--pws
A quest to create life out of synthetics
New science spurs high hopes, worry
CAMBRIDGE - It is science so new that even Harvard does not yet offer a formal course in it, although some of the field's pioneering research has been done at the university as well as down the avenue at MIT.
Sometimes called "genetic engineering on steroids," synthetic biology is a fuzzily-defined but fast-emerging science that some believe will transform genetic approaches to research in medicine, energy, ecology, agriculture, and more in the coming decades. At heart, it is about building living entities from lifeless chemicals.
Instead of just modifying existing organisms - as genetic engineers have done for 30 years - synthetic biologists are itching to build all-new life forms from artificial DNA.
"The idea is to synthesize DNA in an organized way, so we don't have to rely on nature to make useful things," said Pamela A. Silver, a Harvard Medical School professor, who will teach the university's first synthetic biology course in the fall.
Imagined uses include pollution-gobbling artificial microbes, "living" computers made of biocomponents, synthetic body cells programmed to hunt tumors, ecodwellings grown literally from seed, and even roses rigged with genetic "switches" that cause them to bloom and exude perfume on your birthday.
But synthetic biology inspires dread among those convinced it will allow terrorists to easily assemble smallpox-like viruses and other bioweapons. Also alarming to some detractors is that the science may confer on practitioners the most awesome power of all - that of creating life.
"Synthetic biologists aren't just mapping genomes and manipulating genes; they are making life from scratch," said Jim Thomas, an activist with ETC Group, a technology watchdog based in Canada. "The science is proceeding with very little in the way of societal debate or regulatory oversight."
Indeed, J. Craig Venter - the razzle-dazzle researcher-entrepreneur who played a key role in sequencing the human genome - announced earlier this year that his scientific team had assembled the entire genetic structure of a bacterium from off-the-shelf chemical components. That is just a baby step from forging synthetic life, a feat Venter expects to accomplish by the end of this year.
"If our plan succeeds, a new creature will have entered the world," Venter recently told reporters.
While critics warn of dangers, synthetic biologists see their work as just common-sense application of engineering principles to the assembly of biological entities.
Too much of genetic engineering, they say, has involved tweezing a strand of DNA here or inserting a bit of DNA there, and then waiting to see what happens. What is needed are standardized parts and assembly procedures so that swaths of DNA and other genetic structures can be created without the biological equivalent of constantly re-inventing the wheel.
"Old-fashioned genetics was mostly about trial and error and/or single-gene modifications," said George M. Church, professor of genetics at Harvard. "Synthetic biology is about systems-engineering, i.e. computer-aided design using . . . interoperable, standardized parts."
Church, like many academic researchers in the field, is also cofounder of a company aiming to make profit-yielding products - in his case, a California-based venture called LS9. The company is fine-tuning synthetic bacteria to convert corn and other agricultural material directly into gasoline and diesel without need for refineries..
On the medical front, scientist Jay D. Keasling at the University of California, Berkeley - armed with $42.6 million from the Bill & Melinda Gates Foundation - is closing in on a process for mass-producing inexpensive artemisinin, a potent antimalarial drug that now comes from wormwood shrub plantations. The new "factory" would assemble the drug from yeast, E. coli bacteria, and synthetic wormwood genes.
But opponents see this humanitarian endeavor as a threat.
"What happens to struggling farmers when laboratory vats in California replace [wormwood] farms in Asia and East Africa?" asked Thomas, the antisynthetic biology activist.
"It's a microcosm of what's occurring everywhere in the field: Alliances are building between big academia, big chemical companies, big energy companies, and big agribusiness," he said. "Scientists are making strands of DNA that have never existed, so there is nothing to compare them to. There's no agreed mechanisms for safety, no policies."
But "synthetic biology offers far more positive aspects than negative," said Harvard's Church.
At the Massachusetts Institute of Technology, biological engineer Drew Endy and colleagues have created a "Registry of Standard Biological Parts," an inventory of DNA strings that can perform predictable functions, such as switching on a gene or lending buoyancy to cells. The open-access inventory has grown from a few dozen interchangeable biological modules, called BioBricks, to more than 2,000. One playful sequence imparts the odor of mint to poop-smelling E. coli.
"I see it as a bit like the 'matter compiler' on Star Trek," Endy said, referring to a device on the fictional Starship Enterprise that made new objects out of basic atoms.
"Yes, huge new questions are starting to emerge - clearly this technology could be dangerous in the wrong hands. But it could lead to wondrous life improvements in the right hands," Endy said.
While critical early work is quietly ongoing in the engineering of future fuels and pharmaceuticals, much of the limelight is falling on Venter's plan to create a new life form.
Centerpiece of the project is a loathsome bacterium, Mycoplasma genitalium, a parasite that usually haunts the genital tract. It was chosen for its genetic simplicity - with just 582,970 units in its DNA composition, compared with 3 billion in humans - not its loveliness.
In January, Venter and his team at the J. Craig Venter Institute, an organization based in Maryland, grabbed worldwide headlines upon creating the entire genome of the Mycoplasma bacterium, a feat accomplished by using special synthesizing machines to churn out 101 custom-built DNA "cassettes," or snippets, each representing about 1 percent of the bacterium's genome.
These, in turn, were stitched into larger pieces, using bacteria and yeast as natural production lines; until finally the snippets were placed in the correct order - the first true copy of an entire bacterial chromosome.
"This entire process started with four bottles of chemicals, containing what's represented by A, G, C, and T," Venter told reporters, referring to the chemical building blocks of DNA.
Venter has predicted that sometime this year his team will implant the synthetic chromosome into a living microbe, then "boot" it up - effectively creating an entirely new organism.
That will mark an extraordinary milestone for synthetic biology.
"The future of life depends not only in our ability to understand and use DNA, but also in creating new synthetic life forms," Venter said in a recent academic lecture delivered on the BBC. "That is, life which is forged not by Darwinian evolution, but created by human intelligence."
Colin Nickerson can be reached at nickerson@globe.com.
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