A University of Arizona entomologist has bio-engineered a mosquito that is completely resistant to the parasite that causes malaria - a significant step toward creating a malaria-free "super mosquito" to replace current populations.
Michael Riehle predicts it will take another decade to produce a malaria-free mosquito that is engineered to out-compete wild populations of disease-carrying mosquitoes.
Then the world's governments will have to decide whether the unknown risks of replacing mosquito populations with transgenic mosquitoes are outweighed by the opportunity to eradicate a disease that kills more than 1 million people annually, Riehle said.
"I personally think the benefits will outweigh the risks," Riehle said.
The discovery is a collaboration between Riehle's team at the UA College of Agriculture and Life Sciences and a team headed by Shirley Luckhart at the Department of Medical Microbiology and Immunology at the University of California-Davis.
A paper describing the discovery, co-authored by both teams, was published Thursday in PloS Pathogens, a peer-reviewed publication of the Public Library of Science.
The development "sounds very exciting," said Marcelo Jacobs-Lorena of the Johns Hopkins Malaria Research Institute.
Other researchers have genetically altered mosquitoes to be partially resistant to malaria parasites but Riehle's team is the first to engineer 100 percent malaria-resistant mosquitoes, Jacobs-Lorena said.
"It is also the first time it's done with a human malaria parasite," he said. "It's definitely a very big step forward."
The work was funded by the National Institutes of Health and is part of a five-year, $2.8 million grant that explores a number of genetic strategies.
"Malaria is the No. 1 mosquito-borne disease in the world," killing 1 million to 3 million people a year, said Riehle. "Current control strategies are becoming less effective as resistance develops. We need to have more tools to fight malaria."
Riehle and his team at the UA used ultrathin quartz needles to inject Anopheles stephensi eggs with plasmids (circular rings of DNA), inserting a modified copy of the gene known as Akt. That turns on a variety of metabolic processes in the mosquito, including its resistance to parasites.
It also shortens lifespan, another strategy for controlling the spread of malaria that is part of Riehle's research. Most mosquitoes don't live much longer than the two weeks it takes for the malaria parasites called Plasmodium to multiply in the mosquito's gut and make their way to the salivary glands where the bite of the mosquito will infect the next victim. If you can knock a couple days off the insect's lifespan, you can inhibit transmission of the parasites.
Riehle joined with Luckhart to find out what effect the genetic alteration had on the mosquito's resistance to human-borne Plasmodium parasites.
The 100 percent result was unexpected, he said.
Luckhart's team raised mosquitoes from transgenic eggs shipped by Riehle to her lab in Davis and simultaneously cultivated the growth of Plasmodium parasites in human blood, feeding them to female mosquitoes, which require a series of blood meals to develop their own eggs.
Her team then dissected the females, using jewelers' forceps and powerful microscopes, looking for bundles of Plasmodium parasites, known as oocycsts. In mosquitoes that had a copy of each gene on each chromosome, they found no parasites. "We repeated the experiment three times and all three times it was 100 percent blocked and that was pretty impressive," Luckhart said.
A control group of unaltered mosquitoes showed, on average, about 20 bundles of parasites per specimen, Riehle said.
There are many challenges left, said Riehle, both logistical and ethical.
In order for the transgenic mosquitoes to flourish they would have to out-compete native populations, he said. Other researchers are working on "genetic tricks" to give transgenic mosquitoes an advantage in the wild, he said.
Deploying the mosquitoes would be logistically difficult and making the decision to deploy them brings up ethical considerations, he said.
"We don't know really what is going to happen when we release a genetically engineered insect," Riehle said.
Any plan to do so would necessarily involve the people and governments of many countries, said Luckhart, who has worked with African researchers on malaria studies.
"Everyone in our community is very aware of this and it's something that we recognize. We have to make sure that anything we do is safe and is something that is ethically and socially acceptable to the countries we are working with - emphasis on 'with.' It is important for scientists and people in endemic countries to be part of this process," Luckhart said.
Malaria is a parasitic infection of the bloodstream that is spread from one human host to another by one of 20 varieties of the Anopheles mosquito.
The species used in Riehle's research is the malarial mosquito of the Indian subcontinent. Malaria is most deadly in Africa, where most of the estimated 250 million infections and 85 percent of the documented 1 million deaths occur each year.
Jacobs-Lorena called the chances of "noxious" side effect extremely slim. "They just carry an extra gene and that's all. The behavior and all the rest is the same."
A transgenic mosquito has a big public-relations advantage over genetic manipulations that have created controversy, he said.
"In the case of plants, the perception is it's done for the profits of big corporations like Monsanto. In this case, we have the slight advantage that we save lives."
Jacobs-Lorena said his ongoing transgenic research takes a different approach to eradicating malaria. His group is working on bacterial flora in the guts of malarial mosquitoes. The parasite is most vulnerable when it's in the gut, he said.
It's a line of research that was pioneered by Riehle when he worked under Jacobs-Lorena at Johns Hopkins. That former relationship gives Jacobs-Lorena another reason to be pleased with Riehle's latest accomplishment.
"I feel probably almost better that he did it, than if I had done it," he said. "I feel very proud. It gives me a lot of satisfaction that he has done so well."
Riehle said the attack on malaria will ultimately feature a variety of transgenic approaches, done in concert with public-health campaigns such as mosquito netting and insecticides, in addition to a search for vaccines and better treatment.
Contact reporter Tom Beal at firstname.lastname@example.org or 573-4158.