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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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Culture
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Ethics
1 min read

The rights and wrongs of making money with meme coins

When does investing become speculating, or even addictive gambling?
A montage shows Trump with a raised fist against other images of him and the phrase 'fight fight fight'.
$Trump coin marketing image.
gettrumpmemes.com,

Donald Trump’s “liberation day” tariffs may have driven sharp swings in global financial markets, but his actions in markets a few months earlier were in some ways even more peculiar.

On the Friday before his inauguration as the 47th US President in January, the Republican surprised many with the launch of the $TRUMP memecoin, described by its website as “the only official Trump meme”. The cryptocurrency token, in which Trump’s family business owned a stake, initially soared in value to more than $14bn over that following weekend. 

Then, on the Sunday, Trump’s wife Melania launched her own memecoin, $MELANIA, which reached a value of $8.5bn. Even the pastor who spoke at the president’s inauguration subsequently launched his own memecoin. 

For those wondering what exactly a memecoin is, you are not alone. In short, they are a form of cryptocurrency - an asset class that itself has attracted plenty of questions about its substance and purpose - representing online viral moments. They have no fundamental value or business model and, according to the US securities regulator, “typically have limited or no use or functionality”. 

Donald and Melania Trump’s coins subsequently plunged in price, but still have a value of around $2.5bn and $214mn respectively, according to website CoinMarketCap. 

There are plenty of others in existence. PEPE, based on a comic frog, has a value of around $3.6bn; BONK, a cartoon dog, has a market cap of $1.5bn; and PNUT, a reference to a squirrel euthanised by authorities in New York and about which Trump was allegedly “fired up” (although doubt has since been cast on the president’s involvement in the matter), is still valued at around $174mn, despite having fallen sharply in price.  

Dogecoin, seen as the world’s first memecoin and originally created as a joke, boasts a market value of around $25bn. (There are other memecoins which may not be suitable for these pages). 

Some people’s willingness to buy an “asset” with no use or fundamental value may seem strange to more traditional investors. But it can be viewed as just one manifestation of the speculative investor behaviour evident since the onset of the coronavirus pandemic and, indeed, at times throughout history. 

The price of Bitcoin recently rose above $100,000, despite many investors still viewing it as having little or no value (in 2023 the UK’s Treasury select committee described cryptocurrencies as having “no intrinsic value, huge price volatility and no discernible social good”). In early 2021, shares in GameStop - a loss-making US video games retailer that some hedge funds were betting against - rocketed as much as 2,400 per cent, as retail investors piled in, many with the aim of inflicting pain on the hedge fund short sellers (in that respect at least, a highly successful strategy that became the subject of the film Dumb Money). The huge rise in AI and other tech stocks in recent years - until the recent tariff-driven volatility - has also been described as a bubble by some commentators. 

Whether or not such episodes can be compared to infamous bouts of speculative mania in history depends on your point of view (and often can only be judged with the benefit of hindsight) - be it the 17th century Dutch tulip bulb mania, shares in the South Sea Company in the 18th century or the dotcom boom and bust of the late 1990s and early 2000s. 

But it does give rise to the question of when investment should start to be described as speculation or even as gambling? And what are the rights and wrongs of any of those activities? 

There can be negative effects, for instance if the actions of speculators force businesses in the real economy to change their plans or divert time and resources... 

Gambling can be thought of as risking a stake on, for instance, the result of a game of chance or sport in the hope of a bigger payout. While often the result is purely down to chance, in some cases a strategy or an element of research (for instance of a horse or football team’s form) can be used. Investment, in contrast, tends to involve purported economic utility and assets believed to have some sort of underlying value, and holds the hope of future profit (although there are also plenty of bad investments or those that have gone to zero). While an investor must be prepared to lose their entire stake, in some cases such an event is relatively unlikely (for instance, if they buy a fund tracking the performance of a major stock exchange). Speculation is harder to define, but is generally seen as shorter term than investment, with more chance of a bigger gain or loss, and dependent on price fluctuations. Rightly or wrongly, the term has a more negative connotation than investment. 

One writer who explored the ethics of these activities was Oswald von Nell-Breuning, a Jesuit theologian and economist who served as an adviser to the Pope and who was banned from publishing under the Nazis. 

While he found that “one general definition cannot capture all the nuances” of speculation, he identified two different types of speculative activity - one that was purely trying to make a profit from financial market trading, and one based on trying to create a viable business. (See this article in the Catholic Social Science Review for a fuller explanation of Nell-Breuning’s views on speculation). 

As the CSSR article shows, Nell-Breuning found that there can be positive effects from speculation - one might think of better liquidity and price discovery in a market, while, in commodity futures markets, speculators allow producers to hedge risk

But he also argued that there can be negative effects, for instance if the actions of speculators force businesses in the real economy to change their plans or divert time and resources away from production. 

And whereas gambling typically takes place within a circle of players who have chosen to take part, speculation, he wrote, can affect a greater portion of society - for instance, if it affects the price of shares or bonds they hold. 

The Bible - on which Nell-Breuning’s faith and analysis was based - does not take a prescriptive approach to such activities. But it does provide some interesting guidance.  

An entrepreneurial approach to business and investment is applauded, for instance when the writer of the book of Proverbs (traditionally believed to be King Solomon) praises the virtues of “an excellent wife”. These include investing in a field and using her earnings from business to plant a vineyard, and feeding her family from her gains. 

Jesus tells a story of a master who, before going on a journey, gives his property to his servants, each according to their ability. To one he gives five “talents” (a large unit of money), to a second two and to a third servant he gives one. 

The first servant trades with his talents and makes five more talents - a 100 per cent profit - and is applauded by the master on his return. The second servant also trades and similarly makes two more talents and is again applauded. 

But the third servant, being afraid and believing the master to be “a hard man”, hides the money in a hole in the ground. He is condemned as “wicked and slothful”, and told that he should at least have put the money in the bank. 

While Jesus’s story may primarily be about how we view God’s nature, how we use our God-given abilities and whether or not we can take risks in faith for Him, it is also hard not to see investment and indeed wise speculation as being virtuous activities here. Putting the money into a bank account is, in this story anyway, more of a fallback option. 

But the Bible also warns us against putting money above all else in our lives. The love of money is, famously, a root of all sorts of evil, while we are also told to be content with what we have, and that “wealth gained hastily will dwindle”. 

Nell-Breuning similarly warns that a “get-rich-quick” mindset, when this is placed above all else, can be harmful, and advises caution in situations where the lure of big profits can lead the speculator into market manipulation or fraud. 

After all, both gambling and crypto trading have the potential to become dangerous and damaging addictions needing treatment

Ultimately, Nell-Breuning struggled to come to a simple conclusion on the question of whether speculation, in and of itself, is morally wrong. It is, he wrote, a judgment call for those involved. 

When making such decisions ourselves, his - and the Bible’s - warnings may be worth bearing in mind.