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What’s Artificial Life, Anyway?

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?

43 comments on “What’s Artificial Life, Anyway?”

  1. Alex Taylor says:

    I think the field now accepts “xenobiology” as the term to differentiate synthetic biology in which cells contain biomolecules augmented, or completely replaced, by chemistries not found in nature, as well as the use of such synthetic molecules to manipulate biology. Does this work fall under xenobiology? Arguably no, but it’s certainly synthetic biology. Whilst I think its a bit of a stretch to call most synbio “artificial life”, I think in this case it’s reasonably justified on the basis that it goes beyond what Steven Benner calls “tinkering biology”; the entirety of one of the cells’ fundamental components has been engineered.

  2. 12th Doctor says:

    “I discussed this ship thing after my regeneration…”

  3. Some Dude says:

    I think for this sort of stuff the hardware/software analogy works rather well. The membranes, ribosomes, cytoskeleton etc. are the hardware, DNA is the software. The Chin lab replaced the entire software while keeping the hardware. The work is similar to the bottom up approach to artificial cells using biologically produced parts like ribosomes etc., and basically a big in vitro reconstitution experiment.
    In my view, truly artificial life would be assembled solely from small-ish molecules one can buy in the Sigma catalogue, e.g. fatty acid membranes with encapsulated self-replicating and functional nucleic acids, maybe with the help of some cofactors and small peptides. To generate something like this is the ultimate goal of many of the origin-of-life labs.

    1. RandomWok says:

      But doesn’t the hardware/software analogy skip the actual animating principle (electricity)? These DNA-replaced critters still don’t have the wherewithal to come alive without the platform of a pre-existing living critter, correct? True artificial life would be a concoction of hardware/software that met the definition of living spontaneously? And by the way, I’m not championing any “divine spark” origin, perhaps the textbook definition of life is rooted in some as yet undiscovered thermodynamic/quantumphysical/DeepakChopra-ish phenomenon…Waiting for luysii to chime in.

      1. Handles says:

        I’m guessing you and I both agree with the “metabolism first” people, who would say life is the chemical gradient from a primordial hydrothermal vent, trapped and maintained across a biological membrane. In that case you would need to kickstart your own gradient for your lifeform to be artificial. These guys seem to be approaching it from the “information first” POV, which says the self-replicating molecule is the important bit.

      2. zero says:

        The hardware in this case is often also synthetic and used to run the software which in turn builds more hardware. The fact that we are using tools from nature (DNA polymerase for example) does not invalidate the ‘synthetic’ status of the resulting lifeform.

        Synthetic insulin is generated by modified microorganisms. Synthetic bacteria can be generated by modified enzymes if necessary and still be synthetic.

    2. RM says:

      truly artificial life would be assembled solely from small-ish molecules one can buy in the Sigma catalogue,

      “Get your own dirt.”

  4. Trigger says:

    For the less erudite this is called the “Trigger’s broom” problem. Linked in handle

    1. Derek Lowe says:

      Hah! That’s one that as an American I’d never encountered. . .

      1. Diver Dude says:

        Trigger was one of British comedy’s great creations. The scene is very well known in the UK and has introduced an entire generation of Brits to the philosophical conundrum.

        1. Trigger says:

          Cheers Dave.

    2. CTE says:

      American football fans (NFL) also refer to this as the Cleveland Browns/Baltimore Ravens legacy.

    3. Wilhelm cody says:

      Speaking of handles, there is also an even more America version called Washington’s Axe, which my mother told me some 70 years ago.
      Here is a modern rendition, of course exactly as my mother said:
      https://www.hitplays.com/hp/Scripts/Samples/WashingtonsAxe=123112.pdf;; https://yandoo.wordpress.com/2013/08/17/theseuss-paradox/.

      1. loupgarous says:

        South of the Mason-Dixon Line, our version of Theseus’ Ship was sung by Johnny Cash.

  5. Wavefunction says:

    The same Theseus Ship Problem has been applied to asking questions about AI and the brain: if you systematically replaced each neuron in the brain by an electronic one, at what point does the human brain end and the machine brain begin?

  6. Charles H. says:

    This is an example of language being a useful abstraction that doesn’t everywhere match the real world, but rather matches how people think about the world. (I think that last is a safe assumption, and every language seems to share the same characteristic.)

    In this case the particular foible is the assumption of actual boundaries. Most default boundaries fuzz if you look closely enough. A piece of rubber may appear solid, but Hydrogen finds it permeable. You can’t defend any particular nano-meter as where your skin splits inside and outside. Etc. But we even want to put boundaries around clouds.

    It’s a generally useful abstraction that’s almost always wrong if you look closely enough. This is another case where now that we’re starting to look closely, there’s no real boundary.

  7. Witek says:

    What is Real Life, anyway? Where does it start? Are viruses alive? Etc…

  8. V. Frankenstein says:

    It’s alive!!!

  9. Philosopher's_Stone says:

    About 4 decades ago when I was visiting potential grad schools, I asked a very prominent synthetic organic chemist (to be unnamed here, but would be recognized by many readers of this blog) what was the future for organic synthesis. He answered that when he looked at a tree he didn’t know how to synthesize one. I didn’t appreciate at the time that what it takes to synthesize organisms goes well beyond the tools of organic chemistry.

    1. rhodium says:

      I hope you are paraphrasing his answer, which was:
      Terpenes are made by fools like me
      But only God can make a tree

  10. Peter. S. Shenkin says:

    Well, Heraclitus said, “You cannot step into the same river twice.” IIRC, Parmenides then replied, “You cannot step into the same river even once.”

    As me ‘n’ me buddies commented upon learning this, ca. 1966, “Like wow, man!”

  11. Scott says:

    As a Sailor, my answer to the Ship of Theseus question is, “Have you ever changed her name with the rest of the repairs? Then it’s the same ship.” Pretty sure most other nautical types would agree with me.

    A scifi setting I like (link in name) uses ‘neogen’ to describe biological organisms that have been made from scratch, as the underlying assumption is that anything else has been heavily modified from it’s ‘baseline’ as-naturally-evolved version.

  12. x says:

    Thinking about the ship – if we keep all the boards and reassemble them in a storage room somewhere, we could say that was the original ship, if we like. If we burned, repurposed, or threw them away as they were removed, we would say that the ship on display is the original.

    The difference here has to do with intent and identity: which ship do we WANT to be the original one? “Original” has no natural meaning. The molecules don’t care where they are, what they’re part of, or how they got there; it is really only our opinion that creates originality.

    Applying this to “artificial life”, the answer is: it’s whatever we want it to be. If I told you right now I created artificial life, that would tell you nothing at all because you don’t know what I mean by it, let alone what I actually created or how I did it – that should tell you that it doesn’t really mean anything.

    (The same is true for neurons, BTW; identity is preserved if you think it is. This issue is complicated by the pervasive unexamined assumption that people have essential identities which are not altered by disease, injury, or brainwashing, but again, the molecules don’t care.)

  13. Athaic says:

    OT: Re: Ship of Theseus problem

    Terry Pratchett incorporated this issue in his Discworld novel The Fifth Elephant.
    As one of his recurring theme is that we humans should be really called Pan narrans, the storytelling chimpanzee, his answer to this problem is something like “as long as we see it as the original one, this is the original one”.

    Now, as to define artificial life… We are already fighting to define what’s “natural” (agriculture products like maize is a good example), so I don’t expect the dbate to end anytime soon.

    1. SSpiffy says:

      “This, milord, is my family’s axe. We have owned it for almost nine hundred years, see. Of course, sometimes it needed a new blade. And sometimes it has required a new handle, new designs on the metalwork, a little refreshing of the ornamentation . . . but is this not the nine hundred-year-old axe of my family? And because it has changed gently over time, it is still a pretty good axe, y’know. Pretty good.”

      ― Terry Pratchett, The Fifth Elephant

  14. Chris Phoenix says:

    For a bacterium, immunity to all viruses is a big fitness advantage. Seems like they could easily become invasive species: a major factor in a species becoming invasive is being separated from its natural predators/parasites.

    An invasive-species bacterium as flexible as E. coli could be really bad news. How’d you like some screwed-up soil chemistry along with your climate change?

    I raised this point to George Church when he proposed this. He was planning to take all sorts of precautions to make sure the virus-proof E. coli couldn’t survive in the wild. I wonder if the current group will be as careful? What about all future groups?

    It’s worth noting that virus-proof bacteria are worth a lot of money industrially. There’s a strong incentive to make them, and to grow them in large quantities outside the lab.

    I really, really hope I’m wrong about this. As Eric Drexler once said, “We cannot afford certain kinds of accidents with replicating [machines].”

  15. I am kind of spooked by the idea of whipping up synthetic bacteria. Especially ones that are immune to, well, anything that bacteria are normally not immune to.

    1. db says:

      Seems like a semi-cautious way to handle this problem would be to engineer in one (or three or more) “Kill switches”–hooks that common viruses (or specially modified common viruses) would use to infect and kill any rogue “artificial” bacteria that make it out of their pen.

      1. x says:

        Bacteria mutate readily, and they reproduce quickly. Your killswitch is a fantastic idea right up until some instance of the species says “nah, we’re not gonna have that”.

        See also the dramatic visualizations of antibiotic resistance carried out on giant agar plates…

  16. anon says:

    Seems to me that to count as “artificial life” you need to go from non-living components to something that’s alive. Just subbing out the parts in an already living system doesn’t capture the critical transition of making something alive from something that’s not.

  17. Dr 13enster says:

    I think this quote from Gaius Baltar in Season 2 of BSG sums up my feelings on real vs artificial:

    “Love is a strange and wonderful thing chief – you be happy you experienced it all – even if it was with a machine.”

  18. DTX says:

    When I was an undergrad, the Zoology department at the University of Rhode Island had an aptly & wryly named room: “Non-Biological Reproduction”

    It was the copy room.

  19. Isidore says:

    In 1964, after stating that he could not properly and accurately define pornography, US Supreme Court Justice Potter Stewart famously noted that “I know it when I see it.” Perhaps it is (will be) similar with artificial life. Has anyone yet seen it?

  20. SomeGuy says:

    Is this the real life?
    Is this just fantasy?
    Caught in a landslide
    No escape from reality
    Open your eyes
    Look up to the skies and see……

  21. Uudon Rock says:

    When a cell line is immortalized and cultured, are the cells still the donor, or something else?

  22. sgcox says:

    No, they are now out of HTA in UK
    https://www.hta.gov.uk/

    1. sgcox says:

      And just for the clarification:
      “Tissues and cells removed directly from a person are relevant material under the HT Act. Cell lines are not relevant material as all the original cells from the person have been replaced by cells that have divided and therefore have been created outside the human body”

  23. Konstantinos Spingos says:

    It is impossible to know soon, but the golden standard for non-artificiality would be to survive evolution pressure among the rest of natural bugs.

  24. Bagger Vance says:

    The Ship of Theseus problem comes up a lot in discussions on my (political) side. It’s often phrased as “suppose you took every person out of Japan and one by one replaced them with a person from Haiti. At which point would Japan be no longer “Japanese”? Would ‘New Japan’ still be an economic powerhouse? Would the new population be as interested in Imperial succession, traditional aesthetics, engineering precision?”

    However, the problem and its associated answers are well beyond philosophical at this point

    1. loupgarous says:

      The Japanese are actually running that experiment. They know their present population won’t be large enough to pay the taxes to sustain their present nation. They’ve been importing ethnic Japanese-Brazilians, young ones, to fill the gap.

  25. Frank says:

    How long before we can scale this up to dinosaurs?

  26. loupgarous says:

    Eventually, we’ll have a working model of the human brain, all 100 trillion to 1,000 trillion synapses, and may even, once we have that model, be able to create an electrochemical map of the brain, knowing more than we do know about its physiology and fine structure. And we ought, on another line of technology, to be able to record not just brain activity, but organize the record in ways that reflect what that brain is thinking and what it remembers and feels.

    At that point, borrowing an old ad tag line –
    “Is it real, or is it Memorex?”

  27. Wallace Grommey says:

    A shipload of comments! Who cares what we want to call it? As long as it floats!

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