Scent of a man
New Scientist, 10 February 2001
started with a bit of harmless T-shirt sniffing. A group of women were
asked to sniff T-shirts that had been worn by a group of unknown -- and
unwashed -- men. All they had to do was say which shirts smelled best.
The experiment, run by Claus Wedekind, a young Swiss scientist then at
the University of Bern, was designed to find out if humans, like mice,
use body odour to identify genetically appropriate mates. But it
revealed something more worrying.
As Wedekind predicted, most
female volunteers had equivalent preferences to their rodent
counterparts. Numerous studies in mice have shown that, given the
choice, they sniff out mates with genes for immunity that differ from
their own, and that this seems to increase their chances of producing
healthy offspring. But among Wedekind's volunteers there was a
startling exception to this trend. Women on the contraceptive pill
showed the reverse preference. Instead of being attracted to the scent
of dissimilar men, they chose men whose genes for immunity were closest
to their own.
If humans are using smell to find a good partner
for reproduction, and the Pill is turning things upside down, then
there could be serious consequences. By tricking users into falling for
the wrong guy, the Pill could be giving women better protection than
they bargained for -- making it harder for them to have kids long after
they stop taking it.
It's a contentious idea. For a start, not
everyone agrees that the human brain can register such smells, let
alone that they might influence our behaviour. But if they do, then
does the Pill interfere with this form of sexual chemistry? "It's a
reasonable question," says Wayne Potts, a biologist at the University
of Utah in Salt Lake City, who specialises in mate choice. His
colleague, Dustin Penn, goes further: "It wouldn't surprise me if
sabotaging our reproductive machinery would lead to faulty mate choice."
genes at the centre of the debate are a large cluster called the major
histocompatibility complex, or MHC. Each person has a unique
combination of MHC genes that encode various components of their immune
system. These include genes for histocompatibility antigens -- which
determine, for instance, whether your body will reject a foreign tissue
graft -- and for proteins called complements, which help fight off
disease. The idea is that the more varied an individual's MHC, the more
robust their immunity. And if your parents have widely varying MHC
genes, your own MHC is more likely to be diverse. Parental differences
may even increase the chances of your being born in the first place.
Yamazaki at the Monell Chemical Senses Center in Philadelphia has found
that mouse embryos conceived by parents with dissimilar MHCs are more
likely to make it to term. And at the Reproductive Science Center of
the Bay Area in San Ramon, California, Louis Weckstein found that human
couples who fail to conceive after two or more attempts with IVF shared
significantly more MHC genes than successful IVF couples.
olfactory cues about MHC genes are so important, why do women taking
the Pill seem to respond so differently from other women? "My guess is
that the Pill simulates pregnancy and that maybe during pregnancy,
odour preferences change," says Wedekind. This appears to be what
happens in mice, he points out. The theory is that during pregnancy, a
female is attracted to the smell of her own relatives, who have similar
MHCs to her own. After all, family members have the greatest interest
in seeing her offspring survive. Pregnant women -- and women whose
bodies are tricked into thinking they're pregnant -- might have the
same tendency, says Wedekind.
The implications are not lost on
Marian Petrie from the University of Newcastle upon Tyne. "Potentially,
women might affect their chances of becoming [pregnant], not by
something that's an obvious means," she says. "It might be important
generally to infertility problems." In the next few months, she and her
colleague Craig Roberts will run a follow-up to Wedekind's study to
find out whether the Pill really does skew women's smell preference.
They will ask 80 women who are planning to start taking oral
contraceptives to do the T-shirt test, both before and a few months
after they go on the Pill. The researchers will also run the same test
on 80 women trying to get pregnant, both before and after conception.
date, almost all the work on MHC differences, mate choice and their
effects on offspring viability has been done on rodents. But geneticist
Carole Ober from the University of Chicago has come up with a cunning
way to explore some of the same questions in humans. For over a decade,
she has been studying a North American religious community known as the
Hutterites. Following Wedekind's revelations about the women's
preference for certain odours in an artificial laboratory setting, Ober
aimed to get information about real partnerships.
In many ways,
Hutterites are the perfect study group for "natural" mate choice among
humans. They are a socially isolated group who work on communal farms,
marry within their own community, and can trace their roots back to a
handful of European ancestors in the 16th century. Single men and women
visit neighbouring Hutterite colonies, and often end up working or
celebrating special occasions alongside potential spouses. They don't
use perfumes or deodorants. "They are absolutely maximising the
importance of MHC," says Ober. They marry once -- divorce is strictly
prohibited -- and, claims Ober, they marry for love. Once paired off,
they place a high value on big families, and seldom use contraception.
do Hutterites tend to marry people who have dissimilar MHCs? To answer
this question, Ober and her colleagues studied 411 couples drawn from
31 Hutterite colonies. They made two separate calculations of how many
couples would end up matching for certain haplotypes, or "linked" MHC
genes found close together on chromosome 6, if there was no active
avoidance of mates with similar MHCs.
In the first, they
predicted how many Hutterite couples with similar MHCs would just
happen to end up together, having taken into account factors such as
the way women always move to their husband's colony after marriage,
that Hutterites never marry first cousins and that siblings often marry
into the same family. In the second, they used the exact genealogy of
each of the volunteers to establish that there would have been between
60 and 80 unrelated "ancestral" haplotypes for this particular
chromosome among their founding ancestors. They then ran a computer
simulation based on this genealogy to see how many couples with similar
MHCs you would expect to find if Hutterites married at random.
the researchers compared these calculations with the actual situation.
As they had suspected, the Hutterite men and women they studied tended
to avoid pairing off with mates who had similar MHC genes to their own.
Despite the lack of genetic variation within this isolated population,
only 44 of the couples matched for any haplotype -- significantly fewer
than the 65 predicted from the first calculation. The genealogy study
backed that up: if mate selection were random the probability that only
44 couples would have matched was only about 5 per cent. Ober's group
concludes that genes in this region of DNA may indeed influence mate
choice in humans.
The findings were published in 1997, along
with a review by Yamazaki and his colleague Gary Beauchamp, director of
Monell, who were delighted that at last there was some evidence in
humans for the effect they had found in rodents. Their enthusiasm was
dampened, however, by results from another excellent study published
alongside Ober's paper, which had examined the same question and come
to a different conclusion. Philip Hedrick of Arizona State University
in Tempe and Francis Black at Yale University studied 194 couples from
11 Amazonian Indian tribes and found that people seemed to pair off
randomly. Yamazaki and Beauchamp suggested that the large number of
Hutterite couples studied and the special characteristics of the
culture may have made this group better than the Amazonian tribes for
detecting a small but real effect.
The next question for Ober
was whether couples with similar MHCs actually have reduced fertility.
Some of her early research on Hutterites had hinted that couples who
had a large number of MHC matches took longer to conceive. She decided
to look at this effect more carefully, asking 111 Hutterite women to
keep diaries recording all their menstrual periods. If they didn't have
a period on the day expected, the women took a pregnancy test and
recorded the result. The women were also asked to note whether they
were nursing other infants, practising birth control of any kind or
were ill -- any of which could affect the likelihood of conception.
During the course of the study -- the first to examine possible links
between MHC and miscarriage in humans -- she collected information on
Of the 111 women, 27 had miscarriages, and
there were 38 miscarriages altogether. None of the couples was
completely infertile -- all but one had already had at least one child,
and none had more than two consecutive miscarriages. But when Ober
scrutinised the MHC genes from the women and their husbands at 16
separate genetic sites, she found that miscarriage rates were highest
for couples who matched at all these sites. And there was an increased
risk even where there was matching at just some of the sites.
effects we see in the Hutterites are pretty clear," says Ober. But she
adds that Hutterites are an isolated population, and they have a
limited repertoire of certain MHC genes. "At this point, it's difficult
to say whether the same is true of out-bred couples," she says. A
Hutterite couple is much more likely to have matching DNA at these
particular miscarriage black spots than a couple who do not live in a
genetically isolated community. Even so, Ober believes that the actual
risks associated with having one or two such genetic matches could be
similar in any population.
The fertility gods may well frown on
couples with similar MHCs. But where does all this leave Pill users?
Even if using oral contraceptives alters a woman's sense of smell, does
smell itself really play such a big part in choosing a man? The effect
may be subtle and subconscious, argues Penn, but that doesn't mean
smell is unimportant. He points out that chemosensory signals are used
to attract and select mates in many species, from bacteria to plants to
mice. "What we know about mate choice in other species tells us they
use lots of different information," he says. "They use everything --
everything they can."
Studies in female rodents have shown that
the scent of a male can sometimes speed up puberty, activate ovulation
and even induce miscarriage. Humans also use odour cues in at least
some matters related to reproduction. For instance, Martha McClintock
at the University of Chicago showed in 1998 that when women who live
together synchronise their menstrual cycles, they do it through
chemical signals known as pheromones. McClintock has recently teamed up
with Ober to further explore the impact of the Pill on chemical
As far as anyone can tell, whatever chemical
signals do pass between people are subconscious. Nonetheless, Rachel
Herz from Brown University in Providence, Rhode Island, decided to ask
people about it directly. She polled 166 women about what makes a man
attractive -- specifically, attractive enough to go to bed with. Out of
a variety of factors, including appearance, the sound of his voice and
how his skin feels, women respondents said that a man's scent was
paramount. Body odour was particularly important, the volunteers
reported, in decisions not to have sex with a certain individual.
question is not whether there are human MHC smells -- that is more or
less resolved. Rats in the labs of Beauchamps and Yamazaki are able to
distinguish between people with different MHC types simply by sniffing
their urine. This is strong evidence, the researchers say, that MHC
genes influence body odour in humans just as they do in rodents. The
genes may affect the concentrations of volatile acids in body fluids,
such as urine, blood, breast milk or even sweat. These in turn could
act as sexual odorants.
The real question is, even if these
odours are advertising what kind of MHC a person has, do humans still
have the capacity to pick up the scent and act on it? Rodents have
something called a vomeronasal organ (VNO) -- a region high in the nose
that can detect chemosensory signals. That system bypasses conscious
centres of the brain and has direct access to the amygdala and
hypothalamus, which govern sexual behaviour. In most animals with a
VNO, reproductive behaviour is disrupted if you cut this part of the
There is still a debate raging about whether humans
even have a VNO (New Scientist, 25 January 1997, p 36). We do seem to
have a structure similar to a VNO during early development, but there
is no strong evidence that the vestige that remains into adulthood is
functional. Maybe we don't need one. Pigs, rabbits and sheep have a
VNO, but detect some pheromones through their main olfactory system.
It's possible that humans do too. After all, a functioning human
pheromone receptor gene was identified last year (New Scientist, 2
September 2000, p 7). And proponents point out that humans have more
scent glands than any other mammal. What for, if not to communicate?
But there is still no consensus on whether humans have some kind of
working chemosensory perception or just remnants from a once-elaborate
system that evolution decided to phase out.
Still, Hutterites do
tend to marry those with different MHCs. And women did respond
differently to a sniff from those T-shirts when they were on the Pill.
So it's not inconceivable that the Pill is meddling with whatever
chemosensory perception we have. "It makes sense that if you change the
hormonal environment, you change olfaction," says Ober.
glance, the Pill's glittering record should be enough to quash the
whole discussion. Oral contraception has been in use since 1960, and
there is no evidence so far that women who have taken the Pill have
lower fertility when they stop. Several large studies looking at tens
of thousands of women have been reassuring, says Martin Vessey, an
epidemiologist at the University of Oxford. "Studies haven't suggested
an association between fetal loss and Pill use," he says. But then, no
study has looked specifically at women who found life partners while on
the Pill, he admits. And it's only recently that women have been using
the contraceptive pill from such a young age -- sometimes from before
their first sexual encounter straight through to the time when they
want to have kids.
Then there's the fact that the Pill has so
far been the darling of the developed world, where there are relatively
few challenges to the immune system. Would its impact on fertility be
more readily seen if women in the developing world took a shine to it?
"There it might matter," says Wedekind. He cautions, however, that no
research has been done in this area. "I think it's worth
investigating," he adds. Clearly pathogens do affect mate choice in
animals. Research by Wedekind and Thomas Rülicke of University Hospital
Zurich shows that when mouse colonies are infected with a mouse
hepatitis virus, their offspring have more varied MHCs. The researchers
believe this is partly due to the egg selecting specific sperm to
maximise the survival chances of the resulting offspring.
this, no self-respecting woman of the 21st century would want to
disparage the Pill. For the past 40 years it has liberated us from the
threat of unwanted pregnancy, leaving us free to earn degrees, climb
corporate ladders and travel the world, all without having to swear off
sex. Even so, it might be worth taking precautions. Herz suggests that
if you are on the Pill and meet someone you want to have children with,
you should stop taking oral contraceptives. "Go off," she says, "to see
if you're still attracted.
1. Further reading: MHC-dependent mate preference in humans by Claus
Wedekind and others, Proceedings of the Royal Society B, vol 260, p 245
2. HLA and human mate choice by Carole Ober and others, American Journal of Human Genetics, vol 61, p 497 (1997)
3. Differential use of sensory information in sexual behaviour as a
function of gender by Rachel Herz and others, Human Nature, vol 8, p
4. MHC-genotype of progeny influenced by
parental infection by Thomas Rülicke and others, Proceedings of the
Royal Society B, vol 265, p 711 (1998)