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Linda Buck in her lab at the Fred Hutchinson Cancer Research Center, 2011. Courtesy of Linda B. Buck

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Dr. Linda Buck who was awarded the 2004 Nobel Prize in Physiology or Medicine never imagined she would be a scientist. As an undergraduate she studied psychology, but, unknowing of what her “something” was she left school to travel while taking courses intermittently, one of which was a class in immunology gave her an idea of what that “something” was. At the age of 28,  she earned her bachelor’s in microbiology and psychology. Dr. Buck then obtained a PhD in immunology and went to Columbia University joining Richard Axel’s lab where the two studied the molecular and neural mechanisms underlying olfaction. In 1991, Buck and Axel identified a large family of genes encoding olfactory receptors, demonstrating how each receptor responds to specific odor molecules and how the brain processes these signals to create the perception of smell. This Nobel Prize winning discovery revolutionized the understanding of sensory biology and opened new avenues in neuroscience, genetics, and disease research.

https://www.nobelprize.org/womenwhochangedscience/stories/linda-buck

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Linda Buck with her colleague, mentor and research partner Richard Axel of Columbia University Courtesy Fred Hutchinson Cancer Center

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Research at the Columbia University Courtesy Fred Hutchinson Cancer Center

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Research at the Columbia University Courtesy Fred Hutchinson Cancer Center

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Dr. Linda Buck and Dr. Richard Axel’s partnership was key to one of the most important discoveries in neuroscience. When Buck joined Axel’s lab at Columbia University as a postdoctoral researcher, she was determined to uncover how mammals detect and interpret smells. Dr. Axel, already an established scientist with expertise in molecular biology and neuroscience provided the resources, mentorship and guidance needed to solve this question. Dr. Buck’s ambition and problem solving skills combined with Dr. Axel’s deep knowledge of genetics and neural circuits made them a strong team. Their collaboration led to the identification of a large family of genes responsible for detecting odors, showing how the brain translates chemical signals into the perception of smell earning them the 2004 Nobel Prize in Physiology or Medicine and revolutionized the study of sensory biology.  Their work together was a prime example of how scientific breakthroughs come from strong collaborations. Their discovery remains one of the most significant advancements in understanding the brain.

https://www.nobelprize.org/womenwhochangedscience/stories/linda-buck

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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

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In this 2002 photo, Linda Buck stands at the Fred Hutchinson Cancer Research Center in Seattle, with molecular models behind her representing different scent compounds. These molecules are the key to how the brain deciphers smell, each one binding to specific olfactory receptors in the nose, triggering neural signals that travel to the brain’s olfactory bulb. There, patterns of activation are processed and relayed to higher brain regions, where scents are identified, categorized, and linked to memories or emotions. The vast diversity of these molecular structures explains the brain’s ability to distinguish an enormous range of odors.

https://www.nobelprize.org/prizes/medicine/2004/buck/facts/

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Dr. Richard Axel is a distinguished neuroscientist recognized for his research on olfactory perception and neurobiology alongside Dr. Linda Buck. Beyond olfaction, Dr. Axel made major contributions to molecular biology, developing gene transfer techniques with Michael Wigler and Saul Silverstein. Their work enabled the insertion of genes into cells, advancing genetic research and leading to the identification of CD4, the receptor for HIV. These breakthroughs also facilitated the production of vital therapeutic proteins. He is also a professor at Columbia University, an investigator at the Howard Hughes Medical Institute, and a co-director of Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute. His current research focuses on how sensory input, particularly odors, is processed in the brain and influences behavior.

https://zuckermaninstitute.columbia.edu/richard-axel-md#:~:text=Codirector%20Richard%20Axel%20won%20a,olfaction%2C%20our%20sense%20of%20smell.

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Light micrograph (LM) of olfactory cells Photo: De Agostini Picture Library / Science Source Images

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Olfactory sensory neurons reside within the olfactory epithelium lining the nasal cavity. This light micrograph captures the morphology of these bipolar neurons. Upon odorant binding, Olfactory receptors activate intracellular signaling cascades via the olfactory specific G protein, Golf, leading to the generation of cyclic AMP, opening of cyclic nucleotide gated ion channels, and subsequent depolarization of the OSN. The resulting action potentials propagate along the olfactory nerve—cranial nerve I to the olfactory bulb, where synaptic integration occurs within specialized glomeruli.

https://www.nobelprize.org/womenwhochangedscience/stories/linda-buck

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Contemporary Entry: Olfaction and Covid-19

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Contemporary Entry: Olfaction and Covid-19

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Dr. Linda Buck’s research on the olfactory system has become increasingly relevant in the context of COVID-19. Her discoveries about how odorant receptors detect smells and transmit signals to the brain provide a strong foundation for understanding the widespread olfactory dysfunction seen in COVID-19 patients.Studies suggest that the virus may affect the olfactory epithelium or induce neuroinflammation in the olfactory bulb, leading to long term sensory impairment. Dr. Buck’s work on the molecular mechanisms of smell helps researchers study how viral infections like COVID-19 disrupt the olfactory pathway and whether this damage has broader neurological implications. Recent research indicates that persistent olfactory dysfunction could be an early marker of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, conditions that have also been linked to olfactory deficits. Thus, Buck’s pioneering work continues to shape modern neuroscience, guiding new studies on post viral olfactory loss and its potential long term effects on the brain

Post-viral effects of COVID-19 in the olfactory system and their implications

Xydakis, Michael S et al. The Lancet Neurology, Volume 20, Issue 9, 753 - 761

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This quote embodies the intersection of neuroscience and feminism, celebrating the progress women have made in a field historically dominated by men. Neuroscience has long been shaped by male perspectives, yet women have challenged barriers, making groundbreaking contributions to our understanding of the brain. The recognition of women’s achievements, such as receiving a Nobel Prize, is more than an individual honor, it is a powerful message that the scientific world is evolving toward inclusivity. Feminism in neuroscience advocates not only for representation but also for dismantling biases that have shaped research, education, and career opportunities. By encouraging young women to pursue their dreams, Dr. Buck’s statement reinforces the idea that the future of neuroscience and science as a whole depends on diverse voices shaping its discoveries.

https://www.nobelprize.org/womenwhochangedscience/stories/linda-buck

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Aristotle, one of the most influential philosophers of ancient Greece, was among the first to propose a systematic theory of smell. He categorized smell as one of the five senses and suggested that odors were transmitted through the air, requiring a medium such as moisture for perception. Aristotle believed that the nose functioned as an intermediary between the external world and the soul, processing scents much like the eyes perceive light. Aristotle's belief that perception involved both physical and cognitive processes foreshadowed modern neuroscience’s understanding of how the brain interprets sensory information.

https://www.nicks.com.au/info/vintage-school/vintage-school-1-4-761389

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Jean-Baptiste Bouillaud was among the first to suggest a connection between the brain and sensory perception, including olfaction. While primarily known for his work on language and brain function, Bouillaud contributed to early theories of smell by proposing that the olfactory bulb played a critical role in processing odors. His research aligned with emerging ideas in neuroanatomy emphasizing that specific brain structures were responsible for distinct functions. Though Bouillaud’s work did not provide direct experimental evidence of olfactory processing, his theories influenced later neuroscientists to investigate the neural basis of smell more systematically.

https://catalogimages.wiley.com/images/db/pdf/y0471257214.fm.pdf

https://www.researchgate.net/figure/Figura-4-Ritratto-di-Jean-Baptiste-Bouillaud_fig3_307743327

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Expanding on Bouillaud’s ideas, Pierre Flourens conducted experimental lesion studies that provided concrete evidence for the olfactory bulb’s function. Using animal models, Flourens systematically removed different parts of the brain to observe changes in behavior and sensory perception. He discovered that damage to the olfactory bulb resulted in a loss of smell, confirming its essential role in olfactory processing. His work was among the earliest demonstrations of functional localization in the brain, paving the way for later breakthroughs in sensory neuroscience.

https://catalogimages.wiley.com/images/db/pdf/y0471257214.fm.pdf

https://nerd.wwnorton.com/ebooks/epub/pioneers5/OEBPS/chapter3-02.xhtml

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As a child, Dr. Buck’s mother had a passion for puzzles, a love that Dr. Buck herself carried into her scientific career. She views science as “really puzzle-solving” and as her career progressed she sought to solve the puzzle of olfaction, asking:

“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.”

The first piece of the puzzle was understanding how the nose detects odors. In 1988, Dr. Buck began searching for odor receptors and in 1991, with Richard Axel discovered 1,000 distinct G protein-coupled receptors in the mouse olfactory epithelium. These receptors bind specific odorant molecules, initiating a cascade of intracellular signaling events that ultimately translate chemical stimuli into neural activity. While humans possess only 350 receptor types, they function via the same fundamental principles.

The next piece of the puzzle was to uncover how the brain processes these signals. In 1999, Dr. Buck revealed that each receptor detects multiple odorants, and each odorant can be recognized by multiple receptors. This creates a combinatorial code, or a puzzle, to construct high dimensional neural representations of odor identity, to distinguish a plethora of scents. By putting together these pieces, Dr. Buck solved the puzzle of smell, transforming our understanding of how we perceive the world through scent.

https://www.nobelprize.org/womenwhochangedscience/stories/linda-buck

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Perfume has a deep rooted history that intersects with neuroscience, particularly in its impact on memory, emotion, and cognition. Originating from ancient rituals, fragrance evolved from incense used in Mesopotamian and Egyptian religious ceremonies to a personal luxury refined by Greek, Arab, and European advancements in chemistry and distillation.Scent is processed bypassing the thalamus and directly activating the limbic system, which governs memory and emotion. This explains why specific fragrances can trigger vivid recollections and mood. Research also suggests that certain scents reduce stress and enhance cognitive function, with applications in aromatherapy and even academic performance.

https://www.mcgill.ca/oss/article/history/story-perfume?utm_source=chatgpt.com