Monday, November 24, 2008

The Refind

One of the rituals of Thanksgiving at our house — including a (welcome) passel of relatives and the surreally early screening the networks choose for How the Grinch Stole Christmas — is the equally puzzling timing of airing The Wizard of Oz.

Straight men tread on this ice with care, because of the cottage industry gay dudes have made of this movie, as well as of Judy Garland [1]. But this deceptively simple film provides rich mining for all sorts of folks at many levels.

I remember, back in grad school, thinking out loud to one of Heather’s friends about how, at the end of the movie, the two Wicked Witches are gone, the Wizard is gone, and who just happens to be there to pick up the pieces? Glinda, the one who was pulling the strings all along, that’s who [2] [3].

Wide-eyed, his only reply was a sarcastic, “I’d never thought about the power politics of The Wizard of Oz before.” There are none as blind as those who will not see, I suppose.

But that’s not why I called you here today. Today we discuss an issue that is sacred — or ought to be, anyway — among search-and-rescue dog handlers. I’m talking about The Refind.

A bit of definition, since SAR dog handlers are notorious for using the same words to mean exactly opposite things, and getting into eye-gouging fights over whose meaning is the right one.

My definition of a refind is when a dog finds the search subject, returns to the handler, and then leads the handler back to the subject. It is the basic, most critical part of SAR dog training, since as I like to say, any dog knows how to find people — the trick is getting her to tell you she’s done it.

A proper refind is — and I use this word with trepidation — magical. I say trepidation because too many SAR dog handlers seem to think that you get it from pure magic, or at least without a ton of work. There is more than one way to put a refind on a dog — but none of them allow you to shortcut the work, which you have to keep doing to keep it sharp.

But when it does come together, it makes you look much, much smarter than you are. Imagine, you’re in the woods, maybe with a thick layer of undergrowth. You can’t see much farther away than 10 or 20 yards. Suddenly the wind kicks up; your dog lifts her nose into that wind, and she’s gone. Way out of sight, and as it’s a long time before you see her again, you get to count plenty of your own heartbeats.

It’s natural to doubt at this moment. Humans do that. It’s natural to want to call her back, assume she’s chasing a deer, get on the radio and ask anybody in the neighborhood whether they’ve seen her. Shut up; stay still; wait.

She comes running back — not a leisurely trot, she’s a dog who’s clearly on a mission. She runs up to you; she sits; she barks; she lays down; maybe you just look at her and interpret her body language; whatever you’ve trained her to do. But you know she has it.

You tell her, “Show me.” She runs back the way she came — or maybe a slightly different way, she’s been thinking on the way back to you and maybe has a better route in mind. Don’t panic, don’t blow it now that you’re so close. You follow her, knowing that she’s got it because she stops to look back at you — or because she doesn’t look back. And you crash through the brush, and there she is, sitting in your search subject’s lap.

And the state trooper walking beside you, who’d barely concealed a sneer at your silly affectation that a dog could be any use in this venture, throws his eyes wide. And there’s one more believer.

The Refind, as you know unless you’ve been sealed up by a daisy-cutter in Tora Bora for the last 69 years, is that immortal moment when Toto escapes the Wicked Witch (under spear fire, yet), runs back to Dorothy’s friends, and then leads them back to rescue her. I kid you not, my eyes mist every time I see this scene; it’s everything we want of our SAR dogs, the primal expectation working at the back of the minds of maybe everybody who gets into canine SAR.

We actually have our own version of this gantlet, by the way: in our operational testing, we expect our dogs to be able to encounter a scary, agitated subject (entirely possible on a real search, if the lost person is hypothermic or has dementia) and still perform the refind. The dog can protect herself by keeping at a safe distance from the crazy subject; but she can’t growl or bite, and she can’t be too scared to lead you back. (Sophie, God bless her, tried to charm the subject into throwing the stick for her.)

Flash to a much-earlier scene, from our beloved Lilly’s puppyhood, when the 12-month-old SAR trainee, accompanying us on a backpacking trip, needed to walk along a log to cross a rain-swollen stream. She’d done this sort of thing without thinking about it hundreds of time, but that was without roaring water, way too deep for her to walk across, below her. Now she was just plain scared.

We did our best to protect her. We put her harness on, and clipped her into a safety line that Heather held from the shore, while I walked along the downstream side of the log [4] to reassure and coach her. She cried all the way; but she didn’t hesitate, because we’d asked her to do it. And because she trusted us.

I won’t comment on that kind of trust, except to say that no human being deserves it; it’s a gift you take, and be God-damned humble about. This Thanksgiving — every Thanksgiving — one thing I will be thankful for is the responsibility of living up to that trust. Haven’t quite hit that high note yet, but I will keep trying. I think it makes me a better man.

But on the far side of the creek, as we clapped and squeaked and danced and gave Lilly the brave-puppy party she so richly deserved, I do remember thinking that this was the very definition of courage: being scared, but doing what you need to do anyway, without hesitating.

Fast forward to last week, when we were watching The Wizard of Oz and The Refind came on. I turned to Pip — the worthy inheritor of Lilly’s mantle as chief of staff for our little pack (as well as for the farm, which sadly Lilly didn’t live to see) — and just said, “Spears, Pip. Toto did it while they were throwing spears at him.”

Pip eyed me sidelong, without raising her head. Heather commented on the rarity of a sense of sarcasm among dogs.

Sacred to handlers, yes; by God, yes. Sacred to dogs? Well, maybe not so much.

Happy Thanksgiving to yinz and yinz’s from the frosty northern rural-burbs of Pittsburgh.

[1] OK, we’re secure; just not that secure.
[2] My humble proposal for a drinking game: you take a swig every time you want to say, “Glinda, you bitch.” Watch the movie again; you’ll be surprised at how many opportunities you get.
[3] Great minds, it appears, think alike. I haven’t read Wicked, but it sounds like my kinda book and it’s on my “to read” list. But check out Tin Man, one of the few Sci Fi Channel films that didn’t suck (OK, the ending was saccharine pap; but everything before that was great). Folks who tuned in to see a literal retelling of the L. Frank Baum books tended to hate it, but those of us who saw darkness even in the originals loved it. Sci Fi’s producers apparently have literally no taste at all, either good or bad — their films either rock or suck.
[4] Crucial crucial crucial: if you walk on the upstream side, you risk getting swept underneath the log if you lose your footing.

Monday, November 17, 2008

Papal Approved

Visiting the Chicago Field Museum a day before my 25th (yup) college reunion at the U of C, Heather and I noticed a great big sign, posted over the entrance of the new Evolving Planet exhibit. It said:


This unapologetic, non-mealy mouthed acclamation pleased me. Heather, the screaming, blue-painted Celt troublemaker that she is, tasted blood and liked it even more. Particularly in the context of her belief that the Carnegie Museum of Natural History here in Pittsburgh soft-pedaled the issue in their new dinosaur exhibit in order to avoid riling the local religious right wing. [1]

For me, though, the sign took me right down memory lane — specifically, to a 1950s-era Catholic-school edition of Modern Biology, a middle-school biology textbook that I’d inherited from my aunts, still teenagers when I arrived. [2]

I recall a disclaimer in the beginning, which said something to the effect that the Vatican neither accepted nor denied the Theory of Evolution, but only commented on the fact that only human beings had souls and the scientific theory had no bearing on the status of Adam and Eve as the first humans.

I’m sure a lot of folks will read that as sleight-of-hand to evade a scientific steamroller without actually admitting to any changes in doctrine. But this son of Abruzzo and Sicilia (not to mention New Jersey) — steeped, perhaps, in too many centuries of Vatican inevitability — read it differently: It was the Church’s way, the Galileo debacle still smarting in retrospect, of sanctioning a simple acknowledgment of reality with, to put it mildly, considerably more grace than it did in 1633. [3] The Church, let’s face it, is a vast ship that turns only very slowly.

(Hey, along those lines, keep an eye on Cicada magazine — Barnes & Noble usually either carries it or can order it for you. My historical short story “And Yet It Moves” will appear in their Jan./Feb. 2009 issue.)

All by way of saying, I’ve got a deal of cultural baggage, and thus I feel reassurance every time the over-arching theme of natural selection — which really hit me over the head, throughout my graduate school studies in biochemistry — gets a boost, substantive or moral. When it also speaks to an important aspect of my hobby, olfactory science, I’m delighted.

Submitted for your approval: an evolutionary study by Wendy Grus and Jianzhi Zhang of the University of Michigan that confirms some guesses scientists had been making about the difference between the olfactory system and the accessory olfactory system.

Here’s the rub: Most vertebrates (though maybe not us and the great apes) possess two smellers. Within the nasal cavity lies the olfactory epithelium. Embedded in the vomer bone in the nose sits another olfactory organ: The vomeronasal, or Jacobson’s, organ.

Best theory to date said that the olfactory system responds to smells as we understand them, but the VNO gets its signals from pheromones — airborne hormones that play a role in mating and other social interactions. This idea suggested a couple of amazing things off the bat:
* Because pheromones exert their action on a hormonal level, animals (and maybe humans, since VNO-like receptors appear in the human olfactory epithelium) probably respond to them without being aware of it.
* If so, airborne chemical signals may affect human behavior without us knowing it — think on the times you’ve instinctively liked (or not) another person on sight, or the fact that people tend to marry folks with crucial genetic differences linked to the VNO.

Grus and Zhang looked at another prediction made by the odors v. pheromones hypothesis: Namely, that olfactory receptors need to recognize any smell that comes along, while VNO receptors and their signals need to respond only to tightly controlled, species-specific chemical signals that developed on an evolutionary timescale.

This is profound: People have described the VNO receptors, without hyperbole, as a major engine of the evolutionary process: In order to remain within a species (i.e., stay in its mating pool), you have to remain responsive to its airborne mating signals, and only those signals. Once you lose that, you’re well on the road to becoming a new species. On the other hand, if two species respond to each others’ signals (and live close enough to each other to mate), they won’t remain two species for long (hence the concerns about red wolves mating with coyotes).

The Michigan Moleculeers found — after a buttload of lab work, one reason why yours truly is today a scientific dilettante — the evolutionary fingerprint of this distinction, etched in the vertebrate genes. Looking at olfactory receptor genes and VNO receptor genes in the mouse, rat, dog, opossum, platypus, chicken, and frog, they discovered that the olfactory genes don’t vary much between species, but the VNO genes do, in a way that parallels their evolutionary relationships.

You’d expect this, based on the proposed functions of the two organs: The olfactory receptors need to respond to the same huge spectrum of possible smells, and so they should vary as much within a species as between species — but nature has to rework the VNO receptors every time a new species splits off. The investigators followed up with a functional analysis of these genetic changes, nailing down that the VNO-associated changes actually alter the parts of the receptors that recognize odorants.

So that’s it — it’s a pretty neat result, in that it uses the hard facts of the molecules to tie together behavioral and evolutionary theory in a way that strengthens both. And if you’re Catholic, don’t worry: My read is that this result carries Papal approval.

[1] To be fair, I’m not sure I agree with her; certainly, there’s a lot to like about the new Carnegie exhibit, and it’s vastly superior to what it was before the modernization project (in case you didn't know, Andy Carnegie made sure his pet museum was at the forefront of the 19th-century dinosaur craze, and so they have a superlative collection of fossils). Having said that, I think I like the exhibits at Chicago or the American Museum of Natural History in New York better — at least until Pittsburgh opens up its Cretaceous exhibit, the absence of which, frankly, irked me at the reopening.
[2] I haven’t linked to the new textbook of that name, since I’ve no idea whether it bears any relation to my aunts’ book.
[3] Beyond embarrassing, as if that needed to be said. We only officially cleared him in 1992. The Vatican used to have a fantastic historical section on Galileo on its website, but I can’t find it at the moment; they redesigned the site since I last visited.

Monday, November 10, 2008

A Whiff of Ether

My first experience with research — and ether — was in a laboratory I will not name at the University of Chicago. I can say that I learned a lot from both experiences; what I can’t say is that I learned what I was supposed to.

Herr Doctor Professor looked and sounded the part of the biochemistry professor. But the cutting edge of biochem research had, even in the 1980s, passed his little laboratory by; the short-lived undergrad project he assigned me was to try to isolate a bacterial metabolic product, starting with a French Press (though unlike the pic in the Wikipedia entry; this one was enormous, made of steel, and used incredibly high pressures to squeeze the guts out of bacterial cells). This was classic stuff, in the sense that much the same work was going on in biochem labs 40 years earlier.

Somewhere in the procedure was an ether extraction — mixing the water containing the bacteria guts with ether, an organic solvent known for its ability to knock people cold. The idea was that our molecule might be happier in ether than water, and so might be enriched when the two solvents separated.

What nobody told me at the time is that you need to do ether extractions in a fume hood, not out in the open. I’d come to dinner at the dorm every night stoned out of my gourd — but it isn’t a high that I’d recommend to anybody, it’s a headachy, nasty affair that nobody in his right mind would seek out. I may have engaged in conversation at these dinners — my dorm mates in the immortal Fishbein House would know better than me, I barely remember.

Still, these ether-induced trances were nothing compared to the other-worldly head of steam I'd work up in physical chemistry class. I’d stumble in to the dining hall, head filled with Eigenfunctions and atomic orbital maps, literally incapable of (and probably not fit for) human interaction, at least until I got past my entree and the dancing symbols began to fade.

All of which by way of saying, though I have in the past been prepared to and even capable of performing, to a fashion, in that world [1], I’ve never pretended to be a physical chemist or biophysicist. I fully expect to get some stuff wrong in this blog site; occasionally I expect I’ll get something egregiously wrong. But there’s no wrong quite so wrong as the wrong I’m likely to be when I trespass in the land of biophysics.

Having said that, I feel compelled to talk about 1993 report by Doron Lancet and folks at Tel Aviv University that I just discovered. I was digging around for information on binding constants in olfactory receptors, and stumbled across an amazing little article that I’m surprised hasn’t been more heavily referenced. It provides that rare commodity in biology: A theoretical result that may matter.

What Lancet and buds did was ask a simple question: Based on what we know about the olfactory system’s mission and the nature of the molecules it recognizes, can we predict how many receptor types you’d need to do the job? (See Broken Bottle Fight for a discussion of how many they actually have.)

Conceptually, it’s pretty simple. Most enzymes and receptors in the body have been honed by evolution to interact very specifically and tightly to a biological target molecule — for an enzyme, it’s the substrate; for a receptor, the ligand. But for three systems in the body — the olfactory system, the immune system, and the liver’s system for disarming toxins — that kind of 2.7-plus-billion-year prep isn’t possible. All of these systems need to be able to respond to something that’s absolutely brand-spanking new, and respond more or less the moment it heaves into view.
So you need a system containing a randomly generated variety of receptors (or a variety of enzyme binding sites, for the liver’s cytochrome P-450 system) that sit there, waiting for the target that they just happen to recognize.

Here’s where I’m speaking in metaphor not as a didactic tool, but because it’s more or less my own level of understanding. Your mileage may vary, may cause cancer in high doses, don’t stand on top rung of ladder.

The Tel Aviv team concentrated on iodovanillin, a chemical derivative of the molecule that gives vanilla its flavor and odor, as a molecule pretty typical of both the odorants that olfactory receptors have to recognize and the haptens to which the immune system needs to respond. The idea was to estimate how many randomly generated receptors you’d need for a system to recognize iodovanillin about as well as the sense of smell recognizes it.

A random population of receptors should recognize a ligand roughly as the right half of a kind of bell curve [2]. Most of your random receptors will hardly recognize the ligand at all, but a few curve-breakers will latch onto it much better than the average bear:

It’s the right-hand part of that curve that's interesting: The receptors in that tail are the few that have a strong enough recognition for the new ligand that they can trigger a biological response. And making that right-hand tail nice and fat depends on how hard the ligand is to recognize and how many receptor types you have. The harder the ligand is to recognize, the more random receptors you’ll need to have, by pure chance, one or more that can do the job.

Lancet and crew came at the question in two ways, both of which essentially measured how hard iodovanillin is to recognize. Note that I’m not sure whether iodovanillin actually has a smell — again, the idea was to get an estimate for a typical odorant or hapten, and iodovanillin fit the bill.

For the first calculation, they used a random mix of cow antibodies (which they got from blood from a random cow) to see just how well they stuck to this molecule; in the second, they used data from experiments to measure human olfactory sensitivity.

The two methods basically agreed — 300 to 1,000 receptors from the cow data, 500 from the human data. More interesting, those numbers are pretty close to the known number of genes producing olfactory receptors in vertebrates (again, Broken Bottle Fight goes into this in more detail).

Even neater: in terms of number of olfactory receptor types present in each species, the lower bound of that range is where humans seem to be, and the higher bound is close to where animals normally though of as being able to smell very acutely, such as dogs and mice, sit. Not coincidentally, maybe, the theory would predict that animals with more receptor variety would by definition have more potential for developing an acute sense of smell.

Though we may be over-mining the result at this point, and the number of human receptors isn’t completely nailed down, it is interesting that the number of receptors the second determination projects as necessary to really get a good snootful of iodovanillin is more than humans have at our disposal. So maybe our dogs enjoy vanilla more than we can.

Unless I’ve got it wrong. Who knows how much damage all that ether — let alone the physical chemistry — did?

[1] Straight Bs, if you must know, though it was a spectacular pattern: I’d have an A through the quarter, and then crash and burn on the damned final exam — see an early credit of mine in Nature magazine, though I’m not sure whether you’ll be able to download the text.
[2] Actually, it’s technically a
binomial distribution, which isn’t exactly the same thing, but the idea is similar — a few members of the population are going to be curve-breakers that are very good or very bad at the activity in question, but most will be so-so.

Wednesday, November 5, 2008

Sympathy for the Dubya

I promise not to turn this into a political blog, but like many bloggers this morning, I just had to comment.

Full disclosure: I picked Obama as a winner (and the winner) quite some time ago, early in the Democratic nomination process when few would have given him odds (Heather can testify to this). And I'm no fan in any way, shape, or form of the current administration. But yesterday's (hopefully) sea-changing election, and its implied repudiation of the G. W. Bush White House, brought to mind a story that argues against making one's political enemies into cartoon villains. It also, possibly, argues in favor of our president-elect's call for humility among the victors last night.

I can't remember which White House correspondant told this story -- but it came from the dark, dark days immediately after 9/11, when the sky was indeed falling and nobody knew when the next attack might come. The correspondant told President Bush something along the lines of how he sympathized with the latter, because "nobody asks to lead under circumstances like these."

Bush's response was as revealing as it was (to many Democrats, at least) surprising: He shot back, "Some of us do ask for it."

Damn. Just when I had the guy comfortably cubbyholed as a lightweight, he says something, off the cuff (so that you know it wasn't scripted), that gets more profound every time I read it. Contrary to the broad parody that many of us (me included) have accepted for the man, there is clearly an intellect there, an ability for self-reflection I had no idea existed in the guy. There may be layers of rich-kid, frat-boy, and tough-guy-candidate covering it up, but this is in fact a guy who realizes he is fallible, and that his choices carry profound weight. Maybe his political career did not allow him to show that side of himself -- everybody else in his family is pretty sharp, and the best critiques of his intellect I've heard are not that he's not very bright, but that he's just incurious -- but it's there all the same.

So there it is; many of my fellow Dems will say it's precious little after eight years of rock-solid self-assurance in defiance of any contrary evidence. Many Republicans will bristle that I ever bought into the over-simplification. But the story speaks to me, somehow, way out of proportion to its place and time.

God bless America.

Monday, November 3, 2008

A Bite at a Time

The woman behind the T-shirt table — I was at a public safety conference that will remain nameless — leaned back, eying me up and down.

“You’re pretty small,” she said. “You should probably take a large.”

At five feet, nine inches, I tend to weigh in between 160 and 170 pounds. To my mind, that’s decidedly average. But I had to admit that, in a relative sense, her oxymoron was apt: Both I and the large T-shirt I wound up buying were at the bantam end of the conference’s attendees.

I don’t often weigh in on public health issues, but the weird symmetry between a pair of completely unrelated publications really brought the topic of size, as well as that story, to mind recently.

First, in a recent British Medical Journal article, the common wisdom that wolfing down your food makes you more likely to over-eat gained some support. Hrioyasu Iso and crew at Osaka University reported that people who reported that they ate meals quickly were about twice as likely to be overweight as those who said they didn’t. Those who reported eating until they were full were, similarly, twice as likely to tip the scales. If you do both, you’ve got thrice the chance of being overweight.

The idea is pretty simple: Your body has to digest some of the food you’ve eaten to be able to sense that you’ve eaten it. If you wolf it down, your body’s satiation doesn’t catch up with the intake, and you overshoot. Amazingly enough, the fast, full eaters even outdid binge eaters — whom the Osakans analyzed separately — in total calories consumed.

True, any result that assumes people tell the truth when you ask them to report about themselves needs confirmation by another method — but it sure seems credible.

Well, imagine my surprise when, the very next day, I caught a strangely reminiscent Perspectives article in Science by P. Martin Sander and Marcus Clauss at the universities of Bonn and Zurich. Their paper discussed the latest findings on what allowed giant sauropod dinosaurs like Apatosaurus and Brachiosaurus to supersize themselves.

Can you see this one coming? They didn’t stop to chew their food.

Here’s the conceptual problem with these animals’ overly ample size: mammals, such as elephants and the extinct Paraceratherium, can and could get pretty big. So could other, distantly related dinosaurs, such as the duck-billed Shantungosaurus and the perennial favorite, Triceratops (these are all vegetarians, BTW; we’ll get to the carnivores shortly). Interestingly enough, this set of giants tops out at roughly 10 to 20 metric tons. But the sauropods were literally in a class of their own, with masses up to 80 metric tons.

Sauropods got that large for a number of reasons: But one primitive feature — a characteristic they shared with the species they evolved from but not necessarily later species – seems to be the enabling issue. Namely, the fact that they neither chewed their food (their jaws were relatively tiny and weak, their teeth designed for clipping rather than chewing) nor ground it up internally with a crop or rumen.

See, if you’re going to swallow leaves, twigs, and whole branches without grinding them up, you need to give them a lot of time to digest. And that requires a big, huge stomach, which slows digestion to the required rate even if you’re shoveling it in. (Which, if you’re going to grow to 80 tonnes, seems de rigueur.)

’Course, if you are going to grow that large, you need to get hold of food that other animals can’t. Hence the long neck, which would be a huge vulnerability if you weren’t big enough to crush the predators. And an anatomical impossibility if you didn’t have a relatively tiny head: that, in turn, possible because as you have no need to chew, you require no heavy jaw musculature or skeletal structures in your head. Nicely synergistic, no?

One other primitive feature played into the sauropods’ vast size: Big mammals can’t get much bigger, in part, because raising a small number of large, live-borne offspring would be ruinously expensive; since sauropods laid many eggs, they sidestepped this issue. Add the one decidedly modern sauropod characteristic (one that they didn’t share with ancestor species), a bird-like respiratory system that can actually get air down that long windpipe, and it all sounds like a body plan.

And the top predators? Well, they tend to be smaller than their prey, to avoid a metabolic pyramid scheme. But the Jurassic period (when sauropods flourished), and the Cretaceous (when they were present but much less predominant), grew their meat-eaters big, too (think Allosaurus and Tyrannosaurus, vs. the more “normal,” dog-sized Velociraptor). Sander and Clauss suggest that all them herbivore eggs were the reason: Lots of offspring for the veggies meant lots of food for the carnies, while still letting enough of the prey survive to feed the next generation of jabberwockies.

Lest you think I’ve dropped my original thread: Apatosaurus got to its huge size a bite at a time, and so have we. Check out the U.S. data between 1960 and 2002 for adults age 20-29, when we’re supposed to be young and skinny:

Source: U.S. National Center for Health Statistics, Mean Body Weight, Height, and Body Mass Index, United States 1960-2002. Advance Data No. 347. 18 pp. (PHS 2005-1250).

Holy crap. I guess we’d better start chewing.