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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Article
AI
Culture
Generosity
Psychology
Virtues
5 min read

AI will never codify the unruly instructions that make us human

The many exceptions to the rules are what make us human.
A desperate man wearing 18th century clothes holds candlesticks
Jean Valjean and the candlesticks, in Les Misérables.

On average, students with surnames beginning in the letters A-E get higher grades than those who come later in the alphabet. Good looking people get more favourable divorce settlements through the courts, and higher payouts for damages. Tall people are more likely to get promoted than their shorter colleagues, and judges give out harsher sentences just before lunch. It is clear that human judgement is problematically biased – sometimes with significant consequences. 

But imagine you were on the receiving end of such treatment, and wanted to appeal your overly harsh sentence, your unfair court settlement or your punitive essay grade: is Artificial Intelligence the answer? Is AI intelligent enough to review the evidence, consider the rules, ignore human vagaries, and issue an impartial, more sophisticated outcome?  

In many cases, the short answer is yes. Conveniently, AI can review 50 CVs, conduct 50 “chatbot” style interviews, and identify which candidates best fit the criteria for promotion. But is the short and convenient answer always what we want? In their recent publication, As If Human: Ethics and Artificial Intelligence, Nigel Shadbolt and Roger Hampson discuss research which shows that, if wrongly condemned to be shot by a military court but given one last appeal, most people would prefer to appeal in person to a human judge than have the facts of their case reviewed by an AI computer. Likewise, terminally ill patients indicate a preference for doctor’s opinions over computer calculations on when to withdraw life sustaining treatment, even though a computer has a higher predictive power to judge when someone’s life might be coming to an end. This preference may seem counterintuitive, but apparently the cold impartiality—and at times, the impenetrability—of machine logic might work for promotions, but fails to satisfy the desire for human dignity when it comes to matters of life and death.  

In addition, Shadbolt and Hampson make the point that AI is actually much less intelligent than many of us tend to think. An AI machine can be instructed to apply certain rules to decision making and can apply those rules even in quite complex situations, but the determination of those rules can only happen in one of two ways: either the rules must be invented or predetermined by whoever programmes the machine, or the rules must be observable to a “Large Language Model” AI when it scrapes the internet to observe common and typical aspects of human behaviour.  

The former option, deciding the rules in advance, is by no means straightforward. Humans abide by a complex web of intersecting ethical codes, often slipping seamlessly between utilitarianism (what achieves the most amount of good for the most amount of people?) virtue ethics (what makes me a good person?) and theological or deontological ideas (what does God or wider society expect me to do?) This complexity, as Shadbolt and Hampson observe, means that: 

“Contemporary intellectual discourse has not even the beginnings of an agreed universal basis for notions of good and evil, or right and wrong.”  

The solution might be option two – to ask AI to do a data scrape of human behaviour and use its superior processing power to determine if there actually is some sort of universal basis to our ethical codes, perhaps one that humanity hasn’t noticed yet. For example, you might instruct a large language model AI to find 1,000,000 instances of a particular pro-social act, such as generous giving, and from that to determine a universal set of rules for what counts as generosity. This is an experiment that has not yet been done, probably because it is unlikely to yield satisfactory results. After all, what is real generosity? Isn’t the truly generous person one who makes a generous gesture even when it is not socially appropriate to do so? The rule of real generosity is that it breaks the rules.  

Generosity is not the only human virtue which defies being codified – mercy falls at exactly the same hurdle. AI can never learn to be merciful, because showing mercy involves breaking a rule without having a different rule or sufficient cause to tell it to do so. Stealing is wrong, this is a rule we almost all learn from childhood. But in the famous opening to Les Misérables, Jean Valjean, a destitute convict, steals some silverware from Bishop Myriel who has provided him with hospitality. Valjean is soon caught by the police and faces a lifetime of imprisonment and forced labour for his crime. Yet the Bishop shows him mercy, falsely informing the police that the silverware was a gift and even adding two further candlesticks to the swag. Stealing is, objectively, still wrong, but the rule is temporarily suspended, or superseded, by the bishop’s wholly unruly act of mercy.   

Teaching his followers one day, Jesus stunned the crowd with a catalogue of unruly instructions. He said, “Give to everyone who asks of you,” and “Love your enemies” and “Do good to those who hate you.” The Gospel writers record that the crowd were amazed, astonished, even panicked! These were rules that challenged many assumptions about the “right” way to live – many of the social and religious “rules” of the day. And Jesus modelled this unruly way of life too – actively healing people on the designated day of rest, dining with social outcasts and having contact with those who had “unclean” illnesses such as leprosy. Overall, the message of Jesus was loud and clear, people matter more than rules.  

AI will never understand this, because to an AI people don’t actually exist, only rules exist. Rules can be programmed in manually or extracted from a data scrape, and one rule can be superseded by another rule, but beyond that a rule can never just be illogically or irrationally broken by a machine. Put more simply, AI can show us in a simplistic way what fairness ought to look like and can protect a judge from being punitive just because they are a bit hungry. There are many positive applications to the use of AI in overcoming humanity’s unconscious and illogical biases. But at the end of the day, only a human can look Jean Valjean in the eye and say, “Here, take these candlesticks too.”   

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