Yeast engineered to produce potent drug.
The ‘miracle’ malaria drug artemisinin is a step closer to being produced plentifully and cheaply. Synthetic chemists have put plant genes into yeast to make it churn out large amounts of the precursor artemisinic acid. The discovery brings hope to areas such as sub-Saharan Africa, where those who need the drug most can ill afford it.
Researchers have praised the work and are excited that it may soon be possible to get artemisinin to the 300 million to 500 million people infected with malaria each year. But many are also concerned that this will trigger the emergence of resistance to the drug, thus destroying our most effective weapon against the disease.
Artemisinin is extracted from the leaves of Artemisia annua, or sweet wormwood, and has been used for more than 2,000 years by the Chinese as a herbal medicine called qinghaosu. The parasite that causes malaria has become at least partly resistant to every other treatment tried so far. Artemisinin is still effective, but it is costly and scarce.
Artemisinin is the basis of all the new treatments that are going ahead.
“This drug is such an important thing for malaria,” says David Warhurst, an expert in protozoan chemotherapy at the London School of Hygiene and Tropical Medicine. “It is the basis of all the new treatments that are going ahead.”
Jay Keasling at the University of California, Berkeley, and his colleagues tweaked a pathway and used three plant genes to persuade yeast (Saccharomyces cerevisiae) to produce and secrete large amounts of artemisinic acid, which is just a few chemical steps away from artemisinin. The researchers, whose paper starts on page 940 of this issue, hope that once the process is scaled up it will allow artemisinin to be made industrially. A course of artemisinin currently costs US$2.40; cutting the cost to 10% of that should make it affordable for most sufferers.
Work towards industrial production has already been started by the non-profit pharmaceutical company Institute for OneWorld Health, based in San Francisco, California, in partnership with Amyris Biotechnologies and with the help of $42.6 million from the Bill and Melinda Gates Foundation. “We're focusing on producing a known pharmaceutical so that it reaches the people who need it most,” says Jack Newman, co-founder of Amyris, based in Emeryville, California. But he is hopeful that the work will lead to industrial production of other plant-based drugs in a similar way.
The prospect of plentiful artemisinin is encouraging, but if the parasite becomes resistant, increased drug production will be worthless. “The loss of artemisinin could spell disaster for malaria sufferers,” warns Chris Hentschel, head of the non-profit Medicines for Malaria Venture, based in Geneva.
There is no consensus on how likely resistance is, but some think the risk is high. Artemisinin works by disabling a calcium pump in the malaria parasite, and last year researchers reported that the mutation of a single amino acid was sufficient to confer resistance (A.-C. Uhleman et al. Nature Struct. Mol. Biol. 12, 628–629; 2005). When another team gave low doses of artemisinin to parasites taken from patients in French Guiana, some mutated, becoming highly resistant to the drug (R. Jambou et al. Lancet 366, 1960–1963; 2005).
The main way to stop resistance arising is to always give the drug in combination with others. In January, the World Health Organization (WHO) made a plea to pharmaceutical companies to end the marketing and sale of single-drug artemisinin medicines. But as other malaria drugs grow increasingly ineffective, many feel that resistance to artemisinin is inevitable.
“We hope it won't happen,” says Warhurst. “But looking for new drugs is important.”
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Towie, N. Malaria breakthrough raises spectre of drug resistance. Nature 440, 852–853 (2006). https://doi.org/10.1038/440852b
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DOI: https://doi.org/10.1038/440852b
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