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
AI
Culture
Film & TV
4 min read

Ethan Hunt is MI Jesus, and it’s ridiculous

The final instalment of Mission Impossible warns about AI, yet plays out as if written by a chatbot.
Tom Cruise playing Ethan Hunt in an open necked shirt looks perplexed.
Tom Cruise in action.

Is this the FINAL reckoning? I’m not sure. I hope so. There has been speculation whether Tom Cruise will reprise his role as Ethan Hunt in further franchise instalments. He has expressed interest, while also suggesting that the use of the word ‘final’ is purposeful and indicative. Let us all pray that he’s being honest. I mean…he must be exhausted. The stress and strain, the pressure and pain, that he puts his body through for every Mission Impossible film is approaching elder abuse – he is 62 after all. 

In a departure from tradition, Mission Impossible: The Final Reckoning is an immediate sequel to Mission Impossible: Dead Reckoning, which released in 2023. The series which has thrived on a formula of releasing stand-alone spy stories, allowing us to enjoy familiar characters in new scenarios, has decided to make a two-parter…although you wouldn’t know it. You don’t need to have seen Dead Reckoning to pay your money to watch Final Reckoning, as the script assumes you’ve not only missed the immediate prequel, but have never viewed any other Mission Impossible film.  

Goodness me, the film is plodding. It begins with a message from the President (Angela Bassett), delivered to Cruise’s super-spy Hunt. In previous instalments such messages have been a punchy way to set the stakes, roll the pitch, and then give the rest of the screen time over to remarkable action set-pieces. On this occasion we have an interminably long, and irritatingly portentous, monologue detailing why Ethan Hunt is the best of spies, the best of men, and essentially MI Jesus. The only man who can save the world from a literal apocalypse.  

The premise of the film is that the malevolent, power-hungry AI known as ‘The Entity’ (could no one have thought of a better name, REALLY!?), which Hunt failed to stop in the previous film, is now at large and tipping the world towards destruction. It is manipulating the media, gaslighting governments, and slowly infiltrating the nuclear arsenals of the world, all in preparation to annihilate most of the human race in a nuclear holocaust. It then plans to rule the remaining vestiges of humanity and create a new utopia for itself. Only Ethan Hunt can stop it…just as long as he convinces world leaders to trust him, finds the nuclear submarine where ‘The Entity’ originated, defeats hundreds of bad guys, and infiltrates a top-secret bunker in South Africa. 

We’re a world away from the lean and mean story of the first MI, where we only had the identities of CIA assets at stake! 

Its rubbish. Genuinely rubbish. 

The script is ripe. Nay! It is overripe. NAY! Burn the whole house down, because the brie has grown limbs and the fruit bowl is plotting your death. Every other conversation involves either Cruise pontificating on how the only way to defeat ‘The Entity’ is love and trust and the age of Aquarius, or someone explaining to Cruise how this mission is his destiny, because only he is good and pure enough to succeed. He’s MI Jesus, and it’s ridiculous. 

The film plods and plods and plods. The whole point of this franchise is to provide the viewer with regular, breath-taking action, and yet the first hour-plus is a litany of exposition and call-backs. Ethan travels to several European capitals, for about thirty seconds apiece, before formulating his plan. This is confusing and jarring, but to add to this pain, the audience is tortured with disorienting, quick-cut montages of Hunt’s previous adventures. The plot seems to be determined to link this final, world-ending catastrophe to his past escapades…except MI2…no one has love for that. 

Unfortunately, all these positives are packaged in such a self-aggrandising and cack-handed manner as to be rendered inert.

By the time the action really kicks in I was exhausted and in no mood. This is a shame, because the action is truly spectacular. A long sequence in a submarine – which is both well below safe diving depth, but is also slowly falling of an underwater cliff. A breath-taking fight between two biplanes. Gunfire galore. I recognised its brilliance on an intellectual level, but enjoyed none of it. I was too damned bamboozled by over an hour of nonsense beforehand. 

The performances are fine. Cruise is the last remaining true action star, putting himself through a gruelling regimen to ensure he performs his own stunts. This shows on the screen and is very much appreciated and commendable. Simon Pegg returns as Benji to provide the comic relief. Ving Rhames’ Luther has a brief appearance which is bitter-sweet and lovable. Henry Czerny and Rolf Saxon are delightful additions – the only call-backs to the first film which don’t irritate, and actually elevate the film. 

Mission Impossible: Final Reckoning is fine. It is serviceable. It delivers the heart-stopping thrills. It has timely theme: of what true humanity and human relationship is in a world dominated by AI, technology, simulated reality, and simulated interaction. This is all good. Unfortunately, all these positives are packaged in such a self-aggrandising and cack-handed manner as to be rendered inert. For a film whose story serves as an (admittedly histrionic) warning about the dangers of AI, it plays out as if designed by chatbot. 

The Mission Impossible films have always been a vehicle for Tom Cruise. This has been their greatest strength – he is the last true movie star after all, and we may never see such a charismatic and powerful screen idol again. This has also been their greatest weakness. What a shame this only became apparent in the (potential) final outing. 

  

2 stars. 

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