A health worker collects a drop of blood to test a child for malaria. Photo: PATH/Laura Newman.
A new method to produce artemisinin means a surer supply of the gold-standard malaria treatment
For nearly two millennia, Chinese healers turned the leaves of a fern-like weed into a tea to cure fevers and other ailments. During the 1970s, Chinese scientists discovered in the weed a key treatment for malaria. Yet it would take another 30 years before Artemisia annua, the sweet wormwood plant, reached the Western world and achieved a foothold in global efforts to treat malaria.
Today, artemisinin, a material derived from the sweet wormwood plant, is the main ingredient in the most effective treatment for malaria. But its supply depends solely upon a volatile crop that grows commercially in just a small slice of the world and fluctuates drastically in supply and price.
To address this challenge, PATH and our partners figured out a way to create a new, stable supply of the drug. Large-scale production of semisynthetic artemisinin will bolster the botanical supply, improving the artemisinin market and preventing future shortages.
A volatile crop
The global demand for artemisinin first skyrocketed in 2001, when the World Health Organization (WHO) recommended artemisinin-based combination therapy (ACT) as the standard treatment for malaria worldwide. Artemisinin combined with other drugs provides a highly effective and safe cure for uncomplicated cases of malaria, which kills more than 620,000 people a year. It also sidesteps the challenges of drug resistance that threaten people treated with a single drug.
But the world’s supply of artemisinin has not been reliable. Sweet wormwood, mostly cultivated in China and Vietnam, requires up to ten months from sowing to harvest, and its yield and quality vary depending on weather, region, growing practices, and market conditions. For malaria-endemic countries in Africa and Asia already challenged to meet health needs, this volatility puts an added strain on providing fast and effective treatment.
Starting with a soda pop bottle
Others have tried producing artemisinin synthetically, but the process is complicated and expensive to expand from lab bench to factory scale. Scientist Jay Keasling already had successfully engineered artemisinin in small quantities in his lab at the University of California, Berkeley. With a grant from the Bill & Melinda Gates Foundation, PATH pulled together Keasling’s team and researchers from biotechnology start-up Amyris, Inc. to turn a laboratory experiment to a platform suitable for industrial scale-up.
Our challenge was to find a way to scale up the process and expand production from just two liters of artemisinin at a time—about the size of a large soda pop bottle—to enough to fill a vat the size of a three-story building.
By 2007, the team had perfected a method for turning a living organism into artemisinin. They took genes from the Artemisia annua plant, then inserted them into bacteria and eventually into a yeast. The yeast ferments and produces an intermediate product called artemisinic acid. The team used a chemical process to convert the acid into artemisinin. The National Research Council Canada Plant Biotechnology Institute gave royalty-free access to a gene it discovered to make the process even more economically feasible.
To achieve large-scale production of the semisynthetic artemisinin, we partnered with international pharmaceutical company Sanofi to optimize and scale-up the fermentation process for artemisinic acid. We developed an innovative method that uses light instead of chemicals to convert the acid into artemisinin. Sanofi built a new facility for this photochemistry in Italy and began the world’s first commercial production of semisynthetic artemisinin.
A third of the world’s supply
Sanofi will use semisynthetic artemisinin, now prequalified by WHO, to produce their malaria drug ASAQ, and they will offer semisynthetic artemisinin to manufacturers for use in their own products. These buyers, prequalified by WHO, have committed to making high-quality malaria drugs for combination therapy. Sanofi will sell the semisynthetic artemisinin at cost, helping to improve the overall price volatility of artemisinin market.
An additional source will mean a stable cost and steady supply independent of the Artemisia annua crop. Sweet wormwood growers will continue to provide plants for a share of the artemisinin market, and poor countries battling malaria will have greater access to a much-needed treatment.