Monday, December 29, 2008

Now Wait a Minute ...

It was exactly the kind of search that members of our all-volunteer team are not supposed to be doing: A missing despondent, spouse couldn’t account for all the guns in the house, and a very suburban setting to boot. It’s what we simply call a “law enforcement search,” three guesses who has the training, equipment, and authority to conduct it.

Having said that, just because we couldn’t look for the subject didn’t mean we couldn’t help at all. Our folks took places in the incident command post; among other field-search specialists, Barbara Butler, then a rookie member of our team, and I accompanied a local law officer on a house-to-house survey of the neighborhood, to find out if anybody had seen our guy.

I scored some points out of the gate, by asking the officer if he knew if anybody in the neighborhood was out of town or of any houses otherwise unoccupied. He realized right away what I was getting at, and drove us over to a house that we canvassed quickly to make sure there weren’t any open or unlocked doors or windows. Dead end, but it’s always good to be pitching ideas they like [1].

It was also a bit of an education as to how the world looks to our law-enforcement colleagues: I recall our reception at one house. The officer had commented on these folks being frequent fliers, as it were, and they were bristling with hostility the instant they saw the squad car pull up. But when he introduced us as the department’s search-and-rescue team [2], and it became clear we were looking for their missing neighbor and wanted their help, not to roust them, they brightened up and did what they could. They hadn’t seen anything, but I like to think it may have helped both family and cop down the road to have had at least one interaction that wasn’t adversarial.

But the reason I bring this story up is what happened just as we were saying goodbye to those folks: the officer’s radio crackled with the news that a state trooper had found our guy, not too far from where we stood. Barb and I piled into the back of the cruiser and got quite a ride.

As we careened down the suburban avenues, lights and sirens going, other local and state police cars filed in with us until we were something of a parade. It was fantastic, like being the cameraman for an episode of Cops.

So we pull up to the verge of a small, wooded local park, and the officers pile out of their cars, running into the woods. I don’t think that at the time I knew the full story — that the subject had come at a state trooper with a knife — but it was pretty clear that the situation was their bailiwick. Not for us untrained, unarmed volunteers.

Barb is walking after them.

My hand comes down on her shoulder: “No you are not,” I say, in what probably wasn’t the only time I’ve pulled rank on a junior team member, but may be the only time it ever worked. A few minutes later, we see the police escorting the guy to one of their cars — the trooper had had a Knock on Wood [3] moment and come through with flying colors, disarming a mentally ill subject without having to hurt him.

This is not to pick on Barb, by the way: in the rush to go help, rescuers often get themselves into situations they can’t handle. Tunnel vision kills rescuers: that’s why it frustrates me when everybody lionizes a local rescuer who leaves a widow(er) and kids behind attempting something he or she wasn’t trained to do. You’re always supposed to survey any rescue scene and make sure there isn’t a situation that could make you patient number two; you’re always supposed to stay within the limits of what you’ve been trained to do — and just because people make understandable, very human mistakes, teammates are supposed to rein you in now and again.

All the best intentions aside, somebody just has to say, “Now wait a minute ...”

Enter a paper from last year on ground-scent tracking by humans, which came to my attention again because an automated PychINFO search tagged it (possibly because it just entered that database). The leaders of the multi-institutional team that did the study were Jess Porter of UC Berkeley and Noam Sobel of the Weizmann Institute of Science in Israel.

We have to keep one big thing in mind: These guys were studying whether humans could follow a ground trail, much as a search-and-rescue trailing dog does, mainly because they wanted to study the phenomenon of ground trailing with the benefit of subjects that can tell you what they’re thinking and what strategies they’re using, and will accept all sorts of nose and head attachments that might get you bit by other subjects. On these terms they succeeded amply [4].

The idea was simple: Could they produce a trail of a scent that humans can detect — chocolate — that humans could follow, without the use of their eyes or other senses? And what would that experience teach about how other species follow ground scent?

The short answer: People could not only learn to follow a chocolate scent on the ground, they could get much better at it with practice. Even more interesting:
* Just as in dogs, a higher frequency of sniffing allowed a more accurate and speedy trail.
* As in critters as different as maggots and rats, both nostrils have to be in play for a good, efficient trail, further cementing the human subject as relevant to what the animals are doing.

The latter observation was particularly interesting from the SAR perspective, because it isn’t at all clear how two nostrils, right next to each other, can give you any useful information about which direction to move along a trail. How can a dog’s nostrils, maybe an inch apart, tell you anything about the age of scent in either direction when the microscopic skin particles that carry ground-based scent are only a fraction of a second older than those an inch farther down the trail?

The human subjects simply told Porter, Sobel et al. how they did it: They worked along the edges to keep themselves oriented, in much the same way that a smoke-blinded firefighter sticks to the wall to keep form losing his way in a burning building. And much the same way a number of species follow airborne scent plumes. And for that, the small separation of vertebrate nostrils is more than wide enough, as the outside edges of a scent plume can be fairly sharp.

So this pretty much looks like a win for nurture over nature, right? Maybe humans can become good enough at scent tracking to do without the bloodhounds? Even the researchers said their findings “... suggest that the poor reputation of human olfaction may reflect, in part, behavioral demands rather than ultimate abilities.”

The moderation of that statement with “in part” aside, there’s only one problem with this idea, and it’s where the nurture-conquers-all take starts to fall apart. Instead of leaving trace scent on the ground, which is what SAR dogs follow, the researchers used a string soaked in odorant to create their “ground scent.” That means that, instead of the scent impression left behind by a moving point source of scent, which is what a SAR dog has to trail, their subjects were traveling along a linear source of relatively constant scent. The ersatz trail doesn’t vary nearly as much, if at all, in age and, presumably, intensity as you go along. This isn’t immediately important to the researchers’ findings, but it does cast a shadow on the the long-term relevance (though they could re-design the experiment to get around this).

A string soaked in chocolate is a much stronger, more consistent scent source than a moving human being, whose microscopic debris are hitting the ground in a ragged path partly dictated by crosswind and possibly varying quite a bit in intensity as it goes along. The humans may be able to do the scent-string task, and they may even get good at it: but it’s not the same job the dogs do. And when you compare what humans can do with a continuous, presumably strong scent source versus a dog following a trace trail that’s a day or two old — this experimental design can’t even touch the subject of trail aging realistically — and you realize that the dog is achieving something vastly harder.

Worse, the information this experiment gives on how the human subjects followed the scent trail may not be relevant to real-life scent trailing: because the trail doesn’t vary along its length like a real one does, the directional cue is vastly different. The researchers dont say, but it looks like their subjects basically knew which way to turn once they hit the trail, they just needed to know they’d hit it — and to stay with it once they did. As such, the situation is far closer to that of detecting airborne scent plumes, as in the research I cited above and as airscenting SAR dogs do, than it is to ground scenting. That’s because in the former, there’s also a cue as to which direction to head when you hit the scent: the direction of the wind. For modeling ground scent, it maybe isn’t so germane [5]:

[Note that the scent actually takes the form of delicate filaments, not the dots I have here — I haven’t figured out how to draw that effect yet.]

Which doesn’t really constitute a serious critique of the present experiment — as I said, I think they can redesign it to be more realistic, and in any case they succeeded in meeting their initial goal of showing humans can trail at all. But it does remind us that something is going on between the dog’s prominent nose, ample receptor repertoire, massive olfactory bulbs, and who knows what else, that transcends anything our environment can do to help us use our smellers better.

And Barb? Well, she’s been with the team for quite a few years now, and unlike your’s truly, actually went through the official training and certification for incident staff members. At a search, she’s the boss of me.

If you want to know whether she’s ever had to rein me in, you’ll have to ask her.

[1] And you can bet that, if we’d found anything important, I would have happily given him the credit — local law enforcement are our clients.

[2] No, we’re not actually affiliated with that department. But I never argue when they take ownership of us — again, they’re our clients, and it’s a good thing when they want you. Our uniforms, by the way, were designed to look decidedly not like police uniforms.

[3] The version of the song I knew was
The Mighty Mighty Bosstones’, and it’s great — but I was surprised to find that it has a 42-year history I hadn’t known about.

[4] I’m not going to get into the difference between tracking and trailing as dog handlers use the terms, partly because you’ll get different answers from different handler, and partly because the design of this experiment obscures the issue.

[5] Without going into a ton of detail, a scent plume in the air — and probably a trail on the ground, since it’s in effect an imprint of earlier airborne scent — is pretty ragged and intermittent. Though it may seem obvious that you head into the stronger scent, in practice the direction of the stronger scent may be anything but obvious.

Tuesday, December 23, 2008

Latest Fiction Offerings

Happy Holidays.

Today I’m departing from our usual fare to update folks on my latest fiction projects.

I just received my author’s copy of the January/February 2009 issue of Cicada, which contains my short story “And Yet It Moves,” an historical piece on Galileo’s confession. This is my first resale of a story (it appeared in Paradox in 2003), and although it’s a departure from my usual science fiction offerings it is one of my favorites. The Cicada website no longer seems to allow you to buy single issues of the magazine, but I’ve found that most Barnes & Noble stores stock it; if they don’t, they can order it for you; just tell the salesperson that Cicada is the young-adult literary magazine published by the Cricket Magazine Group.

More of a professional risk on my part is A Matter of Gravity, my novel now posted to Briefly, A Matter of Gravity is a book about communication — and how understanding someone's language is crucial to unpuzzling his intent. Michiko Kawachi, a young linguist with humanity’s first-contact mission with the nont’h alien race, must decode the aliens’ language to prevent war — and discover a secret that will upend humanity's understanding of the universe. Please check out the link to the book, which will take you to the site that allows you to read and rank it.

The context: is an innovative site started by HarperCollins to allow new writers to bypass the slush-pile process. For those who aren’t familiar with the industry, the slush pile is the stack of novels they give to an under-paid, over-worked junior editor, with the instruction, “Find the good stuff: But if you take too long at it, or waste our time with books we don’t like, we’ll likely fire you within a year.” For a long time, many writers have suspected the slush-pile process was too overloaded to produce good decisions, and with so few publishers now accepting manuscripts from new writers it’s become rather hopeless even to get noticed, let alone read, considered, bought, etc. represents HarperCollins’ answer to the proposition that the slush pile process is fundamentally broken and needs to be replaced. They say they’ve had luck with it, in that by allowing visitors to the site to read and rank the books they’ve in essence recruited an army of slush-pile readers who may well be more representative of the general readership. Books that do well get considered for publication by HarperCollins: no guarantees, but at this point I have to say that if I don’t have enough confidence in my book to expose it to this process, well ...

So please check it out; you may also find other offerings on that you might want to read and rank. Heck, it’s free books to read, and you may discover your next favorite writer.

Monday, December 22, 2008

The Buzzer Buzzes On

Well. In answer to the question, “Would Americans still do this?” here is the answer.

I’m not terribly surprised that we did do this today — the memory of 9/11, and the ensuing feeling we had to let the authorities do whatever they needed to if we wanted them to protect us, is still fresh enough. You might say Abu Ghraib et al. might have taught us better, but then the original Milgram subjects had been reading about a Nazi war crimes trial in the papers just before recruitment.

I’m maybe less surprised than saddened by the fact that it was so easy for them to find subjects who hadn’t heard of the Milgram experiment.

“Did we need to repeat this experiment?” was the other question that immediately leapt to my mind. At first I wanted to say, “No,” but maybe the identical result it obtained argues otherwise. Maybe every generation needs to repeat this experiment, if Milgram was so easily forgotten.

BTW, check out my wife’s blog on this — I haven’t read it yet, but I think she may have a different take.

Tuesday, December 16, 2008

We All Pressed the Buzzer

I can’t believe I forgot another connection with yesterday’s alcoholism-treatment study — “Buzzer,” the amazing new song from Dar Williams, which I heard on the incomparable WYEP this morning while driving to work. It should be required listening for all human beings.

The song is about the Milgram experiment, a chilling psychology study from the early ’60s. Briefly, Milgram set the experiment up to look like a study of memory and learning in which the experimental (human) subject, called the “learner,” would be punished for wrong answers via an electrical shock delivered by another volunteer participant, the “teacher.” An “experimenter” monitored the process, telling the teacher when to up the voltage.

The trick was that the teacher, not the learner, was the experimental subject; and the study wasn’t about memory, but about people’s willingness, while the Adolf Eichmann war-crimes trial was still under way, to follow an authority figure’s instructions to do something awful. The learner was actually an actor, who received no electrical shocks but agonized and screamed and finally pretended to lose consciousness under the fake torture. If the teacher balked, he or she received the following set of instructions, with the experimenter escalating the commands for every objection raised:

1. Please continue.
2. The experiment requires that you continue.
3. It is absolutely essential that you continue.
4. You have no other choice, you must go on.

The shocking thing was, the experimenters got 65 percent of the teachers to go all the way to 450 volts, the point at which the actor lost consciousness. Only one teacher refused to go on before hitting 300 volts.

Turns out, under the right conditions, just about all of us are shits.

The Milgram experiment, like our alcoholism study, would probably never be approved these days. But though Milgram got his share of flak on ethical grounds, I think what this experiment taught us is too terrible and momentous to ignore, and probably in the long run justifies the damned thing. (Though some of the people who “verified” his results later on did things that make me angry, like doing it for real, with a puppy as the victim — and no, I’m not making that up.)

A lot of people know about Milgram; fewer know about what folks like psychologist Lauren Slater found out many years later. The teachers who went all the way, it turned out, weren’t the people you’d necessarily think, and neither were the folks who, at one point or another, refused to go on. One obeyer was devastated when he learned what the study had been about, and used the experience as a prod to change his life. He came out of the closet and became an activist for gay rights. One refuser went on to a long career in the military; and while I wouldn’t read too much into that, his reasons for stopping the experiment stemmed from the effect the stress was having on him, not out of concern for the victim. Two points don’t constitute much of a data set, but they show us that the details confound our broadest brush-strokes.

So here it is: We can all be shits. We all pressed the buzzer.


We all get to be individuals. We can choose to change ourselves, make ourselves more honest, braver, better. We can rise above our mistakes. Bilbo was meant to find the Ring. Hope isn’t the last refuge of the clueless.

And it begins with a one-syllable word, a word that comes easily when we’re two but not so much when we're 32:


Monday, December 15, 2008

By Any Means Necessary?

The noise damned-near deafened me as I entered the facility — a government-funded center for research on primates, placed in the boonies to avoid attention from animal-rights activists. In front of me stood a huge, Plexiglas enclosure holding dozens of rhesus monkeys, who played, ate, groomed, fought, and above all, screamed.

It measures my own ignorance, I know today, that the sight terrified and dismayed me. I didn’t realize that this is how monkeys act normally, and that the communal enclosure, which allowed them to socialize and interact as they would have in nature, actually represented the pinnacle of humane digs for these cantankerous but brilliant near-relatives of ours [1].

Monkeys are just loud, is all.

I can’t, however, repudiate my feelings as I walked back out, mulling my interview with the addiction researcher I’d come to cover. I remember being struck by the immediate relevance of this person’s work to human addiction, and thinking that this research could very well provide a breakthrough to alleviate the vast human suffering that drug addiction causes.

I also remember thinking that I wouldn’t want a daughter or son of mine to marry someone who could do what that person had done to those monkeys.

Let me give a quote that encapsulates where I’m coming from:

The value of animal experimentation to human health and knowledge is not seriously in doubt. But past “scientific” beliefs — such as that animals cannot feel pain; that an animal rendered motionless by anesthesia cannot feel pain; and that higher animals such as dogs and primates cannot feel anxiety and fear — have been overturned by increased scientific understanding.

That’s from “Vivisection,” Gale Encyclopedia of Science, Third Edition, and I’m the guy who wrote it. I’d remembered adding something to the effect that, in view of the stunning misapprehensions of the past, we should regard our views today on what constitutes humane treatment of animals with humility; but it’s not in the final version. I may well have cut it myself, in editing the piece down to the specified length. But I wish I’d included it now, because it’s an important corollary.

Both my visit to the primate research center and that encyclopedia article came back to me when I encountered a real gob-stopper of a report from 1967. Unfortunately the PubMed entry doesn’t include an abstract, so here’s my summary of what they did: They took a group of people who had been hospitalized for alcoholism and, to help them kick the habit, exposed them to alcohol in coordination with an intravenous dose of succinylcholine chloride. The effect of that injection, from the original:

It was possible to obtain apnea within seconds of the patient having tasted the beverage. When apnea occurred, the patient was ventilated with a breathing bag. After breathing was restored the patient was asked to get up and dress.

A couple of important details: These guys didn’t invent the method, and were neither the first nor the last to report on it. And clearly, alcoholism had profoundly harmed the experimental subjects before the study:

The criteria used in making a diagnosis of alcoholism included a drinking pattern which consistently interfered with some important aspect of the patient’s life; that is, personal health, family life, occupation or social adjustment.

Keeping in mind these guys had entered a psychiatric hospital for alcoholism (in the 1960s — the cocktail party era), I think we can assume their alcoholism was severe. And amazingly, after undergoing what was in effect a near-death experience, these guys actually referred friends with alcoholism to the study. So we can’t argue any profound lack of informed consent, at least after the fact.

But if you’re thinking of A Clockwork Orange and the (barely) fictional Ludovico technique, you’ve got me for company: Alex, too, volunteered for the surreally brutal conditioning to wean him from the joys of committing murder, rape, and general mayhem. Waterboarding also comes to mind, and all the hairy political context that comes with it [2].

Nor was this the only eyebrow-raising item in the paper: The researchers measured the patients’ abstinence and general progress using a post-study questionnaire. Normally I’d be leery of trusting folks’ self-reporting on abstinence, but in this case the researchers confirmed its accuracy by sending the questionnaire to people who knew the subjects well and could confirm whether they were telling the truth.

This would be profoundly out of bounds today, by my understanding of modern psychiatric practice. I suppose it’s possible that you could write a release form that allowed patients to sign away their confidentiality rights in this way; but I can’t help but think you couldn’t get an institutional review board to approve it, on that basis alone.

The effectiveness the method displayed in this single paper, by the way, was quite murky — amazingly enough, control subjects who didn’t receive the drug did statistically no differently than those who did. The folks who got the drug did do better than two other control groups: patients at one of the hospitals involved who did or did not comply with then-standard psychoanalytic alcoholism treatment [3]. I haven’t tracked down the later reports on this method, which may or may not have confirmed whether it works in keeping people away from alcohol; I’ve certainly never heard of anything like this being used nowadays. But is efficacy beside the point, when the means are so extreme?

I just don’t know. And I’m painfully aware that, in the context of the suffering caused by addiction, I may not have the moral standing to make the call. I’m more comfortable with my position on waterboarding, since intelligence professionals have recently begun questioning whether it’s really been all that useful, even in the very few contexts that its supporters like to raise, which pretty much was my suspicion all along [4]. In the case of today’s paper, though, the guys undergoing the nastiness were also its beneficiaries: And it bears repeating, many of them recommended the study to their friends afterward.

But I wouldn’t want my son or daughter to marry anybody who could do this to a human being.

[1] As an admittedly unscientific observation, a friend who served as a Special Forces sniper in Central America in the 1980s reports that similar monkeys were singularly smart at stealing packs, which they rummaged for food. And as they recognized and remembered individual humans, “God help you if you killed one of them,” he added. I didn’t ask him to elaborate; “nature bats last,” as they say.
[2] Though, my God: When did the appropriate context of torture become grist for political debate?
[3] Actually the researchers pointed out that their
experimental patients were statistically better off than these “standard treatment” patients, but their control patients were not. I’m not sure whether they meant to imply a kind of statistical property of transitivity there, but it’s a dubious argument. Since they admit having used parametric statistics on non-normal data, I’m even less certain that they demonstrated anything at all.
[4] Again, a friend whose past includes a stint as a military intelligence officer in the 1980s confirmed his contempt for the post-9/11 changes in interrogation technique. I’ve absolutely no respect for the feckless argument that waterboarding isn’t torture; I have more regard for those who say, “Yes, but ...” To my mind, it was never about what we (and our allies) did to a very small number of pretty-much-100-percent-known terrorists — the roughly half-dozen “high value detainees” — as much as the hundreds of guys that the method’s defenders don’t bring up, because both their guilt and the value of what they could possibly tell us, tortured or not,
seems to be less-than-well established, to be generous. I’m not proud of saying this, but if the issue were what we were doing with a few top al Qaeda leaders, we wouldn’t have had to build a prison and it probably never would have reached public knowledge.

Monday, December 8, 2008

Tasty Wheat

Mouse: Do you know what it really reminds me of? Tasty Wheat. Did you ever eat Tasty Wheat?
Switch: No, but technically, neither did you.
Mouse: That’s exactly my point. Exactly! Because you have to wonder: How do the machines know what Tasty Wheat tasted like? Maybe they got it wrong. Maybe what I think Tasty Wheat tasted like actually tasted like oatmeal, or tuna fish! That makes you wonder about a lot of things. You take chicken, for example: Maybe they couldn’t figure out what to make chicken taste like — which is why chicken tastes like everything.
The Matrix, 1999

It comes off as inane commentary, the kind of maddening banter you get whenever people are confined together by duty, incarceration, or happenstance (and which may be one reason military rifles almost always have safety switches). But in fact the doomed Mouse’s immortal lines touch on a classic question that has long plagued philosophers.

How do I know that your experience of a thing is anything like mine?

Well, olfaction scientists have an answer to the Tasty Wheat Conundrum, and — talk about maddening — the answer is, “It depends.”

I’ve gotten ahead of myself again. Let’s start, as we often do, with Buck & Axel’s Nobel-winning work on the genes that produce the olfactory receptor proteins. Conceptually, the sense of smell starts out with a simple step: Vertebrates can identify many thousands of smelly chemicals in the air because they make around a thousand different versions of the protein sensor that sits on olfactory neurons. One odorant (or a small family of odorants) tweaks one type of receptor, which in turn is present on only one family of olfactory neurons. When those neurons fire, the brain knows that, say, acetic acid (basically, distilled vinegar) is in the air.

It’s a little more complicated than that: Actually one molecule can have several parts that activate different odorant receptors. But the pattern of olfactory neurons set in a tizzy by a single odorant molecule will be constant, and unique to that molecule.

So far so good: If everybody has the same receptor(s) for the aroma of Tasty Wheat, then at that level at least everybody is tasting the same thing (smell accounts for most of the variety of “flavors” we experience).

The next step in the sense of smell is when the olfactory neurons in the nose tweak the olfactory bulb in the brain. The OB is the central routing station for all smells; it coordinates the signals coming in from the nose, and may in addition enhance those signals — for example, as a powerful amplifying system for detecting faint odors.

Every olfactory neuron with the same receptor reports to the same glomerulus — a little ball of relay neurons that sends the signal up to the higher brain — in the OB, and each glomerulus gets signals from only one type of olfactory neuron. They map perfectly, one-to-one.

This is where things get messy, and a new report by Kimberly Grossman and colleagues at my wire-mommy Alma Mater, the University of Chicago, doesn’t make it any cleaner. But it does raise some interesting questions.

What the Chicago Five did was use sophisticated imaging of glomerular activity in concert with some old-fashioned mousie-chooses behavioral experiments (thanks, I’m guessing, in part to collaborator Leslie Kay, an extremely interesting lady who I’ve written about in the U of C Magazine) to compare what a mouse was doing to what its brain was doing.

One question they wanted to answer was whether a behavioral pattern in odor perception called a configural percept exists at the neural level. A configural percept is what happens when a mixture of chemicals that smell similar to each other add up to a completely different smell. Its opposite is an elemental percept, in which different-smelling odorants retain their individual smells when mixed together.

We know these phenomena exist at some level, because humans report them and mice act as if they experience them, too. But when Grossman and her homeys compared simple mixtures of two smelly molecules — pentanal and hexanal (two very similar odorants that arise from hamster litter, and which contribute to the smell of old rice) — elemental percepts depended on the exact mixture, and configural percepts were nowhere to be found. Worse, what was happening in the OB didn’t seem to bear much relationship to how the animals were reacting.

When they tested Mickey’s and Minnie’s ability to recognize the components of a mixture after being trained to spot the mixture, that ability depended on the ratio of the two components. With ratios of pentanal to hexanal smell that were equal to higher-on-the-pentanal-side, the response was purely elemental. Despite the fact that the two odorants were similar, animals trained on these mixtures were able to recognize either component on its own, no problem.

When hexanal smell outweighed pentanal, though, something very different happened: It was as if the mixture no longer contained pentanal, all the mice could smell was the hexanal. This overshadowing percept wasn’t expected.

Things got even loosier-goosier when they looked at the animals’ brains. The pattern of the glomerular activity of the olfactory bulb paralleled the behavior for the elemental percepts -- the pattern of glomeruli activated by the mixture looked pretty much like adding together the glomeruli activated by each separately. But the glomeruli for poor ol’ overshadowed pentanal were firing like crazy even when its smell was in the minority — and when the mice were acting like they couldn’t smell it.

We already suspected that the higher brain mucks up perception of smells — Proust’s over-cited cookie fetish works both ways, odors don’t only trigger powerful memories, memories exert powerful influence on how we experience odors. What this report shows is that there’s even a gap between the brain’s first processing step and what comes afterward. That gap may yet contain a one-to-one translation of chemistry to perception, but it doesn’t seem all that likely.

So let’s split the difference: At the level of hardware we share with snails and insects, my Tasty Wheat tastes like your Tasty Wheat. But once we move beyond the level of brain structures we share with lizards or fish, maybe my Tasty Wheat is your tuna fish.

Think on that over your morning cereal. But try not to irritate your cellmates.

Tuesday, December 2, 2008

What the ...

The scene: Somewhere in Pennsylvania.

The venue: a local politician’s annual meeting with local emergency responders. Intention is to give us a pat on the back, let us listen to some interesting talks by members of our community, and generally give us the elected official’s ear for an evening.

What we were not expecting, at this gathering of largely middle-aged, white-male cops, firefighters, and EMTs, was the opening act: An interpretive dance by a young man and a young woman, to the tune of "Yankee Doodle Dandy," involving lots of saluting, leaping, and tights. Yes, tights.

Look: I don’t want to come across as some kind of Philistine here [1]. And I’m not foolish enough to think that dancers are sissies — we had one join our kendo club in Boston, back in the Before Time, and I can tell you that, within a month, he was kicking our asses with monotonous regularity. But for this audience, in this venue, it was a colossal mismatch.

We middle-aged white males have come along some, as you may have guessed from the recent election. The audience offered polite — maybe even more-than-just-polite — applause at the end. But you could also see the clockwork whirring in all the balding heads, and it went kind of like this:

What in bleeding heck was it that I just saw???

Sometimes science is like that; a new fact pops into view, and its incongruity is so striking that you literally don’t know what to do with it. But it bugs you enough that you just have to try to make sense of it.

Enter a report by Carl Philpott and crew at the universities of Leicester (I’m guessing pronounced "Lester") and East Anglia back in the Empire. This is a preliminary report of an accidental finding of superosmia — the ability to smell an odor at literally superhuman sensitivity — among a stunning 4 percent of 230 healthy subjects.

First, the background: Philpott and his colleagues were carrying out a new protocol for measuring human sensitivity, using two specific odor-carrying molecules: phenylethyl alcohol (a rose-like floral scent) and eucalyptol (three guesses). To their surprise, they found that 2 percent of healthy volunteers recruited in a hospital waiting room demonstrated sensitivity about a thousand times normal to one of the odorants when exposed to it once. When they gave another group of volunteers 10 or more trials apiece, the per-person frequency of super-smelling in at least one of the trials was a gob-stopping 10 percent. The two averaged out to just under 4 percent of all the subjects tested. Even freakier: these super-smellers sooner or later experienced a rapid loss of this hypersensitivity.

What gives? Honestly, I have no idea, and Philpott & Co. aren’t sure either. The researchers really didn’t find anything compelling on this in the past literature — the closest, a 1994 report by Amoore, even Amoore himself apparently thought was an artifact [2]. We’re all aware of the fact that many women become hypersensitive to odors during pregnancy — but the evidence suggests that’s because of a stronger reaction to odors at a "normal" level of sensitivity, not a true enhanced chemical sensitivity.

Hovering over the whole business: this is a new testing method; they might find something squirrelly about how some people test with this methodology that isn’t a bona fide sensitivity.

What biological function a random, temporary burst in sensitivity to a single odorant might have is what’s bugging me. We could be seeing something conceptually like the immune system’s random generation of antibodies with the idea that some of them will be useful for fighting infections. It’s a stretch, but it’s all I can think of.

The investigators did throw out one very neat idea for a mechanism, though. They suggested that superosmia might be “enabled by stimulation of an alternative olfactory pathway, such as the vomeronasal organ.”

Let me contextualize that a bit: The VNO is the suspected receptor organ for pheromones — airborne hormones that members of a species use to affect each others’ hormonal status, for mating, social dominance, or whatever. Its most interesting facet in this context, though, is that the receptor proteins that the VNO uses to sense pheromones are far more specific, and because of that, bind odorants far more tightly, than the olfactory receptors in the nose that detect run-of-the-mill odors.

Care to guess how much more tightly? That’s a tricky one, because the different chemical properties of olfactory (volatile) and VNO (often non-volatile) odorants make for an apples-oranges comparison. But if you guessed a thousand times — roughly the same factor as the superosmia — you’d be in the neighborhood of an admittedly crude, and maybe off-base, comparison.

In reply to some questions I emailed him, Philpott happened to mention that an earlier version of the paper, with more thoughts along these lines, ran into trouble with the reviewers. But he says that in follow-up experiments they’ll give a particularly close look to the idea that the mechanism for superosmia is the unmasking of a pheromone receptor in the human nose (which we already suspected existed).

So that’s the deal. I’m still trying to make sense of it; it feels like it ought to be important. But I still have no idea what it was I just saw. But I’m looking forward for the bigger picture to jete into view.

[1] A remarkably cultured and urbane people, the Philistines. But they picked on the wrong dudes, at least for their long-term PR.
[2] Sorry, no abstract on Oxford University Press or Google Scholar. But if you want to look up hardcopy, it’s Amoore J (1994) Chemical Senses 19:434.

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.

Wednesday, October 29, 2008

Jonathan Coulton

Just a quick note to plug a musician and his website (which includes a fan blog). I've followed Jonathan Coulton's alt-geek-folk-rock music ever since he brought down the house at a National Association of Science Writers do in Baltimore. Hard to describe his stuff, but if you can picture an unlikely but surprisingly apt blend of Fountains of Wayne and Tom Lehrer you won't be far off. Check it out.

Monday, October 27, 2008

Where I Get Off

There are two kinds of professional writer.

The first is the staff writer: the schlub who, day after day, hammers out copy — which may range in quality from routine boilerplate to high art, depending on the taste and needs of the employer — for a regular paycheck. Some of these folks work for publications like newspapers and magazines; but the great majority are “work for hire” employees in some sort of public relations or internal communications shop — they sell their copyright to their employer, who therefore owns everything they write.

The National Writer’s Union considers work for hire to be inherently exploitive; they may be right, but it’s also the only reason why many of us can make a living at writing. Certainly, staff writers’ employment can be precarious, because writers tend to be regarded as a luxury at many companies, and an early item to go when there are cutbacks.

The patron saint of staff writers, therefore, is Scheherazade.

The second kind of pro writer constitutes the glory corps of writing — the freelancers, people who live from project to project and contract to contract. The stars of the writing world number among them; but so do some very under-paid, hard working folks who, because they freelance, live from hand to mouth. So, also, are many people who write the occasional piece, do it well enough to get paid (often very well), but for lack of time, inclination, ambition, or sometimes just luck can’t make a go at it full-time.

The deal with freelancers is that, myths of “choose your own hours” aside, they actually tend to have less free time than staffers. Every full-time freelancer I’ve ever known worked at least as many hours as staff people, because freelancers have to spend so much (unpaid!) time marketing their writing rather than writing.

The patron saint of freelancer writers, therefore, is Thoreau’s basket maker — the fellow who, unclear on the supply/demand thing, made baskets and was puzzled why nobody would buy them as a matter of course.

That may sound stark: Certainly, the literary life has offered me a lot of joy over the years. Eighteen years after they ceremonially ripped the stripes off my lab coat and sent me out into the cold, cruel world of the professional writer, I’m still — so far — making a living at it, so I have far less cause to complain than many.

But I confess: I’m sick of being Scheherazade, and I’m sick of wanting to make baskets nobody (or no publications) seem to want. To pay the bills, I plan to keep the day job; to make some extra money, and to keep myself a bit sharper as a wordsmith, I hope to continue writing paid freelance pieces. But I wanted a space for myself — a space where I could write what interested me, not what I thought I could sell (or had the time to market, anyway).

Maybe it will be a space for things that interest you, too. I hope so; but in all honesty what I’m really doing is nurturing my inner basket maker. We’ll see whether he has enough to offer to warrant a readership. Hell, a writer who can’t take risks isn’t much of a writer.

So what will you be reading here? Well, checking out my bio, you’ll see that I have a peripatetic, typically University of Chicago background. So I plan to have a somewhat peripatetic site. Most of what you’ll see will probably reflect my ongoing fascination, as a former biochemist and current volunteer search-and-rescue dog handler and professional science writer, with the sense of smell (hence the blog’s title). SAR subjects may often come up, in that context or alone; so may navel-gazing pieces on writing like this one (though I promise to try to minimize these, as they get old). I write science fiction as well, so SF topics may also appear.

And like any bloggist, I reserve the right to mouth off on current political (and other) issues about which I’m not well enough educated to illuminate.

Ya fires up yer browser, ya takes yer chances. Reading, like writing, poses its risks.

Sunday, October 26, 2008

Broken Bottle Fight

Ya gotta love a broken bottle fight.

OK, that’s pure hype: I’ve heard no rumors of olfaction researchers actually resorting to smashing Pellegrino bottles and offering to rearrange each other’s faces at any recent symposia. But since Buck and Axel issued the first major installment in their Nobel-winning research on how the nose detects smells in 1991, two schools of thought in the science of smell have shared a major bone of contention.

Namely, is bigger necessarily better?

Here’s the rub: In 1991 Buck & Axel discovered a huge family of genes that encode the olfactory receptor proteins: A family of sensor molecules that sit on the outside of olfactory neurons in the main olfactory epithelium, deep in the nose, and detect the small molecules that constitute smells.

The OR family was one of those rare discoveries that suggest compelling answers to important questions. The sheer quantity of genes for the olfactory receptors, and the subsequently discovered fact that each olfactory neuron appears to express only one type of receptor, suggested how we detect so many complex smells: Olfactory neurons specialize in the specific odor-carrying molecules they respond to by virtue of carrying specialized detectors. Each receptor type matches a specific odorant — or, more likely, a small family of similar odorants [1]. The odorant fits the receptor much as a key fits into a car’s ignition; the receptor fires up its nerve cell, which in turn reports that odorant’s presence via an electrical jolt to the brain’s olfactory bulb.

The idea had legs for two reasons: First, in this model the receptors would act a lot like other receptor proteins and enzymes previously described in detail, and that’s always a reassuring sign you’re not going off the deep end. Second, it offered one explanation for why we use dogs to search for lost people: They can smell more things than we can.

Humans have about 900 olfactory receptor genes; dogs, around 1,200; and mice, 1,500. Now, by biological standards those numbers aren’t terribly different; it really gets interesting when we account for pseudogenes — genes that have a mistake in them that makes them non-functional. In humans, at least a whopping 63 percent of the receptor genes are such molecular dead weight — and so the actual numbers of working receptor types for each species are 350 for humans and roughly 1,000 apiece for dogs and mice.

Aha, a lot of us thought: That’s why they smell better than we do (after a fashion). They’ve got more receptors, ergo they’re detecting smells we can’t even imagine.

That’s when people started busting fizzy-water bottles against lecterns. For scientists love nothing more than to shoot down a simple idea for being too simple: People make careers from demolishing comfortable assumptions.

And some data seemed to do exactly that. Humans had far fewer total types of receptor; but if you looked at a more detailed structural level, much of the mouse "superiority" began to seem redundant. The mouse genes comprise 228 families of similar receptors, and it turned out that humans have a comparable number of gene families — we just have many more "only children" within each family. What this might mean is that mice carry around a bunch of receptors that detect pretty much the same stuff, and therefore, humans’ smaller repertoire of receptors can cover the same ground.

Enter Anna Lesniak and colleagues at the Polish Academy of Sciences: In the Sept./Oct. 2008 issue of the Journal of Heredity, they present a study of a group of 35 detector dogs from different scent specialties (human identification, explosives detection, drug detection, and tumor detection), that may rescue the more-is-better hypothesis after all.

The group tested these dogs for polymorphism — genetic diversity — in five randomly selected olfactory receptor genes. They asked: If a dog inherits two different versions of a receptor gene from its parents, does it carry out a scent-based task better than a dog who inherits the same version from each parent?

The situation turned out a bit differently for each of the five genes: For three of them, the version didn’t matter to the dog’s ability to carry out the scent task. But for the other two, an interesting, if not yet conclusive, pattern emerged [2].
* Dogs with two versions of one of these genes tended to be among the best performers for a scent task based on their specialty.
* The gene seemed to have a "better" version and a "worse" version: With two copies of the former, the dog tended to rank on average among the best performers; two copies of the latter put him among the slackers.
* It’s not clear whether having two versions is actually better than one: It may be simply that the existence of two versions gives you a better chance of having the good one.
* With the other gene, a similar pattern emerged, but only in the explosives dogs — lineup-identification dogs, tumor detectors, and drug dogs showed no difference.
* Taking the above together with the three genes that showed no difference, in no case were the dogs with two versions doing worse: They were either better off or indistinguishable.

So here’s the simple, if tentative, explanation: More receptors — even more versions of roughly the same receptor — give you a better chance of having a more-sensitive version that puts you ahead of the game in scenting ability. So the "redundant" receptors in the mouse and dog genomes may not be so redundant after all. (And yet another nail goes into the coffin of the quaint 19th-century notion that inbreeding produces superior working dogs, but that’s another issue.)

There are always provisos:
* The researchers aren’t completely satisfied with their scenting-ability tests, and they’ve got a point. The specialty based performance test hinges on the dog/handler relationship, and so doesn’t completely isolate pure scenting ability — though creating a more abstract, if lab-friendly, test might miss some important nuances in how the scent task unfolds.
* Worse, a second test, based on the dog’s ability to find treats, showed no effect for any of the genes, and its results didn’t correlate all that well with the specialty-specific tests. I think they might have gotten themselves into trouble here by using a poorly thought-out test, but they did use it, and its lack of a result is awkward.
* All the negative results could devolve from the simple expedient that, in the case of the negatives, those particular tasks simply don’t require those receptors. But we can’t rule out that the few positives were a fluke.
* For our larger, "is more better" question, we have to keep in mind there’s an apples-to-oranges going on here: We were talking about having more receptor types within each family of genes, while this experiment actually suggests what happens when you have more diversity within one type. My bet is that won’t make a difference to the validity of the argument, but it’s a possibility.

The good news is that Lesniak and her crew are well aware that their result is preliminary, and are planning to sharpen up their methods in future reports. So stay tuned.

But I wouldn’t blame conference organizers if they went for the plastic Pellegrino bottles, at least for now ...

[1] The number that people have thrown around is about 10 odorants per receptor, for a total of about 10,000 odorants. The only problem is that it doesn’t seem to come from any published scientific findings (even though the Nobel press release cited it). But here’s a wild one that suggests the whole issue is moot (or at least a vast oversimplification): In a 1993 theoretical biophysics paper that I only just found out about, Doron Lancet and posse calculated — calculated, mind you — that the olfactory system needs 300 to 1,000 receptors with the average sensitivity of the olfactory receptors to recognize, well, everything.

[2] For the wonks, they carried out their analysis with an ANOVA and subsequent Tukey testing, so they’ve presumably ruled out false discovery.