Could Genetically Engineered Insects Squash Mosquito-Borne Disease?

IRA FLATOW: This is Science Friday. I’m Ira Flatow. One of the big challenges in beating the Zika virus is outsmarting the mosquitoes themselves, because one of the species that spreads it, Aedes aegypti can reproduce in just a teaspoon of water. So that crumbled chip bag or that crushed up soda can instantly becomes the perfect breeding ground as soon as a little rain comes by. So rather than use traditional eradication methods, one of the other ideas to find mosquito-borne scourges like malaria, dengue fever, and now Zika is to attack the problem from within using genetic engineering. Why not engineer a mosquito that’s resistant to carrying these parasites and viruses or engineer an all out extinction of those disease carrying species of mosquito?

Technically there’s not a lot standing in our way. In fact, one of my next guests has already developed a malaria resistant mosquito, which can pass that resistance to nearly all of its offspring. But is that a good thing? What ethical concerns do we need to address? What biosafety measures or international accords do we need to put in place before releasing engineering insects into the wild? What are the unintended consequences? As the line goes, nature will find a way pr will it? Anthony James is a vector biologist and distinguished professor at the University of California Irvine. He joins us from the studios of KUCI today. Welcome to Science Friday.

ANTHONY JAMES: Well, hello, Ira. Pleasure to be here.

IRA FLATOW: Nice to have you. Kevin Esvelt is an evolutionary engineer MIT asking what that means an assistant professor in the Media Lab there in Cambridge. He joins us from MIT. Welcome to the show.

KEVIN ESVELT: Delighted to join you.

IRA FLATOW: Tell me, what is an evolutionary engineer?

KEVIN ESVELT: It’s someone who recognizes that a lot of systems are too complex to be rationally designed. But in many cases, we can use evolution to solve the problem.

IRA FLATOW: And is that what you want to deal with the mosquito here? You have a long history of this technology CRISPR and gene drive. Give us an idea of well what exactly is a gene drive? How does this technology work?

KEVIN ESVELT: So it harnesses a natural phenomenon. Gene drive happens when a genetic element spreads through a population, even though it doesn’t help the organisms to survive and reproduce. And the main way they do this is they bias inheritance in their favor. So instead of being inherited by half of offspring like a normal gene, they are inherited by perhaps up to all of them. And that advantage allows them to spread very, very quickly through a population.

And we can use that potentially to alter the traits of the population or in an even more clever trick, to suppress them, or possibly eliminate them entirely. Now this is a technology that is very different from all previous technologies we will be able to alter entire populations of wild organisms and thus shared ecosystems. So ensuring that these interventions are developed responsibly with wisdom and humility really poses a serious challenge for society.

IRA FLATOW: I want to get into the technology a little bit and then talk about these challenges. Anthony James, you engineered mosquitoes with an immunity to malaria. How does that work?

ANTHONY JAMES: We took advantage of the fact that there are a lot of different malaria parasites, those that infect humans and those that infect mice, for example. Humans don’t get mouse malaria and mice don’t get human malaria. So a while back at our colleagues working on looking for ways to develop vaccines took some human parasites and put them into a mouse. And the mouse immune system fought them off. And we could go in along with the discoveries that our colleagues made and take those genes at the mouse was using to fight off the malaria parasites, engineer them, and actually put them into the mosquitoes. So what we’ve done is we’ve given the mosquitoes small parts of the mouse immune system that allows it to fight off the human parasites. And it works.

IRA FLATOW: So you could theoretically crash the mosquito population, make them go extinct with this.

ANTHONY JAMES: No, this technology actually is making the mosquitoes resistant to malaria parasites. So mosquitoes that would normally transmit human malaria can no longer do that because we give them an additional gene that was derived originally from the mice.

IRA FLATOW: And how far along are we in this and does it make sense to go ahead with this?

ANTHONY JAMES: Well, we actually have in the laboratory demonstrated what we call the proof of principle. These mosquitoes, when challenged with blood that has human parasites in it, fail to have parasites in their salivary glands and therefore are incapable of transmitting those to humans. In addition then, so we would consider that to be what we would call a cargo. And in addition, we’ve coupled that now to the types of gene drive systems is Kevin talked about, so that we have a mechanism for spreading these through the target mosquito population.

So we have the blueprints in hand. We don’t really have to the particular strain yet that’s field ready to go. We learned a lot from our recent experiments about how to make a better product, so to speak. But it won’t take long to make that. But then as Kevin indicated, there are the challenges of having the proper environment to test this so that it goes out in a safe, efficacious, and ethical way.

IRA FLATOW: Because once it goes out into the wild, there’s no way to reverse, is there?

ANTHONY JAMES: That’s not entirely true. We have this concept of a phased approach, where we take steps to check safety and efficacy as we move along. So one would first find a place where it would be possible to control the mosquitoes with conventional technologies, so a small ecosystem or an island for example where if some of these unknown considerations came up, we’d be able to use conventional technologies like insecticides for example to eliminate the mosquitoes. So we would be monitoring as we do this. The idea is not to just throw them out there, but to do a stepwise approach with careful controls at each step.

IRA FLATOW: Kevin, you were talking a bit before about wearing a bit about the unknowns that might happen here. Tell us a bit more about your concerns.

KEVIN ESVELT: Well to be honest, a lot of people might be worried about what happens if you alter the mosquito. Is that very Risky well, Tony’s antibodies are pretty specific to the malaria parasite. So I’m actually not worried that alteration of the mosquito is going to change the way that they interact with any other species. That’s pretty darn safe as far as ecological interventions go.

Now, if you remove the mosquito entirely, then you have to ask what other species does it depend on? But there are also advantages to removing the mosquito then the problem, the vector is gone, so the disease is gone. Whereas from an evolutionary perspective, malaria can evolve resistance to Tony’s antibodies, in which case, we’d have to do that again if Tony can come up with new antibodies, which I imagine he can do, yes Tony?

ANTHONY JAMES: Of course. Go ahead and I’ll follow up on that in just a second.

IRA FLATOW: Kevin, would you advocate then using this for Zika virus?

KEVIN ESVELT: No.

IRA FLATOW: No? Why not?

KEVIN ESVELT: No, I would not. Now, we may want to consider using this on this Aedes mosquitoes that carry Zika virus. Right now is Zika virus too new. People are very concerned about it even though we don’t know very much. There have been 4,000 cases, tragedies, of microcephaly, but 4,000. And yet why are we not asking the question of, should we remove these mosquitoes because they carry dengue, which causes millions of cases per year and kills over 20,000 people and also yellow fever, which killed 30,000 people a year.

So why are we not asking the question about those viruses? Well, because they’ve been around for a while. Zika appears new and so we’re scared of it but it hasn’t indicated it’s a big enough threat to even be on the level of the things that we already know about. And all of these are utterly dwarfed by malaria, which in the time that we’ve been talking has killed almost 10 children.

IRA FLATOW: So how close are we to using this technology, both technologies, to then wipe out malaria? If you can engineer those mosquitoes, why can’t you do that to wipe out malaria?

KEVIN ESVELT: Well, here’s the thing. You have to balance the potential benefits against the risks. Now with malaria, the odds that whatever might go wrong, the odds that it would be worse than malaria is pretty close to inconceivable. That said, that’s just my judgment, and it should not be up to me. Because I’m not going to be affected either way. I don’t live in an ecosystem that has malarial mosquitoes. And my risk of getting malaria is zero. It needs to be up to the people who are at risk. They need to make the decision.

IRA FLATOW: Have they weighed in on this yet?

KEVIN ESVELT: Well that’s the problem, right? You’re talking about a lot of people. You’re talking about more than a billion people. What does it mean for informed consent when you’re talking about a billion people? How do you get all of those countries together? Well, the way I would do it is I would say, let’s bring together a bunch of health ministers and set up channels insofar as possible to invite people to say, what are your concerns and what do we need to do in order to meet them? And if everyone can agree on a set of criteria that the technology must meet before it can be released, then it’s up to the scientists to show that we can do that with independent verification, entire thing run by non-profits to avoid any potential bias of the profit motive. And if we can do it, then we can go forward. Otherwise it’s really hard to see how you could do it.

IRA FLATOW: And what kind of mechanism do you have to get together to gather all these people? Are we talking about a technology that is so new that no one’s really thought about the consequences of getting people together to decide how to use it?

KEVIN ESVELT: We’ve never had to before. We’ve never really had a technology that affects everyone all at once. It’s not something that requires people to go out to a store and buy a product, or even go to their local clinic and agree be vaccinated. It’s a, if you build it and release it, it happens. Now getting back to your earlier question, we can propose and we’ve shown that you can build a reversal drive that will overwrite changes or block a suppression drive from crashing the population.

So we do have some measures to intervene in case things go wrong. But at the same time you have to do this risk benefit thing, and you have to have public support. Because it would be incredibly immoral to for anyone to unilaterally alter shared ecosystems.

IRA FLATOW: Anthony James, how do you come down on this?

ANTHONY JAMES: Well I agree. My language is a little bit different. But we put a lot of time into thinking about what would be necessary for the roll out. And so when people ask about how long is it going to take, there’s answers specifically to the science side of things. But is Kevin has indicated, there are some issues that we have to sort out in terms of the community engagement and the regulatory structures.

And it is fair to say, this is a new technology and people are only now becoming aware of it. Though, like I say quite a few of us have been thinking about for a long period of time. The WHO actually have some guidelines that came out in 2014 for testing these types of technologies. But the good part is there’s a lot of interest in this now.

And there are some examples of where genetically engineered organisms have been taken into a country, not released, but actually tested in field environments in large cages, without the excitement that we’re seeing in some of the other places, because of good community engagement was done and the regulatory structures were obeyed. So just it’s just a question now of increasing the awareness and getting coherency in a global manner to this kind of technology. And I’m optimistic that it will happen. It’s is unfortunate happening under a circumstance of crisis and anxiety among the general public.

IRA FLATOW: Well, that’s the story of how things work unfortunately.

ANTHONY JAMES: It sure is. I mean, it’s actually embarrassing. I mean, I started talking about this quite a long time ago. And I remember being in Washington, DC and in the mid ’90s talking to some government agencies saying, look, we’re anticipating this coming. I didn’t know it was going to be 20 years away, but we were anticipating this coming. We should be talking about this. And they told me, well, nothing happens without a crisis. And that was fairly unsatisfying to me because decision-making during crisis times isn’t always the best. But here we are. It’s unfortunate.

IRA FLATOW: Could mention Ebola in the same sentence. Let me just to remind everybody that I’m Ira Flatow and this is Science Friday from PRI, Public Radio International. If you just joined us, we’re talking with Anthony James and Kevin Esvelt about, well, about diseases and fighting them with genetically engineered mosquitoes. Kevin, did you want to jump in and say something there?

KEVIN ESVELT: Yeah, I think it’s also really important that we bring up the need to avoid over-promising. Because just because something works in the laboratory doesn’t guarantee you that’s going to work in the wild. And even though the technology is moving incredibly quickly because it’s based on CRISPR, which you may have heard of in other contexts. It’s a method that allows us to very easily edit genomes. And we’re moving very quickly. I mean Tony, you realized that in mosquitoes in– how long did it actually take you from start to finish?

IRA FLATOW: For the CRISPR technology or the whole story?

KEVIN ESVELT: For the CRISPER gene drive, I mean, yes, making malaria resistant mosquitoes has been your career and you’ve been the pioneer in that. The drive.

ANTHONY JAMES: Yeah. So we’ve been thinking about the CRISPR technology for probably a little over two years and going through the usual academic route, writing grants and submitting grants and getting funded. And we actually had a proposal funded earlier, I guess earlier last year. And we were getting ready to start our work on mosquitoes when this report came out, Drosophila melanogaster, the fruit fly or vinegar fly, that this technology had worked. And so all the sort of fundamental groundwork and legwork that had to be done was already done for us. And it was surprisingly quick, that within a matter of a little less than eight months, we were able to adapt the Drosophila system to the mosquito.

Now, having said that it’s because we have the infrastructure in place in our laboratory to actually do this with mosquitoes. We have people who were doing the microinjection work, the screening work. We had a complete infrastructure that when a potentially viable technology came along, we were able to exploit it quickly. So the 20 years or so that went into being ready culminated in a very quick application. That is correct.

IRA FLATOW: Let me see if I can get one quick call in. Let’s go to Sarasota, Florida. Hi, Fred. Welcome. Fred, are you there? Well, we lost Fred. He dropped out. But I people are wondering about the consequences, the unintended consequences, things that you can’t think about, like if you wipe out all the mosquitoes, what happens to the bats or the dragonflies that eat them, other kinds of things that have to be thought about. And I guess this goes into the bigger picture that takes a worldwide discussion.

ANTHONY JAMES: Ira, can I weigh in on this a little bit?

IRA FLATOW: Yes, please.

ANTHONY JAMES: So the ’80s mosquitoes it transmits Zika virus, dengue fever, and chikungunya are not native to the Western hemisphere. These are insects that have been introduced continuously over the past 200 or 300 years as a index and the consequence of migration of people and goods from Africa into the Americas. And there were efforts to eradicate Aedes aegypti because it transmitted yellow fever in the 1950s and ’60s and significant progress was made. But we got into this situation at my lab that we call the public health paradox. And that is, when public health is working really, well nothing’s happening. And in this case, they got rid of the mosquitoes, declared victory, and went away, and the mosquitoes came back.

And so I could actually see that in the Western hemisphere one could make an argument for total elimination of Aedes aegypti and then the recently invasive Aedes albopictus without having any major consequences on the environment. These are insects that are highly adapted to living around human environments. I hear the argument that these human environments are legitimate ecosystems.

IRA FLATOW: I’ve got 20 seconds. You have another point? Another shoe to drop there?

ANTHONY JAMES: Another shoe to drop is at least for the Aedes mosquitoes, I don’t see any reason why we shouldn’t be targeting an elimination in the Western hemisphere.

IRA FLATOW: All right.

KEVIN ESVELT: But the drive will spread beyond that, back to Asia. And we can protect them, but then they’re all engineered. Are we OK with that? That’s really what it comes down to.

IRA FLATOW: All right. Will talk lots more about it. Kevin Esvelt is an evolutionary engineer at MIT. Anthony James is a vector biologist at the University of California in Irvine. Thank you both for taking time to talk with us today.

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