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April 25, 2007

Building Robust, Malaria-Proof Mosquitoes

marcelo jacobs-lorenaThe following article a is preview from the Spring 2007 issue of Johns Hopkins Public Health, which will be available May 21.  

On the fourth floor of the Bloomberg School, an ocean away from Africa, the Malaria Research Institute houses one of the world's most sophisticated mosquito breeding facilities. Seven large, walk-in vaults are kept at a constant subtropical temperature and have near-perfect humidity levels for the survival of mosquitoes.

It’s here that Professor Marcelo Jacobs-Lorena’s team conducts research into genetically altered mosquitoes. The team’s hope: that these transgenic mosquitoes could hold a key to eradicating malaria, the scourge that takes the lives of more than a million people worldwide each year. In March, the researchers announced an encouraging step toward their goal of breeding a genetically altered mosquito that can resist the malaria parasite and out-compete—and ultimately replace—mosquitoes that spread the deadly disease in the wild. Their findings appeared in the March 19 Proceedings of the National Academy of Sciences.

“Scientifically, this is an important step,” says Jacobs-Lorena PhD, Bsc, MSc. “It dispels the belief that genetically altered mosquitoes are less fit than normal mosquitoes.”

In the study, Jacobs-Lorena and his team fed a diet of malaria-infected mouse blood to normal mosquitoes and to mosquitoes that have been genetically altered to resist mouse malaria. After nine generations, the designer mosquitoes out-survived their counterparts—70 percent versus 30 percent.

The results caused an international stir, raising hopes around the globe that this might be a step toward developing a transgenic insect that could one day be released into the wild to replace malaria-carrying bugs. “We were a bit surprised by the attention,” Jacobs-Lorena says.

In future experiments, he and his team will investigate whether his genetically altered insects will also out-survive normal mosquitoes after consuming human blood tainted with the parasite most deadly to people: Plasmodium falciparum, which accounts for 97 percent of malaria infections worldwide. The School’s Malaria Research Institute is one of few labs worldwide that can easily grow this deadly parasite in a form infectious to mosquitoes.

“We fully expect the results to be transferable,” says Jacobs-Lorena. “But right now, there is no proof. We have to do the experiment.”
He cautions that even if genetically altered mosquitoes show the same survivability advantage, it could be several decades before genetically altered insects can out-compete mosquitoes in the wild. 

The challenge, he explains, lies in finding a way to “drive” or transfer the altered gene into natural populations. Scientists suspect that if they simply release millions of genetically altered insects into the wild, the insects will not survive as well as they do in a laboratory. So researchers are also looking for transposable elements, or selfish genetic elements, that have the ability to self-replicate in the genome.

Jacobs-Lorena is excited by a promising alternative approach, known as paratransgenesis, which aims to alter the bacteria flora of the mosquito gut to make it inhospitable to the development of the malaria parasite. “We're betting it may be easier to find a way to introduce genetically modified bacteria into the midgut of mosquitoes than to drive new genes into the wild populations,” he says.

The current research comes amid more than 15 years of academic work by Jacobs-Lorena and his team into the possibility of controlling malaria through genetically altered insects. In 2002, the team first gained worldwide recognition for their work published in Nature that described the first transgenic mosquito that carried a gene inhibiting the malaria parasite development by 80 percent.

Jacobs-Lorena remains hopeful that he will see a solution to malaria in his lifetime. “As I tell my students,” he says, “if every experiment were to work the first time, there would be nothing left for us to do. There is much work to be done.”  —MBR

Take a video tour of the JHMRI laboratory where transgenic mosquito research is conducted. (QuickTime required)

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