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Harvard, Yale Scientists Develop Technique to Make GMOs Safer

Posted Jan 20, 2015

Reproduced from original publication on Boston Globe by Carolyn Y. Johnson

Two teams of scientists from Harvard and Yale have reached a crucial milestone in the effort to build synthetic life forms: a powerful way to prevent genetically modified organisms from escaping into the wild.

The new technique essentially inserts a built-in self-destruct mechanism into bacteria. The cells carry an alternative genetic code that makes them dependent on an artificial nutrient that is not found in nature.

Harvard Medical School genetics professor George Church, who oversaw one of the studies published Wednesday in the journal Nature, compared the new technique to putting a GMO “on a leash.” If scientists stop supplying a particular unnatural amino acid synthesized in the laboratory, the bacteria die.

The ability to tweak organisms’ DNA to give them new capabilities has long been tantalizing to biologists who already are turning microbes into factories that generate drugs and biofuels. But the wider use of engineered organisms -- for example, creating bacteria that can clean up a hazardous waste spill -- requires an effective leash to make sure they don’t escape scientists’ control.

The worries about escape are rooted in the uncertainty about what could happen. GMO bacteria might outcompete native strains, with unintended ripple effects on the environment. They also could unexpectedly transfer the genes that confer those powerful new traits to other organisms.

“I view us right now at the beginning of the biotech century, where I think a lot of solutions to defining global challenges ... are in large part going to result from advances in biotechnology,” said Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale, who led one of the studies. “In many ways, what we are doing is trying to be a step ahead of any challenges we might face.”

In extensive laboratory experiments, both groups saw no evidence the bacteria could find ways to escape the control measure. The two teams grew about 1 trillion cells and found that without the amino acid, the cells could not live.

“We’re changing the whole genome,” Church said. “So all genes, including the ones involved in producing whatever chemical you’re interested in, all those genes get changed. None of these can go in or out functionally.”

The technique works now in E. coli and although it could theoretically be applied to more sophisticated organisms such as plants, that application is far off today because of technical challenges, Isaacs and Church said.

Outside researchers and watchdog groups concerned about safeguards for genetically modified organisms said the research was an important first step.

Karmella Haynes, an assistant professor in the School of Biological and Health Systems Engineering at Arizona State University, said that what impressed her was that it was the very low rate of “escapers” compared with other techniques that have been tried.

“The problem is that we cannot quickly determine if every single GMO that is produced is absolutely safe or absolutely unsafe to people and the environment. The last thing we want to have happen is to figure out that something is dangerous through accidental release, after it is too late,” Haynes wrote in an email. “I feel that this research represents a step-change towards building reliable control switches for GMOs.”

Jaydee Hanson, policy director of the International Center for Technology Assessment, said that the research was limited because these first tests were done in traditional laboratory environments. It will be important, Hanson said, to test this technology in controlled environments that mimic the wild situations where they might ultimately be deployed.

“The basic idea in them is that can we engineer something so that if it gets out into the environment, or in the case of probiotics -- when it’s in your body -- so it doesn’t morph into something else,” Hanson said. “I hope their next step would be to run the experiment longer, and to make sure that you’re not having any problems after multiple generations.”

Both teams built on a feat they reported in October 2013, when they successfully recoded the genome by making fundamental and widespread changes to the DNA of bacteria. That left the organisms’ functions intact but made them more resistant to viruses.

In the new research, they started with such a recoded organism and decided to give it an Achilles’ heel -- making it dependent on a synthetic amino acid not found in nature that would have to be provided by researchers.

Todd Kuiken, a senior associate at the Woodrow Wilson International Centre for Scholars, said that it was significant that two research groups working separately arrived at almost exactly the same result.

“People have been talking about this as a potential way to deal with biocontainment,” Kuiken said. “This is the frist time there are actual research results and data showing this could work.”