Global Policy Forum

Scientists have determined the complete genetic codes of the single-cell parasite that causes malaria and of the mosquito that transmits it to people, a feat they said would allow them to launch a high-tech assault on one of the world's deadliest and most intractable scourges.

Capping a six-year effort involving hundreds of scientists in nearly a dozen countries, scientists say the accomplishment should speed development of new drugs and vaccines that take aim at the parasite's most vulnerable genes, and could facilitate the creation of environmentally benign insecticides.

Moreover, malaria's genomic unveiling has revealed a host of new research opportunities that could inspire a much-needed shot of international investment in the faltering global war against the disease, researchers said. Malaria kills more than 2 million people annually -- the vast majority of them children younger than 5 -- and has spread in recent years as affordable drugs have lost their effectiveness and mosquitoes have perfected their resistance to the most widely used sprays.

Scientists probing the newly dissected strands of DNA already have found genes that the mosquito uses to sniff out humans -- a discovery that could lead to the creation of sophisticated new repellants -- and genes that the malarial parasite uses to invade red blood cells, which if blocked might prevent human infection. Researchers have even found genetic evidence that malarial mosquitoes' eyes glaze over after a big blood meal, just as humans' do after a Thanksgiving dinner.

In combination with the human genome, unraveled to great fanfare 18 months ago, the new work gives rise to a biomedical trifecta. "For the first time, we have the genetic sequences of all three of the players in the global malaria debacle: the parasite, the anopheles mosquito and the human," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which provided much of the U.S. share of the project's funding. "It's a very important milestone."

But Fauci and others warned that for all the opportunities the new work presents, an extraordinary commitment from the world's wealthier countries will be needed if the fruits of that research are to reach those who need it. "We certainly don't think the genome sequence is going to solve the malaria problem by itself," said Malcolm J. Gardner of The Institute for Genomic Research (TIGR) in Rockville, who led the effort to sequence the malaria parasite's genetic code. "Additional funds and efforts are going to be needed to get the drugs and vaccines out there to people."

Malaria ranks as one of the three leading infectious killers worldwide, along with tuberculosis and AIDS. The disease, spread mainly by the mosquito Anopheles gambiae, infects more than 300 million people each year, 90 percent of them in sub-Saharan Africa. The medical misery inflicted by malaria is matched by its enormous economic toll, having imposed a $100 billion penalty on Africa over the past 30 years alone, said Columbia University economist Jeffrey D. Sachs.

The genome projects -- funded by several public and private institutions, including the National Institutes of Health, the Wellcome Trust of England, the French Ministry of Research and the U.S. Department of Defense -- was conducted at TIGR, the Sanger Center in England, Celera Genomics in Rockville, Genoscope in France and several other university and research laboratories. Results are being published this week in a package of articles in the journals Science and Nature. But the teams have been releasing their raw results to a publicly accessible database as the work has progressed so others could start making use of it.

The mosquito work, led by Robert A. Holt and Stephen L. Hoffman of Celera, started with a painstaking collection of DNA from 760 A. gambiae mosquitoes. Using techniques similar to those used to sequence the human genome, the team determined the exact order of all 278 million DNA units in the mosquito genome. A computer program identified about 14,000 genes in that DNA, as compared with the 35,000 or 40,000 found in humans.

By comparing them with known fruit fly genes, researchers determined the probable function of many. They found 72 genes involved in taste, for example, and 79 involved in smell. Since A. gambiae feeds exclusively on people, scientists presume that many of those genes help the insect detect the scent of a human. "If we can identify the receptors that mosquitoes use to smell humans, we should be able to design novel repellants and attractants that can substantially reduce the incidence of malaria, West Nile encephalitis, dengue and yellow fevers and other mosquito-borne diseases," said project member Laurence J. Zwiebel of Vanderbilt University.

Another study assessed which mosquito genes are turned on or off after the mosquito sucks blood from a person. Mosquitoes consume as much as four times their weight in blood -- equivalent to a 100-pound woman drinking a 50-gallon drum of water. Among the genes that turn on after that feast are some that help the insect detoxify the potentially deadly iron found in human blood.

Scientists want to develop new chemicals that block that process, rendering blood meals fatal to the insects. Other genes apparently help egg cells mature inside the female after a meal of blood, suggesting that a drug able to block those genes might work as an insect contraceptive. At least four genes in the mosquito's visual system shut down after it bites a human, "suggesting a degree of detachment of the mosquito from its environment during digestion of the blood meal," the team notes.

Similar insights are coming from the parallel analysis of the parasite itself, Plasmodium falciparum, which the researchers found to have 24 million DNA units and about 5,300 genes. Encouragingly, about two-thirds of those genes look like no others in the human genome -- suggesting that new drugs produced to disrupt them, or vaccines that attack them, may not have ill effects on patients themselves. One such drug has already been identified and shown to be curative in animals. The drug is now being tested in people.

Fully 208 genes appear to be involved in the parasite's elaborate system for evading the human immune system. Others confer resistance to drugs, such as chloroquine. Both gene groups offer attractive avenues for the development of novel therapies, scientists said.

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