Semi-Synthetic Organisms With A Six-Letter Genetic Code Are Now Reality

Brilliance | Dec. 08, 2017

You, I, and every living thing on Earth formed according to the four bases that make up our DNA. In 2016, scientists announced that they had engineered the world's first semi-synthetic organism—one with not four, but six bases. Welcome to the brave new world of synthetic biology.

How They Did It

This isn't the first time scientists—or even these scientists in particular—have tried giving DNA extra base pairs. The research team, which hails from California's Scripps Research Institute and is led by Floyd Romesberg, actually announced the exact same development back in 2014 with a paper in the journal Nature. For that experiment, the researchers engineered a synthetic base pair they called X and Y, to match with organic DNA's A and T, and C and G. Then, they inserted it into E. coli bacteria. The test went great—the E. coli DNA didn't hack off the new base pairs with its usual repair mechanisms, and the bacteria survived...mostly. It was weak, and the tool they used to enable the new base pair to be copied across the cell membrane (known as a nucleotide transporter) "made the semisynthetic organism very sick," coauthor Yorke Zhang told

So for the study they published in PNAS in 2016, they made some adjustments. They made the nucleotide transporter less toxic. They also changed the molecule they had used to make the Y base, which hadn't been easily recognized by the enzymes the bacteria used to replicate DNA. They then used the gene-editing tool CRISPR to alter other pieces of the E. coli genome in order to make sure it didn't fight off the new base pairs as invaders. It worked! The new E. coli they engineered were healthy, and more importantly, they kept the new base pairs as part of their own DNA for their entire lives.

What It Might Mean

Because the synthetic base pair can't really do anything—it's just a proof of concept—this is still a small step toward fully functional synthetic life. But once scientists can create new forms of DNA, there's no knowing what kinds of novel proteins synthetic life forms can create. Those proteins could lead to new drugs, medical tests, and research tools.

Of course, this possibility raises some safety and ethical concerns. The technology is very new, so governments haven't had time to catch up with safety regulations. After the research team's 2014 attempt, Jim Thomas of the ETC group told The New York Times, "While synthetic biologists invent new ways to monkey with the fundamentals of life, governments haven't even been able to cobble together the basics of oversight, assessment or regulation for this surging field." We'll have to wait and see how government and science deals with the virtually inevitable arrival of synthetic life.

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