Scientists Successfully Engineer Organism With 6-Letter DNA


Mimi Liu
Staff Writer

Researchers at The Scripps Research Institute at La Jolla, Calif., have created a bacterium with a genome containing artificial DNA. This exciting discovery could possibly lead to personalized organisms designed to produce important drugs and vaccines.

All creatures have a genetic code composed of four nucleotides represented by G, A, T, and C. These letters contain the instructions for proteins that perform important functions inside of cells, and deriving new letters could mean the creation of new proteins.

Scripps researchers have chemically created new nucleotides named X and Y, successfully producing the first bacterium with a six-letter DNA. Work on artificial DNA has been carried out for more than 20 years, but it is only now that that it has been successfully integrated and functional in a living cell. Scientists inserted an XY pair of nucleotides into the bacterium e. coli and watched the resulting reproduction. The bacteria reproduced normally and successfully replicated the X and Y nucleotides in addition to its regular ones.

“If you can have a language that has a certain number of letters, you want to add letters so you can write more words and tell more stories,” said Floyd Romesburg, chemical biologist and lead researcher at the Institute.

Romesburg’s lab of chemical biology and biophysics at Scripps aims to further understanding of evolution, explore its possibilities, and develop new antibiotics. Romesburg has co-founded the company Synthorx to pursue the full potential of this development in regard to vaccine and antibiotic synthesis.

His research has been published by the journal Nature, and is predicted to cause controversy over the ethics of altering a living organism’s DNA. This discovery also furthers the arguments of those pushing for more stringent regulation of synthesis biology, which involves creating biological organisms for a specific purpose.

“The arrival of this unprecedented ‘alien’ life form could in time have far-reaching ethical, legal, and regulatory implications,” says Jim Thomas of the ETC group, a Canadian advocacy organization. “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 regulations for this surging field.”

Dr. Romesburg dispelled worries, stating that synthetic nucleotides cannot survive if not routinely injected. Additionally, modification of organisms is a complex process. Romesburg and his colleagues had to create over three hundred variations of nucleotides before finding nucleotides stable enough to be replicated by the bacteria.

The process they used to find the X and Y nucleotides involved chloroplasts, which are present in plants. Chloroplasts are unique in that they are able to import nucleotides from surrounding tissue; the genes controlling this process have already been determined. Romesburg and his team harnessed this ability by splicing certain genes from algae into the e. coli genome, which allowed the bacterium to import X and Y nucleotides from its surroundings.

“This work is an astounding technical feat,” said Irene Chen, University of California, Santa Barbara assistant professor and biochemist. “It represents the ultimate safety mechanism for genetic engineering. If you insert a gene using these new bases, the gene has almost no chance of escaping the lab because the organism must be fed those man-made bases as food.”

Synthorx is currently examining the cultivation of bacteria to be used as live vaccines, but there will be some time before this process is viable. Scientists have not yet proven that the artificial nucleotides can be used to create proteins, and it is unknown how long bacteria can retain the new information.

“Broadly speaking, [this discovery] suggests that you could use the new bases to make as-yet-undiscovered functional molecules… Perhaps more exciting would be to use these bases to define a new genetic code.” Chen said. “That will take a lot more work, but the potential to evolve a new biology is there.”