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
America
Character
Culture
Politics
5 min read

What would make America great again - humility

Hubris, Hope and Humility - and how they fit together in the court of King Donald

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

Elon Musk sits next to Donald Trump on a plan, while giving the thumbs up gesture with both hands.
Office of Speaker Mike Johnson, Public domain, via Wikimedia Commons.

Over the inauguration weekend, I was in Texas. Trump-Vance flags still fluttered in the cold wind, now more in triumph than soliciting votes. This was in the middle of the biggest winter storm to hit the southern coast of the USA in 65 years, where four inches of snow ground cities to a halt. The seemingly endless cycle of American TV news channels were caught between fascination with Storm Enzo, and the return of a political hurricane in Washington DC.  

President Trump’s first few days broke upon the world rather like a fresh storm. When a new government takes over, it is customary to sound a note of hope for the future, uniting the nation, cautious anticipation for a new dawn, pledging to try one’s best for the people and so on. Yet Trump’s speech was optimism on steroids. He announced the beginning of a ‘golden age’ for America. “From this day forward” he claimed, “our country will flourish and be respected again all over the world. We will be the envy of every nation, and we will not allow ourselves to be taken advantage of any longer.” 

Elon Musk went even further. This election, he said, was a “fork in the road of human civilisation.” As a result of the good Republican voters of the USA, “the future of civilisation was secured”, as he looked forward to a day when the stars and stripes would even be planted in the soil of the planet Mars.  

There is a fine line between hope and hubris. Many commentators have contrasted the gloomy outlook of Keir Starmer with the upbeat optimism of the Republicans in Washington. American always outdo us Brits when it comes to can-do optimism, yet this was something else.  

Hope lifts people’s spirits. It gives a sense of possibility and points to an unknown but bright future. St Paul asks “who hopes for what they can see?” Hope recognises that the future is not entirely in our hands, that events - and our own stubbornness and pig-headedness - can derail the best laid set of plans. It knows that the future is uncertain and yet, because of a simple trust that the world came from goodness and will end with goodness, believes that sometimes despite, rather than because of our efforts, the future is bright.  

Hubris, however, is when human confidence goes into overdrive. In the classical world, writers such as Hesiod and Aeschylus saw hubris as the dangerous moment when a mortal claimed to be equal to, or better than a god.  

Phaeton was a teenage boy racer, a son of the sun god Helios. He took hold of his dad’s chariot for a day, thought he could steer better than his aged parent, drove too fast, too close to the earth, burning it up and thus earning a trademark lightning bolt from Zeus for his pains. Arachne was a weaver who thought his cloth more beautiful than that of Athena, the goddess of all weavers. And of course, the most famous of all, Icarus, made himself a pair of wings, soared just a bit too high, melting the wax that held them together, plunging him into the sea like a burnt-out satellite falling, falling and then sinking into the dark blue depths of the vast ocean. A trip to Mars anyone?  

Yet without a dose of humility, the modesty that recognises not everything is in their control, that they will get things wrong, and need to admit it when they do, they will only generate antagonism and disharmony. 

There are, of course, parallels in Christian literature. The Tower of Babel is the story of a civilisation that thought it could build to the skies, to reach and rival God himself. God was not impressed and confused the speech of the uppity humans so they could no longer understand one another. King Herod - grandson of the one visited by the wise men at Christmas - dressed himself in finery, smiled smugly at the acclaim of the crowds that his was ‘the voice of a god and not a mortal.’ No sooner had he said this than ‘an angel of the Lord struck him down, he was eaten by worms and died.’ 

These are ancient stories of brash and overblown self-confidence, that a human could do what only the gods can. They recur in pretty well every human strand of wisdom. Hubris usually arises from an insecure desire to be better than anyone else, better even than the gods, or God. It is essentially competitive. If greed is the desire to be rich, then hubris is the desire to be richer than everyone else. It creates comparison, jealousy, and yes – envy - in fact, that is the point - to be the envy of everyone else. Of course, social media is full of it. It is hard to like hubristic people. They generate envy or resentment, or when they fall, a delicious dose of Schadenfreude. None of which are particularly good for us.  

The opposite of hubris is humility. The root word for humility is the same as humus, humour, humanity. It derives from that ancient biblical story of the human race being fashioned by God out of the dirt. It punctures holes in our self-importance, reminds us of our lowly origins. It is the precious ability to laugh at yourself. Humility is appropriate for us precisely because we are not gods, and woe betide us if we think we are. We are instead poised between the earth and the heavens, sharing in the divine image, capable of great things, maybe one day even reaching Mars. Yet we are also capable of great cruelty and harm, frail and liable to get things badly, sometimes catastrophically, wrong. Once we forget our dual nature, made to be like God, yet moulded out of the earth; with huge potential for creativity and yet with a tendency to over-reach, a flaw within that leaves us vulnerable to temptation, we are in danger of blundering ahead like bulls in the proverbial China Shop.  

And this is the danger that Trump and Musk are flirting with. I wish them well. I really do. Maybe they will make America great again. Maybe they will usher in an age of prosperity and order. Yet without a dose of humility, the modesty that recognises not everything is in their control, that they will get things wrong, and need to admit it when they do, they will only generate antagonism and disharmony. And they will probably do more harm than good.   

Fyodor Dostoyevsky once wrote “Loving humility is a terrible force: it is the strongest of all things, and there is nothing like it.” Humility ends up being stronger and achieves more than hubris. Jesus was said to be “gentle and humble in heart.” And he changed the world more than anyone else. Donald and Elon – watch and learn. 

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