Magdalena Fluegge is devoted to her exercise routine, and she has been training hard for months now. Every morning and afternoon, without fail, she hefts four small brown glass vessels. They contain gauze strips saturated with different fragrances. She opens each flask in turn and inhales deeply. She hopes for a scent--any scent--to register in her brain.

Fluegge, who lost nearly all her ability to smell after striking the back of her head in a bicycle accident, is a volunteer in a study at the Ear, Nose and Throat Clinic at the University of Dresden Medical School in Germany. The goal is to see whether people with smell disorders can regain their abilities through training, similar to the way perfumers and sommeliers can learn to discern expertly among samples.

"Smell is perhaps our most evocative sense," biochemist and molecular biophysicist Richard Axel of Columbia University has written; his work in uncovering the molecular mechanisms of smell garnered him the 2004 Nobel Prize in Physiology or Medicine. Humans can perceive some 10,000 scents, and specific odors can elicit memories or behaviors. In his Remembrance of Things Past, Marcel Proust describes how the fragrance of a madeleine cake dipped in linden tea suddenly sent him back to his childhood. When an intense memory is evoked by a sudden whiff of a fragrance, we call the phenomenon the madeleine effect. Smells evoke memories, without which keys to our own pasts would be missing. The sweet presence in the air of an apple pie baking may instantly awaken fond childhood recollections of cooking with Mom, for instance.

Smell also gives different foods their characteristic flavors, as anyone who has suffered from a bad head cold can attest. Without smell, food loses much of its appeal; taste buds detect only sweet, sour, salty, bitter or umani (savory). The sense confers important survival benefits, too. A pungent stink alerts us to the hazard of a nearby skunk; an unpleasant tang warns us away from spoiled milk.

Smell is, from an evolutionary point of view, one of the oldest senses, and it is more strongly associated with emotions--which evolved early--and less with reasoning.

Without smell, some of the most intimate of all experiences would lose their foundation: a mother not being able to smell her child or a husband the body of his wife. A research team led by psychologist Bettina M. Pause, now at Heine University in Dusseldorf, Germany, demonstrated in 2001 that depressed individuals often have a poorer olfactory sense than healthy people--although it is not yet clear whether this symptom is a cause or an effect of mental distress. As researchers pursue a better understanding of how smell works, they may find clues to restoring the sense.

Scent to the Brain
Every breath draws scent molecules into our nostrils. The mucous membranes inside the nose contain olfactory cells with fine hairs, or cilia, that absorb the tiny airborne particles from gasoline, a rose or manure. They send signals on to the olfactory nerve, a fiber bundle that ends at the olfactory bulb in the brain. From there, scent information is passed to the olfactory center, which is connected to the limbic system, the emotional seat of the brain, where incoming smells are identified and classified.

Many factors can lead to the loss of smell. About 5 percent of all people cannot smell at all, a condition called anosmia; more are like Fluegge, who has hyposmia, a partial inability. In rare cases, the defect is hereditary, and the victims--overwhelmingly female--are anosmic from birth. Smell also declines with advancing years; 25 percent of people older than 60 have to do without it. Sometimes a nasty virus or cold damages receptor cells. "About 8 percent of all cases of smell disorders are caused by accidents," adds Thomas Hummel, who leads the clinics team. "A classic is falling and hitting the back of the head: during rebound, the olfactory lobe, which is in the front of the brain, behind the eyebrows, is jolted forward. There it collides with the bones of the skull. The olfactory nerve is often torn."

"In fact, the human sense of smell is based on two nerves," Hummel continues. "The olfactorius is a pure odor detector, whereas the trigeminal nerve has more to do with feelings and sensing pain, and it comes into play with pungent odors such as ammonia or onions. This second nerve remains, for many anosmics, intact." He picks up an ivory-colored plastic skull from the shelf, opens it, and traces the path of the nerve with his finger. "The bulbus olfactorius, the olfactory bulb, leads directly to the brain. This point is very vulnerable. But for most accident victims with smell disorders, only the olfactory nerve is torn or crushed--and thus the link between the nasal mucosa to the olfactory bulb is cut."

Fluegge lost her sense of smell in a bicycle accident. When she landed on the back of her head, she suffered a concussion. Later, she went for a walk in the woods. "I had always enjoyed the fragrances there," she recalls. "I realized suddenly: I dont smell anything. I would pick up moss and grass and stick them under my nose, but nothing happened. Nothing." Her fears were soon confirmed: "I would deliberately walk behind people smoking and would think, Now I am going to smell something. But I wouldnt. Nothing."

Loss of smell may also be a symptom of another ailment. At the onset of some neurodegenerative diseases, such as Alzheimers and Parkinsons, people often lose the ability to smell. "To begin with, we try to find the underlying disorder," Hummel explains. "Because the rate of misdiagnosis for Parkinsons is about 20 percent, this is an important indicator."

To Smell Again
"For most types of smell disorders, there is no proven method of treatment," Hummel says. But "occasionally the sense of smell suddenly comes back to life--with or without treatment." For between 10 and 20 percent of patients, the sense of smell returns naturally.

The clinics work on smell-training therapy springs from a key distinction of olfaction: our nose possesses a special ability not shared by eyes or ears. Its sensory cells regenerate to replace themselves every four to six weeks. Taking a cue from the educated noses of professional sniffers, the doctors in Dresden hope that continual practice by patients will animate disabled sensory cells to reproduce, making them more sensitive and improving the processing of smell data by their brains. The cost and complexity of such therapy are minimal. In a small, brightly lit lab in the basement of the old building that houses the Dresden clinic stands an unassuming army of brown glass jars in ranks atop a cart--pipettes, an atomizer and the racks holding the three rods of a test called the Sniffin' Stick.

Every six weeks Hummel and his colleagues test Fluegge to see whether her nose has learned anything. Hours into the process, the blindfolded woman continues to hold her nose up in the air out of habit, although her shoulders have begun to sag from fatigue. She whiffs a spectrum of everyday odors in turn, such as lemons, flowers and spices. Some Sniffin' Sticks have such an intense stench--dried fish, for example--that clouds of scent overwhelm the room, causing even Fluegge to grimace. Suddenly, she jumps. Turpentine or coffee? "That may be coffee," she whispers. Right. She also recognizes cloves, and her self-confidence increases.

Wires attached to Fluegges head record her brain activity in response to the samples. Fed a constant stream of data, the computer calculates the results and then spits out the final tallies. Fluegge pulls the blindfold off, and, dazed by the light, she blinks. "Overall the results are a little better than last time," the tester announces.

But the smell marathon is not over yet. Johannes Frasnelli has prepared the next trial. Four squeezable plastic bottles stand ready. "First we worked on the olfactory nerve, now on the trigeminal, the sensory nerve," the young doctor explains. "We will do that with the squeezer," he says as he arranges two of the milky-white plastic bottles in a metal apparatus about four inches tall. One of them contains eucalyptus, the other nothing, he tells her.

Fluegge gets ready, her eyes covered again. Then Frasnelli inserts two of the little red nozzles on the bottle tops into her nostrils. He presses the squeezer together. "Raise your hand on the side on which you smell the eucalyptus," the doctor instructs. Fluegge sits still, waits, then raises her left arm. The routine continues: inserting the nozzles, squeezing, waiting for the hand signal, switching the bottles--each switch is marked by the same hollow sound of the soft plastic sliding into place. Again. And again. Forty times. The rhythm is precisely calculated--a series of eternities, each lasting 40 seconds. When the patient finally removes her blindfold, she learns that this time she got almost everything right. Her trigeminal nerve is relatively undamaged, so that she can still sense penetrating odors.

Now comes the last test of the day. Inside a lab packed full of equipment, an olfactometer awaits. The instrument is a colossus covered with dials, wires and buttons; it fills the room. Through a long tube, various fragrances are blown into the nose. The brain activity each scent arouses will be measured with electrodes that detect so-called evoked potentials.

Wires are quickly attached, and Fluegges head appears as if it is festooned with spaghetti. She is told not to blink. Gas begins to blow through the tube. Little xs on the screen show the strength of the stream of gas entering her nose. It is tiresome work, but Fluegge is resolute. "Being blind is definitely worse," she remarks, "but smells were always important for me. It is only since they no longer exist for me that I have realized just how important. I have lost a warning system. Once my son ran up to me and screamed: 'Can't you smell that?' The skillet on the stove was red-hot."

Even if she does not profit further from the smell-training program herself, Fluegge views the chore optimistically. She hopes that the knowledge gained from her participation will alleviate the condition of fellow sufferers in the future.

(The Author)
ELEONORE VON BOTHMER is a psychologist and science writer who is based in Frankfurt, Germany.