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
Books
Culture
Football
Sport
5 min read

The book to help you fall back in love with football

Neil Atkinson’s Transformer isn’t the straightforward biography of Jurgen Klopp.
A fan holds an upside down football scrarf that reads 'Juergen is a red'.
Fan fervour, Anfield.
Lloyd Kearney on Unsplash.

Transformer is a fun book. I don’t mean to sound trite, or to damn with faint praise when I say that. I mean it. Transformer is a fun book, and frankly too many books I read aren’t fun.  

David Foster Wallace used to say something similar (yes, the same David Foster Wallace whose novel Infinite Jest is over a thousand pages and has actual honest-to-god endnotes): much of contemporary print media has lost its ability to be fun. And isn’t that what we’re in this for anyway? 

And that is, I think, why Transformer feels like such a relief, honestly. None of the trademark scouse humour and levity that has made The Anfield Wrap such a successful and appealing football podcast is lost in the transition to text. It is a funny book. It is a fun book. 

Of course, there’s a lot here that you might expect to find in a book about Klopp, too, like discussions of key games throughout Klopp’s time at Liverpool. There’s also lots of what Atkinson does best: insightful and thoughtful reflection on the nature of contemporary football. Whether this is the nature of tickets and ticket prices, the state of TV football punditry, or why Liverpool fans (generally) don’t sing the national anthem, there’s much here for football fans and non-football fans alike to mull over and learn from.  

But it’s also worth noting what’s not in the book. There’s no real prolonged deep dive into Klopp’s personality here. I don’t say that as a criticism, more as a matter of expectation-management for potential readers. This isn’t a biography or a character study, although there are elements of this, for example, in the chapter on Klopp’s ongoing footballing rivalry with Pep Guardiola.  

Whole pages, even chapters pass without Klopp being mentioned. If you’re going into Transformer hoping to learn about Klopp’s upbringing, his playing career, his faith, you’ll likely be disappointed. But that’s fine, because Transformer isn’t that book. 

So much of the book is awash with the warmth of friendship and humour and life. 

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Transformer is not a book about Jürgen Klopp. Obviously, ostensibly it is. Klopp’s tenure at Liverpool drives the book forward; provides its pulse. But this doesn’t explain why there is a whole chapter on the meaninglessness of football without Divock Origi. And it doesn’t explain the inclusion of sentences like the following: “27 November 2019: Knives Out is released, meaning Sadio Mané has competition for most flamboyant performance from a Liverpudlian in a calendar year.” 

But it’s not even really a book about Liverpool, or football in general. Or Benoit Blanc. It’s a book about fun. About joy. About life, why it matters, why it’s good, and why it’s better with others.  

It’s really a book about love. About loving a football club and loving and being loved by others in the midst of loving that football club.  

Atkinson states up front that this book is about the people he has known and loved during Klopp’s time at Liverpool. It’s his version of this story. But in being his version, he allows it to be my version, too, and yours. “I am going to refer to people and places you may not know and we may not always trouble ourselves with descriptions. You don’t need to worry. That’s because these people, they are your friends. They are you.” 

And this is why the book’s most emotionally fraught moments hit as hard as they do; because so much of the book is awash with the warmth of friendship and humour and life. When moments do stand out in stark relief from the very fun and love that Transformer is keen on have us believe in, they thereby make the case for their importance all the more clearly. 

An insistence of the fundamental unseriousness of football is an act of gleeful rebellion. It is to play a different game. 

Much has been said about Covid and football under Covid. Atkinson’s compassionate, understated treatment of it is genuinely beautiful at times. “People pass away, unmoored from time, separated from loves ones in the grimmest circumstances, and no one quite knows what to do.”  

When reading Atkinson’s memories of the inner turmoil of his last interview with Klopp – “It was hard because I wanted to talk to him. At him. With him. I just wanted to list all these things has been part of with us, but, of course, he is more interested in you, in your world” – it’s hard not to be transported back to the sheer shock of his abrupt leaving.  

In case it’s somehow not clear yet, let me state it here: I think Neil Atkinson is one the most compelling and insightful thinkers in and around modern football. This is in large part because of his insistence on what many forget: football is a game. It is supposed to be fun. It is supposed to be a fun game you enjoy with your mates.  

We are in a world of nation-states and quasi-nation-states acquiring football clubs for political purposes. One with relentless discourse about the minutiae of every refereeing decision. A world where there is a constant, low-level feeling that I am yet again being ripped-off and taken advantage of for having the audacity to want to watch a football match. So, an insistence of the fundamental unseriousness of football is an act of gleeful rebellion. It is to play a different game.  

“I don’t see anywhere near enough people writing about happiness in general, especially within the realm of football where grumpiness has become the order of the day.” Transformer is the apotheosis of modern footballing grumpiness. It is sincere, and earnest, and vulnerable. And I love it for this.  

If you are looking for a comprehensive biography of Klopp, this isn’t it. This is something better.  

When I spoke to him about Transformer, Atkinson said he wanted the book to show that football fans were normal, complex people. That they were accountants from Altringham, and theologians from Liverpool (if we can count theologians as ‘normal’ people). Transformer absolutely bristles with humanity. 

Humans were made for community, for mates, for each other, and for last-minute Divock Origi winners. Humans were made for football.  

If you want to remember why you fell in love with football – or if you want to understand why others fall in love with it – I can’t think of a better book to read than Transformer