This one goes to 11…

The famous Spinal Tap quote (see the video here) is great because Nigel is explaining how  his amp is better than other rockers since you can turn it up to 11. “Why don’t you just make ten louder and make ten be the top number and make that a little louder?” asks the mockumentarian Rob Reiner. Good question.

The humor in this scene reminds me strongly of this recent paper on the introduction of an artificial nucleotide base pair into a bacteria. Essentially they got a bacteria to incorporate an artificial nucleotide pair into its DNA, it replicates stably (that is, the new pair stays in the bacterial DNA for generations), and its not removed by DNA repair mechanisms that look for problems in the DNA. Novel nucleotides are not new- researchers have created a large number of these and incorporation into DNA has been done in limited ways in test tube (in vitro) systems, not in a living organism. This is really a pretty cool technical achievement – the researchers had to solve a number of complicated problems to get this to work and, more importantly, it’s likely that they got very lucky with their choices (where ‘luck’ here is a combination of knowledge, trial and error, and actual bona fide luck).

The paper itself doesn’t really overstate the implications of this paper. The only implications statement in the paper comes at the end:

In the future, this organism, or a variant with the UBP incorporated at other episomal or chromosomal loci, should provide a synthetic biology platform to orthogonally re-engineer cells, with applications ranging from site-specific labelling of nucleic acids in living cells to the construction of orthogonal transcription networks and eventually the production and evolution of proteins with multiple, different unnatural amino acids.

And all of this seems very reasonable and potentially achievable.

However, as happens with many high profile papers, the press coverage I’ve seen on this is terrible. From Gizmodo touting that “scientists have created alien DNA” (only for a very limited definition of ‘alien’) to New Scientist stating that researchers have expanded the ‘genetic code’ of a bacterium (not really, a code needs to have meaning- that is, to be translatable into something that has meaning, this advance doesn’t yet). However, perhaps the most troubling is coverage from NPR, largely based on an interview with the senior author of the paper. In this piece Floyd Romesburg introduces a simple, and largely apt analogy, for what his work has done:

Maybe you get three consonants and one vowel. Maybe there are some words you can write and you can string them together to make, sort of, primitive stories. But if you could have a couple extra letters, there’s more that you could write. Having the ability to store increased information would allow you to write more interesting words, bigger words, more complicated words, more nuanced words, better stories. – from NPR interview

He goes on to say:

It’s not so much that I think life needs more genetic information but I think that there are things that we could really learn and drugs that could be developed by getting cells to be able to do more

So it’s not a bad analogy, but one where he’s essentially said: “This one goes to 11.” . And it points out exactly why this work is so limited in its implications (exactly the opposite of what he’s trying to point out by using it BTW). They have added, in a very constrained and limited way, added two letters to the standard ATCG alphabet used by nearly all life. Will this introduce the ability to build more complex or useful biological systems? Not in the slightest. Imagine that we added a couple of letters to the English alphabet. Now we give those extra letters to someone like William Shakespeare. Does anyone think that he would be able to do more with more letters? Write better, more complex, more interesting, more profound plays or sonnets? No, of course not. Even if you gave him a whole bunch of new words that contained the new letters (which they haven’t done at all in this paper- they haven’t actually introduced this new addition into the code itself, only into the alphabet), he would likely have produced very similar works. Maybe those works would be slightly shorter, but they would NOT contain more information. Adding a letter to the alphabet doesn’t increase the information or the complexity of the code. It just doesn’t. The computer that I’m writing this on is based on a binary alphabet (1 and 0 are the only letters it uses) and yet I’m able to put these together (with the help of the underlying OS and software) into complicated and information-rich constructs. Having a computer based on 0 , 1 AND 2 wouldn’t help me write this post any more better [sic].

An image of ACTUAL (fictional) alien DNA. This one has a 15 stranded double helix, which CLEARLY makes it more complicated than our humdrum double stranded type. Clearly. (from the movie The Fifth Element)

An image of ACTUAL (fictional) alien DNA. This one has an 8 stranded helix, which CLEARLY makes it more complicated than our humdrum double stranded type. Clearly. (from the movie The Fifth Element)

The idea that this would lead to development of new drugs, new forms of life, new biology is a far, far, far distant stretch that causes confusion and even fear. The problem here is not purely driven by misunderstanding and misrepresentation of the work by scientific journalists (though it looks like there’s some of that) but from the actions and statements of the senior author himself. As I mentioned, this is a sound paper and is pretty interesting- a technical achievement. It may indeed lead to some interesting new discoveries and methodologies that may be broadly applicable. But it’s not alien DNA and it’s not going to help us cure cancer with new drugs, and it’s not going to provide the ability to make the biology more complex, but it might make our rocker friends green with jealousy when we reveal that we have six nucleotide bases compared to their paltry four bases because “these go to eleven” (Nigel Tufnel)

2 thoughts on “This one goes to 11…

  1. By adding an extra base pair the information content of the DNA increases from 2 to 2.6 bits pers base pair. This could be valuable if you want the ribosome to translate a wider variety of amino acids since it’s limited to a three (or maybe four) letter code.

    • This is true. It might be helpful to code for a set of introduced amino acids- but that part is still a long way off. As a cool demonstration that this can be done I think this study succeeds, but I think the more immediate implications of the paper have been exaggerated.

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