Professor Anthony James, University of California, Irvine
Malaria infects more than 300 million people each year, leading to hundreds of thousands of deaths, three quarters of them children. A mosquito, genetically engineered to prevent the spread of the disease, has been unveiled by scientists in the US this week. The new mosquito carries genes that enable it to block the growth of the malaria parasite, so that it cannot pass on the disease. This new approach, which is referred to as a gene drive, means that when the mosquitoes mate, they automatically always pass on the anti-malarial genes. Anthony James, at the University of California Irvine spoke to Chris Smith about how this works…
Anthony - What we’re doing here is putting genes into mosquitoes that make it so the parasite will not survive in the mosquito. And if we do that then the parasite can’t complete those aspects of its life cycle that it needs the mosquito for, and can’t be transmitted to humans.
Chris - How do you encourage the gene to find its way into the wild population? Does it give them an advantage so that they’re more likely to pick up the gene because, otherwise, wouldn’t it just fizzle out?
Anthony - This is the beauty of the gene drive system is that it favours its own inheritance. So the way to think about it is, if you have an insect that has your gene it and it mates with a wild mosquito, all the progeny of that wild mosquito will have our gene drive in it, so it doesn’t really need a major fitness advantage to propagate itself.
Chris - And biochemically, what does this modified mosquito do differently that means that malaria just can’t grow in it?
Anthony - It has a number of genes in it that have components that interact with the malaria parasite and prevent the malaria parasite from completing its development in the mosquito. The technology was based on the observations that there are many different malaria parasites, so there are malarias that infect mice, there are malarias that infect humans. So humans don’t get mouse malaria and mice don’t get human malaria. So many years ago a number of our colleagues took the human parasites, put them into mice and then identified components of the mouse immune system that would essentially fight off the human parasites. We took those components and built little miniature genes out of them and then put them into the mosquitos, so basically what we have is a mosquito that has a small part of the mouse immune system that allows it fight off the human parasite.
Chris - Malaria has, notably, become resistant to a large number of drugs and there are only a few left that really work reliably now. So, is there not a danger that quite quickly the parasite would become resistant to this intervention in your mosquito and it would find a way around this blockade and carry on business as usual?
Anthony - Yes. So this is a good question and so we see this actually in many drug treatments, not just to parasites, but bacteria and fungal infections for example. And so the strategy is to, when treating these infectious agents is to not give one, but two different drugs, and the idea is that while the parasite may successfully work its way around one of those, trying to do both at the same time is very difficult, and the probability of that happening is very low. And that’s exactly what we’ve done in our mosquitos, we’ve actually put in two genes, that target different stages of the parasite, and so the parasites may figure out how to get around one of them but, in that same parasite, to figure out how to get around one and the chances of it, at the same time, figuring how to get around the second one make it so that it’s extremely unlikely that we’ll see resistance.
Chris - What about safety. Could this in any way endow the mosquito with any other abilities to cause disease, or spread these sorts of genes into other things that shouldn’t have them?
Anthony - That’s a good question as well, and so we look at the large number of blood-born pathogens that are out there and we look at the fact that there are mosquitoes feeding on people that have these blood-born pathogens, and we see a high degree of whole specificity; meaning things like HIV, things like hepatitis do not actually grow on mosquitos. - if they could, they already would. The changes that we’re making are very targeted and very directed and don’t influence at all portions of the cellular machinery that would make the mosquitos good hosts for that.
Chris - Is the going to work? What evidence have you got that this is a real prospect?
Anthony - The evidence is the fact that we have genes that will make the mosquitoes resistant to malaria parasites, and we have a technology now that allows us, at least in the cages, to spread them through large numbers of mosquitos. And so, just in a laboratory, we can design it so that it has the properties that we hope it will manifest, but we’ve got to test it at every level. So, I can’t guarantee exactly what we made in the laboratory today would be something that would be used in the field, in fact, I doubt very much that it would, but we have the blueprint for making something that could work that way.
Chris - And the possible timescale?
Anthony - For the science, it will go fairly quickly. The confounding factor is a positive one in a sense. We need a regulatory environment , a community engagement environment, and a social environment that will accept the use of these technologies, and it’s very difficult to tell how quickly these things will mature to the point where there will be acceptance for using this. So, while we may make a lot of progress in the science and the laboratory, whether this ever goes to the field will be dependent on the social side of it, and the regulatory side of it, and at this point it’s very difficult to tell you how quickly that will move along.