LINDA B.BUCK
Nobel Prize in Physiology or Medicine 2004
Photo: Dan Lamont Photojournalism
Linda Buck was fascinated by one seemingly simple question: how does our sense of smell work? Once she started to look for the answer, she didn’t let it go. She followed the olfactory process step by step to the very heart of what makes us human: our perceptions, preferences and memories.
Nasal lining, as seen in a coloured scanning electron micrograph (SEM), showing olfactory cells (red) surrounded by numerous cilia (hair-like projections, blue) Steve Gschmeissner / Science Source Images
Smell receptor. Transmission electron micrograph (TEM) of a section through the olfactory epithelium that lines the nasal cavity, showing an olfactory cell (smell receptor, red) and its cilia (hair-like projections) Steve Gschmeissner/Science Source
Nasal lining, as seen in a coloured scanning electron micrograph (SEM), showing olfactory cells (red) surrounded by numerous cilia (hair-like projections, blue) Steve Gschmeissner / Science Source Images
Smell receptor. Transmission electron micrograph (TEM) of a section through the olfactory epithelium that lines the nasal cavity, showing an olfactory cell (smell receptor, red) and its cilia (hair-like projections) Steve Gschmeissner/Science Source
Born in Seattle in 1947, Linda Buck never imagined she would be a scientist, although she had a scientist’s curiosity. Her father (an electrical engineer) and her mother (a homemaker) loved puzzles and inventions, which may have led to her future career, since, as Buck sees it, science “is really puzzle-solving.” Her parents also allowed her to explore, encouraged her to think, and expected that she would do something worthwhile with her life.
Linda Buck, 1996, when she was an assistant professor at Harvard Medical School, USA. Courtesy of Linda B. Buck
It took Buck a while to figure out what her “something” would be. She went to the University of Washington to study psychology, but, uncertain whether she really wanted to be a psychotherapist, she left school to travel, taking classes intermittently.
A class in immunology sparked her interest in biology, and in 1975, at the age of 28, ten years after she began, she graduated with a B.S. in both microbiology and psychology.
Linda Buck with her colleague, mentor and research partner Richard Axel of Columbia University Courtesy Fred Hutchinson Cancer Center
Buck earned a PhD in immunology at the University of Texas Southwestern Medical Center in Dallas. She credits her thesis advisor, Ellen Vitetta, for teaching her how to do research. She then went to Columbia University, and ultimately to the lab of Richard Axel, a neuroscientist doing molecular studies of the nervous system of a sea snail.
Nasopharynx surface as seen in a scanning electron micrograph (SEM). Shown here are tiny microvilli on the surface of a squamous nasal epithelial cell. The nasopharynx (nasal part of the pharynx) lies behind the nose and above the level of the soft palate. DENNIS KUNKEL MICROSCOPY / Science Source Images
Nasopharynx surface as seen in a scanning electron micrograph (SEM). Shown here are tiny microvilli on the surface of a squamous nasal epithelial cell. The nasopharynx (nasal part of the pharynx) lies behind the nose and above the level of the soft palate. DENNIS KUNKEL MICROSCOPY / Science Source Images
How could humans and other mammals detect 10,000 or more odorous chemicals, and how could nearly identical chemicals generate different odour perceptions? In my mind, this was a monumental puzzle and an unparalleled diversity problem.
Linda Buck
The first piece of the puzzle was figuring out how the nose detects odours. Buck embarked on the search for odour receptors in 1988, and worked intensely for three years. In results published in 1991, Buck and Axel pinpointed 1,000 types of olfactory receptors in mice, located in the back of the nose, on a spot called the olfactory epithelium. The receptors are protein molecules that bind to the molecules of certain odorants, allowing for the recognition of individual scents. While humans have far fewer of these receptors (350 versus 1,000), they work the same way for us.
Linda Buck at the Fred Hutchinson Cancer Research Center in Seattle, May 2002. Behind her are molecules representing different scents Photo: Meryl Schenker/SeattlePI.com/Polaris
Buck moved to Harvard University to solve another part of the puzzle. After solving the mystery of how the olfactory system detects odorants, she sought to discover how these receptor signals create the impression of different odours, based on their organisation in the brain.
With only 350 olfactory receptors, how can humans distinguish among 10,000 or more smells, some of which are nearly identical?
Light micrograph (LM) of olfactory cells Photo: De Agostini Picture Library / Science Source Images
In 1999, Buck revealed the answer to be a complicated system in which each olfactory receptor detects more than one odorant and each odorant can be detected by more than one receptor. Working together, the receptors create a “combinatorial code” forming an “odorant pattern” to identify specific odours. This code underlies our ability to recognise more than 10,000 different odours, just as we can spell thousands of words with just 26 letters.
An odorant receptor protein is shown weaving in and out of the neuron surface. Balls indicate amino acids. Red balls indicate amino acids that are hypervariable among receptors. Courtesy of Linda B. Buck
Linda Buck describes her research at a 2004 news conference Photo: Reuters
An odorant receptor protein is shown weaving in and out of the neuron surface. Balls indicate amino acids. Red balls indicate amino acids that are hypervariable among receptors. Courtesy of Linda B. Buck
Linda Buck describes her research at a 2004 news conference Photo: Reuters
Buck next sought to understand how the reception of odour becomes perception and memory. How do we go from receiving odour signals in the nose to processing them in the brain’s olfactory cortex?
In 2001, at age 54, the year she became a full professor at Harvard, she published studies about how olfactory neurons are mapped in the cortex. She had started with the mechanism of perceiving smell in the nose and pushed onward into smell’s profound effects on the brain: memory, emotion, attraction, and aversion.
Linda Buck's signature, together with other Nobel Laureates from 2004 (left), and 2005 (right). From the Nobel Foundation's guest book. © The Nobel Foundation, Photo: Karl Anderson
In 2002, two years before she and Axel received the Nobel Prize in Physiology or Medicine, she went back to Seattle. She established a laboratory at the Fred Hutchinson Cancer Center, dedicated to continuing her exploration of the olfactory system.
As a woman in science, I sincerely hope that my receiving a Nobel Prize will send a message to young women everywhere that the doors are open to them and that they should follow their dreams.
LINDA BUCK
Linda Buck in her lab at the Fred Hutchinson Cancer Research Center, 2011. Courtesy of Linda B. Buck
Buck was obsessed with smell. What she discovered has potential applications for treating people who’ve lost their appetite or sense of smell, but usefulness isn’t the point for Buck. She simply wants to understand, to solve a piece of one of the great puzzles of human biology: how we perceive and respond to the world.
Do something that you’re obsessed with, that you just have to understand, because that’s where the joy comes from, and that also, I think, is where the great discoveries come from.
LINDA BUCK
