Scientists Give Genetically Modified Organisms A Safety Switch

Jan 21, 2015
Originally published on January 21, 2015 4:37 pm

Researchers at Harvard and Yale have used some extreme gene-manipulation tools to engineer safety features into designer organisms.

This work goes far beyond traditional genetic engineering, which involves moving a gene from one organism to another. In this case, they're actually rewriting the language of genetics.

The goal is to make modified organisms safer to use, and also to protect them against viruses that can wreak havoc on pharmaceutical production.

To understand what they've done, you may need to remember a bit of basic biology. The enzymes and other proteins in our bodies are all built from building blocks called amino acids. There are usually just 20 amino acids in nature. But George Church, a professor of genetics at Harvard Medical School, has created a bacterium that requires an additional amino acid, one made in the lab and not found in nature. His lab did that by rewriting the bacteria's genetic language to add a "word" that calls for this unnatural amino acid.

"So this really makes it a completely new branch of life," Church says.

These modified E. coli bacteria essentially speak a different genetic language from all other life on Earth. That means they can't easily swap genes, which bacteria often do to pick up or get rid of traits. And it also means that these modified E. coli must be fed the synthetic amino acid to survive.

"It will die as soon as you remove that essential nutrient," Church says.

The scientists say this radical re-engineering actually makes these synthetic life forms safer, because if they escape into the wild they'll die. One key question is whether these engineered bacteria can shed the traits that make them dependent on the synthetic amino acid. (Bacteria mutate all the time, picking up new traits and dropping others).

Church says that if his lab had modified just one trait, the bacteria would have a one in a million chance of getting rid of this safety feature. But by modifying several traits, he says the odds are more like one in a trillion that the bacteria can survive without the synthetic amino acid.

These modified organisms have another plus: With their altered genetic code, they are resistant to viruses that frequently attack bacteria. Viruses need the conventional DNA language in order to infect bacteria. So this is a selling point for industries that use E. coli.

"If you get your factory contaminated, it can be hard to clean out for a year," Church says, pointing to an episode at Genzyme Corp., a Cambridge, Mass., pharmaceutical manufacturer, in 2009. Viruses there contaminated a plant where bacteria were used to make drugs for two rare genetic disorders, Gaucher disease and Fabry disease, cutting off supplies.

And industrial uses are potentially just the start for engineered organisms.

"This also sets the stage for opening up new types of applications going forward," said Farren Isaacs , an assistant professor of molecular, cell, and developmental biology at Yale University. Isaacs left Church's lab at Harvard to start his own at Yale. He has kept pace with his former boss. He, too, has built some safety features into E. coli. Their reports were published together Wednesday in the journal Nature.

Other uses might include engineering oil-eating bacteria to use on a spill. They could be killed off when they're done by withholding the essential nutrient. Isaacs says scientists could also engineer bacteria to produce probiotics for human consumption.

It's harder to think about how this technology could be used in agriculture. Countless acres of genetically engineered crops would need to be fed this manmade ingredient, from a crop duster or by some other means. Scientists would also need to show that the synthetic protein component is safe to eat.

"I think it's commendable they're starting to design safety into genetically modified organisms," says Jennifer Kuzma, co-director of the Genetic Engineering and Society Center at North Carolina State University. "However, I don't really think it's going to affect the public perception that much or the way we have to deal with the uncertainty anyway. You may reduce the chance of spread, but you cannot eliminate it completely."

Science doesn't offer absolutes. But this technology is evolving quickly, and Church says it's important to engineer in safety features as they go.

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AUDIE CORNISH, HOST:

Genetic engineering is used for everything from crops like corn and cotton to designer drugs, and the technology is getting more sophisticated all the time. Scientists are even changing the language of genes by rewriting the genetic code. Researchers at Harvard and Yale are starting to use these tools to build safety features into designer organisms. Two studies in the journal Nature report a major step forward in that effort, as NPR's Richard Harris reports.

RICHARD HARRIS, BYLINE: First, a two sentence refresher on some basic biology. The enzymes and other proteins in our bodies are all built from building blocks called amino acids. There are usually just 20 amino acids in nature, but George Church at Harvard has created a bacterium that requires an additional amino acid - one made in the lab and not found in nature.

GEORGE CHURCH: So this really makes it a completely new branch of life.

HARRIS: These modified E. coli bacteria essentially speak a different genetic language from all other life on Earth. That means they can't easily swap genes which bacteria often due to pick up or get rid of traits. And it also means that these modified bacteria must be fed this synthetic amino acid.

CHURCH: It will die as soon as you remove that essential nutrient.

HARRIS: It's a radical reengineering of life, but Church says this actually makes these synthetic life forms safer because if they escape into the wild they'll die. And it also makes them less vulnerable to being infected by viruses. Yes, bacteria get infections, too. That's a selling point for the biotech industry which uses bacteria to make things like drugs. Those operations are vulnerable to viral infections.

CHURCH: If you get your factory contaminated, it can be hard to clean out for year.

HARRIS: So Church is hoping that industry will want to start using these highly engineered bacteria not for the safety considerations as much as to help them avoid contamination.

CHURCH: We get two or three things for the price of one.

HARRIS: How do you know it won't mutate and be able to basically shake off these traits that you've added?

CHURCH: Well, we anticipated it would be able to mutate and shake off the traits if we just did one.

HARRIS: With one modified gene, Church found that there's a one-in-a-million chance that the bacteria could once again live in the wild without the synthetic amino acid. But by modifying multiple genes, the odds of that drop sharply.

CHURCH: So the current strains are at least one-in-a-trillion, if not, better than that.

HARRIS: Farren Isaacs who left Church's lab at Harvard to start his own at Yale has kept pace with his former boss. He too has built some safety features into E. coli, and he says it's possible to use this approach for all sorts of other organisms - for example, bacteria that you spray on an oil spill to help clean it up or bacteria that produce probiotics for human consumption.

FARREN ISAACS: This also sets the stage for opening up new types of applications going forward.

HARRIS: It's harder to think about how this technology could be used in agriculture. If you build this into genetically engineered crops, you'd need to feed them the artificial amino acid that they'd require from crop dusters or something like that. And the artificial amino acid would be part of the grain, so you'd need to prove that it's safe to eat. Jennifer Kuzma is codirector of the Genetic Engineering and Society Center at North Carolina State.

JENNIFER KUZMA: I think it's commendable that they're starting to design safety into genetically modified organisms, however, I really don't think it's going to affect the public perception that much or the way we have to deal with the uncertainty anyway. You may reduce the chance of spread, but you cannot eliminate it completely.

HARRIS: Science doesn't offer absolutes, but this technology is evolving quickly, and George Church says it's important to engineer in safety features as they go. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.