A replicating “alien” life-form has been created by scientists who introduced DNA molecules not found in nature to a common bacterium.
The Escherichia coli (E. coli) bugs are able to grow and reproduce as normal despite containing two extra letters in their genetic code.
In future, the research could lead to creation of microbes capable of manufacturing entirely new proteins with potential applications in medicine and nanotechnology.
But the rapid advance of “synthetic biology” also raises the worrying prospect of new life-forms escaping from the laboratory with unpredictable consequences.
Nature’s genetic code consists of a DNA alphabet of just four “letters” - adenine (A), cytosine (C), guanine (G) and thymine(T).
An additional letter, uracil (U), is found in DNA’s close cousin molecule, RNA.
The A, C, G and T building blocks form “base pair” partnerships whose sequences write the text of the “book of life”.
Lead scientist Dr Floyd Romesberg, from the Scripps Research Institute in La Jolla, California, US, said: “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.
“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 work, reported in the journal Nature, involved overcoming a billion years of evolution to get the expanded genetic alphabet into living bacteria.
It started in 2008 when Dr Romesberg’s team of researchers succeeded in replicating unnatural base pairs in a test tube. They also managed to transcribe the semi-synthetic DNA into RNA, a first step towards translating a new genetic code into a protein.
But performing the same trick in the complex environment of a living cell presented much greater challenges.
To solve the problem the scientists first added the artificial base pair molecules – d5SICS and dNaM – to a fluid solution outside the cell.
Then they used a special transporter molecule, made by a species of micro-algae, to import them into the bacteria.
“That was a big breakthrough for us – an enabling breakthrough,” said co-author Dr Denis Malyshev, also from the Scripps Research Institute.
The scientists were able to synthesis circular loops of DNA known as plasmids and insert them into E. coli.
The plasmid DNA contained natural A-T and C-G base pairs together with a d5SICS-dNaM base pair.
Although the plasmids were separate from the organism’s integral chromosomal DNA, they became part of its replicating genetic material.
To the surprise of the team, the semi-synthetic plasmids did not hamper the growth of the E.coli bacteria to any great extent. Nor did they show any sign of shedding their artificial components.
The next step will be to demonstrate that unnatural DNA within bacteria can be transcribed into the RNA molecules that feed genetic instructions to protein-making machinery in cells.
“In principle, we could encode new proteins made from new, unnatural amino acids, which would give us greater power than ever to tailor protein therapeutics and diagnostics and laboratory reagents to have desired functions,” said Dr Romesberg. “Other applications, such as nanomaterials, are also possible.”
Commenting on the research in a Nature “News & Views” article, Ross Thyer and Jared Ellefson, from the University of Texas, wrote: “If the technique.. works for other pairs, then the DNA code could be extended well beyond three base pairs. This raises fundamental questions about why life settled on only two in the first place, and whether semi-synthetic organisms with the capacity to store more information will have expanded capabilities or endure intolerable fitness costs.”
They added: “Attempts to expand the genetic alphabet bravely question the idea of the universal nature of DNA, and potentially draw criticism about the wisdom of tinkering with it. Such criticisms should be solidly countered by synthetic biologists at the outset.”
Molecular biologist Dr David King, director of the watchdog group Human Genetics Alert, said: “Calling this ‘a semi-synthetic organism’ is typical misleading synthetic biology hype, since the exotic DNA contributes nothing to the life, to the functioning, of the bacteria.
“The idea that such systems will make bacteria that carry them safe is completely unproven – the one thing we know about life is its amazing ability to mutate and overcome such barriers to its survival. It’s time that government regulators got to grips with the long term implications of this science.”