What the Nose Knows: The Science of Scent in Everyday Life (27 page)

If there is anything more dispiriting than a flavorless tomato, it is a scentless rose. Along with chrysanthemums, tulips, lilies, and carnations, roses are the top sellers in the cut-flower market, with worldwide sales estimated at $40 billion a year. Where has all the fragrance gone? There are more than a hundred species of roses, yet most of those in commercial production result from crosses between only eight species. Like tomatoes, these varieties were not selected for fragrance, but for traits that the cut-flower industry prizes: flower color and shape, yield, vase life, and resistance to insects and disease.

Perfume chemists analyze floral scents down to the last molecule, but it’s not their job to find out how plants make the scent in the first place. Nor were academic researchers interested: in 1994, not a single floral scent enzyme had been identified. Then the biologist Eran Pichersky began to study a native California wildflower known as Brewer’s Clarkia. This unusual species—a night-blooming, moth-pollinated evening primrose—grows in only the San Francisco Bay Area. Pichersky’s team chemically characterized its scent and found that one ingredient—linalool—is produced by an enzyme called linalool synthase. When they successfully identified the gene that produced the enzyme, they opened up a whole new scientific field: floral scent biochemistry.

Since then, Pichersky and others have looked for the scent-producing enzymes in the Fragrant Cloud rose, and the genes that code for them. They hope to transfer those genes into a scentless rose like the Golden Gate cultivar.

Biotechnologists may ride to the rescue of rose scent. They have a toolbox full of techniques to transfer genes into plants. They can literally shoot new genes into plant cells using microscopic DNA-coated particles of gold or tungsten. Or they can use the microorganism
Agrobacterium
to install the genes for them. Not only can genetic engineers restore a plant’s original scent, they can give it the scent of another species. It’s a dizzying thought: roses that smell like violets, asters that smell like lilacs. The creation of transgenically fragrant flowers will be a victory for biotechnology and may ease public acceptance of biotech crops.

This would all seem like a perfect opportunity for the cut-flower industry. Yet Eran Pichersky tells me that producers are reluctant to make the effort. According to their market research, consumers claim that scent matters, but sales figures don’t reflect it. Consumer choice is driven by color and visual appeal. In any case, most flowers are bought as gifts, which means the purchaser doesn’t live with the scent, or lack thereof. Perhaps it is true, as Shakespeare said, that “to throw a perfume on the violet…Is wasteful and ridiculous excess.”

The Genes of Perception

Imagine a DNA test in which a marketer predicts your fragrance preferences in ten minutes using a drop of your saliva. Rapid, saliva-based clinical diagnostics like home pregnancy tests are already in use. Why shouldn’t there be point-of-sale diagnostics? Wouldn’t you trade a little spit to find your perfect fragrance?

The person-to-person variability in odor perception is enormous. To get an idea of the scale, compare it to color vision. Imagine that instead of three kinds of color blindness there were dozens, and that each type affected up to 75 percent of the population instead of only 6 percent. Smell scientists struggle to explain this variability; it remains one of the biggest mysteries about the sense of smell. Why are some people able to smell a particular molecule and others not? Why do some people find it pleasant and others do not?

Cultural factors—the favorite explanation of academic researchers—certainly play a role in odor preferences. But cultural explanations don’t go too far in explaining the extensive differences between people within the same culture. Biological factors, which receive surprisingly little attention, may account for much of this variation. For example, certain specific anosmias—the inability of a person with otherwise normal smell to detect a specific type of molecule—have a biological basis, namely the lack of a receptor for the molecule in question. There are a couple of dozen specific anosmias, but they account for merely a fraction of the total variation in odor perception.

The key to the mystery may reside more broadly in the human genome. A tantalizing possibility is that your olfactory receptor genes determine how you smell the world, and why you smell it differently than other people. Everyone has roughly 350 olfactory receptors, but not necessarily the same 350 as the next person. In addition, the gene for a given receptor can show subtle variation in DNA sequence from person to person.

The science of genetics links genotype (a person’s DNA profile) to phenotype (a person’s physical and mental traits). Several laboratories around the world are exploring the genetics of odor perception. Their first challenge is to characterize a person’s odor perception phenotype—in other words, to measure the sensitivity to, and preference for, a wide range of smells. The next step is to use DNA analysis to establish a person’s odor receptor genotype. Researchers expect that people with similar phenotypes have certain genetic traits in common. For example, people who like musk, hate grape, and are indifferent to patchouli may have certain odor receptor variants in common, and these biomarkers could become the basis of the in-store perfume preference diagnostic.

The first step toward a functional genomics of olfaction has already been taken. Researchers at Rockefeller and Duke Universities have discovered that variations in one odor receptor gene are responsible for differences in how people perceive the molecules called androstenone and androstadienone. These genetic variations, known as single nucleotide polymorphisms, have the effect of muting the intensity and unpleasantness of these two smelly molecules. It’s astounding that such tiny mutations can have such major consequences for odor perception. Yet this is just the tip of the iceberg—we can expect many more examples in the years ahead.

Knowing the link between genes and odor perception will profoundly change how we think about smell. Pavlovian learning and Proustian remembering will have to share the stage with biology. The discovery of biological markers for scent preference would revolutionize the design and marketing of fragrance. Instead of making products that appeal to the market as a whole (and satisfy no one in particular), perfumers could target scents to biologically defined market segments. A perfumer designing something for the musk-loving, grape-hating, patchouli-indifferent audience will have a tremendous advantage over a competitor working with the old hit-or-miss method.

T
HE GENOMIC AGE
of odor perception will be exciting. We will be able to alter odor perception at a fundamental biological level—enhancing the response of a receptor, for example, or blocking it from working at all. These molecular-level interventions could lead to new types of consumer products. Imagine a long-lasting nasal spray for the medical staff in hospitals and nursing homes. One squirt at the start of a shift would knock out the ability to smell the ammonialike notes in urine, but leave the perception of other odors unchanged. The product would work by stopping a specific class of molecules from triggering a sensation. A narrow-range odor blocker like this would make the hospital a more pleasant place to work; and happier staff make for happier patients. Think of all the other occupations—stockyard worker, plumber, refinery employee—that could benefit from selective molecular nose-filters.

Next, imagine a new kind of diet product—one with an immediate and profound effect on appetite: food would lose its appeal and odor-induced cravings would disappear. In biological terms this would be a wide-range odor blocker that interferes with many types of receptors. By reducing odor perception across the board, including food aroma, the blocker would help dieters stay on their program. A recent patent application makes such a claim for a calcium channel blocker—a type of drug usually used to control high blood pressure. Applied directly into the nose, it would temporarily stop the sensory cells from functioning, and reduce or abolish the user’s ability to smell.

By changing receptor function in other ways, we may be able to enhance odor perception. Imagine a product that selectively boosts the perception of certain body odors, like your husband’s pheromones. It might heighten sexual interest or arousal and be a useful treatment for sexual dysfunction. (It would probably become popular with ravers, clubbers, and swingers too—a nasal Ecstasy.) Another possibility is a broad-range odor booster. The results could be mind-blowing. The neurologist and essayist Oliver Sacks once described a patient who experienced heightened smell awareness while pumped up on amphetamines, cocaine, and PCP. The immediacy and clarity of smells was so great that he could find his way around New York by nose alone. Not everybody would want to have such a peak experience, although it’s a product that Emily Dickinson would have paid top dollar for. At a lower dose, a broad-range odor booster might relieve smell impairment in the elderly. Their food will taste better, they will eat more, and their nutrition will improve. Who knows, it might even alleviate the psychological depression that creeps along in tandem with the sensory deprivation of old age.

The temporary tweaking of existing odor receptors is, from a biotechnologist’s point of view, pretty straightforward. The sensory cells of the nose are in direct contact with the outside world, separated by only a thin layer of mucus. They can be reached easily with a topical nasal spray, which means a minimal amount of active ingredient and less chance of side effects. The really weird possibilities go deeper: imagine acquiring a new odor receptor gene. All you would have to do is take a big snort from spray bottle of genetically modified adenovirus, and within days you’d be having a new smell experience. Perhaps your specific anosmia to androstenone will be cured, enabling you for the first time to enjoy the expensive pleasure of truffles. Perhaps you will have a new, deeper appreciation of musky perfumes. Suppose the inhaled virus particles contained all the odor receptors a dog has and you haven’t. By the weekend you’d be smelling things our species hasn’t picked up in millions of years. The experience might be disconcerting at first, like getting powerful new contact lenses. Your brain would need time to adjust to the new odor input and bring it into focus.

This is a fantasy, but not a completely implausible one. Gene-transfer technology is routinely used in research labs. DNA is carried from one organism to another in a modified adenovirus—the virus that causes the common cold. The virus is unable to replicate on its own, but it can worm its way into the DNA of the host cells and trick them into reproducing the transferred gene.

Gene-transfer technology for humans is usually thought of in terms of treatment for life-threatening illness. But in the spirit of William Gibson’s
Neuromancer
, where characters favor trans-species body modification, I predict it will be used first for nonmedical and entirely unnecessary aesthetic enhancements to the human body. In similar fashion, the first animal-to-human odor receptor implant will take place for kicks, not for cure.

Transspecies genetic engineering of sensory systems is already happening in the lab. Mice have been given new photoreceptor genes, and the sex pheromone receptor of the silkworm moth has been transferred into a fruit fly. One day we will be able to control our own olfactory destiny. What do you want to smell like?

The horizon’s edge, the flying sea-crow, the fragrance of salt

marsh and shore mud,

These became part of that child who went forth every day,

and who now goes, and will always go forth every day.

—W
ALT
W
HITMAN,
Leaves of Grass

Acknowledgments

For encouraging me to write this book in the first place, I thank Barbara Ivins and Mandy Aftel. For advice on how to go about it, and moral support during the writing of it, I thank Tom Higgins and Lisa Verge Higgins, and my excellent agent, Michelle Tessler. The expert guidance of my editor, Lucinda Bartley, made this a better book.

I benefited from the insights and recollections of the many people I interviewed. For helping me reconstruct the history of Smell-O-Vision and AromaRama, I thank Carmen Laube, Novia Laube, Glenda Jensen, Hal Williamson, Ronnie Reade, Luz Gunsberg, Paul Baise, John Waters, Mark Gulbrandsen, James Bond, Steve Kraus, and Denise Garrity. For sharing with me their scientific and technical expertise on olfactory matters, I thank Kari Arienti, René Morgenthaler, Terry Acree, Eric Berghammer, Eran Pichersky, Steven Sunshine, James Woodford, and Paul Breslin. Over the years I have benefited from discussions of smelly topics with Paul Rozin, Gary Beauchamp, and Michael O’Mahoney. Roman Kaiser deserves special thanks for helping me track down the molecule that inspired John Muir in the Sierra Nevada so long ago.

I am grateful to everyone who gave me a hand here or there; without these graciously provided assists, I could not have completed this work. These friends and colleagues include Gregg Rapaport, Owen Brown, Felix Aeppli, Jeff Freda, Dennis Passe, Jim Walker, Jennifer Stevenson (and her pals Marge Kriz, Alan Rafaelson, and Herb Kraus), Peter F. Stucki, Bernadette Meier, Jeanine Delwiche, Charlotte Tancin, Ernest Sanders, Candace Jackson, Laurence Dryer, John Lundin, Kat Anderson, Gordon Shepherd, Mark B. Adams, Gunnar Broberg, John Canemaker, Betty Gilbert, Tirza True Latimer, John Prescott, Harris Jones, Mark Greenberg, Steve Jellinek, Marci Pelchat, Alan Fridlund, John Steele, Sue Van Inwegen, Leti Bocanegra, Tom Rigney, Carol Christensen, Steven Mintz, Melissa Mintz, Diana Hollander, Lilly Hollander, Larry Clark, Jim Bolton, Stephen Porter, Rolf Bell, and Alison Cocotis.

I am grateful to the many colleagues who generously provided copies of their publications and data: Pam Dalton, Jim Drobnick, Bob Frank, Hildegarde Heymann, Devon Hinton, David Hornung, Thomas Hummel, David Laing, Zachary F. Mainen, Florian Mayer, Yoshihito Niimura, Ann Noble, Tim Pearce, Timothy D. Smith, Eric Spangenberg, Dick Stevenson, Denise Tieman, Omer Van den Bergh, Bill Wood, Don Wright, Christina Zelano, Lorie Fulton, Debra Zellner, Joël Candau, John D’Auria, Claire Murphy, Bryan Raudenbush, Ralph Both, and Kirsten Sucker.

Finally, and most importantly, I thank my wife, Susanne, and our beautiful daughters, Alice and Lydia, for their patience and love and support.