Until 2014 every living thing on the planet had four bases in its DNA, just like this mouse. Now, some bacteria have six instead. (NHGRI)
Scientists have created a stable organism containing DNA most likely never seen before on Earth.
The intention was to create "organisms with wholly unnatural attributes and traits not found elsewhere in nature,” as one of the researchers put it. With more advances, these organisms could potentially be used in the creation of medicines and industrial biologicals.
The development is described in a new study published in Proceedings of the National Academy of Sciences.
The building blocks of DNA, and thus of all life on Earth, are represented by a four-letter "alphabet." Each letter represents one of the compounds that form DNA. The letters—A, T, C and G—are used in different combinations to encode the instructions that govern the development and traits of living organisms.
Just as scrawled graffiti, a Harlequin romance and a Shakespeare play are written using the same alphabet, so too are a virus, a pig and a human being written with the same set of four bases.
That started to change back in 2014, when a group of researchers at The Scripps Research Institute synthesized two new letters, then managed to coax E.coli bacteria into accepting them. While that was a significant achievement, the bacteria was not ideal and suffered from multiple problems including a tendency not to pass the new letters on to the next generation. Since the artificial bases were not stable in the DNA, they were lost over time.
Back to the Beginning for CRISPR
One of the ways these researchers managed to get the bacteria to hold on to these new letters was by using one of the biggest things to hit biology in the last few years—the gene-editing system CRISPR/Cas9. This tool provides a way to precisely change the DNA of a living thing. It has already revolutionized science in the lab and may one day revolutionize human health as well.
CRISPR/Cas9 has a very humble origin—it works as an immune system for bacteria. It essentially looks for a certain set of bases found in an invading virus's DNA and cuts the viral DNA at that spot. This destroys the virus.
In creating their new organism, the researchers have taken CRISPR/Cas9 back to its original use. But instead of cutting the DNA of invading viruses, CRISPR/Cas9 now cuts the bacterial DNA, which kills the bacteria. Sounds self-defeating, except that it only does this if the bacteria has lost its new letters.
That means the bacteria that pass on the new letters thrive and continue to divide, while the letter-losing bacteria are wiped out. Now, generation after generation, only bacteria with the new bases are produced.
Of course this wouldn’t be all that efficient if the majority of bacteria lost the artificial bases and so died--there wouldn't be enough bacteria to do anything with.
To make it more likely that the bacteria hold onto their new bases, these researchers also chemically modified one of the bases to something the bacteria liked better. Now the bacteria are more likely to keep these bases, but if they do lose them, they are eliminated from the population. Such an elegant solution!
Though the bacteria has successfully incorporated the new letters, it is not actually using them, because the cellular machinery can’t decipher what the letters mean.
Scientists hope that won't always be the case. They intend on tweaking the bacteria so they can make sense of the new letters. Then the new organisms could be crafted into something useful. Down the line, researchers could also figure out how to expand the alphabet of more complex organisms.
Even if the bacteria the researchers experimented on isn’t yet ready for primetime, it is very cool in that it probably does things that life on Earth has never done before. Which is still a marvel for all science lovers out there.
Said one of the scientists, in a statement:
"We can now get the light of life to stay on. That suggests that all of life's processes can be subject to manipulation."
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