Gene editing mosquitos to curb malaria

Words By Holly Tarn

Mosquitos. The mere mention of the word gets the best of us irritated. And for good reason – aside from the incessant itching, mosquitos are a killer. In fact, they kill more humans than any other animal. The statistics are haunting: several million people die from mosquito-borne diseases each year, with around 3000 children dying of malaria alone every single day. Remember that number – we will come back to it later. 

Efforts to limit the spread of mosquito-borne diseases have been extensive, but only partially successful. You’ve got the obvious insecticides – namely DDT, which during the 40s and 50s eradicated the most disease-ridden of the mosquitos (Anopheles and Aedes species) from North America, and much of Central and South America too. But widespread resistance to DDT happened quickly, and pervasive concern grew about the environmental damage these mass pesticides were causing. So the international community began to look to mosquito nets, which since 2000 have halved deaths from malaria in sub-Saharan Africa. And then there’s the clinics. Malaria is largely treatable if you can get to a clinic on time, if that clinic has the medication required. But nets and clinics and medicines are all significant financial burdens. Many countries can’t afford them, and NGO’s aren’t always willing or able to fork up either. Even if the funds were there, medicines and nets are really hard to distribute – much of rural Africa is extremely hard to access. These drawbacks mean that malaria deaths remain shockingly high, with no end in sight. Until perhaps that is, the idea of gene editing came along. 

The idea is this: mosquitos have their DNA artificially edited to either be less efficient at carrying disease, or to be less efficient at reproducing. Although this sounds like a sci-fi novel, it’s real science, and it’s not as far away as you think. The technology used for gene editing is called CRISPR-Cas9 and it’s absolutely fascinating. To the non-sciency folks reading this, please stick with me; I’m going to explain it as simply as I can. 

CRISPR was discovered when researching bacteria. Bacteria get viral illnesses just like humans. Also like humans, bacteria have an immune system that they use to fight off viruses. But bacteria have something we don’t – when they are infected with a virus their immune system has an ability to take a ‘cutting’ of the DNA sequence of the virus and store it in their own DNA so they can recognise, and mount an attack on the virus next time they get infected. (When researchers found these they saw lots of repeating patterns of DNA that looked totally random and they decided to give them the catchy name of ‘clustered randomly interspersed short palindromic repeats’, but to save my word count, let’s call them CRISPR). Scientists also discovered between these CRISPR’s that there was something called Cas proteins (the most common of which is Cas-9). These proteins are like the cars in which the CRISPR’s travel in to reach the virus. The Cas proteins also have little tools with them, like tiny biological scissors, which we call helicases, which unzip sections of DNA. Once the CRISPR-Cas9 has reached the virus, it uses its tiny scissors to dismantle parts of the virus, killing it – a victory for the bacteria’s immune system. 

In 2012, Jennifer Doudner and Emmanuel Charpentier made the ground-breaking discovery that you could take whatever piece of DNA you liked, and insert it into this CRISPR Cas-9 technology. The new DNA could travel to a section of DNA in a host cell and effectively change what the cell can now code for. The implications of this are huge. A whole new world of science came raining down: it was now within reach to gene edit babies to have specific traits, eradicate genetic diseases, even create armies of superhumans. I kid you not. But I digress – we’re here to talk about mosquitos. 

This technology could now be used to curb malaria by creating a malaria resistant mosquito (called population replacement), or by wiping out mosquitos (called population suppression) (see figure 1). But which genes to use? Many have been tested so far in the lab. The most recent and most promising research focuses on population suppression by targeting a gene called ‘doublesex’ which makes the females infertile and unable to bite. 

It’s important to note that these concepts work by using something called a gene drive. A gene drive is the idea that some genes, rather than being passed down randomly (Mendelian inheritance), have the ability to spread faster and farther than other genes. Although this occurs a little in nature, using CRISPR to create a gene drive makes a gene’s survival rate go up to almost 100% (see figure 2). The importance of this is that this technology doesn’t affect just one generation. It affects them all. And once this technology is released, it can’t be taken back. 

And the reaction to this news in the general population? Well, overall terror. Our culture at large is sceptical, at best, when it comes to gene technology. There’s a broad sense that we shouldn’t mess with nature, and fear about the consequences if we do. What if we cause a wider disturbance in the food chain? What if the mosquitos adapt to have ‘off-target’ effects? What if we end up with giant mosquitos with 10 eyes and dagger teeth? All very natural questions when someone tells you their going to start messing with gene drives in the wild. But these questions have, in fact, all been thought of (OK, maybe all except the last one). 

In terms of the food chain question: scientists have looked at which predators rely on the Anopheles mosquito, and although several animals do eat them (the Vampire Spider is particularly fond of them), there is no animal that relies solely on it. In fact, in order to curb malaria, it’s only the one type of mosquito, Anopheles, which needs to be curbed, so other mosquitos will persist, meaning not a huge impact on the wider chain. Note that I said curbed too, the species will not need to be completely eradicated in order to stop spreading malaria, just enough of them to be infertile to cause a population collapse. And as for the off-target effects, the gene that scientists are experimenting with will have been used many millions of times in the laboratory before any gene drive is released into the wild. The testing is scrupulously rigorous. 

The benefits are obvious: because of the low maintenance costs and the ability of the technology to traverse borders, it has the potential to completely eradicate disease from large geographical areas, something that could never be achieved with nets and medicines alone. And whilst similar goals have been achieved with pesticides, it provides an alternative that potentially is better for the local ecology and won’t be met with widespread biological resistance. 

Although this technology seems promising, and the research outlined above may reassure us that we’re not likely to get an entire food chain collapse, or end up with 10-eyed monster mosquitos, many valid ethical questions about wild gene drives still exist. For example – should the African communities in which these experiments will be taking place have more of a say? Will this gene drive open up to more gene drives that might not be so safe? 

So the question becomes: can we overcome these ethical quandaries in order to have the first gene drive in the wild? I’ll take the opportunity here to remind you of that number we came across earlier – 3000 children die every day from malaria alone. Although many of us have become desensitized to hearing statistics of this sort about children in Africa, can we imagine if the same statistic were here in Europe? Perhaps the international community at large would be more ready to begin to solve these ethical quandaries.

Using CRISPR to gene edit mosquitos is a controversial technology that provides much food for debate. But with millions of children’s lives at stake, it’s a debate, in my eyes, that’s well worth continuing. 

Image Credit: Pixabay