Messing with genes to wipe out malaria


Malaria, a parasitic disease transmitted by mosquito bites, has resisted insecticides, mosquito netting and other eradication efforts. Recently, a team of scientists from Imperial College London and the University of Washington in Seattle reported on a genetic approach.

Mosquitoes were inserted with a fungus gene that can attack specific mosquito genes — making it possible, for example, to destroy genes that allow the malaria parasite to reach humans’ bloodstreams.

Andrea Crisanti, the paper’s senior author and a molecular biologist at Imperial College London, talked about the work, which was recently published in the journal Nature.


Why are you tackling malaria?

Malaria is one of the most important infectious diseases. It infects an estimated 200 million people per year, with about 1 million people dying as a consequence, on the same order as HIV/AIDS and tuberculosis.

If you have enough money, with sustained effort, you can eradicate malaria. In the United States and in Europe, malaria was eradicated. Unfortunately, developing countries don’t have the resources to sustain the use of insecticides over long periods of time and different locations. It requires complex logistics, a lot of money, effort and motivation, and a strong political will.

Ideally, it requires a measure that is affordable, easy to implement and sustainable. And such a measure does not exist at the moment.

So we thought if we developed genetically modified mosquitoes that are unable to transmit malaria — and are able themselves to transmit this genetic modification to local mosquitoes, through mating — that would be an effective solution.

How does it work?


So it’s a sort of cut-and-paste-function: You have a gene able to attack the other gene, destroy it and copy itself in its location.

The technology is based on a gene that makes an enzyme that selectively recognizes DNA sequences and cuts them. Now if you induce a cut in the DNA, a break in the DNA, you trigger the cell’s repair mechanism. The repair mechanism then uses the enzyme’s gene as a template to repair the broken DNA sequence. And so, key genes in the mosquito that are involved in malaria transmission can be disrupted. As the mosquitoes breed, it spreads through the population.

In the lab, we saw the mutation spread to more than half the population of mosquitoes we had living in cages. This happened in a time span of 12 to 16 generations of mosquitoes (each generation being between 18 to 30 days in the wild). So it’s quite efficient.

What would you target for destruction in the mosquito, and why?

These enzymes can be reprogrammed to attack different DNA sequences, so there is flexibility there. The question is, which sequences do you want to attack?

You could, for example, destroy genes that are important for the parasite. There are some genes that are important for the mosquito to recognize and bite humans rather than animals. Or you could destroy genes that regulate sex development for female mosquitoes, so every generation will produce only males. This will, in the span of a few generations, have tremendous impact on the size of the mosquito population.


Which countries do you want to use this in first?

I don’t want to mention any specific countries. I’m thinking sub-Saharan African countries where malaria is highly endemic and they have problems using insecticides or don’t have the infrastructure to use them.

India has made fantastic progress in controlling malaria; so has China. They’re doing very well now.

How long will it take to significantly reduce malaria?

Without new technology, I would guess we’re talking several decades. If our technology works, it can really work in spans of one to two years — once you start to release the modified mosquitoes into the field, they’ll do the job in a relatively short time. That’s why it’s so exciting.

Are people working on other genetic approaches toward controlling malaria?


There’s been work done by a group that released genetically modified mosquitoes in the Cayman Islands, but they released sterile male mosquitoes. They’re monogamous — so once the male mosquitoes mate, they don’t mate again.

The idea is that you make a genetically sterile male, or you introduce genes which kill the females, so in principle, the genes don’t spread.

But the technology requires multiple releases, breeding the mosquitoes is not easy, and the technology would be very difficult to implement in Africa. Also, it’s been used on a different mosquito that’s responsible for the transmission of dengue fever.

This interview was edited for space and clarity from a longer discussion.