Ethics Seminars

[Kate Storey] So hello my name is Kate Storey I'm part of the HDBI, the human developmental biology initiative, and today I'm going to introduce you to the, welcome you to our ethics seminar. So these seminars are part of a series that are intended to facilitate respectful discussion about sometimes contentious subjects related to developmental biology research. In organizing this session we aim to create an open inclusive and safe environment where everyone should feel comfortable to participate and indeed we encourage active participation. And we've also allowed plenty of time for discussion afterwards, after both of our two speakers who are presenting today have given their talks. So please feel free to write things in the chat as questions and comments as, as we go along. And be aware that only the talks and not the discussions are going to be presented, are going to be recorded during the seminar.

So our first Speaker today is is Dr Ilke Turkmendag, hello Ilke. Ilke is a reader in biomedicine and society and law and, er biomedicine and Society at the law school at the University of Newcastle. She's a legal-medical scholar working in the intersection of science technology and she studies bioethics, sociology with an expertise in human reproductive technologies. Her research has addressed human egg provision for stem cell research, mitochondrial replacement techniques, and maternal epigenetics. As well as human genome editing and most recently longevity technologies. In the law school she's the director of the 'law and futures' research group and at the faculty level she's the lead for the biomedical engineering research center. Ilke is also a member of the Wellcome trust 'social sciences discovery advisory group' and the AHRC peer review college, she serves on executive committees of the socio-legal research association and the north of England medico-legal Society. So welcome Ilke, thank you for agreeing to give a talk.

Um I think what do is is is do your talk first, and then follow on with David Lawrence's talk afterwards. So the title of your talk: 'Maternal epigenetics: Sins of women of childbearing age' Thank you very much.

[Ilke Turkmendag] Thank you. Okay hello everyone and thanks for logging on. Today I will talk about transgenerational epigenetics and I know this is a tough audience because I'm not a scientist so I might make some mistakes, please bear with me. So I will talk about how some findings from transgenerational epigenetics especially the ones on maternal effects are presented on social media and in policy, by the policy makers. And so how does this findings find themselves in the public sphere, and what are the ethical legal implications of public discourse on maternal effects. But before doing that I'm going to take you to the world health organization's warning in published in 2021. So they said that: "appropriate attention should be given to prevention of the initiation of drinking among children and adolescents. Prevention of drinking among pregnant women and childbearing age, and protection of people from pressures to drink, especially in societies with high levels of alcohol consumption where heavy drinkers are encouraged to drink even more." Now this was a statement about alcohol, reduction, to reduce the harms in society of course, and I would believe that it was a well-intentioned statement. But the statement was met with immediate backlash on social media because of the definition of the vulnerable group here as 'women of childbearing age' which is according to WHO from 15 to 49 years old that means that any women in childbearing age cannot and should not drink because it will harm potentially the baby that she, they, might have regardless of their plans of having a baby or not. Now I'm going to leave it there because this talk is not about it but about how women's bodies are policed and monitored.

Now this kind of risk messaging that targets women of reproductive age and pregnant women in particular is not new. For example I don't know if you're familiar with Meloni and Muller's work, they looked at the ways in which maternal impression was used in scientific studies and they say that: "The notion that the thoughts, behaviors, emotions and experiences of a pregnant woman could 'imprint' on her offspring ... has stubbornly crossed different cultural and medical frameworks from ancient and early modern biology into the early 20th century". So the idea about controlling maternal body to shape the best possible baby is not new. But what is new is now these kind of notions can be backed up by science, of course this depends on who is interpreting the scientific findings, but there's a place for the scientific evidence to support these claims.

The findings in epigenetics suggesting a link between behavior and experiences of women during pregnancy and after birth and subsequent well-being of their children and even the future generations. Now this is a little bit scary scene if you look at it, apart from alcohol intake before conception and during pregnancy there are other examples including: poor prenatal diet, prenatal exposure to domestic violence, or maternal distress, Cesarean delivery, and also emotional problems, symptoms of attention deficit hyperactivity disorder, or impaired cognitive development, is also explained by epigenetic changes. I am usually using the 'maternal epigenetics' so I just wanted to clarify that term: I mean that the environment that the mother is exposed to may affect the offspring and the, even can be passed to the next generations. So I'm looking at maternal effects in transgenerational epigenetics. But this body of women, or the pregnant woman, is not isolated, so this is a problematic part of this kind of discourse because experiments in epigenetics do not address genetic influences in isolation but also take environment into an account. Now this is a positive thing because it departs from the genetic determinism. Therefore it is embraced by some feminists, for example Malubu and Davis thought that this challenge the anatomic essentialism and gender or genetic determinism. But by contrast a number of studies conducted by feminist science studies scholars suggest that maternal epigenetics not only reinforces anatomic essentialism, but also creates a powerful new discourse to control pregnant women and their bodies.

I'd like to show you video from the former begin before birth foundations website. Please note that the foundation is no longer in operation and the website is closed down, so if if you Google it you may not find it, although there's a link on the slide to find the former pages, and it's no longer operated by a legitimate entity. So on these pages Professor Vivette Glover who is a psychobiologist at Imperial College shares lots of information to help pregnant women, for their pregnancy journey and for the early development, and I think it's a well intentioned foundation to help women, to, benefit from some mental health support during the pregnancy. But there are also lots of materials and videos here, and one of the videos Charlie's story as you can see on the right side of the screen is quite an interesting one. The motto of the foundation was that: 'what happens in the birth' um or: 'what happens in the womb can last a lifetime', and this video is about Charlie, who is wearing a hoodie, Charlie committed criminal offenses and the reason was because his mother was quite stressed during the pregnancy, and she didn't get enough support from her family and friends and also the partner rejected this pregnancy. So she was under a lot of stress and the video suggests that Charlie's criminal tendencies can be explained by this fact.

So I'm going to show you the video, but before I go on to that it's a worth mentioning that Glover says: 'prenatal anxiety or depression May contribute 10-15% of the attributable load for emotional and behavioral outcomes'. So the problem with this is although this is an interesting observation and worth taking into account, that 'what happens in the womb can last a lifetime', is a quite deterministic approach. And it doesn't give any agency to the people, and the babies' future actions. Which might actually change their mental health or potential criminal tendencies. So the video is here, I'm going to turn it on and it will take only two minutes.

[Charlie] I'm Charlie I'm 19 and I spent the last last year of my life in prison. I got caught looting during the riots. [Narrator] like many arrested that night Charlie had previous convictions for theft and was known for his aggressive behavior. [Charlie] You probably think I deserve to be locked up. [Narrator] You may have little sympathy for Charlie but perhaps there is another side to his story perhaps his problems stretch right back to the womb. Charlie's mother was very stressed when she was pregnant and had no support from her family or friends. Charlie's father soon left her. [Charlie] My dad was never around when I was growing up. Mom didn't show me much warmth either. [Narrator] Charlie was a very difficult baby often crying for hours on end. [Baby Crying]. His mother soon became depressed and found it increasingly hard to relate to him. [School Bell Ringing]. [Charlie] I didn't do well at school. I'm [words echoed] a slow learner, easily distracted, a rule breaker. I stopped showing up in the end. Then I was excluded, which was sort of what I wanted anyway. [Narrator] It didn't take Charlie long to turn to Crime. Charlie wasn't born a criminal but research suggests that his time in the womb and his early life could have made his behavior more likely. His mother's stress during pregnancy could have led him to be a difficult baby, and even to his ADHD and behavioral problems in later life. The risk of these problems developing are doubled. So could better care of pregnant women be a new way of preventing crime? Research in the US is showing that supporting vulnerable women during pregnancy and the following 2 years can halve the number of crimes committed by their children. Maybe if Charlie's time in the womb had been different he'd have been different too.

[Ilke Turkmendag] But the annoyingly deterministic motto that 'what happens in the womb can last time', 'can last a lifetime' is surely problematic and I understand the well intention behind that. This, but, in most cases the stress during pregnancy could be caused by lots of different reasons: economic, food insecurity, unemployment, losing someone. So there is really not easily, easy way, to address that and give fetus a safe environment, in the UK where access to mental health care gets increasingly difficult. With waiting times up to six months, that help will not be always available. And If a mother feels that her emotional state is causing detrimental and irreversible harm to the child, like they mentioned in the video, ADHD for example, she's not going to feel any better, will she? So this is a problematic part of translation of epigenetics in the public sphere. And this is another example from social media. Don't worry there's no videos here, this study was presented by Menno Henselmans in August this year. And the study he's talking about suggests that pregnant Mother's diet influences the child's taste preferences. So here he says that: "This begs the question of how acceptable it should be for pregnant women to eat junk food, as this will predispose the child to like those foods, and probably not healthy 'whole foods'." And he also, as you can see in the screen he referring to: "Currently the social norm is that smoking and drinking during pregnancy make you a bad mother. Yet gaining lots of weight, far more than necessary for a healthy pregnancy, and eating unhealthy foods are socially very accepted, sometimes even encouraged." So is actually criticizing so we should not only police women for smoking and drinking during pregnancy but also their food choices.

These examples, I mean I have many and I don't have time to show you. But they all show that, the pregnant body is considered a closed system. A micro environment for fetal development that we can control. And yes we all wish that we can have a happy pregnancy and, not exposed to stress, and we have the sources, so that we can have the best kind of diet and nutrition but that's not the fact for many people. They're also exposed to lots of environmental pollution and hazards, and stigmatizing women, or responsibilizing women, for doing the right things during the pregnancy is a little bit problematic. But what we are going to look at here is the legal process. This is because in the legal process, the social understanding of the normative values around parentage holds a big value. I mean if you think about the debates on abortion and how there is a desire to control the woman's reproductive body, in the US at the moment, this actually gives a lot, a little bit, wider context to this: "Claims associated with epigenetics may influence public notions of maternal responsibility towards future generations and also raise novel challenges for law particularly for transgenerational justice."

Some lawyers talked about this and bioethicists as well they say that for example: when epigenetics research focuses excessively on the maternal effects women may be constituted as hostile, or as potentially hostile, environments for future people and that might have legal consequences. She rightly warns it's not hard to imagine a solution in the form of more regulatory and social constraints on women. And there are lots of examples of that. If you're interested you can read Fentiman's book, she has a book about this kind of interventions on women's bodies and pregnancy, so it's not unheard of or unprecedented. Given the causal relations that may be established in epigenetic studies legal thinkers already started speculating how epigenetics can be used in the court. For instance, Robison notes if: "Connections between present actions and future consequences can be established scientifically via epigenetics a tidal wave of legal claims would potentially arise of children against parents, grandchildren against grandparents, and so on", and actually I saw some news coverage of, you can sue your grandparents for what they ate during pregnancy, this is not, ur, this is already in the social media and news. Furthermore as epigenetic changes can be transmitted to subsequent generations concerns arise as to whether transgenerational claims could be successfully established in the courts. There's also example of this, for example cases relating to diethylstilbestrol (DES) in the US illustrates how the courts were faced with claims as to epigenetic imprints from multiple generations. The initial claims were successful, made by mothers and daughters exposed to DES against manufacturers. So there are, the third generation claims were not successful, but there is also precedent in the law that this might happen.

I have conducted some interviews, this was funded by British Academy and the leverhulme trust, I spoke to legal thinkers and the bio-ethicists to see if these, the, discourse available in the public sphere can rise to legal and moral obligations and whether this can be even used in the court.

Well actually it does look like that there is a risk of that, for example one of the bio-ethicists says that: "We need to be careful we need to put safeguards against bad interpretations and discrimination ... but it is going to be difficult to an anticipate those issues". Another bio-ethicists said that: "The way epigenetic findings are interpreted by policymakers are deeply influenced by the ethical and ideological views of the policy makers". So for example someone who is also have a policy to avoid abortions might have different ideas about how to control that pregnant body, or how to discriminate women for example, when they didn't take care of themselves as much as it was asked by the policymakers.

There are also, there was also, talk of gender biases for example this bio-ethesis says that: "There are ways to articulate epigenetics that are compatible with classic neoliberal logics of responsibilizing the individual. It still makes intuitive sense right can have this kind of idea of the very importance of the mother because we were all raised at this point in some kind of dysfunctional version of nuclear family. We grow up in a society where a lot of women, in one way or another, raise children and in some kind of level of isolation, right?" So the bioethicist here is talking about that there's already that idea of women as carers of the children, and this this might actually affect the ways in which gender biases play out in the court.

A lawyer said that: "I would give very little credence to these victim blaming schemes", So he referred it as 'victim blaming schemes' and he said that: "Start out telling me you are going to now blame men as well as women and their role in this and then I'll pay attention to you". And also he reflected on his work in the past: "In terms of blaming mothers, one issue that I've worked on for many years is policies in the US that excluded from the workplace", excluded women from the workplace, "who not only were pregnant but they were fertile, so they were potentially pregnant." and therefore they weren't given jobs, and it went to the Supreme Court. "so it's the same kind of issue that we've been seeing"

And there is also some concern about the stigmatization of women, especially pregnant women, this lawyer, another legal thinker says that: "It is a well-known fact [women] are already under pressure for their behavioral and other life choices during pregnancy and if you can propagate this idea, well, then it's not only you will be responsible of how the child turns out like, but also for your behavior six generations after. {...} This will kind of drill down even more pressure on women".

So overall, the scientific findings in epigenetics and maternal environment are too preliminary at the moment to provide a solid evidence in courts. But but we don't know how it will play out in the next for example 10 years, and even if the evidence is good science, because it's not always translated in the accurate way. But even if the evidence is good science, it will almost impossible to isolate epigenetic mechanisms from the social context. So you can see the causality between, for example Charlie's, criminal behavior and his mother's exposure to stress, but that that's isolated environment, what's important is where she was living, why she was stressed, and those are the um environmental facts that we cannot control and also this relationship is a very private one, as held in Stallman v. Younquist the relationship between a pregnant woman and her developing fetus was: "unlike the relationship between any plaintiff and defendant". So putting them against each other is very problematic. Almost all bio-ethicists and legal thinkers agree that gender biases play a big role in our understanding of moral responsibility, but also how we understand and translate the epigenetic findings. There's also a lot of evidence coming from transgenerational epigenetics that showing the, for example a father's exposure to bad environmental hazards can cause problems in the sperm quality, of the sperm, but that's not we are picking up in the social media. So finally while the findings from epigenetics research can generate useful insights to enhance people's lives, and of course the pregnant women's lives, by tackling with social inequality they might also bring an undesirable effect of discriminating and stigmatizing certain groups of people, and that's probably something that we have to think about when translating findings from epigenetics to public. So I think that will be all. I welcome all your questions and thanks for listening.

[Kate Storey] Thank you very much Ilke. It's, it's fascinating to think about how advances in science can change the way we perceive our own bodies as women, but also how, how we also framing that in terms of a wider society, and, and the responsibility women have for their for their developing child. So we'll come back with discussion about that after, after David Lawrence has given his talk. So I'll briefly introduce you David, as we I think we're probably running a little bit short on time, I'll try and be quick. [Ilke Turkmendag] Sorry. [Kate Storey] Yeah never mind it's okay. David is a bioethicist researching ethical legal and policy implications of emerging biotechnologies including neurotechnologies, implantable devices, and human enhancement. He has other interests in bioethics and medical law more generally, with a current project focusing on the creation of new life forms through synthetic biology. He's an editor of the clinical journal of neuroethics and the Cambridge quarterly for healthcare ethics. And David's talk today will explore ethical and legal challenges posed by neural organoids and related technologies, particularly the moral and sentience related risks posed by advanced neural models and consider whether these need new forms of regulatory Insight. So a very different topic. Thank you very much.

[David Lawrence] Thank you, I also, just to say there's a lot of people here thank you for coming to listen to this, far more than I perhaps anticipated. I want to preface just by saying um this is a a fairly broad overview. I thought the thing to do would be to discuss kind of what issues are being discuss, what ethical issues and sort of policy related issues, are being discussed, in the places that such things are discussed. So there won't be a huge amount of depth on, on most of the things that are mentioned but I just thought it was important to highlight what is being talked about. Conveniently for me that includes the thing that I most interested in, which is the sort of moral status related, ur thing, we'll come to that in a moment. So yeah this will just be a kind of an overview of the what are probably the more pressing ethical and regulatory questions coming out out of neural organoid research. Specifically thinking about things how these structures are forcing us to rethink some of the fundamental issues in the frameworks that we use to govern them. But my point is that this, you know, this isn't theoretical, as these technologies, or things like neural organoids and related technologies develop, there is a need for a kind of much more nuanced ethical oversight, and this is becoming sort of increasingly urgent. Just trying to start my stopwatch so I don't go over time sorry. There we go.

So look I realize that there are those in the room, there's names that I recognize in the list who are, who are going to be vastly more familiar with some of these concepts, particular the sort of scientific side of things, so I will try to keep this brief. For those less acquainted neural organoids are essentially 3D 'brain-like', and I use that term advisedly, structures grown from pluripotent stem cells. What's gaming about these is that they will help us overcome some of the limits of older models, like 2D cell cultures and animal, excuse me, animal models. They kind of give us a window into, direct window, into human brain development and neurological, the development of neurological conditions. So for example models are being used to better understand diseases like Alzheimer's, Autism, the impact of the Zika virus, I know was, has, been the subject of some research on fetal brain development with organoids. And this is where the, these, things come into their own. They go way beyond what we've been able to... Whoops sorry I've skipped ahead there, they've, they kind of go way ahead what we've been able to achieve with, um you know, traditional cultures. They let us track, you know, human specific neural activity in a, you know, a perhaps a more realistic context, if you like. And lately there have been a number of really exciting developments things like assembloids. These are a step forward, they're combining different regions of the brain to create more comprehensive models. More recently 'organoid on a chip' where these are systems by which we're able to keep these cultures alive longer, provide them with steady steady and directly controlled nutrient supplies, which opens up the possibility for much more detailed, much more extended, studies. But, and it's a big but, there are a lot of limitations. Despite advances, you know, neural organoids are a very long way from replicating anything close to a functioning human brain which if you read, I don't know the Daily Mail, is what they would have you believe. They lack vascular systems, for the most part, which limits their growth, their structure, again for the most part, it's very disorganized compared to, you know, actual human brain tissue. So understanding these kinds of limitations is really important when you are thinking about the ethical implications. I know that that was a very potted version, possibly incorrect In some instances, of the science so please hold your excoriation until the end. So what I'm going to do is just outline a couple of the kind of pressing concerns that stem from this, and then we'll go into a little bit more depth on what I think are the more complex issues on the horizon.

So one of the core ethical dilemmas, perhaps a more prosaic one admittedly, is ensuring truly informed consent, right to to tissue donors. The pace of advancement in this field is giving kind of quite unique challenges. How can you expect, like really expect, a donor to kind of fully grasp how their cells might be used in future research in this area? Because the fact of the thing is, that we, I say we as a research community, we, don't necessarily know what direction things are are going to take, you know, in a year or two years. The kind of traditional... done that again sorry... The kind of traditional consent module, uh model, traditional forms of consent, informed consent, they might not be enough anymore. And I mean this is not just limited to neural organoids, this is true in a lot of, kind of, fast moving areas of of scientific research. But in this context people who are donating tissues, donating cells today might not realize that their cells could end up forming, you know, these brain-like structures and so the question is are they really providing inform consent for that outcome? And the question is that even if we are to try to explain these things, as I say, we don't know exactly what direction the research is going to be taking and it's quite hard to ensure that people fully understand the implications of this in when we're talking about brain related things. There is a tendency, there's some good kind of socio-, medical sociology on this, of people being um sort of overawed by discussion of brain related things and kind of willing to uh so non-critically accept what they're told. So it's actually quite difficult to ensure a full understanding, in some instances, when you're talking about this type of thing. I mean that, actually I say that research is, actually, that's largely been used in neuro-evidence, the use of neuro-evidence in the courtroom, where it's even more crucial, or could be more crucial. So anyway, this issue of content becomes all the murkier when you think about the long-term, right, these unforeseen uses of organoids. We're all aware of, you know, the Henrietta Lacks thing. So you can imagine a donor's cells being created, used to create, an organoid that be could be kept alive and studied for months, for years, a new cell line... These are levels of complexity that most people just don't anticipate when they're giving consent. And there isn't really a clear or particularly great solution for this at the moment. It's something that is currently under discussion. One proposal that has gained a lot of traction is the idea of 'dynamic consent', right. So a model of ongoing communication with donors where they're updated and they, kind of, give fresh consent as new research possibilities arise. Which sounds great in theory but in practice that's so difficult, keeping track of donors over the long term, especially as the research changes unexpected ways, this is a logistical nightmare. And so as researchers, you know, we've got to think about how to find the right balance. We want to be able to move forward with critical scientific research, but you, we, need to be able to continue to respect the autonomy of those who donate cells. If we don't do that then we can kiss goodbye to people donating in the future. So this might just mean being more upfront about the potential and the sort of known unknowns, or it might be you know developing these new consent models that allow for flexibility and finding ways to make those those work as research evolves in unpredictable ways.

A somewhat related further important set of concerns revolves around data protection and issues around commercial commercialization. So neural organoids will often carry genetic information from the individual whose cells we used to create them. There are corresponding, sort of, serious privacy concerns there. How do you respect the the confidentiality of that genetic data? Especially when organoids can be kept alive and studied for extended periods, or that is the goal. So it's not just about privacy in the short term, it's about safeguarding data over months and even years of research. And the further question of commercialization, you know, as neural organoid technology progresses we are likely to see commercial opportunities arise. Which raises all kinds of thorny questions about ownership and profit sharing, which is something that's been faced in other areas of sort biomedicine/biotechnology lately. You know, should the individuals who provided the cells have any claim to profits generated from organoids that become commercially valuable? That's a sticky question. So striking a balance between the interests of donors, researchers, and companies who might be involved is a significant challenge. You also have, kind of, a more, related this as a more broad concern about the commodification of you know brain-like structures. Some people are worried that creating, you know, neural organoid as commercial products might undermine human dignity, they might blur ethical boundaries that we consider to be fundamental to you know biotechnology work and tissue research in particular. And those sort of issues don't exist in isolation, right. They intersect with debates that are, have been, going on for years about genetic privacy, commercialization of human tissue, broader biotechnological ethics questions, so for us it's essential that we remain aware of those concerns and how those conversations are developing in these, like, slightly different fields, or slightly different areas, in order to consider how work on organoids, or indeed whatever, you know, your focus is, fits into that, sort of, larger ethical and societal framework. So that's the more prosaic issues I wanted to touch.

So let's talk about what's maybe a bit more provocative and more comp, more complex, in some ways, the question of moral status and consciousness and like, I can already see some of you in the room rolling your eyes at this. So I want to just preface by putting a couple of words on my position here. This is kind of my core area of Interest more generally, throughout biotechnology. But I don't want to give the impression that I think we're currently in a position where we, you know, have this concern, where we have organoids that are sentient, might suffer, possess sapience, anything like that. I'm fully aware that we're not. That organiods are, you know, not that well developed, and they may never be so well developed. Because of, you know, things about their structure which we'll mention a little bit later, but I have two thoughts on this. Two very brief versions of thoughts on this: One is that, well my intent here is to give an overview of what's been discussed in the kind of ethics and policy sphere around neural organoids, every room that I've been in where we've been having these discussions, at whatever level, this issue has come up. If it, and if not been, the kind of, the core focus of the discussion. And secondly I'm of the opinion that with biotechnology we ought to think proactively. Should this situation never arise then okay well we wasted a little bit of time talking, but if it were to arise, as we'll discuss a little bit later, as well; setting up any kind of regulatory regime will take an awfully long time, decade maybe. And it is taking a long time, and taking a lot of work, and if it needs to account for a scenario with moral status kinds of issues then it will take even longer, because these are difficult to parse out. So it kind of behooves us, in my view, to start thinking about it early. So I'm just going to outline the very basics here. As these organoids become increasingly sophisticated they exhibit more brain-like, or more akin to brain activity, we are forced to think about these challenging questions about the moral status. You know, at what point, if any, might an organoid deserve moral consideration in its own right? And this is not just an academic question, right, it has profound implications for how we conduct research, what limits we place on experimentation, and so on. When we are thinking about moral status, you know, it's sort of the intrinsic value of things. This is in inextricably linked to questions of consciousness. We've seen, you know, reports that have been heavily criticized, studies reporting patterns of electrical activity, there was that paper from 2019 the name of, names of the authors I forget, but that purported to show electrical activity resembling those seen in, you know, like a premature human fetus neural tissue. I believe that that was sort of largely debunked, but these are concerns that people have. You know, there was supposedly showing coordinated waves of activity, which I know does happen. The thing that was in question was, like, whether this was actually representative of something that might happen in a pre-term fetus. So, you know, while it's crucial to emphasize that, you know, current organoids are far too simple to possess anything resembling what we might think of as human consciousness. Then these findings, kind of, raise really important questions about the future trajectory this technology is going to take. And so I feel like I should say what we mean when we talk about consciousness in this context then. Within bioethics more generally consciousness could refer to a range of capacities, and it's you know, this is something that is a constant argument. But for my purposes at it is most basic it might mean the ability to have, you know, any kind of experience, even if it's not something self-reflective. You know I, this is all as I say, this is not widely agreed, everyone has their own interpretations, so every paper that talks about this will set it out at the beginning. But for my purposes I tend to divide like this: Sentient beings can experience positive and negative sensations, right. That we can think of as representing the, sort of, most basic level of consciousness. Above this we might think of beings that are self-aware, or to different extents capable of experiencing like a wide range of subjective mental states, and that might encompass a broad spectrum of cognitive abilities. And within that category there's, there's you know, significant variation as the kind of complexity and richness of conscious experience can differ greatly between between the sort of subjects. Beyond that we have what we might think of as sapient entities. Things that are in possession of advanced cognitive abilities, reasoning, abstract thinking, moral agency. These are things that we would, you know, associate with personhood, and what we sometimes call 'full moral status'. The kind of thing that, you know, we like to think that we possess. Obviously not an issue for organoids just yet. There are also of course various kind of competing theories of consciousness that we we have to throw into the mix in these discussions, we might think about things like 'Higher Order Theory' where it's arguing that consciousness requires the ability to reflect on your thoughts, which you know organoids don't have obviously. Things like integration, uh excuse me, 'Integrated Information Theory', it's quite popular, on the other hand, suggests that, you know, even simple neural networks might have basic awareness. There's other things like 'Global Workspace Theory' which I'm personally less familiar with, but you know, these see consciousness as the product of widespread neural activity right which is maybe a level of complex that organoids haven't yet reached. This is something that goes hand in hand with complexity science, which is something I'm starting to try and learn about myself, but because there's this big range of interpretations it becomes quite challenging to pinpoint exactly what constitutes sort of morally relevant consciousness in organoids.

But I like to be pragmatic right, this is kind of my my thrust in a lot of what I write. I think that we can cut through a lot of this to get to the heart of the matter and the lawyer Hank Greely did this really nicely he asked: "If it looks like a human brain and it acts like a human brain at what point do we just treat it like a human brain?" and I think that encapsulates the core of the ethical quandary, like, quite nicely, it's like a nice little nutshell. It's a bit sound bitey, it makes some assumptions, but I think the thrust of it, yeah I'm on board. So to kind of address that some ethicists really go for a precautionary approach, right. They argue that given the uncertainty the high stakes that could be involved here, then we should err on the side of caution, and that might mean treating organoids like they have a, you know, a degree of moral status worth protecting, once they reach a certain level of complexity, even if we're not actually certain that they do possess sentience or consciousness of any kind. The rationale being that if we're wrong, because we don't really understand consciousness, if we're wrong about them lacking it, then the moral cost of causing that kind of suffering, or the potential kind of suffering, is a severe moral cost. On the other hand some researchers, ethicists, kind of contend that ascribing moral status to organoids is premature, right, and doing so would unnecessarily hinder really valuable, really important, research. Some of they, some of these, kind of, argue further that without the broader context of a body sensory inputs, interactions with an environment, an organoid no matter how complex it is, can't meaningfully be said to have experiences that, you know, some people consider to be vital for the granting moral status. So they would tend to emphasize the sort vast difference between even the most advanced organoids, organoids excuse me, and, you know, a functioning piece of human brain tissue. At the moment they simply lack structures that are considered to be fundamentally necessary for things that, you know, cognitive processes that we think are necessary for consciousness. So lacking the cortical plates for instance. And then there's another level of complexity, which we'll come to a moment, the, kind of, question of moral status within chimeric models, you know, where um, transplanting neural organoids into animal brains. But as we, sort of, navigate these sorts of questions it's worth, sort of, thinking about the concept of moral status as a continuum rather than a binary state. You know, maybe as organoids develop more sophisticated neural activity they could be granted increasing levels of moral consideration. Mirroring in some ways how we often can afford different levels of moral status to various forms of life that we're familiar with. This is, you know, shamelessly, this is the subject of a book I'm working on the minute, so you know look out for that in, who knows how long sometime. Ultimately as researcher is pushing the boundaries of what's possible with with neural organoids, you know, you'll need to think about these profound questions I think. It's crucial, in my view, to remain informed about the the latest ethical discussions, what's going on in the policy sphere, in the area and to be prepared to justify the moral considerations in your research designs. It might be that we need to develop new ethical frameworks and guidelines that can evolve alongside this kind of technology. You know, that can ensure that our moral reasoning keeps pace with the science, which, you know, it doesn't always do.

I mentioned another issue here, sort of a growing concern, that you, around neural organoid research, the use of human animal chimeras. The ethical questions here are not new, particularly, but in this instance, you know, you're transplanting neural organoids, or organoid tissue, into animal brain tissue. Primarily to side step, or my understanding is primarily to side step, the sort of size and vascularization limitations that we have in in vitro models. I could be mistaken about that. Which is exciting, there's exciting research opportunities there, but it opens up the door to a number of significant ethical questions that, kind of, have been going on in the chimeric sphere for a while. The first being, more obviously, animal welfare. How does introducing human neural tissue impact on the host animal? Or suffering?, could it change the animals cognitive behavior in ways that might raise serious, sort of, welfare issues? There's a broader question about humanization, you know, if part of an animal's brain is made up of human neural cells, like, at what point do we need start reconsidering its moral status, right? You know, could they, could chimic animals, be developing cognitive capacities that are in some way resemblant of those of humans? And if so what ethical obligations do we then have to these strange new creatures, you know in, in how they're treated? And we could push it even further and say, you know like, or we push that last idea further rather, there's a really tricky issue is the potential of the development of you know mental states that we might recognize, or cognitive abilities that we might recognize, from humans. Whilst we are not at that stage of research it's an incremental risk that we can't afford to ignore. You know, experiments as I understand it, have already shown, sort of, some degree of integration between human animal neural tissues and there are suggestions, again as I understand it, I could be mistaken, of behavioral impacts. So these questions, as I say, they connect to, like, larger debates that have been going on for since the year dot about the ethics of animal research, the moral states of non-human animals. But, you know, we need to weigh the benefits of chimeric research against the ethical concerns and we need to think about what our safeguards ought to be.

So with all that in mind as this kind of research advances one of the biggest challenges that we face is how to regulate the, sort of, science around these kinds of models, or the development, of these kinds of models. You know, the pace of the technological development, kind of, outstrips the ability of regulatory frameworks to keep up, right. A the moment, to my belief, no country has any kind of dedicated agency or body that's, you know, specifically overseeing neural organoids. In many places they do fall under the jurisdiction of broader regulatory agencies but these agencies by their own admission are largely not equipped to handle the kind of unique ethical and legal issues that arise from this kind of research. You know, I realize this is sort of an international audience, and I'm forgive me for only addressing the UK, but that's my my chief familiarity and also time constraints. In the UK we have the, um I've done it again, the HFEA, the human fertilization and embryology authority, which regulates research on human embryos and we have the human tissue authority, the HTA, overseeing the sourcing and the use of human cells. But neural organoids fall outside of their jurisdictions once the cells have been dissociated, disaggregated, or developed in the lab, since the organoids are lab grown structures the HFEA's oversight ends after that dissociation and the HTA only covers the sourcing of the initial tissue. So that means that neural organoids are not regulated, they don't come under what's known as the category of "relevant material", and so they occupy this strange unregulated space, despite showing complex, you know, neural activity. And this is a significant, kind of, ethical / legal gray area that existing frameworks just don't address. You know, the issue is then compounded by, as I say, the glacial pace of regular development when compared to the rate of scientific advancements.

And this problem is not limited to the UK. to mention a couple of things very briefly, Globally the situation is is very inconsistent. A lot of countries, the US, Japan, China, The collective countries of the EU, have a variety of regulations on chimeric work, on embryo research, on stem cell research of various types, but, to my knowledge, and again this this could be somewhat out of date because this is moving quickly, none of them have specific regulation pertaining to neural organoids just yet. There've been a number of white papers, major reports, come out over the last few years: The US National Academy consensus study from 2021, The German leopoldina white paper from 2023, both very interesting. The Nuffield Foundation UK has recently had a briefing come out on this, but there there's no action that's been forthcoming based on those, in those countries, or or elsewhere. The international society for stem cell research, the ISSCR, gives us some, kind of, general guidelines on stem cell research, but they don't directly tackle the ethical challenges posed by neural organoids. They have the quote that's there on the slide: [(Researchers) should be aware of any ethical issues that may arise in the future as organoid models become more complex through long-term maturation or through the assembly of multiple organoids]. And it should be noted that, you know, this guidance is being updated and is due to come out in the not too distant future, so hopefully that will have something, kind of a little bit more meaty on it. As I say countries have laws on animal-human chimeras but, you know, they don't really apply to organoids. I'm sorry I don't know why that keeps flicking forward um, so anyway: What I think we need, urgently, is forward thinking guidance, even regulation, that can anticipate the ethical challenges on the horizon, right, these models are only going to become more complex and as they do our current frameworks will become, sort of, increasingly insufficient, they're insufficient already. We might need to think about creating, kind of, new legal categories for things like neural organoids, entities that exist somewhere between, you know, traditional tissue models and those with, you know, the potential for moral status, sentience. But we're at this kind of tricky phase, this critical phase, in the research where you know regulatory oversight needs to be flexible, it needs, to be interdisciplinary, and it needs to be proactive. You know, the major challenge is to ensure that any regulation that's put in place, guidelines put in place, don't stifle innovative research, but at the same time protect the, kind of, ethical, legal, social, rights of all parties involved. And then, I'm conscious of the time, I'm coming towards the end.

As we look ahead, it's pretty clear that neural organoid research is moving into, like, this this critical phase, I say, and one that really places, places us, at a crossroads of innovation and ethical responsibility. These models have already shown us all kinds of massive potential in helping us understand the brain and developing treatments for, you know, neurolog-, excuse me neurological conditions. But as it advances, as the technology advances, we need to make sure that our ethical frameworks and our regulatory frameworks can evolve with it. You know, I mentioned earlier things that we're faced with, like the organoid on the chip, we're also faced with things like, you know, so-called "organoid intelligence" the beginnings of, like, "biocomputing" by networking organoids and that's, on the slide is an image of a an early example of this. So a major challenge that arises from this will be moral status. As these organoids and as, kind of, assembloids and everything else, become more complex we're going to start to blur the lines between biological models and something more valuable, right. So we will need new ways to evaluate cognitive function, we will need new ways to evaluate moral status, consciousness, within these systems it, I just don't think it's a question we can afford to ignore and it's going to require serious scientific reflection and serious ethical reflection. Even though, you know, it is in some some way a speculative problem, on the regulatory front we have to ensure adaptability. So whether that means the creation of new oversight bodies, expanding existing regulations or the remit of existing bodies, which, you know, they are broadly resistant to, for good reason. It's crucial that we handle this responsib- responsibly. Again goal is to ensure that we don't stifle innovation, but that we have kind of clear robust boundaries to work within. It's also worth saying, just as a last thought, that most of the issues I've talked about here, however briefly, are pretty much applicable to other related technologies as well the really hot button one at, the moment that's just seeing the same sort of attention, possibly even more attention, in the same kinds of rooms, with the same themes coming up is the stem cell derived embryo model, most if not all of the issues there are similar to those here, though more particularly and more immediately around moral status, and possibly more contentious, anything involving the word 'embryo' tends to be. So, to end. I think that interdisciplinary collaboration is just essential here, right. This is not just a problem for neuroscientists or for bioethicists, it's a challenge that's across neuroscience, ethics, law, public policy soc-, you know, sociological studies as well. Policymakers, scientists, ethicists, we need to come together to think of frameworks that can encourage innovation and safeguard our principles. And as well as this, public engagement, I think is quite key, the societal implications of this kind of research are quite big, to understate it, and we need to make sure that the public is part of the conversation as we go forward. So to conclude, you know, this is an area with extraordinary potential but it's somewhere where we must tread very carefully and so, you know, how as we encounter new challenges do we, as a scientific community, and as an ethical community, how do we ensure that we're balancing those, with, kind of, innovation. So thank you for listening. Sorry that that was a very whistle stop tour, but um thank you for your time.

[Kate Storey] Thank you very much David. I think it's a great start to having the discussion, which as you say really needs to be across disciplines and across peoples, from scientists doing experiments, and ethicists, and social-sociologists and everybody in the public. Will be affected by these issues. So thanks again. I should have said at the beginning though, that I didn't introduce you properly because I just wanted to say that you are an assistant professor in biolaw at the Durham law school so just to get that clear.

[David Lawrence] Thank You.

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Maternal epigenetics and sins of ‘women of childbearing age’

Dr Ilke Turkmendag, Reader in Biomedicine and Society, Newcastle Law School, Newcastle University

In biomedicine, the accessibility of pregnant bodies for biomedical intervention raises important

social, ethical and philosophical questions about exploitation and control (Turkmendag 2022).

Maternal epigenetics has an interest in individuals’ reproductive capacity with the aim of developing

therapeutical or environmental interventions to improve human health down the generations.

Drawing on examples from social media and interview accounts of bioethicists and legal thinkers,

this talk focuses on whether the increasing focus on “maternal effect” exerts power over women to

take on new responsibilities.

Kenney and Müller (2017: 27) suggest that “as evolutionarily adapted to being optimal gestational

environments and caregivers, women’s bodies become de facto sites for research and intervention

in relation to the health of her offspring.” In recent years, there has been an increase in the research

into linking children’s early development to their mother’s lifestyle and behaviour during pregnancy,

and even before conception. Poor prenatal diet, prenatal exposure to domestic violence, exposure

to maternal distress, Caesarean delivery, alcohol intake before conception and during pregnancy are

all linked to epigenetic changes that may cause health problems in the offspring. In this field, the

uterus is seen as a micro-environment in which new generations take shape for better and worse.

Hence scientists, especially those who work in the developmental origins of health and disease

(DOHAD), seek to find out how to control the maternal environment and behaviour to advance the

health of the offspring and next generations (Richardson et al 2014). Because epigenetics concerns

how gene expression is influenced by the social realm, including a range of environmental conditions

such as exposure to chemicals, pollution, and environmental hazards, the research findings in this

area have direct policy relevance. For policy makers, rather than controlling the complex range of

determinants of health, isolating and targeting the maternal body and “responsibilizing” mothers for

the control of this micro-environment might seem more feasible (Turkmendag and Liaw 2022).

While the findings from epigenetics research can generate useful insights to enhance people’s lives

by tackling social inequality, they may also bring an undesirable effect of discriminating and

stigmatising certain groups of people if they are used to make individuals accountable to

circumstances that they may not have the capability to control (Richardson 2014, Turkmendag and

Liaw 2022).

Suggested reading material:

Kenney, M. and Müller, R. (2017) “Of rats and women: narratives of motherhood in environmental

epigenetics,” BioSocieties 12(1): 23–46, https://doi.org/10.1057/s41292-016-0002-7.

Richardson, S., Daniels, C., Gillman, M. et al. Society: Don't blame the mothers. Nature 512, 131–132

(2014). https://doi.org/10.1038/512131a

Ethical Dimensions of Neural Organoids: Navigating Moral Status and Regulatory Challenges

Dr David Lawrence, Assistant Professor in Biolaw, Durham Law School, Durham University

Neural organoids, advanced three-dimensional models mimicking aspects of human brain

development, are transforming our understanding of neurodevelopmental processes and diseases.

Recent advancements—including the creation of assembloids, which integrate multiple organoid

types, and other nervous system organoids like spinal cord models—further expand the scope of this

research. By replicating more complex neural circuits and interactions, these innovations amplify

ethical considerations surrounding their use.

This talk explores the ontological, ethical, and regulatory challenges posed by neural organoids and

related technologies. As these models increasingly emulate brain-like functions, they blur the lines

between in vitro models and biological neural systems, raising pressing questions about sentience,

consciousness, and moral status. Are neural organoids and assembloids merely research tools, or do

they possess a form of moral status that warrants special ethical consideration?

Further complicating this landscape is the challenge of informed consent, particularly as the long-

term and unforeseen applications of organoid research evolve. Traditional consent models may no

longer suffice, prompting the exploration of dynamic consent approaches that can adapt to the

shifting terrain of biotechnological innovation. Additionally, we will discuss the ethical dilemmas

associated with creating human-animal chimeras through neural organoid transplantation, focusing

on potential cognitive implications and animal welfare.

We will also address the regulatory gaps in current oversight mechanisms, especially concerning the

moral and sentience-related risks posed by advanced neural models. Existing legislation and

guidance can struggle to keep pace with rapid technological advancements, leaving key questions

unresolved. This underscores the need for flexible, interdisciplinary regulatory frameworks that can

evolve alongside scientific progress, ensuring ethical governance without stifling innovation.

Suggested reading material:

Nuffield Council on Bioethics Neural Organoids in Research: Ethical Considerations (2024).

https://www.nuffieldbioethics.org/assets/pdfs/Neural-Organoids-in-Research-Briefing-FINAL.pdf

Pichl A, Ranisch R, Lawrence DR, Árnason G, et al. Ethical, legal and social aspects of human cerebral

organoids and their governance in Germany, the United Kingdom and the United States, Frontiers in

Cell and Developmental Biology 2023;11. https://doi.org/10.3389/fcell.2023.1194706

Hartung T, Morales Pantoja IE, Smirnova L, Brain organoids and organoid intelligence from ethical,

legal, and social points of view, Frontiers in Artificial Intelligence 2024;6.

https://doi.org/10.3389/frai.2023.1307613

Croxford J, Bayne T, The Case Against Organoid Consciousness, Neuroethics

2024;17(1):13. https://doi.org/10.1007/s12152-024-09548-3