Cloning Genetic Engineering

By: Rejaul Alam

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Cloning & Genetic Engineering - Video

Scientists reprogrammed the common bacterium E. coli so it requires a synthetic amino acid to live. BSIP/UIG via Getty Images hide caption

Scientists reprogrammed the common bacterium E. coli so it requires a synthetic amino acid to live.

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).

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Scientists Give Genetically Modified Organisms A Safety Switch

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Synthetic biologists hope to treat disease in the gut by making Lactobacillus bacteria (pictured) that are dependent on an artificial amino acid.

Critics of genetic engineering have long worried about the risk of modified organisms escaping into the environment. A biological-containment strategy described this week in Nature1, 2 has the potential to put some of those fears to rest and to pave the way for greater use of engineered organisms in areas such as agriculture, medicine and environmental clean-up.

Two US teams have produced genetically modified (GM) bacteria that depend on a protein building block an amino acid that does not occur in nature. The bacteria thrive in the laboratory, growing robustly as long as the unnatural amino acid is included in their diet. But several experiments involving 100billion or more cells and lasting up to 20days did not reveal a single microbe capable of surviving in the absence of the artificial supplement.

Our strains, to the extent that we can test them, wont escape, says Dan Mandell, a synthetic biologist at Harvard Medical School in Boston, Massachusetts, and an author on one of the two studies describing the strategy.

The microbes also do not swap their engineered DNA with natural counterparts because they no longer speak lifes shared biochemical language. Establishing safety and security from the get-go will really enable broad and open use of engineered organisms, says Farren Isaacs, a synthetic biologist at Yale University in New Haven, Connecticut, who led the other study.

Biocontainment could provide added safety in the biological production of drugs or fuels, where microbes can be kept separate from their surroundings. But the modified bacteria could also permit controlled release into the human body or the environment. Containment might no longer be of the physical kind, says Tom Ellis, a synthetic biologist at Imperial College London who was not involved in the research.

The new technique originated in the laboratory of George Church, a geneticist at Harvard Medical School. Two years ago, Church and his team (which included Isaacs) reported the synthesis of a strain of Escherichia coli that had a reprogrammed genetic code3. Instead of recognizing a particular DNA triplet known as the amber stop codon as an order to terminate protein synthesis, the recoded bacterium read the same instruction as a directive to incorporate a new kind of amino acid into its proteins.

Church and Isaacs have independently made this engineered microbe reliant on unnatural amino acids. The Isaacs team used genomic sequencing to identify sites in essential bacterial proteins where the microbes could incorporate synthetic amino acids without affecting overall function, whereas Churchs group started with the protein structures and added elements to help integrate and accommodate the artificial amino acids.

This is really the culmination of a decade of work, says Church.

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GM microbes created that cant escape the lab