Keasling realized that the tools of synthetic biology, if properly deployed, could dispense with nature entirely, providing an abundant new source of artemisinin. If each cell became its own factory, churning out the chemical required to make the drug, there would be no need for an elaborate and costly manufacturing process, either. Why not try to produce it from genetic parts by constructing a cell to manufacture amorphadiene? Keasling and his team would have to dismantle several different organisms, then use parts from nearly a dozen of their genes to cobble together a custom-built package of DNA. They would then need to construct a new metabolic pathway, the chemical circuitry that a cell needs to do its job—one that did not exist in the natural world. “We have got to the point in human history where we simply do not have to accept what nature has given us,” he told me.
By 2003, the team reported its first success, publishing a paper in Nature Biotechnology that described how the scientists had created that new pathway, by inserting genes from three organisms into E. coli, one of the world’s most common bacteria. That research helped Keasling secure a $42.6-million grant from the Bill and Melinda Gates Foundation. Keasling had no interest in simply proving that the science worked; he wanted to do it on a scale that the world could use to fight malaria. “Making a few micrograms of artemisinin would have been a neat scientific trick,” he said. “But it doesn’t do anybody in Africa any good if all we can do is a cool experiment in a Berkeley lab. We needed to make it on an industrial scale.” To translate the science into a product, Keasling helped start a new company, Amyris Biotechnologies, to refine the raw organism, then figure out how to produce it more efficiently. Within a decade, Amyris had increased the amount of artemisinic acid that each cell could produce by a factor of one million, bringing down the cost of the drug from as much as ten dollars for a course of treatment to less than a dollar.
Amyris then joined with the Institute for OneWorld Health, in San Francisco, a nonprofit drugmaker, and, in 2008, they signed an agreement with the Paris-based pharmaceutical company Sanofi-Aventis to make the drug, which they hope to have on the market by 2012. The scientific response has been reverential—their artemisinin has been seen as the first bona-fide product of synthetic biology, proof of a principle that we need not rely on the whims of nature to address the world’s most pressing crises. But some people wonder what synthetic artemisinin will mean for the thousands of farmers who have begun to plant the wormwood crop. “What happens to struggling farmers when laboratory vats in California replace farms in Asia and East Africa?” Jim Thomas, a researcher with ETC Group, a technology watchdog based in Canada, asked. Thomas has argued that there has been little discussion of the ethical and cultural implications of altering nature so fundamentally. “Scientists are making strands of DNA that have never existed,” Thomas said. “So there is nothing to compare them to. There are no agreed mechanisms for safety, no policies.”
Keasling, too, believes that the nation needs to consider the potential impact of this technology, but he is baffled by opposition to what should soon become the world’s most reliable source of cheap artemisinin. “Just for a moment, imagine that we replaced artemisinin with a cancer drug,” he said. “And let’s have the entire Western world rely on some farmers in China and Africa who may or may not plant their crop. And let’s have a lot of American children die because of that. Look at the world and tell me we shouldn’t be doing this. It’s not people in Africa who see malaria who say, Whoa, let’s put the brakes on.”
Artemisinin is the first step in what Keasling hopes will become a much larger program. “We ought to be able to make any compound produced by a plant inside a microbe,” he said. “We ought to have all these metabolic pathways. You need this drug: O.K., we pull this piece, this part, and this one off the shelf. You put them into a microbe, and two weeks later out comes your product.”
That’s what Amyris has done in its efforts to develop new fuels. “Artemisinin is a hydrocarbon, and we built a microbial platform to produce it,” Keasling said. “We can remove a few of the genes to take out artemisinin and put in a different gene, to make biofuels.” Amyris, led by John Melo, who spent years as a senior executive at British Petroleum, has already engineered three microbes that can convert sugar to fuel. “We still have lots to learn and lots of problems to solve,” Keasling said. “I am well aware that makes some people anxious, and I understand why. Anything so powerful and new is troubling. But I don’t think the answer to the future is to race into the past.”
For the first four billion years, life on Earth was shaped entirely by nature. Propelled by the forces of selection and chance, the most efficient genes survived, and evolution insured that they would thrive. The long, beautiful Darwinian process of creeping forward by trial and error, struggle and survival, persisted for millennia. Then, about ten thousand years ago, our ancestors began to gather in villages, grow crops, and domesticate animals. That led to stone axes and looms, which in turn led to better crops and a varied food supply that could feed a larger civilization. Breeding of goats and pigs gave way to the fabrication of metal and machines. Throughout it all, new species, built on the power of their collected traits, emerged, while others were cast aside.