Synthetic DNA Soon to Yield Artificial Life

By Rick Weiss
Washington Post, December 17, 2007

Edited by Andy Ross

Scientists in Maryland have built the world's first entirely handcrafted chromosome. It is a large looping strand of DNA made from scratch in a laboratory, containing all the instructions a microbe needs to live and reproduce. In 2008, they hope to transplant it into a cell, where it is expected to boot up and take over the cell.

Some companies are already gaining monopoly control over the core operating system for artificial life and are poised to become the Microsofts of synthetic biology.

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, then use a synthesizer to convert that digital code into actual DNA. Experiments indicate that when a chromosome is put into a cell, it will direct the destruction of the cell's old DNA and take over, 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. Knight 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, but in many cases that urge has been genetically suppressed, along with some other biological functions, to maximize productivity.

J. Craig Venter, chief executive of Synthetic Genomics in Rockville, wants his cells to make ethanol, hydrogen and other exotic fuels for vehicles, to fill a market 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. 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, 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 DNA modules to make synthetic fuels or other products.

It will be a challenge to cultivate fuel-spewing microbes, Venter acknowledged. Among other problems, he said, is that unless the fuel is constantly removed, "the bugs will basically pickle themselves."

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 once fully synthetic organisms are brought on line to work on 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 U.S. Patent and Trademark Office has been flooded with aggressive synthetic-biology claims. Some of Venter's applications "are breathtaking in their scope," said Knight. And with Venter's company openly hoping to develop "an operating system for biologically-based software," some fear it is seeking synthetic hegemony.

"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.

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 DuPont says the company's bugs are too spoiled to survive outdoors.

But the technology is quickly becoming so simple that it will not be long before biohackers working in garages will be downloading genetic programs and making them into novel life forms.