Modified mosquitoes that only make males

17 June 2014

Interview with

Nikolai Windbichler, Imperial College London

For years people have been trying to wipe out malaria by using insecticides to A mosquitocontrol mosquito populations, but they can develop resistance to the chemicals, and the disease still kills hundreds of thousands of people around the world every year.

Now scientists at Imperial College London have genetically engineered mosquitoes so that they only produce male offspring; and that's important because it's the females that bite and spread disease.

Kat Arney went to see Nikolai Windbichler, who led the research, to find out how changing the ratio of male to female.

Nikolai - Well the idea is, if you progressively shift the sex ratio of a population towards males and there are fewer and fewer females in the population then the overall size of the population will decrease up to a point where the population cannot sustain itself anymore and will actually crash.

Kat - What did you to try and skew this sex ratio?

Nikolai - We introduced into the mosquito a gene which essentially destroys the X chromosome. As you know, as in humans, so also in mosquitoes, there are two types of sperm produced by males, sperm that carried a Y chromosome and sperm that carried the X chromosome. The sperms that carry the Y chromosome produce sons. The sperms that carry the X chromosome produce daughters. So, we found a way to specifically eliminate the sperm that carried the X chromosome so that only the sperm that carried a Y chromosome would be functional and this male would produce only sons.

Kat - This sounds really clever. How did you do that to target and destroy the X chromosomes?

Nikolai - What we found is essentially an Achilles heel, a genetic Achilles heel of the malaria mosquito. There's a certain DNA sequence that is present in many, many copies on the X chromosome only and nowhere else in the mosquito genome. So, we use a DNA cutting enzyme that cuts the chromosome. You can imagine like with a scissor, and in many, many places, it cuts the X chromosome. So, this chromosome becomes destroyed. It's no longer functional.

Kat - So, you've these kind of lines of mosquitoes that have these DNA scissors in. What happens?

Nikolai - And then what happens is, as you can imagine an enzyme that cuts DNA, targeting the X chromosome is lethal for most cells. But we are making sure that this chain is active only when sperm are produced. So then what happens is the sperm that would have carried the X chromosome in those sperm, the X chromosome is destroyed. But the sperm that carried the Y chromosome, they do not have to sequence that we're targeting. So they're totally unaffected. So, they are produced normally and transmitted to the female and you have male offspring.

Kat - The next generation is mostly all male offspring. They're going to be looking for some ladies. What happens then?

Nikolai - Well, one thing that we probably should add is that this gene is also transmitted to the offspring, but only to half of the offspring. So, half of those males looking for ladies, they will do the same thing again in this generation. They will produce only sons. Over time, progressively over many generations, there are fewer and fewer females in the population. And eventually, there are no females in a population and the population crashes.

Kat - So, this could be a really fantastic way of basically getting rid of mosquitoes. They're the bane of my life. They always bite me. I hate them. What would be the consequences of completely getting rid of a population of mosquitoes, say, in a town or even a country?

Nikolai - There are many. There are 3,500 different species of mosquitoes. We are only targeting one specific species which transmits malaria to humans. So that's in a sense a much more targeted intervention than for example insecticides is the current control method which targets all sorts of insect species.

Kat - Obviously, this could be fantastic if you could get rid of the mosquito populations and that would eradicate malaria, but how close is this to being something you can roll out and are there risks of releasing these modified mosquitoes into the wild?

Nikolai - This is a very promising technology, but we're still many steps away to rolling this out. We have both technical hurdles to overcome still, but as I have to make sure that all aspects of biosafety, ethical concerns and regulatory concerns would be addressed before we go any further with this. The next step is to take these mosquitoes and test them at a large scale. We have tested this technology in small population cages, but we have a facility in Italy where we have larger, cages to the more field-like controlled environment and there, we want to test the technology to see how it performs.

Kat - What's it like working with so many mosquitoes around you?  Does it make you a bit twitchy?

Nikolai - Yeah, some people get quite twitchy.

Kat - How much do you get bitten?

Nikolai - We get bitten once in a while but it's really alright. It would be the same if you go in a camping trip probably.

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