Édition de gènes, science lente et responsabilisation du public, avec Françoise Baylis

ALEX WOODSON: Welcome to Global Ethics Weekly. I'm Alex Woodson from Carnegie Council in New York City.

For the fourth podcast in our series on gene editing, I'm speaking this week with Dr. Françoise Baylis. Françoise is university research professor at Dalhousie University in Canada.

Françoise is the author of the excellent book Altered Inheritance: CRISPR and the Ethics of Human Genome Editing. For someone who doesn’t have a science background and didn’t know too much about gene editing a few months ago, Altered Inheritance was the perfect book to introduce me to the concepts, debates, events, and people involved with this technology.

Françoise and I covered a lot of ground in our talk—we discussed the concepts of slow science and broad societal consensus, marginalized groups who need to be heard in conversations about gene editing, public empowerment, and some of the governance ideas and structures that are being put in place around this technology. Towards the end of the talk, we spoke about the future of gene editing and and the responsibilities owed to women research participants.

For more on gene editing, I encourage you to listen to my last three podcasts Columbia University's Robert Klitzman on an overview and some of the current issues, Johns Hopkins' Jeffrey Kahn on governance, and Oxford University's Julian Savulescu on ethics.

For now, calling in from Halifax, Nova Scotia, here's my talk with Françoise Baylis.

Thank you so much for speaking with me today. I really enjoyed your book, Altered Inheritance: CRISPR and the Ethics of Human Genome Editing.

FRANCOISE BAYLIS: I'm glad to hear that.

ALEX WOODSON: I thought we would start off with a couple of definitions because I think they'll probably come up in the course of our discussion. These are definitions that people can probably put together themselves when they hear the terms, but I think you can explain them in a much more detailed fashion. The first definition that I would like to go over is "slow science" and what slow science means in the context of gene editing.

FRANCOISE BAYLIS: I think the idea of slow science is to ask people to stop and think and reflect on the direction in which they're moving in terms of the science that they have embraced and are promoting. For me, it is building on same ideas you hear around "slow food" or "slow teaching." The idea here is to say we seem right now to be caught up with speed, as though velocity in and of itself was sufficient motivation for doing things: "You got to get there. You got to get there fast."

What I'm asking for here is to say to people, "Well, what would happen if you slowed down and you actually started thinking about why you're doing the science that you're doing and how you might do it better?" I think in that context what I'm hoping is for people, when they take that step back, to think about the bigger question.

For me, the bigger question is, what kind of world do we want to live in? Once we have an answer to that question, we move on to the next question, which is, can genome editing help us achieve or move in the direction of that kind of world that we're trying to build?

My experience right now is: "Really cool science. What can we do?"—looking around for something to do—and I'm saying that's not the right way to think about this technology or quite frankly any other kind of technology.

ALEX WOODSON: Another term that comes up in your book a lot and that I would like to speak about during this talk is "broad societal consensus." Again, those are terms that we can figure out what they mean, but what does this mean for gene editing, "broad societal consensus?"

FRANCOISE BAYLIS: I think the thing that's interesting is that this term enters the debate/discussion in December of 2015. It's a phrase that gets used for the first time in connection with CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) in the context of the final statement by the organizing committee following the first International Summit on Human Gene Editing. At the end of that meeting, the organizing committee, when it issued its final statement, said two things: "It would not be appropriate to move forward with any kind of heritable genome editing unless there was evidence of safety and efficacy and there was broad societal consensus." At the time, I don't think anybody had a really good understanding of what that meant. What I have been doing since December of 2015 is trying to unpack that notion.

One of the things that I have said really clearly is that we need to think about consensus not in terms of unanimity but in terms of unity. In that context, I'm arguing that we need to think about the human genome as something that belongs to all of us. When I say that, clearly I'm using this idea metaphorically because there is no such thing as the human genome. But what I'm saying is, "Look, it's something that we all have in common or we all share in some sense, and that if we're seriously thinking about taking over the human evolutionary story"—which is what I think this technology ultimately represents—"then we need to say, 'The decision doesn't belong to some elites, be they scientific elites or political elites.'" What we really need to do is to say, "Everybody has to have a say. In that context we need to look for unity."

What that means is we have to actually commit to engaging and empowering other people to take part in the discussions and debates. So "broad societal consensus" means we all get to have a say, and that means things have to slow down—so it ties back into slow science—and we have to decide on what are the priorities going forward.

ALEX WOODSON: You mentioned public empowerment in that answer. That's something I want to speak about in a little bit, but just to make this a little bit more specific and more current, you called for a moratorium on genome editing in March 2019 with several other experts in the field. I know that "moratorium"—I talked about this with Julian Savulescu—is a bit of a controversial term. Why do you think a moratorium is necessary at this moment?

FRANCOISE BAYLIS: First of all, I think it's wrong for anyone to suggest that the word "moratorium" is controversial insofar as its meaning is absolutely clear. A moratorium is a temporary prohibition. It's also not controversial insofar as honestly, except for a handful of scientists, everyone agrees that at this moment in time we should not be doing heritable genome editing, we should not be creating genome-edited babies. Pretty much everybody agrees on that, which to my mind means pretty much everybody agrees on a moratorium. What they don't agree on is they don't want to call it that. I think we really need to think about what does that mean.

To me that's ultimately about an exercise of power. It's about saying: "We can all agree on this, but we can't call it that; we can't call it a 'moratorium' because a moratorium comes with psychological baggage or weight, and some people are going to think that a moratorium means a permanent ban." I don't understand why it is that people who choose to give it a meaning other than its clear meaning in a dictionary are in fact able to control the discourse, but the fact that they are, meaning the fact that they have tried—and in some measure succeeded—in making this seem like a controversial term, speaks to this issue.

If we go back to what I think happened, in March of this year a number of eminent scientists—and others trained in the humanities and social sciences—came together and penned an article calling for a temporary prohibition. It was very clear it was temporary because we even suggested a time limit; we suggested perhaps five years.

What's the purpose of a moratorium? It's to allow for slow science. It's to allow for the scientific community to stop and reflect on the direction of the science, for them to be able to ask good questions about where should they invest their time, talent, and treasure. In that context, the idea is that if you're going to move forward, you then had an opportunity to think carefully about appropriate governance structures and oversight mechanisms. There's nobody who doesn't want that, as I said, except for maybe a handful of maverick scientists who really don't want to be constrained by anybody.

One of the things that I think is really unfortunate from my point of view is, if you take the time to read the article and you actually look at authorship, two out of the three CRISPR pioneers signed on and called for the moratorium. The one who did not is Jennifer Doudna, and I'm really regretting the fact that she was unable to lend her voice and her power to something I know she believes in. She just wants to call it a "pause" instead of a "moratorium."

As I said, what I think is really fascinating and is worth interrogating, is how power is being exerted by a small minority to make the word "moratorium" controversial when it's not. It's a temporary prohibition, and ultimately pretty much everybody agrees that that's what we should have.

ALEX WOODSON: I think this leads into something else that I've heard you speak and write about, that there need to be more, different voices involved in the discussion around gene editing. What are those voices exactly? Who is not being heard right now in these discussions?

FRANCOISE BAYLIS: I think there are a number of different voices that have to be heard that are not often deferred to or in the rooms where these kinds of conversations take place. I'll give you one example, which is one that I've been championing for some time, which is to say that I think it's really important that we listen to indigenous groups and peoples from around the globe.

When I say that, I mean aboriginal peoples, I mean the Maori, I mean Native Americans, I mean indigenous groups in Canada. What I'm saying is there are a number of groups, communities, around the world that actually have a different worldview, a different understanding of our relationship with nature and with each other. They have different priorities, different understandings of community, and I think we need to hear from those groups and to hear very clearly what they think about this project, for example, of taking over human evolution.

That's one very discrete group that I think we don't typically hear from because we typically will say, "Oh, we need to hear from all these religious perspectives." Well, that's not unimportant, but it's a group of people that we're used to going to, to say, "Well, we'd like to understand the Christian perspective, we'd like to understand the Jewish perspective, we'd like to understand the Muslim perspective," all of which are important. But why is it, for example, that on many of these kinds of issues around technology and innovation we don't actually go to people who have a different kind of communitarian worldview and a different kind of understanding of the relationship between different kinds of animals on this planet, human and nonhuman animals, and both the relationship between humans and the Earth, etc.? I think that's critically important.

I genuinely believe we can learn. I will draw on previous experience. Many years ago I was doing some research on embryonic stem cells and in that context had the privilege of discussing some of my ideas with an aboriginal woman and learned that her community was far less concerned about the ethics of destroying human embryos in the context of research and much more concerned about what happens to the umbilical cord. That would not have occurred to me but for this conversation. All I'm saying is that I don't know in terms of their experiential knowledge and other sources of knowledge what they would contribute to this debate, but I sure want to learn from them.

ALEX WOODSON: One thing that we're interested in—I've talked a little bit about this with Jeffrey Kahn. You're on—I just want to make sure I have the name correctly—the World Health Organization (WHO) Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing.

FRANCOISE BAYLIS: Correct.

ALEX WOODSON: I talked about that with Jeffrey Kahn. He's on the International Commission on the Clinical Use of Human Germline Genome Editing, and I believe you are working on similar projects, somewhat together, somewhat not.

Maybe you can't talk about it too specifically, but just broadly what is the work that you're doing on the WHO committee? I imagine that you're bringing up these points that we have been talking about within that group.

FRANCOISE BAYLIS: First of all, I think it's really important to understand that the two committees actually have different mandates. I do believe a number of organizations and a number of authors and articles have conflated the two. In fact, at one point there was an editorial in Nature suggesting that we should get our act together and come up with one set of recommendations. I think that's a real failure to understand the difference between the two committees.

One of the things that is really important is that the WHO Committee is charged, mandated by the director-general to look at both somatic and germline editing. That's not the case for the International Commission. The International Commission, which is made up of members of the different academies around the world, is really supposed to be focusing on the science and looking at some questions that have to do with safety and efficacy. The WHO Committee is very clearly tasked to look at governance and ethics, and so its oversight mechanisms.

My understanding of how the International Commission is working is that they're working on a shorter timeframe. They're expected to report in the spring of 2020, and in that context we will know what their thoughts are when they issue their report in 2020. The WHO Committee will not be issuing a report until much later, so we will be able to take into consideration their findings, but different from them we're actually issuing recommendations or edicts along the way.

For example, the WHO Committee has already recommended to the director-general—and the director-general has acted on this—that we need to have a registry. The reason we need to have a registry is because good ethics has to be grounded in good facts, and we don't have access to sufficient information about what is or is not happening around the world. We have already put that in place, and we're in the process right now of building the architecture for that kind of registry.

Also, earlier this year, in June–July, a Russian scientist, Denis Rebrikov, announced that he too was going to do heritable genome editing. He was going to follow in He Jiankui's footsteps and was going to try to create children that would be genetically modified to have resistance to HIV. He said he was going to do it better than He Jiankui because he was going to do better science, and he was also going to start with HIV-positive women. He then changed his mind and for a variety of reasons decided he was going to modify the GJB2 gene to deal with a particular type of hereditary deafness.

Again, the WHO committee, when we learned of these plans, gave a recommendation to the director-general. The director-general acted on that recommendation and issued a press statement calling upon other jurisdictions to look carefully at their oversight and to ensure that they did not give permission for this kind of research to go forward. Interestingly, the Russian Federation responded and said that they endorsed the WHO perspective and that they would not be giving a green light to this kind of research. Again, I think you're seeing there an important difference between how the two committees are working.

Another thing I would just draw attention to is that the WHO really has a different kind of global perspective I think because we have representatives from low, middle, and high-income countries, and in that context we're actually looking to do our work in a way that will respond to the different needs and capacities of those different kinds of economies.

Why is that important? Because quite frankly, if you only focus on high-income countries, these are countries that have infrastructure in place and capacities to deal with frontier science. We just don't know that to be true, for very good reasons, in low and middle-income countries. If you were a country that is struggling to deal with providing food, for example, to your population, writing up rules to govern heritable genome editing is just not a priority for you, and it shouldn't be.

The reason that's important is because we live in a context of global travel, global science, global medical and scientific travel/tourism, and so we're very attentive at WHO to what might or might not happen in terms of scientists choosing to set up shop in countries where they don't have, as I said, the resources or the capacity to put up a regulatory framework that might be in place in other parts of the world.

ALEX WOODSON: I want to get to public empowerment now. You write about this in the book. You wrote earlier this year that we need to move from public education to public engagement to public empowerment. What do you really mean by that when it comes to gene editing?

FRANCOISE BAYLIS: One of the things I worry about is a focus on public education as the be-all and end-all, a focus on public education that starts with a knowledge-deficit model, which basically has as a starting assumption, "Oh, if you don't agree with me, it's because you don't understand, and therefore you need to be educated." I think that's really an unfortunate way in which some have approached the particular challenges around heritable genome editing.

When I think about education, I think it's important to see this as a two-way street and an understanding that everybody could stand to be educated about different things. Maybe some people need to learn more about science, but maybe other people need to learn more about ethics.

Right now we have a frame of reference that says, "Oh, we really need to do some capacity building around science, and we need to improve 'science literacy.'" I and other colleagues are saying, "Well, there's also something called 'ethics literacy,' and there are a lot of people who could do with some upgrading in that domain." Education for me has to be a two-way street, and we have to understand that there are all kinds of knowledge, and we ought to be thinking that all of us can learn from each other.

When I think about engagement I'm thinking about, How can we take that conversation to a different level? Part of what I'm thinking about there is we have relied on surveys to somehow tell us what's important to the general public, and I think that's a very poor tool for beginning to understand what it is that people do or don't know, do or don't believe, or do or don't want, etc. So, I'm looking for engagement in the context of trying to use different kinds of mechanisms to actually help people make clear the connection that they have between their values and possible future worlds. I think there is really interesting work that can be done there.

The last idea with empowerment is that it's actually about the distribution of power, and it's about recognizing that the decisions that need to be made cannot happen solely in the lab; they cannot happen solely in the boardroom. They have to happen in other places.

So I talk about the role of the ethics consultant as architect: How do you create those other spaces that are welcoming, where people who have different kinds of knowledge and values to contribute get to have a say? I think it's empowerment that people are most leery about, and it's especially those who have power who are less likely to want to share power.

ALEX WOODSON: In the book you mention New Zealand. I was talking I believe to Jeffrey Kahn about the United Kingdom. I'm not sure if it was public empowerment that he was referring to specifically, but just in terms of—maybe we'll start with the first two, educating the public and engaging the public: Do you see countries that are doing this well? Is there an example for other countries, like a big country like the United States, to follow?

FRANCOISE BAYLIS: I think different jurisdictions are trying different things with more or less success. I have used the example of New Zealand in terms of directing people to their website because I think they've actually done a really good job of making information accessible and not just about human genome editing but genome editing in other arenas, whether it be agriculture, livestock, aquaculture, etc. I think there are some things that can be done there.

But I also think there is something very interesting that has been happening with worldwide views, and this has been mostly efforts around climate change to say, "What would it be like to try to have a global conversation about an issue that's of interest to the planet?" I actually think genome editing probably fits at that level. For example, I think it would be interesting to think, What would it be like to try to see how we can use technology to have a global conversation about something that's important for everyone?

ALEX WOODSON: I'm glad you mentioned climate change, because I think that's a very interesting connection.

What are the overlaps? I know you just mentioned one, but what are some other overlaps between the genome editing conversations and the climate change conversations that are going on right now?

FRANCOISE BAYLIS: I think one of the things that I'm trying to impress upon people is the importance of not looking at this technology in isolation. The reason that's important is because it will never be used in isolation, and it cannot take place in isolation. What I mean by that is that if you think about genome-editing technology, it will likely at some point be used in combination with gene drive, in combination with artificial intelligence, in combination with robotics, etc. It will be a very complicated kind of world that we're moving into.

But at the same time, I think of this technology and its capacity to make changes to our genes the same way I think about gene-environment interaction. Basically, if we think about ourselves as a gene in the environment, we need to pay attention to what's happening to our environment in terms of how it might influence our decision making about what kinds of modifications we do or don't make to our genes if we think that's a project worth embracing.

For example, we have lots of problems with climate change. Are there ways in which it would make sense to modify the human body in order to try to indirectly address a problem with the climate? One fanciful example that I give in the book is that we might tweak our genetics such that we really would not be carnivores, and therefore we would reduce our meat consumption, and that would be good for the climate.

At the same time, though, I also ask: "Really? Really? Should we be doing those kinds of things and making biological changes when really the problem is a social change?" We could in fact just use our brains and change our eating patterns if that was what we thought was important as a contribution to trying to address problems with climate.

I think one of the things that becomes interesting is that if you pay attention to the technology in a broader social-environmental context, you then see the importance of slow science, because to do that kind of reflection where, for example, you would seriously say, "Look, we have a problem; we can solve it through biology, or we can solve it through politics." Politics might actually take longer but might be more sustainable, or it might take longer, but it might be more respectful of the autonomy of people, or what have you. You can't have those conversations if you have people racing ahead because they're so thrilled about having this new tool that they can use to do—what? Anything that they can imagine.

ALEX WOODSON: For my last question, I just want to look ahead to the future, the near future, to the far future. I was talking to Julian Savulescu about this, and he says: "I think that what will happen is someone will gene edit successfully, and it will have benefits. There will be a market for it, people will make a lot of money, and we will engineer new preferences for people in certain sorts of gene edits, and there will be more money made for it, and we won't necessarily progress in a direction that either promotes people's freedom or promotes their well-being."

He's worried that the science is going to move ahead and we're not going to ask the right ethical questions about it before it gets there. Is this a view that you share as well? More broadly, where do you see this going in the future?

FRANCOISE BAYLIS: I certainly think that it's a very real risk that people will just race ahead without doing the kind of reflection that I think is required in order to make good decisions. I will come back to one of the things I said at the beginning: I think the critical question to consider is, what kind of world do we want to live in; and second, how can this technology help us achieve that world? But then what has to happen is a really important conversation about that world.

I'm committed to the view that what we should be striving for, what counts as progress, is movement toward equality. One of the things I worry about with this technology is the very real potential to increase the gap between the haves and the have-nots. Because, in fact, I imagine it's those who are already privileged members of society who will now be able to take that privilege and use it to entrench that in their DNA.

One of the things I think it's important to think about is, there is a part of me that wonders if all of this at the end of the day isn't science fiction. The reason I say that is because we really need to see this technology in all of its complexity and to recognize it's actually very onerous technology.

What do I mean by that? You cannot make the kinds of changes that people are talking about—whether you're thinking about them in the context of some kind of a therapeutic intervention or whether you're thinking about them in the context of some kind of an enhancement—without the use of expensive, onerous, and potentially harmful technology.

First of all, you have to have a couple agree to in vitro fertilization. That, in and of itself, is costly and risky. Second, they then have to agree to the genome editing of their embryo. That too is going to be costly and potentially risky. We haven't talked about that, but already people are concerned about off-target effects, mosaicism, etc.

Once you have a number of genome-edited embryos, you then would have to do something along the lines of preimplantation genetic diagnosis to try to make sure that the embryos you have are healthy, but if you have a mosaic, you may in fact never know that, so you might think that you have a healthy embryo and transfer that. Then you have to think about how many times you have to do that over how many generations, and how many embryos are you going to have to modify before you get a live birth?

But when you start thinking about this in those terms, it's not really clear to me that we're actually going to see this world that many of us, myself included, hypothesize where you've got these completely modified beings roaming the planet in small or large numbers. So, I think we need to really think about how that technology could meaningfully be used to make the world a better place.

When I think about that question, it seems pretty obvious to me that our efforts ought to be focused on somatic cell interventions. The somatic cell interventions are the ones where really you're working with patients. You've got a live patient with a potential challenge in terms of their health or a live patient who is healthy and who wants to make changes. It's in that context where you would perhaps genetically modify them without having an impact on subsequent generations, without having to manipulate embryos in the lab, and without those kinds of potential repercussions.

ALEX WOODSON: That's great. That's a different perspective than I think I've heard. I've done several podcasts on AI too, and it reminds me of what some researchers say that we're actually pretty far off from AI making consciousness and things like that. As you said, it might just all be science fiction, and I guess we'll have to wait and see.

FRANCOISE BAYLIS: I think we really should think about how much of this might just be science fiction. We also, in a more concrete sense, ought to really be reflecting on the opportunity costs, though again that brings me back to slow science.

It takes time to really figure out what our priorities are, and that means we have to start with a clear understanding that if we invest time, talent, and treasure in this science, it means that it's not there to be invested in some other kind of science. I think that's an important thing to think about. That means we have to make priorities not so much in terms of what potential solutions are but rather in terms of what are the problems that we want to address and what are the burning priorities.

Yes, it's possible that we would go down this path of trying to create a new species. Quite frankly, if we really thought our species was at risk of extinction—which we should believe if we believe in Darwin—then we need to ask a question about, is this the kind of thing that we ought to try to challenge, and if so, to what end?

In that context, again when I do have some fanciful ideas about what the future might look like, I have two sets of hypothetical scenarios. One of them says: "Look, we're busy destroying our environment, this planet. We can't breathe the air, and it's getting worse. We're having problems with water pollution. We're having problems with—"

ALEX WOODSON: Natural disasters. Lots of stuff.

FRANCOISE BAYLIS: I'm drawing a blank right now, but the bottom line is we're having a number of environmental challenges, and we could choose to say, "Oh, well, we'll just modify the humans such that they can breathe the polluted air, they could drink the polluted water," etc. Again, I would say: "Really? We're going to go and make those kinds of sophisticated biological changes when all we need to do is change our behavior?"

The flip side is that if we continue down this path—and there's a very real risk that we will because capitalist interests seem to prevail right now, and no one wants to take responsibility for the planet as a whole—you could then say: "Well, no, we're not going to modify ourselves to be able to live on this polluted planet. Let's modify ourselves to get off this planet and to live somewhere else."

Those are two kinds of long-term science fiction scenarios, but if you really believed in one or the other and you really thought it was appropriate to use this technology—which, as I've said, I would call into question—you still need slow science to figure out which kinds of modifications do you want to make, because if you're trying to make the human to live on the polluted planet or you're trying to make the human that can live off the planet, those are radically different kinds of modifications.

So you can't even know what to set as a priority if you haven't pulled back to do that sort of groundbreaking work to figure out where are you trying to get to and what kind of world do you want to live in? My hope is that if you actually started that conversation, you would very soon see that ought not to be a priority and you ought to pull back from that perspective on the frontier science.

I think part of what I'm trying to say there is, I get it. It's really cool science. But beyond that we have a number of very real, clear challenges now on this planet with this population, and we need to figure out what the priorities are and direct our attention to those priorities.

ALEX WOODSON: Yes. I agree with that. Thank you so much. This has been really interesting.

FRANCOISE BAYLIS: Great. Thank you for the interview. I've enjoyed it.

ALEX WOODSON: Of course. Anything else that you wanted to get to? I think we're pretty good here.

FRANCOISE BAYLIS: Nothing comes to mind, except there is one question you haven't asked, and I do think it would position me differently than the other people you've spoken to, and that has to do with the typical approach to questions about the harms and benefits of this technology.

One of the things that I try to stress is that a lot of these conversations fail to pay attention to the women research participants. People are very quick to name the fact that, "Oh, there could be potential harms to the offspring" as a result of some of the safety issues I referred to earlier, whether that be off-target effects, on-target effects with unintended consequences, etc.

But one of the things I try to say to people is: "Look, these embryos"—and if you go back and you are working with gametes—"these gametes, they're not just sitting in the lab there somewhere. You have to get them out of women's bodies." It's onerous to get eggs out of women's bodies and to make the embryos, and we need to actually pay attention to the contributions of women.

So, there's the woman as a potential egg provider, there's the woman as the potential gestational carrier, there's the woman as the potential prospective mother to these children. I worry about the fact that we don't ever focus clearly on: Who are these women? What are they being asked to do? Are they at risk of exploitation or coercion? How is it that we understand our responsibilities to them?

I think if we were to start with some of those conversations, it might again have us think differently about the technology and who we think is going to benefit from this technology.

ALEX WOODSON: That's a very important point. I'm glad we have that.

Thank you so much.