No more malaria

Malaria is one of the world's most deadly diseases. As of 2008, nearly 250 million people worldwide were infected with the disease, and 1 million people died from it - most of them in Africa, according to reports by the World Health Organization. The disease is caused by a parasite, plasmodium, which is transmitted via the bites of infected mosquitoes. When left untreated, the parasites reproduce in the human liver and eventually can infect red blood cells and cause death.

However, in a new paper published earlier this month in the journal Nature, a team of American and European scientists worked together to show how genetically modified mosquitoes might be used as a way to eliminate malaria. Andrea Crisanti, a professor of molecular parasitology at London University's Imperial College and the paper's lead author, spoke to Deutsche Welle about the new research.

Deutsche Welle: Explain the idea of genetically modifying mosquitoes so they are less capable of carrying malaria.

Andrea Crisanti: We describe a method to spread a genetic modification from a few laboratory-bred mosquitoes to enormous wild populations. Without this technology, it would be impossible to implement measures for malaria vector control based on genetically modified mosquitoes. Currently, the bottleneck here is spreading the genetic modification as it would rely on dispersal of a huge number of mosquitoes in order to replace the existing ones. This would require a lot of logistics, a lot of money and a lot of effort. Those factors make it unsuitable for developing countries.

So we ask the genetic modification to do the work that otherwise humans would have to do. This is why this technology is anticipated to be affordable, easy-to-use and, most importantly, sustainable. The real problem of malaria control in endemic countries is sustainability. Usually these countries have very few resources, they don't have the logistics, they have a poor health system and the major problem they face is sustaining a long-term effort to control the vector.

So far your work has only taken place in the laboratory. How would you implement your technique in the wild?

We have tested the ability of the genetic modification to spread in large laboratory populations. The results we obtained are very close to what the mathematical model predicts for spreading a genetic modification using the system that we have developed. Now, to spread this technology to field populations of mosquitoes, we need to carry out additional experiments. This means to model a field situation. We are now developing a facility which will allow us to have a big, indoor, confined space, which will mimic - in terms of light, illumination, humidity, temperature - an entire season for a malaria-endemic country. At the same time we can introduce a large number of mosquitoes into this confined space. This will let us better study the dynamic of spreading of this genetic modification.

What happens genetically speaking once you've introduced this modification?

The underlying genetics are quite complex, but it's important to understand a couple of concepts. First of all, we are introducing a gene that codes for an enzyme. The enzyme is a particular protein that has a specific function. In this particular case, its function is to cut the DNA at specific locations in the genome. Usually this enzyme is designed in such a way that it can cut only once in the genome. They're very selective.

When the mosquito has this gene in their genome and the stem cells are formed the gene is activated, then the enzyme is produced and the enzyme introduces a break in a specific point in the mosquito's chromosome. At this point, in the presence of the break, the DNA repair machinery is activated. It tries to repair the break, using the intact chromosome as a template. Like all of us, mosquitoes have two pairs of chromosomes: one inherited from the mother and one inherited from the father.

But in the intact chromosome, at the site of the break, there is a gene that we have used to attack the DNA. So what happens is that during the repair process it copies itself, and it generates a continuous process of cut-and-paste, and generation after generation the modification is transmitted to the offspring. It doesn't spread like a virus, this is an important concept, but it increases its frequency of the gene in the offspring of the following generation.

How does the piece of genetic code you've introduced into the mosquito genome make it less likely to transmit malaria?

This was done only as a proof of principle to show that such a genetic modification could be spread to a large population of mosquitoes. We will engineer this enzyme to selectively attack mosquito sequence that we know will interfere with the mosquito's ability to transmit malaria.

For example, the mosquito uses particular receptors to identify the target to bite, in particular the human. It has a unique preference to bite humans rather than animals. If you destroy this receptor, you could re-direct the behavior of the mosquito towards animals, and in this case, it will not be able to transmit malaria.

So the mosquito will still carry malaria, but it won't bite humans?

It theoretically would be able to carry malaria, but it will feed on animals' blood rather than humans'. In this case, malaria would not be transmitted because animals do not transmit malaria. You can modify the behavior in such a way so that mosquitoes don't bite humans anymore. Whether they carry malaria or not, is relevant. Animals don't carry malaria, so they are not able to transmit it.

You could also re-design these genes you introduce to attack genes that are designated to female sexual differentiation, so that the mosquito only produces male offspring. In this way you could unbalance the ratio between males and females. There are two reasons this would be very favorable: Because males do not transmit malaria, and because, in the long run, the excess of males will make the populations of mosquitoes crash so that there won't be any more mosquitoes left to transmit malaria.

For you and me, mosquitoes are a pest, but surely there must be other animals in the ecosystem that rely on them. Is there any danger in really altering the genome of the mosquito at such a fundamental level?

This is quite a challenging question. Our experiments right now are at the proof of principle level. So at this stage this question is a little premature, but is very dear to us. We want to understand if there is any harm to human and animal health. That's why we have made a huge effort to build this indoor facility. We are building the capacity and mobilizing the resources to understand this question clearly.

This mosquito will never be released without us first having the comfort that this technology is not dangerous, and, of course, we will produce all the documentation and material for the regulatory authority to judge. It all depends on us whether this mosquito is released or not. But ultimately it will depend on the political will of the country that eventually may use this. In this respect, I should also say, that we are committed to using countries that have a clear body able to judge ethical and genetically sensitive issues.

Interview: Cyrus Farivar

Editor: Sean Sinico