ARTIFICIAL DNA YIELDS NEW LIFE FORMS

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 plagiarised 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 synthesising life?

At the core of synthetic biology’s new ascendance are high-speed DNA synthesisers 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 synthesiser 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.

“I see a cell as a chassis and power supply for the artificial systems we are putting together,” said Tom Knight of MIT, who likes to compare the state of cell biology today to that of mechanical engineering in 1864. That is when the US began to adopt standardised thread sizes for nuts and bolts, an advance that allowed the construction of complex devices from simple, interchangeable parts.

If biology is to morph into an engineering discipline, it is going to need similarly standardised parts, Knight said. So he and colleagues have started a collection of hundreds of interchangeable genetic components they call BioBricks, which students and others are already popping into cells like Lego pieces.

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 maximise productivity.

“Most cells go about life like we do, with the intention to make more of themselves after eating,” said John Pierce, a vice president at DuPont in Delaware, US, a leader in the field. “But what we want them to do is make stuff we want.”

J. Craig Venter, chief executive of Synthetic Genomics in Maryland, 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 products.

LS9 Inc., a company in California, is already using E. coli bacteria that have been reprogrammed with synthetic DNA to produce a fuel alternative from corn syrup and sugar cane. Engineers studied blueprints of E. coli’s metabolism and used synthetic DNA to help the bacteria become more efficient than with ordinary genetic engineering.

Yet another application is in medicine, where 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.

Bugs such as these will seem quaint, scientists say, once fully synthetic organisms are brought on line to work 24/7 on a range of tasks, from industrial production to chemical cleanups. But the prospect of a flourishing synbio economy has many wondering who will own the valuable rights to that life.

In the past year, the US Patent and Trademark Office has been flooded with aggressive synthetic-biology claims. Some of Venter’s applications “are breathtaking in their scope,” Knight said. And with Venter’s company openly hoping to develop “an operating system for biologically-based software,” some fear it is seeking synthetic hegemony.

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 in the environment outside of a living body—raises new concerns about contamination, contagion and potential for mischief.

“Ultimately synthetic biology means cheaper and widely accessible tools to build bioweapons, virulent pathogens and artificial organisms that could pose grave threats to people and the planet,” concluded a recent report by the Ottawa-based ETC Group, an advocacy groups that want a ban on releasing synthetic organisms pending wider societal debate and regulation. “The danger is not just bio-terror but bio-error,” the report says.

Many scientists say the threat has been overblown. Venter notes that his synthetic genomes are spiked with special 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. “They are designed to grow in a cosseted environment with very high food levels,” Pierce said. “You throw this guy out on the ground, he just can’t compete. He’s toast.”

Andrew Light, an environmental ethicist at the University of Washington in Seattle, said synthetic biology poses a conundrum because of its double-edged ability to both wreak biological havoc and perhaps wean civilisation from dirty 20th-century technologies and petroleum-based fuels. “For the environmental community, I think this is going to be a really hard choice,” Light said.

He adds, “It could be that synthetic biology is going to be like cellphones: so overwhelming and ubiquitous that no one notices it anymore. Or it could be like abortion—the kind of deep disagreement that will not go away.” The question, if the abortion model holds, is which side of the synthetic debate will call itself “pro-life.”
-Rick Weiss
(The Washington Post)