(see Cell 65, 175–187; 1991). The receptorswere indeed part of the same family as visualreceptors — a family that signals through aclass of protein known as G proteins. But theolfactory sub-family wasn’t the anticipatedtight-knit group: it had about a thousandmembers. Similarly unexpected was thefinding that each cell in the lining of the nosecontains only one type of olfactory receptor.Each of these cells sends projections to theolfactory bulb. The two researchers went onto show independently that all cells bearing a particular receptor converge on a preciseregion in the olfactory bulb.

The next big advance will be to under-stand exactly what happens next — how thesignal becomes the perception of a smell with all its associations — the danger of fire,for example,or the hope of love in a perfume.Scientists believe that olfaction will serve as a model for understanding how our brainprocesses all the sensory informationgleaned from our world.

Both Axel and Buck are still working onthe higher processing of olfactory signals,but the field is much more crowded now.Their seminal 1991 paper drew researchersinto the field in droves. Among them wasLawrence Katz, a self-confessed “hard-corevision scientist” at Duke University MedicalCenter in Durham, North Carolina. Katzsays that Buck and Axel’s work “had atremendous influence on how I thoughtabout how sensory systems could be orga-nized in the brain”.

Like many of his colleagues, Katz soonbecame convinced that the olfactory system was much more likely to help illumi-

Alison AbbottHow would you react if you got that call fromStockholm? Linda Buck, a neuroscientistfrom Seattle, fumbled her phone in the darkand accidentally hung up. It was 2.30 in themorning, mind you. Co-winner RichardAxel, her former lab chief at ColumbiaUniversity in New York, managed to take hiscall without mishap.

The pair won the 2004 Nobel Prize inPhysiology or Medicine this week for theirseminal work on olfaction — the sensorysystem concerned with smell.Smell is crucialto animals: they use it to recognize other ani-mals, identify territories and seek out mates,for example. Humans rely on it rather less,but still benefit from being able to smellburning from a distance, for instance, or tellif meat has gone bad.

Twenty years ago, olfaction was the Cin-derella of sensory physiology. Back then,neuroscientists were more enamoured ofthe visual system — and were making greatprogress towards cracking its mysteries. By1986, the three main colour receptors — forred, blue and green light — had all been dis-covered, and scientists had a clear idea of thecombinatory code that allows us to perceivelight of different wavelengths and identify allthe colours of the rainbow.

The small community of olfactory scien-tists were still working in the dark, however.It was understood that the cells in the liningof the nose bind the molecules that compriseodours, then send electrical signals to theolfactory bulb in the brain, and that fromthere the information must be relayed tohigher parts of the brain concerned withsmell recognition. But researchers were con-fined to sticking electrodes into brains with-out even knowing what receptors the odourmolecules bind to.

Persistent effortBuck and Axel changed all that. As a post-doc at Axel’s Howard Hughes MedicalInstitute (HHMI) laboratory at ColumbiaUniversity, Buck became fixated with theproblem of the mysterious olfactory recep-tors. Picking up on recent hints in thescientific literature that smell receptorscould be related to the small family ofvision receptors, she adapted a freshlydeveloped tool, the polymerase chain reac-tion (PCR), to serve her ends. PCR ampli-fies specific genes to detectable levels, andBuck used it in an effort to flush out herreceptors in rats. This approach was novelat the time, but has since become routine.After initially failing, she modified theapproach — and failed again. And again.Then, after six years, she succeeded.

Together with Axel, she published a paperthat shook the world of sensory physiology

nate the general problem of sensory percep-tion than was vision.“The perception of theolfactory signal — smell — is probablygoing to be much more closely linked to themolecular signal itself, in contrast to visualperception, whose complexities requiremuch more processing of the signal input,”he says.

Colleagues ascribe Axel and Buck’s suc-cess in unearthing the roots of olfaction totheir personal doggedness, underpinned bythe steady, powerful support that the HHMIgives its researchers. “It would have beenhard to do this if you were required to pro-duce regular publications to support yournext grant,” points out Stuart Firestein, aneuroscientist at Columbia University inNew York, who also works on olfaction. TheHHMI has nurtured 13 Nobel prizewinnerssince it was established in 1984.

Firestein says that the award is also a shotin the arm for basic research,because there is,as yet, no direct medical application for Axeland Buck’s findings. He notes, nonetheless,that half of all drugs work through G-proteinreceptors of different types.So having anotherthousand to investigate as a result of theirapproach “is certain to help medicine indi-rectly”,he says.

Buck becomes only the seventh woman towin the Nobel prize for physiology or medi-cine: fewer than one in 25 laureates in thiscategory have been women. ■

news

616 NATURE | VOL 430 | 7 OCTOBER 2004 | www.nature.com/nature

Science of smell wins medicine Nobel

Perfect sense: Richard Axel and Linda Buck discovered the receptors that bind odour molecules.

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