line – left to fend for himself. (You’re here, after all, so things must have worked out, anyway.) 

What happens, though, when the oldest son is not fit to assume this role in succession? How does he respond if he is passed over? And what happens when he’s actually needed by the younger brother, the successor?  

As Peaky Blinders opens in its first series, we are presented with a perspective that Arthur Shelby, the older brother, is the boss of the family bookmaking syndicate and racketeering operation only to soon discover that his smarter, more ambitious, and more capable younger brother, Tommy, leads the family. 

Being passed over naturally plagues Arthur, and his behavior consistently confirms why he isn’t fit to lead: he is quick tempered, demonstrates poor judgement, and goes on drug-induced benders. He is loyal when he is sober, and you can’t help but love him, but you wouldn’t hire him to run your company, either. By the opening of the show’s concluding series, he is shown passing his days in an opium shop, strung out and all-but-abandoned by his family.  

Knight revisits this theme within the Guinness family in his newest show, set in the 1860s and three generations after the founding of the brewery, the family well-established as the first family of Ireland and wealthy beyond measure.  

From the start, family tension and doubts about the brewery’s continued success are palpable. At the time of his father’s death, the oldest Guinness brother, also named Arthur, is frivolous, irresponsible, and debonair, having returned to Dublin for his father’s funeral after years of carousing in London. He is unkind, arrogant, and frankly does not care what happens with the company, so long as its sale finances the rest of his life. (You don’t root for him like you root for Arthur Shelby.) 

At the time of the reading of his father’s will, anticipating he would inherit the brewery and the bulk of the family property only to sell it, Arthur Guinness finds his father had other plans, haunting him from the grave. He learns that he and his younger brother Edward – responsible and having apprenticed at the brewery – would inherit an equal stake of the brewery and family wealth, but that Arthur would be entitled to nothing if he did not participate in the running of the business, something he neither wants nor cares to do. He wants to be the older brother to inherit but has less-than-no desire to lead the family. 

Saddled with expectations that he neither wants nor could succeed under, he continues his path of ruination – marrying for convenience, partying in unfit circles, and participating in election fraud, all bringing the family into public scandal and private torment. Moreover, and perhaps of greatest importance, he knows that he is the oldest son who cannot succeed, who was never built to, and that his father did not trust him. Thus, he pursues the only thing he is good at – willful self-destruction.  

Well, this is great saga material – one that we will undoubtedly follow in the Guinness family in the coming years – but for us poorer mortals, why care?    

I believe, and I don’t think this is an overstatement, that there is an older brother in all of us. We may not be the actual older brother ourselves waiting to be handed a family fortune only to not receive it, but odds are that at some point there was an expectation thrust upon us – or even one we placed on ourselves – to be a certain type of person or to achieve a concrete level of success, and that didn’t work out.  

Have you, for instance, taken a chance in bringing the antiquated family business into the twenty-first century only to watch it go belly up? Have you found yourself in a relationship for too long “for all the right reasons” because everyone wanted it but you didn’t? Did you want to study architecture at university but read law instead because your father and grandfather were called to the bar and now you find yourself drawing neo-classical designs in the courtroom?  

What happened, then, when that expectation or dream did not come to fruition? Have you, even to a small extent, arrived at the future and found you’re not who you thought you’d be? To not achieve that thing we were destined for, to not rise to the standard, as it turns out, can often leave us in the same state of the black sheep older brother – directionless, lacking a clear station in life and without a sense of worth. 

What is interesting and what is helpful, if I can go so far as to say, is that we find this dynamic at the moral heart of family and social relationships across millennia, a dynamic which is presented in the Christian understanding of relationships. 

Christianity’s understanding of relationships – with both God and one another – rests on two essential claims. The first is that humanity was created for one clear purpose – to love God and to live in perfect harmony with creation and fellow man. According to Genesis, the first book of the Bible, this was the expectation of our divine father, the role destined for all children of God. Yet Adam and Eve, the original children, failed to live righteously according to the standard God gave them and were viewed, thus, as guilty before God. All their descendants (which is to say all humanity) inherit that guilt because of what Christian teaching calls original sin.  

That may sound both celestial and like Sunday school at the same time, and you, by the way, don’t have to take my word for it. But if you were to say that you do live in harmony with God, creation, and fellow man perfectly, I might be compelled to ask, “How’s that really going?”  

When we look around and are honest, we are free to admit that things are not perfect, and we live with the weight of imperfection.  

How do we feel, for example, when we let someone else down? How does it feel when we wake up with a moral hangover? How does it feel when we don’t get the position because of an unexplainable gap in our CV, even though we think we’re fit for it? We can see quickly enough that sublime internal or cosmic harmony does not, in fact, exist in our lives or in any of the created realms. More so, we find that it’s not actually attainable.  

Are we left, then, to live lives with potential unrealized, spiritually incongruent, and unfulfilled? Will the black sheep part of ourselves – perhaps not evidently front and center but certainly left in the margins – become the core of who we are and how we interact with the world?  

As it pertains to Knight’s dramas, a curious occurrence happens to each of these older brothers during the arc of their respective shows, particularly in relation to their younger brothers.  

At some point in every series, Tommy Shelby realizes that despite everything, the one person he needs by his side is his older brother, Arthur. He needs him as he takes down crime boss Billy Kimber and expands the family business; he needs Arthur to be the one to end the vendetta with the American mafia, and, finally, to be his strength and support as Tommy faces his dark and uncertain future in the final series, telling Arthur in the darkness of a damp cellar, “You will change because I need you.”  

Similarly, in House of Guinness, faced with looming political trouble, wanting to expand the brewery, and to continue the family legacy of philanthropy in Ireland, Edward Guinness looks to his older brother Arthur – the only person he can – to fulfill the other half of the inherited partnership and to gain political ascendancy, their father’s MP seat, for the cause of good. He needs him.  

How do these older brothers—otherwise unfit for duty—respond?  

In each case, paradoxically, they don’t crumble under the weight of expectation, but heartily rise to the occasion, becoming the man who their younger brother needs them to be. They are able to do this, by the way, not because there was some secret unfulfilled potential inside them all along (clearly they are who they are), but because despite their self-destructive patterns, the older brothers actually step up when needed because the younger brothers treat them as though they are worthy of being needed.  

Put another way, having worthiness ascribed to them makes them feel worthy, and the result is that they change, they deliver, and their own self-worth changes with it. They each become, as it were, a new man. 

What are we to draw on from this?  

Returning to Christianity’s understanding of relationships – with both God and one another – we find its second essential claim: it is that God knows that our lives are not perfect and harmonious, that we do struggle, that we do have dreams and expectations unrealized, all of which can, depending on the severity, leave one quite weighed down and without a clear path forward.  

If there is good news that can be spoken into that state (and there is), it is that God is not a father with his arms crossed forever disappointed in his firstborn. He is a father who sees the whole picture, knows all the facts, and he has done something about it in the great narrative arc of the Christian story – the crucifixion and resurrection of Jesus. The result of which is that we flawed individuals are seen not as those who fail to love and obey God perfectly but as those who are worthy of being wanted.  

If we can learn anything from these brothers in Knight’s dramas, it is that we need not climb out of imperfection and into success to be unburdened. We find that being seen as worthy is enough. And that changes – as it does for Arthur Shelby and Arthur Guinness – everything.  

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