Researchers use microbes to fight malaria

By PAUL ELIAS : AP Biotechnology Writer
Jun 1, 2003 : 1:53 pm ET

SAN FRANCISCO -- Genetic engineers in California say they're close to perfecting a new biotechnology recipe of an ancient Chinese remedy for malaria.

The researchers at the University of California, Berkeley hope to inexpensively manufacture a malaria fighter called artemisinin in E. coli bacteria, rather than finely grinding the wormwood plant as Chinese herbalists do.

Each year, 300 million to 500 million new cases of the mosquito-borne disease are diagnosed, according to the World Health Organization, and many of those who become ill -- children are especially vulnerable -- can't afford the drugs to treat it. Drug resistance is also a growing problem.

If the Berkeley technique is perfected, the researchers said their work could yield low-cost drugs produced in abundance.

The scientists also have high hopes that their multi-species gene splicing technique, which produces a family of chemicals called isoprenoids, could someday be used to make a wide range of drugs and food additives. Companies now create those chemicals in laboratories or extract them from plants -- both time-consuming and expensive processes.

Led by Berkeley chemical engineering professor Jay Keasling, the researchers spliced chemical-producing genes from the wormwood plant and yeast genes into E. coli and coaxed the production of a chemical precursor to artemisinin. Keasling said he and others are still searching the wormwood's genome for the needed genes to produce artemisinin itself.

The work of Keasling and his colleagues was published Sunday in the online edition of Nature Biotechnology.

Producing such chemicals in bacteria could also preserve plants now destroyed for their chemical benefits, the researchers said. For example, the popular cancer-fighting drug Taxol is extracted from the Pacific yew tree. Only about four million Pacific yews grow in the Northwest. The researchers say Taxol could be manufactured in their genetically engineered bacteria.

"This process could be of interest to everybody -- drug companies making cancer agents, the government producing antibiotics against bioterror agents or industries making flavors or fragrances," Keasling said. "A company could tweak the bacteria a bit, adding any number of plant genes involved in making the chemical of interest, to get pretty much any isoprenoid."

Malaria researchers said artemisinin is an effective malaria treatment when used in combination with other drugs.

"It's potentially important," said Dyann Wirth, a microbiologist who directs the Harvard Malaria Initiative. "In the long term, it will probably be best to find a more efficient way to do this than with plants."

Any new antimalarial drugs or development processes are welcomed in a field long ignored as unprofitable by large pharmaceutical companies, Wirth said.

Chinese first extracted artemisinin from the sweet wormwood plant for medicinal use more than 2,000 years ago. Since then it has been applied to a variety of ailments including hemorrhoids, coughs and fevers. U.S. researchers are also investigating artemisinin potential in fighting breast cancer.