Chemical Senses Dr.

Sjoerd Stuit

See: http://physrev.physiology.org/content/86/2/409

odors: identification of foods; judging the edibility; detection of impending danger such as
predator; recognition of their mate, parents, and offspring; and detecting signals for a variety
of social behaviors including the maintenance of territories.

 Today

❖ A little bit about chemical senses in general

❖ A bit more on olfaction
❖ A lot on the social relevance of olfaction

2
 Chemical Receptors
Taste

The Five Basic Tastes

Taste and smell, our chemical senses, are

important in distinguishing between foods that are
nutritious versus those that are harmful, as well as those
❖ Direct effect on ion channels
providing pleasure.

The tongue is as sensitive to touch, temperature,

❖ Sour (H+)and pain as is the thumb. In addition, the tongue performs
Salty
a chemical (Na+)
analysis of substances dissolved in the saliva.
It senses 5 basic tastes: bitter, sour, salty, sweet and,
the recently discovered, umami.
❖ Second messenger
Each tasteeffects
can be sensed everywhere on the
tongue but, as seen in Figure 7.22, different areas show
preferences. The middle of the tongue has relatively few
❖ bitter, sweet,
taste cells.umani
As we sip a wine or juice, it first activates the
sweetness receptors at the front of the tongue, then the
sour receptors in the middle, and finally the bitter
receptors at the back. Thus the tongue sends a spatial
❖ Smell temporal pattern to the brain that allows us to
differentiate between a variety of wines or juices.

Sourness (H+) and saltiness (Na+) act on cell ion

channels directly.

Bitterness, sweet and umami tastes are amplified

by specific G protein-coupled receptors which activate Figure 7. 22 The Areas of the Tongue that
3
second messenger cascades to depolarize the cell, as in have the Greatest Sensitivity to Different
the retina’s receptors. Flavours

The newly discovered Umami receptors are activated by monosodium glutamate and
other proteins and give bacon a savory taste.

Each receptor site is rather specific for the ends of a particular molecule, like a lock that
can only be opened by a specific key. However there may be several molecules that have the
same shaped ends. For example, there is one specific site for glucose but other sweet molecules
may have the same ending or key. The goal of the artificial sweetener industry is to make
molecules whose ends look like a sugar but has no nutritional value.

15
Revised 15/10/2014

Second messenger effect are all about fit. Doen’t mean only one molecule fits of course
 Taste buds
The Taste Bud

On the tongue one finds taste buds, a cluster of about

100 taste cells.

about 100 cells per bud

❖ Each taste cell is most sensitive to one of the 5 tastes.
Because the tongue is exposed to hazards such as heat,
infections and toxins, these taste cells are constantly being
❖ Sensitive to all/most but biased
replaced. Over a 2 week life span, basal cells become
supporting cells, which become taste cells.
❖ Short life span
Taste cells need innervation to survive. If the afferent
fibers are damaged, taste cell degenerate. Axonal transport
along fibres provides an important trophic factor that
maintains a healthy taste cell.

. Figure 7. 23 The taste bud

contains about 100 taste cells. These
4 are replaced from basal cells which
turn to supporting cells and finally taste
cells over a two week period

The Taste Pathway

Taste afferents project via

cranial nerves 7, 9 and, 10 to the
nucleus of the Solitary Tract. From
there the signal projects to the ventral
posterior medial nucleus of the
thalamus and then to several areas of
the cortex including the
hypothalamus, which regulates
hunger and insular taste cortex,
which has a rough somatotopic
representation of different tastes
(Figure 7.24). The taste signal is
projected to the cortex using a labeled
line system similar to that of touch.

Figure 7. 24 Taste afferents synapse onto neurons in the nucleus

of the solitary tract. These in turn project to the thalamus and to the
insular taste cortex.
2000-4000 in total

Regenerate trough going through stages: Basal 16—> supporting —> taste cell
Revised 15/10/2014
 Olfactory receptors

pass trough the skull, sometimes damaged with head trauma. Recovers in about a month

many receptor types: high discriminatory powers

Individual sensory neurons in the olfactory epithelium project a single axon to a single
glomerulus

Responsive to about 400.00 chemicals, but no 2 have (yet) been found to smell alike.

Subject experience is related to chemical variations at the molecular level

 Olfactory bulb

Individual sensory neurons in the olfactory epithelium project a single axon to a single
glomerulus in the OB.

Only within-receptor type convergence in the glomeruli (increases sensitivity)

Maps: each odorant elicits a characteristic spatial pattern of glomerular activities in the OB
and provided the first information regarding the relationship between molecular structure of
odorants and the spatial pattern of glomerular activities.

Consistent: The odorant-specific spatial positions of activated glomeruli are conserved across
different animals of the same species.
 ❖ Note the symmetry 8

http://gara.bio.uci.edu/

Lateral interaction, First models were based on the retina due to similar connectivity/
organisation.

Recent evidence shows spatial interactions are more specific than in the retina:

Fantana et al. show that lateral interactions do not occur in a predictable spatial pattern.
Instead, they argue that mitral cells make sparse and specific lateral connections.

Mitral cells receive direct excitation from their primary glomeruli but receive inhibition from
only a small number of specific spatially distributed mitral cells representing different
glomerular inputs.

Functional implication still matter of debate. One interesting view suggests it serves to reduce
probability of seizures since OB is very prone to these.
 Flavour

❖ Combining the senses

❖ Usually refers to taste and smell

10
Summary of Taste and Smell

Flavour
Both olfactory cells, and taste cells in the taste bud, are constantly replaced.

Both taste and smell project to the newer cerebral cortex, the neocortex for perception,
and to the older cortex in the limbic system for automatic responses of hunger, pleasure, etc.

Flavour

Figure 7. 28 11A Comparison of the Pathways for Taste and Smell

See problems and answers posted on

http://www.tutis.ca/Senses/L7Touch/L7TouchProb.swf

20
Revised 15/10/2014
 Aversion
❖ Innate taste aversion: sour & bitter
❖ poison / rot

❖ Quick learning (from food poisoning for example)

❖ Long lasting
❖ Specific

12
Summary of Taste and Smell

Flavour
Both olfactory cells, and taste cells in the taste bud, are constantly replaced.

Both taste and smell project to the newer cerebral cortex, the neocortex for perception,
and to the older cortex in the limbic system for automatic responses of hunger, pleasure, etc.

Figure 7. 28 13A Comparison of the Pathways for Taste and Smell

See problems and answers posted on

http://www.tutis.ca/Senses/L7Touch/L7TouchProb.swf

20
Revised 15/10/2014
 Beyond food
❖ What do we use the chemical senses for?
❖ Some weird examples:
❖ giraffes taste urine
❖ Ants have chemical alarm systems that call for help
❖ Dogs smelling disease
❖ Pheromones…. vomeronasal organ

14
 What about humans?

❖ No vomeronasal organ

15

not pheromones but chemosignals…

Syncing menstrual cycles

 What about humans?

❖ but…check the anatomy

16

not pheromones but chemosignals…

Syncing menstrual cycles

 Smelling others

❖ Smell can trigger

behaviour…
❖ Social smells…

17
 Social Smells

❖ Sweat generated during fear caused more vigilance in

receiver compared to sweat generated during sports
❖ Without people noticing…
❖ How specific is this?

18
 Emotional contagion

❖ Affective, behavioural & perceptual processes observed

in a receiver are a partial reproduction of the state of the
sender

❖ Different behavioural patterns during fear and disgust

❖ Groot et al, 2012

19
 Emotional contagion
❖ Sensory acquisition
& rejection

20

Susskind et al, 2008: nasal volume, perception, eye movement speed effects
 Chemosignalling experiment

❖ Double blind
❖ Within subjects
❖ Absorbent compresses for fear, disgust and neutral
states

21
State induction

22
 Results
1420 de Groot et al.

a b
Disgust-Sweat Condition Disgust-Sweat Condition
Fear-Sweat Condition Fear-Sweat Condition
❖ Facial-muscle configuration 12
Control Condition
20
Control Condition

9 15

Medial Frontalis Activity (µV)

Levator Labii Activity (µV)

6 10

3 5

0 0

–3 –5

–6 –10
e 1 2 3 4 0 0 e 1 2 3 4 0 0
lin 21 42 lin 21 42
se 0– 0– se 0– 0–
Ba 21 Ba 21
Time (s) Time (s)
23
Fig. 1. Mean (a) medial frontalis and (b) levator labii muscle activity as a function of time and odor condition (fear sweat, disgust
sweat, or control). Results are shown for baseline, Epoch 1 (0–4 s), and Epoch 2 (0–420 s). Error bars indicate ±1 SEM.

levator labii muscles (Fig. 1b) to be activated, F(4, 116) = odor condition and sniff number, F(2, 60) = 9.13, p < .001,
15.36, p < .001, η2 = .02, and maintained, F(1, 29) = 15.44, η2 = .11, an effect that was not observed from the third sniff
p < .001, η2 = .01. Moreover, fear chemosignals generated an onward, F(14, 420) = 1.18, p = .287.
expression of fear and not disgust, F(4, 108) = 3.82, p = .006, Follow-up paired t tests on the first two sniffs indicated that
η2 = .01, disgust chemosignals induced a facial configuration the magnitude of the first sniff was lower for fear than for
of disgust rather than fear, F(4, 112) = 6.32, p < .001, η2 = .01, disgust, t(32) = −2.87, p = .021, whereas the magnitude of the
and neither fear, F(4, 100) = 2.04, p = .095, nor disgust, second sniff was lower for disgust than for fear, t(32) = −3.83,
F(4, 104) = 1.69, p = .159, were evoked in the control condi- p = .003. Exposure to emotional chemosignals thus modulated
tion (see Additional Analyses in the Supplemental Material). sensory-regulation processes temporarily, after which adapta-
Chemosignals thus served as a medium for communication. tion seemed to have taken place. Figure 2 shows that sniff
Mere inhalation was sufficient to induce a facial expression in magnitude gradually decreased after nose clips were removed
receivers that reflected the emotion experienced by senders in the control condition. A cyclic pattern of air intake emerged
while they produced the chemosignal. after emotional chemosignal exposure, in which each substan-
Next, we examined whether chemosignal-induced facial tial reduction in sniff magnitude seems to be compensated for
expressions modulated sniffing behavior (see Additional in the subsequent sniff. The reversed systematicity in air intake
Analyses in the Supplemental Material). Whereas the first observed in the fear and disgust conditions arguably occurred
sniff was expected to be reflexively elicited and exploratory, as a function of the type of chemosignal received. By tempo-
the subsequent sniff was modulated in magnitude (Mainland rarily increasing the sniff magnitude in the fear condition,
& Sobel, 2006), consistent with the communicated emotion. a larger number of chemical compounds could potentially
We analyzed 10 sniffs to meaningfully chart the unfolding of reach the olfactory epithelium (i.e., sensory acquisition). The
sniffing magnitude over time. A 3 (odor condition: fear sweat, opposite pattern (i.e., sensory rejection) was observed after
disgust sweat, control) × 10 (sniff number: 1–10) repeated exposure to disgust chemosignals, which presumably served a
measures ANOVA revealed significant changes in sniff mag- protective function.
nitude over time as a function of the olfactory stimulus, F(18, Next, we examined whether changes in facial-muscle activ-
540) = 3.24, p < .001, η2 = .05 (Fig. 2). A further examination ity induced by chemosignals altered perception in the visual
of the first two sniffs revealed a significant interaction between search task (see Additional Analyses in the Supplemental

Downloaded from pss.sagepub.com at University Library Utrecht on September 4, 2015

 Results
Communicative Function of Chemosignals 1421

❖ Sniff volume Disgust-Sweat Condition

Fear-Sweat Condition
Control Condition
0.70

0.65

Sniff Magnitude (mm H2O/time)

0.60

0.55

0.50

0.45

0.40

0.35

0.30
1 2 3 4 5 6 7 8 9 10
Sniff Number
24
Fig. 2. Mean sniff magnitude (nasal air pressure in mm H2O over time) on the first 10 sniffs after
presentation of chemosignals in the three conditions (fear sweat, disgust sweat, or control). Error bars
indicate ±1 SEM.

Material). A 3 (odor condition: fear sweat, disgust sweat, con-
trol) × 2 (task: easy, difficult) repeated measures ANOVA
demonstrated that detection sensitivity (d ′; Macmillan &
Creelman, 2005) was significantly lower on the difficult task
than on the easy task, F(1, 35) = 19.04, p < .001, η2 = .07, and
varied significantly among odor conditions, F(2, 70) = 5.37,
p = .007, η2 = .03. However, the interaction between odor con-
dition and task was not significant: F(2, 70) = 2.82, p = .066.
As predicted, a post hoc ANOVA revealed that detection sen-
sitivity was lower in the disgust-sweat condition than in the
control condition (p = .001), but sensitivity was not affected
by task difficulty in the disgust-sweat condition, t(35) = 1.72,
p = .282. In the fear-sweat condition, differences in detection
sensitivity between the easy and difficult tasks were not sig-
nificantly different from such differences in the disgust-sweat
and control condition (F < 1; Fig. 3a). Follow-up analyses on
difference scores, however, indicated that detection sensitivity
decreased from the easy to the difficult task in the fear-sweat
condition in comparison with the other odor conditions—
control: t(35) = 2.56, p = .015; disgust sweat: t(35) = 1.82, p =
.049. Taken together, these data suggest that perceptual bene-
fits from a fear state may interact with task difficulty.
In addition to detection sensitivity, response bias (β) also
varied as a function of task type, F(1, 35) = 12.25, p = .001,
η2 = .07. Response bias is an individual’s decision rule and is
quantified as the ratio between the likelihood of responding
that the target is absent and the likelihood of responding
that the target is present; higher ratios indicate a more conser-
vative response tendency. As Figure 3b shows, response bias
increased markedly in the fear-sweat condition when the task
became difficult, t(35) = 3.62, p < .001. Thus, fear chemosig-
nals induced caution on the difficult part of the search task.
Exposure to disgust chemosignals reduced detection sensi-
tivity (sensory rejection) under all circumstances. In the fear-
sweat condition, however, detection sensitivity was higher
(sensory acquisition) when targets were easily detectible,
whereas it was lower when targets were embedded in
excessive distractors. These combined results suggest that
perceptual benefits associated with fear are limited to easy
target-distractor configurations.
We examined eye scanning behavior to corroborate the
connection between detection sensitivity and the visual sys-
tem. Eye scanning is facilitated by fear, as widely opening the
eyes increases the visual field (Susskind et al., 2008). Two 3
(odor condition: fear sweat, disgust sweat, control) × 2 (task:
easy, difficult) repeated measures ANOVAs revealed signifi-
cant differences in the number of target fixations, F(2, 70) =
4.43, p = .016, η2 = .03, and fixation durations, F(2, 70) = 4.45,
p = .015, η2 = .03, among odor conditions. Compared with the
control condition, chemosignals in the fear-sweat condition
induced sensory acquisition, as evidenced by fewer target fix-
ations (p = .014) and faster target and distractor fixations (p =
.011; see Additional Analyses and Table S3 in the Supplemen-
tal Material). Sensory rejection was evidenced by avoidance
behavior rather than a decrease in scanning speed and effec-
tiveness. A facial-muscle expression of disgust (i.e., raising
the cheek) restricted the lower visual field, which is already
limited during neutral viewing conditions (Susskind et al.,

No relation to pleasentness
Downloaded from pss.sagepub.com at University Library Utrecht on September 4, 2015
 Chemosignalling
❖ Body odour transfers chemical signals reflecting emotional
state (bio marker unknown)
❖ Similar results for happy body odours (de Groot et al.,
2015)
❖ Social contagion
❖ Some sex differences:
❖ Males send stronger signals (for stress)
❖ Females have greater sensitivity (Wysocki et al., 2009)

25
 What else can we smell?
lites, electrolytes, and traces of drugs (9). In mice,
tears contain a chemosignal or pheromone (10–12).
Because the chemical makeup of human emo-
REPORTS
tional tears differs from that of reflexive eye- We first asked whether emotional tears have a
protective tears (13), we hypothesized that human discernable odor. We obtained negative-emotion
tears may similarly convey a chemosignal. tears from two donor women (ages 30 and 31)

Fig. 1. Emotional tears are odorless. (A) To obtain tears,

donor women watched sad films in isolation, using a
mirror to capture tears into a vial. A typical donation con-
tained ~1 ml. (B) For continuous exposure, tears deposited
onto a pad allowed ongoing nasal airflow exposure but not
transdermal diffusion. (A) and (B) are illustrations. (C) Ac-
curacy of discrimination of tears from saline. (D to F)
Scatterplots of (D) intensity, (E) pleasantness, and (F) fa-
miliarity estimates of tears and saline in all experiments.
❖ Human tears
Within-participants comparisons [(D) to (F) here and in all
other figures] are presented in scatterplots along a unit slope
line (x = y), where each point reflects a participant. If data
accumulate under the line, then values were greater for
tears; if data accumulate above the line, then values were
❖ emotional tears
greater for saline. If data accumulate on the line, then there
was no difference between tears and saline. (Insets) Bars
reflect the number of participants on each side of the unit
different make up than
slope line (left ordinate), and the horizontal dashed line
reflects the mean values and standard error (right ordinate).

protective tears
❖ Are they chemosignals?
(Gelstein et al, 2011)

26

Fig. 2. Sniffing tears reduces attributed sexual attraction. (A) and (B) Typical
VAS questions from the face-rating experiment. (C) Attributed sexual at-
traction by 24 men. Data accumulated above the line, indicating reduced
attributed sexual attraction after sniffing tears. (Inset) Bars reflect the number
of participants on each side of the unit slope line (left ordinate), and the
horizontal dashed line reflects the mean values and standard error (right
ordinate).

www.sciencemag.org SCIENCE VOL 331 14 JANUARY 2011 227

protective: clean eye etc.

Emo tears compared to saline trickled down women face

What else can we smell?

Fig. 2. Sniffing tears reduces attributed sexual attraction. (A) and (B) Typical
VAS questions from the face-rating experiment. (C) Attributed sexual at-
traction by 24 men. Data accumulated above the line, indicating reduced
attributed sexual attraction after sniffing tears. (Inset) Bars reflect the number
of participants on each side of the unit slope line (left ordinate), and the
horizontal dashed line reflects the mean values and standard error (right
ordinate).

www.sciencemag.org SCIENCE VOL 331

27
14 JANUARY 2011 227
 sniffing saline, indicating no change. (Insets) Bars
reflect the number of participants on each side of the
unit slope line (left ordinate), and the horizontal
dashed line reflects the mean values and standard
error (right ordinate).

What else can we smell?

❖ Effects on testosterone

228 14 JANUARY 2011 VOL 331 SCIENCE www.sciencemag.org

28

Also fMRI data showing decrease in sexual arousal related areas and in subjective scoring
(both of women and of own state)
 What else can we smell?

❖ MHC: Major histocompatibility complex

❖ genes with product that is part of immune systems
❖ Having more different alles = better
❖ Smelling mice and vice versa

29

humans can smell difference between mouse families only differing in MHC

mice can recognise human MHG-types from urine

 What else can we smell?

❖ Is it useful?
❖ Students with 3 types of MHC (Wedekind 1995)
❖ t-shirts (two nights)

30
 number of dissimilar HLA-antigens = 2.7, s.d. = 0.74). We
tried to present every T-shirt as often to MHC-dissimilar MHC-type of women who MHC-type of women who
women as to MHC-similar women (average difference of do not take oral contraceptives take oral contraceptives
presentations to thc two groups: -0.02, s.d. = 0.73). The Figure 1. Average score per male (taking each male's odour
presentation was random in every other respect, and the as a statistical unit) by females who are similar or dissimilar
women did not know the degree of MHC-similarity of the +
on their M H C (medians and quartiles). (a) (c) The odours
men who had worn the T-shirts. The T-shirts were provided were judged by females who did not take oral contraceptives
in numbered, glazed cardboard boxes laid out with plastic +
(number of males = 38), and ( 6 ) (d) judged by females who
foil ( P ~ D Ca) triangular
, hole allowed the women to sniEthe take the pill (number of males = 23). All p-values are two-
contents. Alone in a room, every woman scored the odours of tailed (Wilcoxon signed rank tests).
246 C. Wedekind and others MHC-dependent mate prefe >rences
the in humans
T-shirts Male results
for intensity (range 0-10) and for pleasantness
Female results
and sexiness (range 0-10, 5 = neutral). A marked box with
mainly Gom chemistry, physics and geography) and were a n unworn T-shirt was provided to allow the women to
unlikely to meet each other during the study. The men were control for the T-shirt's own odour. The women were tested
asked to wear a T-shirt (100 Oj, untreated cotton, distributor: whenever possible in the second week after the beginning of
Virya, Zurich ( C H ) ) during a Sunday and Monday night, to menstruation (with pill: 11.4 d, s.d. = 4.3, without pill:

Sexiness

Sexiness
keep the T-shirt in a n open plastic bag in between, and to live 12.4d, s.d.=4.3, t = -0.80, p,<0.40, two-tailed), as
as much as possible 'odour-neutral' during these two days. women appear to be most odour-sensitive a t this time (Doty
They were provided with perfume-free detergent to wash et al. 1981). We also asked them to prepare themselves for the
clothes and bedclothes, and perfume-free soap to use from experiment by taking care of their sense of smell. Therefore,
Sunday morning onwards. They were also provided with a the women had been asked to use a nose spray during 14 days
list of odour-producing foods and asked to avoid them as well before the experiment to support regeneration of the nasal
as any activities that could produce disturbing smells (for mucous membrane if necessary (and also as a prophylactic
example, staying in smelly rooms, sexual activity, etc). They against colds or 'flu), and each was given a copy of P.
were advised not to use any deodorants, perfumes etc., to Suskind's novel ' Das Parfum ' (Diogenes-Verlag) to sensitize
refrain from smoking tobacco or drinking alcohol, and to their smell perception.
sleep alone in their bed. Each female subject scored the odours of six male subjects
O n the following Tuesday test women were asked to rate which resulted in 294 combinations of individual women
the odours of six T-shirts each, three of them worn by men sniffing on individual men's odours. Additionally each male
who were dissimilar to the rating woman's M H C (average odour was scored by two or more females (one of similar and
number of dissimilar HLA-antigens = 5.9, s.d. = 0.26), and one of dissimilar MHC-type). For the analyses shown in
three worn by men who were more similar to it (average figures 1-3 * we used the average scorings per male odour or *
dissimilar similar dissimilar similar dissimilar similar dissimilar similar
number of dissimilar HLA-antigens = 2.7, s.d. = 0.74). We per scoring female.
tried to present every T-shirt as often to MHC-dissimilar The data MHC-type
analysesofwere
womendonewho
with MHC-type of women
SYSTAT (version forwho MHC-type of men MHC-type of men
women as to MHC-similar women (average difference of Macintosh-computer) do not take oral. contraceptives take oral contraceptives
31 Figure 2. Average score per female of the body odours of
presentations to thc two groups: -0.02, s.d. = 0.73). The Figure 1. Average score per male (taking each male's odour males being similar or dissimilar on the M H C to the scoring
presentation was random in every other respect, and the 3. R asEaSstatistical +
U L T S unit) by females who are similar or dissimilar females (medians and quartiles). (a) (c) Females who do
women did not know the degree of MHC-similarity of the +
on their M H C (medians and quartiles). (a) (c) The odours not take the contraceptive pill (n = 31), and ( 6 ) (4 females+
men who had worn the T-shirts. The T-shirts were provided The
werescores
judgedforbysexiness
females are
whonot
didshown
not takeinoral
the contraceptives
figures as who take the pill (n = 18). P-values are two-tailed (Wilcoxon
in numbered, glazed cardboard boxes laid out with plastic they(number were of highly
males = correlated +
38), and ( 6with
) (d)pleasantness
judged by females (allwho signed rank tests).
foil ( P ~ D Ca) triangular
, hole allowed the women to sniEthe scorings: = 0.85,
take ther pill (number 294;
n = of for=women
males 23). All who do are
p-values nottwo-
contents. Alone in a room, every woman scored the odours of take tailed pill: r = 0.87,
the (Wilcoxon signedn= 186;
rank for women who take
tests).
the T-shirts for intensity (range 0-10) and for pleasantness the pill : r = 0.83, n = 108, p always 4 0.001). M H C is more similar to that of the test man (see figure
and sexiness (range 0-10, 5 = neutral). A marked box with The pleasantness of men's body odours scored by 1a). This difference in the scoring of odour pleasantness
a n unworn T-shirt was provided to allow the women to different women depends on their respective MHC. was reversed when the judging women were taking oral
control for the T-shirt's own odour. The women were tested Women who are not taking oral contraceptives and contraceptives. In this case, a man's body odour was
whenever possible in the second week after the beginning of who are dissimilar to a particular male's M H C perceive
scored as being more pleasant by women who are more
menstruation (with pill: 11.4 d, s.d. = 4.3, without pill:
his odour as more pleasant than do women whose similar on the M H C (see figure 1h ) .
12.4d, s.d.=4.3, t = -0.80, p,<0.40, two-tailed), as
women appear to be most odour-sensitive a t this time (Doty
Proc. R. Sac. Land. B (1995)
et al. 1981). We also asked them to prepare themselves for the
experiment by taking care of their sense of smell. Therefore,
the women had been asked to use a nose spray during 14 days
before the experiment to support regeneration of the nasal
mucous membrane if necessary (and also as a prophylactic
against colds or 'flu), and each was given a copy of P.
Suskind's novel ' Das Parfum ' (Diogenes-Verlag) to sensitize
their smell perception.
Each female subject scored the odours of six male subjects
which resulted in 294 combinations of individual women
sniffing on individual men's odours. Additionally each male
odour was scored by two or more females (one of similar and
one of dissimilar MHC-type). For the analyses shown in
figures 1-3 we used the average scorings per male odour or *
per scoring female. dissimilar similar dissimilar similar
The data analyses were done with SYSTAT (version for MHC-type of men MHC-type of men
Macintosh-computer) .
Figure 2. Average score per female of the body odours of
males being similar or dissimilar on the M H C to the scoring
3. R E S U L T S +
females (medians and quartiles). (a) (c) Females who do

x-as = pleasantness highly correlated to ‘sexiness’

+
The scores for sexiness are not shown in the figures as
they were highly correlated with pleasantness (all
difference in pleasantness, not intensity
scorings: r = 0.85, n = 294; for women who do not
take the pill: r = 0.87, n = 186; for women who take
the pill : r = 0.83, n = 108, p always 4 0.001).
The pleasantness of men's body odours scored by
different women depends on their respective MHC.
Women who are not taking oral contraceptives and
who are dissimilar to a particular male's M H C perceive
his odour as more pleasant than do women whose
not take the contraceptive pill (n = 31), and ( 6 ) (4 females
who take the pill (n = 18). P-values are two-tailed (Wilcoxon
signed rank tests).
M H C is more similar to that of the test man (see figure
1a). This difference in the scoring of odour pleasantness
was reversed when the judging women were taking oral
contraceptives. In this case, a man's body odour was
scored as being more pleasant by women who are more
similar on the M H C (see figure 1h ) .

Proc. R. Sac. Land. B (1995)

 number of dissimilar HLA-antigens = 5.9, number
s.d. =of0.26),
dissimilar
and HLA-antigensnumber of = 5.9, s.d. = HLA-antigens
dissimilar 0.26), and = 5.9, s.d. = 0.26), and
three worn by men who were more similar three to worn by men who were
it (average * more
three worn similar
by men to who
it (average
were more *
similar todissimilar
it (average *
dissimilar similar dissimilar similar similar dissimilar
dissimilar similar
similar dissimilar similar
number of dissimilar HLA-antigens = 2.7, number
s.d. =of0.74).
dissimilar
We HLA-antigensnumber of = 2.7, s.d. =HLA-antigens
dissimilar 0.74). We = 2.7, s.d. = 0.74). We
tried to present every T-shirt as often tried to present every T-shirt
to MHC-dissimilar MHC-type
tried as tooften
present toof MHC-dissimilar
women who MHC-type
every T-shirt as often toofMHC-type
women who
MHC-dissimilar of women who MHC-type of of women
women who MHC-type of women who
women as to MHC-similar women (average women difference
as to MHC-similar
of do not take
womenas(average
women oral contraceptives
to MHC-similar differencewomen oftake oral do not take
contraceptives
(average difference oforal contraceptives do take
not oral
take contraceptives
oral contraceptives take oral contraceptives
presentations to thc two groups: -0.02,presentations s.d. = 0.73).toThe thc twoFigure
groups: -0.02, tos.d.
presentations
1. Average thc
score 0.73).
= two
per male The(taking
groups: -0.02,eachs.d.
Figure = 0.73).
1. Average
male's odour The per Figure
score male (taking each score
1. Average male'sperodour
male (taking each male's odour
presentation was random in every other presentation
respect, and wasthe random as in every other
apresentation
statistical was
unit) respect,
byrandom andinwho
females the
every as
are othera statistical
similar respect, unit)
and the
or dissimilar by femalesas awho are similar
statistical unit) or bydissimilar
females who are similar or dissimilar
women did not know the degree of MHC-similarity women did not of know
the the ondegree
their MofH
women didMHC-similarity
not know and
C (medians of
the quartiles).
degree +
the of on (a)their(c) M
MHC-similarity
The H Codours
(medians
of the andonquartiles). +
their M H(a) (c) The and
C (medians odours +
quartiles). (a) (c) The odours
men who had worn the T-shirts. The T-shirts men who werehad worn the T-shirts.
provided were men The by
who
judged T-shirts
hadfemales
worn were
the
who provided
T-shirts.
did not The takewere
oraljudged
T-shirts werebyprovided
contraceptives females whowere did notjudgedtake by
oral contraceptives
females who did not take oral contraceptives
in numbered, glazed cardboard boxes laid in numbered,
out with plastic glazed cardboard boxes
in numbered,
(number of males laidglazed
=out38),with + plastic
cardboard
and ( 6 ) (d)boxes (number
judged laidbyout of with
males
females plastic
who + ( 6 ) (d)of
= 38), and(number judged
malesby +
= females
38), andwho ( 6 ) (d) judged by females who
foil ( P ~ D Ca) triangular
, hole allowed thefoil women a) triangular
( P ~ DtoCsniEthe
, hole allowed
takefoilthe( Ppill Dthe
~Male Ca) women
(number, results
triangular of tomales
sniEthe
hole=allowed
23). Alltake
the the pillare
women
p-values to(number
two- of males
sniEthe take=the 23).pillAll(number
p-values ofare two-= 23). All p-values are two-
males
contents. Alone in a room, every woman contents. scored theAlone odours in of
a room, every woman
contents.
tailed (Wilcoxon Alonescored in athe
signed odours
room,
rank every of woman
tests). tailed (Wilcoxon
scored the odours signed
of ranktailed
tests). Female results
(Wilcoxon signed rank tests).
C. Wedekind and the others
T-shirts for MHC-dependent
intensity (range prefe >rences
mate0-10) and in pleasantness
the T-shirts
for humans for intensity (range 0-10) and
the T-shirts for pleasantness
for intensity (range 0-10) and for pleasantness
and sexiness (range 0-10, 5 = neutral). and sexiness
A marked box with 0-10, 5 and
(range = neutral).
sexinessA(range marked 0-10,box5with= neutral). A marked box with
y Gom chemistry,a nphysicsunworn andT-shirt
geography) and were to allow
was provided a n unworn
the women T-shirt to was provided
a n unworn to allowT-shirt the was womenprovidedto to allow the women to
ly to meet each other during
control the T-shirt's
for the study. The ownmen were Thecontrol
odour. womenfor werethetested
T-shirt's owncontrolodour.for The thewomen
T-shirt's were owntested
odour. The women were tested

Sexiness

Sexiness
to wear a T-shirt (100 Oj, untreated cotton, distributor:
whenever possible in the second week after the beginning of whenever possible in the second week after the
whenever possible in the second beginning of week after the beginning of
, Zurich ( C H ) ) during a Sunday and
menstruation (with Monday night,
pill: 11.4 d, tos.d. =menstruation
4.3, without (with pill: pill: 11.4 d, s.d. = 4.3,
menstruation (with without
pill: 11.4 pill:d, s.d. = 4.3, without pill:
he T-shirt in a n open plastics.d.=4.3,
12.4d, bag in between, and to live
t = -0.80, p,<0.40, 12.4d, s.d.=4.3,as t = -0.80,
two-tailed), 12.4d, p,<0.40,
s.d.=4.3, two-tailed),
t = -0.80,as p,<0.40, two-tailed), as
ch as possible 'odour-neutral' during these two days. women
women appear to be most odour-sensitive a t thisappear
time (Doty to be most odour-sensitive
women appeara to t this time (Doty
be most odour-sensitive a t this time (Doty
were provided with perfume-free detergent to wash et al. 1981). We
et al. 1981). We also asked them to prepare themselves foralso
the asked them et al.to1981).
prepare Wethemselves
also asked for them theto prepare themselves for the
s and bedclothes, and perfume-free soap to use from
experiment by taking care of their sense experiment by taking care ofexperiment
of smell. Therefore, their senseby of taking
smell. Therefore,
care of their sense of smell. Therefore,
ay morning onwards. They were also provided with a the women had been asked to use a nose spray during 14 days
the women had been asked to use a nose spray during 14 days
odour-producing foods and asked to avoid them as well
the women had been asked to use a nose spray during 14 days
before the experiment to support regeneration of the nasal
beforeproduce
y activities that could the experiment
disturbingto smells
support (forregeneration of the nasal before the experiment to support regeneration of the nasal
mucous membrane if necessary (and also as a prophylactic
mucous
ple, staying in smelly rooms, membrane if necessary
sexual activity, etc). They(and also as a prophylactic mucous membrane if necessary (and also as a prophylactic
against colds or 'flu), and each was given a copy of P.
advised not to useagainst colds or 'flu),
any deodorants, perfumes each towas given a copy of P.
and etc., against colds or 'flu), and each was given a copy of P.
Suskind's novel ' Das Parfum ' (Diogenes-Verlag) to sensitize
Suskind's
n from smoking tobacco ornovel
drinking' Dasalcohol,
Parfum and' (Diogenes-Verlag)
to to sensitize Suskind's novel ' Das Parfum ' (Diogenes-Verlag) to sensitize
their smell perception.
alone in their bed.their smell perception. their smell perception.
Each female subject scored the odours of six male subjects
the following Tuesday Each testfemale
women subject
were scored
asked totherateodours of six male subjects Each female subject scored the odours of six male subjects
which resulted in 294 combinations of individual women
dours of six T-shirtswhich
each,resulted
three of in 294worn
them combinations
by men ofsniffing individual women which resulted in 294 combinations of individual women
on individual men's odours. Additionally each male
sniffing on individual
were dissimilar to the rating woman's M H C (average men's odours. Additionally each male sniffing on individual men's odours. Additionally each male
odour was scored by two or more females (one of similar and
odour was scored
er of dissimilar HLA-antigens = 5.9,bys.d. two=or moreand
0.26), females (one of similar and odour was scored by two or more females (one of similar and
one * of dissimilar MHC-type). For the analyses shown in
worn by men who onewereof dissimilar
more similar MHC-type).
to it (average For the analyses shown in one of dissimilar MHC-type). For the analyses shown in
figures 1-3 dissimilar
we used similar
the average scorings per male
dissimilar similarodour or *
figures 1-3 we
er of dissimilar HLA-antigens useds.d.
= 2.7, the =average
0.74). We scoringsper perscoring
male odour
female. or figures
* 1-3 we used the average scorings per male odour similar
dissimilar or * dissimilar similar
to present every per scoring
T-shirt female.
as often to MHC-dissimilar MHC-type of women who MHC-type
per scoring dissimilar
female. ofsimilar
women who dissimilar similar dissimilar similar dissimilar similar
Thedo datatake
not analyses
oral were done
contraceptives with
take SYSTAT
oral (version for
contraceptives MHC-type of men MHC-type of men
n as to MHC-similar Thewomen (averagewere
data analyses difference
done with of SYSTAT (version for .
Macintosh-computer) The dataMHC-type analyses of menwere done with SYSTAT
MHC-type (version for
of men MHC-type of men MHC-type of men
ntations to thc two groups: -0.02, s.d.. = 0.73). The
Macintosh-computer) Figure 1. Average score per Macintosh-computer)
male (taking each male's . odour Figure 2. Average score per female of the body odours of
Figure 2. Average score per female of males the body 32
ntation was random in every other respect, and the as a statistical unit) by females who are similar or dissimilar beingodours
similarofor dissimilar
Figure on 2.theAverage
M H C toscore per female of the body odours of
the scoring
n did not know the degree of MHC-similarity of the
3. R E S U L T S
3.
on R E SM
their UL HT +
males being similar or dissimilar on the M
C S(medians and quartiles). (a) (c) The odours
3. R E(medians +
S U L T Sand quartiles). (a) (c) Females who do
H C to(medians
females the scoring and quartiles).+
males being
(a) (c) similar
Females or dissimilar
who do on the M H C to the scoring
+
who had worn the T-shirts. The T-shirts were provided females
were judged by females who did not take oral contraceptives not take the contraceptive females
pill (n = (medians
31), and ( 6 ) +
and (4quartiles).
females (a) (c) Females who do
mbered, glazed cardboard The scores boxesfor laidsexiness
out with are plastic
not shown
The scores for sexiness
(number
in the of males =
figures as 38),
notare
and take+not shown
) the
( 6The (d)scores
judged
in the figures
contraceptive
for bysexiness
femalespill who
(n =
are
as31), and +
who (take
6 ) the (4 females
pill not takeare
(n =as18). P-values thetwo-tailed
contraceptive (Wilcoxon +
pill (n = 31), and ( 6 ) (4 females
P ~ D Ca) triangular
, hole allowed the women to sniEthe they
take were
the pill highly
(number correlated
of who
males take with
the pill pleasantness
(n = 18). P-values
= 23). All p-values are two-
(allnot shown
are two-tailed
in the
signed rank
figures
(Wilcoxon
tests). who take the pill (n = 18). P-values are two-tailed (Wilcoxon
they were highly correlated with scorings: pleasantness r = 0.85, (all n = theyrank
294;
signed were
for women
tests).highly who correlated
do not with pleasantness (all signed rank tests).
nts. Alone in a room, every woman scored the odours of tailed (Wilcoxon signed rank tests).
scorings: r = 0.85, n = 294; for women
-shirts for intensity (range 0-10) and for pleasantness take the whopill:do rnot = 0.87, n scorings:
= 186; for r= women0.85, who n = 294; take for women who do not
take the pill: r = 0.87,
exiness (range 0-10, 5 = neutral). A marked box with n = 186; for women who take take
the pill : r = 0.83, n = 108, p always 4 0.001). the pill: r = 0.87, n = 186; for women who take
M H C is more similar to that of the test man (see figure
nworn T-shirt wasthe pill : r =
provided to 0.83,
allow nthe = 108,
women p always
to 4The 0.001).
pleasantness ofMmen's HtheC ispill
more
body: r =odours0.83, nto
similar 108,of
=that
scored p the
by always
test 4This
1a).man 0.001).
(see figure in the M
difference H C isof
scoring more
odour similar to that of the test man (see figure
pleasantness
ol for the T-shirt's own The pleasantness
odour. The womenofwere men's testedbody different
odours scored womenby depends 1a). ThisThetheir
on pleasantness
differencerespective in the ofMHC.
men's of
scoring bodywasodours
odour scored
pleasantness
reversed when by 1a). This
the judging women difference
were taking in theoral
scoring of odour pleasantness
ever possible in thedifferent
second week women depends
after the beginning on of their Women
respective who MHC. are not was different
taking oral women
reversed when thedepends
contraceptives judging andon their
women respective
were taking oral
contraceptives. MHC.
In this case,was areversed
man's body when odour the judging
was women were taking oral
ruation (with pill: 11.4 d, s.d. 4.3, without
Women who are not taking oral contraceptives pill: and to a contraceptives.
Womenmale's whoInare
=
who are dissimilar particular MthisHnot taking
C case,
perceive oralscored
a man's contraceptives
body odour
as beingwas and pleasant
more contraceptives.
by women who In thisare case,
more a man's body odour was
d, s.d.=4.3, t = who -0.80, p,<0.40, to
are dissimilar two-tailed),
a particular as male's M H C perceive whoas
scored are dissimilar
being to a particular male's Mon Hare
C perceive
his odour as more pleasant than domore women pleasantwhose by women similar who the more
M H C (seescored figure as1hbeing
). more pleasant by women who are more
n appear to be most odour-sensitive a t this time (Doty
his odour as more pleasant than do women whose his odour
similar on theasM more H C (see pleasant
figure than 1h ) . do women whose similar on the M H C (see figure 1h ) .
1981). We also asked them to prepare themselves for the
iment by taking care of their sense of smell. Therefore, Proc. R. Sac. Land. B (1995)
omen had been asked Proc.toR.use
Sac.a Land. B (1995)
nose spray during 14 days Proc. R. Sac. Land. B (1995)
e the experiment to support regeneration of the nasal
us membrane if necessary (and also as a prophylactic
st colds or 'flu), and each was given a copy of P.
nd's novel ' Das Parfum ' (Diogenes-Verlag) to sensitize
smell perception.
ch female subject scored the odours of six male subjects
resulted in 294 combinations of individual women
ng on individual men's odours. Additionally each male
was scored by two or more females (one of similar and
f dissimilar MHC-type). For the analyses shown in
s 1-3 we used the average scorings per male odour or *
coring female. dissimilar similar dissimilar similar
e data analyses were done with SYSTAT (version for MHC-type of men MHC-type of men
ntosh-computer) .
Figure 2. Average score per female of the body odours of
males being similar or dissimilar on the M H C to the scoring
ESULTS +
females (medians and quartiles). (a) (c) Females who do
not take the contraceptive pill (n = 31), and ( 6 ) + (4 females
e scores for sexiness are not shown in the figures as who take the pill (n = 18). P-values are two-tailed (Wilcoxon
were highly correlated with pleasantness (all signed rank tests).
ngs: r = 0.85, n = 294; for women who do not
the pill: r = 0.87, n = 186; for women who take

now same smellswas better for men. Moreover, women don’t use it anymore
ill : r = 0.83, n = 108, p always 4 0.001). M H C is more similar to that of the test man (see figure
e pleasantness of men's body odours scored by 1a). This difference in the scoring of odour pleasantness
rent women depends on their respective MHC.
reversed when the judging women were taking oral
men who are not taking oral contraceptives and contraceptives. In this case, a man's body odour was
are dissimilar to a particular male's M H C perceive scored as being more pleasant by women who are more
dour as more pleasant than do women whose similar on the M H C (see figure 1h ) .

R. Sac. Land. B (1995)

 mate preferences in humans
❖ Do we use it?
odour intensity
33 and
Figure 3. Relations between scores of odour pleasantness
odour intensity (all females pooled, n = 49 each). Average
scorings per female of the body odours of three males each (a)
being dissimilar on the MHC, and (b) being similar on it to
the scoring female. The correlations do not differ significantly
between females who take the contraceptive pill ( 0 )and
females who do not take the pill (0) (comparison between
independent correlation coefficients (a) Z = -0.13, fi =
0.90, (b) Z = 1.28, @ = 0.20; all @-valuesare two-tailed).
By taking each man as a statistical unit (see figure I ) ,
we control for odour differences which are not MHC-
dependent. The data are replotted in figure 2 using
each woman as a statistical unit. Despite a certain loss
of statistical power in this kind of analysis, we still
observe analogous trends although not significant in
the case of women taking the contraceptive pill (see
figure 26).
The female evaluations of odour intensities did not
differ significantly between MHC-similar and dis-
similar men in any comparison (see figure lc,d and
figure 2c,d). However, the relation between odour
intensity and its pleasantness differed in the two
groups: more intensive odours tend to be more
unpleasant for women when they scored odours of
MHC-dissimilar men (see figure 3a), whereas intensity
and pleasantness did not correlate for women when
they scored MHC-similar male odours (see figure 3b).
This difference could indicate some properties of the
physiology of odour perception which seem to be
independent of steroids administered by the pill (see
legend of figure 3).
Odours of MHC-dissimilar men reminded the female
test persons of their own mates or ex-mates twice as
often as those of MHC-similar men (see figure 4). This
R. SOC.
PTOG. Lond. B (1995)
Contraceptives seem to interfere with natural mate selection: actually a big deal since it
seems similar MHC tends to lead to less and less successful pregnancies
Paper actually states negative consequences should be made known by parfume industry
and contraception industry
C . Wedekind and others 247
'reminds of mate I ex-mate'
"
dissimilar similar
MHC-type of men
Figure 4. Frequency of women's memory associations by
sniffing the odours of MHC-dissimilar men and of MHC-
similar men with relatives, and with current or previous
mates, respectively (Fisher exact tests, two-tailed). Most of
the memory associations in the lower graph were by women
who stated that they were sure they had not taken the
contraceptive pill when they chose the particular mate they
were remembered during the experiment (31 of total 39
cases, Z = 3.68, fi < 0.01).
indicates that MHC-dependent body odour prefer-
ences play a role in actual mate choice.
4. D I S C U S S I O N
The contraceptive pill seems to have a strong influence
on odour preference. This indicates that steroids which
are naturally released during pregnancy could change
body odour preferences, leading to a preference for
odours which are similar to those of relatives. This
preference is probably not related to mate choice but
may be comparable, to a certain degree, to the
observation that female mice prefer MHC-similar
individuals for communal nesting (Manning et al.
1992). Therefore, the contraceptive pill seems to
interfere with natural mate choice. If the pill changes
preferences for familiar as well as unfamiliar body
odours then starting with the pill could have an
influence on the stability of an already existing pair
bond by influencing odour preference.
There is an increasing amount of work which indi-
cates that the M H C may not only influence mate choice
but also maternal selection thereafter. Couples who had
not achieved a recognizable pregnancy after two or
more attempts of in vitro fertilization (IVF) or tuba1
embryo transfer (TET)shared a significantly greater
number of HLA antigens than did control couples who
achieved a viable pregnancy with their first IVF or TET
 t al. • Human Chemosignaling Where does it come from? J. Neurosci., February 7, 2007 • 27(6):1261–1265 • 1263

ssayed in duplicated wells. Tubes from a given subject were all assayed
e same plate, and tubes from different visits obtained at a given time (for
1–5) were assayed on the same column of the 96-well plate to avoid
matic errors between conditions. After completion ofAndrostadienone
the immunoas-
he absorbance of the fluorescent cortisol conjugate–antibody complex
(AND):
wells were obtained at 450 nm and corrected at 490 nm with a Bio-Rad
Steroid present
in human
ules, CA) multiplate reader (model 680). Standard dilutions male
of cortisol
012, 0.037, 0.1, 0.333, 0.1, 0.3, 1, 3 !g/dl) were used along a nonspecific
secretions such as
ng well in the first two columns of the kit for calibration. Defined high
ow control concentrations were used to calibrate each column of the and
sweat, saliva,
The absolute salivary cortisol concentration was estimatedsemenfrom the
scence of the cortisol conjugate–antibody complex by computing the
e value on the four parameters sigmoid fit obtained with the standard
. All data with !15% error between duplicates were retested. All anal-
ere conducted blind to the condition of collection. Finally, one subject
xcluded from the cortisol analysis because of nonphysiological values 34
!g/dl).

reduction
ological data were first expressed as a change score for each period
erest by subtracting the baseline value from that period. Results
then expressed as z-scores to combine them into a composite index
o compare them between subjects. To standardize the representa-
of our data, the psychological data were also expressed as change Figure 1. Smelling androstadienone altered mood and autonomic physiology. Androstadi-
s for each period of interest by subtracting the baseline value from enone is shown in the white bars and control in the black bars. A–C, All variables are shown as
period. To reduce the number of comparisons, the psychological a change from baseline in z-score. Smelling AND maintained better mood (A), higher sexual
ptors were grouped into three categories: positive mood descrip- arousal (B), and a higher physiological composite index (C).
negative mood descriptors, and sexual arousal. This grouping was
rmed according to previously reported criteria (Bensafi et al., 2003,
,b). In particular, the positive mood index was computed as the with CONT (F(1,167) " 13.61; p # 0.0005) (Fig. 1 A), and in-
combination of z-scores from ratings of the six positive adjectives creased composite physiological arousal score after AND com-
sed, calm, confident, content, interested, and happy). Similarly, to pared with CONT (F(1,248) " 19.11; p # 1.9e-005) (Fig. 1C).
e multiple comparisons, all physiological measures were equally Subjective sexual arousal was also not significantly different at
ted in a physiological arousal index such that an increase in physi- baseline (t(20) " %1.3068; p # 0.2061), but a postexposure
cal arousal was associated with an increase in NS-SCR, ECG, FP, EP,
ANOVA revealed a significant main effect of compound, reflect-
R, TR, and MOV, and with a decrease in ST. This weighting was
n because it was the exact weighting used previously, based on
ing increased sexual arousal after AND compared with CONT
endently (in time) obtained data (Bensafi et al., 2003). Corroborat- (F(1,167) " 10.3857; p # 0.002) (Fig. 1 B), a significant main effect
is weighting, all measures were positively correlated in the current of time, reflecting increased sexual arousal as the study pro-
Increased
s well (mean mood
r " 0.35; all p # and
0.05), except arousal
ST, which was negatively gressed (F(3,167) " 6.6713; p # 0.0006), but no interaction
ated with most measures. (F(3,167) " 0.4148; p # 0.7430). As noted, both the direction and
cause absolute cortisol values have meaning (not only as relative magnitude of the above effects on mood, autonomic physiology,
ge scores), both analysis and presentation were conducted on the and subjective sexual arousal, were all highly consistent with pre-
alues. The cortisol data were also expressed as a change score for vious reports (Grosser et al., 2000; Jacob et al., 2001b, 2002;
period of interest (by subtracting the baseline value from that pe- Lundstrom et al., 2003; Bensafi et al., 2004a; Lundstrom and
and as a z-score to compare between subjects.
Olsson, 2005).

ults Smelling AND maintained elevated cortisol

ling AND maintained better mood, higher sexual
sal, and increased physiological arousal
and CONT were perceptually similar in terms of perceived
antness (pleasAND, 2.2084 $ 0.2482; pleasCONT, 2.04 $
t(20) " 0.6899; p # 0.49) and intensity (intAND, 2.86 $
intCONT, 3.06 $ 0.24; t(20) " %0.6519; p # 0.52) (supple-
al Fig. 1, available at www.jneurosci.org as supplemental
rial). However, AND affected mood and physiological
sal in a manner that was significantly different from CONT
highly consistent with previous studies (Grosser et al., 2000;
b et al., 2001b; Bensafi et al., 2004a; Lundstrom and Olsson,
). Whereas mood and physiological arousal were not signif-
ly different at baseline (before smelling either AND or
NT) (all t # 0.68; p ! 0.5), separate ANOVAs on postexpo-
mood and physiology with main effects of compound
D/CONT) and time (four postexposure experimental ep-
) revealed no main effects of time (all F # 0.9; p ! 0.4), no
actions (all F # 1.89; p ! 0.14), but main effects of com-
nd reflecting increased positive mood after AND compared
Having validated that AND was acting in this study in a manner
similar to previous reports in which it improved measures of
mood (Jacob et al., 2001a, 2002; Bensafi et al., 2004a; Lundstrom
and Olsson, 2005) and increased physiological measures of auto-
nomic arousal (Grosser et al., 2000; Bensafi et al., 2003, 2004a),
we now turn to the focus of this paper: the influence of AND on
salivary cortisol. As in the case of mood and physiology, levels of
cortisol were not significantly different at baseline (before smell-
ing either AND or CONT) ([Cortisol], ANDbaseline, 0.237 $ 0.048
!g/dl; CONTbaseline, 0.226 $ 0.036 !g/dl; t(19) " %0.7209; p #
0.4793) (supplemental Fig. 2, available at www.jneurosci.org as
supplemental material). However, an ANOVA on postexposure
salivary cortisol with main effects of compound (AND/CONT)
and time (four postexposure experimental epochs) revealed a
significant main effect of time reflecting decreased levels of sali-
vary cortisol as the study progressed (F(3,152) " 3.3794; p #
0.0253), and critically, a significant main effect of compound,
reflecting significantly higher levels of salivary cortisol after AND
compared with CONT (F(1,152) " 11.88; p # 0.0011) (Fig. 2 A, B),
 Where does it come from?
1264 • J. Neurosci., February 7, 2007 • 27(6):1261–1265 Wya

nose rather than smelled (Stern and McCl

al., 2003), here we found that merely sme
without skin contact, a method of exposur
ural setting, was sufficient to alter levels of
complements previous reports regarding t
physiological influences of smelling AND
may qualify as a human pheromone.
❖ Affected cortisol levels
Human chemosignals may have clinical a
In addition to addressing one of the key cr
action, these results suggest a potential th
whereby merely smelling synthesized or pu
signals may be used to modify endocrin
1971). Diseases associated with altered horm
treated with hormone therapy that often ha
For example, Addison’s disease, characteriz
Figure 2. Smelling androstadienone maintained higher levels of salivary cortisol. Androsta- hormone cortisol, is treated with cortisol
dienone is shown35in the white bars, and control in the black bars. Smelling AND maintained (Marzotti and Falorni, 2004). However,
higher levels of cortisol (A) as a change from baseline in z-score, and in absolute levels of corti-
therapy may cause peptic ulcers, osteoporos
sol (B).
disorders, and other pathologies (Marzott
Triggering endogenous mechanisms of h
but no interaction (F(3,152) ! 0.2632; p " 0.8516) (supplemental have several advantages over traditional h
Fig. 2, available at www.jneurosci.org as supplemental material). tion. For example, consistent with previou
Finally, we replicated the entire study a second time in 27 addi- al., 2000; Jacob et al., 2001b; Bensafi et al., 2
tional subjects, with minor methodological differences, and ob- Olsson, 2005), AND had an anxiolytic-like
tained nearly identical results. This replication is detailed in the mood. However, in contrast to typical a
supplemental material and supplemental Figure 3 (available at creased rather than decreased sexual arou
www.jneurosci.org as supplemental material). highlights the potential advantage of trigg
sponses. Furthermore, we speculate that e
Discussion of hormone release is likely to generate fewe
Androstadienone is a human chemosignal than exogenous hormone administration.
Given the sex-specific and sexual orientation-specific effects of that human chemosignals present a nov
AND on brain mechanisms involved in hormonal regulation mechanism of endocrine therapy.
(Grosser et al., 2000; Jacob et al., 2001b; Savic et al., 2001; Bensafi
et al., 2004a; Lundstrom and Olsson, 2005), we hypothesized that
References
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smelling AND, a chemosignal present in male sweat, may alter to cortisol in serum. Eur J Clin Chem Clin Bioc
endocrine levels in women. Our results are consistent with this Angeli A, Frajria R, Dogliotti L, Crosazzo C, Rigol
hypothesis. Smelling pure AND had a repeatable (supplemental ferences between temporal patterns of plasma co
Fig. 3, available at www.jneurosci.org as supplemental material) binding globulin binding capacity throughout
effect on levels of cortisol, apparent within 15 min, and main- and the menstrual cycle. J Endocrinol Invest 1:
Bensafi M, Brown WM, Tsutsui T, Mainland JD, J
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that given the timescale of changes in mood and changes in cor- Sobel N (2003) Sex-steroid derived compoun
tisol, we cannot unequivocally determine whether AND influ- fects on autonomic nervous system function in
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AND influenced mood through some nonhormonal mechanism, Bensafi M, Brown WM, Khan R, Levenson B, Sobe
and the change in mood then led to a change in cortisol. man sex-steroid derived compounds modulate
tonomic nervous system function in specific b
That humans have an endocrine response to human chemo-
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signals is consistent with observed alterations in menstrual cycles Bensafi M, Tsutsui T, Khan R, Levenson RW, So
after exposure to conspecific sweat alone (Stern and McClintock, human sex-steroid derived compound affect
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and in previous studies the identity of the molecules in female mones in lesbian women. Proc Natl Acad Sci U
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Do we sample smell?

36
 Smelling behaviour

37

Source: A social chemosignaling function for human handshaking

Idan Frumin, Ofer Perl, Yaara Endevelt-Shapira, Ami Eisen, Neetai Eshel, Iris Heller, Maya
Shemesh, Aharon Ravia, Lee Sela, Anat Arzi, Noam Sobel
Smelling behaviour

38
Smelling behaviour

39
 Recap
❖ Flavour is a multi sensory phenomenon
❖ Olfaction and gustation strong connections to limbic
system
❖ Chemo-signalling affects behaviour, perception and affect
❖ emotion specific
❖ Chemical senses appear to have a strong link to social
behaviour
❖ Humans sample smell

40