Mosquitoes Losing Malarial Bite in Genetics Laboratory
As insecticides fail and vaccine efforts falter, scientists combating malaria have created genetically engineered mosquitoes that do not transmit the lethal disease, a feat hailed as a milestone in the effort to conquer a pestilence that infects 300 million people every year.
Working with a strain of malaria in mice, researchers created a gene in the hardy insect that normally spreads the malaria parasite, turning it into a cleverly designed trap that one day could eradicate a disease that kills as many people as AIDS and tuberculosis, according to work made public Wednesday.
There are serious safety concerns and regulatory issues that must be resolved before any of these experimental insects could be released, experts said. There have been no approved releases into the wild of genetically modified insects.
But eventually, the researchers hope to transform the entire species. Swarms of such modified mosquitoes could wipe out malaria by transferring this gene to the entire population of malaria-carrying mosquitoes, said Marcelo Jacobs-Lorena, a geneticist at Case Western Reserve University in Cleveland, who led the research team.
This new breed of modified mosquitoes arises from a determined effort to turn insects into the living tools of public health against malaria, dengue and yellow fever, as more conventional pest controls lose their effectiveness.
“This is a significant achievement,” said UC Irvine’s Anthony James, who pioneered the techniques for genetically altering mosquitoes. “It is a clear demonstration that it is possible to make this type of mosquito. This is a big milestone.”
The work, published today in the scientific journal Nature, “represents a new era of malaria-related research,” said Gareth J. Lycett and Fotis C. Kafatos of the European Molecular Biology Laboratory in Heidelberg, Germany.
Safety Questions
The big question, said entomologist Peter Atkinson at UC Riverside, is whether any manufactured insect can be safely released into the wild--an issue that taps into public concerns about the safety of genetically engineered organisms.
“There are a lot of problems--scientific and regulatory and ethical--to solve,” Jacobs-Lorena said.
“We have to be very careful before we move to release anything into nature. We have to be sure genetically modified mosquitoes do not acquire any other [harmful] properties. In principle, they should not, but we need to do careful work to prove that.”
Not so long ago, malaria was all but eradicated in many parts of the world, mostly through large-scale public sanitation efforts and the use of prodigious amounts of insecticide. In an evolutionary arms race, however, mosquitoes have grown immune to pesticides faster than new ones can be found, while the malaria parasite has become immune to most common medications. With global temperatures rising, the insects may find themselves at home in areas that have never known malaria.
As the disease’s resistance to drugs increases, malaria deaths have soared to 3 million a year.
In Africa, where 90% of all malaria cases occur, the disease claims an African child every 30 seconds. In India, the government spends almost half its health budget combating malaria.
“Malaria is a reemerging disease,” James said. “It is becoming a problem again.”
The economics of malaria compound the difficulties. The disease is resurging most strongly in the world’s poorest countries, which offer few commercial incentives for pharmaceutical companies to develop new treatments.
Deaths Could Double
Unless new control measures are found, the death toll is expected to double in the next 20 years.
By harnessing the power of molecular biology, researchers hope that natural forces may take care of the problem as effectively and economically as possible.
The researchers made a new gene, called SM1, and used it to add a molecule to the mosquito’s makeup that stops the malaria parasite from passing from the gut to the saliva of the mosquito. That keeps the insect from infecting humans. The gene is activated when the insect bites and sucks blood. It is passed to all offspring.
The parasite simply can’t get a grip on the mosquito’s stomach, throwing it off track at a critical point in its life cycle.
In the research reported in Nature, two of three groups of modified mosquitoes were unable to transmit the disease to mice, and a third group of mosquitoes was only about 50% effective.
Dyann Wirth, a Harvard University microbiologist and director of the Harvard Malaria Initiative to battle the disease worldwide, called it “a very fundamental scientific discovery” that offers a way to attack malaria without using chemical pesticides such as DDT, which can have harmful side effects.
Jacobs-Lorena did his experiments with a breed of mosquito called Anopheles stephensi. The most important malarial carrier is a breed called Anopheles gambiae, the type largely responsible for the resurgence of the disease in Africa.
His experiments were conducted with mice for safety reasons, but its application to the mosquitoes that infect humans should be straightforward technically, experts said.
The virulence of the malaria parasite, however, varies depending upon the species it infects. Only a few kinds of mosquitoes transmit malaria, while other mosquito breeds carry yellow fever or dengue.
Bird Trials Successful
What works in a mouse, therefore, may not be effective enough to block transmission of the disease in humans, UC Irvine’s James said.
Using a different experimental technique in his laboratory, James has genetically engineered mosquitoes that reduce transmission of the disease among birds.
By fall, researchers expect to have in hand the complete genetic sequences of all three major players in the tragedy of malaria--the genome sequence of the mosquito, the malaria parasite and the human being.
With those in hand, it then may be only a matter of time--no more than a few years at most--before the creation of mosquitoes that can block the parasite from infecting humans.
“It is coming quite soon,” Atkinson said. “Very soon now there will be mosquitoes made in the laboratory that will be reduced in their ability to transmit malaria to humans.”
