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Creating the genetic firewall

Genetically recoded organisms could be safe enough to use to clean up oil spills or break down toxic chemicals

Scientists have created genetically modified organisms that can do vital tasks without the risk of escaping into the wild and causing damage

Synthetic amino acids may one day allow scientists to create "genetic firewalls" that prevent genetically modified crops or animals from escaping into the wild and causing environmental damage, according to Harvard and Yale researchers in the US.

The scientists have created the first genetically modified organisms that can only survive in the presence of designer compounds not found in nature.

The work represents a major step towards the creation of genetically modified life forms that are completely reconfigured to perform an important job and then die without trace when their task is done.

"I don't want to be alarmist or anything, but I think the point is that these organisms do spread," said George Church, a lead researcher and Harvard Medical School genetics professor.

"It's a scenario. You want to get ahead of these things, rather than wait until you have a problem," he said.

Vats of genetically modified microbes are already used to make various chemicals, drugs and dairy products, but the newly designed organisms could be safe enough to use outside, for example to clean up oil spills or break down toxic chemicals on contaminated land. Other bugs based on the same procedure might be put in drinks as probiotics to cure diseases.

Church and his colleagues at Harvard and Yale universities made changes throughout the genome of E coli bugs to make them resistant to viruses and reliant upon designer amino acids to survive. Amino acids are the building blocks of proteins that the organisms need to live and multiply.

The researchers call the new microbes "genetically recoded organisms", because they have a new kind of genetic code that ensures they can only thrive when they have been fed the synthetic amino acids.

A similar procedure could be used to improve genetically modified crops, but the task is far tougher because plants have about 10 times as many genes that are used to make proteins.

"We do consider this a new class of organism," Church said. "It's not just a new species. In a way it's a new kingdom."

Scientists have created genetically modified bugs before that need a particular chemical to survive, but the safety mechanism has always been vulnerable.

The bugs might find the chemical in the environment, pick up DNA from other microbes that lets them use other nutrients, or mutate into a form that can survive without the chemical.

In two separate papers published in the journal , teams led by George Church at Harvard and Farren Isaacs at Yale demonstrate that their designer bugs are far less able to overcome the "kill" mechanism engineered into their DNA.

There are two reasons. The first is that the E coli was engineered in such way that it would need tens of precise mutations to survive without the artificial amino acid. Second, the synthetic amino acid that the bugs live on was designed to look like no other compound found in nature, slashing the chances of the bugs finding a way to live off a similar natural compound.

In lab tests, Church grew a trillion of the modified E coli and found that none had evolved to survive without the synthetic amino acid.

Other changes in the microbes' DNA made them resistant to viruses that attack bacteria, giving them a built-in defence against infections that can wipe out fermentation and other industrial processes that rely on healthy microbes. To spread, viruses need to hijack a cell's molecular machinery, but the genetic changes in the E coli made it extremely hard for at least two viruses to do that.

Church said he developed the procedure to prevent genetically modified bugs spreading after spillages, leaks or their intentional use in the wild. "You want to get ahead of these things rather that wait until you have a problem," he said. "It's good to get a safety mechanism in place."

Isaacs said the new technique paved the way for wider use of engineered bugs. "Endowing them with safety guards now is going to be important in allowing the field to go forward," he said.

This article appeared in the South China Morning Post print edition as: Creating the genetic firewall
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