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
5 min read

Captain America's impossible task

Brave New World struggles despite some acting heroics.
Captain America crouches expectantly beside his shield
Ready for the next review.
Marvel Studios.

Captain America: Brave New World is the thirty-fifth film in the Marvel Cinematic Universe (MCU), and the fourth film focusing on the character of Captain America. It’s also something of a sequel to a passible Marvel TV series. There is so much baggage, so much lore, so much build-up to this film; a production which has the unhappy task of honouring the seventeen years of previous storytelling, setting up plot points that can be explored in future films, and giving us a satisfactory stand-alone cinematic spectacle. I wouldn’t wish such a burden on anyone – an impossible task. 

Brave New World sees Sam Wilson fully inhabiting the role of superhero Captain America, a mantle bestowed on him by his friend and original Captain, super soldier Steve Rogers. Still doubtful of his worthiness and abilities, he seeks to wield the Vibranium Shield with style. He is sent on a mission to retrieve a stolen military secret from a group of mercenaries. He does so – with a few decent action set pieces – and is rewarded with an invitation to the White House.  

The newly elected President, General Thaddeus ‘Thunderbolt’ Ross, is seeking to shed his past reputation as a warmonger by negotiating an international peace treaty. A newly discovered resource has the capability of changing the face of medicine, technological innovation, and especially warfare. Every great power covets it, and Ross wants to foster collaboration for the betterment of the planet. The gala event is ruined when Sam’s friend Isaiah Bradley, a super soldier from the Koren War who was wrongly imprisoned, goes all Manchurian Candidate and shoots at the President. 

The peace treaty is in jeopardy. The President’s inner circle is compromised. There are secrets and lies that will not stay buried. There is a shadowy villain operating behind the scenes, determined to destroy the President’s reputation. Only one man can fight for truth, justice, and the American way: Captain America. 

This is as much as I can say without spoiling the entire film. 

Not that it would matter. The film is a bit of a mess.  

Sam is proposed as an underdog (having not actual superpowers, only a suit of armour), but is shown to be essentially indestructible…he literally disables a missile by flying into it headfirst. There is no sense of tension or risk. This is not helped by lacklustre action and some genuinely appalling CGI. The plot is all over the place – a result of some rather obvious reshoots featuring green screen that even the most amateur filmmaker could’ve improved. Most of the secondary storylines peter out. New characters and introduced and given almost no personality or progression. 

The script compensates for this by giving characters long monologues where they deliver clunky plot exposition and background information. This was inevitable. To understand the plot and characters requires one to have been a careful watcher of the previous films and television shows. I was somewhat impressed how the film managed to give a gentle introduction to the casual viewer, but it is very much at the expense of pacing and character development. 

All of this is a great shame, as the performances are rather good. Anthony Mackie has always been a magnetic screen presence and manages to combine both charisma and pathos is an uncharacteristically restrained performance. Tim Blake Nelson enjoys himself as the puppet-master villain, oozing bile and sympathy in equal measure. Every minor friend and villain delivers their lines with real feeling. Bloody hell…even lovable grump Harrison Ford looks like he’s actually trying as President Ross. 

Unfortunately, no amount of charisma can make up for a film that has no sense of itself. The shambles of a plot is matched by the shambles of a theme; a sadness, as there is so much potential. Sam Wilson is one of only a handful of black superheroes, and his friendship with Isaiah Bradley is partly based on their shared experience of race and discrimination in the face of honour and duty. This was introduced in the TV show and could’ve been explored further. Sam’s lack of superpowers could have been explored, had he been put in positions of genuine peril. His sense of inadequacy and overwhelming responsibility are mentioned, only to be quickly dismissed with a pep-talk from a throwaway cameo character. The concepts of conspiracy and disillusionment with authority are hinted at, but they formed the thematic thread of the previous three Captain America films, and when this film does approach them, it is by echoing the better storytelling of previous films. 

There is one plot thread, one theme running through the story, which goes some way to redeeming the film. President Ross is haunted by his past. A patriot, a soldier, and tireless worker for American security, Ross has a past littered with sins and mistakes. His anger, his bullishness, his obstinacy (physically manifested at the end of the film), has left him all alone. His daughter doesn’t trust him, Sam doesn’t trust him, and his international partners don’t trust him. He is seeking to become a better man, working towards cooperation rather than force and violence. However, his past life and secrets continue haunt him and stall his progress at self-improvement. 

In the end, by being open and honest and taking responsibility for his mistakes, Ross does achieve a certain amount of peace. He is able to be the figure of nobility and unity that he longs to be by sacrificing his power and prestige, and truly atoning for his misdeeds. Despite all the problems with the film, this (admittedly underdeveloped) bit of character study kept me engaged. Perhaps it was Harrison Ford’s performance. Perhaps it was because we’re approaching Lent, when Christians make an extra effort to acknowledge their past mistakes and resolve to do better. Whatever it was, it furnished the film with a truly sympathetic and improving theme. I wouldn’t spend money in the cinema, but wouldn’t mind seeing it in the TV guide in the future. 

2.5 stars. 

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