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There are four building blocks to all life - the catchily named adenine, thymine, cytosine and guanine, or A, T, C and G. They are the nucleotides found in DNA, and every living creature is "built" upon combinations of pairs of these nucleotides. Now, a team from The Scripps Research Institute has upended this fabric of life to create two new synthetic nucleotides (X and Y) and has embedded them in the genetic code of E. coli bacteria.
The team first attempted this task in 2014, but the bacteria failed to hold on to the additional genetic code as cell division took place and died shortly afterwards. "Your genome has to be stable for the scale of your lifetime,” explained professor Floyd Romesberg in a statement. “If the semisynthetic organism is going to really be an organism, it has to be able to stably maintain that information."
Working with graduate student Yorke Zhang and American Cancer Society postdoctoral fellow Brian Lamb, Romesberg returned to engineer these new building blocks. They first modified the nucleotide transporter previously used by the Scripps team to transport the synthetic base pair to the cell. This transporter is responsible for moving molecules around cells. The Y building block was modified further so that the enzymes responsible for synthesising DNA recognised it and would cause it to replicate.
Gene editing tool CRISPR-Cas9 was then used as a means of building genetic self-protection measures into the E. coli. Consequently, the new organism was able to recognise any genetic sequence lacking X or Y as an outside threat meaning only the cells containing X and Y survived.
"We were able to address the problem at a fundamental level," said Lamb. As a result of the changes, the new organism replicated 60 times. The team has taken this as a sign the organism will replicate and hold onto the code indefinitely. Romesberg boldly - and broadly - concluded: "That suggests all of life's processes can be subject to manipulation."
In the Proceedings of the National Academy of Sciences paper, the team says it believes that by “expand[ing[ the alphabet” of genetic building blocks, they have managed to create a “stable form of semisynthetic life [that] lays the foundation for efforts to impart life with new forms and functions”.
The real-world applications, or even existence, of these kinds of “new forms and functions”, are a long way off and would largely be constrained to the lab and drug discovery fields. While human gene editing has already taken place in the search for cancer treatments, and manipulation of embryos legalised in the UK under specific circumstances in an attempt to put an end to an inherited disorder, there is absolutely no suggestion the kind of methodology described in the PNAS paper would be translated to organisms more complex than single-cell bacterium.
This article was originally published by WIRED UK
