To Drew Endy, all the great breakthroughs in biotechnology of the past 30 years were mere tweaks. Wonders such as mass-produced insulin, cancer-fighting drugs, pest-killing crops and glowing fish--they're simply the result of moving a single gene from one organism to another. Endy has a grand ambition: to edit living organisms. Or more precisely, to rewrite DNA one unit at a time, using this genetic data to make proteins-to-order, which in turn would define entire living cells. If this venture or anything like it succeeds it will change the way mankind interacts with the living world.
The 36-year-old professor at Massachusetts Institute of Technology is the intellectual ringleader of a cadre of "synthetic biologists" who are building useful devices out of genetic material, much as bits of mortar or silicon are used to erect complex objects. "Biology is incredibly cool, you've got programmable reproducing machines. To program these wonderful living objects that make copies of themselves, this is pretty exciting," says Endy.
In coming years, Endy says, we'll begin to see the first custom-crafted biomachines: cells that can keep track of how old they are or bacteria engineered to hunt down and kill tumor cells. These "devices" will guard against disease, create new fuels, manufacture chemicals and, in the wrong hands, produce horrific bioweapons. These are still the very early days; scientists do not know how to build such devices right now. They are just beginning to know how to build the tools that would build the biological micromachines.
Endy, along with three synthetic-biology comrades, started a company called Codon Devices in Cambridge, Mass. in late 2004 to industrialize the construction of genes. With $13 million in backing from Flagship Ventures and three other firms, Codon plans to sell its genetic material to the companies that will make the micromachines. Eventually it intends to produce its own creations, but that accomplishment is a long way off.
Initially Codon's goal is to dominate the gene-synthesis market. Its robot-filled lab can produce DNA to order at a cost of 79 cents per unit, down from $4 in 2003. Codon recently shipped the biggest piece of DNA ever made, a hunk of 35,000 base pairs, big enough to hold ten genes, to Cambridge biotech Microbia.
Codon claims it will have more production capacity by year-end than all of its competitors combined. Its rivals include firms such as Blue Heron Biotechnology, founded in 1999, and DNA 2.0, founded in 2003, both of which also deliver DNA on demand. "We're trying to create a whole new industry," says John Danner, the chief executive of Codon.
Endy came to synthetic biology in a roundabout way. He earned a bachelor's degree in civil engineering at Lehigh University but decided to pursue a Ph.D. in biology at Dartmouth after a senior-year class made him realize that cells could become the building material of the future. He arrived at MIT four and a half years ago assuming that truly understanding how cells work was the main hurdle facing synthetic biologists. But he found that the greater hurdle was a lack of organization, not discovery. What were needed were standards. The Industrial Revolution got a serious boost in 1864 when a machinist standardized screws. Henceforth someone trying to build an engine could pluck a standard 8-gauge, 32-threads-per-inch machine screw off the shelf.
Endy aims for similar standardization in the new field of synthetic biology, and embraces the radical approach of creating a free registry of building blocks. In 2002 MIT professors started a not-for-profit called BioBricks that has collected 2,000 biological components, including gene sequences that sense light, produce light, send messages between cells and switch cell functions on and off. Bioengineers, like computer programmers in the Linux open-source software movement, are encouraged to contribute "bricks" voluntarily, and can order the parts they need over the Internet.
"I don't think I've ever seen that level of leadership in a young person," says Harvard genetics professor George Church, who helped start the Human Genome Project and is another of Codon's founders. "What he's done would be hard for a Nobel Prize winner," says Church. "Drew just does it and doesn't have a big ego."
Christopher Voigt, a biochemist at the University of California, San Francisco, has already built a device from biological parts: a bacterium programmed to seek out cancer tumors. His researchers put two BioBricks sensors in E. coli bacteria. One senses a lack of oxygen in tissue, which is a sign of a tumor. The other detects the presence of similarly programmed bacteria. If enough bacteria are present, they employ another gene to invade the tumor and, potentially, kill it. Voigt's E. coli bacteria are still years away from being anything other than a research tool.
UC, Berkeley professor Jay Keasling, another Codon cofounder (the company is the dream team of synthbio), got $43 million in 2004 from the Bill & Melinda Gates Foundation to implant bacteria with genes from plants and yeast to make artemisinin, a malaria-fighting chemical normally derived from wormwood trees.
Other geneticists, such as J. Craig Venter, are taking a more far-out approach: building highly efficient organisms from scratch. Venter's firm, Synthetic Genomics, is figuring out the minimum number of genes one would need to create a useful microcreature.
Synthetic biology would not have happened without the industrialization of DNA production. For years biologists made DNA in a tedious process that involved copying thousands of DNA molecules and checking them for errors by putting them back into cells. Even tiny errors ruin experiments or make manufactured drugs poisonous.
Codon's founders brought with them new ways to catch errors in DNA synthesis,
allowing them to produce much larger strings of base pairs. This summer Codon
enlisted Craig Muir, the roboticist who industrialized gene-finding at
One roadblock to synthbio's future is the messed-up patent environment in biotech, where every tiny protein pathway and gene sequence has an owner wanting to get paid. Both Endy and UC, Berkeley's Keasling say that unless basic components are made freely available it will be too expensive to make anything useful or complex. "We're going to succeed or fail based on how we organize ourselves. If somebody comes up with a better system in Singapore or India, we could lose," says Endy.
The bigger fear is that synthetic biology could be the end of us all.
Technology like Codon's could be set up as a munitions factory, replicating
viruses such as the 1918 influenza, Ebola or smallpox. Codon Chief Danner and
John Mulligan, the founder of Blue Heron, have started an industry trade
organization that will prevent misuse by flagging potentially dangerous gene
sequences and doing checks on researchers who request DNA transcripts. "I don't
have a perfect answer," says Endy. "I live in a society where I depend on and
trust the intentions of other people."
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