Genetics Unzipped is the podcast from the Genetics Society - one of the oldest learned societies dedicated to supporting and promoting the research, teaching and application of genetics. Find out more and apply to join at genetics.org.uk

Driven to extinction

Driven to extinction

Mosquito 43.jpg

Tiny mosquitoes are a big problem. Altogether, diseases caused by bacteria, viruses and parasites transmitted by mosquitoes affect nearly 700 million people every year and kill more than a million, many of them in the poorest parts of the world.

Although malaria is probably the most famous one, there’s a cavalcade of mosquito-borne nasties including dengue, West Nile virus, chikungunya, yellow fever, various types of encephalitis and Zika, to name just a few. 

But while it’s tempting to blame all mosquitoes for carrying diseases - and I certainly blame them for making me come back from my holidays covered in itchy bites - most of the 3,500 known species don’t even bite humans at all. 

In fact, only around 200 species like to feed on us, but only around 100 of these carry human diseases. And even then it’s only the female insects that need our blood in order to lay their eggs. 

Many mosquito-borne diseases can’t be prevented or treated effectively and, in the case of malaria, the infectious parasites are rapidly evolving resistance to every drug in our arsenal. The insects themselves are also evolving resistance to insecticides, and other control options like bed nets can’t provide complete protection against mosquitoes all the time.

So, why can’t we just get rid of them altogether? 

The answer may be yes, thanks to something known as Super-Mendelian inheritance, or as it’s more commonly called - a gene drive.

Gene drive might sound more like the presenter of a cheesy TV motoring show, but it’s a clever genetic engineering tool that means one of the two copies of a particular gene will be passed on to the next generation rather than the other.

Mosquitoes have two copies of every gene, and indeed two copies of every chromosome - one that they got from mummy mosquito and the other from dad. According to the laws of Mendelian inheritance, there should be a fifty:fifty chance of either of those copies ending up in a single egg or sperm, which only contains one copy of each gene, and being passed on to the next generation.

But there are some strange ‘selfish genes’ that influence their own inheritance. Imagine two chromosomes - one containing a selfish gene drive and one without. You’d expect there to be a fifty-fifty chance of a sperm or egg ending up with the chromosome containing the drive. But that’s not what happens. 

This selfish gene encodes molecular scissors that snip a gap in the unaffected chromosome, triggering the cell to repair the damage by pasting in a new copy of the gene drive. So now both chromosomes carry it, and there’s a 100% chance that every egg or sperm cell will inherit it, as will all the offspring. 

So, once those mosquitoes start breeding, all of their offspring will pass on the gene drive, and all of their offspring will too. And sooner or later, virtually all the population will carry it. Clever, huh?

Scientists have known about naturally-occurring selfish genetic elements for a long time, but the discovery of CRISPR - a gene editing system that allows researchers to alter any gene in any way - has opened up a world of possibilities. 

Now scientists can put any gene in to mosquitoes hooked up to a drive, and it will quickly spread through the population. And if that gene does something useful, like prevents the insects from being infected with the malaria parasite, then that’s got to be a good thing.

Even more clever is an approach from researchers at Imperial College in London, who used a gene drive to turn female mosquitoes infertile if they end up with two copies of it. Males can still spread the drive, whether they have one or two copies, and females with one copy will pass it on to all their offspring. So once the drive starts to spread through the population, every single insect carrying it will either pass it on or be sterile. 

In one test in mosquitoes in the lab, it took just seven generations for the drive to spread from one in eight insects to the whole lot, leading to a total collapse of the population. There was no generation eight - that little lab population had gone extinct.

Insects aren’t the only branch of the animal kingdom where gene drives could be applied. A paper published in the journal Nature in January this year showed that the inheritance of one version of a gene affecting coat colour [in mice] could be skewed using a CRISPR gene drive. It’s not 100%, but it’s definitely more than half.

That’s nice if you want to guarantee a nice crop of mice with rather charming mottled grey coats rather than dark brown ones, but there are more useful applications too. For example, unwanted invasive rodents such as rats and mice on islands can quickly cause devastation and wipe out local species. 

Trying to get rid of them with conventional pest control techniques is virtually impossible, but releasing a gene drive that crashes the population might be an effective alternative.

Other uses for gene drives might be to simply spread a beneficial or protective gene through a population that you actually want to keep around, such as a gene blocking the transmission of a deadly disease. Or using genetic engineering to protect endangered species like corals from environmental stresses.

There are significant scientific, ecological and ethical concerns around the use of gene drives. And there are also fears about what might happen if this technology was used in a harmful way - for example, by deliberately trying to cause crop failures or inherited diseases. And we don’t know whether the drives can jump species and cause unintended damage.

Coming back to where we started, could this technology be used to render real life mosquito populations immune to malaria, or even get rid of them all together? Well, probably yes. But is it a good idea? 

With the right application of genetic technology, we wouldn’t need to eradicate all mosquitoes - only the ones that cause us so much harm.

But while it’s broadly thought that getting rid of the really nasty ones such as Anopheles gambiae, which transmits malaria across most of sub-Saharan Africa, would probably be just fine, ecologists are currently finding out whether completely obliterating these bugs might affect the local ecosystems, just in case.

References and further reading

The darkest side of genetics

The darkest side of genetics

The dark heart of the genome

The dark heart of the genome