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 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 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 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. "Evolutionary processes are no longer seen as sacred or inviolable."
Beyond philosophical debates, there are basic questions: What kinds of organisms will scientists, terrorists and others make? How will these self-replicating entities be contained? And who might own the patent rights to the tools for synthesizing life?
Some experts worry that a few maverick companies are already gaining monopoly control over the "operating system" for artificial life.
At the core of synthetic biology are DNA synthesizers that can produce long strands of genetic material from 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, or a medicine, or a bio-based gasoline substitute.
A cell is "a chassis and power supply for the artificial systems we are putting together," said Tom Knight of MIT.
If biology is to morph into an engineering discipline, it will need standardized parts, Knight said. So he and colleagues have started a collection of hundreds of interchangeable genetic components they call BioBricks.
So far, synthetic biology is not completely 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 "distracting" biological functions, to boost productivity.
J. Craig Venter, chief executive of Synthetic Genomics in Rockville, Md., wants his cells to make ethanol, hydrogen and other exotic fuels for vehicles, to fill a market estimated to be worth $1 trillion.
It will be a challenge to cultivate fuel-spewing microbes, Venter acknowledged. Among other problems is that unless the fuel is constantly removed, "the bugs will basically pickle themselves."
But the hurdles are not insurmountable. LS9 Inc., in San Carlos, Calif., is already using E. coli bacteria that have been reprogrammed with synthetic DNA to efficiently produce a fuel alternative from a diet of corn syrup and sugar cane.
At a DuPont plant in Tennessee, semi-synthetic bacteria are living on cornstarch and making the chemical 1,3 propanediol, or PDO. Millions of pounds of the stuff are being spun and woven into high-tech fabrics, putting the bug-begotten chemical on track to become the first $1 billion biotech product that is not a pharmaceutical.
Yet another application is in medicine: Synthetic DNA is allowing bacteria and yeast to produce the malaria drug artemisinin far more efficiently than it is made in plants, its natural source.
The prospect of a flourishing synbio economy has many wondering who will own the valuable rights.
In the past year, the U.S. Patent and Trademark Office has been flooded with aggressive synthetic-biology claims. Some of Venter's applications, in particular, "are breathtaking in their scope," said MIT's Knight.
Safety concerns also loom large. Already a few scientists have made viruses from scratch. The pending ability to make bacteria - which, unlike viruses, can live and reproduce outside of a living body - raises new concerns about contamination, contagion and mischief.
"Ultimately synthetic biology means cheaper and widely accessible tools to build . . . artificial organisms that could pose grave threats to people and the planet. The danger is not just bio-terror but bio-error," concluded a recent report by the Ottawa-based ETC Group, one of many advocacy groups urging a ban on releasing synthetic organisms pending societal debate and regulation.
Many scientists say the threat has been overblown. Venter notes that his synthetic genomes are spiked with genes that make the microbes dependent on a rare nutrient not available in nature. And Pierce, of DuPont, says the company's bugs are too spoiled to survive outdoors.
"We've heard that before," said Jim Thomas, ETC Group's program manager, noting that genes engineered into crops have found their way into other plants despite assurances to the contrary. "The fact is, you can build viruses, and soon bacteria, from downloaded instructions on the Internet. Where's the oversight?"
Government controls on trade in dangerous microbes do not apply to the bits of DNA that can be used to create them. And while some industry groups have talked about policing the field themselves, the technology is quickly becoming so simple, experts say, that "bio hackers" will be able to download genetic programs and make novel life-forms.
Andrew Light, an environmental ethicist at the University of Washington in Seattle, said synthetic biology poses a conundrum. It has the double-edged ability to wreak biological havoc and also perhaps wean civilization from dirty 20th-century technologies and petroleum.
"For the environmental community, I think this is going to be a really hard choice," Light said.