Modified genes may fight malaria

O8217;Brochta creates mutant insects. Not the kind in the horror movies that grow 30 ft tall and menace the city. He8217;s trying to create the kind whose genes have been tweaked just enough, in just the right way, that the insect8217;s bad habits are made benign. Just enough so it can8217;t harbour the parasite.

That is not easy: Anopheles gambiae is about as small as an eyelash. Hundreds of its minute, gray, banana-shaped eggs resemble a pinch of gunpowder. But the state-of-the art lab, which debuted last month, is designed for the microscopic tasks of gene-tweaking. Injections into mosquito eggs are done with a quartz glass needle the size of a strand of hair.

8220;We8217;re building a bug,8221; in much the way inventors would design a new airplane, says O8217;Brochta, 51, an insect molecular geneticist. 8220;We know we can do it.8221; The new lab, the only one of its kind in the world, has been designed to perfect the process.

The lab has an insectary where mosquitoes such as Anopheles gambiae and Aedes aegypti are reared in warm, humid chambers that look like walk-in freezers. They feed on mice.

Female mosquitoes8212;the ones that bite8212;require 8220;blood meals8221; every few days to nourish their eggs, and it is their excretions that stain the plastic buckets in which they are kept. None of the feeding mosquitoes is infected with pathogens that cause disease, he says. But Anopheles remains a 8220;flying syringe,8221; O8217;Brochta says, and a superb vector for Plasmodium falciparum, the deadliest form of the parasite that causes malaria.

The mosquito picks up the parasite by biting an infected person. The parasite mates and produces offspring that are deposited in the next person the insect bites. The insect8217;s taste for people is baffling. 8220;They smell us,8221; O8217;Brochta says. 8220;They specialise on us.8221; It is unclear why.

But the cycle is devastating. Malaria is believed to have killed more people than wars and other illnesses combined. Although drugs to combat the disease exist, economics and politics, along with drug and insecticide resistance, have hampered the fight, O8217;Brochta says. There is no malaria vaccine, he says. Scientists at Walter Reed Army Institute of Research in Maryland, and scores of their colleagues elsewhere are seeking to develop one.

O8217;Brochta8217;s work, along with the work of others around the world, has focused on breaking the disease cycle by altering the characteristics of the mosquito. And much of that focus is on the mosquito8217;s ability to harbour the parasite.

8220;Most mosquitoes in Africa do not serve as a host for Plasmodium falciparum,8221; O8217;Brochta says. 8220;The ability to serve as a host for malaria parasites is a very narrow trait.8221; So the question is: Could Anopheles be made to resist the parasite?

8220;That8217;s kind of the big idea,8221; he says. Science has learned how to alter the mosquito8217;s genome and has learned, roughly, which gene to add to make it resist the parasite, O8217;Brochta says.

But this new mosquito must also be made able to transmit the beneficial traits rapidly among the rest of its population. And that part has been difficult to engineer. 8220;With mosquitoes, we8217;ve had virtually no success,8221; he says.

8212;Washington Post / Michael E. Ruane