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. The Details of Wedekind's Experiment: What Was Actually Measured
Participants: 44 men and 49 women, students at the University of Bern. All were typed across six HLA loci: HLA-A, HLA-B, HLA-C (class I) and HLA-DR, HLA-DQ, HLA-DP (class II).
Procedure: men wore T-shirts for two nights, then stored them in plastic bags with cardboard inserts (to neutralise extraneous odours). Women evaluated six T-shirts: three from men with similar HLA and three from men with dissimilar HLA.
Part 2. Replications and Criticism: What Has Been Complicated
After Wedekind'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 dissimilar HLA 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 between HLA distance and relationship satisfaction. However, it did find that couples with greater HLA 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. The Mechanism: How the Body 'Smells' HLA
If HLA-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 whom HLA-dependent mate preference is well studied) can distinguish individuals by HLA 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 with HLA. The nose thus 'reads' the microbiome, and the microbiome encodes HLA.
- 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 and Contraceptives: Practical Implications
The effect of contraceptives on HLA 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, her HLA 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. The Roberts 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 in Reproductive Medicine
HLA compatibility has direct medical relevance in several contexts:
- Recurrent pregnancy loss. Some studies show that couples with high HLA 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 offering HLA typing when selecting donors — to ensure maximum HLA divergence between donor and recipient. The evidence base for this approach is currently limited, but interest is growing.