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Ancestral Climates May Have Shaped Your Nose

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A study led by Penn State researchers looked at nose shape in people whose parents and ancestors came from four regions of the world.

Ask anyone what the nose does, and the reply will most likely be related to smell. We appreciate our noses because they help us experience flowers and fresh-baked cookies.

In fact, our honkers have another, more important function: They warm and humidify the air we breathe, helping prevent illness and damage in our airways and lungs. Because of this, scientists have long suspected that nose shape evolved partly in response to local climate conditions. In cold, dry climates, natural selection may have favored noses that were better at heating and moisturizing air.

A team led by scientists at Pennsylvania State University has found more evidence of the relationship between the noses we have now and the climates where our ancestors lived.

In a study published in PLOS Genetics on Thursday, the researchers found that nostril width differed significantly between populations from different regions around the world. Moreover, the higher the temperature and absolute humidity of the region, the wider the nostril, the researchers found, suggesting that climate very well may have played a part in shaping our sniffers

Physical traits that are in direct contact with the environment often undergo natural selection and evolve faster, said Arslan Zaidi, a postdoctoral scholar in genetics at Penn State and an author of the paper. “This is one of the reasons why we looked at nose shape.”

All in all, Dr. Zaidi and his colleagues measured seven nose traits, including the nose’s height, protrusion and nostril width, along with skin pigmentation and overall height in men and women whose parents were born in regions that corresponded with their genetic ancestry. They looked at four regions — West Africa, East Asia, Northern Europe and South Asia — with at least 40 participants in each group.

“We selected these to maximize the distance across populations,” Dr. Zaidi said, adding that his team wants to sample more groups in future research.

Between the groups in this study, only nostril width and skin pigmentation showed greater differences than would be expected because of chance accumulations of genetic mutations.

Over all, people whose parents and ancestors came from warm, humid climates tended to have wider nostrils, whereas those from cold, dry climates tended to have narrower ones. Correlations between nostril width and climate were strongest for Northern Europeans, the researchers found, suggesting that cold, dry climates in particular may have favored people with narrower nostrils.

These findings align with those of previous studies of the skull, which have shown that narrower internal nasal inlets tend to be more efficient at warming and humidifying air, said Katerina Harvati, director of the paleoanthropology department at the University of Tübingen in Germany, who was not involved in this study.

Dr. Zaidi and his colleagues also demonstrated that nose shape is a heritable trait. They did this by showing a relationship between shared genes and similarities in nose shape in large groups of unrelated people.

This is important because natural selection can act only on characteristics that can be passed from one generation to the next, said Todd Yokley, a biological anthropologist at the Metropolitan State University of Denver, who did not participate in the study.

The fact that nose shape is subject to natural selection and showed evidence of varying with climate paints a convincing picture that climate adaptation played some role in the evolution of nostril width, Dr. Zaidi said.

He added, however, that nostril width does not seem to correlate with climate as closely as skin pigmentation does. That may indicate that other factors are involved in what kinds of noses are passed down, he said, such as “cultural differences in what is considered an attractive nose or not.”

It’s also important to note that less than 15 percent of genetic variation in humans can be attributed to differences between people from different continents, Dr. Zaidi said.

In actuality, the genes that differ because of geographic origin, such as those affecting skin color, hair texture and nose shape, are the rare exception, rather than the rule.

“People are more similar than they are different. What this research does is offer people a view of why we’re different,” he said. “There’s an evolutionary history to it that, I think, kind of demystifies the concept of race.”

Studying how certain traits evolved as environmental adaptations that may no longer be relevant could also help us understand disease risk today, Dr. Zaidi said.

“We know there are variable risks of respiratory diseases across different populations in the U.S.,” he said. “Can we find an explanation for that in morphology?”

Source:nytimes.com

A Pungent Life: The Smells in My Head

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I am in my kitchen smelling dirt. Three new plants — a white kalanchoe and two red begonias — sit on a stand at my window. It is April, nearly a decade ago, and I have bought them because it is finally spring. I admire their small, dense flowers and green, waxy leaves.

But I hadn’t planned on their powerful, raw smell. Working around the house, I try to think about something else. When I go upstairs, the smell follows me, earthy, pushy, almost wet. I wonder how it is that I can smell three small houseplants on the floor below.

That afternoon, at the grocery, I can’t shake their dank odor. Could the smell somehow have gotten into my clothes? A day later, miles away at my doctor’s office in Manhattan, I am shocked that it smells there, too. But she has no potted plants.

I finally get it. This assertive smell, my uninvited companion for almost two days, is inside my head, not out. Mortified, I think I must smell. Talking to friends, I cover my mouth with my hand. I brush my teeth more often, swish mouthwash compulsively. But my husband says I smell fine — no bad breath. I finally call my doctor.

I discover that I suffer from phantosmia. “Osmia,” from the Greek osme, means “smell.” Coupled with “phanto” (like “phantom”), it refers to an illusory sense of smell. I smell a smell when no odorant is present.

Inevitably, medical tests followed. I had an M.R.I. of my brain (ruling out a tumor), then a CT scan of my sinuses (looking for infection), and finally, an EEG (olfactory hallucinations do occur in epilepsy). The results were negative, and two rounds of antibiotics (was there a hidden nasal or sinus infection?) constituted my only — and fruitless — treatment.

One day a year later I realized that the earthly smell was finally gone. But to my dismay a new smell immediately took over. My husband had burned a big pot of chili. Burned chili became my new default odor. At least it smelled better than dirt.

Then, about seven years ago, a trip to Provence erased the chili. Lavender wafted in the air, becoming my new smell du jour. Southern France’s lavender-infested landscape — dried bouquets, scented soaps and candles, even flavorings for food — trailed me back home. Some might think me lucky — lavender is hugely popular. But I hated this smell that had squirmed its way into my brain.

I tried in vain to fool my nose. Holding lemons under my nose didn’t kill the odor. Smearing pungent perfumes and lotions around my nose didn’t work either. A powerful odor like ammonia might trump the lavender for a moment, but that cure is worse than the disease.

Sometimes I can’t tell whether a smell is inside or outside my head. Walking my dog, I cried as I smelled manure, convinced it would lodge in my head. At home, I rejoiced that the stink was gone. The next day, the horrid smell reappeared at the same spot. This time I noticed the warning sign: gardeners had spread fertilizer. Only then did I know the smell was real.

Avoiding gruesome odors is my first line of defense. There’s a coffee shop nearby that I simply won’t enter. It’s jam-packed with wooden barrels of reeking coffee beans; locals complain they can smell the roasting blocks away. I send my husband to buy coffee while I wait in the car with the windows up.

I’ve tried the opposite tactic, going out of my way to imprint favorite perfumes, fresh flowers, that wonderful bakery smell. Alas, my phantosmia specializes in the disagreeable.

That is typically the case, I now know. Dr. Donald Leopold, chairman of the department of otolaryngology at the University of Nebraska Medical Center in Omaha, has studied smell disorders for 30 years. In phantosmia, Dr. Leopold says, both the upper nasal passages and the brain play a part, especially the brain, “where the actual smell perception is generated.”

Almost always the patient has lost some ability to smell. Dr. Leopold says that the brain, “which has a propensity to make smell,” overcompensates by offering up odors, usually disagreeable ones, that may have existed previously but were suppressed. It appears that certain “traffic cop” neurons, which had worked to exclude such odors, turn off.

Though Dr. Leopold assures me that “treatment is available,” I haven’t tried the nasal saline drops, antidepressants, antiseizure medicines or sedativesrecommended by one doctor or another. Mainly I try to think past the phantosmia, forcing my attention elsewhere. If that fails, I try to laugh at it, more absurd than awful. I win more of these skirmishes than one might expect.

I learn that this disorder is best kept private. Some friends squirm when they hear about it, as if I were crazy. For that matter, phantosmia is linked to certain psychiatric disorders (schizophrenia, depression, Alzheimer’s), but I don’t have them. I do wonder, though, what it means to hallucinate smell. Those neurological explanations aren’t entirely satisfying. There’s nothing plainer than the nose on my face, but nothing more mysterious, either.

Source:nytimes.com

Smell Turns Up in Unexpected Places

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A team of biologists has found that our skin is bristling with olfactory receptors.

Smell is one of the oldest human faculties, yet it was one of the last to be understood by scientists. It was not until the early 1990s that biologists first described the inner workings of olfactory receptors — the chemical sensors in our noses — in a discovery that won a Nobel Prize.

Since then, the plot has thickened. Over the last decade or so, scientists have discovered that odor receptors are not solely confined to the nose, but found throughout body — in the liver, the heart, the kidneys and even sperm — where they play a pivotal role in a host of physiological functions.

Now, a team of biologists at Ruhr University Bochum in Germany has found that our skin is bristling with olfactory receptors. “More than 15 of the olfactory receptors that exist in the nose are also found in human skin cells,” said the lead researcher, Dr. Hanns Hatt. Not only that, but exposing one of these receptors (colorfully named OR2AT4) to a synthetic sandalwood odor known as Sandalore sets off a cascade of molecular signals that appears to induce healing in injured tissue.

In a series of human tests, skin abrasions healed 30 percent faster in the presence of Sandalore, a finding the scientists think could lead to cosmetic products for aging skin and to new treatments to promote recovery after physical trauma.

The presence of scent receptors outside the nose may seem odd at first, but as Dr. Hatt and others have observed, odor receptors are among the most evolutionarily ancient chemical sensors in the body, capable of detecting a multitude of compounds, not solely those drifting through the air.

“If you think of olfactory receptors as specialized chemical detectors, instead of as receptors in your nose that detect smell, then it makes a lot of sense for them to be in other places,” said Jennifer Pluznick, an assistant professor of physiology at Johns Hopkins University who in 2009 found that olfactory receptors help control metabolic function and regulate blood pressure in the kidneys of mice.

Think of olfactory receptors as a lock-and-key system, with an odor molecule the key to the receptor’s lock. Only certain molecules fit with certain receptors. When the right molecule comes along and alights on the matching receptor, it sets in motion an elaborate choreography of biochemical reactions. Inside the nose, this culminates in a nerve signal being sent to brain, which we perceive as odor. But the same apparatus can fulfill other biological functions as well.

Dr. Hatt was one of the first scientists to study these functions in detail. In a study published in 2003, he and his colleagues reported that olfactory receptors found inside the testes function as a kind of chemical guidance system that enables sperm cells to find their way toward an unfertilized egg, giving new meaning to the notion of sexual chemistry.

He has since identified olfactory receptors in several other organs, including the liver, heart, lungs, colon and brain. In fact, genetic evidence suggests that nearly every organ in the body contains olfactory receptors.

“I’ve been arguing for the importance of these receptors for years,” said Dr. Hatt, who calls himself an ambassador of smell, and whose favorite aromas are basil, thyme and rosemary. “It was a hard fight.”But researchers have gradually awakened to the biological importance of these molecular sniffers and the promise they hold for the diagnosis and treatment of disease.

In 2009, for instance, Dr. Hatt and his team reported that exposing olfactory receptors in the human prostate to beta-ionone, a primary odor compound in violets and roses, appeared to inhibit the spread of prostate cancer cells by switching off errant genes.

The same year, Grace Pavlath, a biologist at Emory University, published a study on olfactory receptors in skeletal muscles. She found that bathing the receptors in Lyral, a synthetic fragrance redolent of lily of the valley, promoted the regeneration of muscle tissue. Blocking these receptors (by neutralizing the genes that code for them), on the other hand, was found to inhibit muscular regeneration, suggesting that odor receptors are a necessary component of the intricate biochemical signaling system that causes stem cells to morph into muscles cells and replace damaged tissue.

“This was totally unexpected,” Dr. Pavlath said. “When we were doing this, the idea that olfactory receptors were involved in tissue repair was not out there.” No doubt, few scientists ever imagined that a fragrance sold at perfume counters would possess any significant medical benefits.

But it may not be all that surprising. Olfactory receptors are the largest subset of G protein-coupled receptors, a family of proteins, found on the surface of cells, that allow the cells to sense what is going on around them. These receptors are a common target for drugs — 40 percent of all prescription drugs reach cells via GPCRs — and that augurs well for the potential of what might be called scent-based medicine.

But because of the complexity of the olfactory system, this potential may still be a long way off. Humans have about 350 different kinds of olfactory receptors, and that is on the low end for vertebrates. (Mice, and other animals that depend heavily on their sense of smell for finding food and evading predators, have more than 1,000.)

Despite recent advances, scientists have matched just a handful of these receptors to the specific chemical compounds they detect — an effort further complicated by the fact that many scent molecules may activate the same receptor and, conversely, multiple receptors often react to the same scent. Little is still known about what most of these receptors do — or, for that matter, how they ended up scattered throughout the body in the first place.

Nor is it even clear that olfactory receptors have their evolutionary origins in the nose. “They’re called olfactory receptors because we found them in the nose first,” said Yehuda Ben-Shahar, a biologist at Washington University in St. Louis who published a paper this year on olfactory receptors in the human lung, which he found act as a safety switch against poisonous compounds by causing the airways to constrict when we inhale noxious substances. “It’s an open question,” he said, “as to which evolved first.”

Source:nytimes.com

What Does Cancer Smell Like?

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On a lab bench in Philadelphia sits a tiny box lined with nearly invisible nanotubes and gold. A clear plastic pipe runs through it, and a thicket of pins, each sprouting a red or blue wire, protrudes from its end. As air from the pipe wafts over the nanotubes, electrical signals surge out of the box along the wire threads. The whole apparatus is situated near a vial of blood, “sniffing” the air above it through the pipe.

The box, an electronic nose, is a key part of a theory being explored by George Preti, an organic chemist at the Monell Chemical Senses Center, and an interdisciplinary team that includes physicists and veterinarians at the University of Pennsylvania. Preti is an expert on human odors, having studied them for more than 40 years. He has sniffed — both with machines and with his nose — breath, sweat and other secretions in search of answers about why we smell the way we do. This latest project seeks to answer a question others might have never thought to ask: Does ovarian cancer have a smell?

In modern cancer medicine, doctors tend to rely on advanced imaging techniques and the detection of lumps. The widely acknowledged problem with these methods, though, is that by the time doctors have reason to order a scan or feel something, it’s often too late. Ovarian cancer has usually spread to other organs by the time it’s detected. If it is caught early — which happens only 15 percent of the time, often by accident when doctors are looking for something else — 92 percent of patients live for at least five years. But when it’s caught late, that rate drops to 27 percent. Scent might be a way to get there sooner.

Discovering earlier and better markers for all kinds of cancer, especially in blood, is a priority, said Dr. J. Leonard Lichtenfeld, deputy chief medical officer of the American Cancer Society. Ovarian cancer already has a blood test that has turned out to be not as useful as hoped — giving out both false positives and negatives. A smell-based test would need to perform better.

Diseases can subtly alter people’s fragrance. In the normal course of metabolism, thousands of waste products are swept out in our breath, blood and urine, or simply released into the air above the skin. Metabolic disorders, like diabetes, interfere with the way the body breaks down nutrients and thus make that exhaust especially stinky. People with phenylketonuria (or PKU) tend to smell musty. A faulty or missing digestive enzyme makes people with trimethylaminuria (or TMAU) smell fishy. Untreated diabetics can smell like nail-polish remover: Unable to get energy from sugar, their bodies burn fat for fuel and release acetone as a by-product. (These scents don’t always smell bad; there exists a disorder known as “maple syrup urine disease.”) For Preti, originally from Brooklyn, this makes a subway ride unusually informative. “I often tell people I work with, ‘I bumped into the guy with isovaleric acidemia today.’ ”

Cancer cells, though they don’t alter human metabolism overall, can have altered metabolisms themselves. That means the substances they release could differ from those generated by healthy cells. This idea has been around for decades, but only very recently have biochemical and sensor technology advanced to the point where we can develop portable, hand-held sniffing machines.

Electronic noses have the potential to detect even very small amounts of molecules — but they need to be programmed to look for specific signs wafting up from patient samples. To do that, A.T. Charlie Johnson, a physicist and collaborator of Preti’s at Penn, has the electronic nose sniff blood samples from both sick and healthy patients. As the air passes through the tube, molecules from the samples alight on strands of sticky DNA attached to the carbon nanotubes, changing the electrical signals running out of the box. The team can look for patterns in the signals and use the difference — if there is one — between cancer samples and healthy samples to create an odor-based ovarian cancer test. (Preti is also attempting to identify the specific molecules present in ovarian cancer sufferers’ blood using a much larger machine called a gas chromatograph-mass spectrometer.)

A work in progress, the electronic nose is, for now, an example of how modern medicine can look for answers in unusual places. The impetus that finally pushed Preti and his team to seriously investigate the possibility of cancer detection by smell traces its roots to a dog. In 1989, a letter published in The Lancet reported that a woman had come into the doctor’s office to have a mole looked at. She hadn’t noticed it until her collie-Doberman mix began to sniff the spot intently — even through her pants — and tried to bite it off when she wore shorts. The mole turned out to be an early-stage malignant melanoma, inspiring researchers to test whether dogs, whose smell machinery is at least 10,000 times as sensitive as ours, can tell healthy samples from cancerous ones.

The results from the dog tests have been inconclusive, but to Preti, who has mulled the idea that hidden cancers could be detected from smell molecules since the 1970s, they suggested that there was a real possibility for a new diagnostic. “We think that they’re present very early in the carcinoma process,” Preti said of the scents. “The main question is: Can we be as sensitive as the dogs in picking these things up?”

Source:nytimes.com