Coolness. Bring on the mutants.
Chemical biology: DNA's new alphabetDNA has been around for billions of years — but that doesn't mean scientists can't make it better
When Steven Benner set out to re-engineer genetic molecules, he didn't think much of DNA. “The first thing you realize is that it is a stupid design,” says Benner, a biological chemist at the Foundation for Applied Molecular Evolution in Gainesville, Florida.
Take DNA's backbone, which contains repeating, negatively charged phosphate groups. Because negative charges repel each other, this feature should make it harder for two DNA strands to stick together in a double helix. Then there are the two types of base-pairing: adenine (A) to thymine (T) and cytosine (C) to guanine (G). Both pairs are held together by hydrogen bonds, but those bonds are weak and easily broken up by water, something that the cell is full of. “You're trusting your valuable genetic inheritance that you're sending on to your children to hydrogen bonds in water?” says Benner. “If you were a chemist setting out to design this thing, you wouldn't do it this way at all.”
Life may have had good reasons for settling on this structure, but that hasn't stopped Benner and others from trying to change it. Over the past few decades, they have tinkered with DNA's basic building blocks and developed a menagerie of exotic letters beyond A, T, C and G that can partner up and be copied in similar ways. But the work has presented “one goddamn problem after another”, says Benner. So far, only a few of these unnatural base pairs can be inserted into DNA consecutively, and cells are still not able to fully adopt the foreign biochemistry.
The re-engineering of DNA, and its cousin RNA, has practical goals. Artificial base pairs are already used to detect viruses and may find other uses in medicine. But scientists are also driven by the sheer novelty of it all. Eventually, they hope to develop organisms with an expanded genetic alphabet that can store more information, or perhaps ones driven by a genome with no natural letters at all. In creating these life forms, researchers could learn more about the fundamental constraints on the structure of genetic molecules and determine whether the natural bases are necessary for life or simply one solution of many. “Earth has done it a certain way in its biology,” says Gerald Joyce, a nucleic-acid biochemist at the Scripps Research Institute in La Jolla, California. “But in principle there are other ways to achieve those ends.”
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Topic: Chemical biology: DNA's new alphabet