One of the world's biggest killers, malaria takes millions of lives each year and that number is on the rise. But genetic engineers are working on modifying mosquitoes so they can't transmit deadly diseases.

As this ScienCentral News video reports, malaria is their first priority.

Genetic Control

Malaria is so rampant in many parts of the world that experts and health groups like the World Health Organization and the National Institutes of Health are both serious and hopeful about "genetic control" of this disease. The most urgent situation is in Sub-Saharan Africa, where malaria kills as many as a million children each year.

Malaria is spread by Anopheles mosquitoes, which transmit the tiny Plasmodium parasites in their saliva when they bite people. Four of the 150 known species of Plasmodium infect humans, and 60 of the 380 known species of Anopheles mosquitoes carry malaria.

Genetic control advocates want to develop mosquitoes with genes that interfere with the part of the parasite's complex life cycle that takes place inside the mosquito. If such genetically-modified or “transgenic” mosquitoes could compete and mate with wild mosquitoes in malaria-ridden areas, they could make big dents in disease-spreading mosquito populations.

"The weapons that we have to fight the disease right now are very limited," says Marcelo Jacobs-Lorena who leads the genetic control research at Cleveland’s Case Western Reserve University. "We have drugs and insecticides. Drugs that kill the parasite, but as with bacteria that become resistant to antibiotics, the malaria parasite is becoming resistant to the drugs that have been used, and in the same vein, the mosquitoes are becoming resistant to insecticides that are used to control their numbers."

"What is happening is that the number of malaria cases is increasing rather than decreasing," Jacobs-Lorena says. "That's why it's so urgent to find new approaches to fight the disease."

Jacobs-Lorena's group created modified mosquitoes in the lab with a single artificial gene that impairs their ability to transmit malaria. The research, published in the journal Nature, was a "proof of principle"— it demonstrated that the idea could work.

The researchers discovered a small protein they dubbed "SM1" that can attach to cells in the mosquito's stomach or gut and act as a barrier to prevent the parasite from getting in. If the parasite never gets past the gut, it will never reach the mosquito's salivary glands and the mosquito's bite is rendered harmless. The scientists created a synthetic gene that codes for the SM1 protein, and inserted it into mosquito eggs. As they hoped, the resulting transgenic mosquitoes are no longer good at transmitting the parasite.

Psychological barriers

There remain many significant hurdles before field tests could even be considered, says Jacobs-Lorena. "It will be very important to find other gene products that can also interfere with the parasite development in the mosquito," Jacobs-Lorena says. "First of all, because this block is not 100 percent, and second, because parasites can mutate to overcome this barrier, like it does to become resistant to drugs," he explains. "This search will be greatly enhanced… by the availability of the parasite genome and of the mosquito genome."

Next, scientists would have to figure out a safe and reliable way to get the gene to spread into wild mosquito populations. "It's work that is proceeding in different laboratories, including ours," he says. "Several approaches are being tried and it is not clear yet which one will work, so I would foresee that it will take at least five or ten years until we have something that has been perfected to the extent that it can be applied in the field."

"Then there's the psychological factor," Jacobs-Lorena says. "We are talking about the release of genetically modified organisms in nature, and understandably, people are concerned about this possibility." Indeed, he admits, if the research does proceed to the point of planning field tests, public opposition could be the ultimate hurdle. "One of the efforts that we have to put into future research is to show that this approach is completely safe and there is no harm to be done to any environment or to people by using transgenic mosquitoes."

Jacobs-Lorena's research is funded by the National Institutes of Health (NIH) and the World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases (TDR).