(Dec. 10th, 2009) A German-Swiss research collaboration between a huge cosmetics company and one of the world’s foremost ‘creators of tastes and scents’ has finally pinned down the gene responsible for that heady mix of sweet and savoury aromas oozing out of some human armpits (Don’t look at me! – I’ve just had a shower). Jeremy Garwood reports on the unexpectedly complex world of smelly underarms and the global earwax connection.
Deodorants and masking perfumes are big business, running from cheaper aerosols and roll-ons to luxury designer blends. Hence it is hardly a surprise to learn that the biggest companies actively research into the very essence of the human aromas their products are seeking to suppress and/or complement. Now, Annette Martin and Matthias Saathof from Beiersdorf AG (whose “NIVEA brand is the world’s largest skin and beauty care brand”) have identified a single protein that they hold responsible for why sweating is always associated with odors. For their report, “A functional ABCC11 allele is essential in the biochemical formation of human axillary odor” (in the Journal of Investigative Dermatology, advance online publication 2009), the Beiersdorf researchers teamed up with Andreas Natsch from Givaudan Schweiz AG (whose “perfumers and flavourists create fragrances and flavours for the world’s most respected brands”).
Sweaty basics
In fact, Andreas Natsch has made quite a research niche out of the human armpit, publishing a number of key findings tracing the origins of underarm (or axillary) odor. Although the skin from human armpits contains a dense arrangement of sweat glands, the volatile substances that evaporate from these areas are initially odorless. So, what makes it stink? The answer lies in the skin microbes that happily coexist in the clammy warmth of our armpits, an unusually dense bacterial population dominated by the genera, Staphylococcus and Corynebacteria. These bacteria drink up our sweat and convert the non-smelling substrates dissolved in it into distinctly recognisable smells. These substrates include odoriferous steroids and short branched fatty acids.
For years, Natsch has had volunteers engaged in heavy physical workouts in the gym to give him the raw material – sweat that is directly absorbed onto underarm pads. Using chromatography to separate out the components, and a combination of mass spectroscopy and the trained noses of perfumers to analyse them, he has traced other substances, including a broad diversity of unsaturated or hydroxylated odorant acids that are released from the glands in the form of odorless glutamine-conjugates (Chemistry and Biodiversity 3(1):1-20) and the volatile sulfanylalkanols, released from a cysteine-glycine conjugate by bacterial enzymatic activity (Chemistry and Biodiversity 1(7):1058-72). Givaudan have even patented one of Natsch’s sulfanylalkanols “as a potential artificial flavouring with a meaty onion-like taste”. Something to look forward to in our food additives!
Meanwhile, most current deodorants simply kill off the entire skin microflora and antiperspirants aim to clog up the sweat glands. Thanks to Natsch, another possibility might now be to add specific inhibitors of the odor-releasing bacterial enzymes. Or to make them produce nice fragrances instead – Natsch has taken the Zn2+-dependent aminoacylase from Corynebacteria that produces underarm ‘malodor’ and used it as a “screening target for novel deodorant formulations”. The enzyme’s activity on substrates in the deodorant might be used to produce perfume instead of pong.
The Earwax Connection.
Where did the underarm genetics come from? In fact, the crucial genetic analysis was made by a Japanese group looking at earwax. Yes, more bodily secretions! In 2006, Kohichiro Yoshiura and co. announced in Nature Genetics (vol. 38(3):324-30) that: “A SNP in the ABCC11 gene is the determinant of human earwax type”, staking their claim to having discovered the first example of a human DNA polymorphism that determines a visible genetic trait. The trait in question is dry earwax.
In this case, most of the human population secrete ‘wet’ earwax, a brown sticky substance, from the ceruminous apocrine glands in the ear. However, most East Asians (from China, Korea, Japan, etc.) have ‘dry’ earwax that lacks cerumen (80-95% frequency). Although the phenotypic implications of earwax remain unknown, Yoshiura mentions possible functions including self-cleaning, prevention of dryness of the external auditory canal and “insect trapping”! What is clear though is that the ‘wet cerumen phenotype’ is completely dominant to the ‘dry’ one. In Europeans and Africans, less than 3% have ‘dry’ ears.
Comparing genomic DNA samples from individuals with ‘wet’ or ‘dry’ earwax, the earwax gene locus was localised to the “pericentromic region of chromosome 16”. Intensive DNA sequencing of the 341,290 base pairs in this region revealed the presence of just four genes. After a lot of analysis, the key difference between the ‘wet’ and ‘dry’ DNA turned out to be a single nuclear polymorphism (SNP) in the fourth exon of the gene ABCC11 that converted a single DNA base from a G to an A at position 538 in the protein-coding sequence. The ABCC11 protein (also known as MRP8) is an amphipathic anion transporter that functions as an “efflux pump” for purine and pyrimidine analogs such as cAMP and cGMP – it can also transport a variety of lipophilic compounds, that might include aliphatic earwax compounds and aromatic hydrocarbons.
The ‘538 G to A’ SNP changes one amino acid in the ABCC11 protein – a glycine for an arginine in the first transmembrane domain. To test their hypothesis that the protein’s transport was affected by this SNP, Yoshiura and co. transformed cells with ABCC11 cDNA for both the G (wet-type allele) and A (dry-type) and compared the resulting ATP-dependent transport of cGMP. Sure enough, the A (dry-type) protein displayed little, if any, transport activity compared to the G (wet-type).
In their conclusions, Yoshiura and co. remark that “axillary odor is known to be associated with wet-type cerumen and intensfied by sweating” with the implication that the ‘538 G to A’ SNP could play a role.
Asian Sweat
This brings us back to our researchers from Beiersdorf/Givaudan AG. Spurred on by Yoshiura’s discovery, they hunted down sweaty volunteers displaying the three possible genotypes for the ABCC11 SNP, namely GG, GA and AA. Armed (literally) with pads to absorb their sweat, the volunteers were subjected to intensive physical exercise, yielding around 1 gram of sweat from their two underarm pads. This was rapidly processed to prevent bacterial action.
Natsch then analysed the sweat for the presence of three key human body odor precursors. Sure enough, the AA allele contained none of these compounds that were present in the GG and GA sweat samples.
This discovery also explains why East Asians don’t have smelly sweat. Whereas the vast majority of Europeans and Africans, who have the GG or GA genotypes, “possess a strong axillary odor”, most East Asians (and Native Americans) “have only a faint acidic odor”.
Selective Advantage?
Yoshiura and co. noted the striking expansion of the ‘dry’ earwax phenotype from North China and Korea. Might this be a “result of a certain selective advantage of the dry cerumen”? They speculate that “ancient Northeast Eurasians” lived in a cold environment and that “selective advantages, such as less axillary odor or sweating” might have been acquired “as an adaptation to the cold climate.”
Well, the Beiersdorf/Givaudan AG researchers have also noted the presence of the ‘538 G to A’ SNP at >95% frequency in certain populations. However, in a concluding phrase that sounds remarkably similar to the marketing strategies of companies that sell deodorants and perfumes, they explain that: “A strong positive selection in mate choice for low-odorant partners with a dysfunctional ABCC11 gene seems a plausible explanation for this striking frequency of a loss-of function allele.”
In Beiersdorf’s press release, Annette Martin further reassures investors that even Asians with the AA genotype display “a slight odor, which is perceived to be extremely objectionable, even by fellow Asians. The results of this study are an exciting starting point for further research work and enable us to develop specific deodorant concepts which respect the differences between different population groups.”
Gentically-inspired desodorants – something to look forward to at the ‘body care’ shops?