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
Music
6 min read

The biblical undercurrent that the Bob Dylan biopics missed

In the best of Dylan’s work is a contemporary Pilgrim, Dante or Rimbaud on a compassionate journey.

Jonathan is Team Rector for Wickford and Runwell. He is co-author of The Secret Chord, and writes on the arts.

A colorful mural depicts the eyes of Bob Dylan staring to the side.
Dylan mural, Minneapolis.
Nikoloz Gachechiladze on Unsplash.

The Bob Dylan biopic A Complete Unknown begins with his arrival in New York and concludes with his performance at the Newport Folk Festival in 1965. He begins the film as a complete unknown, as he arrives with no backstory to share or, where he does, one that he has invented. He ends it as a complete unknown, because he consistently refuses all the boxes or labels in which others want to imprison him. 

This aspect of Dylan’s life and career has also characterised many of the earlier biopics, such as 2007’s I’m Not There which features six different versions of Dylan as poet, born-again Christian, outlaw, actor, folk singer, and electrified troubadour. Suze Rotolo, his girlfriend throughout much of the time covered by A Complete Unknown, described the way in which he absorbed influences at this time like a sponge:  

“He had an incredible ability to see and sponge – there was a genius in that. The ability to create out of everything that’s flying around. To synthesize it. To put it in words and music.” 

Focusing on this aspect of Dylan’s life and practice can, however, lead to a minimising of his upbringing and also to a misleading sense of brilliant but entirely disconnected phases – essentially a series of rejections – as having characterised his career. There are some important elements of Dylan’s life and ideas that are overlooked, underplayed or simply lost as a result. Many of these involve the particular expression of spirituality that has informed his work from the beginning. 

As Rabbi James Rosenberg has explained: “Robert Allen Zimmerman was born in Duluth, Minnesota, on May 24, 1941. He spent the majority of his childhood, including his high school years, in Hibbing, about 60 miles northwest of Duluth. His father and mother, Abram and Beatie, whose parents were immigrants from Eastern Europe, sent both him and his younger brother David to the local synagogue for their Jewish education leading to Bar Mitzvah at age 13.”  

As a result, Dylan’s songs have from the beginning of his career been suffused with the phrases and imagery of the Bible; interestingly, not just the Hebrew Bible, but the Christian Bible too. Whether it’s the references to Judas in “Masters of War” and “With God on Our Side” or quoting Jesus in ‘the first one now will later be last’ (“The Times They Are A-Changin’”) or the Old Testament stories that feature at the end of “When the Ship Comes In”, wherever you look within Dylan’s lyrics the influence of the Bible is apparent. 

Follow that thought with another which notes the prevalence of apocalyptic images (storms, hurricanes etc) and events (‘The hour when the ship comes in’, the moment when “The Times They Are A-Changin’” or the night when the “Chimes of Freedom” ring, for example). Then think from where images of apocalyptic events primarily derive in the Western imagination and you’ll be circling back to the Bible, and the Books of Daniel and Revelation in particular. That is of course what Dylan himself did following his born-again experiences in the late ‘70s and early ‘80s, but the Bible was always the original seedbed for his images and ideas. 

Then, look deeply into one of the most apocalyptic of his early songs – “A Hard Rain’s A-Gonna Fall” – and you’ll see a manifesto to which he has held throughout his career and which illuminates his work in every decade and every change of direction within his lengthy career. The central character in “A Hard Rain’s A-Gonna Fall” commits to walking through an apocalyptic world in order to tell and think and speak and breathe and reflect what he sees in order that all souls might see it too. In a much later manifesto song – “Ain’t Talkin’” – he puts it like this:    

Ain’t talkin’, just walkin’ 

Through this weary world of woe … 

Heart burnin’, still yearnin’ 

In the last outback, at the world’s end 

Throughout Dylan’s career, he writes songs about people travelling through life in the face of apocalyptic storms seeking some form of relief or salvation or entry to heaven. So, what we have in the best of Dylan’s work is a contemporary Pilgrim, Dante or Rimbaud on a compassionate journey, undertaken in the eye of the Apocalypse, to stand with the damned at the heart of the darkness that is twentieth century (and then twenty-first century) culture. 

It's actually all there right at the beginning in the song that he wrote for and sang to his hero Woody Guthrie:  

I’m out here a thousand miles from my home 

Walkin’ a road other men have gone down 

I’m seein’ your world of people and things 

Your paupers and peasants and princes and kings 

  

Hey, hey, Woody Guthrie, I wrote you a song 

’Bout a funny ol’ world that’s a-comin’ along 

Seems sick an’ it’s hungry, it’s tired an’ it’s torn 

It looks like it’s a-dyin’ an’ it’s hardly been born

(“Song to Woody”) 

Dylan’s songs, from that point onwards, have documented where his pilgrim journey in the eye of the apocalypse has taken him; often with imagery of storms lighting his way. He has travelled the paths of political protest, urban surrealism, country contentment, gospel conversion and world-weary blues. On his journey he: saw seven breezes blowing around the cabin door where victims despair (“Ballad of Hollis Brown”); lightning flashing for those who are confused, accused and misused (“Chimes of Freedom”); surveyed “Desolation Road”; talked truth with a thief as the wind began to howl (“All Along the Watchtower”); sheltered with an un-named woman from the apocalyptic storm (“Shelter from the Storm”); felt the idiot wind blowing through the buttons on his coat, recognised himself as an idiot and felt sorry (“Idiot Wind”); found a pathway to the stars and couldn't believe he'd survived (“Where Are You Tonight? Journey Through Deep Heat”); rode the slow train up around the bend (“Slow Train”); was driven out of town into the driving rain because of belief (“I Believe in You”); heard the ancient footsteps join him on his path (“Every Grain of Sand”); felt the Caribbean Winds, fanning desire, bringing him nearer to the fire (“Caribbean Wind”); betrayed his commitment, felt the breath of the storm and went searching for his first love (“Tight Connection to My Heart”); then, at the final moment, it's not quite dark yet but he’s walking through the middle of nowhere trying to get to heaven before the door is closed (“Tryin' To Get To Heaven”): 

The air is getting hotter, there's a rumbling in the skies 

I've been wading through the high muddy water 

With the heat rising in my eyes. 

Everyday your memory grows dimmer. 

It don't haunt me, like it did before. 

I been walking through the middle of nowhere 

Tryin' to get to heaven before they close the door.

(“Tryin' To Get To Heaven”) 

Whatever the crises we face, whether personal or political, there’s a Dylan song that says there’s light at the end of the tunnel if you keep walking toward it and, whatever the song, there’s a depth of insight and compassion for those who are struggling along the way. 

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