ANNALS OF SCIENCE
A LIFE OF ITS OWN
Where will synthetic biology lead us?
by Michael Specter
SEPTEMBER 28, 2009
The first time Jay Keasling remembers hearing the word “artemisinin,” about a decade ago, he had no idea what it meant. “Not a clue,” Keasling, a professor of biochemical engineering at the University of California at Berkeley, recalled. Although artemisinin has become the world’s most important malaria medicine, Keasling wasn’t an expert on infectious diseases. But he happened to be in the process of creating a new discipline, synthetic biology, which—by combining elements of engineering, chemistry, computer science, and molecular biology—seeks to assemble the biological tools necessary to redesign the living world.
Scientists have been manipulating genes for decades; inserting, deleting, and changing them in various microbes has become a routine function in thousands of labs. Keasling and a rapidly growing number of colleagues around the world have something more radical in mind. By using gene-sequence information and synthetic DNA, they are attempting to reconfigure the metabolic pathways of cells to perform entirely new functions, such as manufacturing chemicals and drugs. Eventually, they intend to construct genes—and new forms of life—from scratch. Keasling and others are putting together a kind of foundry of biological components—BioBricks, as Tom Knight, a senior research scientist at the Massachusetts Institute of Technology, who helped invent the field, has named them. Each BioBrick part, made of standardized pieces of DNA, can be used interchangeably to create and modify living cells.
“When your hard drive dies, you can go to the nearest computer store, buy a new one, and swap it out,” Keasling said. “That’s because it’s a standard part in a machine. The entire electronics industry is based on a plug-and-play mentality. Get a transistor, plug it in, and off you go. What works in one cell phone or laptop should work in another. That is true for almost everything we build: when you go to Home Depot, you don’t think about the thread size on the bolts you buy, because they’re all made to the same standard. Why shouldn’t we use biological parts in the same way?” Keasling and others in the field, who have formed bicoastal clusters in the Bay Area and in Cambridge, Massachusetts, see cells as hardware, and genetic code as the software required to make them run. Synthetic biologists are convinced that, with enough knowledge, they will be able to write programs to control those genetic components, programs that would let them not only alter nature but guide human evolution as well.
If the science truly succeeds, it will make it possible to supplant the world created by Darwinian evolution with one created by us.
No scientific achievement has promised so much, and none has come with greater risks or clearer possibilities for deliberate abuse. The benefits of new technologies—from genetically engineered food to the wonders of pharmaceuticals—often have been oversold. If the tools of synthetic biology succeed, though, they could turn specialized molecules into tiny, self-contained factories, creating cheap drugs, clean fuels, and new organisms to siphon carbon dioxide from the atmosphere.
In 2000, Keasling was looking for a chemical compound that could demonstrate the utility of these biological tools. He settled on a diverse class of organic molecules known as isoprenoids, which are responsible for the scents, flavors, and even colors in many plants: eucalyptus, ginger, and cinnamon, for example, as well as the yellow in sunflowers and the red in tomatoes. “One day, a graduate student stopped by and said, ‘Look at this paper that just came out on amorphadiene synthase,’ ” Keasling told me as we sat in his office in Emeryville, across the Bay Bridge from San Francisco. He had recently been named C.E.O. of the Department of Energy’s new Joint BioEnergy Institute, a partnership of three national laboratories and three research universities, led by the Lawrence Berkeley National Laboratory. The consortium’s principal goal is to design and manufacture artificial fuels that emit little or no greenhouse gases—one of President Obama’s most frequently cited priorities.
Keasling wasn’t sure what to tell his student. “ ‘Amorphadiene,’ I said. ‘What’s that?’ He told me that it was a precursor to artemisinin, an effective anti-malarial. I had never worked on malaria. So I got to studying and quickly realized that this precursor was in the general class we were planning to investigate. And I thought, Amorphadiene is as good a target as any. Let’s work on that.”
Malaria infects as many as five hundred million of the world’s poorest people every year and kills up to a million, most of whom are children under the age of five. For centuries, the standard treatment was quinine, and then the chemically related compound chloroquine. At ten cents per treatment, chloroquine was cheap and simple to make, and it saved millions of lives. By the early nineties, however, the most virulent malaria parasite—Plasmodium falciparum—had grown largely resistant to the drug. Worse, the second line of treatment, sulfadoxine-pyrimethanine, or SP, also failed widely. Artemisinin, when taken in combination with other drugs, has become the only consistently successful treatment that remains. (Reliance on any single drug increases the chances that the malaria parasite will develop resistance.) Known in the West as Artemisia annua, or sweet wormwood, the herb that contains artemisinic acid grows wild in many places, but supplies vary widely and so does the price.
Depending so heavily on artemisinin, while unavoidable, has serious drawbacks: combination therapy costs between ten and twenty times as much as chloroquine, and, despite increasing assistance from international charities, that is too much money for most Africans or their governments. Artemisinin is not easy to cultivate. Once harvested, the leaves and stems have to be processed rapidly or they will be destroyed by exposure to ultraviolet light. Yields are low, and production is expensive.
Although several thousand Asian and African farmers have begun to plant the herb, the World Health Organization expects that for the next several years the annual demand—as many as five hundred million courses of treatment per year—will far exceed the supply. Should that supply disappear, the impact would be incalculable. “Losing artemisinin would set us back years, if not decades,” Kent Campbell, a former chief of the malaria branch at the Centers for Disease Control and Prevention, and director of the Malaria Control Program at the nonprofit health organization PATH, said. “One can envision any number of theoretical public-health disasters in the world. But this is not theoretical. This is real. Without artemisinin, millions of people could die.”
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