Transcript generated by machine and may contain errors

Dani Paci Hi, all. Thank you for attending our webinar, Should We Change Chimeric Human Animal Research today. You will not be visible or audible during the webinar, but we do encourage you to ask questions through the Q&A function. This session is being recorded and it will be available at the Hastings Center website later today for viewing with closed captioning. This webinar will focus on the recommendations recently addressed in the Hastings Center Special report Creating Chimeric Animals Seeking Clarity on Ethics and Oversight. It’s now my pleasure to introduce today’s speakers. We will be joined by Josephine Johnston and Dr. Insoo Hyun Josephine Johnston is a research scholar at the Hastings Center and is an expert on the ethical, legal and policy implications of biomedical technologies. She is also a lecturer at the University of Otago. Dr. Hyun work focuses on ethical and policy issues in stem cell research and new biotechnologies, and he is the inaugural director of the Center for Life Sciences and Public Learning at the Museum of Science in Boston. Dr. Hyun is also a member of the Center of Bioethics at Harvard Medical School.

Josephine Johnston Welcome. And thank you, Dani, for that kind introduction. Thank you to everyone who’s online now, zooming in from wherever you’re zooming in from around the world. Maybe I’m zooming in from the other side of the world myself. Just full disclosure. So thanks for joining us for this conversation about the ethics and oversight of human nonhuman animal chimera research. In just a minute, we will say a little bit about a little bit more about what that is, what we mean when we say that. But let me first of all, acknowledge that a lot of the what we’re going to say today draws on a NIH funded research project that my colleague Karen Maschke, Insoo and I lead with collaborators working collaboratively with Patricia Marshall at Case Western and Carolyn Neuhaus at the Hastings Center and with the very amazing support and involvement of Caitlin Craig, Meg Matthews, Isabel Bolo and Ben Wells. And drawing on the expertise of an interdisciplinary international interdisciplinary work that we put together. And many of the findings of the project are in the November December. Hastings in a report, special report, that you can access open access on the Hastings in his website and through the Wylie platform. So this project that we and so Karen and I co-lead had various components and we will draw tonight into an eye on the qualitative analyzes that we did or interviews and content analysis and on the conceptual normative and policy analysis we did, especially with the work group. But in so and I also have, you know, our own histories of looking at and researching and playing roles related to this kind of research. So and so it’s been a member of the and a leader at the International Society for STEM Cell Research for quite a long time, who say more about that, which I know informs his his thinking and his understanding of these issues. And I’ve been following and writing about the same sort of biases. And so sort of for since 1999 or something when it all kind of took off. And and that’s very much related to to that to the history of this issue from a policy perspective. I also stepped on an embryonic stem cell research oversight committee, which will say what that is in a second. But they looked at studies, including ones that involve the creation of chimeric animals. And so, you know, we’re going to draw on lots of things, including our study. But not just that when we in our discussion today. Okay. Well, before I go much further, I just wanted to ask I’m going to ask Enzo if he can give us a sort of working definition of chimeric research so that we can sort of all be on the same page from that beginning.

Insoo Hyun Yeah, I agree. Thank you, Jesse. Thank you, Danny, for the introduction. It’s great to be here. I believe also along the way, when you have questions that come up, our participants can ask questions and make sure if a security function or the chat. But maybe Danny can put up under the chat instructions for how to submit your questions. We’ll be happy to take those later on. Yeah. So, yeah, out research, as Jose says, it’s been something that we’ve been thinking about for quite some time. I don’t know how many of you in the audience are really all that familiar with coming out of research, so I just wanted to say a few brief things about what Chimeras are and and why they’re being used for research. First, you know, what are chimeras? Chimeras are organisms that are composed of cells that come from at least two different segments. So that’s like the most general definition of a chimeric. Now, together, a little more specific, these two zygote could be of the same species or different species in the in nature. Sometimes you get embryos fuzed in the womb very early on in development, and when the embryos fuzed together and survive, they will form a species of species. The species chimera, which could be a combination of a male and female zygote or both of the same sex. But but in these cases you have one organism that’s composed of cells that are side by side, genetically distinct. Okay, Now that’s different than creating an organism through breeding of two different species. That’s what we call the hybrid hybrids. When you mix sperm and egg from two different species. And then the mixture appears at the genetic level within every single cell in that animal. Okay, so mule ride, etc., etc.. So we’re not talking about hybrids because to make a chimeric research, what you would then have to do sorry, a hybrid for research would you have to do is you don’t have to combine sperm and egg. And that’s not the kind of experiment we’re talking about. So is any animal that has cells that. Integrator from another zygote. And like I said, the most common ones are same species in research, in stem cell research early on. Most of the cameras were mouse chimeras from different strains. So they would take, you know, to prove that mouse embryonic stem cells were truly powerful. They would inject researchers, then inject embryonic stem cells from one side, go from one blastocyst of, let’s say, a white coated mouse into the blastocyst of a brown could announce a different zygote. And if that integrated, then you would get a mouse that was born that has patches of brown and white, which meant then that these cells didn’t integrate at the nuclear level throughout the body, but rather you had white coded cells next to brown cells and their existence side by side. So those are the same species ones, you know, in the in the human case, we do have clinical chimeras, we don’t call them that. We call them the transplant recipients. Right. But you get, you know, somebody who gets a donor heart from clearly a different zygote, a different human being, and that’s transplanted into clinically into the person, the recipient. So that person would have either male or female, right. Solid organ in their body and they would be technically a climber, one organism composed of cells that come from different different cycles. But again, you know, nobody really fears the human to human chimeras. I guess there are also cases where people, you know, individuals were fuzed in the womb during development. So we might have some some forms of hermaphrodites might be from that. You can get cases where people just for whatever reason a genetic draw, genetic blood test from blood and it to from the gut and you get two different genetic readings, which is crazy. But that meant that you had an absorbed twin in the body at some point. So those are naturally occurring chimeras for clinical chimeras to come here. So Josie and I are going to talk with you folks about our research chimeras and really not the mouse, the mouse studies that I mentioned or even the rat two mouse studies, although that might come up later. We’re talking about human to animal chimeras. So the dinosaur donor cells come from human and they’re transplanted into a research laboratory animal and allowed to integrate and and go on from there. Now, I do not mean that’s the just we do not mean to suggest that of our research is really that new. It’s been around for decades. The stem cell camera work is relatively new, but other kinds of camera work where, you know, you you would transplant human tumor cells into an immune deficient mouse, for example, or even you you might supplant thymus tissue into a newborn mouse to create what’s called a human immune system model. Within within the mouse. There’ve been lots of examples from, you know, blood studies, leukemia studies, cancer studies where people had mixed human donor materials into an animal and had it integrate. I think the whole issue of that stem cell chimera, you know, really took the possibilities of chimeras, some theoretically to a much higher level than in the past. So in the past people didn’t really worry too much. And still today don’t worry too much about very like limited chimeras and where you have, you know, again, an immune deficient animal, but a transfer of human cells to biologically humanize the animal in some way to study it. But with stem cells, there is the possibility theoretically that they that the chimeras and could be much more severe, much more acute. And the reason for that is the stem cells are very powerful cells and you can put them at various stages of development, you can put it, as I suggested, in like the pre-implantation stage of an animal embryo. You can put a, you know, within the in utero, within, you know, the developing fetal animal or postnatal. So basically there’s a whole continuum of different types of research cameras using stem cells. And the variables are what are the species of the host animal, What is the developmental stage of the host animal? How many human stem cells are you putting in? Where are you putting them in? How long are you letting them develop? And and, you know, for what purpose? So those are the broad array of activities. Maybe I’ll turn it over to you, Jesse. I mean, you know, there are certainly issues that come up where people ask questions like, well, why would you even make a chimeric for research? Maybe we can kind of get into some of the. Yeah, you’ve heard that all the time. You know, like, is it just curiosity or, you know, why would anybody want to put like you might understand the cancer cells. Yeah. You want to make that mouse into a little human cancer patient and test your drugs. But why would you pick human stem cells into an animal in like, I was wondering if you ever got that kind of, like, question or, you know, people wondering out loud to you, like, why are people even making these.

Josephine Johnston Yeah, well, I think people’s hope. I mean, I don’t know what people intuitively would think, but certainly the way that I’ve been thinking about it is that there are sort of. Main drivers for creating either an A and an organism like a blastocyst that has a mixture of human and non-human animal cells or actually having that happen in a living animal. And it seems like they either primarily about modeling, so creating models of human disease. And if you want to model some human diseases, you might want quite an integrated cells, integrated the human cells integrated in quite a significant way, and the living animal to model the disease or in the future to be able to sort of help with regenerative medicine. So be able to have a pig that has got human kidney living in it. And that that would be the kind of output of of chimeric studies. So I think one of the distinctions so that’s a distinction that I found helpful thinking about modeling of human disease, creating hopefully or trying to create more accurate models for things that we can easily model in living, you know, just by studying humans or by studying animals that haven’t been modified. And in the other main purpose being in order to sort of move towards various kinds of regenerative medicine goals. The other distinction that I think is quite helpful is thinking about climate research as being done in a lab and a dish. You know, there is no living chimeric animal. You still probably have had to use animals to get to that point, whether it’s by taking sperm or eggs or some other or some other cells from animals, non-human animals. So it’s not that nonhuman animals uninvolved, but what you’re studying is not a living animal or in distinguishing that a little bit from in vivo or living animals that we either are creating as part of this study. So I do think that that’s a distinction that I’ve also found quite useful in this sort of just lying, the landscape of this debate out of it.

Insoo Hyun Right, Right. I’m glad you pointed that difference out. I did so much of my work within the context of the International Society for STEM Cell Research, while I was ethics chairperson and I helped draft all the guidelines. And within that scientific community, somebody like me coming from philosophy and bioethics who sort of was learning the science sort of unasked need, need to know basis along the way. Very quickly realize this is such an enormously broad area of research. I think a lot of what I think about her research and the controversy surrounding the how something kind of particular in mind. But I think what people need to realize, this is extremely broad and there could be some really quite different reasons why a research team might put human cells into a, you know, an animal model at some station farmer. So I think a really interesting like category just to kind of think about is is the host is the animal host preimplantation result done in a dish. So from a scientific point of view or even from an over oversight like regulatory point of view, that’s sort of not viewed surprisingly maybe to some people, not viewed as like super contentious or controversial hot button because it’s not using what is thought to be, you know, like a living animal with the central nervous system for which you need an animal oversight committee there to monitor pain and suffering, etc.. Of course, there may be animal monitoring. If you’re clearly procuring the gametes, sperm and eggs to make the little embryo to then put the stem cells and procuring those from living animals, of course you’re going to have some animal welfare, not just looking at the welfare of the gammy donors. But once you have the gametes in the lab and you combine them in addition to make your preimplantation embryo, so basically animal IVF, when you’ve done that and all you’re doing is just keeping it in the dish, even after you put the human cells in there. If you’re just keeping it in the dish from a regulatory point of view, that’s not really like that big of a deal. But for many people, because it’s so early in the animal’s development and depending on the species of the of the embryo you’re talking about, whether it’s mouse, which doesn’t work very well at all, or something closer to a human, like a non-human primate, people do get a little bit worked up about these experiments. It really does start to kind of like seem like you’re really crossing a line there somehow, but from kind of a general and really a regulatory point of view. It’s not that hot, hot button because it doesn’t seem to trigger like the normal red flags that come up in review, like pain and suffering, because the thing doesn’t even have like nerve cells at that point. Right. That little embryo doesn’t. So one big category is kind of like in the dish. It’s going to stay in the dish. Well, we realized that the ESCRO in US International Society for STEM Cell research, as things get a little more complicated, that when you transferred into the womb of a surrogate animal and then you just stayed that mixture. A mixed embryo for some time, and there could even be theoretically all the way to gestation for gestation and delivery or, you know, birth of the animal. So there are like these various stages you almost like think like what are the different stages of the development of any animal And at any time point you might imagine cells going in And then the other big like hot button issue for people is not just human cells in the animal, but once the animal’s like, you know, just gestated in birth. And if it’s postnatal, if the cells go away and if the human cells go into the central nervous system, there tends to be a lot more like red flag waving than just like, let’s say, you know, human pancreatic cells put into a pig or put into, you know, another animal just to see how well the cells survive in a living context. Like those kinds of like non drone or cells tend to be less red but like hot button and the closer you get to the brain or stuck cells, the more kind of hot button it gets. I love one time hangry, which many of you, many of you know you said it’s brains and go necessarily get people all worked out and I think he’s right when it comes to timing versus the brain and anything involving sex thoughts that kind of really raised the issue. Yeah, I would add to that the embryo also forgot putting it in the idea.

Josephine Johnston So actually, I think maybe that’s a good shift over to sort of like what some of the ethics and oversight issues are in this area. And maybe I can just like kind of explain that like maybe like some other people on the zoom. I mean, I came into this via the embryonic stem cell controversy. And so, you know, in 1998 or I think it was there was the Dira phase derivation of embryonic stem cells from know. So derivation of these pluripotent stem cells from human embryos. And I was just starting my career in bioethics, actually doing a mass is a bioethics. And I wrote a paper about like a scoping paper for the New Zealand government actually, about what sort of countries around the world were doing in terms of regulation and oversight of this area of science. And that was very focused on the fact that we were the science involves taking stem pluripotent stem cells out of human embryos. Mostly those embryos have been created in the course of IVF by patients who then don’t want to donate them to anyone else but also don’t want to use them themselves or have finished having their family or just finished with IVF. And and the embryo is therefore destroyed. And, you know, various countries have very different reactions to it. But as we know in the US, anything involving embryos has a long history of being fairly very controversial. And even before the derivation of embryonic stem cells, there was already a law limiting the have the use of federal funds for any research involving sort of harm to or destruction of human embryos. So this research fell into that and hit up against all of those abortion and embryonic embryo related issues in America. So that’s kind of how I started thinking about it. And then over the course of, you know, I think many people know this, of course, that like 1998, this is a derivation, not 2001, is that President George W Bush is pretty well-known policy, very putting pretty significant limits on the funding of research with embryonic stem cells, with federal money, then private donors and states, including, you know, quite notably California, through a referendum with its voters like, you know, step in. And it’s a it’s a very interesting political and science kind of mix there of states and private founders stepping in and funding the research. And then you have this thing where researchers would have sort of like one set of equipment for federally funded research and then a completely separate sort of set up for the non-fatal refunded embryonic stem cell research. And already in that was this possibility is a kind of subset of the embryonic stem cell debate. This possibility that embryonic stem cells would be mixed with from humans would be mixed with nonhuman animal cells. And so in 2005, when the National Academies of Science Group put out its first set of guidelines for this work, sort of stepping in to provide guidelines for research that the federal government was not funding, therefore, you know, didn’t have guidelines for. So they put guidelines out. They already had a subset of those that were addressing chimeric studies. And as you said, those guidelines in various iterations and then ESCAS guidelines when those started to come out, was at first in 2012 was I think, set right or 20.

Insoo Hyun So where we did touch on camera research, I was actually all the way back in 2000. Six.

Josephine Johnston The first thousand steps a little bit. Okay. Yes. So those guidelines all had something about climate research and those studies that I would the guidelines focused on studies where well, the concern, I guess, that there might be human gametes produced by these non-human animals. So like you said, go ahead. So nobody wanted and the usual mechanism for that was like the animals can’t breed but wouldn’t really explain why. But behind that presumably is this concern that there might be human gametes produced and then also that you would.

Insoo Hyun Get in that case the hybrid you had actually.

Josephine Johnston With it? And then and then the other big sort of focus would be on like those studies in which there was a significant possibility that or a possibility that significant contribution to the non-human animals nervous system or brain would be part of the study. And what that means for oversight committees that were at various different institutions looking at this research is that you would and I know this from experience, you’d be sort of asking scientists to tell you things like, Do you think that the animal is going to produce human sperm, or do you think that the animal is going to have a significant portion of its brain with human cells? And it sometimes felt like we were asking sort of very sci fi questions and not really having a lot of background behind us of like, what’s this really about? What’s the main ethical concern driving this? Something probably about like. What would it mean for humans to have these creatures out there that had something like human brains to some degree, But it was a I felt like it was a rather inchoate discussion. And that’s sort of part of the motivation for our project, was to try to dig in a little bit on this stuff and sort of try to clarify like what do we think is mainly at stake here? How can we express it? What kinds of oversight make sense, what’s already being done? And so that’s sort of where we started to dig in in our project.

Insoo Hyun I think you raise some really interesting points. I think it’s crucial that the audience think about the actual timeline, how long. So some of these concerns have been around and how some of them just did not stand up to the test of time. I remember in the early days of this debate, there were some people this is back in the George W Bush era summit, you know, like 2005, 2067 around there where there were even, like bioethicists. I’m not going to say who, but somebody on George W Bush’s bioethics council who raised like some really provocative concerns but really were kind of scientifically nonsensical. So one person said, you know, I will be very concerned if somebody made a sheep with a human face. All right. Well, what would be the scientific reason for doing that? And by the way, how would that even be possible? Because the human face on the sheep would have to involve technically the mesoderm, ectoderm and endoderm ofthe germ layers, but only on the face. Like how would you actually make a chimera model that could do that? So I don’t even think it’s scientifically possible to do that. So anyway, it was it was startling to think about something like that happening or, you know, a pig with human hands again. And, you know, it involves technically all these dermal areas. And you can get that result using the transfer of human stem cells necessarily. So. So that was like a very provocative kind of thing to be worried about. Right. But it did not stand the test of time for a number of reasons. One, it was just ill forms, developmental biology. But I think another key aspect is people have found over the past few decades it is really hard to get human cells to survive and human stem cells even to survive and to integrate and even like grow or, you know, do anything in a foreign animal host. And so, like, even to get like more than like 3%, you know, it’s like a really big deal. And the scenarios people were thinking about were like close to like 30% or 50% human. So it’s just not like the science isn’t there yet. Which brings up a really interesting point about, you know, so now that people know there’s a very high xeno barrier between human and human species, how would you actually overcome that? And I guess it’s just sort of like why people are doing the embryo work. Okay. So some of you may have heard about some recent experiments maybe a year or two ago where they got monkey blastocysts and they put human stem cells in them. And they found that some of them kind of, you know, integrate it for a little while. You got a little bit of cell survival. There are a couple of what. So the reason for that is not that they want to eventually grow human organs and monkeys, right. For transplantation, but to better understand this barrier between human and non-human, to better inform livestock animal models that have human stem cells put into them. But that again, just kind of in the DISH system, the rationale for doing some of that work with non-human primate embryos is to better understand how to make the cells survive in other species. So you kind of need to see a little bit more of like what the context is or why people did that kind of work. But a key a key development that also happened from like 2005 to now is the discovery. The suspicion later confirmed that human embryonic stem cells, you see, the ones that come from the embryos, from fertility clinics are not kind of at the same developmental power level as mouse embryonic stem cells. So if you get mouse IVF and you get a stem cell line from a mouse blastocyst, that mouse pluripotent embryonic stem cell is so much more powerful than what you get from an embryo from a human stem cell clinic, infertility clinic. And it was like it was quite different. I mean, they’re both called pluripotent stem cells, but the human version is kind of what we would think in the mouse is the at the last cell. This is like after it’s implanted and it’s got already going down one of the three germ layers and of indeterminate term mesoderm, the human version is kind of a little bit further along in development. So the key development since then was to drive it back to about equal to the mouse power, the powerful stem cell. And it’s what we call naive stem cells or growl state some cells, you actually have to do something further to the human embryonic stem cells or now. IPS cells that you can make from scan to make them even more basic. And so you kind of get them a little bit more developed monthly on par with the mouse embryonic stem cells. And because we now use naive stem cells, IPS or human stem cells that better enabled some of the chimeric work to go forward and actually get a little bit more success. But they’re still a long ways to go. I remember back when, you know, all the that the key to controversy around human embryonic stem cells kind of shifted over into the camera work because obviously are using like these very precious cells that have come from very controversial biomaterials in the in the human embryo debate. And I remember when the IPS cell revolution came out, this is, you know, the ability to make some embryonic stem cells from any human cell to reprogram it. To do that, I remember thinking, you know, they’re going to start using those in animal studies and they already have potentially living donors who donated it like a biopsy and maybe have to kind of ask them, are you okay with your cell line? It used to make neurons and, you know, put into the. And also there was that whole other complication you didn’t have with the amount of stem cells because the embryo was destroyed in the process of getting the cells, but not for the adult or the pediatric patient to provide the cells that are now making this, like, humanized biologically humanized animal models. So I thought that was a very interesting to kind of have that addition to the to the IPS so work. But I remember also thinking at that time, even if people support a human embryonic stem cell research, so they were not part of the group that thought it was wrong to make to derive human embryonic stem cells. I thought there are people out there in the United States and elsewhere that care more about animals than they do about human embryos and and IVF clinic like like they were place the moral centers of animals way higher than an embryo before an implant implanted that’s sitting in a dish. So I just you wait even the supporters of human cell research might when they come to find out that during the course of research, a cell wide might be transferred over to an animal. That’s going to be a whole other generation of people involved in this debate. So so we’re I think, seeing some of that now. Right. So the apes saw revolution didn’t insights credit is actually brought in much more human bio material into the camera well.

Josephine Johnston Yeah. So, I mean, that’s really my experience with this show and especially during this project. And I really have to thank Carolyn Newhouse for sort of waking me up pretty early on. It’s like I came in from the stem cell debate and discussions about human embryos and and then like, what does it mean for humans if we create nonhuman animals that have some of our cells in their brains? Does that mean we show them something different? And I think some of those issues are definitely here. But one of the things that I think, you know, our project really emphasizes in its in its recommendations and analysis that we published in the special report is that, like this is often nonhuman animal research, non-human animal welfare is at stake here. The changes and societal shifts in how we think about non-human animals and about non-human animal research changes, including movements away from primate research that that secrecy sometimes or the the challenges associated with discussing non-human animal research. Those are massively at play in this area. And those of us in bioethics have not really not with exceptions, but not really focused on that we’ve been mostly focused on. I take myself in this on questions about, you know, these sort of moral status questions and also those donor questions of like, do the embryo donors know what they’re donating to if it’s coming, if the IPO sells, do the cell donors know, you know, understand what they’re donating? Dude, who have we got the right consents. Those are important. But those human centric concerns are very distinct in a way from these animal centric concerns that are like these are non-human animals we’re creating and using in the study. We don’t want to be talking about this in a way that inadvertently ignores that. You know, in an app report, we really elevate that issue and draw more attention to it and know that, like, it would be a tragedy if by focusing on these other issues, we sort of inadvertently don’t notice that, like, this is an area of non-human animal research. There could be novel forms of suffering that come to the non-human animals as a result of being in these studies. That’s a big thing to be looking for related to oversight. And so we’re really kind of trying to put the spotlight more in that area and noting also that, like chimeric studies, these will intersect with ongoing larger debates about non-human animals, non-human animal research, you know, court cases about the status, legal status of different non-human animals. You know, there’s very good you can imagine those intersecting very publicly with chimeric studies. So I felt like that was a really a big shift in my own thinking as a result of doing this work.

Insoo Hyun Yeah, that’s terrific. I’ll also kind of give a little bit of a confessional to I know we’re going to turn to questions in a moment, but back when I was at Case Western Reserve University School of Medicine for for many years, one of the things that I did very early on as a junior faculty member was I was assigned to serve on the Iucn’s Animal Use and Care committee. So the animal IAB. And so at that point, you know, I was a young faculty member. I didn’t really want to do anything. But this is kind of I guess I have to do it as a low person on the totem pole. They told me, you got to be on this committee, but I was so glad I was on it because although in the very beginning it would be quite a while to kind of catch on to like what’s going on, How do you actually you and of course, I come from philosophy. I didn’t even, you know, do any experiments as an undergrad. It was it was so interesting to see kind of that world. The case of the animal care and use committees will go through a whole checklist at the beginning of kind of like, you know, how many animals are using, what’s the species, Why are you using that species and not one that’s quote unquote, lower on kind of like the scale of complexity? And for how long are you going to take, you know, use the animals and what’s the pain category like? Are all these really specific questions that you ask along the way? And when I started them working on the camera issue for the international society, I kind of thought having had that experience, I thought, well, what else are we supposed to be looking for? Because our guidelines, I have them. We just said a special escrow committee has to look at Chimeras permits using human stem cells. And I thought, Well, what are we supposed to do that’s different from the either? And that was really kind of a question that kept sort of haunting me. I kind of thought, Well, we don’t want to just do exactly what I could then, because that’s what we know what they’re supposed to do. What are we supposed to look at? And I realized a lot of people’s concerns about climate research to me initially just seemed like they were just concerns about animal research. It’s just the use of animals. If your concern is not that, is there anything extra that you’re worried about, anything unique about camera research? And that’s when we kind of got into the whole like dignity issues or like it’s not pain and suffering, but it’s gain of function and it’s kind of like, you know, getting close to the human. And this ambiguous moral says these are definitely not things that are on that checklist. I’ll tell you that. There’s no boxes that is. Our dignity issue here. You know, nobody discusses in committee whether or not there is, you know, enhanced cognition and therefore maybe a benefit or elevation of the animal’s capabilities related to moral status, like no mention of moral status at all, just pain, just, you know, that the animals like agitation, you know, environmental regimen, those kinds of basic things. So it’s really interesting to think, well, what else will we be talking about when we’re talking about the advocates who come here, research that’s not simply reducible to animal welfare issues. And I think our project really kind of brought that out even further, that the need to like say, well, if there’s really nothing else there realistically at this point in the science to to mull over the maybe really the key issue is animal welfare. And I think that was a really, for me, a good place to land because I think it do kind of institutionally kind of give people a handle on what we can. We kind of already do this. Is there any additional help we need or sort of reason to kind of be monitoring the horizon to see if anything new might come out, that we need a little tweaked approach? And I think that that kind of grounding of like, okay, no matter what you think about animal research, here’s how it normally is covered and then trying to like ask like what else is there? That was a very fruitful way to frame everything. And I think that’s what we tried to do in the special report.

Josephine Johnston Yeah, I think that one of the sort of realities of some of this research is that there’s actually a lot of oversight happening at research institutions, at universities and other research institutions from different committees, and that can be a bit siloed. And so like trying to make sure that it’s, you know, and that the ethics discussion is also a bit siloed. And so we’ve tried to kind of like bridge that. I just want to quickly show a little bit. I need to show a couple of things related to the project, and then we’re going to turn to the Q&A. So let me just just explain a little bit about the project. As I said, we were looking at what was ethically at stake in climate research, trying to be really clear about what language captures those concerns. There are a lot of terms like even Chimera, that’s like actually if you look it up, a kind of a monster and mythology that we thought was, you know, we in our tests to preview find helpful, not to mention saying we’ve humanized the mouse and then wondering why everybody thinks that might be a problem. So we did say, you know, look at language and then look at how research is overseen and governed and whether there’s room for improvement. Here is the acknowledgments that the investigators is a nice picture of the way that some of this was done in person, but most of it was done ultimately over Zoom, of course, thanks to the pandemic. And then this is just the beautiful cover by fantastic artist for our report. And there’s a lead article that’s fairly long and has set of ten recommendations, and they encourage you to look at and share. And then there are also articles reporting on interviews with scientists and oversight committee members about moral status and coming your animals that you were involved in, and so that you and that Patty lead with Caitlin and you. So that’s less like empirical research reporting on interviews and then some essays, including one about, you know, really from two people who who have very committed to animal welfare, animal rights and animal welfare. And so we really made sure to investigate and integrate that perspective into the work as well as we have a lot of people who actually do do the science or are involved in, you know, the the ICAC’s and other institutional mechanisms of reviewing the site. So we have these conversations with researchers and animal welfare experts so that work is available and we can get into it in the Q&A. But I just want to make sure that I made that really clear, that people can find that that research. So, yeah, I think maybe with that we can just go over to the Q&A. Danny How do you want us to do that?

Dani Paci I can just offer you some questions, and then whoever feels up to answering it can take the question.

Josephine Johnston Right.

Dani Paci So we’re getting some questions, asking for a bit more unpacking on moral status and species membership. Why or why not? Is using species categorization as a proxy for moral status not ideal?

Josephine Johnston Okay, That’s a question. So I want to acknowledge that there are people whose entire academic research careers are devoted to the issues around animal welfare and animal rights. And this whole debate and I am not one of those researchers. Like I said, we did have some of those people involved in our study and we learned a huge amount from them. I also what I do understand of what I am saying is that people come to some of the same conclusions from different places on this issue, as many as they do on many other ethics issues that we, you know, we deal with in our work. So you could have the same view about moral status of a non-human animal, but have different reasons for that view. For some people, I think it is to do with species type. For other people it might be to do with capacities for other people that may be that that is a really human centric and limited way of thinking about what makes full moral status. So I don’t even know if it’s helpful for me to give my own view on this. You know, I like many people I have I think I’ve been kind of it’s confronting but also helpful to think about the ways in which a capacity base view might be quite limited. So, you know, octopuses have a lot of capacities that we don’t and also don’t have capacities that we do. What does that tell us about their moral status? I think that’s a very complex question, actually, and one in which in my own life I’ve had sort of 180 degree kind of change from thinking that maybe because they can’t do what we do with their high status morally or then starting to think that that’s almost a nonsensical question. So I do think it’s my personal view. I do think that that species ism and species based moral hierarchies are problematic, but also they are what we use. So I don’t know in a lot of like just a law and a legalization. And so, you know, this is what I meant when I said that these debates about climate research really do intersect with these much larger shifts and debates and public discourse, and individuals own kind of moral thinking about non-human animals and, you know, and raise questions that have nothing to do with climate research in a way which is like, what do you eat? You know, what do you what do you kill, etc.. So I think it gets very big very quickly. And it’s part of what was really stimulating, honestly and on a personal level for me just to be involved in and this project. But I can’t kind of categorically answer that question. I don’t think I’m not sure anyone can.

Insoo Hyun Yeah, I mean, I think it’s a very interesting question. You know, sort of what’s relationship between moral status and species type. And I think there’s so many interesting nuances here to talk about. I don’t think saying something has moral status or not gets you very far. I mean, there are people in the Animal Research Committee itself think that mice have a certain level of moral status. You could wrong them by making them suffer unduly or unnecessarily or extremely. So they say they have some moral status, but doesn’t mean that you can’t use them for research. So the more interesting question for me is not whether they have moral scientists or not aware that threshold for intervention is right. So animal research, all the oversight of regulations around it for research institutions kind of is part of the Animal Welfare Act. And that’s kind of an acknowledgment that animals have some kind of rights that not to be, you know, harmed or or unduly suffered. The question is, is there like a no go zone or are there some species for which, you know, no amount of any kind of use is ever justified? And that’s the more interesting question for me, rather than it’s sort of like a species type and it’s sort of level of moral sense attached to that. I think it has to do more with thresholds. I think we can generally say all animals that are sentient of because of their sentience have some degree of moral claims on the US of how we treat them. The other thing I find interesting about species is that you might have a view that. A particular species of animal shouldn’t be used for research in basic research purposes. Maybe behavioral research is fine, but invasive research where you’re doing operations on them is not permitted, period. So so you can kind of be that person. Another might be I’m okay with this hypothetical species being used for invasive research, but if the transfer of human cells gives the capacities that give it, make it extra like it’s no longer equivalent moral status member to its other species, like in the control group. So let’s say hypothetically, you have mice in the control group, you have experimental mice that same same strain, strain, same Brady put the cells and they somehow have a gain of function. It would be wrong then to then do any further studies on them that involve invasive studies or euthanasia because you’ve somehow elevated them. So that’s an interesting line as well, right? A threshold because I could just of move my in my experience, I think that the transfer of any kind of modification or cells typically makes them less competent or less species typical. And so you actually see a a drop in welfare rather than like gain of function. And slowly, you know, they’re enjoying life a little bit more. I mean, it usually is a drop. So that’s kind of the more likely outcome. And then you have people who think that there are some species that are so close to human that if you if you didn’t do anything, they made them gain function, they would be okay. But like, let’s say some hypothetically, some non-human primate might get mental capabilities, cognitive capabilities. I was kind of bumping up to this zone where it’s above the capabilities of a control group, and that’s somehow problematic. So there are all these like dimensions to this question of the relationship of species and, well, science. I think it’s really about thresholds and whether the intervention kind of like raises the threshold and people have thresholds of different places for intervention. It’s a really intriguing question. So I don’t think there’s you can’t because of that, you can’t give like one like common answer across the board because there’s all that variance in how people think about go or no go on the on the experiment.

Josephine Johnston You know, I just want to acknowledge as well that nonhuman animals can have different moral status for people with different moral significance based on very different things than their species function or their capacity. So I live in my home again of New Zealand out here. ROA and like native bird species, have really high significance here, moral significance that’s not about there. I mean, honestly, there are birds that can’t fly, right? Like some of them have kind of go like, what is the capacity is not the issue. It’s to do with the relationship to native native culture and native beliefs and systems. They’re they’re rare, you know, that sort of thing. So there are many different things that feed into it. I’m sorry, we’ve got a question here about. Oh, sorry, Denny, you want to read the question? Sorry.

Dani Paci You can also read it. You just so.

Josephine Johnston It’s just about I think it’s a question that and so maybe how to address. We had members. It’s about whether or not we queried our cooks to identify with the diocese research using the welfare concept and. We did have our members on our expert working group so that we had input at that at that level. But you did empirical interviews involved with interviews. So you’re on, right?

Insoo Hyun Yeah. So the case Western team did a series of qualitative interviews with people who either were doing research as scientists in in the camera field or were people part of oversight committees or were Animal Research Oversight Committee members. And so some of these conversations, these interviews were summarized in like this conversation piece that’s in our special issue, so moderated by Caitlin Craig, a research assistant. She went through and she she had a really interesting conversation, which she then transcribed and read it with our cook members and their views. And many of these people actually, like reviewed kind of their research protocols and were there to kind of monitor the welfare of the animals. So there’s a lot there. I’ll turn the question person who asked that question to that so sort of conversations or essays in the special issue.

Josephine Johnston Yeah. And I think, you know, they are attuned to the issue of I think that’s fear that they very attuned to this question of whether or not there might be novel changes. But it’s also a tricky question is what I understood from that research. So it’s not you’re already looking at non-human animals in an unusual environment because it’s a lab. So I think this this question about whether we would expect non-human human cells to have sort of no result in novel changes and what those might look like and novel and unexpected, I guess as well. So that was like a focus of of our study and definitely something that, you know, was a rich kind of vein that we looked at in the work.

Insoo Hyun Yeah, yeah. I do want to say in this webinar something that I actually don’t think I’ve ever like written anywhere, but, but, but I can share with you some of this experience. So in my conversations with community researchers, you know, when I bring up the issue of. Do you monitor the chimeric animals to see if there’s any kind of like behavioral changes? And they say, well, to a very limited degree, because they’ll look at the control group. Now look at that experiment to see if there are any noticeable differences. But there’s a kind of there’s a limit to what kinds of tests they’ll do because of the kind of false eye outside the aims of the study. If it’s kind of meant to be like, okay, so let’s say hypothetically, Bhaskara committee, some subcommittee says, we really want you to assess whether or not there’s like this kind of gain in function in their cognitive capacities. And they say, well, all we were trying to do is create an animal model of this like brain disorder. So yeah, that the first wave will be using healthy cells. There may be a gain of function, but we’re really interested in the disease cells and we’re going to put in the step too, to see if that actually gives you the model of the disease. So for the healthy first wave group, they’ll say we’re not we’re not like animal behaviorists. We’re not people who research that. So if you want that assessment, someone else is going to have to do it. And to really like do that, like gain of function assessment, that’s a really different kind of study like that. We have to go under a different ECOG, you know, rationalized in some other way and a union to use more animals. And that’s not what we’re interested in. So it’s really kind of an interesting challenge of like bioethicists might say, Look, we need to see if there are these like morally significant changes. Cognitively, the research team will say, Oh great, who’s going to do that? Because that’s not part of our study. We we are really sticking to the High Court. Standards have reduced for fine. Keep the numbers small, only use exactly what you need for your research question. This is not our research question. This is your interest rate or the bioethicist interest. And as I kind of like an interesting sort of like, well, how do we ever get this like assessed? And, and so I just wanted to raise that observation that, that that’s a really interesting rebuttal by the research. And they’ll say, look, if that’s what you want us to do, we have to somehow put it into our grant application, justify it to our funders that we’re going to have this third arm, this other assessment for people who are really interested in like the cognition issue, we’re, you know, we’re a disease group and and that’s why you kind of like practically have a hard time actually getting that information, because if that’s true, you’re going to actually burn through more animals.

Josephine Johnston Well, I imagine that like that is like imagine that you were consumed. And then that’s the result was that more nonhuman animals would be involved.

Insoo Hyun Right. It’s kind of.

Josephine Johnston Like that’s one of those things where you just absolutely have to think very carefully about the implications of various different sort of concerns that you might raise and like suggestions. So we and we keep coming back to that, like trying to be, you know, returning to this issue of of the the preciousness, I guess, or the importance of non-human animals and the and the challenges and and responsibilities around the use and research and and not losing sight of it. And our kind of honestly like slightly human centric kind of set of worries about what this might mean for us, you know, and who we are and where we stand in the hierarchy. So we really did try to keep coming back at something.

Insoo Hyun Also, I should point out that people seem to forget this about chimeras is like each chimeric model that you make is like a one off bespoke model. It’s not like you’re making a new strain. Like if I’m really worried about like the generic chimera research concerns, I would be much more worried about genetically modified animals. To have like that. You can start breeding, you can make like a whole new strain of an animal species, monkeys or whatever that that kind of you are creating a new type. The the chimeras are just like one at a time. Transfer cells just because you did it like one time you do the same protocol, you repeat it, you’re not always going to get the same result. And so it’s not like you say, we have an experiment. We’re going to create ten chimeric, you know, neurological models, and then somehow that’s going to like change how these animals are going to be indefinitely in the future. It’s just it’s one at a time. And they don’t always kind of end up the same because the cells are not always integrated. There’s a lot of variation. So they kind of that worry that I think people are trying to get out of like, are you creating a new morally concerning type of animal? And I think a little bit less basic. One at a time. One at a time is bespoke. It’s not breeding, it’s not creating a new strain. If you’re really worried about a new type of animal with ambiguous moral says, I think you should really focus on genetic modification.

Josephine Johnston And I do want to just point readers as well to Carolyn New House’s Science and our special report, which talks about some concerns about sort of we you know, we noted that there are these animal welfare concerns that are in that are much bigger than climate studies, but definitely, you know, needs to be front and center when thinking about this research. And and she also raises and talks about they’re about they’re not animal welfare concerns and primarily the concerns about the rigor and the usefulness of these model of non-human animals as models in making and and they. 26 with this much larger ongoing discussion about some of our regulatory rules requiring non-human animals to be used in clinical studies, for instance. And we saw with Kiva that there was an exception made. And then there’s a new, you know, FDA policy that that will not necessarily always require nonhuman animal experiments before moving into human trials if it’s not scientifically required. So there’s a whole set of issues that are are that scientific rigor that that, you know, could also result in fewer non-human animals being used in science out of a concern for like just doing, you know, using different things in a dish that can be more helpful. So there’s another sort of big debate that intersects with this work as well that we, you know, we wanted to bridge and here and now in our work.

Insoo Hyun Yeah. And I should point out that the technology that enables these alternative animal use come from the stem cell world are organoids.

Josephine Johnston Yeah.

Insoo Hyun Yeah. Or organ and assistance, which the FDA has very recently said they might accept this as an alternative to animal testing. So so you know just just you way you might see that that some of the conundrums that were raised by the stem cell field end up being resolved by other kinds of stem cell technologies.

Josephine Johnston Yeah. Great. Then Is there anything else we should address?

Dani Paci I think we have enough time for just one more question, and this is one that’s more broadly about the field of bioethics throughout the report and in this webinar. It seems like there’s a common thread of understanding this relatively new problem through older questions and through older issues. So I was wondering if you could just talk more broadly about the lessons gleaned from this project and what bioethics can carry forward from it. Specifically, how can the field better learn how to lean on these quote unquote old insights?

Josephine Johnston Hmm. That’s a great question.

Insoo Hyun Let me.

Josephine Johnston I was just going to say that. I think so. One of the things that I think about that that you made me think of with that question, I’m not sure if it’s a the answer is that, you know, in academic work, it’s very easy to be quite narrow and specialized in a project like this. Shows to me that one of the beautiful things about bioethics is that you have to be a little bit of a big picture person who looks across different disciplines, different types of questions and sees the recurring questions and puts them back together. And that is something that comes from going a little bit wide and not just narrow. And so I do think that, you know. One of the great things, and certainly one of the rewarding things for me as an individual of being in this area is that you can you need to go wide sometimes. And that’s a very you know, we live in this even more special. It’s kind of universal. And I think that’s the thing that I think that, you know, is one of the most exciting and also honestly for ending things about working in this area, about where I think this project somewhat typifies that that particular. Sort of a benefit of the field.

Insoo Hyun Yeah. When I take a step back and look at sort of our approach in this special report and in our project, I think if it says anything about where bioethics is going, I think to me it’s like very unabashedly heading into the secular bioethics area. So, you know, traditionally people looked at coming to research kind of almost from like a religious or natural law tradition of like unnatural and mixed species and kind of like we were really focusing on harms and benefits and and a little bit more of a universal language that people could sort of in from different cultures kind of point to and reason out. I think it just underscores when I look at kind of our approach to the climate issue, the problem of chimeras, it’s it’s. Further along the pathway of like Camille, were the reasons that other people can publicly discuss and examine. And I think animal welfare and suffering is kind of a it’s a it’s a pretty common, like publicly available set of reasons to deliberate about. And I think our report, our approach only reinforces that kind of trend of bioethics to kind of go secular. There are, of course, many other approaches to bioethics that are much more rooted into like, you know, communitarian or kind of more like, you know, traditional value systems that are a little bit more coherent, not so pluralistic. We’re definitely not doing that. So I think that that’s apparent. Anybody reading the report?

Dani Paci I think we’re out of time. But thank you so much for joining us today for this webinar and a special thank you to Dr. and Soo Hyun and Josephine Johnston for speaking on this really interesting and important topic. I think eventually, of course, like we mentioned earlier, a recording will be available later today on the Hastings Center website, including Closed Captioning and other accessibility features.

Josephine Johnston Thank you so much. Thanks, everyone, for joining in.

Insoo Hyun Thank you, everybody.