A Step Toward Malaria Cure Announced : Health: Scientists clone chromosome of organism that causes the disease, which kills 3 million people a year. Full map of parasite’s genes sought.
Scientists at Sloan-Kettering Institute announced Wednesday that they have succeeded in cloning an entire chromosome of the organism that causes malaria, opening new avenues of potential treatment for the disease, which has become increasingly resistant to drug therapy.
Malaria, which infects about 300 million people a year, kills up to 3 million--mostly young children--far more than AIDS.
The discovery leads the way to mapping the other chromosomes of Plasmodium falciparum, the protozoan parasite that causes the worst form of malaria. Laboratories in Britain and Australia have joined Sloan-Kettering in the mapping project.
“We now have the capacity to develop the road map for the parasite,” said Dr. Jeffrey V. Ravetch, who led the team of scientists at Sloan-Kettering. “It is a critical first step in being able to understand the organism and identify the genes associated with drug resistance. . . . It is a major step in the basic biology of the organism. There is a good ray of hope.”
Ravetch, head of the Laboratory of Biochemical Genetics, predicted the parasite’s 13 other chromosomes could be cloned within three years.
“Malaria is on the rise,” he said at a news conference at Sloan-Kettering. “About half the world’s population is exposed to the disease. In some countries, it is the No. 1 health concern.”
Malaria is transmitted when an infected mosquito deposits the parasite in a victim’s blood stream. It occurs chiefly in the tropics and subtropics, but the speed of world travel has brought increasing numbers of cases to the United States. It is an ancient disease; Romans named it.
The illness is marked by recurring chills, fever, nausea, vomiting and headaches. Children infected with a particularly virulent strain can die within hours. Physicians commonly prescribe several drugs, including chloroquine and the much older medication, quinine. But resistant strains of malaria flourish.
By building a chromosome-by-chromosome map of the parasite, scientists believe they can determine what genes are involved in virulence and drug resistance and eventually design “smart drugs” or genetically altered vaccines to better control the disease.
Sloan-Kettering scientists worked for six years before being able to clone the chromosome. They faced several difficult problems. Plasmodium falciparum has a complex life cycle, crossing between two hosts--mosquitoes and primates. In addition, the parasite’s DNA proved to be unstable when traditional gene-cloning techniques were used.
Finally, the Sloan-Kettering team cloned the chromosome by using yeast cells as the host. DNA from the parasite was linked to DNA from the yeast cells in a test tube. The mixture was reintroduced into live yeast cells. When these yeast cells were analyzed, the parasite DNA was quite stable.
“It (the parasite DNA) did not undergo any deterioration,” said Ravetch. It could be grown for hundreds of generations in the yeast cells and it kept its stability. . . . Thus we had the ability to construct a virtual library of parasite DNA. With that capacity, we could see if we could identify the DNA fragments that would span one complete chromosome.”
When the chromosome was finished, it had a unique structure that allowed the organism to mutate constantly while keeping its essential genetic makeup. While about 80% of the genetic material in the chromosome was stable, 10% of the DNA at either end was unstable. It could be lost or rearranged spontaneously.
The chromosome cloning is being reported in the current issue of the scientific journal Nature. The report was authored by Ravetch, Michael Lanzer and Derik de Bruin, who adapted methods so that yeast cells would accept genetic material from the parasite.
Sloan-Kettering Institute is the research arm of Memorial Sloan-Kettering Cancer Center.
