Linda Buck

Neurobiologist

Born Linda B. Buck, c. 1956, in Seattle, WA. Education: University of Washington, Seattle, WA, B.S. (psychology and microbiology); University of Texas Southwestern Medical Center, Dallas, TX, Ph.D. (immunology)

Addresses:

Office—Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., A3–020, Seattle, WA 98109.

Career

Took a postdoctoral position at Columbia University working with Richard Axel on olfactory system in mammals; identified genes for olfactory receptors with Axel, 1991; set up own lab at Harvard, 1991; explained organization of odor receptor neurons in the nose, 1994; deciphered combinatorial code that allows odor receptors to work together, 1999; transferred lab to Fred Hutchinson Cancer Research Center, 2002.

Member:

American Association for the Advancement of Science; National Academy of Sciences.

Awards:

Lewis S. Rosenstiel Award; Louis Vuitton–Moët Hennessy Science for Art Prize; R.H. Wright Award in olfactory research; Unilever Science Award; Perl/University of North Carolina Neuroscience Prize; Gairdner Foundations International Award.

Sidelights

Linda Buck is a preeminent researcher in the science of sense perception. She is responsible for groundbreaking work on the olfactory system in mammals. Buck made clear for the first time how odors are perceived and identified. Before Buck's work, scientists had only surmised that the nose contained special receptors to identify smells. Buck showed that mammals have as many as a thousand different receptors that allow us to receive and categorize odors. The olfactory system is more primitive and complex than other sensory systems. The eye, for example, uses only three receptors for color, but is able to identify thousands of different shades. In the nose, thousands of receptors track tens of thousands of odors, and mapping this system was thought to be impossibly difficult. Buck showed it could be done. Her work has many implications for medicine and industry. She looks at how scents affect behavior, emotion and memory. Buck is also investigating ways to help cancer patients who often have to take unpalatable drugs. Chemicals that block bitter tastes, for instance, might help patients tolerate their drugs better. Chemicals that enhance taste or odor could also induce ill people to eat.

Buck was born and raised in Seattle, Washington. She enrolled in the University of Washington for her undergraduate education, eventually earning a double degree in psychology and microbiology. From there she moved to the University of Texas Southwestern Medical Center in Dallas, where she earned her doctorate in immunology. Her first postdoctoral position took her to Columbia Universityin New York. At Columbia she worked with Richard Axel on a baffling, unsolved problem: how the sense of smell works.

The sense of smell is evolutionarily more primitive than our other sensory systems. Neuroscientists had thought that mammals used specific smell receptors to identify particular scents, but no one had identified the actual receptors yet. Researchers surmised that there must be several groups or classes of receptors, but nothing was known for sure. It was known that humans, for example, have five specific taste receptors—bitter, sour, sweet, salty, and umani (the taste associated with monosodium glutamate or MSG)—and from these the brain puts together all the complex tastes of meals we enjoy.

Neuroscientists believed odor might also be divided into a few main classes of receptors. A team of researchers led by Solomon Snyder at Johns Hopkins University worked on finding olfactory receptors in the 1980s. After years of work, Snyder's team was unable to solve the problem. Buck read Snyder's work when she arrived at Columbia and got excited about it. Her work in immunology gave her a good background for olfactory research, because she was used to dealing with molecular systems that had to recognize and code complex data. She and Axel began working on the olfactory system of rats. Buck was looking for a family of genes that would be found only in one place in the back of the nose, called the olfactory epithelium. If she could find these genes, she believed she would have located the olfactory receptors. Buck refined her methods several times when her early attempts ran into dead ends. She was completely dedicated to her work. She told Daniel Lyons of Forbes that she worked round–the–clock for three years. "I was putting in 12 to 15 hours a day," she said. "Basically I just got up and went to the lab, and stayed there until the wee hours of the morning."

Buck's final results were astonishing. In 1991 she and Axel published their olfactory study, which identified at least 1,000 different genes that were active exclusively in the noses of rats. No one, including Buck herself, had predicted such a large number of genes. This seemed to mean that processing of odors was done more at the level of the nose than in the brain itself. Though this was unexpected, it also made sense. Early animals that were highly reliant on sense of smell for survival would not have needed large brains to process odor information if the nose itself was doing most of the work. Vision, where most of the processing is done in the brain, developed later.

After Buck's work with Axel was lauded, she secured a position in the neurobiology department of Harvard Medical School. Here she refined her work on the olfactory system. In 1993 and 1994 Buck published explanations of how the nerve cells in the nose function. Buck claimed that neurons on the olfactory epithelium are grouped by type, with about 5,000 neurons for each of the 1,000 different odor receptors. She described the shape of the neurons, which stretch from the olfactory epithelium in the nose into a part of the brain called the olfactory bulb.

She fitted more pieces into the puzzle in 1999, when she laid out the method by which receptors work together to identify particular odors. Even though she had identified as many as 1,000 receptors, mammals can distinguish ten times that many individual scents. Buck's research revealed a kind of code by which several receptors together spell out a particular odor. In 2001, members of her laboratory team traced the neural connections between the olfactory bulb and the larger olfactory cortex that controls it. This led Buck into more complex explorations of behaviors or instincts that are triggered by smell. Certain scents called pheromones that animals release can trigger aggressive behavior, for example. Buck hoped to figure out which odor receptors were linked to unique behaviors, and how the connection worked in the brain. Buck also became interested in aging and life span. She began to investigate whether pheromone perception could be linked to the onset of puberty in animals. She also began a study with roundworms looking for chemicals that influenced these primitive animals' life span. In 2001 Buck also published a report that possibly identified a specific gene for the perception of sweetness. In popular parlance this was called "the sweet tooth gene."

In 2002 Buck moved back to Seattle to take a post at the Fred Hutchinson Cancer Research Center. It was important to Buck that her work find applications that help people. In locating her lab in a cancer research center, Buck hoped to collaborate with researchers who could apply her work with smell and taste to new pharmaceuticals. While she worked to broaden our basic understanding of the olfactory system, she hoped others would build on her achievements, perhaps by developing chemicals that blocked the bitter taste of some cancer medicines. Other possible applications of her work included chemicals that would block our perception of foul odors; this was imagined as a solution to smelly public restrooms. Another possibility was the artificial reproduction of the scent receptors dogs use to sniff explosives. This might mean a machine could do that job more accurately and reliably than trained animals. While others dreamed of possible applications of her research, Buck herself continued to work on the basic science of scent perception.