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
America
Culture
Film & TV
Politics
5 min read

Trump: from apprentice to master of contempt

The Trump biopic is a morality tale for our times
An 1980s business man looks contemptuously at the camera.
Sebastian Stan as a young Donald Trump.
Scythia Films.

He won. Donald Trump is, once again, the President of the United States. The controversial property tycoon, controversial ‘billionaire’, controversial reality TV star, and highly controversial one-term (or so it seemed) President, has done it again! Sweeping not only the Electoral College but also the popular vote, Trump will have another four years to ‘Make America Great Again’…whatever that means. The question on most pundits’ lips today is: how? The man who was written off from the first moments he descended into his campaign on that golden escalator; the man who was guaranteed to lose his first (let alone his third!) Presidential bid; the man who has been mired in sexual, financial, constitutional, and legal scandal…how could he win again!? 

Rather than seek answers in the election coverage of last night I went to an alternative source of information. I popped down to my local cinema to watch The Apprentice, Ali Abbasi’s biopic of Trump’s rise to power and prominence, focusing on his ‘apprenticeship’ under pugnacious, pugilistic, flamboyant, and flamingly foul-mouthed lawyer and mentor Roy Cohn. Whether consciously or not – and believe me, it’s so consciously on the nose as to feel like a punch to the nose – the film draws a ruler-straight line from Trump’s early days as Cohn’s disciple to his electoral success in 2016…and now in 2024. 

How did Trump win, not once but twice…? 

…by selling his soul to the Devil. 

We meet Trump and Cohn in an exclusive New York Members Club. Trump is shy and awkward – none of the bombast we know him for – clumsily trying to impress his date by mentioning how he is the youngest member to ever be admitted. Cohn is holding court with some mob-coded friends. Cohn stares at the handsome, golden-haired ingénue (Trump, not his date) across the room through sunken domes. He invites Trump to join him for dinner. The date has gone to ‘powder my nose’ and seemingly has made a lucky escape through the lavatory window. Trump joins Cohn. Cohn bloviates, always with his hand firmly gripping Trump’s thigh. Trump is enamoured…smitten…in love. Cohn becomes his lawyer and Trump his protégé. 

The film goes on to chronicle how, under Cohn’s tutelage, Trump becomes the man we now know. Cohn is committed to winning – under the guise of being committed to America. He teaches Trump his three rules for success:  

  1. Attack, attack, attack. 
  2. Admit nothing. Deny everything. 
  3. Even in defeat, claim victory.  

There is a nice bit of mirroring in the final scene as we see Trump regurgitate these rules, introduced pithily and wittily in the first 30 minutes of the film, in his final exaggerated and bloviated style to a ghost-writer employed to write The Art of the Deal. This is how Trump wins. Throughout the film we watch Trump evolve from the nervous young man, protective of his alcoholic brother and under-the-thumb of his overbearing father, into a monstrous, ad absurdum form of Cohn…a man who will demand absolute submission to his will. 

The film, I wager, is partly a morality tale. It gives us a (slightly) sympathetic young Faustus, and chronicles his descent into Hell, but without a hint of real redemption or pity.

The film is sickeningly enjoyable. Sebastian Stan gently invites us to root for Trump in his timidity, and transforms with a subtlety which leaves the audience questioning their own culpability. Maria Bakalova brings a good-natured innocence to Ivana Trump (née Zelníčková) which steals the few scenes she’s afforded. Jeremy Strong – always watchable – brings his magnetic charisma to the screen. His Cohn is akin to Pacino’s John Milton in The Devil’s Advocate: delightfully chewing the scenery and ingratiating himself to the viewer while being hateful. The film is just over two hours long but doesn’t feel it. Never dragging, never boring. The soundtrack revels in the period, and the needle-drops are near perfect. It’s a really rather fun watch. 

However. 

The film is not nourishing. It is the cinematic equivalent of the junk food that leads to Trump’s expanding waistline (and the liposuction scene that is so difficult to watch). The film painstakingly draws parallels between Trump’s early success and his later political career. Cohn’s rules, Reagan’s campaigning slogans, the arrogance, the (sexual!) violence…everything we associate with Trump today is found in its nascent form in his 1980s career. Yet, none of it really matters because we have no character we want to attach ourselves to. No one, except perhaps Trump’s mother and his first wife, neither of whom have the chance to make enough of an impact, is likable or redeemable. Cohn is slime personified, until a sudden AIDS related conversion to conscience, and we don’t see nearly enough of the pathetic and put-upon Trump to care about his descent into the demonic realm of absolute self-absorption. The script is razor-sharp, but not incisive. The characters are riotously funny, but nowhere near emotionally engaging enough. 

The film, I wager, is partly a morality tale. It gives us a (slightly) sympathetic young Faustus, and chronicles his descent into Hell, but without a hint of real redemption or pity. Mortality makes Cohn recognise the monster he has been the Dr Frankenstein to, but in about ten minutes. We see a relative innocent made villain, but barely having had the chance to care for him in his infancy. No amount of slick script or genuinely bravura performance (Jeremy Strong deserves an Oscar) can make up for the cold and emotionless lens that the film has. In a sense, this gives us a more realistic explanation of Trump’s victory than the film seeks to muster…disdain. 

Like Trump, I deployed ‘alternative facts’. 

I lied. 

I did watch some of the election coverage in the early hours of the morning. As the Trump victory became inexorable, I watched pundit after pundit – who had been excoriating Trump supporters as either stupid or malign only 24 hours before – earnestly explain that it was a lack of engagement with middle-America which had lost it for the Democrats. Tony Hinchcliffe may have made a predictably unpleasant joke about Puerto Rico being a ‘garbage island’, but it was Biden calling even reluctant Trump voters ‘garbage’ which swung the election. We live in a new polarised age where the genuine concerns of the ordinary man or woman, if they can be associated with someone as aesthetically and morally compromised as Trump, make them functionally fascist.  

The Apprentice, simply by being unable to empathise with anyone not in favour, gives us the secret to Trump’s victory. It wasn’t Cohn’s rules. It was his overactive ability to demonstrate his contempt for everyone, and therefore seem to have contempt for no one. His detractors demonstrated the reverse. In the end Trump hasn’t needed to attack, or deny, or claim illegitimate victory. He simply has had to be himself. 

Saaaad. 

 

**** Stars