Do you know the Ship of Theseus problem? That one was first stated in its canonical form by Plutarch in his Parallel Lives, speaking of the ship that the hero used to return to Athens from Crete after slaying the Minotaur. Here we go:
The ship on which Theseus sailed with the youths and returned in safety, the thirty-oared galley, was preserved by the Athenians down to the time of Demetrius Phalereus. They took away the old timbers from time to time, and put new and sound ones in their places, so that the vessel became a standing illustration for the philosophers in the mooted question of growth, some declaring that it remained the same, others that it was not the same vessel.
That one’s been kicking around in philosophical discussions ever since. Thomas Hobbes, for example, wondered if the old boards had been stored once they were removed and eventually used to build another ship, whether that one one have a better claim to being the original and so on. You can set off all sorts of arguments about what’s authentic, what’s original, and whether there’s a definable threshold for such descriptions at all.
Why am I starting us off in ancient Athens, as described later in ancient Rome? Because we’re in the middle of just another such question: what is artificial life? We’ve made all sorts of modifications to living cells and entire living creatures, with tools of increasing power and specificity. We actually started long before genetic engineering, with an extraordinary example being the long, complex, multicenter breeding of a wild Mexican grass into what we know as corn (maize). Even the most old-fashioned heirloom variety of corn you can find is nowhere near a “natural” plant; it never evolved in the wild and is entirely a human creation.
And these days we have far faster and well-defined techniques, all sorts of ways to introduce mutations into plants and animals ranging from the sledgehammer (radiation, colchicine) to the surgical instruments of CRISPR and the like. The number of engineered cells and whole organisms that have been produced is surely beyond our ability to specify. Are they artificial? How about if you introduce genes (and their associated mRNAs and protein products) from completely different organisms (as is done all the time)? Artificial? There has been a great deal of work put into engineering strains of Mycoplasma, in an effort to see how far down its genome can be pared and still have a living creature, and also to transfer a completely human-synthesized genome into the cells themselves. Now those, are they artificial life, or not?
I ask because there’s a new paper out that takes the latter technique even further: this one works with the (much larger) E. coli genome, and the new replacement DNA was not only synthesized, but substantially reworked (here’s coverage at Stat). The number of duplicate codons that read for a given amino acid have been reduced: specifically, the serine codons TCG and TCA have been replaced by existing synonyms, a modification that has previously been shown to work in shorter stretches of the genome. This recoded DNA was introduced in sections, with the eventual production of a completely recoded bacterium whose genome was synthesized from scratch. There were plenty of hitches along the way, as the paper details – some codons were tricky, because they’re involved in downstream regulation of other genes (promoter and enhancer effects), and a lot of these had to be addressed one by one. Swapping out to an upgraded memory chip, this is not.
What the team at Cambridge ends up with, though, is a living bacterium (Syn61) that is capable of reproduction. It looks a bit funny, to be sure – it’s longer than the original type, and reproduces more slowly. But its protein expression profile is very close to the original. And it passes some important tests: the serT gene is essential for handling the TCA codon in wild-type bacteria, but you can delete it with impunity in Syn61, because it doesn’t have any TCA codons any more. And if you try to reassign the TCG codon to use a noncanonical amino acid (an experiment of a kind that’s had a great deal of work put into it over the years), that’s quite toxic to the wild-type, but has no effect on Syn61, either. It doesn’t have any endogenous TCGs to get messed up. This also means that it’s quite possible that such recoded cells are resistant to most (perhaps all) viruses. After all, the viral infection machinery is expecting those codons to still be in place (why wouldn’t they be?), and attempts to hijack the cellular machinery to produce viral proteins might well just bog down.
Is this artificial life, then? There are headlines all over the place using the term, just as there have been for all the stages leading up to this point. And as there no doubt will be for the experiments to come. But I have no idea, because I don’t know where to draw that line. I don’t know when the ship in Athens’ harbor became different, and I don’t know when precisely these organisms did, either. But if I’d walked up to a ship of Theseus that contained no original part whatsoever from the one that sailed back from Crete, I would have to wonder. And when I encounter a bacterium whose original parts have all been replaced?