Strange replicators

New from the "Well, I See No Way This Could Go Wrong, Do You?" department, we have: some researchers who have built living things from stem cells that went on to discover how to reproduce themselves in a completely novel fashion.

A team of scientists at the University of Vermont, Tufts University, and Harvard University created what they call "xenobots" -- clusters of living stem cells taken from the African clawed frog (Xenopus laevis) that were on their way to becoming skin cells, but were excised and then arrayed in spherical clusters.  These clusters began to reproduce, creating new clusters.

"Well, so what?" you may be saying.  "Cells reproduce.  It's one of the characteristics of life.  What's so weird about that?"

What I haven't told you is that the clusters (1) reproduced not by mitosis, or at least not solely by mitosis -- they reproduced by scooping up loose cells in the petri dish and assembling them into new clusters; and (2) when the scientists noticed that the original clusters usually died after reproducing, they turned a supercomputer on the problem of whether it was possible to adjust the shape of the cluster to make it better at reproducing and more likely to survive -- and the model worked.

"[W]ith an artificial intelligence program working on the Deep Green supercomputer cluster at UVM's Vermont Advanced Computing Core, an evolutionary algorithm was able to test billions of body shapes in simulation -- triangles, squares, pyramids, starfish -- to find ones that allowed the cells to be more effective at the motion-based 'kinematic' replication reported in the new research," said Sam Kriegman, lead author on the paper, which appeared in Proceedings of the National Academy of Sciences this week.  "We asked the supercomputer at UVM to figure out how to adjust the shape of the initial parents, and the AI came up with some strange designs after months of chugging away, including one that resembled Pac-Man.  It's very non-intuitive.  It looks very simple, but it's not something a human engineer would come up with.  Why one tiny mouth?  Why not five?  We sent the results to Doug [Blackiston, of Tufts University] and he built these Pac-Man-shaped parent xenobots.  Then those parents built children, who built grandchildren, who built great-grandchildren, who built great-great-grandchildren."

One of the xenobots picking up a smaller cluster of cells

The scientists say they named them "xenobots" because of the genus name of the frog species they were created from -- Xenopus -- but I don't think it's a coincidence that the root word of both, the Greek word ξενος, means "strange."

"This is profound," said study co-author Michael Levin.  "These cells have the genome of a frog, but, freed from becoming tadpoles, they use their collective intelligence, a plasticity, to do something astounding.... We were stunned that these biological objects -- a computer-designed collection of cells -- will spontaneously replicate.  We have the full, unaltered frog genome, but it gave no hint that these cells can work together on this new task, of gathering and then compressing separated cells into working self-copies."

The whole thing unfortunately brought to mind an episode of the highly scientific documentary series Kolchak: The Night Stalker called "Primal Scream," wherein some scientists brought back tissue samples from a drill site in the Arctic.  The samples, which looked like (and probably were) a tin can full of Silly Putty, were kept in cold storage until one day the cooling system failed.  This somehow spurred the tissue to spontaneously grow into a creature that looked like the love child of Ron Perlman and Sasquatch, which of course went on a rampage and killed lots of people.

Kolchak eventually figures out that being a cave man (as it were), it would try to find caves to hide in.  Despite (1) being from the Arctic, and (2) being frozen for millions of years, the creature apparently knew all about the geography of Chicago, and figured out that there were tunnels underneath a sports stadium where it could live.  Kolchak followed it there, and after some tense moments where he bumbled around in his usual fashion, dropping his camera, gun, flashlight, hat, etc., he was able to kill the creature and save the day.

But I digress.

The researchers, for their part, don't seem worried about their creation getting loose and causing problems.  "These millimeter-sized living machines, entirely contained in a laboratory, easily extinguished, and vetted by federal, state and institutional ethics experts, are not what keep me awake at night," said study co-author Joshua Bongard.  "This is an ideal system in which to study self-replicating systems.  We have a moral imperative to understand the conditions under which we can control it, direct it, douse it, exaggerate it."

Because we've never seen movies before where the scientist says, "Stand back!  I know how to control the monster!" and promptly gets messily devoured.

In all seriousness, this does once again turn the spotlight on how we define "life."  The xenobots aren't that near the edge of the definition; they are, after all, made from living cells, not from off-the-shelf chemicals.  But given our ability to synthesize biological compounds (including DNA) pretty much to order, it may not be much longer before we see a truly artificial life-form -- something that shares no common ancestry with terrestrial life at all, and is entirely created in a laboratory.  Couple that with the last few years' awe-inspiring work in artificial intelligence, and we are truly looking at the fulfillment of the line Shakespeare gave to Miranda in The Tempest: "O, brave new world, that has such people in it!"

Even if those "people" are currently little blobs of cells, you have to wonder how long they're going to stay that way.

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It's astonishing to see what the universe looks like on scales different from those we're used to.  The images of galaxies and quasars and (more recently) black holes are nothing short of awe-inspiring.  However, the microscopic realm is equally breathtaking -- which you'll find out as soon as you open the new book Micro Life: Miracles of the Microscopic World.

Assembled by a team at DK Publishers and the Smithsonian Institution, Micro Life is a compendium of photographs and artwork depicting the world of the very small, from single-celled organisms to individual fungus spores to nerve cells to the facets of a butterfly's eye.  Leafing through it generates a sense of wonder at the complexity of the microscopic, and its incredible beauty.  If you are a biology enthusiast -- or are looking for a gift for a friend who is -- this lovely book is a sure-fire winner.  You'll never look the same way at dust, pollen, algae, and a myriad of other things from the natural world that you thought you knew.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

New life

New from the "Don't You People Even Watch Science Fiction Movies?" department, we have: bioengineers at Cornell University recently created a DNA-based material that has three of the main characteristics of life -- metabolism, self-assembly, and organization.

Oh, and they pitted different versions of the material against each other, and triggered two more: competition and evolution.

The research was published last week in Science: Robotics, in a paper called, "Dynamic DNA Material With Emergent Locomotion Behavior Powered by Artificial Metabolism," authored by a team led by Cornell bioengineer Shogo Hamada.  Working with substances they call DASH (DNA-based Assembly and Synthesis of Hierarchical) materials, they ended up creating something so close to a living thing that even the most ardent life-is-unique-and-unquantifiable proponents are sitting up and taking notice.

What they did is start with 55-nucleotide pair DNA fragments, which were then injected into a machine that provided raw materials (free nucleotides) and a source of energy.  The DNA fragments began to extend, adding new bases to the front end while slowly losing them from the back end, so the entire fragment crept along.  The addition process was faster than the degradation, so eventually there were fragments a few millimeters long -- corresponding to tens of thousands of base pairs.

"The designs are still primitive, but they showed a new route to create dynamic machines from biomolecules. We are at a first step of building lifelike robots by artificial metabolism," said Shogo Hamada, who led the research.  "Even from a simple design, we were able to create sophisticated behaviors like racing. Artificial metabolism could open a new frontier in robotics."

The fragments then began to compete against each other in terms of speed and growth rate, something that has never been seen before in an artificially-created DNA-based material.  "Everything from its ability to move and compete, all those processes are self-contained," said study co-author Dan Luo.  "There’s no external interference.  Life began billions of years from perhaps just a few kinds of molecules.  This might be the same...  [T]he use of DNA gives the whole system a self-evolutionary possibility.  This is huge."

The researchers are currently trying to design ways to have the DNA fragments move toward sources of light, warmth, or sources of nutrients, and away from dangers, not to mention ways to speed up the process to create new generations within seconds.  "We are introducing a brand-new, lifelike material concept powered by its very own artificial metabolism," Luo said.  "We are not making something that’s alive, but we are creating materials that are much more lifelike than have ever been seen before."

Hamada added, "Ultimately, the system may lead to lifelike self-reproducing machines."

Okay, now, just hang on a moment.

I'm not really buying Luo's comment that they're "not making something that's alive," because we don't really have a good working definition of life to start with.  Viruses, commonly referred to as "alive," have no metabolism, are not made of cells, do not respond, and outside of the host do not use energy.  Honestly, they're more like self-replicating chemicals than they are living things.  Then there's the life characteristic "has a limited life span," which doesn't seem to apply to some plants (such as the essentially immortal bristlecone pines) and cancer cell lines (such as the famous HeLa cells).  There's a lot of speculation on whether life even has to be carbon-based -- speculation that's been around for a long time (remember the original Star Trek episode "The Devil in the Dark," about a silicon-based life form that has hydrofluoric acid instead of water as the solvent in its blood?).

So don't tell me the new Cornell DASH-material isn't alive because it's missing a couple of characteristics of life from the canonical list.  The number of naturally-occurring exceptions is long enough.

And I'm right up there with the folks who think this is amazingly cool -- my background is in evolutionary genetics, after all -- but for cryin' in the sink, doesn't this concern anyone?  Especially if you design DASH-materials that avoid danger and seek out sources of nutrients?  Because I can think of one really great source of nutrients they'd probably be attracted to:

They're called "us."

And the problem is, we don't set up a good immune response to DNA fragments.  Up till now, this has been a good thing; we take in DNA fragments in our food every time we eat.  If you eat a carrot, you're swallowing carrot DNA.  If you eat a steak, you're swallowing cow DNA.  If you eat Slim Jims, you're swallowing...

... well, the DNA of some kind of organism.  I think.  Who the hell knows what those things are made of, anyhow?

But my point is, you have one shot at breaking these foreign DNA strands down into their component nucleotides, and that's using the nuclease enzymes in your small intestine.  If they get past that...

Cf. my earlier comment about the new artificial DNA fragments learning how to "avoid danger."

Okay, maybe I'm being alarmist, here.  But -- and I mean this with all due affection -- humans have a really good track record of fucking things up royally, sometimes out of the best of intentions.  So I'm not sure that creating a self-replicating, competitive life form that can evolve to become more efficient at seeking out sources of nutrients is really all that great an idea.

But that's not gonna stop 'em.

Oh, and did I mention that I live ten miles from Cornell University?  At least I'll be amongst the first people to get devoured, and won't have to sit around wondering when the DASH-monsters will arrive.

But I'm gonna try not to worry about it.  After all, we've got enough other things to worry about, such as climate change, the threat of war, and whether today'll be the day Donald Trump decides to open the Seventh Seal of the Apocalypse.

Maybe that's what Michele Bachmann meant by saying Trump was "highly biblical."

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Monday's post, about the institutionalized sexism in scientific research, prompted me to decide that this week's Skeptophilia book recommendation is Evelyn Fox Keller's brilliant biography of Nobel Prize-winning geneticist Barbara McClintock, A Feeling for the Organism.

McClintock worked for years to prove her claim that bits of genetic material that she called transposons or transposable elements could move around in the genome, with the result of switching on or switching off genes.  Her research was largely ignored, mostly because of the attitudes toward female scientists back in the 1940s and 1950s, the decades during which she discovered transposition.  Her male colleagues laughingly labeled her claim "jumping genes" and forthwith forgot all about it.

Undeterred, McClintock kept at it, finally amassing such a mountain of evidence that she couldn't be ignored.  Other scientists, some willingly and some begrudgingly, replicated her experiments, and support finally fell in line behind her.  She was awarded the 1983 Nobel Prize in Physiology and Medicine -- and remains to this day the only woman who has received an unshared Nobel in that category.

Her biography is simultaneously infuriating and uplifting, but in the end, the uplift wins -- her work demonstrates the power of perseverance and the delightful outcome of the protagonist winning in the end.  Keller's look at McClintock's life and personal struggles, and ultimate triumph, is a must-read for anyone interested in science -- or the role that sexism has played in scientific research.

[Note: If you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]