SWEET SMELL OF SUCCESS
American duo wins Nobel for work on olfactory system
STOCKHOLM
American researchers Richard Axel and Linda Buck were awarded the 2004 Nobel Prize for Medicine for pioneering work on our most enigmatic sense, that of smell, which helps us survive and enjoy some of life's subtlest pleasures.
How we recognize thousands of odors and remember them has long been a complete mystery to science, but Axel and Buck "have in several elegant, often parallel, studies clarified the olfactory system, from the molecular level to the organization of the cells," the jury said in its citation.
They discovered a large family of a thousand genes, and a corresponding number of olfactory receptor types.
"A good wine or a sunripe wild strawberry activates a whole array of odorant receptors, helping us to perceive the different odorant molecules," the jury said.
The smell of a lilac in childhood provokes a print of a memory pattern amid the molecules, which stays with us for the rest of our lives, allowing us to recognize the smell when we come across it again, and it activates associated memories.
"A unique odor can trigger distinct memories from our childhood or from emotional moments--positive or negative--later in life," the jury said.
This faculty has been celebrated as one of man's great assets, most famously in Marcel Proust's novel Remembrance of Things Past, where the smell and taste of a single madeleine cake triggers a long string of memories.
But smell is not only about sensual experiences, it is also about staying alive in a dangerous world. "It is obviously of great survival value to be able to identify suitable food and to avoid putrid or unfit foodstuffs," the jury said.
For all newborn mammals, smell is essential to find the teats of their mother and obtain milk. "Without olfaction the pup does not survive unaided," it said.
Many adult animals observe and interpret their environment largely by sensing smell.
"To lose the sense of smell is a serious handicap," the jury said.
Fish have just about 100 odorant receptors while mice, the species studied by Axel and Buck for a landmark paper published in 1991, have around 1,000. Humans have fewer receptors than mice, having lost some sense of smell during evolution.
Axel, 58, works at the Howard Hughes Medical Institute at New York's Columbia University, and Buck, 57, at the Fred Hutchinson Cancer Research Center in Seattle, Washington.
The prize rewards their contribution to the understanding of the human body, rather than any immediate medical application, but their findings are beginning to be felt in many areas of daily life.
American animal instructors have started to train rats to sniff out earthquake survivors buried under rubble, and by implanting electrodes in their brain, hope to receive the brainwave that indicates a human find. Japanese engineers are designing an "air cannon" to shoot a smell at shoppers, hoping to incite them to purchase certain goods as a result. And the next generation of mosquito repellents is likely to be based on the discovery that insects' sense of smell relies on a single gene. Blocking the gene could stop them from locating their human prey.
Jurgen Hecker, Agence France-Presse
AHEAD BY A NOSE
Nobel winners unlock the mysteries of smell
PARIS
You catch a whiff of burning plastic, and instantly you are alert and tensed for danger. Your seafood stew has been carefully prepared but with one sniff of it, you have to pass--it contains clams. Years ago a dodgy clam made you sick for days and you have never forgotten the smell. A woman passes you in the street, and for some reason you start thinking about your first girlfriend, from years ago. Both women wore the same perfume, and just the barest hint of it unleashes a torrent of memories.
Of all the human faculties, olfaction may well be the strongest and most complex, the fine-tuned product of millions of years of evolution, designed to help us survive and mate.
Very little was understood about how this extraordinary mechanism worked until the early 1990s, thanks to work by two US scientists, Richard Axel and Linda Buck, who were awarded the 2004 Nobel Prize for Medicine on October 4.
They focused on the molecular pathways in the olfactory epithelium, which responds to airborne molecules breathed in through the nostrils.
The epithelium comprises two rich clusters of some five million nerve cells just a few square centimeters, which lie at the top of the nasal cavity, on a horizontal line just below the eyes.
At the tip of each neuron are tendrils, which bathe in thin mucus. On those tendrils are receptors: cells to which odorant molecules adhere. The adhesion activates the cell that in turn sends a signal to the brain.
Axel and Buck's core achievement, using lab rats and tissue samples, was to identify the genes responsible for these vital receptor cells, to sketch the cells' molecular mechanism and gain insights into how the signals are processed.
In a 1991 joint study that fundamentally changed knowledge of olfaction, the pair identified a large group of about 1,000 specialized genes, each of which gives rise to an equal number of types of receptor cells. Each of those cells is highly specialized, able to respond to only a limited number of odorant substances, and to differing degrees of intensity.
The pair's other breakthrough, in separate and parallel work later, was to ascertain how the olfactory receptor cells work.
The answer is a molecular cascade. The odorant molecule adheres to the membrane of the receptor cell, activating a so-called G protein. This in turn triggers a messenger, a protein molecule called cAMP, which unlocks electron gates in the cell surface. That switches on the cell and sends a signal to two grape-shaped microregions in the brain, called the glomeruli. These are staging posts for organizing the data and for advising the higher cerebral regions via nerve cells known as the mitral cells. Each type of receptor cell is connected to a different glomerulus.
Most odors consist of a bouquet of different molecules, and each molecule activates different receptors. That combination is the basis for our ability to recognize and memorize some 10,000 different smells.
If Axel and Buck are right, around three percent of all human genes are devoted to smell receptors, a tally that is smaller than animals such as dogs and rats, which depend far more than us for their survival on the ability to sniff out food.
Over millions of years, evolution has sharpened our sense of smell so that it focuses on the essentials, for example, to discard rotting substances that could make us sick, to distinguish between sweet and bitter odors (things that are sweet in nature are generally edible, those that are sour are often toxic for us), and to detect pheromones, the hormone-drive molecules given off by the opposite sex. Richard Ingham,
Agence France-Presse
How smell research can change our lives
Fundamental research into olfaction is starting to have an impact on daily life.
BUZZ OFF
The next generation of mosquito repellents is likely to be based on the discovery that insects' sense of smell relies on a single gene, Or83b, which codes for the receptor cells that bind to odor molecules. The gene was found among fruitflies by Rockefeller University researchers, but is common across a wide range of insects. A chemical that blocks its function would prevent mosquitoes from locating their human prey.
RESCUE RATS
Rats are being trained to sniff out earthquake survivors buried under rubble. The rats are fitted with electrode implants in their brains, connected to a tiny radio transmitter that transmits a signal of their cerebral activity. The rats are trained over months to get a reward when they reach a target smell such as a human odor, and they send back a characteristic "aha!" brainwave they reach their goal. By triangulating the radio signals, search teams can spot where the rat made the find. The instructors, at the University of Florida in Gainesville and the State University of New York in Brooklyn, hope to have a squad of rescue rodents ready by mid-2005.
BROTHER, YOU STINK
People can identify the odor of close family members, but they don't like it. Wayne State University researchers in Detroit asked 25 families, which each had at least two children to sleep in the same T-shirt for three consecutive nights so that the garment was impregnated with their individual smell signature. They were then asked to sniff two T-shirts, one worn by a family member and one worn by the outsider. The volunteers notched up a high rate of accuracy, and most said they far preferred the smells of outsiders to their own family, a finding which suggests our olfactory genes are designed to prevent incest.
SCENT GUN
Japanese engineers are designing an "air cannon" to shoot a smell at you as you walk around a shopping mall. Their hope is to excite a sense of pleasure or anticipation, such as the smell of fresh bread or a new perfume that will prompt you to open your wallet at a nearby stand. The gadget is made up of a jet that forces a smell-laden vapor into a chamber, where it is compressed by a diaphragm and then forced down a fine nozzle towards, the target.
SMELL BY THE WEB
The British service provider Telewest Broadband is testing a scent-generating gadget to let Internet users to transmit aromas of their choice across the Web. The "Scent Dome" can generate up to 60 smells from a mix of 20 liquid-filled odor capsules, unleashed by emails or web pages. The company says the smells could be used to enhance a holiday web site by generation the scent of sun-tan lotion, or help a grocery store by unleashing the smell of fruit or fresh cakes.
AFP
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