Boffinry breakthrough: First self-replicating life with 'alien' DNA

After 15 years of trying, researchers have created a living, self-replicating, "semi-synthetic" organism with DNA that contains not just the four paired bases that occur in all living things, but also an alien base pair created in the labs.

"What we have now is a living cell that literally stores increased genetic information," lead researcher Floyd Romesberg of the Scripps Research Institute in La Jolla, California, told Nature, which published the paper, "A semi-synthetic organism with an expanded genetic alphabet," online on Wednesday.

"Life on Earth in all its diversity is encoded by only two pairs of DNA bases, A-T and C-G, and what we've made is an organism that stably contains those two plus a third, unnatural pair of bases," Romesberg said in a Scripps Institute press release.

"This shows that other solutions to storing information are possible and, of course, takes us closer to an expanded-DNA biology that will have many exciting applications – from new medicines to new kinds of nanotechnology."

The DNA bases to which Romesberg was referring are adenine (A), thymine (T), cytosine (C), and guanine (G). The "unnatural pair", discovered after years of research on 60 candidates and 3,600 combinations, are d5SICS and dNaM, which pioneering synthetic biologist Steven Benner told Nature bear little chemical resemblance to the four natural ones.

What Romesberg and his team managed to do was insert a small loop of DNA – a plasmid into an Escherichia coli cell – that's E. coli to you and me, a bacteria that's usually harmless but can occasionally be quite nasty, indeed.

When the E. coli bacteria replicated, it not only copied its natural DNA, but also created a new pair of the alien bases, and kept doing so generation after generation for nearly a week, until the supply of the nucleoside triphosphates necessary to build the alien bases, which were in a fluid surrounding the bacteria, ran out.

That need for an alien feedstock might make you breath a little easier, knowing that when it runs out, the new E. coli simply reverted to their normal state. So much for mutant bacteria escaping into the wild and recreating a middling Hollywood potboiler starring Dustin Hoffman and Rene Russo.

But don't relax too quickly. According to Nature, some researchers – including the highly-respected Benner – are working to engineer cells that can replicate alien bases from scratch, thus making a supply of feedstock unnecessary.

"There are a lot of people concerned about synthetic biology because it deals with life, and those concerns are completely justified," Romesberg told The Guardian. "Society needs to understand what it is and make rational decisions about what it wants."

That is, do the dangers of continually self-replicating synthetic organisms outweigh the benefits of the ability to create new forms – or, at minimum engineer forms – of life? After all, semi-synthetic life forms could very useful – Nature, for example, cites inserting a toxic amino acid into a protein that would ensure that it would kill only cancer cells, or creating glowing amino acids that help researchers track biological reaction with optical microscopes.

And then there's the matter of creating completely artificial, self-replicating organisms – and on this Benner and Romesberg disagree. "I don't think there's any limit," says the former; "That's just not going to happen," says the latter.

"We're not going to bet on either," says The Reg. ®