Pulling Malaria From Mosquitoes to Fight Disease
Gently, no smushing allowed. Malaria parasites lurk in these mosquitoes salivary glands, and a small company on the outskirts of the nations capital needs them unharmed for a dramatic test – attempting the first live vaccine to fight malaria.
Mutant mosquitoes, too, might help one day. Their eyes glow green under a special microscope, a sign that the University of Marylands genetic engineering has taken hold: These bugs should become super malaria incubators, a bid to eventually get more of the vaccines key ingredient per mosquito.
If the two experiments sound far-fetched, consider: A global push is on to eradicate this ancient scourge, and increasingly scientists are exploring how to use the mosquito itself to help – not just with the vaccine research but also, conversely, by breeding insects that are less able to spread malaria.
“Its really gene therapy for insects,” says Dr. David OBrochta, who heads the Maryland universitys novel laboratory and, with government funding, is creating both bug types.
Its a change in philosophy, and OBrochta cautions that its far from clear that any of the mosquito research will pan out.
A vaccine made of living malaria parasites “was considered laughable five to seven years ago,” says Dr. Stephen Hoffman, CEO of Rockville, Md.-based Sanaria Inc.
In the Navy in the 1990s, Hoffman irradiated malaria-carrying mosquitoes to weaken the parasites inside them, and he and 13 colleagues subjected themselves to more than 1,000 bites. Usually malaria parasites race to the liver and multiply before invading the bloodstream to sicken. These weakened parasites instead sat harmlessly in the liver, unable to multiply but triggering the immune system to fend off later infections. All but one of the people in Hoffmans test, himself included, were immune when bitten by regular malaria-infected mosquitoes over the next 10 months.
The question was how to turn that protection into a long-lasting shot. Critics said “it couldnt possibly be made,” Hoffman recalls. “We were dismissed by 99 percent of the people in the malaria field.”
Yet two weeks ago, with the Food and Drug Administrations OK, the first of about 100 U.S. volunteers started receiving test doses of Sanarias vaccine, in a first-stage safety study.
Nearly a quarter-billion people get malaria each year, and it kills almost 1 million, the vast majority of them young children in Africa. Species of Anopheles mosquitoes spread the parasite. Bed netting and insecticides are the chief protection. Advanced testing of a different experimental vaccine from GlaxoSmithKline is under way in Africa, an exciting first but one expected to provide only partial protection.
Hence the push by about a dozen labs worldwide to breed malaria-resistant mosquitoes in various ways, including altering their genes.
In OBrochtas lab, Robert Harrell peers through a microscope and jabs a mosquito egg – so small it takes a clump of them to resemble specks of dirt – with a hair-thin glass needle. Hes aiming new DNA near a spot that should develop into reproductive organs, so the resulting mutant mosquito can pass its new trait to next generations.
In a humid insectary that resembles a walk-in safe, OBrochta pulls out a bucket swarming with Anopheles gambiae, the species that drives malaria in Africa. Deprived of human blood in the lab, these mosquitoes will suck on a sedated mouse for food. (The lab mouse, which loses a little blood, then gets a two-week vacation – and no, mosquitoes dont make mice itch.)
But in the wild, this particular species hunts people like a bloodhound, so a malaria-resistance gene would have to spread a lot faster through mosquito populations to work. How to speed that spread is OBrochtas main focus.
The flip side of his research brings us back to Sanaria.
It takes 3,000 mosquitoes – relatives of A. gambiae, dissected by hand – to make a batch of the experimental vaccine, says Sanaria entomologist Adam Richman. In an FDA-sanctioned “clean room,” workers dunk frozen mosquitoes in alcohol, killing them but not the stunned parasites inside. Then, peering through a microscope, the workers carefully pull each mosquitos head from its body. Out pops an almost translucent glob, the glands, ready for purification.
The companys eventual goal: a mosquito that can harbor 200,000 sporozoites, the immature parasites, twice the typical amount. In his nearby university lab, thats what OBrochta is trying to create by switching off a gene that protects the bug when it eats malaria-infected human blood.