Ethics Seminars

So I'm Andrew Copp, I'm very pleased to welcome you all to the third in the HDBI ethics seminar series. So on bioethical and social aspects of human embryo research today. And for those of you who've been to these before we you you'll remember that we have two speakers so I'm delighted to to have Sarah Chan and Sarah Franklin here to speak to us today.

And then we're going to have, we hope, quite a long period, because they'll probably talk for about 15 minutes each, and then we'll have quite a long period for questions and discussion and so on. And we realize that that the discussion of these topics is some sometimes covers contentious issues, particularly in relation to human developmental biology research which the HDBI is involved with. And so we hope that we'll be able to have a completely open inclusive and safe sort of environment for this discussion everybody will feel welcome and able to participate.

As we go along please do write any comments or or questions in the chat and then we can return to those towards the end. But we'll take questions and discussion at the end of the of both the talks, I think that will be the best way.

So let's get started then. So our first speaker is Professor Sarah Franklin so I'm delighted that she's able to join us so Sarah's a professor of Sociology at Cambridge where she's been since 2011 or at least in that role since 2011. She's extremely well known in the area of of sociology in relation to new reproductive technologies. She's established two initiatives that have been very influential the 'IVF histories and cultures project' and the 'reproductive sociology research group' and so she's really been a Pioneer in considering social change in relation to new reproductive technologies. She's published extensively on many different aspects of this including cloning, and pre-implantation genetic diagnosis, and human embryonic stem cell derivatives. So without further ado then I'll ask Sarah to give us her talk. I think she's probably going to cover the 14-day rule as part of her presentation, I hope so anyway. And we'll look forward to hearing what she has to say, so Sarah over to you.

Thanks so much Andy it's really great to be here today and obviously I'm not an ethicist, but I would like to talk about the UK legislation of human embryo research and in particular the 14-day rule. Because this is an obviously very important ethical area. But it is what we might call a kind of hybrid ethical area in the sense that the UK legislation has been based on very strong ethical principles but formulated with a great deal of input from scientists, social scientists, public engagement, initiatives, policy people. And so I really want to talk about the 14-day rule as a case in point about what kind of social contract the UK has around human embryo research. And this is of course very important because this legislation is now up for review. So it may be that some of this is quite familiar to some of you and, if so, apologies for telling you things you already know. But I think this is a story that really shows us what's at stake in this area not only for ethicists but for as I say scientists and social scientists as well.

So the birth of Louise Brown 1978 was widely seen to have created what was often referred to as a legal vacuum. You know there was no ethical oversight, no legislative infrastructure for the clinical practice of of IVF when it first appeared in 1978. And the establishment of the Warnock committee here in the UK was established to provide legislative guidance for what was termed human fertilization and embryology. The UK is the only country that has ever had had extensive regulation in this area. So the achievement of the Warnock committee in first writing their report in 1984 and eventually passing legislation in 1990 was exceptional. It was a highly exceptional achievement and so it's worth keeping that in mind when we think about what might be the successor to the human fertilization and embryology act. Which would be the regulatory instrument for the next phase of human embryo research.

Following the publication of the report there was a very long period of legislative, parliamentary, and public debate culminating in the passage of the first HFEA. This was then revised in 2008 and is now, as I said, being revised again to take into account things like embryo models. Which is something that we might want to talk about later. So the 14-day rule is particularly important because it's the centerpiece of the human fertilization and embryology act. And the way it works is along a principle we could describe sociologically as a reciprocal principle in the sense that the 14-day rule instituted a kind of social contract based on an exchange. So that in exchange for allowing controversial scientific research, research on human embryos would be allowed but subject to the very strictest regulations including a time limit, a strict enforceable time limit, and criminal sanctions backed up by parliament. So that was really the sort of principal basis for the legislation.

And this was devised largely by Mary Warnock and Anne McLaren. And so the principle of the 14-day rule, the reciprocal principle for the 14-day rule, could also be considered the foundation for much of the legislation around biotranslational science here in the UK. And that model, the model of a reciprocal social contract, underlying biotransational research is at once a very general model, but in the case of the 14-day rule also a very specific one.

And I want to tell you a little bit about its specificity in order to make some suggestions about what might be needed in order to have a new time limit, a new regulatory centerpiece as it were, for human embryo research.
So the Warnock principles were, I think you could say, not strictly ethical they were also somewhat anthropological or sociological. For example Warnock argued that if the 14-day rule, or whatever other regulation of embryo research was devised, wasn't 'right' in the strict ethical sense then it would be at least 'all right' to the largest number of people because some limit, or indeed any limit, would be better than none which as she put it: 'nobody wants'.
She also argued along with Anne McLaren that consensual limits don't need to be non-arbitrary to be effective. She didn't like using the 'ar' word arbitrary and the rule was often criticized for being arbitrary, but for Warnock it was sufficient that it be workable and consensual, and it could still also be a rule that could be changed. She therefore argued that such limits are more likely to win support if they don't appear to be entirely arbitrary. But they can be somewhat arbitrary and we'll come back to that. She argued the limits were both literal and also in a sense symbolic and, as I noted, she argued the limits could be changed.

So the 14-day rule is a literal limit it's a 14-day limit but it's based on a biological fact that may or may not take place exactly at 14 days. So this represents the idea that there should be some limit even if the limit isn't entirely clear, and we'll come back to this. They argue that IVF and human embryo research should be allowed for the greater good of society. They argued that if IVF were to be allowed embryo research had to be allowed in order to ensure it was safe and to and could be improved. They argued that if these were allowed there had to be a firm line, beyond which the research couldn't go. They argued the line had to be credible and enforceable, it had to be clear precise and pragmatic, and it had to be based on robust scientific evidence. And it had to stand as a means of ensuring that there would be a moral expression of social limitation on research, as well as a legal one.

So that was a lot to try to put together and here to cut to the chase is exactly how they did it. This is one of the drawings from one of the most important documents that was distributed at the key meeting on the 9th of November in 1983. The penultimate meeting of the committee. Where a linear illustration of the very precise process of implantation, embryonic implantation, is Illustrated. And as you can see there is really an actual line. Which for some is understood as the formation of the embryonic disk, for some is understood at the formation of the primitive streak, but is in either interpretation a physical developmental landmark as it was often described. However that wasn't quite sufficient and so the two week limitation was also argued to be necessary in order to make the law enforceable.

So let's just consider for a second what the 14 day rule is not. It's not a measure of the moral status of the human embryo, in fact it doesn't really address the moral status of the human embryo at all. It's not a line that establishes when human life should be protected, it's not a line that applies to any other issues, in particular abortion. It's not importantly, strictly speaking, technically purely a line based on biological development or scientific evidence. It's not an entirely arbitrary line and it's not a permanent line. it's none of these things so what is it?

Well actually technically it's a bit of a mishmash. It's Loosely based on scientific facts and on highly specific biological landmarks such as the formation of the embryonic disk, which makes it not entirely arbitrary. It's it's indeed tightly based on a detailed map of early embryonic development but equally on an overarching sociological principle of reciprocity, of exchange. The act which eventually emerged in 1990, is a legal document that enforces a social contract for biological research overseen by a statutory body, charged with enforcing the will of parliament. So the 14-day rule is at once a sort of hybrid ethical marker, a sociological process, a social contract, a legal process, a policy process, and of course a scientific process. And it results in the 14-day rule which is at once arbitrary and non-arbitrary.

So another interesting fact about the 14-day rule is how long it has lasted. It has now lasted into its fourth decade. It has now endured as the anchor for the unique system of governance of research in the UK and it has withstood number of substantial amendments over time. The 14-day rule is the most emulated feature of the HFEA, and remember no other country has ever managed to have comprehensive legislation of this kind. And it has become the default standard for all of the other countries that don't have laws. It's been singled out out by policy makers and legislator legislators worldwide as quote unquote 'a textbook case' for successful regulatory policy in this area. And it's continued to uphold, and indeed to help to build, public confidence in bio-innovation, creating a unique climate for translational bioscience in the UK.

And this has been noted by a number of commentators including in this 2019 article by Sheila Jasanoff and Ingrid Metzler two of the world's most prominent political scientists, who work in this area.

Who describe the Warnock consensus, as it's known, based in large part on the 14-day rule. As a legislative framework that 'has enabled controversial bioinnovation to proceed markedly more smoothly than in any other Western Nation. One by one The HFA has approved an array of practices and entities, [from] derivation of human embryonic stem cells ... to somatic nuclear transfer, ... to human admixed human embryos ... to mitochondrial donation' and so forth. Nevertheless, they say, sorry: 'all of these Innovations were subjected to extensive public consultation. [and]. Nevertheless, or perhaps precisely for this reason, none produced the public uproar or political deadlock that characterized comparable debates in Germany and the United States'. They suggest.

Okay so all of this really began to become the subject of more intensive public engagement and discussion when it became physically possible to culture embryos for longer than 14 days. And the possibilities of the scientific and potentially clinical benefits that would result emerged as a subject of of more concerted discussion.

And alongside a progression of research developments, which has continued since 2016, have emerged a number of new questions about the 14-day rule. Whether it should be changed, whether it should be extended, whether the governance of human embryos should be removed from the human fertilization embryology act and become subject to a new act. That's more specific to fertility research, with a different set of legislation that's designed for science including embryo models?

Should there be in effect a new social contract in this area? This is the big question on the table right now for which the history of the 14-day rule is a very important guide. If there were to be a new new social contract what would it involve, I'd be very interested to hear the thoughts of people here. Obviously the new social contract also has to be a new ethical contract, a new legal contract, a new kind of bridge between the scientific community and the wider public. Would it be important, I'd be very interested to know what you think of these questions, would it be important to take into account that fertility care is now in some ways a greater cause of public concern than embryo research in the post IVF era? Could a new social contract be orientated towards regulating research, but also towards enabling transparent equitable access to high quality health care, including fertility care? Or should it be? Would it be be advisable, or not advisable, to introduce a more graduated system of enforcement. Where some types of embryo research are more subject to higher levels of oversight or indeed of legal protection? Would it be possible to have this be based on many of the same Warner principles or or should the 14-day rule remain? Or should it remain with the proviso that there could be exceptions to this rule and if so how would they be regulated? These are the questions that are on the table at the moment.

So what are we going to need to answer them? Well I would say we need, importantly, to look at the history of how we got to where we are. But secondly we will need new public engagement and outreach, and some of you here may already be engaged in some of the extensive public engagement and outreach activities orientated around the prospective new regulation in this area. There will be a need as there was in Warnock for excellent scientific communication, for a real dialogue between the scientific community and the general public. There will need to be the ability to build on the very significant history of existing consensus around legislation in this area. There will obviously need to be high public trust in scientific credibility, transparency in the legislation or regulatory apparatus that succeeds the current arrangement. And I would argue there will need to continue to be a very strong sense of reciprocity that this legislation is facilitating work that is in the public good. And of course that will need to be credible, which was a crucial part of the 14-day rule. So I'm just going to leave it there. Looking forward to your responses, questions, and comments. And I will stop sharing my screen.

Thank you very much thank you Sarah that was tremendous very thought-provoking and made me feel quite excited but also daunted that we're really at a position in a similar way to Anne McLaren and Mary Warnock all those years ago and trying to sort of Blaze the trail towards some new system. So I'm sure we'll return to this in due course. Okay so our second speaker this afternoon is Sarah Chan. and Sarah apart from anything else has the dubious, uh she she she's actually, attend, she's actually been a speaker at two of these seminars, last time she was on the agenda for our second seminar and was forced to leave the seminar within minutes of starting because of a fire alarm. So I'm really delighted that she's now here without any fire alarm going on in her Department. Sarah's reader in bioethics at the Usher Institute in the University of Edinburgh and she's associate director of the center for biomedicine, self and society. And she has done a great deal of research on the ethics of new biomedical technology. So very relevant to the topic that Frankin's just addressed as well. So this has included gene therapy, genetic modification, stem cell and embryo research, various different aspects of reproductive medicine, synthetic biology, and also human and animal enhancement as well. So I'm very much looking forward to hearing Sarah's presentation which is going to be on 'the future of human embryo research regulation'.

Okay so having, I think, been presented with a very convincing case that now might be the time to revisit the regulation of human embryos, not just for research but for reproduction, I want to spend my talk thinking about what that future might look like.

Specifically what I want to walk us through is why might we want to change the rules on human embryos. How might we go about doing so, and what some of the challenges and issues are that we might face along the way.
And I'm going to argue overall that changing the rules is going to require us to understand both what the rules are but what their role is in public bioethics and policy. So as you've already heard from Professor Franklin the regulation of both human embryo research and assisted reproduction in the UK is generally a permissive one. We're allowed to do many activities but we're allowed to do this under a complex and comprehensive system of regulation that sets out what may and may not be done with embryos. And in particular some activities involving human embryos are permitted when those embryos are to be used in research but not currently for reproductive use. And we've heard that developments in science and medicine are now posing challenges to this regulatory framework.

The key elements, so I won't go through the historical background because again Professor Franklin has has done that very comprehensively. But the key regulatory elements that I want to focus on, in terms of what we might want to change, or we might need to change in the future, are that, as we know, use of embryos whether for research or reproduction is regulated by the human fertilization and embryology Authority. Uses of embryos and gametes are controlled under a licensing system. In particular we have the 14-day rule, or the 14-day limit, for how long embryos can be maintained in culture. And we also have this distinction between embryo research versus their reproductive use. And as I said there are particular things that may be done to embryos that render them, what's called for the purposes of the act as it stands in its modified form, a non-permitted embryo. That is an embryo that is no longer permitted to be used in reproduction. So genetically modified embryos, hybrid embryos, so inter-species embryos, are embryos that now fall under the non-permitted distinction. With a very specific exception that allows for embryos that have had their mitochondrial DNA modified for the purposes of treating mitochondrial disease, can be permitted embryos under the human fertilization and embryology mitochondrial donation regulations passed in 2015. And as we've heard the development of this regulation has established a sort of model for how public bioethics can be enacted in the policy sphere when it comes to controversial areas of research.

So we have a system, it works well, why might we want to change it? Well first of all as we've just heard there are scientific prospects that might challenge the current regulatory system. We now have the technical ability to grow embryos potentially Beyond 14 days and doing so might help us to understand mechanisms of development that happen at this crucial stage of embryonic development. We also have the prospect of what has been called synthetic embryos, or gastruloids, or embryoids, the self-organizing entities assembled from pluripotent cells that seem to recapitulate the embryo at that stage of development and don't have a clear 14-day limit from when we should start counting. So what do we do with these scientific challenges to the 14-day rule? But there are also therapeutic prospects that under our current system of regulation would not be possible. In particular human reproductive genome editing. So we can perform genetic modification, genome editing, on embryos for research but at the moment we can't use it in reproduction for example to try to cure genetic disease. So these scientific and therapeutic prospects together give us reasons to say well we might want to change the law. Now of course just because we can do something doesn't mean we should. So we can grow embryos Beyond 14 days, we can genetically modify embryos and use them reproduction, but that doesn't mean that we ought to do this. Gulia Cavaliere calls this: 'the argument from technical feasibility', well we can do it now so we should be allowed to do it. That's not necessarily the case, but if we can do good, on balance, all things considered. Then we should do that. And so the question for us becomes, what benefits might be made possible possible if we were to change the regulation to allow embryos to grow past the 14-day limit? To allow reproductive genome editing. So not only can we do it, but can we do good with it, can we realize the benefit? And of course because that question is on balance and all things considered, we also need to take into consideration what the risks might be of doing so, and these might include both scientific and medical risks. The discourse around the use of genome editing in human reproduction has concentrated very much on what might be the risks of this still largely untested procedure, for future children, for future Generations. But we also need to think about what we might call 'social risks' to science. So would for example a change in regulation that somehow breached the social contract that we've talked about, that engendered a lack of public trust in science, what risks might that pose to the good that science is able to achieve?

What sorts of issues might we face when it comes to thinking about how we how we might go about changing the rules? First of all, how can and how should, regulatory change be achieved? Now as we've heard regulating the human embryo in the UK has established a history, if you like, of public bioethics as a mode of policy making. And I think we've learned a lot along the way about what effective ethical policy making looks like. First of all from the IVF era and the Warnock report, through the major changes to the act that happened in 2008, and then the mitochondrial donation regulations in 2015. And so the lessons that we can learn from the way in which this process has been achieved each time, show that certain key aspects have been important in the successful establishment and maintenance of regulation and in regulatory change. These include public discourse and consultation they include the involvement of scientists alongside experts from other disciplines and lay representatives. So the at the time unique feature of the Warnock committee, was that it brought together this diverse group of individuals to represent different perspectives. The modes of discourse and of public involvement have evolved and changed at each step. So the consultation around the changes to the act in 2008 was a little different. The consultation and the public involvement, when we, when the mitochondrial donation regulations were enacted. Again different, and the involvement of scientists as well has evolved over time. So for example in relation to the mitochondrial donation regulations. There were a series of steps of proofs of safety and efficacy. There was a scientific committee that was specifically tasked with examining the these aspects. But the other component that it has been shown that we need for this for regulatory change to be effective and to maintain that that social license around research it takes time. So Louise Brown born in 1978, Warnock committee took another six years to report back 1984, took another six years after that for the human fertilization and embryology act 1990 to be made into legislation. Similarly the consultations and discourse around the 2008 changes to the law, the 2015 changes to the law, started years before any reform went into the legislation. And so we need to be starting to think now about how we might change the regulation in the future, and to be aware that it's not going to happen tomorrow, or next year, it will take time for this to happen. And so that's why now is the time to start thinking about the changes we want to see in the future.

Okay I want to address two challenges in particular that I think we need to consider when we talk about changing regulation. One of these is, if you like, an ethical objection, or an argument about moral consistency and the role that regulation plays in expressing a moral position. So the 14-day limit has often been described as a 'bright line'. Certainly it was a clear limit it was something that was, as Mary Warnock said, was countable, everyone can count to 14 and it provided that sort of certainty that here is a limit. And, as we've heard, that clear, not necessarily non-arbitrary, but at least justifiable limit, provided the cornerstone of our regulatory system and remains so to this day. So the first question is, can we think about moving that 'bright line' without falling foul of what we might call 'slippery slope' objections. Now let me explain this, this is tending towards the sort of ethical philosophical side. The slippery slope argument is often used to object to advances in technology and changes in what are we doing in these controversial areas. So the argument would go that: Allowing research on human embryos is the first step on a path that will inevitably lead to: Something obviously impermissible such as, destructive research on adult humans, or so forth. And that would have been the argument at the time when we were considering, will we allow research on human embryos. And in some ways the 'bright line' may have been perceived as a response to a slippery slope. So if we draw a line and we say you cannot cross this line it will prevent us from slipping. So there's a question about whether willingness to consider crossing the line, crossing the 14-day line, or moving the limit. Would that be evidence of the slopes slipperiness, giving weight to arguments that say: 'look we told you so we've allowed research on human embryos and now we're going to start growing them in culture up to 28 days, 2 months, 3 months, we're going to grow human babies in culture. The slope is slippery and this proves it.' Is that a consistent moral position? Is that correct?

And I'm going to say it's not because the 14-day limit, I think we should view more as a regulatory fence. So with slippery slope arguments we need to argue, we need to question, what lies at the bottom of the slope, and how bad is it actually, and how likely are we to slip. Now the slippery slope argument seems to imply that there is one single way down the slope and at the bottom of the slope lies something very bad, such that we must not even start to go there. But research as we know, is not a singular route from A through, B, C, D, all the way to Z. It's more like what I would describe as a garden of forking paths. Each development in science, it's true might, if allowed to slip, lead to a very bad consequence but we also need to take those steps to get to the good consequences that we want to see. There's not a single route down the slope. What we need to do is navigate the slope rather than close the gate to to the garden. And so the 'bright line' we need to see not as a line that may never be crossed, but something that exists for the time being as a regulatory fence. It gives us a place of security from which we can look at what's on the other side of the fence and see whether or not we want to go there. So I've been willing to revisit our rules, and think about the moral basis on which they were enacted, and whether it's time to move on from those is actually a necessary part of ethical policy. I won't go through, I wanted to draw a sort of comparison in terms of moral consistency from an argument in the early days of stem cell research about whether the time limit that used to exist on human embryonic stem cell funding was, could be moved. I won't go through the argument in detail, but suffice to say that, as you heard Professor Franklin explaining. The 14 day rule isn't in itself a moral boundary. I think of it as a boundary object. So it's not that before 14 days embryos have no moral status and after 14 days they suddenly acquire it. The 14-day limit instead is representative of the special status of the embryo. The idea of, as we heard, the symbol of, a moral idea of society not a moral limit in itself. And so therefore the 14-day rule has enabled discourse among different perspectives, amongst different views of embryos as being reproductive futures, and repositories of reproductive choice, resources for research, and resources for therapy. Moving where that boundary object is, or being willing to move it, signals not a moral step change, not a step down the moral slippery slope, but an evolution in the discourse.

The second issue that I want to mention um is around the global context for regulation and what scientific responsibility requires. Now in thinking about how we regulate cutting-edge research an argument that sometimes comes up is: 'well if we don't allow it somewhere else will'. If we don't permit this in the UK, UK scientists might go to other countries where regulation is more permissive. or more lax, we will lose the benefits of the research being done in this country, we'll lose our position as world leaders in the field. So there are concerns there about, missing out, losing ground, due ... [faint barking] sorry not a fire alarm only a dog ... Due to overly restrictive regulation. And you know I want to ask whether is this a sound argument to say: 'well we need to we need to relax our regulation otherwise we're going to miss out'. But regulation is not just about stopping science, although I think it does have that role, of an exchange, of reciprocity, as Margot Brazier described it as: 'regulation being the price of assuring research'. But it's not a strict social contract in the, the sort of Hobbesian sense of: 'you agree to something you otherwise wouldn't agree to', just to to stop being nasty and brutish to each other. Scientists don't want to do bad things anymore than publics want them to be able to do bad things. Regulation can also facilitate research especially in controversial areas, it provides scientists with the certainty to operate and it provides that social license, it ensures support well-governed research.

So what does it mean if scientists then go about escaping that regulatory system through scientific tourism. What does it mean for scientific responsibility when scientists exploit regulatory gaps, or lacunae, in order to do something that the rest of the scientific community deems to be irresponsible. And there are two obvious examples of this within recent years in the reproductive research field. The first obviously the creation of genome edited babies, three four years ago yeah four four years ago now. And about seven years before before this. The creation of children using mitochondrial replacement therapy at a time when this had not yet fully been approved in any of the countries concerned. And the scientist who did this he was a, he US scientist, carried out the procedure and did the embryo transfer in Mexico because he said: 'in Mexico there are no rules'. Similarly when the genome medic babies were created in China, many of the world's scientists commented: 'well in China there are no rules'. In fact neither of those things are true, but the perception that in certain countries there are no rules and the actions of scientists in taking advantage of that perception have consequences. Decisions about where and when to conduct research affect the global politics of science. The mitochondrial tourism incident in Mexico had a number of consequences. In the first place it fueled a regulatory push back and a disruption to the delicate evolving process of regulation in the country. More restrictive regulation being being introduced as a sort of knee-jerk response to this. This then hampers scientific development in these under-resourced countries and it increases to burden on local oversight mechanisms. But it also reveals a deep, what I call scientific chauvinism, and an underlying political hegemony in terms of who sets standards of good science, who says what constitutes good governance, in which countries does good science get done. When it comes to ethically questionable research who do we blame? And if you look at the cases in Mexico, in China, people said well of course it would happen in places like that where there are no rules. By contrast there was a very high-profile case of a stem cell clinician conducting ethically questionable research in Sweden. Nobody said in Sweden there are no rules. So blaming the destination countries both allows scientists to escape individual responsibility but also reinforces these hegemonic power structures within global science that disadvantage countries that are already lower in scientific capital, lower in resources.

It reinforces the systemic power disadvantages that exist within science, and it creates a problem of justice with respect to regulatory resources and capacity because it increases the burden of oversight in countries where ethics and governance structures are already struggling to develop. So scientific tourism is an unjust appropriation of human resources and scientific capital. And so the moral of the story, and where I'm going to finish, is that responsible science requires that we not go elsewhere and we try and make things better here.

Thank you very much.

Thank you very much Sarah. Another very thought-provoking talk. I guess most of us are interested in making things better here and carrying on our research which is exactly what you're saying.

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