The Essence of a Sniff
A new look at forgotten or overlooked science
EDITOR'S NOTE: Re-Discovery is a new, not necessarily humorous, regular column in AIR. It looks at genuine scientific discoveries that have fallen by the wayside, but that raise intriguing -- and perhaps important -- questions.
Our most ancient, most reliable sense -- the sense of smell -- may be more
simple, more complicated, and more intriguing than most scientists realize.
Several researchers have spent forty years and more learning how to measure
exactly what a frog's nose tells the frog's brain. They want to understand
how the frog's brain knows what the nose is saying.
They have found things that are different from what anyone expected. And
different from what most biologists believe about how noses talk to brains.
Do Frogs and People Smell Differently?
Why a frog? Because it's been easier (and most, but these days not all, would say more palatable) to experiment with a frog's nose in a frog than with a person's in a person.
The only way to tell what's really going on in the system -- the olfactory
system -- is to measure what's happening there while a creature is smelling
a smell. (You can learn a lot by removing pieces and studying them outside
the body. But each piece is in there for a reason -- and can behave differently
when it's been yanked out.)
It is possible to monitor individual cells in the business end of a nose,
in the frog. People have gotten detailed information about how those cells
-- the sensory neurons -- actually behave when they get a whiff of something.
Frogs were the first to reveal their nasal secrets, because they were the
easiest to work with. Now rats and other animals are being studied this
way, too. How much does the frog nose-and-brain tell us about the human
nose-and-brain? Probably quite a lot. The olfactory system seems organized
pretty much the same way in amphibia (frogs, salamanders, newts), in mammals
(rats, mice, probably humans, too) and even in some of the simplest eukaryotes
(a eukaryote, remember, is any creature whose cells each have a nucleus.)
A Little Background About How We Smell
The sensory neurons are the business end of the nose/brain system. Any smell information that reaches the brain comes, directly or indirectly, from them and them alone.
The olfactory system is the only one of the senses in which the sensory
nerve cells come directly in contact with chemicals from the outside world,
without any other cells physically shielding them from harm. (Even in the
taste system, the sensory nerve cells have some safety layer of protection
from the things that stimulate them.)
The olfactory sensory neurons are distinct among sensory nerve cells. They
have very, very long, very thin axons, with no heavy wrapping of the myelin
coat that insulates the thicker nerve fibers. It proved rather difficult
to measure their internal electrical activity. The pulsations there are
a monologue, by the neuron, about what it is and isn't smelling.
(By the way: of all the neurons, sensory or non, in the vertebrate body, only a tiny percentage have a thick, myelin-wrapping -- yet myelinated neurons are almost the only ones that have been studied. The activity of more than nine tenths of the nervous system is largely a mystery to most scientists.)
The olfactory system seems to be organized pretty much the same way in many animals, including all of those pictured here. Drawing: John Tenniel, from Alice in Wonderland.
"How Does It Work?" vs. "What Are the Parts?"
In the late 1950s and early 1960s a small group at MIT became adept at
measuring electrical signals from small nerve cells, first of the eye and
then of the olfactory system. They were, and in many respects still are,
pioneers at this.
It was a peculiar group of people, electrical engineers who became interested
in biology and then turned their unusual skills and much of their lives
to poking, measuring, and trying to make sense of nature's most complex
electrical system: the brain and the nervous system connected to it.
who is now a professor of neurobiology at the University of Cincinnati,
became the guru of olfactory system measurement, developing ways to reliably
measure the activity of individual sensory neurons in living, smelling frogs.
It is even now just a small community of scientists who do this kind of
Other scientists, far more numerous, have been investigating the individual
nuts and bolts of the olfactory system. They concentrate on the smell-related
genes and on the odor receptors, the specific parts of the sensory neuron
surface that respond to particular odor molecules.
The two lines of approach have unfortunately been somewhat disconnected.
One measures and describes the workaday activities inside the olfactory
system. The other examines the system's design and structure: its DNA blueprints
and chemical components.
Gesteland and the rest of the "let's look at how it works" gang have discovered some puzzling activities in the olfactory system. The DNA/biochemical research groups, which are dominant both in size and in funding, have generally dismissed those activities as being puzzling, irrelevant, or apocryphal.
Certainly, these things are puzzling. They are also well documented.
Why Are These Cells Different From All Other Cells?
Here's some of what Gesteland, and his colleagues and competitors around
the world, have discovered.
In the frog, olfactory sensory neurons behave differently from all other nerve cells. Here are some peculiar things about them:
<> On average, each olfactory receptor cell lives for only a few
weeks, and is then replaced by a new cell. (All other neurons in the olfactory
system -- and in the rest of the nervous system -- last for years, in many
cases for the lifetime of the animal. Replacement of those dead cells is
sluggish, if it occurs at all.)
<> In the frog's nose, every sensory neuron responds to a large number
of different stimulus substances, typically to a quarter or a half of all
the odors presented to it. (This is very unlike the nerve cells in the eye.
The eye has several different kinds of sensory cells, and each kind responds
only to some particular, limited range of stimuli -- a certain range of
color, for example.)
<> No two of these cells behave the same way. Expose twenty different
olfactory sensory neurons to the same odor, and each neuron will produce
a different electrical signal. It's as if each nerve cell looks at the world
from a different point of view. (This, too, is unlike the visual system.)
<> They are also not very reliable, in the sense that any particular
cell does not always react to the same odor in the same way.
By the way: all this variability is not necessarily a bad thing, considering what a nose is expected to do. In general it has to notify the creature when it's smelled something new (something putrid, for example), but not so much when that smell has been lingering ("still smells putrid!"). And because these sensory neurons come in contact with chemicals -- virtually any kind -- from the outside world, they are more at risk than any other nerve cells in the body, and so more often in need of replacement.
The Big Question
There's a big question lurking in the background -- a tantalizing, juicy
question that no one seems close to answering.
In a system where the sensing parts are all different from each other,
where every one of them gets replaced frequently, and where every replacement
part behaves differently from its predecessor, how do smells get remembered
To put this another way: now that we know what information the sensory
cells are picking up, and we know that the pickup system is composed of
varying, ever-changing parts, how is the information processed and used
Smell memory is the most permanent and strongest kind of memory, yet it depends on the greatest variation. The solution to this puzzle could open many interesting doors.
Where to Start
Perhaps you could be the person who figures this out. If you want to dig into it, here are some good places to start:
For the basic early work on frog olfactory receptor neurons, see "Speculations
on Smell," Jerome Y. Lettvin and Robert C. Gesteland, Cold
Spring Harbor Symposium, vol. 30, 1965, pp. 217-25. (For a more technically
detailed version of it, see "Chemical Transmission in the Nose of the
Frog," Robert C. Gesteland, Jerome Y. Lettvin, andWalter H. Pitts,
Journal of Physiology, vol. 181,
1965, pp. 525-9.)
For a summary of recent single receptor neuron physiological studies, see
"Peripheral Odor Coding in the Rat and Frog: Quality and Intensity
Specification," P. Duchamp-Viret, A. Duchamp and M.A. Chaput, Journal
of Neuroscience, vol. 20, 2000, pp. 2383-90.
To see a very different, contrasting view, from one of the leaders of the molecular genetics approach, read "The Molecular Architecture of Odor and Pheromone Sensing in Mammals," L.B. Buck, Cell, vol. 100, 2000, pp. 611-18.
© Copyright 2000 Annals of Improbable Research (AIR)