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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Review
Culture
Film & TV
Fun & play
Justice
5 min read

Boom! I love this new Superman!

Eschewing ennui, it’s a great fairy tale for the modern age
Superman talks to his dog amid the ice.
Superman and Krypto the dog.
Warner Bros.

…and that’s what makes this film so enjoyable! 

Oh, apologies for any confusion.  

No tortuously ‘relevant’ preamble from me today. I’m starting the review right in the middle of the action, because that is exactly what Superman does. No initial slog through a ‘backstory’ that everyone knows – even my wife, who has never read a comic book in her life, is familiar with who and what Superman is. The closest we get to contextualisation is a quick sequence of text: informing us that Superman landed 30 years ago (adopted by the Kent couple, and given the name Clark), began his superhero career three years ago, stopped the fictional nation of Boravia invading the equally fictional Jarhanpur three weeks ago, and three minutes ago lost a battle for the first time. 

Boom! 

Then straight into the action! 

Superman lands in the frozen tundra of the Antarctic and can barely breathe. He lets out a whistle and the next thing we know there is a tremendous snowy disturbance. Krypto the Superdog dashes into view! No explanation – just delight in the fact that there is a mischievous canine with unbelievable power. Krypto drags Superman ‘home’ to the Fortress of Solitude. There the Superman robots heal him with a concentrated dose of radiation from the Yellow Sun which gives him his power. He immediately departs to continue his bout against the nationalist supervillain ‘Hammer of Boravia’, who is secretly being controlled by the evil genius and billionaire Lex Luthor. 

The pace of this film isn’t fast…its hypersonic. It flies by at the speed of Superman himself. There isn’t any lag, any let up. Even the quieter moments, such as those meditating on Superman’s dual identities (the alien superhero Kal El/Superman and the human reporter Clark) or his burgeoning relationship with investigative journalist Lois Lane, keep the story moving. Exposition doesn’t take place through inexplicable monologues; it is always pacy conversation, which teaches us something about the characters and their relationships and their motivations. 

This is the great triumph of writer/director/producer James Gunn. After his success over at Marvel Studios, he has taken the helm of DC and started to create a universe of characters and stories that doesn’t waste time with painful ‘exploration’ and moralising. This was always the issue that held DC films (arguably featuring the more beloved and well-known characters in comic-book culture) back from matching the success of Marvel. Christopher Nolan is a genius, giving us a superb Batman trilogy, and Zac Snyder produced an underrated dark take on Superman, but neither seemed to delight in the bright, bubble-gum, kaleidoscopic colourfulness of the comic-book medium. 

Gunn refuses to make his Superman film gritty or realistic. Characters appear in all their flash and bombast and are welcomed as cheery additions. The ‘Justice Gang’ are simply there – including the always enjoyable Nathan Fillion with an arrogant smirk and an almost offensive bowl cut. Luthor’s genius allows his to create a parallel dimension…why couldn’t he!? If we can suspend our disbelief to accept a protagonist who is an alien superhero, why not a mini-universe?  

There is none of the former focus on psychological trauma and existential crisis and the sheer overwhelming ennui of being. In previous films the ethical lesson wasn’t just ‘on the nose’…it flattened your nose with a Mike Tysonesque haymaker! Here, Superman simply IS. He IS good. He IS upstanding. He IS fighting for truth and justice. He refuses to allow political and public-relations considerations to corrupt and dilute his absolute commitment to do (and to BE) what is right. One of the most dramatic scenes isn’t a grand battle, it is a quiet moment where Clark allows Lois to interview him as Superman. The more she questions the realpolitik implications of stopping an invasion, the more Clark becomes incensed. How could someone not allow themselves to save innocent life and serve justice to the oppressed against the oppressor? 

The film is such a ‘sigh of relief’ in a bloated comic-book-film market. Yes, the script is hilarious – this is Gunn’s forte. Yes, the music is sublime – both John Murphy and David Fleming’s score (with wonderful nods to the John Williams original) and Mr Gunn’s own needle-drops. The performances are excellent across the board – special mention to David Corenswet, who doesn’t quite look like Superman to me…but boy does he embody the very essence of the character, to the point where you can’t imagine anyone else having played the alien since Christopher Reeve. But its truest strength and victory is its joy in the simplicity (especially moral) of this comic-book genre. 

This is what is so refreshing about Gunn’s vision. Superman IS pure. Lex Luthor (Nicholas Hoult not missing a baldy beat) IS so prideful and vain that it has warped him into something twisted and evil and collapsing in upon his own ego. Watching the film, I was put in mind of C. S. Lewis’ writing on the nature of fairy tales: 

“For in the fairy tales, side by side with the terrible figures, we find the immemorial comforters and protectors, the radiant ones…” 

Comic-books are the great fairy tales of the modern age…why would we make them brooding deconstructions of the human condition, a la Cormac McCarthy? That isn’t their point or purpose. Lewis again: 

“Since it is so likely that they [children] will meet cruel enemies, let them at least have heard of brave knights and heroic courage. Otherwise you are making their destiny not brighter but darker.” 

Gunn has given us a film that isn’t just fun and fluffy, but important. In his sugary, childlike wonder and delight in the genre, he has given us a tale of good versus evil that is a true fairy tale: something gleaming and good, something radiant and right, something attractive and aspirational. Superman is a fairy tale where we can be comforted and emboldened by the moral (nay, ontological!) certainties of love and hope.  

5 stars

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