Why wasn’t this machine in my life 35 years ago?

Let me tell you about this miserable year I had in grad school. Judith Eisen and I had figured out that there was this repeating pattern of spinal motoneurons in zebrafish — this was special because it meant that we had a new set of identified neurons, cells that we could name and recognize and come back to in fish after fish, and that had specific locations and targets. I had flippantly suggested that we name them Primary Zebrafish Motoneurons (PZM cells, get it?), but a colleague, Walt Metcalfe, talked me down from that bit of vanity — it is so 19th century to name a cell after yourself, even indirectly — and I came up with the rather more mundane names of CaP, MiP, and RoP, for caudal, middle, and rostral primary motoneurons, for their location within each segment. So yay, interesting result, and it fit well within the overarching project I was working on for my thesis, which was on the development of connectivity in the spinal cord.

Specifically, I was looking at how another famously named neuron, the Mauthner cell, grew an axon down the length of the spinal cord and hooked up to the motor neurons there. Mauthner is a command neuron; when it fires, it sends a signal to one side of the spinal cord, triggering the motoneurons on that side to make all the muscles contract — the fish bends vigorously and quickly to one side as part of an escape response. Finding out that our one named cell, Mauthner, was making synapses on another set of named cells, our primary motoneurons, was an opportunity to look at connectivity in an even more detailed way.

But then my committee asked a really annoying question: how do you know Mauthner is making synapses on CaP? Have you looked? Thus began my miserable year. I said no, but how hard can it be? I’ll just make a few ultrathin sections, look at them in the transmission electron microscope, snap a few pictures, and presto, mission accomplished. Except, of course, I hadn’t done EM work before. Our EM tech, Eric Shabtach, made it look easy.

So I started learning how to fix and section zebrafish embryos for EM. It turns out that was non-trivial. I was working with nasty chemicals, cocktails of paraformaldehyde, glutaraldehyde, and acetaldehyde, which all had to be just right or you’d end up with tissue blown up full of holes. I had to postfix with osmium tetroxide, with all the fun warnings about how just the fumes can fix your corneas. And then I had to master using an ultramicrotome and making glass knives, and cutting those fish just right. There were times I’d get the fixation perfect and then find I’d screwed up on the sectioning, and produced a lot of crap as the knife chattered across the section, or there was a bit of a nick in the blade that gouged furrows across every one. And then the way we got these extremely thin slices into the scope was to scoop them up on these delicate copper grids, and of course every time you were closing in on the synapse you wanted, that section would have the most interesting part fall right on an opaque copper grid wire. Or you’d find that that was the section you lost.

It takes a lot of skill and practice to do electron microscopy well, and it also takes a little luck, at least in the old days, to find the one thing you were looking for. I failed. I struggled for about a year, going in every day and prepping samples and spending hours slicing away at tiny dead embryos imbedded in epoxy, before finally giving up and deciding I needed to do stuff that was more immediately successful, because I needed to do this graduation thing.

I still kind of cringe remembering that long fruitless year, but now I can ease my conscience by just telling myself the technology wasn’t yet ready. Here’s a cool new paper, Whole-Brain Serial-Section Electron Microscopy In Larval Zebrafish. They’ve automated the process. Just look at this goddamn machine, it’s beautiful:

Serial sectioning and ultrathin section library assembly for a 5.5dpf larval zebrafish. a, Serial sections of resin-embedded samples were picked up with an automated tape-collecting ultramicrotome modified for compatibility with larger reels containing enough tape to accommodate tens of thousands of sections. b–c, Direct-to-tape sectioning resulted in consistent section spacing and orientation. Just as a section left the diamond knife (blue), it was caught by the tape. d, After serial sectioning, the tape was divided onto silicon wafers that functioned as a stage in a scanning electron microscope and formed an ultrathin section library. For a series containing all of a 5.5dpf larval zebrafish brain, ~68m of tape was divided onto 80 wafers (with ~227 sections per wafer). e, Wafer images were used as a coarse guide for targeting electron microscopic imaging. Fiducial markers (copper circles) further provided a reference for a perwafer coordinate system, enabling storage of the position associated with each section and, thus, multiple rounds of re-imaging at varying resolutions as needed. f, Low-resolution overview micrographs (758.8×758.8×60nm3 vx –1) were acquired for each section to ascertain sectioning reliability and determine the extents of the ultrathin section library. Scale boxes: a, 5×5×5cm3 ; b, 1×1×1cm3 ; c, 1×1×1mm3 . Scale bars: e, 1cm; f, 250µm.

Then they scanned in all those tidily organized thin sections into the computer for reconstruction. I am impressed.

We next selected sub-regions within this imaging volume to capture areas of interest at higher resolutions using multi-scale imaging. We first performed nearly isotropic EM imaging by setting lateral resolution to match section thickness over the anterior-most 16000 sections. All cells are labelled in ssEM, so this volume offers a dense picture of the fine anatomy across the anterior quarter of the larval zebrafish including brain, sensory organs (e.g., eyes, ears, and olfactory pits), and other tissues. Furthermore, this resolution of 56.4×56.4×60nm3/vx is ~500× greater than that afforded by diffraction-limited light microscopy. The imaged volume spanned 2.28×108 µm3 , consisted of 1.12×1012 voxels, and occupied 2.4 terabytes (TB). In this data, one can reliably identify cell nuclei and track large calibre myelinated axons. To further resolve densely packed neuronal structures, a third round of imaging at 18.8×18.8×60nm3/vx was performed to generate a high-resolution atlas specifically of the brain. The resulting image volume spanned 12546 sections, contained a volume of 5.49×107 µm3 , consisted of 2.36×1012 voxels, and occupied 4.9TB. Additional acquisition at higher magnifications was used to further inspect regions of interest, to resolve finer axons and dendrites, and to identify synaptic connections between neurons.

Thirty five years ago we were storing most of our image data on VHS tape, and our computers all used floppies with about 100K capacity. I wonder how many floppies we would have needed to store all that? Oh, I did get my very first hard drive about the time I graduated, which held five million bytes. I was very proud.

I was wondering if they actually had the EM section demonstrating the Mauthner-to-CaP synapse. Probably. Now it’s such a minor issue that has already been shown elsewhere and with multiple techniques that it isn’t even mentioned. It’s in their data set, though, I’m sure. They’ve reconstructed the entire axon arbor of CaP in serial EM sections.

The position of a caudal primary (CaP) motor neuron in the spinal cord and its innervation of myotome 6 projected onto a reslice through ~2200 serial sections.

2200 sections! I spent a year on that project and probably got half that number. I don’t know whether to cry or steal the data, invent a time machine, and go back and hand myself a photo at the start of that year.

What do Louise Mensch, Milo Yiannopoulos, and Piers Morgan have in common?

They’re all British grifters, notable incompetents in their own country who came to America to exploit the cachet of an otherwise useless accent. These are people so stupid and obnoxious that people were mocking them ceaselessly at home, so they came to a country where gullible people think a British accent makes you sound intelligent. It’s a really familiar con, too.

So prevalent is the British mountebank in America that it has long been a literary trope. Perhaps the earliest specimens of the genre were the King and Duke from Mark Twain’s Huckleberry Finn. Claiming to be disinherited British royalty, these two “rapscallions” swindle their way across the Midwest, conning gullible, small-town Americans with their schemes. A century later, F. Scott Fitzgerald described the type in The Great Gatsby. “I was immediately struck by the number of young Englishmen dotted about,” Nick Carraway observes while in attendance at one of Jay Gatsby’s magnificent parties. “All well-dressed, all looking a little hungry, and all talking in low, earnest voices to solid and prosperous Americans. I was sure that they were selling something…They were at least agonizingly aware of the easy money in the vicinity and convinced that it was theirs for a few words in the right key.”

It’s too bad it doesn’t also work the other way. I think the impression an American accent leaves in the UK is that one is crass and loud and vulgar, which doesn’t help leave a good impression at all. If you’re going to try and dump Piers Morgan on us, it would only be fair if we could send you a Bill Maher, you know.

Ha ha, charade you are

So perfect. An artist is going to float 4 helium-filled pigs over the Trump logo in Chicago. Thank you, Pink Floyd. Roger Waters must be prescient — they released the Animals album 30 years ago. I guess they saw Trump coming.

If you don’t remember the lyrics…

Big man, pig man
Ha, ha, charade you are
You well heeled big wheel
Ha, ha, charade you are
And when your hand is on your heart
You’re nearly a good laugh
Almost a joker
With your head down in the pig bin
Saying ‘Keep on digging’
Pig stain on your fat chin
What do you hope to find
Down in the pig mine?
You’re nearly a laugh
You’re nearly a laugh
But you’re really a cry

The Cult of Instant Pot

My daughter got me one of these infernal devices for Christmas, and I am becoming a devotee. Yesterday, I made split pea soup in it, tossing in 5 cups of water, two cups of split peas, a few carrots and tiny potatoes and a pinch of salt and garlic (garlic goes with everything), and zapped it in the pressure cooker for 15 minutes, and the results were perfection, the creamiest tastiest pea soup I’ve ever made. None of that overnight presoak nonsense, either.

I’m only mentioning it because I’ve been looking forward to day-old split pea soup all day long, and shortly I will be consuming it again. It was so quick and easy I’m going to have to fix it more often, like every day. If there are drool marks on this post, you know why.

OK, I might have to exercise a little more restraint than that, unless I am willing to be served divorce papers.

Oh, great — that’s how they acquire a taste for human flesh, you know

One of those forensic research facilities in Texas — the kind where you leave human bodies out to rot to figure out the progression of decay — has discovered deer nibbling on the corpses. Every November I’ve got students skipping class for the hunting season, and now I’m going to just have to excuse them, and encourage them to get out there and slaughter the man-eating monsters…before they get us.

Man-eating deer. Or is it deer eating man?

On second thought, maybe some humans are alien enough

This is the trailer for a house for sale in Beverly Hills. It is not safe for work.

OPUS | Red Band Trailer from Drew Fenton on Vimeo.

It’s going for $100 million. I have no plans to sell my house, but if I do, it’ll be going for a lot less than that. I am going to steal one idea from them, though, and put up a video. It’ll be shot on my iPhone, and it’s going to feature me, in a speedo, painted gold and writhing on our couch. The offers will come pouring in.

Guardians of the Galaxy vol. 2 and the taxonomy of aliens

I watched Guardians of the Galaxy, vol. 2 this weekend. It was a fun bit of fluff. I’m also a fan of movies that portray god-like aliens as inherently inimical to humans and evil by nature, and that therefore our purpose, if we have any at all, is to kill gods. And then there are lots of space battles with funky ’70s music and funny one-liners. Groot is adorable, but my favorite character had to be Drax.

But, I have to say, I was also distracted by the horrible science. I know, I know, this is a fantasy story based on a comic book, but I am compelled to judge.

First up, the video game-style space battles. They’re fun to watch, but come on — World War I dogfights and weapons with such high energies that you can use them to carve your way to the center of a planet? And when your ship gets hit by them it might chip the paint but otherwise just bounce off? Also, those streams of little ships in formation getting zapped by the good guys, I recognized those — I played Galaxian in my misspent youth.

Secondly, everything in this galaxy seems so cramped and close-up. “Radio” your coordinates to the galaxy at large, and in minutes hordes of space ships show up to hunt you down. Activate your doomsday device on your remote world and all of the evil death weapons start blossoming simultaneously on worlds separated by a hundred thousand light years. It’s a cartoon, but I miss the idea of the vastness of the universe.

My biggest gripe, though, is with the lazy biology. All these alien races from the far-flung corners of the galaxy, and mostly what they are is humans with different colors of body paint. This is less like a congerie of aliens and more like Burning Man costumery, only with less nudity.

But really, the movie was good mindless fun and I’ll see it again. I confess, though, in slow moments I was thinking about a SF taxonomy of alien universes. And I sort of assembled a preliminary draft in my head, which I’ve now set down in bits on the interweb. Basically I looked at these aliens and thought about how long ago these creatures would have hypothetically shared a common ancestor with Earth humans as a measure of how far out of the box the creators were thinking. The answer is usually not far at all — most aliens are Weird Americans In Space.

Here’s my classification scheme. Please do argue with it.

I. Every alien is human. They might have latex bumps on their forehead or fluorescent purple skin, but any Earth-type person is capable of breeding with them. Also, they tend to conveniently speak English.

These stories cannot comprehend the idea of a different species, and typically portray every distant alien world as having diverged from American culture roughly 100 years before.

II. Every alien is humanoid. No, you can’t mate with them, and probably don’t want to. They don’t speak English, at least, but they do have a vocal apparatus that produces sounds of the same type and range as ours, with concepts that are easily translatable.

These aliens are basically members of our genus, possibly family, and divergence occurred sometime in the Cenezoic, typically within a million years.

III. Every alien is a vertebrate. They have a head, paired eyes, jaws, a small number of limbs. They may be based on Earthly reptiles, for instance, but are often strangely distorted into a bipedal form; faces tend to be flattened and made expressive to human eyes.

Divergence is at the level of class/order, representing maybe 100 million years of evolution.

IVa. Every alien is a member of a terrestrial phylum. One type might be insectoid, another squid-like, another reptilian. Every form fits into a familiar type, although again usually the main characters will be humanoid.

Divergence at the level of the phylum implies maybe 500 million years of independent evolution.

For an interesting take on this category, Russell Powell points out that we seem to constrain ourselves to fixed sets of morphological modules that are only coupled by evolutionary contingencies, so we shouldn’t expect to see Type IVa aliens.

IVb. Every alien is a chimera with characteristics of multiple phyla. Put insectile compound eyes on the face of a humanoid; tentacles on your 4-legged vertebrate iguanoid.

The components might be separated by 500 million years of evolution, but the combination implies some kind of anastomosing lineage with fusion of wildly different species. This doesn’t happen.

V. Every alien clearly has a completely unique evolutionary history and is not in any way related to any Earthly form. There may be some convergence in general form — they may have legs, for instance, for locomotion — but they are completely different in detail — different pattern of joints, for instance, and they don’t necessarily terminate in a radial array of digits.

These represent billions of years of independent evolution from a different starting point.

Aliens like this don’t exist in movies, because they’d be visually disturbing. You know how some people freak out at the sight of spiders? It would be like that for the entire audience, who’d be struggling to interpret what the creature is doing and trying to fit it into a threat/non-threat category. You occasionally find them in science fiction novels, where the author doesn’t have to show you every distressing detail in every scene.

How about some examples?

The Star Trek universe is Type I across the board, unrelentingly vanilla. They even have a totally bullshit rationalization, that all those species are related. Also, the idea that two species could have radically different internal anatomy and physiology (green blood and two hearts in one, red blood and one heart in another) yet still look superficially similar and be able to interbreed is painfully stupid.

Speaking of painfully stupid, James Cameron’s Avatar managed to have a Type I main species (they were just big, blue, long-limbed people) with a visually well-developed background fauna with unique biological characteristics that would never in a billion years have produced the Na’vi.

The Star Wars is primarily Type I; almost all the main characters are indistinguishable from Homo sapiens, but there are a few exceptions. Chewbacca is Type II; a few of the background characters, like Admiral Ackbar or Jabba the Hut are type III.

Babylon 5 is an interesting case. Once again, it’s primarily Type I — this is simply a necessity to allow human audiences to identify with the cast. So you have Earth humans plus Centauri, Minbari, and Narn that are basically Type I humans with varying degrees of latex appliances. But then you also have the Shadows, who are Type IVa insect-like aliens, and the Vorlons are the very rare Type V, conveniently hidden away in strange-looking environment suits so you don’t have to see them…and the creators don’t have to portray a truly alien species.

The heptapod aliens in Arrival are space-faring octopuses, putting them squarely in the Type IVa category.

For the horror fans, the Alien xenomorph is Type III. It’s not that alien, sorry. It really relies on its similarity to familiar predatory morphologies to provide the scares. I just wish Cameron would stop fucking the story up with his totally bogus bad evolutionary biology.

The Predator from those movies is Type II. Those are some impressively elaborate mouthparts glued on, but it really is just a standard humanoid with some strange facial prosthetics.

As for the Guardians of the Galaxy series, it’s once again a biologically boring Type I universe where the primary species delineator is, distressingly, skin color. The colors tend to be Day-Glo hues of blues and greens and purples and oranges and gold, and fortunately no one seems to be judging people by the color of their skin, but it’s otherwise completely retro, with aliens that are only a shade different from what we got in Star Trek.

And that’s OK. These movies are for the entertainment of Earth humans, not thought-exercises in alien evolution for the delectation of freakish biologists. Don’t let my obsessions ruin what is definitely a fun movie for you.

One godless thumb up for god-murder, one primate thumb up for humor and action, one chitin-sheathed mucus-oozing appendage down for unimaginative biology, one electromagnetic flux capacitor down for bad physics, one protruding ciliated sensory apparatus emitting fluctuating phase fields radially for zgrarrl!(ptang). Obey the digits that correspond best to your cognitive and perceptual biases.