Scientists Add New Letters to Life’s Genetic Alphabet

Scientists have created the first organism with synthetic DNA that can replicate in a cell, an achievement that promises to add new letters to the genetic code underlying life on earth.

In the natural world, just two chemical base pairs, known simply as A-T and C-G, constitute the building blocks of DNA in all life forms. Research published yesterday in the journal Nature describes the creation of a cell that contains a man-made base pair, dubbed d5SICS-dNAM.

By expanding the natural boundaries of what constitutes life, scientists hope they can one day create new proteins that can handle a variety of chores in the body, potentially leading to unique ways to attack disease. The approach is safe, the researchers said, because it includes a chemical additive that the cell needs to survive.

“We created an organism that lives and stably harbors genetic information in its DNA,” said Floyd Romesberg, a chemist at La Jolla, California-based Scripps Research Institute, whose laboratory created the new organism. “Instead of two base pairs, it has a third.”

All life on earth is based on the combination of four chemicals. Adenine bonds naturally with thymine to create the A-T section of the formula, while guanine and cytosine make up the C-G part. The joining of these base pairs in different combinations creates amino acids and proteins that power life.

Romesberg’s work differs from other research in the field of genetic engineering in that it involves creation of components that are purely synthetic and “integrated into the machinery of life in a cell,” he said in a telephone interview.

5-Year Push

Other scientists in the field, notably J. Craig Venter, work by constructing genetic material from natural building blocks, or natural components of DNA and proteins.

Starting in 2009, Romesberg and his laboratory created about 300 nucleotides with the newly constituted DNA before landing on ones they believed might be able to replicate in a cell. They then used a special chemical transporter to get the synthetic base pair into an E.coli cell, where it replicated without affecting cell growth. That suggests it wasn’t recognized as atypical by the body’s natural DNA repair machinery, according to the paper.

Synthorx Inc., a San Diego-based biotechnology company, has exclusive rights to the synthetic biology from Scripps. The company plans to focus on developing the technology for use in vaccines, medicines and diagnostics, the company said yesterday in a statement.

Raised Eyebrows

The research, though promising for fields of medicine and drug development, will probably raise ethical and safety concerns, said Arthur Caplan, head of the division of bioethics at NYU Langone Medical School. He called the research promising.

“Adding alphabetic letters to the genomic code will raise eyebrows about making novel life forms, but I really don’t believe the ‘playing god’ objection has much traction,” Caplan said in an interview. “There are many potential benefits, if they can control it.”

More concerning, Caplan said, are inadequate guidelines to ensure safety and preventing the use of techniques by those outside responsible spheres of universities and research institutes.

“We still don’t have good guidelines about releasing genetically altered microbes into the environment, into humans,” he said. “We’re not there yet with good rules. But we do need some standards and guidelines in place internationally.”

Making Proteins

For Romesberg’s team, an important next goal is to see whether the synthetic bases can be made to produce proteins, a feat he predicts may happen in just two years.

“From a practical perspective, we are interested in exploring the potential of expanding the evolution of proteins to include proteins with unnatural amino acids,” Romesberg said. One potential application may be the ability to combine protein-based medications that are the hallmark of biotech with traditional small molecule drugs.

“We have now given the genetic alphabet a new letter,” Romesberg said.

To contact the reporter on this story: Angela Zimm in Boston at azimm@bloomberg.net

To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net Andrew Pollack

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