Ethics and Embryos.

John writes ...

Embryo development. Credit: onlinebiologynotes.com

Introduction
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% of IVF cycles lead to a live birth. At the same time, there have also been very significant advances in genetics, genomics and stem cell biology all of which, in relation to human embryos, raise interesting and sometimes challenging ethical issues.

A brief diversion: non-human IVF
I will return to the ethical issues later in this article but for now I want to look beyond the field of human fertility and out into the wider animal kingdom. IVF and related techniques have been used extensively in breeding of farm animals but more recently have been applied to wild animals. Thus, my eye was caught by a headline in The Guardian: ‘Australian scientists produce kangaroo embryos using IVF for first time’ (1). The scientists who did this say that their intention is not to produce hundreds of ‘joeys’ but, having shown its feasibility, to use the technique with endangered marsupial species, including koalas, Tasmanian devils and northern hairy-nosed wombats. Actually, this was far from being the first application of IVF with wild animals, as is evident from an earlier Guardian article (‘Rewinding human mistakes’: can IVF save the world’s most threatened species?) (2). There is a hint of ethical discussion here too – science is being used to undo some of the deleterious effects of human activity, albeit mainly in respect of the ‘poster boys’ of biodiversity conservation.

Scientists Dr Patricio D Palacios and Dr Andres Gambini from the University of Queensland who have carried out IVF with kangaroos. Credit: Andres Gambini.

Tasmanian Devil. Credit: Getty Images.

Genetics, ethics and human embryos
Returning to my main theme, 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, as I have discussed elsewhere, 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 (PGD) (3) 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 should we 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.

A cell being removed from an eight-cell human embryo in order to carry out pre-implantation genetic diagnosis/testing (PGD/T). (Note that sampling one cell at this stage had been the method most widely used for many years but now, many practitioners take more than one cell from a later-stage embryo). Credit: unknown.

British long-distance runner and multiple champion, Mo Farah. We already know of several genes that are involved in the stamina and muscular activity which contribute to long-distance running ability. In theory, these genes could be looked for via PGT in order to select an embryo which had at least the ‘right genes’ to become a long-distance runner. Credit: playersbio.com.

This leads us on to think about altering human genes. Initially, the issue was genetic modification (GM) which in general involves adding genes. Readers of this blog and/or my writing elsewhere will already be aware that 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 (first such case was in 2004). 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.

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 (4). Further modification and sophistication of the technique has opened-up a large array of applications in research, agriculture and medicine; some of the latter have been previously discussed in this blog. 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 who 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, including coronary artery disease, Alzheimer’s disease, major depressive disorder, diabetes and schizophrenia (5). 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 (6). 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 …’ (7). It is therefore abundantly clear that the moral and ethical questions relating to editing the genomes of human embryos remain very pertinent.

Harder still and harder
I have no doubt that amongst different readers of this blog 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. Further, it also became possible to get both induced stem cells and natural stem cells to actually develop into functional differentiated cells corresponding to specific body tissues. This obviously 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 (8). However, similar synthetic embryos, implanted into mouse uteruses, did not develop to full-term.

Mouse embryos, natural at the top, synthetic at the bottom, showing similar development of brain and heart. Credit: Gianluca Amadei and Charlotte Handford.

Professor Magdalena Zernicka-Goetz, leader of the embryo development research team at Cambridge University. Credit: Simon Zernicki-Glover.

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 (9). 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 (HFE 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 one English national newspaper, The Daily Telegraph, who wrote that this research is irresponsible.

But there is more. In addition to synthetic embryos, the HFEA also discussed at its recent meeting the possible use of gametes – eggs and sperm – grown from somatic stem cells (e.g., from skin) in the lab (10). 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? Feel free to add a comment at the end of this article.

Postscript
I had already decided to devote this month’s blog post to embryos, genes and related topics when my attention was drawn to an article in the January 31st issue of Church Times, ‘A theology of embryos needed’ (11). The article is written by Dr Christopher Wild, a former director of the WHO’s International Agency for Research on Cancer (and he is also a member of Christians in Science). In the article, the author discusses several of the topics that I have presented here but does so from a much more theological perspective. I thoroughly recommend it: it is clear, well-written, helpful and thought-provoking.
 
John Bryant
 
Topsham, Devon, UK
February 2025

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(1)   Australian scientists produce kangaroo embryos using IVF for first time | Mammals | The Guardian.
(2)   Rewinding human mistakes’: can IVF save the world’s most threatened species? | Endangered species | The Guardian.
(3)   Although many practitioners are now switching to call it ‘pre-implantation genetic testing’ (PGT). 
(4)   Reviewed in Biological Sciences Review September 2019, pp 20-22 and Emerging Topics in Life Sciences (2019) 3: 687–693. Click here.
(5)   Heritable polygenic editing: the next frontier in genomic medicine? | Nature
(6)   See discussion paper from the Hastings Centre:
Do We Have a Moral Obligation to Genetically Enhance our Children? | The Hastings Centre.
(7)   Human embryo editing against disease is unsafe and unproven — despite rosy predictions | Nature; Will genome editing transform our children's health? Some have doubts | New Scientist.
(8)   ‘Synthetic’ embryo with brain and beating heart grown from stem cells by Cambridge scientists | Cambridge University.
(9)   Synthetic human embryos created in groundbreaking advance | Biology | The Guardian.
(10)   Technology for lab-grown eggs or sperm on brink of viability, UK fertility watchdog finds | Reproduction | The Guardian.
(11)    A theology of embryology needed | Church Times.