Normal DNA, which is characterized by the double helix and its the four bases that bond it together – known as T, G, A, and C – is at the heart of all living organisms. While permutations and differences exist between species, this basic structure has existed unchanged for billions of years. That is, until now. This past May, researchers announced that they had created the first ever organism with synthetic DNA that has two new bases – X and Y. Mary Shelley and H.G. Wells must be turning over in their graves, as scientists are officially playing God now!
This landmark study, 15 years in the making, was carried out by scientists at the Scripps Research Institute and published in Nature today under the title “A semi-synthetic organism with an expanded genetic alphabet”. In normal DNA, the four bases combine in predictable ways. A always bonds with T, and C always bonds with G, creating a fairly simple “language” of base pairs — ATCGAAATGCC, etc. Combine a few dozen base pairs together in a long strand of DNA and you then have a gene, which tells the organism how to produce a certain protein.
If you know the sequence of letters down one strand of the helix, you always know what other letter is. This “complementarity” is the fundamental reason why a DNA helix can be split down the middle, and then have the other half perfectly recreated. In this new study, the Scripps scientists found a method of inserting a new base pair into the DNA of an e. coli bacterium. These two new bases are represented by the letters X and Y, but the actual chemicals are described as “d5SICS” and “dNaM.”
A previous in vitro (test tube) study had shown that these two chemicals were compatible with the enzymes that split and copy DNA. For the purposes of this study, the scientists began by genetically engineering an e. coli bacterium to allow the new chemicals (d5SICS and dNaM) through the cell membrane. Then they inserted a DNA plasmid (a small loop of DNA) that contained a single XY base pair into the bacterium.
As long as the new chemicals were available, the bacterium continued to reproduce normally, copying and passing on the new DNA, alien plasmid and all, and continued to carry on flawlessly for almost a week. For now, the XY base pair does nothing; it just sits there in the DNA, waiting to be copied. In this form, it could be used as biological data storage which, as a new form of biocomputing, could result in hundreds of terabytes of data being stored in a single gram of synthetic, alien DNA.
Floyd Romesberg, who led the research, has much grander plans:
If you read a book that was written with four letters, you’re not going to be able to tell many interesting stories. If you’re given more letters, you can invent new words, you can find new ways to use those words and you can probably tell more interesting stories.
Now his target is to find a way of getting the alien DNA to actually do something, such as producing amino acids (and thus proteins) that aren’t found in nature. If Romesberg and his colleagues can crack that nut, then it will suddenly become possible to engineer cells that produce proteins that target cancer cells, or special amino acids that help with fluorescent microscopy, or new drugs/gene therapies that do weird and wonderful things.
Ultimately it may even be possible to create a wholly synthetic organism with DNA that contains dozens (or hundreds) of different base pairs that can produce an almost infinitely complex library of amino acids and proteins. At that point, we’d basically be rewriting some four billion years of evolution. The organisms and creatures that would arise would be unrecognizable, and be capable of just about anything that a researcher (or mad scientist) could dream up.
In the future, this breakthrough should allow for the creation of highly customized organisms – bacteria, animals, humans – that behave in weird and wonderful ways that mundane four-base DNA would never allow. At the same time, it raises ethical dilemmas and fears that may be well founded. But such is the nature of breakthroughs. The potential for harm and good are always presumably equal when they are firts conceived.