Driving genes

10 January 2017

Interview with

Tony Nolan, Imperial College London

Now it’s time to look at another application of genetic engineering - something known as a gene drive, which can force particular genetic modifications through populations. Kat Arney asked Dr Tony Nolan from Imperial College London to explain what it’s all about.

Tony - Well a gene drive is a genetic element that is able to balance its inheritance with each generation. Whereas a normal gene, one copy of a gene in an organism with two chromosomes had over 50 per cent chance of being inherited. A gene drive will increase that to some level above 50 per cent. In the best case, to 100 per cent and therefore, with respect to a normal gene that will double in frequency with every generation.

Kat - So, instead of half the family have it and then a quarter of the grandchildren have it, it’s in everything and everything is likely to inherit this particular variation.

Tony - Not immediately but with each generation, it would increase in frequency, up to a point where most of the organisms in the population will have it.

Kat - This sounds really useful, but what can you actually use it for?

Tony - Well, there are different potential uses of it. One of them is to introduce with the gene drive some sort of cargo that affects the population in a way that’s useful so we work on mosquitoes. One way would be to introduce some target that interferes with the mosquitoes’ ability to transmit disease such as malaria. Another way is to introduce some genetic change that affects the mosquitoes’ fertility. So, as the gene drive element spreads through the population, at the same time, it’s actually damaging the potential of that population to reproduce. And therefore, you reduce the number of mosquitoes. And therefore, you reduce their overall potential to transmit disease.

Kat - So you could basically use it to force a modification through a whole population or effectively eventually make a population extinct?

Tony - In the case of mosquitoes which is what we work on, yes, the idea of localised suppression and in some cases, that could be local eradication of the mosquito.

Kat - This sounds in some ways a good idea. I hate mosquitoes. They bite me. They're awful. They spread disease. Are there risks to eradicating an entire population like that?

Tony - Well, that’s something that we’re obviously keenly aware of. What I would say is with the gene drive, it’s a species-specific tool so it will be contained within that species and any attempt to modify on a population level needs a thorough evaluation of the risks and benefits. You need to consider some of these technologies against more conventional approaches such as insecticide spraying or general attempts to reduce mosquito numbers which are nonspecific.

Kat - So actually, if you're spraying all the insects in an area, that’s doing more harm than just trying to get rid of the mossies?

Tony - Right. Compared to a gene drive that is species-specific, in that case, you get rid of all mosquitoes. You get rid of a wide range of different insects so you’ve got a much broader acting ecological consequence.

Kat - Let’s go into a little bit more detail about, how does the gene drive actually work? What's going on at the sort of nuts and bolts level?

Tony - Gene drives can take several forms but the one that we’re developing and the one that’s making the most impact at the moment relies on a very specific nuclease. So a nuclease is a DNA cutting enzyme that will cut the very precise sequence on one of the chromosomes of your organism and it will cause a double stranded break so you'll have a broken chromosome. The way it’s designed, that broken chromosome uses the copy of the nuclease as a template to repair. So the nuclease gets copied across from one chromosome to another. And so, instead of being just only on one chromosome, it’s now present on both chromosomes. And therefore, is inherited among all offspring.

Kat - And along with that, that would be modification for sterility or for disease resistance.

Tony - Right. Along with that, there will be some effects.

Kat - And finally, I would personally like to see an end to all mosquitoes in the world, but would there be environmental consequences for getting rid of mossies? What about the things that eat them?

Tony - Well, in the specific case of malaria, malaria is transmitted only by a handful of mosquitoes of a genus called Anopheles and that’s a handful of mosquito species amongst several thousand, 3,000 or 4,000 species of mosquitoes. So this would be a very targeted approach and would be removing specifically those mosquitoes capable of transmitting malaria. So there would still be plenty of mosquitoes around where it’s successful. And furthermore, as far as we know, there are no dedicated specialist predators on this species of mosquito. But of course, the technology is in very early stages. It’s got a huge amount of potential but it’s going to be part of the risk assessment. It’s to fully evaluate the ecological risks, and if there are any risks, they will be taken into consideration before applying this technology.

Kat - Tony Nolan from Imperial College London.

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