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Happy birthday, DNA: Part 3

Of an ageless Clint Eastwood

Corrado Nai 23 February 2014

Timeless: DNA still has tricks up its sleeve

Still: are scientists playing God? Probably yes. But is this bad?

Editor's note: We are pleased to present the final instalment of a three-part essay in celebration of 60 years since the discovery of the double helix. You can use the navigation links above right to catch up.

Despite huge advancements in the study of molecular biology, DNA is still paramount. At its 60th birthday, people around the world are still interested in it because it is like the Clint Eastwood of molecules: charismatic and well-preserved despite its age.

Many things about DNA are still mysterious. The majority of sequences initially thought to be “junk” DNA, namely regions predominant in every genome that do not code for any protein, are now recognized as essential for protein synthesis due to their regulation of gene expression [31]. In fact, about 80% of the human genome is transcribed into RNA, while only about 1% accounts for protein synthesis. (In humans, that translates to DNA being composed of over 6 billion nucleotide bases yet coding for only about 20,000 proteins. [27]).

A few years ago scientists led by biotech entrepreneur J. Craig Venter edited a new book: they created a “synthetic cell” in the laboratory by transplanting a chemically synthesized DNA sequence into a recipient bacterium [32]. This cell was able to double itself and have a life of its own, which raises several ethic considerations. It should be noted that these “editors” were prone to plagiarism: the synthetic DNA in question was largely derived from the genome of a “related” organism, Mycoplasma mycoides. They were creative editors, though: the “fake” genome in the synthetic cell included some “watermark” sequences, that when deciphered resulted in coded messages including a quote by James Joyce, “To live, to err, to fall, to triumph, to recreate life out of life.”

Still: are scientists playing God? Probably yes. But is this bad? I believe not, if we are cautious with the powerful tools, not well understood by the vast majority of people, which are available today. And scientists need to be on careful lookout for the public showing signs of demonizing particular advancements in science, a phenomenon that can be primarily and effectively pre-empted and defeated by science communication.

Recently, molecular biologists honed their skills even further. Just as was the case 60 years ago, all it started down at the pub, where scientists Ewan Birney and Nick Goldman had a chat over a beer about how to write a new DNA text – literally [33].

In a study published in the journal Nature [34], the authors exploited the text features of DNA (linearity, readability and writeability) to design a biological way to store large amount of data. Instead of a binary code as in computer programming, they created a ternary code based on the nucleotide bases. Since there are four bases, though, the three-letter code was defined in a scheme excluding the formation of homopolymers (adjacent repetition of A, T, G or C), an important feature because to read the DNA with next-generation sequencing, and thus retrieve the stored information, stretches of identical nucleotide bases pose a challenge.

The scientists were able to encode a bunch of digital information with DNA text including all 154 of Shakespeare’s sonnets, a colour picture, an excerpt of Martin Luther King’s “I have a dream” speech and Watson & Crick classic paper. The information was converted into a hypothetical long DNA molecule comprising several short overlapping pieces. Since the ability to chemically synthesize very long DNA molecules from scratch in the lab is still a challenge as of today, the scientists synthesized 117-nucleotides long stretches of DNA fragments that, when merged due to the overlapping, result in the total stored information. Overlapping and redundancy resulting from multifold coverage of same DNA regions therefore enabled robust information storage.

The scientists then dried the DNA to a tiny amount of whitish powder that can be kept unaltered virtually forever with zero maintenance, as DNA is very stable and can be easily stored at room temperature. Compared with the efforts required to maintain digital data, biological data storage is thus very attractive. As a proof of the validity of the method, the researchers re-hydrated the dried DNA and sequenced it, retrieving all of the stored information with 100% accuracy.

The fascination of the method is that DNA, besides its intrinsic stability and easy maintenance in dried form, is and will (probably) always be a scientific hotspot. It’s like if people in 300 years’ time would watch Clint Eastwood’s westerns with increasing enthusiasm as it acquired more and more retro-chic cache. High costs of using DNA for data storage and retrieval, about $12.5k each MB – at present the main drawback of the method – will probably be reduced as a side-effect of scientific advancements in molecular biology.

The data-storing DNA is of course an artificial molecule and as such, incapable of coding for life. Just to make an example, natural production of several amino acids is impossible without homopolymers in the genetic code. So the common bugbear in people’s collective imaginations when talking about manipulation, synthesis and storage of DNA is (at least here) largely unjustified.

Possible science-fiction scenarios are a long shot too. But parallels with famous books and films are sublime. If DNA is exploited as a new text code, will there be a future in which people read DNA letters instead of the current alphabet, as for Morpheus reading binary codes from a huge screen in The Matrix trilogy? And what about book censorship in dystopian societies? Repressive governments won’t need a fire department as in Fahrenheit 451 k – only a sprinkle of nucleases.

To show how DNA is still fascinating mankind, it’s interesting to note how its obstetricians are glorified. In April this past year, a 1953 letter from Francis Crick to his then twelve-years-old son, in which he announces how he and Watson built the DNA model, was auctioned at £3.45million [35]. As if a prepubescent child would give a hoot about his daddy’s achievements in the lab. Crick writes how “we made a most important discovery” and that “our structure is very beautiful” [36]. Unfortunately the latter cannot be said about his awkward drawing of the DNA structure, from which one could assume that as a child Crick was more versed with Lego than with crayons.

Anyway: Happy Birthday, DNA.