Friday, April 10, 2009

Some Assembly Required

I don’t know if it’s ironic or merely pathetic, but despite almost 20 years as a medical science journalist, as a patient I am as clueless as any.

Monday morning, we roll up to the same-day surgery center and undergo the million bureaucratic steps that I know help the staff keep track of who’s who and ensure safety — but are no less irritating for the knowledge. Finally, in my pre/postop suite, the IV line started in my hand and the anesthesiologist en route to deliver the sleepy time, my doc’s resident — a young, tall woman who could have been a fashion model [1], came to discuss the operation they were going to do on my right foot.

“Right foot?” I asked. “I thought we were going to do both.”

She looked dubious. “I don’t think Dr. ——— ever does both at the same time. But you can discuss it with her when she gets here.”

We did discuss it, and although my doc gave a number of good reasons for doing them one at a time, the most obvious to me now, two days later, is that I wouldn’t be able to move myself around at all if we’d done them both. Nevertheless, it was an unwelcome miscommunication to discover at that point, particularly since it meant the six to eight weeks I’ll be spending at limited activity will only be half the time I lose to the damned thing.

I was more than a little crestfallen; since we operated on the worst foot first, I’m seriously considering seeing how I get around with only one repaired, and maybe putting off getting the second one done indefinitely. We’ll see.

Anyhow, the moment we discovered the misunderstanding — or so it seemed — my doc started talking to Heather instead of me. That may well have been because they’d given me the sedative and I wasn’t going to be with them for much longer, but I confess that it felt like she’d decided which of the two was smarter.

Thanks to the magic of anesthesia, that’s all I remember, until waking up to see Heather there, my foot swathed in a nearly spherical bandage, ouchie ouchie. Better Half drove me home, where I’ve been slowly regaining something approaching normality, given the fact that I’m going to be off work this week and on crutches for at least a week longer.

Yes, pay no attention to the blog of last Sunday behind the curtain, my three days of crutches have lengthened to two weeks — another miscommunication, discovered yesterday when the doc’s office called to follow up and see how I was doing.

Now, I have a postop release form in my living room right now that says, “partial weight bearing, heel only.” But the first time I tried that, my foot told me, “Oh, no you will not,” and I figured I’d take it seriously. So when the assistant told me, “No, you don’t want to put weight on it, just keep it elevated and talk with Dr. ——— on Friday,” I was relieved to find out I hadn’t been babying it, just being appropriately prudent.  Today I had my post-op appointment, and the picture was a little rosier than that: Monday I'll get the stitches out, and at that point I'll be off the crutches as well.

Still, I could take an attitude. I could dwell on 18 years of physicians insisting to me that the gobbledygook they’d put on paper was perfectly comprehensible to their lay-level patients, and I didn’t dare edit it. Let alone tell the story from earlier life when, as a biochemistry grad student, I was looking up drug names for my grandmother so she’d understand what the hell her doc had prescribed for her.

The fact of the matter is, I don’t really have that out. I speak gobbledygook pretty fluently. So I think, rather, that it’s more likely an issue of “presumed comprehension,” in which doc tells patient 90 percent of the message, and they both fill in the remaining 10 percent — only differently. Yeah, part of the doc’s job, just like mine, is to make sure the patient/reader understands. But I’m in no position to cast asparagus on that point. At least everything is going well in the recovery, so I’m not inclined to complain.

One thing I have learned in 18 years is that you can’t word anything so that everybody understands it; attempts to reach universal comprehension wind up with worse gobbledygook than if you just try to make it clear and direct in the first place.

Getting a clear message across is the gist of another entry from Donald E. Frederick & Co. from Leslie Kay’s group at Wire Mommy [2], in Behavioral Neuroscience this month. This is another installment in the ongoing quest to decipher the code by which odor-carrying molecules are translated into perceptions of smell in the brain.

DACSIH? has touched on this issue before; but this time I think it’s appropriate to take a step back and discuss more fully the standard hypothesis that the new work is overturning.

One good summary of the hypothesis can be found in a review paper about insect odor processing by Hong Lei and Neil Vickers, in volume 34 of Journal of Chemical Ecology (that issue, by the way, being a trove of information about how critters perceive and then home in on the scents that are important to them).

We first need to remember that, unlike enzymes and the chemicals they have evolved to recognize, odors and their receptors are not specifically matched to each other. The body creates a spectrum of different receptor types in the nose (or antenna, if you’re an insect or crustacean) and then tries to make sense of how the odors it happens to encounter stimulate those receptors.

Even a simple, molecular odorant, then, will likely interact with more than one receptor — it’s the range and intensity of interactions that mark each odorant. So, complex smells, made up of dozens or hundreds of odorants, wind up being a smear of overlapped spectra of their different components. In the simplest formulation, say odorant A tweaks the spectrum of receptors like this:

With the darker boxes representing receptors with which odorant A is interacting most strongly. Now, say you have another odorant, B, that shows this pattern of activation:

Well, if you combine A and B into one complex smell, you get:

Which, it isn’t hard to see, is a combination of odorants A and B. This is what smell researchers call elemental processing — because the elements of the complex smell are still there and identifiable when you look at the higher-level perception. For a real-life example, think of smelling apple pie, but being able to smell the apples and cinnamon as separate components of the smell.

It gets more complicated when you have two odorants, A and A′, that smell similar to each other. If A′ looks like:

Then the combination of A and A′ will look something like:

If the code were this simple, you’d already have a mishmash that wouldn’t allow you to tell whether A and A′ were both there, or you just had a lot of either A or A′ alone. But it gets even more complicated, because similar odorants actually interfere with each other. The resulting perception actually looks more like:

So that, not only can’t you recognize that the A and A′ patterns are there, you actually start getting something that doesn’t look much like either one. This is called configural processing, in which the combination of two similar smells actually smells different than either does separately, and there’s no way of picking out components. This one is harder to give an example for, but one (possibly stretched) example would be how, on different people’s skin, the same cologne starts to smell very differently.

So that’s been the given wisdom: similar smells undergo configural processing to create utterly new sensations; different smells undergo elemental processing and retain their character. It was simple, clear, and explained a lot of what people were seeing in lab experiments with organisms as different as insects, fish, and mammals.

In retrospect, it almost had to be wrong.

Enter Mssr. Frederick & associates of the fine metropolis and University of Chicago, who’ve put yet another nail into the coffin of the simple configural/elemental duality. They did this by showing how a series of odorant pairs, selected so that both their subjective sensations and the pattern of glomeruli they activate in the rat olfactory bulb differ incrementally, don’t follow the pattern at all.

Briefly, they chose a bunch of odorants ranging from the indistinguishable — (+)- vs. (–)-limonene (orange smell) — to the very different hexanal (green, leafy smell) vs. ethylbenzene (gasoline smell) — and checked to see whether a rat trained to recognize the combined odorants could then recognize the components. Things just about immediately went wrong with the configural/elemental hypothesis, with rats recognizing the (+,–)-limonene mixture elementally — in other words, the mixture and the components looked the same, once you corrected for differences in intensity.

Still, that one was slippery — if the two versions of limonene were truly indistinguishable, they might not actually represent different odors. [3] You wouldn’t expect an odorant to interfere with itself. [4] The hexanal/ethyl benzene combination was more interesting along these lines, since you’d expect the two very different smells to maintain their character in the mixture. Once again, the simple expectation was wrong: rats trained on the mixture recognized hexanal, but not ethyl benzene. Similar to the group’s earlier paper, they were seeing overshadowing processing, in which one component effectively masked the other. They got the same result with the similarly mismatched odorant pair of isoamyl butyrate (fruity/banana) and butyric acid (depending on context, either sharp cheese or sour/nasty). If you plot the similarity of their odorant pairs to the results they saw, you get no significant pattern.

So where does that leave us? Well, as the researchers point out, nowhere is it written in stone that dissimilar odors can’t interfere with each other, at some point in the chain of events from receptor to higher-brain perception. In addition, the configural/elemental hypothesis had come from a limited data set of not-completely defined odorants. In particular, the fact that the current study is based on the extent to which the odorants they’re working with affect differently the smell-routing center of the brain is new. It looks like we’re at the beginning of a (possibly long) process to figure out how it all really works.

As with my damned foot, some assembly is going to be required. One week off work, and then the long, semi-mobile Mickey-Mouse-boot recovery period. The aim is, again, to make Fire School in early June. Wish me luck.

[1] I note this only because, thinking about it, it seems logical that a female surgeon might attract female residents, surgery still being a bit of a Boy’s Club.
[2] They’re going to start thinking I’m some kind of groupie, but the fact is this paper caught my eye before I saw the authors.
[3] I’m skipping over a world of possible significance here: on a purely theoretical basis, two mirror-image isomers like (+)- and (–)-limonene should not smell the same. Look to a soon-to-come blog about isomers and the vibration theory of smell for the missing detail. For the present, let’s just accept that they’re virtually indistinguishable smells.
[4] Nothing if not thorough, they actually tested whether (+)-limonene could interfere with its own odor — and excepting a little statistical noise, it didn’t.

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