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Nobel for Scientists Who Solved Mystery of the Human Nose

Posted on: Tuesday, 5 October 2004, 06:00 CDT

TWO SCIENTISTS who discovered how we smell the difference between a lilac and a lily - and how such scents can rekindle old memories - have won this year's pounds 1m Nobel Prize in medicine and physiology.

Richard Axel, 58, of Columbia University in New York and his former student Linda Buck, 57, of the Fred Hutchinson Cancer Research Centre in Seattle, unravelled the mystery of smell.

Until Professor Axel and Dr Buck made their discoveries in 1991, no one understood exactly how the human nose could recognise up to 10,000 different odours, the Nobel Assembly at the Karolinska Institute in Stockholm said yesterday.

"This year's Nobel laureates in physiology and medicine have solved this problem and in a series of pioneering studies clarified how our olfactory system works," said the assembly.

The scientists looked for the genes involved in smell and found there were about 1,000 different specialised cells in the nose which can distinguish up to 10 times as many odours.

Peter Brennan, an olfactory scientist at the University of Cambridge, said: "The discovery of this large family of genes has revolutionised our understanding of this sense. Although this work is not directly related to any major human diseases, it has opened windows on the way the brain interprets the world around us and how this effects behaviour."

An important outcome of the research was that it led to an understanding of how odours and tastes - a sense intimately connected to smell - can be remembered many years later.

"Smell is different from the other senses in that the sensory cells are continually dying and being replaced by new cells that have to be wired up correctly in the brain," Dr Brennan said.

"Their work has increased our knowledge of how the complex patterns of connections in the brain are formed during development," he said. Professor Axel and Dr Buck jointly wrote the scientific paper that described for the first time a set of about 1,000 genes involved in the sense of smell in mammals - including man.

Each gene is responsible for a single protein that acts as a "receptor" molecule for odour molecules floating in air. When an odour molecule binds to a receptor protein, it causes an electrical signal to be sent to the brain via the olfactory nerve.

The two scientists also discovered that each receptor protein is found in only one type of cell in the specialised olfactory bulb inside the nasal chamber.

By registering the electrical signals coming from single olfactory receptor cells, the researchers showed that each cell responds to several related odour molecules, albeit with varying intensities.

"Most odours are composed of multiple odorant molecules, and each odorant molecules activates several odorant receptors," the assembly said.

"This leads to a combinatorial code forming an odorant pattern - somewhat like the colours in a patchwork quilt or a mosaic. This is the basis of ability to recognise and form memories of approximately 10,000 different odours," it said.

Professor Axel and Dr Buck went on to show how we can recall an odour of many years ago even when all the cells of the olfactory system have since been replaced many times over.

They found that although there is a constant turnover of receptor cells, their replacement cells send their electrical signals to the same well- defined regions within the olfactory bulb, called the glomeruli.

Professor Axel explained: "The brain is saying, `I'm seeing activity in positions 1, 15 and 54 of the olfactory bulb, which correspond to odorant receptors 1, 15 and 54, so it must be jasmine." He said he was honoured but had never considered the possibility of winning a Nobel. "This is nothing I have been thinking about. I think about my science," he told Swedish radio yesterday.

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