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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Explainer
Culture
Gaza
Israel
Politics
5 min read

Politics is the only way to solve the tragedy of Gaza

Trump is not the first person to want to create a Riviera by the Mediterranean.

Graham is the Director of the Centre for Cultural Witness and a former Bishop of Kensington.

A sign projected on to the Houses of Parliament reads: how many is too many.
A projection protest sign, London.
Christian Aid.

Whichever side you take in the Israel-Gaza conflict, the stories can't help bring a sense of desperation. Images of starving children, the fate of Jewish hostages still held in darkness - either way, this remains a place of unimaginable suffering. And meanwhile, the bombs keep dropping, people die, and Hamas retains its hold. 

Among Israel’s friends, voices have been murmuring a radical solution to the problem of Gaza. Donald Trump’s plan was to raze the territory to the ground, shift 50 million tonnes of debris and displace its people to neighbouring countries to build the ‘Riviera of the Middle East’ in what had until now, been Gaza. The plan might have been met with some amusement when it was aired, but it gave permission for many within Israel to think similar thoughts.  

Bezalel Smotrich, the Israeli finance minister, recently claimed that after the Israeli operation, “Gaza will be entirely destroyed” and its Palestinian population will “leave in great numbers to third countries.” Many within Israel seem to think the stubborn, Hamas-ridden enemy living next door needs to be eradicated. To a population weary of decades of conflict, fearing that there will never be peace while Hamas remains in Gaza, and aware of how difficult it is to winkle out the Islamic terrorist group while the Palestinian population remains there, you can understand the attraction of this radical solution. 

However, the Israelis might have good reason to be cautious. And that is not a counsel from their opponents - but from their own history.  

In the early 130s AD, the boot was on the other foot. It was the mighty Gentile Roman Empire that ruled over the same patch of land, which they were soon to call Palestina. Jews were a minority, but they still harked back to their long roots in the land, the days of Joshua and King David, and even more recently to the Jewish Hasmonean kingdom 200 years before - the last time before the modern state of Israel that Jews were in control of the land. 

The emperor at the time, Hadrian, passed through Jerusalem in 130 AD, along with his entourage and his lover, the young slave boy Antinous. He started to paganise the city, erecting statues of gods and emperors, even of his young favourite, all of them offensive to Jewish sensibilities. The smouldering resentment soon erupted with a revolt led by a fierce and determined Jewish fighter, Bar Kokhba. This was the second Jewish uprising after the earlier one in the 60s that had led to the destruction of the great Jewish Temple in Jerusalem by Titus, under the reign of the emperor Vespasian in 70 AD. For the Romans, one revolt might just be tolerated, two was too much.  

Hadrian came to the same conclusion as Bezalel Smotrich – a rebellious territory had to be erased from the map, although this time, it was Jerusalem that was to be eliminated, not Gaza. Its Jewish population was to be scattered, its name deleted, and memories of past glories buried for good.  

And so, in 135 AD, the bulldozers moved in. Jerusalem was effectively flattened, and a Roman city built on its ruins. Aelia Capitolina was its new name, a smaller city, yet decadently built around the worship of Greek and Roman gods, with splendid gates, pagan Temples, a classic Roman Forum, expansive columned streets – not quite the Riviera of the middle east, but maybe the Las Vegas. ‘Jerusalem’ was scrubbed from the map. 

At the centre of the sacred Jewish Temple Mount, Hadrian erected a statue of himself. He deliberately planted a statue of Aphrodite over the very spot where the early Christians insisted that the death and resurrection of Jesus had taken place – where the Church of the Holy Sepulchre stands today. Circumcision was outlawed, many Jews were killed, and those remaining were banned from the city, dispersed anywhere where they could find shelter. In fact, the map of the Old City of Jerusalem today is still marked by this design, with the two main Hadrianic streets diverging south from the Damascus Gate, with archaeological remains of the Roman city still visible for visitors. 

Yet of course it didn’t work. No-one calls it Aelia today. People's attachment to land goes deep. The Jews could not forget their roots in this patch of the earth's surface. As Simon Sebag Montefiore put it: “the Jewish longing for Jerusalem never faltered”, praying three times a day throughout the following centuries: “may it be your will that the temple be rebuilt soon in our days.” 

Palestinian attachment to land is similarly strong. Nearly 80 years after the creation of the state of Israel in 1948, families still cling on to the keys to homes that were taken from them during that traumatic period. Like the Jewish yearning for Jerusalem, they too, like people across the world, have a deep attachment to ancestral lands, which go back to the ‘Arabs’ mentioned in the book of Acts, to whom St Peter preached in the early days of the Christian church.  

Executive decisions by distant rulers such as the emperor Hadrian or President Trump might seem like neat solutions to intractable problems. But they seldom work in the long term.  

The famous biblical injunction ‘an eye for an eye, a tooth for a tooth’ was meant not as an encouragement to violence but the exact reverse. It was mean to set a limit to the development of blood feuds, which could, out of anger and trauma, so easily lead to disproportionate reaction and never-ending vendettas. When St Paul wrote “Beloved, never avenge yourselves, but leave room for the wrath of God; for it is written, ‘Vengeance is mine, I will repay, says the Lord’”, he was recalling an ancient piece of Jewish wisdom that set limits on human capacity to sort out intractable problems by violence. He knew a better way: “Do not be overcome by evil, but overcome evil with good.” 

Luke Bretherton, Regius Professor of Moral Theology at Oxford and a Seen & Unseen writer, argues that there are really only four ways you can deal with neighbours who prove difficult: you can try to control them, cause them to flee, you can kill them, or you can do politics – in other words, try to negotiate some form of common life, as ultimately happened in Northern Ireland, South Africa, and so many places of long-standing conflict. 

Politics, the business of learning how to live together across difference, is messy, complicated and hard work. Especially so when there are deep hurts from the past. Yet, as the failure of Hadrian’s radical solution shows, there is no real alternative in the long term. 

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