Malaria genome research brings new hope

Efforts to battle infectious diseases in developing countries have crossed what many see as an important threshold with this week's unveiling of the genetic blueprints for two key malarial agents.

International teams of scientists have sequenced the genomes of both the parasite responsible for malaria infections in humans and of the mosquito that carries the parasite.

Armed with this information, scientists hope to unlock the biochemical workings of the parasite and better understand its interactions with mosquitoes and humans. That information can then be used to develop new drugs, vaccines, and control strategies that could dramatically reduce the disease's reach.

From 300 million to 500 million people a year contract malaria, which kills as many as 2.7 million people annually, according to public health officials.

Collectively, the genomes represent "a major milestone," says Regina Rabinovich, director of the Malaria Vaccine Initiative. "This is precisely the research we need to have happen."

The six-year, $17.9 million gene-sequencing work, led by labs in the US, Britain, and Australia, also highlights the increasingly important role genomics is playing in biomedical research.

Armed with cheaper, more efficient, and faster machines and computers, scientists are sequencing the genomes of a range of other infectious disease agents, many of which take their highest toll among developing countries.

"There will be many more of these genomes to follow," says Malcolm Gardner, a researcher at the Institute for Genomic Research in Rockville, Md., and leader of the group that sequenced the parasite's genome.

The researchers sequenced the genomes by separating the organisms' chromosomes, long chains of DNA organized into genes. The chains were randomly broken, and each segment was inserted into bacteria and cloned. The segments were analyzed to tease out the patterns of DNA's four chemical "bases." The teams then used computers to sort through the information from the segments and put the genetic Humpty Dumpty back together again in a virtual form.

The reassembled sequences were then checked for accuracy, Dr. Gardner says, yielding a "final draft" of the parasite genome that is 98 percent complete.

The work on malaria is being reported and analyzed in more than 30 papers appearing in today's edition of the journal Nature and tomorrow's Science.

Because researchers have been publishing intermediate results, other teams have used the data to analyze various aspects of the parasite's life cycle. Two key topics, Gardner says, are the parasite's metabolic processes and its ability to change its molecular armor to thwart attacks by the immune system.

In addition, researchers say they have uncovered the gene that, through mutation, has given the parasite resistance to one of the leading antimalaria drugs. Several new targets for development of antimalarial drugs have emerged from early genome studies.

They are also looking at the mosquito genome for possible pathways to engineer a mosquito inhospitable to the parasite.

Yet for all the promise many scientists see in high-tech approaches to malaria, others are concerned that developed-world research teams are applying high-end solutions to a problem best addressed with simpler means.

At first blush, it seems as though the millions being spent on malaria research and control ought to be enough to attack the problem medically. Last July the world's eight largest industrial countries pledged to raise $1.3 billion to combat AIDS, tuberculosis, and malaria. But by many accounts, this still falls far short.

Chris Curtis, a researcher at the London School of Hygiene and Tropical Medicine, argues that in countries with health budgets averaging $10 a person per year, the best solutions may be the simplest. He cites insecticide-soaked mosquito netting or recuperative trips to highland areas free of swamps and mosquitoes as low-cost alternatives.

Others worry that the development of new drugs and vaccines could trigger another row between developed and developing countries similar to the one that occurred over the cost and availability of AIDS-related drugs.

Yet many scientists hold that both approaches are needed. They note that the long lead times to develop new pharmaceuticals make it necessary to adopt low-cost, flexible approaches for the present.

"We will need all these tools working together," Dr. Rabinovich says.