No Easy Answers in Bioethics Podcast
Ethical Implications of Gene-Editing Human Embryos: Eijkholt and Fleck – Episode 13
March 26, 2019
What are the ethical implications of gene-editing human embryos? Do we risk stifling scientific advancement by banning such medical research? Guests Dr. Leonard Fleck, Acting Director and Professor in the Center for Ethics, and Dr. Marleen Eijkholt of Leiden University Medical Center in the Netherlands discuss the pros and cons, stemming from the recent news out of China of gene-edited babies. They share thoughts on the ethical implications of using such technology to alter human embryos, both now and in the future.
This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: "While We Walk (2004)" by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License.
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- Cohen J. What now for human genome editing? Science. December 2018;362(6419): 1090-93. DOI: 10.1126/science.362.6419.1090.
- Daley GQ, Lovell-Badge R, Steffann J. After the Storm — A Responsible Path for Genome Editing. New England Journal of Medicine. 2019;380(10):897-899. DOI: 10.1056/NEJMp1900504.
- Kolata G, Wee S, Belluck P. Chinese Scientist Claims to Use Crispr to Make First Genetically Edited Babies. New York Times. November 26, 2018. https://nyti.ms/2DPqmR5.
- Kolata G, Belluck P. Why Are Scientists So Upset About the First Crispr Babies? New York Times. December 5, 2018. https://nyti.ms/2E41TYg.
- Rosenbaum L. The Future of Gene Editing — Toward Scientific and Social Consensus. New England Journal of Medicine. 2019;380(10):971-975. DOI: 10.1056/NEJMms1817082.
- Yong E. The CRISPR Baby Scandal Gets Worse by the Day. The Atlantic. December 3, 2018.
Liz McDaniel: Hello and welcome to another episode of No Easy Answers in Bioethics, the podcast from the Center for Ethics and Humanities in the Life Sciences at the Michigan State University College of Human Medicine. This episode features guests Dr. Leonard Fleck, Acting Director of the Center for Ethics, and Dr. Marleen Eijkholt of Leiden University Medical Center in the Netherlands. Together they discuss the recent news out of China of gene-edited babies, offering pros and cons of the gene-editing technology used, and thoughts on the ethical implications of using such technology to alter human embryos, both now and in the future.
Leonard Fleck: Hello everyone, this is Leonard Fleck speaking, and I am a professor of philosophy, medical ethics, and health policy here in the Center for Ethics in the College of Human Medicine. And joining me today is Marleen Eijkholt, who I will ask to introduce herself.
Marleen Eijkholt: Hello! Len, thank you for introducing me. I'm Marleen Eijkholt, I used to work at MSU, but now I moved back to the Netherlands. I work at Leiden University Medical Center where I'm primarily a health lawyer, but I cannot deny my ethics background either. So. thank you for inviting me to join you.
LF: Now what we're going to be talking about afternoon is the topic of gene editing. In particular the editing of embryos. And part of the reason why we're addressing this particular issue is because in late November, Dr. He, a Chinese researcher, successfully edited, at the embryonic level, two twin embryos. And what he did was he wanted to provide these embryos with protection against being infected with HIV. And so there is a part of our genetic code called the CCR5 gene, that in fact is an entry point for the HIV virus. But, approximately one percent of our population has a mutation in the CCR5 gene that results in their having a kind of natural immunity to being infected with HIV. So what Dr. He did was that he in fact created a mutation, he hoped it was the mutation that naturally occurs and that would confer the same kind of protection against those future possible children being infected with HIV. Since that time, those twins were born, but at the time when he announced this there was a very negative kind of reaction to his having performed this particular experiment. And, so I guess one of the things we wanna understand is what would be some of the concerns that other researchers have had about what Dr. He did. In particular, a lot of researchers called attention to the two different ways in which gene editing can occur. One of which has to do with somatic editing as opposed to germ line editing. And I'm going to ask Marleen to explain that difference.
ME: Thanks Len. I am, I'm not a biologist or a germ line expert, so probably my explanation will be a little bit of a lay person. But before I do that, you know what's interesting, and I don't know if this is too much conspiracy for the podcast, is you're saying he successfully edited them, and, and I think from reading what I've read, we're still kind of a little bit unsure if this is all hype or if it's real, because none of his reports have been published. None of them have been like peer-reviewed, as far as I understand it. I don't know if you're, you have heard differently about it. But you know in the past we've heard of experiments coming out of different countries that have been more of a hype rather than a, than a fact. So, but I'm happy to assume that the claims that he made are, are real. Did you hear anything about this in more detail whether his claims have been confirmed? Before I go into the distinction between germline editing and somatic cell.
LF: No, Marleen as far as I know his actual claims have not been fully confirmed by any members of the scientific establishment. The basic problem is as you pointed out that he has not published these results in any refereed scientific journal. He presented them at a meeting, but even in his presentation at the meeting a number of researchers who actually looked at some of the data and the pictures that he presented, they were not at all confident that he had successfully achieved what he wanted to achieve. The particular objection they raised was that he may in fact have created a mutation in the CCR5 gene, but the very specific mutation that naturally occurs for that one percent of the population that is immune to HIV, it wasn't clear that in fact he had successfully created that mutation. He created a mutation and that mutation may or may not in fact confer any resistance to HIV for those twins.
ME: Right, right. So then we're at least on the same page. So I think one of the, the points that people have really referred to is that his type of editing was a term of germ line editing. And that means he brought modifications to germ line, meaning that any, well, every cell of any, you know, any resulting baby—I think they're called Lulu and Nana—would then also be passed on to future generations. So basically he would not just be affecting the genome and the genes of the babies that were born, but if these individuals would reproduce they would reproduce individuals with the same, the same type of cell lines. And this is different from if you edit somatic cells, which are basically cells that do not, do not impact future generations. So that are really, yeah, of the entity itself. So, if you would edit, you know, in case of Lulu and Nana, if they, they are babies now, but if you would repair or change anything in their cells then the, these would not give rise to modifications in their progeny. But because there have been germ line modifications, they will pass on these germ line modifications to their offspring. So this is one big distinction, and so it will also affect, his changes will affect future generations. I, yeah. I think that's, that's a big one because, so it doesn't just affect Lulu and Nana but they will also affect you know people down the line. And that, well, yeah, that's a biggie.
LF: So, one of the, one of the things we want to focus on are what are some of the ethics issues that are raised by this kind of intervention at the embryonic level, and what you've already pointed out is that the changes that are made in these embryos are changes that can affect future generations. And if it’s the, and so we can imagine a couple things, we can imagine that this researcher got it exactly right and so he was doing something that would be in effect therapeutic, preventive, and worth, and from a medical point of view quite worthwhile for these, for these children in the future. On the other hand, one of the things that we don't know because one of the challenges seems to be that this was a premature kind of medical experiment that was done, that in fact we do not have, researchers do not have the confidence that they ought to have that they would be absolutely certain not to pose any risk, that something would not have gone wrong. Because if something goes wrong, then this could affect not just the wellbeing of those two children, but that it could affect the wellbeing of any progeny that those two children might have.
ME: Yeah I think you're, you are really pointing to like one of the cons, the hesitations around this intervention that refer to the risks and benefits. So there, a lot of people say there's so many risks, so many unknowns, what's gonna happen to Lulu and Nana or to, or to the future so we shouldn't do this. And, and if we're like, some of the risks that have been identified here specifically are like referred to as "off-target," so, you know, He targeted the CCR5 gene and it might have, you know, brought about changes in any other cells, but also they refer to mosaicism, they refer to well maybe it's not like very efficient, on target. What I, the other day I gave a little talk for, for scientists and, and what I was really interested in is to hear them not worry so much about these risks. So, but they were mostly referring to, you know, food, and plants, and all that stuff. So I'm, I'm really curious is this a feeling that you have too that these risks are maybe somewhat exacerbated when it comes to humans? Or are we as a bioethicists too worried about them?
LF: Well, I don't know that we're too worried about them. It's really, I mean to my mind it's really a matter of whether or not the researchers who are involved in doing this kind of gene editing—which by the way is what's referred to as CRISPR Cas9 gene editing, that's the specific kind of gene editing that was done here—the question really is whether or not that technology has been perfected to the point where we can be very, very close to 100 percent confident that we're not going to, in one way or another, adversely affect the wellbeing of either those two children, or any descendants of those children. And that's something that at least as far as I can tell there is not sufficient scientific research to, that would really justify the claim that this technology is something that is ready to be brought into the clinic. That if, if parents, for example, are concerned, if they know that they are at risk of having a child with some serious genetic disorder such as cystic fibrosis or Duchenne’s muscular dystrophy, they could safely choose to have this as an intervention at the embryonic level for their future possible children. It just doesn't seem like there is sufficient scientific evidence to justify that claim, which makes a lot of people believe that there's really a significant risk here and that we have no right to go forward with this, in terms of actually producing any children.
ME: Hmm. It's a very interesting thing being back in Europe. So, I believe that in, like, overall the regulation, regulatory situation in the Netherlands, and in Europe, there is this principle, it's called the precautionary principle. And, and it kind of suggest as long as we're not really sure, we might hesitate to, you know, to do such excessive things. On the other hand I feel a lot of people are also worried that if we don't allow this, we are hindering science, and we're maybe even, so in the Netherlands, for example, where this is not allowed, people are worried about a brain drain. And people are worried that, you know, science gets stifled. So how do you feel about this stifling of science?
LF: Well, at one level, I don't want to stifle science. At another level, of course, I want to, I have to be committed to protecting the welfare of human beings who might be affected by the, this research going forward. Ordinarily you know, as adult individuals you and I can make informed choices if we wish to be part of a medical experiment of one kind or another. And in the case of children, we typically trust the parents of children to make informed choices for medical interventions on behalf of their children. Though when it comes to medical experimentation with children we are extremely cautious about seeking sufficiently informed consent. And we have to trust the physicians and medical researchers themselves that they're, they're being open and honest in terms of explaining what the risks are of some of these interventions when it's the case that children are put at risk. In this case of course, we're not just talking about the children of the parents who consented in one way or another to have this work done by Dr. He, but, and to go back to this question there are all the future descendants of those children who would also be affected and for whom nobody it seems is qualified to speak. And so that suggests that we have to be extraordinarily careful in terms of what we're doing with this particular technology.
ME: Mmm. At the risk of, you know, being very confusing, it's funny because maybe before we started this podcast we were talking, or we communicated a little bit about how we would approach this, and then we said, all right, Marleen, maybe you can address the cons a little bit, and then Len you would do a little bit of the pros. And I must say myself I'm a little, I feel a little bit hesitant about, about this technology because of the risks and because of all the other things. But, maybe for the sake of the listeners, shall we just do a little overview of all the arguments that are in there, or at least a few, and then we can go into a little bit more detail on some of them, so that you know there is a little bit more of an overview? Would, how would you feel about that?
LF: Okay, that sounds good. I mean, on the pro side, the obvious good that you hope to be achieved is eliminating, either eliminating some kind of defective gene in an embryo, a gene that would otherwise result in a serious genetic disorder for that future possible child at some point in its life. And it seems like that's a very great kind of good to accomplish. It seems like this is something that would be preferable to another technology we have, which is pre-implantation genetic diagnosis. The limitation of pre-implantation genetic diagnosis from several points of view is that you have to produce a large number of embryos, and they have to be genetically analyzed, and you, basically you can only identify embryos that are in one way or another free of one particular genetic defect that you're trying to avoid. As opposed to if there are several defects, you can't really use pre-implantation genetic diagnosis for that purpose. And, and then from the point of view of advocates for a strong right-to-life view, with pre-implantation genetic diagnosis there are all these excess embryos that are produced that are ultimately going to be discarded or destroyed in some way, and that's something that they would oppose very vigorously. In this, in the case of gene editing an embryo, you're, you're not producing any excess embryos because you're going to "fix" the embryo that you have. So there's, that sounds like, feels like this is a sort of therapeutic thing that medicine typically does. That, that I think it would, is a major argument in favor of this technology.
ME: Hmm. Yeah, that sounds, that sounds pretty nice. So it's about, you know, effective use of the embryo.
ME: And if I consider some of the cons against this, I, you know, a question about is this intrinsically, could it be intrinsically wrong? Then, of course, on the one hand you've got this efficient embryo use and efficient creation of the embryo, but on the other hand, you know, especially in the research phases, the question is how many, how many do get destroyed and is this an instrument, you know, is this instrumentalization or commodification of human nature and, and embryos. And is there, are we, are we kind of playing God by, by doing this. This is an often heard argument, and I'm not saying that I'm endorsing it, but I can kind of see how we're stretching like what we consider acceptable with human life. On the other hand, I think, well not on the other hand, some more cons that I find, that I do find pretty pressing is at this stage, if these claims are true and if something bad happens, if this would lead to a setback in science. And that's actually very interesting because we've seen that in gene therapies at the time of the Jesse Gelsinger trial, you know, when gene therapy went wrong. I think the literature says that we were put back about ten years from where we are. So there's a lot of concerns about setting back science. I think one of the, one of the arguments that I also find quite interesting when you were saying so this is a therapeutic intervention is, you know, are the lines between therapeutic and enhancement, you know, very clear? This is the designer baby argument. Like what, are we, is this really social engineering, and is this, or is this, is this a therapy for infertility, or are we using it to eliminate, for example, traits that we don't necessarily think are necessary to eliminate. And, and you know there's the disability studies argument that talks about, yeah, what does a society without illness look like, would that be a better society? I think to some extent it is, but at the other hand I also appreciate that there's variety of people and variety of human life conditions. And, and, you know, are we, yeah, are we instrumentalizing this research. I think what's also an interesting argument is if this is the right time, because there are alternatives to achieving at least what He achieved. So He was trying to eliminate HIV.
ME: And interesting they we're having this podcast today because I think, was it today or yesterday that news came out that HI, someone cured, got cured of HIV by a, by a—
LF: It was a bone marrow transplant.
ME: Correct, yes, thank you. So, are there alternatives that, instead of, you know, destroying embryos in this research, can we find these types of solutions elsewhere? Of course there is, yeah, there is many more arguments that are, there are wondering is this is a good use of the technology, that talks about justice and access issues, but, yeah. What are some of, do you have any more pros? Or should we go into some of these arguments a little bit more detail.
LF: Well I'd, I'd consider some of your arguments a little more detail. I myself am not too terribly concerned about the designer baby objection because I think that's just a gross exaggeration. I cannot see anywhere in the very, very far foreseeable future that we would literally be able to design a baby in the way that we design a computer. That, that suggests a kind of understanding, a total complete absolute understanding of the human genome and how DNA works, and how DNA is connected to every else going on inside our bodies, that we are very, very, very far from achieving. So, I don't get too terribly concerned about that particular argument. However, the other argument you brought up I think is, is quite reasonable and relevant, namely the argument having to do with the stifling of this science if in fact we end up with a bad result, and we get a bad result because really fully understand what it was that we were doing. So, for example, in what I have read about Dr. He's research, one of the things that some other scientists have pointed out is that the particular CCR5 mutation that results in conferring almost absolute resistance to HIV also exposes an individual is more vulnerable to the West Nile virus and to some of the more serious versions of the flu. So a lot of times, we tend to think of a particular gene as having one particular function, or a mutation of a gene having one particular result, but genes are connected in very, very complex ways throughout the entire genome. And so oftentimes these genes have multiple functions, multiple consequences, and these are things that are only, we're only beginning to understand right now. And, so this is a reason for being much, much more cautious about allowing this technology to actually result in the birth of any future children, and certainly at this point and for some number of years I would guess into the foreseeable future.
ME: The, you know, Len what you, hmm. I think it's, yeah, very, very good what you're suggesting. You know there is this one thing that keeps popping into my mind and it's this thing that the UNESCO statement suggests, and it suggests, at least a part of it suggests this is why the human genome is one of the premises of freedom itself, and not simply raw material to manipulate at leisure. Do you feel that the human genome is one of the premises of freedom?
LF: I don't, I'm, I guess I'm not entirely sure what that means. Is it intended to suggest that given the genome as we have it now, it has in fact yielded human beings who are capable of doing very creative things and expressing themselves and with a degree of freedom related to our rationality that might be at risk if we start tampering with the genome? Is that kind of what those folks have in mind?
ME: You know, I am not completely sure what they have in mind. But I, yeah, I don't know there is something that feels, that feels, which of course is not an ethical argument, that there is something to be undetermined, and to be, yeah, I don't know. So, yeah… people, I don't think that, you know, it limits flourishing, this editing process. But I'm wondering if there is, if flourishing also comes from, from a certain type of freedom, I don't know. Maybe this is not a good, [laughs] a good thing to bring up here, maybe I don't [audio warps].
LF: That might, that might be a little too wooly, a little too confusing to try to get into right here. I guess one of the other practical political questions that's gonna get raised, as things are, for example, right now here in the United States, the research itself that would allow gene editing technology to go forward, well, is not going to be funded by the federal government. And using and engaging in experiments with embryos is something that is in many respects legally forbidden. So that's a problem, to my mind that's a problem, in a, in a liberal pluralistic society. I am confident that Dr. He should not have done what he did, that he should not have actually made these changes in the DNA of those two embryos and implanted them and allowed these children to be born. Because we just don't know exactly what we're doing. But, the technology itself can have I think many good uses in the future, and, and so the research should go forward, and it will require, it will involve the destruction of many embryos. I understand from the point of view of advocates for a strong right-to-life point of view that this is something that is seriously objectionable, but the thing is in a pluralistic society those objections can be taken note of but they're not objections that I think should be seen as being overwhelming and controlling and determinative of what research scientists are allowed to do. And so as long as the research work is done responsibly, and, so that at some point researchers can be confident that they know what they're doing, and can in fact implant an altered embryo into a woman's uterus and know that that child will be okay, until we reach that point then there should not be any more experiments in which any of these embryos are implanted for birth purposes.
ME: Hmm. There's two things that I, that your comment raises. One is, you're talking, and I'm going to take a little bit of a contrarian view here. One of the points that you're raising is, you know, there will be a lot destruction of embryos, but once we get into the process of course, we might also have to consider, you know, if research trials would involve animals and large animals, and if this justifies destruction of large animals. And then, so are animals, should they be part of the discussion here, and even, you know, in terms of, you know, getting the research to benefit humans. Who should be sacrificed? And then on your point of a democratic society, what I'm always struggling with, and I haven't found the answer but maybe I need to read more, is are there any limits, well, are there any limits that one can set in a, in a democratic society that says, you know, science should not go forward. And then one of the traditional viewpoints is, you know, harm to self or harm to others. And are we harming the others now, the future generations and when can we stop, when can we say like it's too risky.
LF: It's when we-
ME: But maybe that's a discussion for different, you know, a different time.
LF: That is a discussion that's going to have to be for a different time because I think we've exhausted the time limit that's allowed for these podcasts.
ME: Oh man.
LF: So Marleen I want to thank you for joining me on this particular podcast. Say hello everybody else in the Netherlands that we might both know. And I want to wish you well. Thank you.
ME: Thank you Len, thank you for having me, and say hi to everyone at MSU and in the U.S. that we both might know right, alright? [Laughs]
LM: Thank you for joining us today on No Easy Answers in Bioethics. Please visit us online at bioethics.msu.edu for full episode transcripts and other resources related to this episode. A special thank you to H-Net: Humanities and Social Sciences Online for hosting this series. This episode of No Easy Answers in Bioethics was produced and edited by Liz McDaniel in the Center for Ethics. Music is by Antony Raijekov via Free Music Archive.