Wedekind's 1995 experiment is cited in hundreds of papers and dozens of popular science books.But few know what happened next: several attempts to replicate the results produced mixed data, opened new questions — and ultimately led to a considerably more nuanced picture than 'we choose partners by the smell of their immune system.'
Part 1.TheDetails ofWedekind'sExperiment:WhatWasActuallyMeasured
Participants: 44 men and 49 women, students at theUniversity ofBern.All were typed across sixHLA loci:HLA-A,HLA-B,HLA-C (classI) andHLA-DR,HLA-DQ,HLA-DP (classII).
Procedure: men woreT-shirts for two nights, then stored them in plastic bags with cardboard inserts (to neutralise extraneous odours).Women evaluated sixT-shirts: three from men with similarHLA and three from men with dissimilarHLA.
Part 2.Replications andCriticism:WhatHasBeenComplicated
AfterWedekind's publication, several groups attempted to reproduce the results.Findings were inconsistent:
- Replication 2002 (Wedekind &Füri): confirmed the core effect, but with a smaller effect size.The preference for dissimilarHLA was observed primarily in women not using contraceptives.
- 2008 study (Roberts et al.,Proc.R.Soc.B): on a sample of 97 real couples found no significant association betweenHLA distance and relationship satisfaction.However, it did find that couples with greaterHLA similarity reported lower sexual attraction to their partner and a higher rate of infidelity.
- Large meta-analysis 2020 (Winternitz et al.): analysed 30 studies.Conclusion: the effect exists, but is considerably weaker and less universal than the original publication suggested.HLA influence on partner choice is statistically real, but modest in size.
Part 3.TheMechanism:How theBody 'Smells'HLA
IfHLA-dependent preference is real — what is the mechanism?Several non-mutually-exclusive hypotheses:
- Volatile organic compounds (VOCs).HLA molecules may directly influence the composition of volatile substances released through the skin.Several experiments showed that mice (in whomHLA-dependent mate preference is well studied) can distinguish individuals byHLA profile from the smell of their urine alone.
- The microbiome as intermediary.HLA shapes the host's immune profile, which in turn determines the composition of the skin microbiome.Skin bacteria produce odorous metabolites — and their composition varies withHLA.The nose thus 'reads' the microbiome, and the microbiome encodesHLA.
- Peptide ligands in saliva.HLA molecules on oral cavity cells may release specific peptides into saliva — and these could be transmitted during kissing.This is a speculative hypothesis, but biochemically plausible.
Part 4.HLA andContraceptives:PracticalImplications
The effect of contraceptives onHLA preferences is the most practically significant finding across this entire line of research.Potential consequences:
- Partner selection.If a woman meets a man and begins a relationship while taking hormonal contraceptives, herHLA preferences may be inverted.When she stops — for any reason — she may find that her partner's smell seems less pleasant than it did before.
- Sexual satisfaction.TheRoberts et al. 2008 study (500+ women) found that women who met their partner while on contraceptives and subsequently stopped taking them reported lower sexual satisfaction than those who did not change contraceptive status during the relationship.
- This does not mean 'don't take contraceptives.'It means: recognising that hormonal context is part of the setting in which attraction arises.Awareness, not alarm.
Part 5.HLA inReproductiveMedicine
HLA compatibility has direct medical relevance in several contexts:
- Recurrent pregnancy loss.Some studies show that couples with highHLA similarity have an elevated risk of miscarriage.The hypothesis: the mother's immune system does not 'recognise' a sufficiently foreign embryo and fails to form normal immunological tolerance.The data are contradictory — this question is actively being studied.
- Transplantation.HLA compatibility between donor and recipient is the key determinant of success in organ and stem cell transplantation.The higher the compatibility, the lower the risk of rejection.
- IVF and donor selection.Some reproductive medicine clinics have begun offeringHLA typing when selecting donors — to ensure maximumHLA divergence between donor and recipient.The evidence base for this approach is currently limited, but interest is growing.