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Biology
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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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Column
Culture
Digital
Film & TV
Justice
4 min read

Data scientists should stop watching Minority Report and start watching The Shawshank Redemption

A justice ministry’s prejudicial database leaves no room for redemption.

George is a visiting fellow at the London School of Economics and an Anglican priest.

Tom Cruise gestures with his fingers in an e-glove in front of his face
Tom Cruise takes the measure.
20th Century Fox.

The go-to for any news item about using AI to predict crimes before they happen is Steven Spielberg’s Minority Report from 2002, starring Tom Cruise as a futuristic cop, who employs human “precogs” as clairvoyants to get ahead of the villains. 

So, I’m far from the first to name-check it as showing the dystopian future that the UK’s Ministry of Justice heralds with its test project to “explore alternative and innovative data science techniques to risk assessment of homicide.” 

That use of “homicide”, rather than the more British “murder”, is telling, almost like the Ministry wonks have just watched the movie. The pressure group Statewatch has no doubt where they’re heading, with data being used on people who may never have been convicted of an offence and “will code in bias towards racialised and low-income communities.” 

Spielberg was always ahead of the curve. But my fear is less the chilling dystopia that Statewatch sees in its precog. Actually, I’m more worried about the past in this context, or rather in how we treat the past. 

If I haven’t to date done anything wrong, then I have committed no offence. I am literally innocent. And that’s an absolute. An interpretation of data that indicates that I’m more likely to commit a crime than others is neither here (in my conscience) nor there (in the judicial system). 

Furthermore, there’s a theological point. If it is so, as we’re told, that no one is without sin, then we’re all culpable in the pasts that we have lived so far, but the future contains all we have to play for.  

To suggest that some of us are more likely to screw up in that future than others is very dangerously deterministic. It’s redolent of Calvinism’s doctrine of the “elect”, those who have already been marked for salvation and eternal bliss, regardless of what they do or don’t do in this life, while the rest of us, however virtuous our mortal deeds might be, will rot in hell. 

Neither Calvin’s determinism nor the Ministry of Justice’s prejudicial database leave any room for redemption. They’re just trying to identify events that will definitely (the former) or are likely to (the latter) happen. Conversely, we live in hope (for some of us a sure and certain hope) of a future in which we can be redeemed, whatever we have done in the past. 

And that’s why I find Minority Report an unsatisfactory analogy for the development of real-life precrime technology. It is a film that is only about determinism, which leaves no room for either free-will or redemption. And that’s applying a form of intelligence that is truly, er, artificial. 

The vital thing is that hope is fulfilled, the prisoners make it to their paradise after worthless lives spent in jail. Justice is seen to be done.

A more helpful movie, richer in its development of these themes – and not just because it’s got the word that I favour in its title - is 1994’s The Shawshank Redemption, based on a novel by Stephen King. Here we have the idea explored that the past isn’t only irrelevant to our futures, but doesn’t even really exist in time in relation to the future. 

It’s bursting with more religious themes even than Clint Eastwood’s spaghetti westerns, which are really only the righteous saviour turning up to defend flawed goodies from evil baddies, again and again. For a start, The Shawshank Redemption is set in a prison, where whole lives are spent atoning for crimes that have or haven’t been committed. See? 

Lifers who are released after decades struggle to cope or kill themselves. The central character, a messianic figure, lives in hope with his convict friend of reaching a beach in the Virgin Islands, while the prison warden describes himself as “the light of the world”, but is assisted by his prisoners in money-laundering – washing clean – his ill-gotten gains. 

I could go on. But the vital thing is that hope is fulfilled, the prisoners make it to their paradise after worthless lives spent in jail. Justice is seen to be done. But the important thing here is that there is no pre-crime determinism. The future, which often looks hopeless, is rolling out towards the possibility of redemption, which ultimately becomes the only certain reality. 

One can dwell on movie plots too long. They are only, if you’ll excuse the pun, projections of life. But it is nonetheless irritating both that a government department with Justice in its title can believe it worthwhile to explore how it might deploy AI to predict who tomorrow’s criminals are likely to be and its critics condemn it by using the wrong dramatic analogies. 

Minority Report was a dystopian thriller that suggests that the future can only be changed by human intervention. The Shawshank Redemption showed us that inextinguishable human hope is in a future we can’t control, but can depend on.     

Anyone who is interested in justice, especially those who work in a ministry for it, might benefit from downloading it.  

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