MadSci Network: Neuroscience

Re: What life form is the smelling Champion?

Date: Mon Mar 13 18:07:36 2000
Posted By: Amanda Kahn, Grad student, neuroscience, UCSF
Area of science: Neuroscience
ID: 952025465.Ns

Hi Micah!

You've asked some really good questions, and I don't think that there's 
enough data out there to unequivocally declare one life form to be the 
smelling champion.  As you suggest, sensitivity to low concentrations of an 
odorant and to a broad range of molecules are important characteristics.  In 
addition, you would want your smelling champion to be good at discriminating 
a particular odor from the rest of the smells that are present (or to be 
able to distinguish among similar molecules).  Lab experiments (and some 
observations outside the lab) have provided insight into some of these 

Underlying any organism's ability to smell is its repertoire of olfactory 
receptors.  Olfactory receptors are fairly large proteins which reside in 
the cilia of olfactory neurons; the known olfactory receptors are members of 
the G-protein coupled receptor family.  When an odorant molecule binds the 
receptor, a conformational change ensues, causing the activation of an 
associated G-protein (which then goes on to activate other molecules in a 
cascade of biochemical interactions).  If you're familiar with the way light 
activates the visual pigment rhodopsin, the process in olfactory neurons is 
somewhat similar.

Recent advances in genomics have enabled scientists to look at large numbers 
of olfactory receptors within and across species.  The really groundbreaking 
work in this field was done by Linda Buck, who was a postdoctoral fellow in 
Richard Axel's lab at Columbia University.  Buck and Axel found a large 
family of genes for G-protein coupled receptors in rats; these genes were 
specifically expressed in the olfactory epithelium.  Work by other labs 
(including the Firestein lab at Columbia and the Reed lab at Johns Hopkins) 
has shown that these genes do, indeed, encode functional olfactory 
receptors.  Until the rat genome is cloned, we won't know exactly how many 
olfactory receptor genes there are in that species.  Still, work on mouse 
and human olfactory receptor genes has suggested that there are about 1,000 
receptor genes in those species, perhaps corresponding to about 1% of the 
rodent or human genome.  That number will be clearer with the completion of 
the human genome in the next few years.  

Buck and another former Axel lab postdoctoral fellow, Catherine Dulac, 
independently discovered a smaller family of ~100 potential pheromone 
receptors in rodents, although nobody has figured out which pheromones 
interact with which receptors ... yet.  There's limited experimental 
evidence that pheromones play a part in human behavior, but functional human 
pheromone receptors have yet to be cloned. 

For animals with completely sequenced genomes, the picture is a little 
clearer.  The nematode (roundworm) C. elegans has had its genome sequenced 
in its entirety.  Of ~19,600 genes, roughly 700 look like olfactory 
receptors -- good news for a creature which relies on smell and taste to 
navigate through its environment.  Last year, some olfactory receptors for 
the fruit fly drosophila were finally discovered by the Carlson and Axel 
labs.  The fly genome is just about complete, and perhaps other families of 
olfactory receptors will be found, too.

So, from all of these studies, it seems that animals devote a large 
proportion of their DNA to encoding olfactory receptors.  How sensitive are 
they?  In vitro studies of rodent olfactory receptors by Buck, Reed, and 
Firestein show sensitivity in the micromolar to millimolar range.  
Behavioral studies in living worms show sensitivity to 1:1000 dilutions of 
an odorant placed on an agar plate.  Meanwhile, studies of odorant 
sensitivity in humans show, for a large battery of smells, sensitivity in 
the nanomolar range -- although components of mucus may create higher 
concentrations in the vicinity of olfactory receptors. 

Some of the more compelling data comes from observations of animals in their 
daily routines.  Certain breeds of dogs are widely revered for their ability 
to track scents.  Turkey vultures can smell prey (or leaks from a gas 
pipeline!) from miles away, suggesting that their olfactory systems are 
profoundly sensitive.  Humans are pretty good at discriminating enantiomers 
(left vs. right-handed molecules) such as (d) or (l) carvone, one of which 
smells like peppermint and the other, caroway.

Knowing something about the receptors underlying olfaction, we can ask 
questions about the ways that the olfactory system works to discriminate 
among different smells.  Can receptors/cells detect more than one odor 
molecule?  Does discrimination happen within one neuron or between neurons?  
What are the mechanisms for adapting to an odorant (like getting used to a 
bad smell in a room)?  How does the presence of one odor influence your 
ability to perceive other odors?  People in the olfaction field are working 
on these sorts of questions, which may ultimately enable us to answer your 
original question, and find the planet's champion smeller.

By the way, there's a TON of interesting work out there.  I've provided you 
with information on some widely-used experimental animals, but you may also 
want to look up information on olfaction in moths (manduca sexta) and salmon 
for some other perspectives.

Amanda Kahn

For information on work by Richard Axel (rodents and flies), Cori Bargmann 
(worms), Linda Buck (rodents), Randy Reed (linking odors and receptors), and 
Catherine Dulac (rodents), follow the links on this page:

For information on John Carlson's work with flies, click here: http://

For information on Stuart Firestein's work on odors and receptors, click 
here: http:/

for information on a bunch of odorants, click here:

Here's an interesting paper on human pheromones:
Stern, K; McClintock, MK.  Regulation of ovulation by human pheromones.
Nature, 1998 Mar 12, 392(6672):177-9. 

Here are some of the references for the sensitivity data I cited above:

Zhao, H; Ivic, L; Otaki, JM; Hashimoto, M; Mikoshiba, K; Firestein, S.  
Functional expression of a
mammalian odorant receptor 
Science, 1998 Jan 9, 279(5348):237-42.

Krautwurst, D; Yau, KW; Reed, RR.  Identification of ligands for olfactory 
receptors by functional expression of a receptor library.
Cell, 1998 Dec 23, 95(7):917-26. 

Bargmann, CI; Hartwieg, E; Horvitz, HR.  Odorant-selective genes and neurons 
mediate olfaction in C. elegans.
Cell, 1993 Aug 13, 74(3):515-27.

Malnic, B; Hirono, J; Sato, T; Buck, LB.  Combinatorial receptor codes for 
Cell, 1999 Mar 5, 96(5):713-23.

Devos, M, F. Patte, J Rouault, and P Laffort. 1990.  Standardized Human 
Olfactory Thresholds.  IRL Press, Oxford UK.

For information on turkey vultures and their ability to sniff out gas leaks:

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