Remembering Smell by Bonnie Blodgett Read Free Book Online

Life is a one-way street. Though olfactory genes are present in every cell in the body, the genes' sole purpose is to allow us to smell. In olfactory cells, the genes are turned on. In other cells, they are not. Without smell genes to guide odorant and receptor binding, the smell brain wouldn't be able to tell a rose from a rotten egg.
    How we recognize odors and how odorants bind to receptors has been a focus of the work of Columbia University geneticist and smell researcher Richard Axel. He's also concerned with what he refers to as the binding problem; as he put it in a lecture at Columbia in 2004, "How are bits of electrical activity integrated to allow for meaningful recognition of a sensory image?" How does the brain take a variety of sensory inputs and bind them together to form a full and complete perception of any one thing?
    Richard Axel has long been intrigued by the binding problem in the context of the olfactory system. Unlike smell, the other senses take a direct route to the high brain. They don't pick up input from memory and emotion first, as smells do. Even taste and touch have proven relatively easy to understand, mainly because they're hard-wired. The taste of sugar remains sweet regardless of whether or not you were having a bad day when you first tasted it. But ask two people to sniff a cup of coffee and there's no telling what each will perceive. One might love the smell but call it tea; the other might know it's coffee all right but recoil in fear owing to a bad experience with burning hot coffee as a child.
    Before Axel could begin to address this issue, though, he had to find the smell genes encoding odorant receptors. He assumed (correctly, as it turned out) that each gene coded for a specific smell receptor, and that each smell receptor opened the door of the olfactory system for just one particular odorant.
    In 1988, Linda Buck, a sixth-year postdoctoral fellow in Axel's lab, came up with a way to identify the large family of genes encoding G protein-coupled smell receptors in the rat olfactory epithelium. These proteins tell enzymes inside the cell how to respond to an odorant. Based on what the receptor proteins
should
look like according to their genetic job description, Buck created a sort of smell-receptor-gene template consisting of three characteristics: (1) the genes that expressed the odorant-receptor proteins had to be active
only
in the olfactory epithelium; (2) the genes had to be abundant, because there were hundreds of thousands of individual odorants out there, each expecting to be greeted by a party of one; and (3) the genes had to code for proteins with a specific molecular structure that enabled them to deliver information across a cell.
    Buck volunteered to put her smell-receptor-gene search engine to work on actually finding the genes. This meant she had to go through reams of lab data on mouse DNA. (The mapping of the human genome has allowed scientists to compare the human genetic blueprint with other creatures'. What separates man from mouse is minuscule, and the sense of smell isn't one of the separators.) Buck had to do her gene searching after hours; she knew that isolating the genes for the odorant receptors using all three parameters simultaneously would be tedious and time-consuming, but it was also an irresistible shortcut—and Axel didn't like shortcuts. A die-hard reductionist and devotee of the pure scientific method—he lived by the Austrian philosopher Karl Popper's doctrine that knowledge should be acquired through a process of verifying or falsifying hypotheses—Axel told Buck to take her project home.
    Buck found the genes on a Saturday night. They coded for proteins with the necessary loops, all where they should be. She immediately told her boss the good news. The group of genes she'd teased out of the mouse DNA proved to be huge enough to make receptors for that warm one-on-one welcome for each odor molecule.
    She and Axel coauthored the paper describing