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Extracts from the Artemisia annua plant (green leaves above red flower), known as sweet wormwood or sweet annie in the U.S., have a long history of treating malaria. Scientists are now taking genes from the plant and putting them into yeast microbes to produce artemisinic acid, which can later be purified into malaria medicine.

Curing malaria by reconstructing life: the promise of synthetic biology

by Kristen Minogue
Feb 15, 2009

Scientists have developed a promising new malaria medicine that one day could lead to better treatment for the hundreds of millions of people infected with the deadly disease each year. Using genetically altered yeast microbes, a team of researchers led by University of California Berkeley chemical engineer Jay Keasling is developing a cheaper way to make the medicine.

Keasling presented his findings at the annual meeting of the American Association for the Advancement of Science in Chicago Friday as just one example of how synthetic biology – the engineering of life forms – is changing the world.

Malaria is a mosquito-borne disease that claims more than 1 million lives each year according to the federal Centers for Disease Control and Prevention. More than 90 percent of fatalities occur in sub-Saharan Africa, and most of its victims are children under five. Symptoms include high fever, chills and sweats.

Today doctors use a medicine called artemisinin to treat malaria. The drug is extracted from Artemisia annua, a yellow-flowering plant also known as sweet wormwood that the Chinese used to treat malaria for centuries.

“That can be very costly,” said Stanford University assistant bioengineering professor Christina Smolke, who spoke at the conference but was not part of Keasling’s research. “That can also actually be very damaging to the environment if you have to use extraction processes to remove these chemicals.”

And researchers predict the plant will be in short supply next year, according to Keasling. Meanwhile the parasites that cause malaria are growing more resistant to the drug, making the treatment less and less effective.

Keasling said it is possible to chemically synthesize the drug, but it’s a long and expensive process. Instead, his team decided to reconstruct living organisms to make them produce artemisinic acid, which could then be purified to make the medicine.

“We haven’t created a new organism,” he said. “We’ve modified existing life forms.”

The process involves taking genes from the artemisia plant and putting them into microbes like yeast or E. coli bacteria, turning them into what Smolke called "microbial factories." At first the process was less than one-millionth as effective as it had to be to make production worthwhile. But after altering the genes and tinkering with a few chemical pathways, Keasling’s team managed to boost production to high enough levels to be economically viable.

To solve the problem of resistant parasites, the World Health Organization advocates mixing the drug with other treatments, a solution doctors call “co-therapy.” Unlike monotherapy, which relies solely on one drug, co-therapy is designed to prevent the parasite from becoming resistant by confusing it with multiple drugs.

Keasling said he hopes by manufacturing the drug in labs, vendors can prevent the drug from going into monotherapy or hoax treatments, assurance artemisia plant farmers can’t provide.

“They can sell it to anyone and anyone can get a hold of it,” Keasling said. “If you produce the drug in a tank, you can restrict access. You can produce the cheapest artemisinin and you can only sell it to people who are going to put it into drugs where there is a co-therapy. So in this way you can in fact prevent or at least reduce the risk of resistance occurring.”

Keasling said his team partnered with international pharmaceutical company sanofi-aventis in March to develop the drug, which he predicted will go into production in one to two years.

But while the possibilities are glamorous, Keasling said what synthetic biologists really need is a more efficient toolbox.

“A lot of times when you think about technology and engineering, you think about the applications,” said Drew Endy, an assistant professor of bioengineering at Stanford with Smolke. “I’m going to cure malaria, I’m going to solve the energy crisis, I’m going to get computing in the household. That’s not really what drives the revolutions. What drives the revolutions is the tools.”