Synthetic DNA makes 'What is life?' a business question, too

WASHINGTON

It has been 50 years since scientists first created DNA in a test tube, stitching ordinary chemical ingredients together to make life's most extraordinary molecule. Until recently, however, even the most sophisticated laboratories could make only small snippets of DNA -- an extra gene or two to be inserted into corn plants, for example, to help the plants ward off insects or tolerate drought.

Now researchers are poised to cross a dramatic barrier: the creation of life forms driven by completely artificial DNA.

Scientists in Maryland have already built the world's first entirely handcrafted chromosome -- a large looping strand of DNA made from scratch in a laboratory, containing all the instructions a microbe needs to live and reproduce.

In the coming year, they hope to transplant it into a cell, where it is expected to "boot itself up," like software downloaded from the Internet, and cajole the waiting cell to do its bidding. And while the first synthetic chromosome is a plagiarized version of a natural one, others that code for life forms that have never existed before are already under construction.

The cobbling together of life from synthetic DNA, scientists and philosophers agree, will be a watershed event, blurring the line between biological and artificial -- and forcing a rethinking of what it means for a thing to be alive.

"This raises a range of big questions about what nature is and what it could be," said Paul Rabinow, an anthropologist at the University of California at Berkeley who studies science's effects on society. "Evolutionary processes are no longer seen as sacred or inviolable. People in labs are figuring them out so they can improve upon them for different purposes."

That unprecedented degree of control over creation raises more than philosophical questions, however. What kinds of organisms will scientists, terrorists and other creative individuals make? How will these self-replicating entities be contained? And who might end up owning the patent rights to the basic tools for synthesizing life?

Some experts are worried that a few maverick companies are already gaining monopoly control over the core "operating system" for artificial life and are poised to become the Microsofts of synthetic biology. That could stifle competition, they say, and place enormous power in a few people's hands.

"We're heading into an era where people will be writing DNA programs like the early days of computer programming, but who will own these programs?" asked Drew Endy, a scientist at the Massachusetts Institute of Technology.

At the core of synthetic biology's new ascendance are high-speed DNA synthesizers that can produce very long strands of genetic material from basic chemical building blocks: sugars, nitrogen-based compounds and phosphates.

Today a scientist can write a long genetic program on a computer just as a maestro might compose a musical score, then use a synthesizer to convert that digital code into actual DNA. Experiments with "natural" DNA indicate that when a faux chromosome gets plopped into a cell, it will be able to direct the destruction of the cell's old DNA and become its new "brain" -- telling the cell to start making a valuable chemical, for example, or a medicine or a toxin, or a bio-based gasoline substitute.

Unlike conventional biotechnology, in which scientists induce modest genetic changes in cells to make them serve industrial purposes, synthetic biology involves the large-scale rewriting of genetic codes to create metabolic machines with singular purposes.

So far, synthetic biology is still semi-synthetic, involving single-cell organisms such as bacteria and yeast that have a blend of natural and synthetic DNA.

The cells can reproduce, a defining trait of life. But in many cases that urge has been genetically suppressed, along with other "distracting" biological functions, to maximize productivity.

J. Craig Venter, chief executive of Synthetic Genomics in Rockville, Md., knows what he wants his cells to make: ethanol, hydrogen and other exotic fuels for vehicles, to fill a market that has been estimated to be worth $1 trillion.

In a big step toward that goal, Venter has now built the first fully artificial chromosome, a strand of DNA many times longer than anything made by others and laden with all the genetic components a microbe needs to get by.

Details of the process are under wraps until the work is published, probably early next year. But Venter has already shown that he can insert a "natural" chromosome into a cell and bring it to life. If a synthetic chromosome works the same way, as expected, the first living cells with fully artificial genomes could be growing in dishes by the end of 2008.

The plan is to mass-produce a plain genetic platform able to direct the basic functions of life, then attach custom-designed DNA modules that can compel cells to make synthetic fuels or other products.

LS9 Inc., a company in San Carlos, Calif., is already using E. coli bacteria that have been reprogrammed with synthetic DNA to produce a fuel alternative from a diet of corn syrup and sugar cane.

So efficient are the bugs' synthetic metabolisms that LS9 predicts it will be able to sell the fuel for just $1.25 a gallon.