Leslie Vosshall (left) and Hiroaki Matsunami (right) collaborated in their olfactory research.

One of the famous problems in the olfactory science field is why the perception of androstenone, an odorous steroid found in high levels in the urine and sweat of men, varies. Some describe the smell as pleasantly floral and sweet, others as an offensive urinous reek, and many can't smell it at all.

Researchers have suspected a link between genes and odour perception for about 40 years. In 1967, olfactory biochemist John Amoore found that some people are insensitive to certain odours, a condition he called specific anosmia. Amoore predicted that the root of odour 'blindness' would be traced to genes. Some years later, researchers discovered that the ability to smell androstenone was genetically determined, but they never pinpointed the gene.

Leslie Vosshall, a neurogeneticist at the Rockefeller University in New York, learned about Amoore's research as a postdoctoral researcher in 1993, which sparked her interest in the genetic underpinnings of the perception of smell. At the time, she thought “This is something I really want to figure out”.

Her most recent work contributes part of the answer. On page 468, Vosshall and colleagues establish how genetic variation in the odour receptor OR7D4 alters people's perception of androstenone.

Vosshall says the project developed slowly out of an impasse her group reached while studying olfactory responses in fruit flies. “As wonderful as fruit flies are, they don't talk,” she says. “You cannot get them to give a declarative answer to the question: how does this smell?” Gradually, they realized that humans would be the perfect experimental organism.

But Vosshall had no experience with human subjects, and colleagues thought it a risky venture. She and her team recruited hundreds of volunteers from all walks of life, from “ladies who lunch to graduate students”, drew blood and tested the volunteers' responses to a panel of 66 odours, including androstenone. Soon, the freezer was packed full of blood samples.

“We had this vague idea that DNA sequencing would get cheap enough and then we would sequence their genomes,” she says. Meanwhile, Hiroaki Matsunami and his group at Duke University Medical Center, in Durham, North Carolina, had taken a mirror approach, expressing the genes for various odour receptors in tissue-culture cells, including OR7D4, which responded selectively to androstenone.

The field of smell is tiny, and it wasn't long before word of Matsunami's discovery reached Vosshall. They hammered out an agreement and began a collaboration in June 2005.

Matsunami's laboratory sequenced the coding region of the OR7D4 gene of 391 of Vosshall's volunteers. “Very quickly there was a clear and strong correlation between having the functional receptor in your genome and being very sensitive to androstenone,” says Vosshall. People with the common version of OR7D4 found androstenone strong and unpleasant and described it as sickening. Those with two one-letter changes in the gene's code found it less so — some even said it smelled like vanilla.

Some studies show that androstenone can cause arousal, sweating and a surge of stress hormones in women, particularly around ovulation. So for males, says Vosshall, success in landing a date may lie in the woman's genes.