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Stanford Report, October 9, 2002

Medical center team helps sequence malaria gene


Researchers at the medical center have sequenced one chromosome from the parasite that causes malaria, Plasmodium falciparum. These results, along with sequence of the other 13 chromosomes, were published in the Oct. 3 issue of the journal Nature.

The malaria genome sequence is being published in conjunction with a draft sequence of the parasite’s mosquito host, which was published in the Oct. 4 issue of the journal Science. Together, these data will help researchers develop vaccines to prevent malaria and discover drugs to treat the 300 million to 500 million new cases of malaria worldwide each year.

The Malaria Genome Project at the Stanford Genome Technology Center includes (from left) Ron Davis, Richard Hyman, Molly Miranda, Eula Fung and Don Rowley. PHOTO: COURTESY OF RICHARD HYMAN

"These data present a very robust platform for future experiments," said Richard Hyman, PhD, a research associate at the Stanford Genome Technology Center and the scientist who led the Stanford team. "Other groups of scientists have already gotten into the vaccine and drug business."

Although sequencing genomes has become streamlined compared to the early days of the human genome project, the P. falciparum genome posed a novel problem. Most organisms’ genomes have an even scattering of the four bases (A, T, G, and C) that make up DNA. The P. falciparum genome has 81 percent A and T. The Stanford team had to devise new ways of sequencing this troublesome DNA.

"All the technology is worked out for DNA of 50 percent A and T," Hyman said. "As the percentage of A and T increases from 50 percent, those techniques still work, but as you go very far from 50 percent — such as in P. falciparum — you have to work out the techniques from scratch." Hyman is first author on the Nature paper, which describes the novel techniques. These techniques will help other researchers sequence equally tricky genomes in the future.

Other papers in the Oct. 3 issue of Nature focus on the parasite’s genome and proteins. "The members of the international consortium that sequenced the P. falciparum genome decided several months ago that my paper was going to concentrate on these methods so that down the road anyone who undertakes the sequencing of an AT-rich DNA can learn from our work," Hyman said. "For example, our paper will help in the sequencing of the AT-rich genome of a simple organism called a slime mold," Hyman said.

In addition to pioneering new sequencing techniques, the Stanford group posted sequence data overnight, providing scientists everywhere immediate access to the information. "It’s raw sequence data, so we also posted a big caveat so that people would treat the data as such," Hyman said. Because the posted sequence data started becoming available four years ago, two vaccines are headed to field trials in Gambia now with another drug on the way — much earlier than if Hyman and his collaborators had waited until the papers on their work were published. "We’ve given scientists a four-year head start," he said.

Since malaria is primarily found in the tropics where people don’t have money for drugs and vaccines, large pharmaceutical firms have overlooked the disease, Hyman said. Instead, the U.S. Department of Defense and non-profit organizations such as the Burroughs Wellcome fund (which supported the work at Stanford) are investing in vaccines, drugs and the methods of delivering those products to the developing countries where they are needed. "Right now the disease is virtually confined to the tropics," said Hyman, since the parasite can survive through winter in warm climates.

Hyman added that if global warming heats up European and U.S. winters by only a few degrees, malaria may return to regions of the United States and other developed countries where it was once a seasonal disease.

Stanford Genome Technology Center