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NewsvineMan-made mosquitoes that are resistant to malaria have an evolutionary advantage over wild-type mosquitoes. Using this, researchers have engineered mosquitoes in the laboratory that may soon be used to prevent the spread of malaria in the countries that need it most.
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Plasmodium, the parasite responsible for malaria, needs two hosts to complete its life-cycle: a female Anopholes mosquito and a vertebrate. Parasites enter a mosquito’s body when the insect drinks infected blood, before moving to the mosquito’s gut and forming a cyst. When this cyst bursts, spores are sent to the insect’s salivary glands. When the mosquito bites its next vertebrate, it will leave the parasite behind-thereby spreading malaria in a population.
So what gives malaria-resistant Anopholes their advantage?
“There’s a fitness cost to being infected,” parasitologist Hillary Hurd explained to MIT’s Technology Review.
Infection by Plasmodium parasites impairs Anopholes’ fertility. But previous efforts to make mosquitoes malaria-resistant overtaxed their immune system, imposing another fitness cost. In March, Johns Hopkins professor Dr. Mauro Marrelli discovered a new method that promotes malaria-resistance while maintaining the evolutionary advantage of resistance.
Dr. Marrelli and colleagues looked at SM1, a small protein that keeps the parasite from infecting the mosquito in the first place. The SM1 protein blocks the parasite’s access to the mosquito’s gut so that the mosquito’s immune system never has to be activated.
Dr. Marrelli and colleagues created genetically modified (GM) mosquitoes by inserting into their genomes one copy of the SM1 gene. But in tracking the mosquito population over several generations, it would be difficult to identify which insects had been successfully modified-so he inserted another gene to make the modified mosquitoes’ eyes glow green.
But would Marrelli’s gene work?
To establish malaria-resistant mosquitoes in the wild, Marelli would need to at least show that they outcompeted normal mosquitoes in the lab. And by the ninth generation of his experiment, 70 percent of the mosquitoes carried the SM1 gene versus 50 percent at the start of the experiment-demonstrating a clear evolutionary advantage.
Unfortunately, the SM1 prevalence rate in the population never climbed above 70 percent — most likely because getting copies of the gene from both parents hurts Anapholes’ fitness.
So is this the last we’ll see of malaria?
“We’re not anywhere near a field release [of GM mosquitoes],” stated Jason Rasgon, one of the researchers who worked on the study, to the Associated Press.
Most importantly, the Plasmodium parasite studied by Dr. Marrelli and his team causes malaria in mice, not humans. The next task for the researchers, then, will be to create a mosquito resistant to human malaria.
In addition, outside of the laboratory, the malaria-resistant mosquitoes’ advantage is not so significant. Only a small proportion of wild mosquitoes become infected with malaria; to succeed, GM mosquitoes would have to have an advantage over wild-type mosquitoes even when not exposed to malarial parasites.
And even if malaria-resistant mosquitoes did become dominant, it’s possible parasites would evolve to overcome SM1, as they have with many anti-malaria drugs and insecticides. Ultimately, the researchers project that it will be at least another 10 years before we see GM mosquitoes in the wild.
Computer models propose that malaria-resistant mosquitoes would have to completely wipe out a native wild-type mosquito population in order to prevent the spread of the disease. But once GM mosquitoes became established in a region, it would be much more challenging for the parasite to reappear there. The best solution for preventing the spread of malaria would be to combine the introduction of GM mosquitoes with other drugs, insecticides and vaccines.
Every year, malaria is responsible for 300 million cases of illness and one million deaths. The majority of malaria cases —90 percent are in sub-Saharan Africa, and the vast majority of victims are children. There is currently no vaccine for the disease and most treatments are too expensive for people living in poor communities to obtain. The work of Dr. Marrelli and his colleagues in engineering malaria-resistant mosquitoes is a promising first step towards ending this devastating disease.
Contact Rachel Whelan at rpwhelan at stanford.edu.