Wiping out Malaria with a GM Mosquito

Adding a sea cucumber gene to a mosquito may be the key to eliminating malaria

by Ruth Tennen, Stanford University

January 17, 2008

Malaria infects almost half a billion people each year and kills more than a million. Every 30 seconds a child in sub-Saharan Africa dies of malaria.

According to a new report published in PLoS Pathogens, the answer to wiping out malaria may lie in adding a gene to a mosquito. To understand how this would work, we need to understand how malaria works. And how it's spread.

The key to wiping out malaria?

We start with a person with malaria. This person has malaria because he or she is infected with a parasite called Plasmodium. But Plasmodium can't jump directly from person to person. It needs to hitch a ride inside a certain type of mosquito called Anopheles.

When a female Anopheles mosquito bites an infected person, the mosquito sucks up blood containing thousands of Plasmodia. These parasites are immature and need to develop inside the mosquito's stomach. Once they're mature, the Plasmodia travel to the mosquito's salivary glands.

When the mosquito bites another person, she releases saliva. And thousands of Plasmodia come along for the ride. These parasites swim to the person's liver, where they live for a week or two and make copies of themselves.

The newly copied parasites then invade the person's red blood cells. They gobble up hemoglobin, the special molecule that carries oxygen to our cells. The Plasmodia make more copies of themselves. And then they burst open the red blood cells.

Thousands of new parasites spill out and infect new cells. This causes a fever and other symptoms of malaria. When another mosquito drops in for a meal on this person, the mosquito will suck up more Plasmodia from the blood. And this mosquito can transmit these parasites to another person with her next bite.

There are medicines that can treat people with malaria (although they aren't as effective as they used to be). But the best answer would be to make a vaccine to wipe out malaria like we wiped out smallpox. So far, scientists haven't been able to
make an effective malaria vaccine. There are a few reasons for this.

First, Plasmodium is much more complicated than most other creatures that cause disease. For example, it has 5000 genes, while the polio virus has only 11.

Second, all Plasmodia are not alike. There are different species and different strains. This means that a vaccine against one strain might not work against the others.

And third, Plasmodia are sneaky. They slink between mosquitoes and humans, and they're experts at hiding inside human cells to escape from the immune system.

This is why scientists are looking at new ways to stop malaria. Instead of going after the parasite, some researchers are going after the mosquito.

More Information

Movie of Plasmodium life cycle

Mosquitoes: a double-edged sword?

A sea cucumber gene might
make a malaria-resistant
mosquito.

Mosquitoes help malaria jump from person to person. But they might also hold the key to stopping malaria in its tracks.

For a while, scientists dreamed of making a ‘malaria-resistant' mosquito. They wanted to make a mosquito that would kill the Plasmodia in her gut, or block the Plasmodia from developing into their mature form.

Until recently, scientists couldn't create these sorts of mosquitoes. But now they can. Scientists can add bits of DNA to genetically modify the mosquito. Frankenmosquito to the rescue!

The scientists decided to add a gene called CELIII to the mosquito. This gene is normally found in ocean critters called sea cucumbers, not in mosquitoes.

The gene codes for a molecule called a lectin. Lectins are made of proteins and sugars and can poke holes in the outside of cells. So scientists thought that a lectin might poke holes in the Plasmodia (or the red blood cells) and prevent them from developing. (Click here to see what CELIII looks like up close!)

When scientists tested the CELIII molecule in a Petri dish, it bound to immature Plasmodia. This binding prevented the Plasmodia from developing into the mature parasites that actually cause malaria.

So the scientists put the sea cucumber gene into Anopheles mosquitoes. These new genetically modified (GM) mosquitoes now made CELIII specifically in their stomachs.

Then the mosquitoes were allowed to feast on human blood or on mice infected with Plasmodium. And just as the scientists had hoped, CELIII blocked the parasites from developing in the mosquitoes' stomachs.

Maybe most important, these GM mosquitoes were resistant to two different species of Plasmodium. And one of these species was Plasmodium falciparum, which causes 90% of malaria deaths.

More Information

Another GM malaria-resistant mosquito

Ready for prime-time?

Image of Plasmodium infection of
blood cells.

So now we've got malaria-resistant mosquitoes. But are we ready to use them to combat malaria in the real world? Not quite yet.

First, these mosquitoes are only partially resistant to malaria. They can get rid of some—but not all—of the Plasmodia in their stomachs.

Second, the scientists only studied Plasmodium development. They didn't look to see whether CELIII prevents the GM mosquitoes from spreading malaria between mice. And figuring that out in humans is even tougher!

Third, scientists need to introduce these GM mosquitoes into the wild. And the GM mosquitoes need to replace all the ordinary mosquitoes. If there are lots of regular mosquitoes left—ones that can transmit malaria—then malaria can't be wiped out.

How can we do this? Well, scientists decided to set up a survival-of-the-fittest contest. They put equal numbers of ordinary and GM mosquitoes together, along with some mice infected with Plasmodium. And then they waited.

After 9 generations, 70% of the mosquitoes—up from 50% at the beginning of the experiment—were GM mosquitoes. This means if we release GM mosquitoes into the wild, they might naturally replace ordinary mosquitoes.

In the end, mosquitoes might be the bad guys and the good guys. Ordinary mosquitoes help malaria spread. But GM mosquitoes might hold the key to wiping out the disease.

Ruth Tennen

More Information

Content provided by the Department of Genetics, Stanford University.