James Joyce's Words Come To Life, And Are Promptly Desecrated

By Carl Zimmer | May 21, 2010 1:51 pm

jamesjoyceThis old English major’s heart is warmed by the news that the new synthetic cell carries a line from James Joyce, inscribed in its DNA: “To live, to err, to fall, to triumph, to recreate life out of life.”

What would Joyce have thought if someone had told him that one day the synthesized genome of a goat pathogen would carry his words? I would hope that whoever told him would make sure that he did not think this moment marked his literary immortality. In fact, his deathless prose is probably being desecrated by the relentless erosion of evolution right now.

The scientists who produced the new synthetic cell copied the genome of a microbe, letter for letter, and then inserted the synthetic version into a host cell. To determine that their experiment worked, they needed a way to tell the genomes of their synthetic cells from the natural genomes that were their model. So they inserted “watermarks” into the artificial genome. These sequences of DNA (which spelled out the work of Joyce and others through the genetic code) sit in non-coding regions of the microbe’s DNA. As a result, these watermarks cannot disrupt any essential protein-coding genes or stretches of DNA that are vital for switching genes on and off.

It turns out that the genome of the synthetic cell is not identical to its original, even if you ignore the watermarks. Mutations slipped into its sequence during its synthesis. Yet those mutations caused no harm to the microbe, presumably because they didn’t disrupt an essential function encoded in its DNA. Once the synthetic cell came to life and began to grow and divide, it copied its entire DNA, including Joyce’s words. But as lovely as those words may be, and as important as they may have been to the scientists during their experiment, they mean nothing to the microbe. Every time an organism replicates, each spot in its DNA has a tiny chance of mutating.

In the growing colony of synthetic cells, now numbering in the billions, it’s almost certain that Joyce’s watermark has already been defaced by a mutation. The bacteria that carry these degraded versions of Joyce presumably do not suffer from these mutations, since the watermarks don’t matter to them anyway. So they can keep replicating.By contrast, the DNA in the really useful parts of their genome is changing very little over the generations, thanks to selection.

Inserting Joyce into the first synthetic cell was certainly a kind gesture, but not a timeless memorial. It would be fascinating to go back to the synthetic cell colony in a few years and sequence Joyce’s line again. I’d bet that it won’t even be recognizable anymore.

The fate of Joyce’s DNA points up something important about this project. There have been lots of headlines over the past day about how the scientists who made this cell were playing God. Yet our power, even over synthetic cells, is limited. Once this new cell came into existence, it started changing through evolution, slipping away from its original form. In fact, evolution is the great enemy of all scientists who want to use synthetic biology to supply us with medicine, fuel, and other valuable things. Once they engineer a microbe, they start to lose control of their handiwork. Life takes its own course from there. It is life, ultimately, that recreates life from life.

CATEGORIZED UNDER: Evolution, Synthetic Biology

Comments (37)

  1. jim

    How did they encode the “o”‘s and the “u”‘s?

  2. Barry Roth

    Be interesting if after a few generations the sequence reads “Commodious vicus…”

  3. NewEnglandBob

    “How did they encode the “o”’s and the “u”’s?”

    As Ventner said: a code within a code within a code.

    You see Carl? I knew you could add more to the discussion (as I said we need you over at WEIT).

  4. duderino

    @Barry, even cooler if they spelled out “Tom Marvolo Riddle”

  5. Sili

    How did they encode the “o”’s and the “u”’s?

    That was my question too, since that’s the sum total of my knowledge of the genetic code.

  6. Darren Garrison

    If they wait long enough, it will mustate into Finnegans Wake.

  7. A fascinating aspect of this breakthrough that’s in the (scientific and bioethics) news everywhere. Thanks!

  8. Quinn O'Neill

    I wonder what kind of protein his words might make (if not for the added stop codons).

    Great piece!

  9. natselrox

    Apparently, they invented a new alphabet with variations of random stop-codons. So it has all the letters in the English alphabet plus a few more characters.

  10. Patrick

    If it were me I’d just use Q and V for O and U, but what’s bugging me is that I downloaded the supplemental data to get the DNA sequences for the watermarks and none of the translated amino acid sequences is anything even resembling English.

  11. JMW

    Given an infinite amount of time and an infinite number of bacteria, one of them will genetically encode the complete works of Shakespeare.

  12. marcel

    “Once they engineer a microbe, they start to lose control of their handiwork. Life takes its own course from there. It is life, ultimately, that recreates life from life.”

    Engineering a microbe is in this way remarkably similar to raising a child. Are microbes equally thankless?

  13. Steven Smith

    it’s almost certain that Joyce’s watermark has already been defaced by a mutation.

    Great post Carl. This is a wonderful example of what R.A. Fisher had to say about the futility of any “intelligent designer”:

    If we imagine, then, some extra-natural agency endeavouring to influence the organic evolution of mammals and birds by the production, on millions of different occasions, of this single mutation, we can recognise that its efforts were futile and inoperative.

  14. Steven Smith

    FYI: I was curious how Venter et al. coded Joyce’s words, so I did a quick Google search. I didn’t find the answer, but found this:

    Encoded in the watermarks is a new DNA code for writing words, sentences and numbers. In addition to the new code there is a web address to send emails to if you can successfully decode the new code, the names of 46 authors and other key contributors and three quotations: “TO LIVE, TO ERR, TO FALL, TO TRIUMPH, TO RECREATE LIFE OUT OF LIFE.” – JAMES JOYCE; “SEE THINGS NOT AS THEY ARE, BUT AS THEY MIGHT BE.”-A quote from the book, “American Prometheus”; “WHAT I CANNOT BUILD, I CANNOT UNDERSTAND.” – RICHARD FEYNMAN

    Wonderful. There’s no doubt that this genome has plenty of Easter Eggs hidden in it. Very curious to know what these are.

    But what’s the code? ASCII, with A=0, C=1, G=2, T=3? E.g., the LETTER ‘A’ is 0x41 (hex) in ASCII, thus the LETTER ‘A’ would be coded in DNA as

    ASCII ‘A’ = 0x41 = binary 1000 0001 = quaternary 2001 = GAAC using DNA

    The choice of code is philosophically and practically interesting: it would be quite tempting to choose a binary code that is a lot more efficient than DNA itself, which is inefficient by

    DNA inefficiency: log2(4*4*4/20)/3 = 0.56 bits/nucleotide

    (only 20 amino acids for 64 possible codons from 3 nucleotides). Using 8-bit ASCII to encode capital letters with a space and a few punctuation marks [A-Z <space> , . -] is quite a bit (ha-ha) more inefficient than DNA itself,

    8-bit-ASCII-using-DNA inefficiency: log2(256/30)/4 = 0.77 bits/nucleotide

    Anyone bold enough to create synthetic life should be bold enough to use a more efficient coding strategy than does nature itself. Perhaps something sophisticated as a Huffman code or better?

    On the other hand, using good old 8-bit ASCII would allow synthetic life researchers from around the world to easily code their names and favorite literary quotations in the language of their choice using UTF-8, just the way all computers and web browsers do (עברית العبرية हिन्दी). What did Venter use?

    Also, I’m curious if the choice of James Joyce, aside from being perfect, was motivated at all by Murray Gell-Mann’s source for the word quark, along with a desire put these accomplishments on the same scale.

  15. rosetta

    “As Ventner said: a code within a code within a code.”

    Yep, there’s a rosetta stone encoded in the watermark sequences, find it and you can decipher the whole thing. All 64 codons are in the rosetta stone sequence but only about 51 can be deduced by their use in other watermark sequences, about 13 codons are unused.

  16. aidel

    I’m just glad to know that there are some scientists in the world reading Joyce.

  17. Ginger Yellow

    The idea of the Joyce quotation mutating is pleasingly reminiscent of the Tom Stoppard play Travesties, in which Dadaist poet Tristran Tzara clashes with Joyce, the former cutting up Shakespeare’s sonnets and plucking the words out of a hat (Joyce’s) and combining them at random to form new poetry.

  18. Daniel J. Andrews

    I’ve always disliked that line about how we shouldn’t play God. We’ve been playing ‘God’ since we first started breeding animals and plants together to get preferred traits. We do it when we take medicines, vaccinate against disease, perform surgeries, grow crops and even seed clouds in attempts to make it rain. Next time someone suggests we shouldn’t play God, ask if they’d be willing to give up medical aid, or even just their morning coffee.

  19. Interesting take on the watermark. Is there any point putting watermarks in genome’s if they’re only going to be destroyed by evolution anyway?

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The Loom

A blog about life, past and future. Written by DISCOVER contributing editor and columnist Carl Zimmer.

About Carl Zimmer

Carl Zimmer writes about science regularly for The New York Times and magazines such as DISCOVER, which also hosts his blog, The LoomHe is the author of 12 books, the most recent of which is Science Ink: Tattoos of the Science Obsessed.

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