Of the five senses, only one remains a mystery
to scientists: scent. Despite decades of study, the theories of how
we detect odors remain, at least on a molecular level, theories.
Now, in an attempt to cast new light on how
the nose works, Rockefeller’s Leslie
Vosshall has, for the first time,
put a controversial scientific theory of smell to the test. Her
results should lay to rest a debate over the “vibration
theory” of scent that has until now largely been based on
speculation and hearsay.
There are two theories of smell. Most
researchers believe that the shape of a chemical determines how it
smells. That is, the sense of smell works like a lock and key: the
shape of a chemical (the key) fits into odorant receptor proteins
on the outside of cells (the lock) that are dedicated to the sense
Then there’s the vibration theory. It
states that mol-ecules in every substance generate a specific
vibration frequency that the nose interprets as a distinct smell.
Though both theories are unproven, vibration
theory has recently received some press attention, first by a
BBC-TV documentary, then by a book titled The Emperor of Scent.
The book’s author, Chandler Burr, argues that the
biophysicist who came up with vibration theory, Luca Turin, is a
pioneering researcher who is being ignored by the smell research
community because of his unconventional ideas. Many reviews of his
book parroted that theme.
Turin, a physiologist by training and a
recognized expert on perfumes, expanded upon a theory first offered
in the 1930s that suggested smell was dependent on intramolecular
vibrations, or the stretching of chemical bonds, within an odor
molecule. He hypothesizes that the receptors lining the nose
function as a biological “spectroscope” to measure the
vibrational energy of odorant molecules.
Yet Turin never undertook a series of
that he said, in a theoretical paper, would
prove his theory. “Since Turin’s theory was based
solely on his unverified reports about the smell of certain
odorants, the scientific community rejected it as a universal
theory of smell based on one man’s olfactory
impressions,” says postdoc Andreas Keller, first author of a
report on the research published in the April issue of Nature Neuroscience.
But problems exist with the shape theory as
well: humans can detect many more smells than there are odorant
receptors, and even if the locks are a little “loose,”
the shape theory can’t explain how two chemicals, each with a
unique shape, can smell essentially the same.
“There are cases that are not intuitive
for the shape theory, and that is why scientists have been looking
for alternative theories for a very long time,” says
Vosshall, head of the Laboratory of Neurogenetics and Behavior.
A few months ago, Keller and Vosshall —
who normally study olfaction in fruit flies — decided to
conduct the human studies that Turin never did.
“This is a theory that has been
universally rejected by every scientist, so you might ask why we
bothered,” Vosshall says. “We felt that his theory has been
given, by virtue of press coverage, some degree of credibility
although it was never been put up to scientific
Keller designed a series of three controlled,
double-blind human tests with several dozen human volunteers. In
the Rockefeller University Hospital Heilbrunn Outpatient Clinic, he
asked volunteers to smell different odors presented in coded vials
and answer a series of questions.
In the first experiment, Keller tested
Turin’s prediction that if two different chemicals, one that
smells like smoke and one that smells like bitter almond, were
mixed together, they would smell like vanilla, because their
combined molecular vibrations would match those of vanilla. None of
the volunteers agreed.
A second experiment tested whether aldehydes
(the major components of Chanel No. 5 perfume), composed of an even
number of carbon atoms, smell different from those with an odd
number. Turin hypothesized that they would because vibrational
frequencies between the two groups would be different. But the
participants did not detect such a trend.
The final experiment was based on
Turin’s proposal that two chemicals which have almost
identical shapes but markedly different molecular vibrations would
have distinct smells. In several different tests, none of the
subjects could tell the difference between the similarly shaped
“In order for science to have integrity,
you have to do studies properly. You can’t just sniff the
substances yourself, decide in advance what the answer is supposed
to be, confirm by testing it yourself and then publish a
paper,” says Vosshall.
“I did the boring work of actually doing
Turin’s experiments and showing what the real answer
is,” says Keller, with a laugh.
Because the study was not designed to prove
either theory, the results say only how smell doesn’t work. They
don’t bring us any closer to knowing how it does work.
“This is a paper of solely negative
results,” Vosshall says. “We didn’t disprove the
vibration theory, we just didn’t find anything to support it.
The results show that molecular vibrations alone cannot explain the
perceived smell of a chemical. And while all of our data are
consistent with the shape theory, they don’t prove the shape