AI finds ‘smell’ genes might have a role beyond the nose

Credit: CC0 Public Domain

by University of Oxford

Humans have around 400 “smell-sensing” genes which activate in a combination of ways to allow us to smell the ranges of smells that we do. However, the genes have been found to be expressed in parts of the body other than the nose, with their role previously remaining a mystery. Now, a new study published in Molecular Systems Biology. has found that patients whose colon cancer cells show the “expression” of certain smell-sensing genes are more likely to have worse outcomes, especially those with more severe cases of cancer.

The expression of a gene is when the information that is stored in our DNA is translated into instructions for making proteins or other molecules. Gene expression can act as an on/off switch to control when proteins are made and how many. So, the expression of these smell-sensing genes means that the instructions for these particular genes are in use. The levels of the genes can be reduced by experimental techniques called “perturbations” to study the role of the gene in the cell.

When researching the development of cancer, a key thing to look at is the organisation of cells in body tissue. Dr. Heba Sailem, Sir Henry Wellcome Research Fellow at the Institute of Biomedical Engineering and lead author on the study, along with Professor Jens Rittscher and Lucas Pelkmans (University of Zurich), explains: “Cancer is often characterised with the loss of tissue structure which can be driven by certain gene alterations or stresses. It is crucial to understand which genes play a role in this process to be able to develop therapies that target cancer development.”

The researchers used multiple layers of Artificial Intelligence including a computer vision algorithm to detect changes in cell appearance and organisation. The algorithm was fed information from robotic microscopy, in collaboration with researchers from the University of Zurich, to image millions of colon cancer cells.

Following the perturbation (or decrease in the expression) of every gene in each individual colon cancer cell the study found that smell-sensing genes are strongly associated with how cells spread and align with each other. Reducing the expression of smell-sensing genes can inhibit cells from spreading, potentially by restraining the ability of cells to move. The same behaviour is also observed in the perturbation of key cancer genes. In contrast, having higher levels of these genes might increase cell motility.

Dr. Sailem says: “It is like activating a sixth sense that allows cancer cells to smell their way outside the toxic tumour environment which can result in spreading cancer to other parts of the body and make things worse for the patient.”

Artificial intelligence was crucial in accelerating the speed and efficiency of this research. The computer is trained using an encyclopaedia of knowledge on the functions of genes collected over decades and automates the process of identifying cell patterns in the images. Previously, this type of research would have relied on the slower and more costly method of human experts identifying examples of changes in cell appearance.

Dr. Sailem says: “Using the developed AI system, we can now learn much more from these experiments and accelerate the identification of genes that alter the structure of tissues in cancer.” Gene editing technology CRIPSR (Clustered Regularly Interspaced Short Palindromic Repeats) is now routinely used to reduce the level of every gene in the cell out of around 20,000 genes to study how changing the level of the gene affects cancer cell behaviour.

Parallel with advances in gene editing technologies, such as CRISPR, this research could enable new avenues in identifying the functions of genes in different cancer types which is vital for cancer therapy and understanding cancer evolution.

The paper is published in Molecular Systems Biology.

Posted in Biology, Fragrance, Perfumery | Leave a comment

Our Pungent History: Sweat, Perfume, and the Scent of Death

— March 8th, 2016

mum-crop edited

Consider the sweet, intoxicating smell of a rose: While it might seem superficial, the bloom’s lovely odor is actually an evolutionary tactic meant to ensure the plant’s survival by attracting pollinators from miles away. Since ancient times, the rose’s aroma has also drawn people under its spell, becoming one of the most popular extracts for manufactured fragrances. Although the function of these artificial scents has varied widely—from incense for spiritual ceremonies to perfumes for fighting illness to products for enhancing sex appeal—they’ve all emphasized a connection between good smells and good health, whether in the context of religious salvation or physical hygiene.

“People felt that eliminating all these smells was the single most effective way to improve public health.”

Over the last few millennia, as scientific knowledge and social norms have fluctuated, what Westerners considered smelling “good” has changed drastically: In today’s highly deodorized world, where the notion of “chemical sensitivity” justifies bans on fragrance and our tolerance of natural smells is ever diminishing, we assume that to be without smell is to be clean, wholesome, and pure. But throughout the long and pungent history of humanity, smelling healthy has been as delightful as it has disgusting.

The desire to surround ourselves with ambrosial fragrances can be directly traced to the unavoidably rank smell of unwashed humans, and to get to the root of body odor, you have to start with sweat. According to journalist Sarah Everts, who’s conducted extensive research on the science of perspiration, human sweat by itself typically barely smells at all. “The problem is that bacteria living on our body like to eat some of the compounds that come out in our sweat,” she says. Eccrine glands all over the body and apocrine glands found mostly in the armpit and genital areas secrete various compounds that are consumed by bacteria, which in turn release molecules with a smell we recognize as body odor. “In particular, it’s one kind of bacteria called Corynebacterium, and they make a molecule which is really a top note of human body odor,” Everts says. “It’s called trans-3-methyl-2-hexenoic acid.”

Top: A Mum deodorant advertisement from the 1920s captures the rise of the modern deodorized era. Above: This Egyptian relief carving in a tomb illustrates the making of lily perfume, circa 2500 B.C.

Top: A Mum deodorant advertisement from the 1920s captures the beginning of the modern deodorized era. Above: This Egyptian relief carving illustrates the making of lily perfume, circa 2500 B.C. Via Wikimedia.

Of course, humans were unaware of such compounds throughout most of recorded history, which is why the first efforts to smell civilized consisted of smothering the odors with more favorable scents. “The ancient Egyptians applied concoctions made of ostrich eggs, tortoise shell, and gallnuts to help improve their personal body pong,” Everts says. Fragrances made during this time were often worn on the head, neck, and wrists as thick pastes or oil-based salves incorporating ingredients from fragrant plants like cardamom, cassia, cinnamon, lemongrass, lily, myrrh, and rose. One of the most complex and well-known Egyptian perfumes was kyphi, a mixture made up of 16 ingredients that was used in religious ceremonies but also to treat lung, liver, and skin ailments.

Besides direct application on the skin, Egyptians burned fragrances as incense and developed jewelry that incorporated scented materials, a tradition still practiced by cultures throughout northern Africa. Hieroglyphics also depict men and women wearing small cones above their wigs, which are believed to have been made of perfumed wax and animal fats.

A Roman perfume flask made from banded agate, circa late 1st century B.C.–early 1st century A.D. <a href="">Via the Met</a>.

A Roman perfume flask made from banded agate, circa late 1st century B.C.–early 1st century A.D. Via the Metropolitan Museum of Art.

Today, we know that humans can smell essential oils in extremely miniscule amounts—early alchemists believed these concentrated extractions were a spiritual embodiment of nature, sort of like a plant’s soul. For centuries, such botanical essences were distilled via two primary methods: “maceration,” meaning plant material was pressed to remove oils and then ground into powders or pastes, or the more complicated method of “enfleurage,” in which leaves or petals were placed in a thin layer of fat, which absorbed the plant’s essential oils.

In ancient Greece and Rome, aromatic spices and perfumes gained traction as coveted luxury goods, spreading along trade routes between the Mediterranean and the Middle East. “From the moment people start to trade internationally, migrate, and cross borders, you encounter references to foreign scents,” says Jonathan Reinarz, a professor of medical history who published a book called Past Scents: Historical Perspectives on Smell in 2014. “Travel literature is saturated with references to smell. You can imagine in every new market that people entered in Africa or Europe or Asia, they’d smell something they didn’t recognize, but were nevertheless still quick to judge.”

John Singer Sargent painted the Moroccan-inspired "Fumee d'Ambre Gris," or "Smoke of Ambergris," in 1880, long after the substance had become popular in the West for its aromatic qualities. Via the <a href="">Clark</a>.

John Singer Sargent painted the Moroccan-inspired “Fumee d’Ambre Gris,” or “Smoke of Ambergris,” in 1880, long after the substance had become popular in the West for its aromatic qualities. Via the Clark.

Though travelers often had instinctive negative reactions to such foreign smells, many exotic herbs were becoming desirable, stimulating a global scent market. The earliest known perfumeries date to the Roman Empire, a rare period when it was normal to bathe daily, both as a social custom and for religious purposes. Following a soak, the body was typically anointed with scented oils, and these salves were sometimes carried in small bottles tied around the wrist.

Early fragrance concoctions incorporated floral scents like jasmine, rose, iris, lavender, violet, or chamomile, as well as spicy smells from natural materials such as yellow amber, camphor, and cloves. Perfumes derived from animals included civet (from civet cats), musk (found in musk deer), or ambergris (a secretion of the sperm whale). As a bonus, these animal scents were also thought to be natural aphrodisiacs.

Before the ability to suspend natural essences in alcohol, aromatic oils were prone to go rancid if not protected from heat, so most products were designed for immediate use by local customers. However, complex scents weren’t only intended for applying directly to the body: Scented powders made from talc were carried within fabric sachets, hardened pastes were made into beads and worn as jewelry, and garments were sewn from fabrics steeped in perfume.

By the 5th century A.D., scented oils and incense had become entwined with religious rituals across Europe, including those of Judaism and Christianity, even though such indulgences were previously shunned for their Pagan roots. In part, the mixing of various social classes at public worship spaces meant that everyone brought their own particular smells, and incense helped to mask the God-fearing funk. “In Katherine Ashenburg’s book, The Dirt on Clean, she wrote that Catholic priests were so overwhelmed by the stench of their worshipers that they would avidly burn incense to counteract the worshipers’ body odor,” Everts says.

Even while the clergy were exalting religious incense, they sometimes derided perfume as a sinful, decadent indulgence. For several centuries, many Christians rejected bathing for its connection to the sin of pride or vanity, which explains, if only in part, why they were seen as dirty and malodorous by the rest of the developed world. “With the emergence of Christianity, the whole meaning of smell changes and the vocabulary expands,” Reinarz says. “There were frequent references to the early saints with the devout often saying that, when these first martyrs died, their bodies had emitted fragrant scents. The problem, of course, is that when the scent industry started to develop, anybody could smell like a saint, so the religious language changed and instead of talking about the smell of a saint, people began to focus on detecting the false odors of sanctity—since even the harlot or prostitute could now buy perfume and wear these ‘sacred’ scents.”

Left, a 17th-century jar inscribed with "Mesue’s French Musked Lozenges of Aloes Wood" (in Latin) held lozenges made from aloe wood, ambergris, and musk to be taken for health purposes and to freshen the breath. Via the <a href="">Wellcome Library, London</a>. Right, a 1785 painting of a Turkish bath by Jean-Jacques-François Le Barbier.

Left, a 17th-century jar inscribed with “Mesue’s French Musked Lozenges of Aloes Wood” (in Latin) held lozenges made from aloe wood, ambergris, and musk to be taken for health purposes and to freshen the breath. Via the Wellcome Library, London. Right, a 1785 painting of a Turkish bath by Jean-Jacques-François Le Barbier.

While Christians preferred not to wash (the ritual cleansing of hands and feet being a rare exception), Islamic communities kept the tradition of bathing alive and well. In the eastern part of the Byzantine Empire, Roman bathing customs evolved into the hamam, or Turkish bath. Around the 11th century, the return of Crusaders brought the hamam tradition back to Europe along with scented treasures like musk and civet.

At the time, most household soaps were rough and smelled like the ash and animal fats they were made from, so were rarely used on the skin. But during the medieval period, Middle Eastern inventors developed better formulas incorporating vegetable oils that were more gentle on the body, and soap-making became the primary application for perfumes.

By the 13th century, chemists had mastered the art of distilling, whereby a natural specimen is boiled along with water and the evaporating substance—a combination of water and essential oils—is captured and separated during the cooling process. Inventors combined these essential oils with alcohol to create the stable, quick-drying perfume that we know today. The first major alcohol-based fragrance was a late 14th-century rosemary perfume known as Hungary Water, since it was designed for Queen Elizabeth of Hungary.

This woodcut engraving from the mid-16th century depicts the process of distilling essential oils from plants with a conical condenser. Via the <a href="">Wellcome Library, London</a>.

This woodcut engraving from the mid-16th century depicts the process of distilling essential oils from plants with a conical condenser. Via the Wellcome Library, London.

By this time, most of Europe’s public bathhouses had been closed due to the bubonic plague, which killed more than a third of the population. Without a scientific understanding of germs, people believed that diseases like the plague were contagious through the air. “Before germ theory, there was the widely held belief in miasma or malaria,” which Reinarz says described unhealthy or disease-causing odors. “Today, of course, we associate malaria with a specific disease, but if you take the literal Latin translation ‘mal-aria,’ it’s bad air, which was thought to impact dramatically on people’s health and even create epidemics.”

The distinctive beaked mask worn by plague doctors was filled with aromatic substances supposed to prevent them from catching the illness, as seen in this illustration, circa 1656. Via Wikimedia.

The distinctive beaked mask worn by plague doctors was filled with aromatic substances supposed to prevent them from catching the illness, as seen in this illustration, circa 1656. Via Wikimedia.

Thus the stinking smell of sickness was fought with the sweet scent of other aromatics. “Specific diseases, like plague, believed to be conveyed by impure or corrupt air were frequently countered by building bonfires in public spaces and, in private, by burning incense or inhaling perfumes such as rose and musk,” Reinarz says. Doctors tending patients with the plague adopted a gas-mask style facial covering with a curved beak over the nose and mouth containing sweet-smelling substances to ward off the disease. Small bouquets of herbs and flowers called posies, nosegays, or tussie-mussies became popular accessories carried to overcome the stench of death.

In their book, Aroma: The Cultural History of Smell, Constance Classen, David Howes, and Anthony Synnott detail other fragrant methods used to protect one’s health: “Municipal authorities had bonfires of aromatic woods burnt in the streets to purify the atmosphere. Individuals fumigated their homes with, among other things, incense, juniper, laurel, rosemary, vinegar, and gunpowder. Even burning old shoes was thought to help, while, for added olfactory protection, some families kept a goat in the house.”

Today, we know that some of the odors used to overpower this miasma of illness were unhealthy pollutants, like the coal smoke of 18th and 19th centuries. “Coal burning was seen as an antidote to all the bad smells that accumulated in urban centers,” Reinarz says. “People at the time more likely thought, ‘Thank goodness we live in a manufacturing city where all of these chimneys belching out smoke are disinfecting the air.’”

A tiny, ornately decorated scent bottle meant for carrying on a chain, circa 16th century. Via the Museum of London.

A tiny, ornately decorated scent bottle meant for carrying on a chain, circa 16th century. Via the Museum of London.

Meanwhile, the true antidote to major epidemics—better hygiene via bathing and handwashing—was unattainable as long as most Europeans believed that bathing was dangerous to one’s health. In the 15th and 16th centuries, prominent scientists helped spread the falsehood that water’s ability to soften skin and open pores actually weakened the flesh, making it more susceptible to the foul smells of sickness. With this in mind, the few who did bathe regularly often took special precautions, like anointing the body with oil and wrapping themselves in a scented cloth immediately afterward.

Instead, layers of linen clothing and undergarments were thought to cleanse the body by absorbing its oils and smells, and clothing was believed to be much safer to wash than the skin. Hair could be rubbed with aromatic powders and bad breath was improved by chewing pungent herbs.

With its growing wealth and powerful trading ties to the East, Venice led Europe in the adoption of perfumed goods, especially devices to be carried or worn on the body that would mask unseemly odors. One popular form was the pomander, a word that came from the French phrase “pomme d’ambre” or “apple of amber,” referring to the ambergris often contained in the spherical pendants. While the original pomanders were simply fruits like oranges studded with cloves, the term eventually described a pendant made from precious metals with several small compartments for different fragrances.

This spherical pomander opens into separate compartments for different scents, circa early 17th century. Via the <a href="">Victoria &amp; Albert Museum</a>.

This spherical pomander opens into separate compartments for different scents, circa early 17th century. Via the Victoria & Albert Museum.

As animal essences fell out of favor and more refined herbal or floral scents became trendy, France came to dominate the international perfume industry. One of its most popular fragrances was Eau du Cologne, a recipe originally produced as protection against the plague, which included rosemary and citrus essences suspended in a grape-based spirit.

In the 17th and 18th centuries, the French aristocracy took perfumery to a new level, installing scented fountains at their dinner parties and making their own custom essences, sometimes wearing a different perfume each day of the week. In France, perfume also became closely linked with leather goods, as tanneries used them to cover the strong odors of chemicals used in the tanning process. Leather gloves infused with Neroli, an orange-blossom fragrance, were one of the country’s most successful products.

Small scent boxes designed to hold liquid perfumes eventually replaced pomanders as the fragrant accessory of the moment. Called “smelling boxes,” “pouncet boxes,” and, later, “vinaigrettes,” these decorative perforated cases held small sponges or fabric swatches soaked with alcohol- or vinegar-based fragrances hailed for their medicinal qualities, which worked to defend against unpleasant odors encountered on city streets. Other vinaigrettes contained a mixture of smelling salts, an ammonia-based inhalant used since ancient times to revive people who were feeling faint.

An agate-topped silver vinaigrette with an engraved interior grill, circa 1857.

An agate-topped silver vinaigrette with an engraved interior grill, circa 1857.

In the late 18th century, vinaigrettes were often attached to chatelaines, which held utilitarian objects from small chains and typically attached at the waist of a woman’s dress. While not as popular, other forms of jewelry were also adapted to the perfume craze, including necklaces with pendant flacons of liquid fragrance and perfume rings with tiny hidden compartments for storing scented powders or pastes.

Yet even with access to all manner of perfumes, wealthy people often still stunk. “Descriptions of Versailles by a lot of people visiting the court of Louis XVI and his bride Marie Antoinette just before the revolution are really striking,” Reinarz says. “They described it as a stinking cesspit where everyone was relieving themselves in the corridors and even the ballrooms.”

This 1866 political cartoon by George John Pinwell plays on epidemiologist John Snow's work linking London cholera outbreaks to contaminated water.

This 1866 political cartoon by George John Pinwell plays on epidemiologist John Snow’s work linking London cholera outbreaks to contaminated water.

During the French Revolution, clothing styles shifted towards simpler silhouettes, fewer layers, and lighter fabrics made from cotton, which could also be more easily washed. Bathing had finally come back in vogue, as doctors now believed that accumulated filth prevented the body from releasing corrupt fluids. Despite concerns of sexual impropriety, bidets began appearing in the homes of the wealthy. By the end of the 18th century, chemists had also developed a way to produce soap using soda ash made from salt, avoiding the use of timber ash and resulting in soaps that were harder, milder, and less offensive-smelling. Meanwhile, steamboat trade allowed the soap market to expand and made it easier to import olive-oil-based soaps.

Outbreaks of cholera in the mid-1800s, like the 1854 London epidemic studied by Dr. John Snow, pointed to the importance of clean water and inspired cities across Europe to improve their sanitation practices by expanding access to fresh water, systemizing garbage disposal, and constructing new sewer systems to remove excrement, which were particularly beneficial to the lower classes. Some also focused their efforts on building new public baths, as was encouraged by Britain’s Baths and Washhouses Act of 1846.

As better hygienic practices took over, strong perfumes were no longer essential to combat stench, and their association with the aristocracy was becoming a hindrance to sales; the industry thus aligned itself more with fashion. When perfumes moved from the pharmacy to the cosmetics counter, their use was increasingly linked with the feminine, especially as Victorian-era notions about separate spheres for each gender took hold of Western society. While some scents, like tobacco and pine, remained connected to popular ideas of masculinity, the general concept of good smell was increasingly associated with the world of women. The cultural fervor for celebrated male explorers and scientists meant that Victorians placed a higher value on sight than the other senses. “Smell, in turn, was now considered the sense of intuition and sentiment, of homemaking and seduction, all of which were associated with women,” explain Classen, Howes, and Synnott in Aroma.

Perfume was positioned as a feminine cosmetic by the turn of the 19th and 20th centuries, as seen in this 1901 advertisement for Parfumerie Violet by Louis Théophile Hingre.

Perfume was positioned as a feminine cosmetic by the turn of the 19th and 20th centuries, as seen in this 1901 advertisement for Parfumerie Violet by Louis Théophile Hingre.

In the 1860s, Louis Pasteur first demonstrated the relationship between tiny microorganisms and infectious disease, work that Robert Koch expanded upon in the 1880s. Their research would establish what’s now known as “germ theory,” furthering development of antiseptics by doctors like Joseph Lister who advocated carbolic acid as a disinfectant for wounds and surgery. This represented a huge shift in thinking about illness and gave further support to the movement for better sanitation, which continued to reduce the olfactory assault of urban areas. Foul smells, whether from human waste or industrial byproducts, were increasingly pushed further from cities via zoning policies and waste management.

Americans had been as reluctant to bathe as Europeans, but by the late 19th century, the United States leapt toward the eradication of dirt and smells, adopting novel cleaning devices like showers and toothbrushes, which were supported by the latest studies on hygiene. In her book, The Dirt on Clean, Katherine Ashenburg points out that America’s clean regime was also made possible by the young country’s abundant space. “Water mains and sewers were more easily installed in new cities than in ancient ones,” she writes. “With abundant, cheap land, houses with ample space for bathrooms became the domestic norm, in contrast to Europe’s old, crowded apartments. Because servants were always in short supply in democratic America, labor-saving devices were prized. High on the list was plumbing, and from the 1870s, American plumbing outstripped that of every other country.”

Modern economies like that of the United States depended on an increasingly urban population, and as more people lived and worked in close quarters with others, body odor became a social issue. Unlike farm fields, offices and factories provided no respite from the trans-3-methyl-2-hexenoic acid emanating from your sweaty colleague.

Antiseptics like Listerine caught on as a way to prevent infection, but were eventually applied to specific areas of the human body, including the mouth, armpit, and genitals. The ad above is from 1917.

Antiseptics like Listerine caught on as a way to prevent infection, but were eventually applied to specific areas of the human body, including the mouth, armpit, and genitals. The ad above is from 1917.

“Doctors were already using antiseptics to clean their tools and benches,” Everts says. “After they’d finished washing a whole bunch of surfaces, they started looking for new surfaces to wash, and why not the armpit? In fact, the earliest deodorant patent I’ve tracked down was given to a doctor in 1867 for ammonium chloride. Even in the patent he writes that this was a known disinfectant, and that it has ‘great value in counteracting the odor of the human body.’”

The earliest successful brand of commercial deodorant was developed in 1888 by an inventor in Philadelphia and dubbed Mum, as in “keeping silent” or “mum’s the word.” The first patented version of Mum was sold as a waxy cream that quickly inspired imitations, but these cumbersome products were unpleasant to apply and often left a greasy residue on clothing. In 1903, Everdry introduced the world’s first antiperspirant, which used aluminum chloride to clog pores and block sweat. Regardless of their success at preventing sweating, early antiperspirants were also highly acidic, meaning they often damaged clothing and left the wearer with a stinging or itching sensation. Despite their unappealing format, many early deodorants and antiperspirants included perfumes to minimize their chemical scents.

In the early 20th century, American marketers were also creating new standards of personal hygiene, like the importance of bathing daily to eliminate odors, with the ultimate goal of selling more products. In 1927, the Association of American Soap and Glycerine Producers created a lobbying arm called the Cleanliness Institute to publish marketing materials under the guise of education. The Institute distributed teacher’s curriculum, posters, and books, like 1928’s A Tale of Soap and Water: The Historical Progress of Cleanliness, which taught children and teens the value of hygiene throughout the ages. “Most of us want the good and beautiful and worthwhile things of life,” the book explained. “Soap and water alone cannot give them to us, but we know that they help.”

In 1928, "A Tale of Soap and Water" spread the good word of the soap and glycerine industry to schoolchildren via illustrations like this.

In 1928, “A Tale of Soap and Water” spread the good word of the soap and glycerine industry to schoolchildren via illustrations like this.

Although doctors had supported better sanitation to improve public health and curb major epidemics, companies now exploited this authority, using it to vilify normal bodily functions, like sweating. Early in the 20th century, a Cincinnati surgeon wanted his hands sweat-free while operating, so he invented an antiperspirant called Odo-Ro-No. In 1912, his daughter Edna Murphey hired an ad agency to boost the company’s sales, and their first successful ad positioned excessive sweating as a medical disorder with a doctor’s endorsement of Odo-Ro-No. A few years later, the company tried a new tack: Convincing self-conscious women that their body odor (which it dubbed “B.O.” for short) was a problem nobody would directly tell them about.

American marketers played on insecurities to make deodorant a must-have product, like with this Odo-Ro-No ad from 1939.

American marketers played on insecurities to make deodorant a must-have product, like with this Odo-Ro-No ad from 1939.

Odo-Ro-No helped launch a trend of advertising-by-fear, sometimes known as “whisper copy,” which focused on gossip around topics considered impolite to address in public. Similar campaigns were soon waged against every imaginable imperfection, whether it was flawed makeup, gray hair, torn stockings, acne, underarm hair, bad breath (strictly using the clinical-sounding term “halitosis,” so as not to offend), or the ultimate—bad “feminine hygiene.” To describe the “life-destroying” impact of bad breath, an oral antiseptic brand called Listerine (after Dr. Lister) coined the ubiquitous phrase, “Often a bridesmaid, but never a bride.”

During the 1920s, brands like Lysol began promoting disinfectant douches—long believed to be an abortifacient—as a way to keep women’s privates smelling fresh. Eventually, doctors recognized that douching actually disrupted the body’s natural pH balance, causing a number of health issues.

By the 1930s, American deodorant companies had secured a female customer base, so they began including subtle advertising copy referencing men’s body odor. In 1935, Top-Flite, the first deodorant targeted at men, hit store shelves in its sleek black bottle, followed by other stereotypically male designs, like the Seaforth bottle resembling a miniature whiskey jug. Advertisements for men’s deodorant products often focused on financial insecurities, positing that foul body odors might ruin one’s career.

Just as manufacturers had gendered deodorant, fragrance companies developed their own parallel language for men’s products, using terms like cologne, aftershave, and eau de toilette. Scents for men focused on the enhancement of sexual attraction with “masculine” names like Brut, Centaur, Dante, Old Spice, Macho, English Leather, and Denim.

At this point, manufactured scents were no longer bound to the natural world of essential oils, as chemists developed entirely new man-made compounds. “Today, we’re familiar with abstract, man-made scents like Chanel No. 5,” Reinarz says. “But people who first smelled that perfume in 1921 must have thought, ‘What a bizarre flower,’ because the tradition was distilling from nature, and most scents could be identified by naming a single floral ingredient.”

During the 20th century, deodorant companies marketed many damaging products as healthy, like the spray seen in this 1969 ad.

During the 20th century, deodorant companies marketed many damaging products as healthy, like the spray seen in this 1969 ad.

Meanwhile, the delivery method of deodorant was shifting from messy creams to more pleasant roll-on sticks, like the 1940s applicator developed by Mum employee Helen Diserens based on the design of a ballpoint pen. In the early 1960s, Gillette introduced Right Guard, the first aerosol antiperspirant. Despite a brief heyday, aerosols lost favor when the FDA banned aluminum zirconium complexes in 1977 and the EPA restricted chlorofluorocarbons (CFCs) in 1978, stemming from concerns for consumer and environmental safety.

In the 1960s, a Swiss company invented a deodorizing spray for female genitalia, adding a layer of specificity to the coy concern of “feminine hygiene.” The first American version, named FDS for “feminine hygiene deodorant spray,” launched in 1966 and quickly became a hit. Though the sprays fell out of fashion after an FDA ban on hexachlorophene in the 1970s, scented “feminine wipes” are just as popular today.

As with many products before them, advertisers continue to convince women that their natural odor is repellant, and they need to perfume their privates to get laid. Meanwhile, such companies are still suppressing information about the dangerous side effects of their products, as seen with the recent Johnson & Johnson lawsuit over talcum powder.

“Once the ball started rolling, there was no stopping it,” Reinarz says. “People felt that eliminating all these smells was the single most effective way to improve public health and make the environment more tolerable for everyone.” Today, we’re bombarded with a cornucopia of deodorants, antiperspirants, soaps, colognes, perfumes, and douches, all aiming to eradicate smells associated with the human body—even if those odors are the result of healthy processes.

“I think my favorite weird patent was based on baker’s yeast,” Everts says. “I just don’t think I’d want to put baker’s yeast in my armpit.”

Posted in Biology, Fragrance, Perfumery | Tagged , , , , , , , | Leave a comment

The human sense of smell: It’s stronger than we think

Rutgers researcher debunks 19th century myth that animals are better at sniffing out scents


When it comes to our sense of smell, we have been led to believe that animals win out over humans: No way can we compete with dogs and rodents, some of the best sniffers in the animal kingdom.

But guess what? It’s a big myth. One that has survived for the last 150 years with no scientific proof, according to Rutgers University-New Brunswick neuroscientist John McGann, associate professor in the Department of Psychology, School of Arts and Sciences, in a paper published on May 12 in Science.

McGann, who has been studying the olfactory system, or sense of smell, for the past 14 years, spent part of the last year reviewing existing research, examining data and delving into the historical writings that helped create the long-held misconception that human sense of smell was inferior because of the size of the olfactory bulb.

“For so long people failed to stop and question this claim, even people who study the sense of smell for a living,” says McGann, who studies how the brain understands sensory stimuli using information gleaned from prior experience.

“The fact is the sense of smell is just as good in humans as in other mammals, like rodents and dogs.” Humans can discriminate maybe one trillion different odors, he says, which is far more, than the claim by “folk wisdom and poorly sourced introductory psychology textbooks,” that insist humans could only detect about 10,000 different odors.

McGann points to Paul Broca, a 19th century brain surgeon and anthropologist as the culprit for the falsehood that humans have an impoverished olfactory system — an assertion that, McGann says, even influenced Sigmund Freud to insist that this deficiency made humans susceptible to mental illness.

“It has been a long cultural belief that in order to be a reasonable or rational person you could not be dominated by a sense of smell,” says McGann. “Smell was linked to earthly animalistic tendencies.” The truth about smell, McGann says, is that the human olfactory bulb, which sends signals to other areas of a very powerful human brain to help identify scents, is quite large and similar in the number of neurons to other mammals.

The olfactory receptor neurons in the nose work by making physical contact with the molecules composing the odor, and they send this information back to that region of the brain.

“We can detect and discriminate an extraordinary range of odors; we are more sensitive than rodents and dogs for some odors; we are capable of tracking odor trails; and our behavioral and affective states are influenced by our sense of smell,” McGann writes in Science.

In Broco’s 1879 writings, he claimed that the smaller volume of the olfactory area compared to the rest of the brain meant that humans had free will and didn’t have to rely on smell to survive and stay alive like dogs and other mammals.

In reality, McGann says, there is no support for the notion that a larger olfactory bulb increases sense of smell based solely on size and insists that the human sense of smell is just as good and that of animals.

“Dogs may be better than humans at discriminating the urines on a fire hydrant and humans may be better than dogs at discriminating the odors of fine wine, but few such comparisons have actual experimental support,” McGann writes in Science.

The idea that humans don’t have the same sense of smell abilities as animals flourished over the years based on some genetic studies which discovered that rats and mice have genes for about 1000 different kinds of receptors that are activated by odors, compared to humans, who only have about 400.

“I think it has been too easy to get caught up in numbers,” says McGann. “We’ve created a confirmation bias by working off a held belief that humans have a poor sense of smell because of these lower numbers of receptors, which in reality is still an awful lot.”

The problem with this continuing myth, McGann says, is that smell is much more important than we think. It strongly influences human behavior, elicits memories and emotions, and shapes perceptions.

Our sense of smell plays a major, sometimes unconscious, role in how we perceive and interact with others, select a mate, and helps us decide what we like to eat. And when it comes to handling traumatic experiences, smell can be a trigger in activating PTSD.

While smell can begin to deteriorate as part of the aging process, McGann says, physicians should be more concerned when a patient begins to lose the ability to detect odors and not just retreat back to the misconception that humans’ sense of smell is inferior.

“Some research suggests that losing the sense of smell may be the start of memory problems and diseases like Alzheimer’s and Parkinson’s,” says McGann. “One hope is that the medical world will begin to understand the importance of smell and that losing it is a big deal.”

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Getting Clean: The Science of Soap

By Rachel Ross, Live Science Contributor |


Public health officials encourage handwashing with soap and clean, running water to prevent the spread of germs and infections. If clean water is not available, using any water with soap is essential, according to the Centers for Disease Control and Prevention. Soap, then, is the key element in hand hygiene.

The ancient Babylonians invented soap around 2800 B.C. Their recipe of animal fats, wood ash and water has been found carved onto clay containers. The rough concoction was mainly used for washing wool and cotton in order to prepare the materials to be woven into cloth. Ancient Romans, Greeks and Egyptians also independently developed recipes for soap. Arabic chemists made the first soap from vegetable products in the seventh century.

The basic recipe for soap has not changed in thousands of years. Soap is made by combining fats and oils with an alkali, according to Soap History. Oils are plant-based, such as olive oil or coconut oil, and the fats come from animal sources (beef tallow, for example). Alkalis traditionally were obtained from wood ash; other sources exist today, such as sodium hydroxide (lye or caustic soda) or potassium hydroxide (caustic potash). Chemically, an alkali is a base — the opposite of an acid — that reacts with and neutralizes acid.

Soap making entails a chemical process called saponification, according to the American Cleaning Institute. During the process, the alkali causes the fats or oils to split into fatty acids and glycerin. The sodium or potassium part of the alkali joins with the fatty acid part of the fat or oils. This mixture is called soap or the potassium or sodium salt of the fatty acid, according to Soap History.

There are two ways that soap cleans:

  1. Soap lessens the surface tension of the water so that it more readily wets what needs to be cleaned rather than simply balling up on the surface.
  2. Soap molecules are like a bar magnet — but instead of north on one side and south on the other, the molecules are hydrophilic (water-attracting) on one side and hydrophobic (water-repelling) on the other.

Surface tension is what causes water to form droplets or beads on surfaces. This phenomenon slows the process of water wetting many surfaces and can also slow the cleaning process, according to the American Cleaning Institute. The bond that each water molecule makes with other water molecules creates the surface tension, in which all molecules are pulled into the water droplet. Soap is a surface active agent, or surfactant, according to the Essential Chemical Industry, help to reduce the surface tension of the water so it can spread and wet the surface and speed up the cleaning process. Some people describe this as soap making “water wetter.”

Soap molecules are long and thin with one end being hydrophilic and the other hydrophobic. According to the Royal Society of Chemistry, the hydrophobic ends of the molecules are attracted to dirt and oil. The dirt and oil particles are surrounded by many soap molecules and being held onto by the hydrophobic ends while the hydrophilic ends stick outward waiting to be rinsed away by water.

These two processes work together to clean surfaces. Soap may also contain other ingredients, according to the Cleaning Institute, which are added to increase the effectiveness of the soap or to adjust the pH (to either control or modify the pH to make it safer and gentler). Some soap contains abrasives to help scour surfaces to better remove stubborn dirt and grime; water softeners to help additionally with making the water easier to clean with; and enzymes to help with biological stains such as grass or blood by digesting proteins, fats, and carbohydrates.

Some soap is labeled antibacterial or antimicrobial. These soaps go beyond washing away dirt, oil and anything else on your hands and kill any bacteria or other microbes (such as yeast, fungi, and possibly viruses) on your skin, in your clothes, or on your dishes, according to Clean Link.

According to University of California, Santa Barbara’s Science Line, antibacterial soaps are made just like regular soap with the addition of triclosan or triclocarban. These are hydrophobic molecules that can penetrate through fatty substances such as bacteria cell membranes, where the molecules then poison the bacteria. The residues are held in suspension and rinsed away with water. Triclosan and triclocarbon have antibacterial and antifungal properties that are not only commonly used in soaps, but in toothpaste, cosmetics, and some plastics used for toys and kitchen utensils.

However, the Food and Drug Administration has banned companies from marketing hand soaps containing triclosan or triclocarban. In announcing the ban, the FDA cited questions about the antibacterials’ safety for long-term use. In addition, there is no evidence these chemicals add any benefit to people’s heath beyond those of regular soap, the agency said.

“Consumers may think antibacterial washes are more effective at preventing the spread of germs, but we have no scientific evidence that they are any better than plain soap and water,” Dr. Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research (CDER), said in a statement. “In fact, some data suggests that antibacterial ingredients may do more harm than good over the long term.”

Additional resources

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Scents and Sensibility: A History Lesson in Base Notes

How a perfumer is breathing new life into the fragrance industry.


Ally is working to encourage the next generation of entrepreneurs to embrace their financial futures and take a chance on their passions. They are furthering that mission by telling the stories of business owners who seized the moment and made drastic career shifts to build brands from scratch. Each of these creators are bringing a fresh perspective to their respective industries and inspiring our audiences to build better businesses for themselves, and the community at large.

Beyond serving merely as historical reference or inspiration, the iconoclasts of the past are still shaping contemporary culture and politics—now in an entirely new way. The heady glamour of the international jet-set mecca of the 50’s that influenced St. Barths and the political dynasty that ruled long before the Windsors or Kennedys, are just some of the seminal moments and eras that luxury perfumer Carlos Huber has bottled in his collection of unique, artisanal fragrances, called Arquiste. The line combines Huber’s passions for fashion, architecture, design, and fragrance with a master’s degree in historical preservation from Columbia University, to create a one-of-a-kind history lesson. Starting with a career in store design for Ralph Lauren, Carlos switched gears to make his love of personal scent his life’s work.

But tracking down first-hand accounts of the trees that grew in the forest where Alexander the Great waged a battle or the exact wood of the table in the room where Louis XIV of France and Maria Teresa of Spain first laid eyes on one another, is no easy feat—let alone combining these errant notes into something beautiful for everyday wear. Creating just one bottle of an Arquiste fragrance takes years of research and attention to detail. Below, Huber shares his process for crafting two of his latest scents El Y Ella and Fleur De Louis/Infanta en Flor and connects the dots from the past –both decades and centuries ago—to our present.

The moment when Maria Teresa, the 17th century princess of Spain and later Queen of France met her future husband Louis XIV of France is remembered in history as the Meeting on the Isle of Pheasants that ended the Franco-Spanish War and began a long-tenured affinity between France and Spain. Fleur de Louis and Infanta en Flor capture the male and female essences of that meeting, from the perspective of both Louis and Maria Teresa, as well as the elements of the room they were standing in, recreating a centuries old scene.

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Meet the Woman Who Is Preserving the Smell of History

One scientist’s quest to capture old scents.

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67P/Churyumov-Gerasimenko comet perfume

The comet perfume is mainly composed of chemical odors emerging from the components of its atmosphere.

The scientific curiosity reached the maximum point with the new question that seemed to have intrigued researchers. A comet perfume was replicated by using samples taken by Rosetta, the spacecraft that orbited the flying object.

The actual comet perfume has a quite powerful and foul scent.

The comet that sourced the samples is known as 67P/Churyumov-Gerasimenko and it was discovered in 1969. The Rosetta probe reached the comet on August the 6th, 2014, and since then it had sent to Earth samples from its atmosphere. Rosetta came as close as 19 miles to the comet, and it mapped the surface for the first time.

During the orbiting, the spacecraft identified five potential landing sites, and a Philae lander was sent to the surface of the comet. In two days, ESA lost contact with the lander. However, Rosetta already reached Mars, the 2867 Šteins asteroid, and the 21 Lutetia asteroid.

The project had been initiated by the astronomers participating in the Rosetta mission, in order to interpret the compounds detected in the micro-atmosphere of the comet.

The smell is a mix of bitter almonds, cat pee, and rotten eggs. However, some say that a few floral notes are emerging from the full aroma blend. The person said the flowers seemed to be lilies.

The astronomers detected a possible emergence of an unusual smell when Rosetta flew over the comet’s trail. The mission did not include humans on the board of the spaceship, and scientists agree that the actual comet smell would be difficult to be sensed as in space, people would need to wear a costume separating them from the outer space and its ingredients.

The instruments detected volatile compounds such as hydrogen cyanide, ammonia, methane and hydrogen sulfide, which were blending with other odorless chemical substances like water vapor, carbon dioxide, and monoxide.

The scientists hired a company from Oxfordshire, UK, to replicate the smells produced by the comet’s mixed atmospheric ingredients. As the real components of the atmosphere are toxic, the company used similar odors to create the comet perfume.

The comet perfume will be available to the public at the Summer Science Exhibition in London that will be held in July. Organizers say they impregnated postcard with the special scent, and people will be able to buy them and mail real comet smelling wishes to their friends and families.


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Odorant receptors of Drosophila are sensitive to the molecular volume of odorants
  • Scientific Reports 6, Article number: 25103 (2016)
  • doi:10.1038/srep25103


Which properties of a molecule define its odor? This is a basic yet unanswered question regarding the olfactory system. The olfactory system of Drosophila has a repertoire of approximately 60 odorant receptors. Molecules bind to odorant receptors with different affinities and activate them with different efficacies, thus providing a combinatorial code that identifies odorants. We hypothesized that the binding affinity of an odorant-receptor pair is affected by their relative sizes. The maximum affinity can be attained when the molecular volume of an odorant matches the volume of the binding pocket. The affinity drops to zero when the sizes are too different, thus obscuring the effects of other molecular properties. We developed a mathematical formulation of this hypothesis and verified it using Drosophila data. We also predicted the volume and structural flexibility of the binding site of each odorant receptor; these features significantly differ between odorant receptors. The differences in the volumes and structural flexibilities of different odorant receptor binding sites may explain the difference in the scents of similar molecules with different sizes.


We know which properties of visible light are measured by our eyes, and we also know how our eyes process light. This knowledge has assisted in the production of cameras and displays. Unfortunately, we do not have the same knowledge regarding olfaction. We do not know the relationship between the molecular properties of a stimulus and the sensory response (i.e., the quality of a smell).

Olfactory receptor neurons (ORNs) are at the front end of the olfactory system. Each ORN expresses only one type of odorant receptor (OR). ORNs of the same type converge into the same glomerulus of the antennal lobe in insects (or the olfactory bulb in humans)1,2,3,4,5,6,7,8,9.

The olfactory system uses a combinatorial code. Unlike many other receptors that are activated by only one specific ligand, such as a neurotransmitter or a hormone, an OR can be triggered by many odorant molecules. Furthermore, an odorant molecule can interact with different types of OR10. The combinatorial code enables humans to discriminate many odors11 by using a repertoire of only approximately 350 ORs. However, it is not yet clear which properties of a molecule contribute to its smell. This question is a topic of ongoing research, and many theories have been proposed12,13,14,15,16,17,18,19,20,21,22,23,24,25,26.

Odorant receptors are transmembrane proteins, and in vertebrates, they are metabotropic receptors that belong to the G-protein coupled receptor (GPCR) family27,28. In insects, the signaling methods of ORs are a topic of debate. Insect ORs are thought to be ionotropic receptors but may also use metabotropic signaling29,30,31,32,33. The topology of ORs in insects is different from that in vertebrates34,35, and most insect ORs function in the presence of another common receptor known as Orco36.

Many similarities exist between the olfactory system of insects and that of vertebrates37,38. Regardless of the signal transduction pathway utilized, all ORs have the same function: they have a binding pocket (also known as a binding cavity or a binding site), where odorants (also known as ligands) bind. Binding to an odorant activates an OR, and the activated OR changes the potential of the cell either directly (ionotropic) or indirectly (metabotropic); therefore, knowledge regarding the olfactory system of Drosophila could potentially help us to decode human olfaction.

The amplitude of the change in the membrane potential of an ORN depends on the number of activated ORs and the duration of their activation, which are both determined by various physicochemical properties of the odorant and the OR12,14,18,39,40. One important factor is the size of the ligand relative to the OR binding pocket. Another factor is the flexibility of the binding pocket. Proteins are not rigid bodies and can change shape depending on the amino acids involved41,42,43. The size and flexibility of binding pockets have been used in computational drug design to predict the binding pocket of a given ligand44.

Herein, we focused on the volume and flexibility of the binding pocket. The molecular volume of a ligand should match the dimensions of the OR binding pocket. Subsequently, the ligand can fit into the binding pocket of the OR and trigger signal transduction. Mismatches in volume decrease the neural response; however, flexibility of the binding pocket can compensate for volume mismatches (Fig. 1).

Figure 1: This figure shows different scenarios that may occur when an odorant molecule (ligand) binds to an odorant receptor according to the coarse-grained model.
Figure 1

The red disks represent the odorant molecule, and the blue shapes represent the odorant receptor (OR) and binding pocket. The top schematic shows a mismatch because of the small molecular volume on the left, a perfect match in the center and a mismatch because of a large molecular volume on the right. The bottom schematic shows how the flexibility of an OR may compensate for molecular volume mismatches.

We can determine the volume and flexibility of a binding pocket if we know its three-dimensional structure. However, the structures or ORs are unknown because it is difficult to determine the structure of integral membrane proteins45,46. To investigate OR protein structure, various research methods have been used, including molecular dynamics (MD) simulations, mutagenesis studies, heterologous expression studies, and homology modeling47,48,49,50,51,52,53,54,55.

In the current study, we develop a mathematical framework that utilizes available experimental data, and we apply this developed mathematical framework to investigate the relationship between the molecular volume of odorants and the ORN response. Our results suggest that although molecular volume is a considerable factor, it is not the only factor that determines the neural response of ORNs. We predict the in vivo volumes and flexibilities of OR binding pockets (supplemental file volume-profiles.csv) by applying our mathematical method to neural data from the Database of Odorant Receptors (DoOR)56, which is a well-structured database that includes the neural responses of mostDrosophila ORs to many odorants56. This database aggregates data from many sources17,19,57,58,59,60,61,62,63,64,65,66,67,68,69.

We suggest that a functional relationship exists between molecular volume and the neural response. We also provide a methodology to estimate the molecular receptive range or tuning function of ORs. Finally, we predict the structural properties (i.e., volumes and flexibilities) of OR binding pockets. Our results may aid in the selection of odorants for future experimental studies (supplemental file proposed-odorants.csv) and may contribute to the study of olfactory coding by unmasking the effects of other possible factors.

Material and Methods

We used the neural data of the DoOR 1.056 database for our calculations, and we reserved the additional data in the DoOR 2.018,70,71,72,73,74,75database to use as a test set. We calculated the molecular volume (supplemental file odorants.csv) using the computational chemistry software VEGA ZZ76. We used GNU R statistical computing software to analyze the data77.

The DoOR database includes an N × M matrix. Its elements, rnm, are the response of ORN n to odorant m. This matrix is normalized to have values between 0 and 1, so 0 ≤ rnm ≤ 1, where 1 is the strongest response. This matrix has many Not Available (NA) values, and different ORNs are excited by different sets of odorants. We accounted for this feature by removing NA values from the summations and calculating ; however, for brevity, we used the usual notation .

The response rnm may depend on the molecular volume of the odorant,vm, and other physicochemical properties of the molecule m; therefore, we separated the response rnm into two terms:

The first term, fn(vm), depends only on the molecular volume of the odorant. The second term, the volume-independent term ψnm, includes every other influential property of the odorant molecule, with the exception of molecular volume or any other property that correlates with molecular volume (e.g., molecular weight). Of the molecular parameters that correlate with molecular volume, we used molecular volume because it fits the acceptable picture of protein-ligand interaction (Fig. 1). Using molecular weight would have implied receptors use some type of mass spectroscopy analysis. We tested a few other important parameters, including polarity, functional group, and polar surface area; however, none of the parameters were as dominant as molecular volume. Therefore, we primarily focused on molecular volume (fn(v)) and may consider other parameters (ψnm) in future studies.

Each of the two terms was characteristic of the OR and varied for each OR. In fact, the first term, fn(v), can be considered to be the tuning curve of an ORN n with respect to the molecular volume. We approximate this term with a Gaussian function,

where vn is the preferred molecular volume of the OR n, and σnrepresents the flexibility of the OR binding pocket. We used a Gaussian function for the tuning curve for the following reasons: (a) it is among the simplest forms that can describe a preferred volume and flexibility, and (b) the mathematics was easy to follow and the final solution was simple.

In this work, we wanted to estimate vn and σn. Thus, we first calculated the response-weighted average of the molecular volumes, , and then we used (1):

We approximated ∑ with ∫, which is common in statistical physics:

In this equation, denotes the average of ψnm over all . We moved 〈ψnmm out of the integral because it is independent of v. Here, g(v) is the density of states, and g(v)dv indicates how many molecules have a molecular volume in the range of v and v + dv. This function was approximated by a Gaussian function (Fig. 2),

Figure 2: The graph shows the density function of molecular volumes, g(v), for all molecules in the DoOR database.
Figure 2

The solid line is a Gaussian fit (Eq. 5), and the dashed line shows the median, which is slightly different from the mean.

Ideally, g(v) must not depend on the OR n because it is a property of the ensemble of odorant molecules and not a property of the OR. We also had many missing values (rnm = NA) that did not overlap, and we had to calculate g(v) for each ORN separately; therefore, and are the average and standard deviation, respectively, of the molecular volume while rnm ≠ NA. We rewrote equation (3) using equation (4):

To obtain a simpler form, we replaced the product of fn(v) and gn(v) in the above equation with hn(v) = fn(v)gn(v).

The function hn(v) is a Gaussian function because it is the product of two Gaussian functions,

Thus, the right side of equation 7 was nothing but , and in a similar manner, we calculated from the neural data.

We know the mean, , and standard deviation, , of gn(v) from the molecular volumes of the ensemble of odorants. We calculated the mean and standard deviation of hn(v) from the neural data. Using these values, we calculated the mean vn and the standard deviation σn offn(v). First, we calculated σn using

and then we calculated vn:

The calculated vn and σn are provided in the supplemental file volume-profiles.csv. The resulting fn(v) are plotted over the actual data for the 28 ORs (Fig. 3) in which the p-values were <0.05.

Figure 3: The response of ORs versus the molecular volume of odorants (circles).
Figure 3

The fitted functions fn(v) from Eq. 1 (solid lines) and the error bars of the mean of fn(v) (red vertical lines) for 28 ORs showed that their responses were significantly dependent (p-value < 0.05) on molecular volume. Except 2 (ORs name in light gray), 26 were significant according to the FDR correction (ORs named in gray), and 11 were significant according to the Bonferroni correction (ORs with names in black). The function fn(v) was calculated based on data from the DoOR 1.0 database (blue circles). The red circles are additional data from the DoOR 2.0 database.

We calculated p-values using permutation tests and shuffled the data 105 times. We shuffled the association between odorants and the responses of a given OR and then checked the null and alternative hypotheses. The alternative hypothesis was that “ the response of the ORN depends on the molecular volume of the odorant”, which requires a finite value for σn. The null hypothesis was that “ the response of the ORN is independent of the molecular volume of the odorant”, which requires σn → ∞. Therefore, the p-value is the probability of having , where σn is calculated from the original data, but is calculated using the permuted version.

We tested the hypotheses on ~60 ORs simultaneously (only 44 were present in the DoOR 1.0 database). Using a simple threshold of 0.05 for the p-value of each OR would have resulted in many false positives. To address the issue of a multiple-comparison problem, we used the Bonferroni correction (by multiplying the p-values by 60). The problem with the Bonferroni correction is that it may increase the number of false negatives. This problem can be addressed by using another method called the false discovery rate (FDR) that keeps the rate of false positives below a threshold78,79. We used the Bonferroni and FDR methods as well as no correction. We used the function p.adjust of GNU R to calculate the corrected p-values. The results were labeled accordingly in Figs 3 and 4.

Figure 4: The preferred volumes vn (right) and flexibilities σn (left) of 28 ORs.
Figure 4

The error bars were calculated using the Jack-Knife method. Some ORs, including Or59b, Or67a and Or85a, preferred smaller molecules, but some ORs, including Or19a, Or1a and Or49a, preferred larger molecules. Some ORs, such as Or46a, Or22b and Or30a, were volume selective, but other ORs, including Or19a, Or67b and Or22a, responded to a broader range of molecular volumes. Asterisks indicate the updated results using the DoOR 2.0 database, and the numbers in parentheses show the percentage of DoOR 2.0 results relative to the total amount of data for each receptor.

We also wanted to show the diversity of volumes and flexibilities of binding pockets among ORs. To estimate the p-values, we used any pair of ORs that were sensitive to molecular volume (28 ORs), calculated their difference, used a permutation test (6 × 104 shuffles) and measured the probability of obtaining different results (Fig. 5).

Figure 5: Pairs of ORs that differed significantly in their binding-pocket volumes (upper triangle) and flexibilities (lower triangle).
Figure 5

All blue shades indicate a p-value less than 0.05. The two darker shades indicate FDR-corrected p-values less than 0.05, and the darkest shade has a Bonferroni-corrected p-value less than 0.05.

Results and Discussions

The relationship between molecular volume and the ORN response was evident (Figs 3, 4, 5). The function fn(v) was considered to be the tuning curve of OR n in response to molecular volume (Fig. 3). Each OR had a preferred molecular volume vn and showed some flexibility σn. The calculated fn(v) values are shown in Fig. 3. This figure includes 28 ORs that showed a significant dependence on odorant molecular volume in their response (p-value < 0.05).

The flexibility of a receptor may affect the broadness of its tuning curve (flexible receptors may bind to more odorants), but we did not see any significant relationship when using three definitions of broadness: depth of selectivity, breadth of selectivity and kurtosis70,80,81.

The results of 28 ORs indicated that 11 ORs were significant according to the Bonferroni correction (ORs with black names), 26 of them were significant according to FDR correction (ORs with gray names), and the remaining receptors (2 ORs with light gray names) only satisfied the criteria of a p-value < 0.05 without any corrections. After applying the FDR correction, more than half of the available ORs in the DoOR 1.0 database (26/44) showed significant sensitivities toward molecular volume. The remaining receptors may be sensitive to molecular volume as well; however, the current evidence is not sufficient, and more experiments are necessary.

One interesting case in this regard was Or82a, which did not fit our hypothesis. Or82a binds to geranyl acetate much better than to any other molecule. When we removed geranyl acetate from the data, suddenly Or82a fit perfectly to our model with a Bonferroni-corrected p-value of 0.03 (Fig. 6). The underlying interaction between geranyl acetate and Or82a is therefore a special case that requires more investigation.

Figure 6: The response of Or82a to odorants.
Figure 6

Geranyl acetate (the outlier) did not confirm our theory and had a p-value of 0.55 (left); however, when geranyl acetate was removed from the data, Or82a confirmed our model with a Bonferroni-corrected p-value of 0.03 (right).

The parameters of fn(v), vn and σn are shown in Fig. 4. Figure 4demonstrates that the molecular volume preferences of ORs were different (right), and the flexibilities of the ORs were also different (left). To support these claims, we estimated the p-values of having different volume preferences and flexibilities for each pair of 28 ORs (Fig. 5). The comparison of the volume preferences of all 378 possible pairs indicated that 133 had a p-value less than 0.05. This number was reduced to 89 after using the FDR correction and further reduced to 32 after using the Bonferroni correction. The corresponding number of pairs with a p-value less than 0.05 was 168, 134 and 77, respectively, for the flexibility comparisons. The union of these two sets confirmed that 226 (p-value < 0.05), 171 (FDR corrected), and 91 (Bonferroni corrected) pairs of ORs showed distinct differences in their binding-pocket characteristics.

The diversity of ORs is important in perceiving the quality of smells. In a hypothetical experiment, assume that all odorant molecule characteristics are the same with the exception of molecular volume. If all ORs have the same preferred volume and flexibility, any change in the molecular volume will change only the intensity of smell and not its quality. Here, we showed that ORs have different preferred volumes and flexibilities. Therefore, any change in the molecular volume of an odorant results in a different combinatorial encoding, which affects the quality and intensity of the perceived smell. This conclusion is in agreement with the work of M. Zarzo that suggested that larger molecules smell better82 and might account for differences between the scents of methanol, ethanol, propanol and butanol. Methanol smells pungent, ethanol smells pleasant and wine-like, and propanol and butanol smell like ethanol; however, butanol has a slight banana-like aroma. We argue that molecular volume affects combinatorial encoding and that combinatorial encoding determines odorant quality.

Herein, we showed that the responses of ORNs are related to odorant molecular volume. However, it is not clear what other features of molecules are measured by ORs. Many studies have attempted to connect the physicochemical properties of molecules to the evoked neural response and/or the perceived smells; however, the nonlinear volume dependence (Eq. 1 and Eq. 2) may mask important correlations between molecules and neural responses. When fn(v) is close to zero, the value of ψnm does not matter.

We predicted that odorants with a molecular volume in the tail regions of fn(v) remain undetected, regardless of any of their other physicochemical properties. This prediction can be confirmed in future experiments.

When studying the ψnm of an OR, it is better to have many data points, and it is better for the data points to be close to the preferred volume of the OR; however, the current data do not meet these conditions. For many ORs, most data points are in the tail regions of fn(v), with values close to zero. We have included the best selection of odorants for each of the 28 studied ORs (see Venn diagram in Fig. 7 and supplemental file proposed-odorants.csv); this information can be used to save time and expenses during future experiments.

Figure 7: Venn diagram of the DoOR 1.0 database and our suggested important odorants for each OR.
Figure 7

The database includes 240 molecules. Some of the 240 molecules have been used to study an OR (blue areas); however, data for the rest of the molecules are not available for some of the ORs (pink). The hatched areas represent odorants with molecular volumes that are close to the preferred volume of each OR . We already know the neural responses of the hatched blue areas, but the hatched pink odorant areas can be the target of future experiments. We predict that the remaining odorants will only yield no response.

We have also predicted some in vivo structural aspects of OR binding pockets: the preferred volume of each OR results from the volume of the binding pocket, and the flexibility of an OR results from the rigidity or flexibility of the binding pocket. These data provide additional constraints on the 3D structure of ORs, which may aid in the prediction and calculation of the 3D structure of these proteins.

The methods of the current study can also be combined with mutagenesis. When an OR gene is mutated, the response to a selection of molecules can be subsequently measured, and finally, the preferred volume and flexibility can be calculated. In this way, we could potentially understand which amino acids affect the function of the OR and contribute to both the volume and flexibility of the binding pocket.

In this manuscript, we have excluded many factors because the nature of the problem is inherently complex; it would not be feasible to study this problem with all possible factors. Many factors affect the concentration of odorant molecules at ORs, including the molecular mass, the method of mixing odorants and air, the vapor pressure, the solubility of odorants in water, the sensillum lymph and odorant-binding proteins (e.g., LUSH)83,84. It is difficult to control for all of the aforementioned factors in the current experimental paradigm, and the model would be very complex with many sets of parameters. For example, if we introduce an odorant into air, there will be a mixture of air, vapor and mist. Then, the mixture reaches the sensilla, mixes with sensillum lymph fluid, may bind to odorant-binding proteins and finally reaches ORs. Two important parameters in this process are vapor pressure and water solubility. Vapor pressure limits the vapor concentration of a liquid. Water solubility limits the amount of odorant that can dissolve in water. Both factors are nonlinear at high concentrations; therefore, we can neglect the effect of vapor pressure and water solubility. However, if we are close to the critical concentrations, vapor pressure and water solubility are very important.

We expect these factors to have minimal effects on smaller molecules because they evaporate easily, readily dissolve in water and might not need the help of odorant-binding proteins. Therefore, we have greater confidence about the lack of response to small molecules than we do about the lack of response to larger molecules. Using an experimental paradigm similar to a luciferase assay85 may provide valuable complementary information to our simple model. When using a luciferase assay, the concentrations are accurate, but the experiment isin vitro.


We showed that molecular volume is an important factor, but it is not the only factor that determines the response of ORNs.

We hypothesized that the ORN response results from OR binding-pocket volume and flexibility. We predicted the actual in vivo volumes and flexibilities of OR binding pockets. The results are provided insupplemental file volume-profiles.csv, and they can be verified when the 3D structures are resolved and/or when more experimental results are available.

Now that we understand the extent to which molecular volume contributes to the ORN response, it is possible to study the effects of other parameters.

We approximated a molecule as a rigid isotropic sphere of a given volume, but our model does not consider the shape13,14,40, vibrational mode12,16,24, chirality86 or many other potentially interesting properties of a molecule. Our methods and results actually provide a starting point that may lead to the study of other factors.

An improvement to this model would be to include the anisotropy of the molecules by modeling them as ellipsoids. This modeling will capture more aspects of the molecular shape and may aid in the inclusion of constitutional isomers.

Approximating fn(v) and g(v) with a Gaussian function makes the mathematical formulation simple and readable. However, a semi-infinite function may be a better choice for molecular volumes, which cannot have negative values.

Although this work utilized data from Drosophila, we expect that the general principles and methodologies of this work will also apply to vertebrates. We are working to apply the same method to human odorant receptor data85.


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Scents of the Middle Ages

Uses of the aromas of herbs, spices and resins

Incenses and Fumitories * Strewing Herbs * Moth and insect repellents * Clothing Scents * Potpourris, dry and moist * Body Powders * Essential Oils * Soaps * Waters and splashes * Hair Rinses * Pomanders * Rose and Spice Beads * Nosegays or Tussie-mussies * Scented baths & Saunas * Insomnia recipes * Mouthwashes * List of Resources

Incenses and Fumitories

There is a long-standing tradition (pre-dating ancient Egypt) of burning dried herbs, barks and resinous gums either for the appreciation of the gods (incenses) or to purify the air (fumitories). Cumin, dill and mint were all mentioned as tithes in the old testament, presumably to be used for incense. Sandalwood and Rosewood (Lignum Rhodium) have long been known as bases for incense or incense on their own. Rosemary, lavender and o ther ‘astringent’ herbs were burned as fumitories, to keep away the noxious humors of the plague and other illnesses, and to clear rooms where illness had been. Mixed incenses were often made into ‘pastilles’ (tablets) for burning. Sandalwood, Frankincense, rosewood, myrrh, cloves, cinnamon were all used as single incenses and in blends.

To make perfume to burn:
Take half a pound of Damask Rose-buds, Benjamin [benzoin] 3 ounces beaten to a powder, half a quarter of an ounce of Musk and as much of Ambergris, the like of Civet. Beat all these together in a stone Mortar, then put in an ounce of Sugar, and make it up in Cakes and dry them by the fire.”
From Sir Kenelm Digby, Reciepts in Physick and Chirurgery, 1668.

Strewing Herbs

Strewing herbs were used mixed with, or instead of, rushes or straw to cover floors.

From Thomas Tusser’s Five Hundred Points of Good Husbandry:
“Strewing Herbs of all sorts:

  1. Bassell [basil], fine and busht, sowe in May.
  2. Bawlme [Lemon Balm?], set in Marche
  3. Camamel [Camomile]
  4. Costemary [Costmary/Bible Leaf]
  5. Cowsleps and paggles.
  6. Daisies of all sorts
  7. Sweet fennell
  8. Germander
  9. Hop, set in Febru arie.
  10. Lavender
  11. Lavender spike
  12. Lavender cotten [santolina]
  13. Marjorom, knotted, sow or set, at the spring.
  14. Mawdelin
  15. Peny ryall [Pennyroyal]
  16. Roses of all sorts, in January and September
  17. Red myntes [peppermint?]
  18. Sage
  19. Tansey
  20. Violets
  21. Winter savery.”

Gerard mentions using meadowsweet aka queen of the meadow as a strewing herb and to ‘deck up houses’.

Moth and insect repellents

With no access to bugkillers and exterminators, medieval people made use of scented herbs to discourage vermin. Tansy was considered proof against flies; lavender, lavender cotton, and southernwood against moths, camphor against anything, and pennyroyal, then as now, against fleas.  Southernwood was considered so strong a preventive that it was called ‘garde robe’. Wormwood was considered to be a mouse preventive, and mint was used against mice and ants.  Rue was grown in gardens to discourage pests. Apparently, strongly scented moth repellents work by confusing the mother moth so that she does not lay her eggs in the protected clothing, so they have no effect against existing infestations.

Though this doesn’ t count as a scented recipe, it is an herb use against insects: Hildegarde of Bingen says, “Pound the nigella, and mix honey with it. Where there are many files, you may streak it on the way, and the flies on tasting it will sicken and fall dead.”

“To prevent damage by moths to clothes:
Take wormwood and rue and boil them in water/and brush your clothes with the same water.”
— from Manuscript Pepys 1047, late 15th century, published as Stere Hit Well, modernized by G.A.J. Hodgett

Clothing scents

Laying herbs with your clothes would scent them; the Menagier de Paris gave directions for drying roses to put among clothes: “Roses from Provence are the best to put in clothing, but they should be dried, and in mid-August sift them over a screen so that the worms fall through the screen, and then spread them in your clothes.”  Linens might  also be scented by herbs added to the wash-water, or, when starch became popular, to the starch solution.

Jeanne Rose quotes a ‘Sweet Water for Perfuming Clothes’ which she says is a sixteenth-century recipe:

“To 1 qt. rose water, add the following: 1/2 oz. lavender, 2 oz. orris, 1/2 oz. jasmine flowers, 1 t. musk, a pinch of ambergris and civet, 5 drops of clove oil. Put it all into a glass jar, fasten down the lid, and place it in a sunny window for 10 days. Then strain and set aside the liquid for use.”

From Bulleins Bulwarke, 1562 (quoted by Jacqueline Heriteau, in Potpourris and other Fragrant Delights):
Sixteenth-Century Sweet Water for Linens

Three pounds of Rose water, cloves, cinnamon, Sauders [sandalwood], 2 handful of the flowers of Lavender, lette it stand a moneth to still in the sonne, well closed in a glasse; Then destill it in Balneo Marial. It is marvellous pleasant in savour, a water of wondrous swetenes, for the bedde, whereby the whole place, shall have a most pleasaunt scent.

From Hugh Platt’s Delights for Ladies, 1594 (quoted by Jacqueline Heriteau, in Potpourris and other Fragrant Delights)

To make a special sweet water to perfume clothes in the folding being washed. Take a quart of Damaske-Rose-Water and put it into a glasse, put unto it a handful of Lavender Flowers, two ounces of Orris, a dram of Muske, the weight of four pence of Amber-greece [ambergris], as much Civet, foure drops of Oyle of Clove, stop this close, and set it in the Sunne a fortnight: put one spoonfull of this Water into a bason of common water and put it inot a a glasse and so sprinkle your clothes therewith in your folding: the dregs, left in the bottome (when the water is spent) will make as much more, if you keepe them, and put fresh Rose water to it.

Sachets or Sweet Bags

Powdered ingredients, sewn up in sachet bags to be stored with linens were popular by the end of period. Hugh Platt’s  Delights for Ladies (1594) gives a recipe that he claims will keep seven years. But a simpler one is Gervase Markham’s:

‘Take of Orris six ounces, of Damask Rose-leaves as much of Marjerom and sweet Basil of each an ounce, of Cloves two ounces, yellow Sanders [sandalwood] two ounces, of Citron pills seven drams, of Lignum Aloes one ounce, of Benjamin one ounce, of Storax one ounce, of Musk three dram; bruise all these, and put them into a bag of Silk or Linnen, but silk is the best.’

Potpourris, dry and moist

Potpourris had their heyday in the 17th and 18th centuries, though they may be older. There are two kinds of potpourris, dry and moist: dry are made with crisp-dry herbs and spices, plus fixatives and possibly oils; moist are made with half-dry herbs and flowers, mixed with spices and salt or brandy. I have not yet found a period recipe for either type.

Body Powders

Essential to prevent chafing as well as achieving that fashionably pale look, body and face powders were concocted by mixing powder bases (rice powder, talc, ground orris root, ground calamus root, starch) with various ground spices and herbs: cloves, dried rose petals, lavender. Discorides says that powdered myrtle leaf is good spread on moist thighs and underarms.

‘An Excellent Damask Powder’ (from Ram’s Little Dodoen, 1606, cited by Jeanne Rose), lists the ingredients: rosepetals, cloves, lignum Rhodium (rosewood?), storax, musk, and civet.

Essential Oils

Essential Oils can be obtained by distillation, enfleurage (soaking blossoms or herbs in liquid and collecting the oil that floats to the top), and other means. Tusser lists ‘Herbs to Still in Summer’: blessed thistle, betonye, dill, endive, eyebright, fennell, fumetorie, hop, mints, plantine, roses (red and damaske), respies, saxifrage, strawberries, sorrell, suckerie, woodroffe (for sweet waters and cakes).” The earliest mentioned essential oil is actually otto of roses; oil of lavender and oil of spike (lavender) were widely known by the fourteenth century. Culpeper warns against oil of peppermint, as it is too sharp and strong.


Scented soaps, made by mixing Castile soap with aromatic herbs and waters, seem to have been known at the end of period. Ram’s Little Dodoen (cited by Jeanne Rose) calls for orris, cypress, calamus, rosepetals and lavender flowers, ground fine and mixed with Castile soap dissolved in rosewater. The Queen’s Closet opened (1655), cited by Jeanne Rose, gives a recipe for an Ipswich ball, incorporating castile soap, rosewater, marjoram, winter savory, oil of spike, oil of cloves, musk, ambergris, and almond flour. Thyme, lavender, and other herbs were used in bathwaters and as oil rubdowns from the time of the Greeks onward.

There is a scented lye-based soap recipe in The treasurie of commodious conceits, & hidden secrets by John Partridge (Imprinted at London : By Richarde Iones, 1573).

“To Make Muske Soape Take stronge lye made of chalk, and six pounde of stone chalk: iiii, pounde of Deere Suet, and put them in the lye; in an earthen potte, and mingle it well, and kepe it the space of forty daies, and mingle and [styr? fyr?] it, iii, or, iiii times a daye, tyll it be consumed, and that, that remayneth, vii, or, viii, dayes after, then you muste put a quarter of an ounce of Muske, and when you have done so, you must [sty?re] it, and it wyll smell of Musk.”

Waters and splashes

‘Waters’ are the ancestors of both alcoholic cordials and modern alcohol-based perfumes and bodycare products, being herbs, vegetables, etc, mixed with wine or beer and distilled. The best known waters are rose and orange flower, both by-products of creating oils (rose and neroli). Simple herb and vegetable waters of all kinds were the rage also in the 16th century, made by either ‘cold’ distillation or by mixing the vegetable matter with wine or spirits and ‘hot’ distilling. However, other recipes included Water Imperiall (for wounds) and aqua vitae (for healing), Hungary Water, Carmelite Water, etc. Hungary Water, the first documented perfume using distilled spirits, seems to have included rosemary, and perhaps lavender and myrtle, among its original components. Waters were also used as astringents and handwashes, and as well as medical drinks. Rosewater is a special case: we have a number of rosewater recipes from various sources. Clarkson, in Magic Gardens, quotes William Lawson, William Lawson (1600):
“The rather because abundance of Roses and Lavender, yeeld much profit, and comfort to the senses: Rose-water, Lavender, the one cordial (as also the Violets; Burrage [borage] and Bugloss)  the other reviving the spirits by the sence of smelling, both most durable for smell, both in flowers and water.”

Plain handwashing waters were used at the medieval table, being water with rose or violet petals in it, or an infusion of herbs. Le Menagier de Paris (as edited & translated by Tania Bayard), says:

To make water for washing hands at table: Boil sage, then strain the water and cool it until it is a little more than lukewarm. Or use chamomile, marjoram, or rosemary boiled with orange peel. Bay leaves are also good.

Parkinson says, “The ordinary Basill is in a manner wholly spent to make sweet, or washing waters, among other sweet herbes, yet sometimes it is put into nosegays. ”

From Hugh Plat (Delights for Ladies):

Diverse sorts of sweet handwaters made suddenly or extempore with extracted oyles of spices.First you shall understand, that whensoever you shall draw any of the Oyles of Cinnamon, Cloves, Mace, Nutmegs or such like, that you shall have also a pottle or a gallon more or lesse, according to the quantity which you draw at once, of excellent sweet washing water for your table; yea some doe keepe the same for their broths, wherein otherwise they should use some of the same kinds of spice.

But if you take three or foure drops only of the oyle of Cloves, Mace, or Nutmegs (for Cinamon oyle is too costly to spend this way) and mingle the same with a pinte of faire water, making agitation of them a pretty while togther in a glasse having a narrow mouth, till they have in some measure      incorporated themselves together, you shall find a very pleasing and delightful water to wash with and so you may alwaies furnish yourself of sweet water of severall kinds, before such time as your guests shall be ready to sit downe. I speake not of the oyle of Spike (which will extend very far this way) both because every Gentlewoman doth not like so strong a scent and for that the same is  elsewhere already commended by another Author. Yet I must needs acknowledge it to be the cheaper way, for that I assure myself there may be five or six gallons of sweet water made with one ounce of the oyle, which you may buy ordinarily for a groat at the most.”

William Edward Mead, in The English Medieval Feast (1931, reprinted in 1967) gives suggestions for how to offer scented wash waters.

Boccaccio’s Decameron (14th century) mentions washing waters in a love scene (from the translation by Richard Aldington, courtesy Melandra of the Woods):

“Without permitting anyone else to lay a hand on him, the lady herself washed Salabaetto all over with soap scented with musk and cloves. She then had herself washed and rubbed down by the slaves. This done, the slaves brought two fine and very white sheets, so scented with roses that they seemed like roses; the slaves wrapped Salabaetto in one and the lady in the other and then carried them both on their shoulders to the bed . . . They then took from the basket silver vases of great beauty, some of which were filled with rose water, some with orange water, some with jasmine water, and some with lemon water, which they sprinkled upon them.”

Hair washes

Modern folk medicine recommends rosemary washes to remove residue & gunk in the hair, sage for dark hair and camomile for light. I haven’t yet found documentation for camomile as a light hair wash in period. However, a strong infusion (tea) of herbs, or herbal vinegar in water, seems to have been used to scent the hair.

Trotula gives the following recipe for a scented powder to brush into the hair:

“But when she combs her hair, let her have this powder. Take some dried roses, clove, nutmeg, watercress and galangal. Let all these, powdered, be mixed with rose water. With this water let her sprinkle her hair and comb it with a comb dipped in this same water so that [her hair] will smell better. And let her make furrows in her hair and sprinkle on the above-mentioned powder, and it will smell marvelously.”


Pomanders were generally made by softening resinous substances and mixing them together, often with dirt or clay, or wax. These pomanders were generally carried in metal cases, with piercings to let the scent out.  Cases were used as weights on belts, cane-tops, pendants and other jewelry accessories. Some pomander cases had sections for several different scents of pomanders, as well as compartments for a sponge soaked in aromatic vinegars. Clarkson also says that nutmegs, mounted in silver, were used as pomanders on their own. Pierced cases or hollowed out fruit were also stuffed with herbs and spices.

The ‘cloven fruit’ flirting game is NOT period. However, the use of clove-studded fruit, dusted with ground spice mixes, as pomanders, were introduced by the Arabs.

Materials commonly used in pomanders:

  • Benzoin (Benjamin)
  • Storax (Styrax)
  • Gum Traganth (Gumdragon), usually in Rosewater
  • Gum arabic
  • Labdanum (resin of the rock rose)
  • Calamus (Sweet Flag) Root
  • Orris Root
  • Musk
  • Civet
  • Ambergris
  • Nutmeg & Mace
  • Cloves
  • Cinnamon
  • Lavender, oil of lavender (spike)
  • Otto of roses, Rosewater
  • Lignum Aloes
  • Camphor
  • Marjoram
  • Balm
  • Rosemary
  • Spikenard

‘A Comfortable Pomander for the Brain’
Take Labdanum, one ounce, Benjamin and Storax of each two drams, Damaske powder finely searced, one Dram, Cloves and Mace of each a little, a Nutmeg and a little Camphire, Musk and Civet a little. First heate your morter and pestle with coales, then make them verie cleane and put in your labdanum, beate it till it waxe softe, put to it two or three drops oil of spike, and so labor them a while; then put in all the rest finely to powder, and work them till all be incorporated, then take it out, anoynting your hands with Civet, roll it up and with a Bodkin pierce a hole thorow it.”
Ram’s Little Dodoen, 1606. [Quoted in Jeanne Rose’s Herbal]”To make Pomanders, take two penny-worth of Labdanum, two penny-worth of Storax liquid, one penny-worth of calamus Aromaticus, as much Balm, half a quarter of a pound of fine wax, of Cloves and Mace two penny-worth and of Musk four grains: beat all these exceedingly together, till they come to a pe rfect substance , then mould it in any fashion you please, and dry it.”
Gervase Markham, The English Housewife.

Rose Beads and Spice Beads

To make Rose beads, you supposedly take fresh or half-wilted rosepetals, add rose water to cover, cook over a low heat in an iron pot for an hour, then allow to cool. Repeat once a day for three days. It will be rendered into black, oxidized pulp; you can then oil your fingers with rose oil and form beads, then pierce them with a needle and string; allow to dry for several days, rotating on the string so they don’t stick. Spice scented beads are made by mixing dry spices with binders like benzoin and gum acacia and glycerin, and forming beads. I have not yet found a period recipe for rose ‘beads’: I suspect these are a special case of pomanders. On the other hand, the Spanish work  Manual de mujeres en el cual se contienen muchas y diversas recetas muy buenas, has a recipe for Rose pastilles:

“101 Receta para hacer pasticas de perfume de rosas     Tomar una libra de rosas sin las cabezuelas, y siete onzas de menjuí molido. Echar las rosas en remojo en agua almizclada y estén una noche. Sacar después estas rosas y expremidlas mucho del agua, y majadlas con el menjuí. Y al majar, poner con ello una cuarta de ámbar y otra de algalia. Y después de majadas, hacer vuestras pasticas y ponedlas cada una entre dos hojas de rosas, y secadlas donde no les dé el sol.

Recipe for making rose-scented tablets
Take a pound of roses without the flower heads, and seven ounces of ground benzoin.  Put the roses to soak in musk water for a night.  Remove these roses afterwards and thoroughly squeeze out the water, and grind them with the benzoin.  And when grinding, put with it a quarter of amber and another of civet [musk].  And after [they are] ground, make your tablets and put each one between two rose leaves, and dry them away from the sun.”

Text from; translation by Dana Huffman.

Nosegays, or Tussie-Mussies

For those who could not afford the expensive resin pomanders and their cases, or enough cloves for cloved fruit, bouquets of aromatic, astringent herbs like sage, rosemary, and rue, as well as flowers such as roses and violets served to keep off ‘Noxious Odors’. The concept of flower messages was popularized by the Victorians, but Elizabethans and before kept such scented nosegays– the term ‘tuzzy-muzzy’ and its variants, used for scented nosegays, are dated to 1500 and before by the Oxford English Dictionary. Elizabethans sometimes concealed messages in their flower choices– consider Ophelia’s flower speech in _Hamlet_:

“There’s Rosemary, that’s for Remembraunce. / Pray loue remember: and there is Paconcies, that’s for / Thoughts . . .There’s Fennell for you, and Columbines: ther’s / Rew for you, and heere’s some for me. Wee may call it / Herbe-Grace a Sundaies: Oh you must weare your Rew / with a difference. There’s a Daysie, I would giue you / some Violets, but they wither’d all when my Father dyed… “

Scented baths and steam baths

We all know about the scented oils and ointments that rich women supposedly used after their baths; but putting herbs in a steam bath (sauna) seems to have been a favorite trick of herbalists like Hildegarde of Bingen and the author of Banckes’ herbal. Margaret Freeman cites the Booke of Nuture: “To give your soveriegn a’bathe or a stewe so-called,’ says Russell,you should have ready ‘a basin full in your hand of herbs hot and fresh and with a soft sponge in hand his body…wash’. William Langham’s Garden of Health (1579) suggests Rosemary:  ‘Seethe much Rosemary, and bathe therein to make thee lusty, lively, joyfull, likeing and youngly.'” (Clarkson, Magic Gardens, p 118). Parkinson advocates spearmint in the bath ‘as a help to comfort and strengthen the nerves and sinews’.

Insomina Remedies

Apparently, fragrances were used then as now to combat insomnia. Rosemary was tucked under the pillow to assure dreamless sleep; little stuffed pillows of dill seed were tucked into babies’ cradles to sooth them. Ram’sLittle Dodoen (1606) gives the recipe:

“Take drie rose leaves keep them in a glasse which will keep them sweet and then take powder of mynte, powder of cloves in a grosse powder, and putte the same to the Rose leves thanne putte all these togyther in a bagge and Take that to bedde with you and it wyll cause you to sleepe and it is goode to smelle unto at other tymes.”

Rosetta Clarkson gives a narcotic pomander recipe which “calls for opium, mandrake, juice of hemlock, henbane seed and winelees ‘to which must be added musk that the scent it will provoke him that smells unto it. Make a ball as big as a man may graspe in his hand; by often smelling to this it will cause him to shut his eyes and fall asleep.'” I’d say it would!


The Manual de Mujeres gives a perfume recipe which may or may not be a body perfume:

109 Pasticas de olor para perfumar
Dos libras de agua rosada y una libra de agua de azahar, una libra de menjuí y media de estoraque, una onza
de ámbar y media de almizcle, un cuarto de algalia. Junto todo y molido, ponerlo con el agua en una redoma, y poner la redoma al fuego sobre unas brasas. Menearlo con un palo y cueza hasta que mengüe de tres partes la una. Y desque haya menguado, sacar de aquella pasta y hacerla, si quisieres pasticas, y si no, guardarla así en pasta.Scented tablets for perfuming
Two pounds of rose water and a pound of citrus blossom water, a pound of benzoin and half of balsam, an ounce of amber and half of musk, a quarter of civet [musk].  All together and ground, put it with the water in a flask, and put the flask on the fire over some embers.  Stir it with a stick and cook until it reduces three parts [from?] one.  And when it is reduced, remove the paste from that and make it [into tablets], if you wish tablets, and if not, keep it thus in paste.

Text from; translation by Dana Huffman


A number of recipes for tooth powders and mouthwashes were suggested. Banckes advocates mint sodden in vinegar, and polishing the teeth with the ashes of rosemary. Clarkson, in Magic Gardens (p. 118), says “Halitosis was a matter of consideration even in the time of Gerard, who says, ‘The distilled water of the flowres of Rosemary being drunke at morning and evening first and last, taketh away the stench of the mouth and breath, and maketh it very sweet, if there be added thereto, to steep or infuse for certain daies, a few cloves, Mace, Cinnamon, and a little Annise seed.'”

A short list of Resources

Secondary Sources:

Bayard, Tania. Sweet Herbs and Sundry Flowers: Medieval Gardens and the Gardens of the Cloisters. (New York, Metropolitan Museum of Art, 1985) ISBN:  0-87099-775-0.
Booth, Nancy M. Perfumes, Splashes and Colognes. (Pownal, VT: Storey Publishing, 1997) ISBN: 0-88266-985-0
Clarkson, Rosetta. Green Enchantment. (New York, Macmillan, 1940). ISBN: 0-02-009 461-2.
Clarkson, Rosetta  The Magic of Herbs, Chapters XIV – XVI. (New York: Macmillan, 1939). ISBN: 0-02-030976-7. *
Fettner, Ann Tucker. Potpourri, Incense and other Fragrant Concoctions. (NY: Workman, 1972) ISBN: 0-911104-97-6
Forbes, R.J. Studies in Ancient Technology. volume III, 2nd ed.(Leiden, E.J. Brill, 1964).
Freeman, Margaret B.  Herbs for the medieval household for cooking, healing, and divers uses. (NY: Metropolitan Museum of Art, 1943). ISBN: 0-87099-776-9 *
Garland, Sarah The complete book of Herbs and Spices, “History and Traditions,” “Household herbs and spices,” “Distillation techniques and herb scents.” (New York: Reader’s Digest, 1993). ISBN: 0-89577-499-2.
Heriteau, Jacqueline.  Potpourris and Other Fragrant Delights. (NY: Penguin, 1973). ISBN: 0-14-046320-8 *
Rohde, Eleanor Sinclair. The Scented Garden. (London: The Medici Society, 1931) ISBN: 0-85503-099-2 *
Rose, Jeanne. Herbs & Things: Jeanne Rose’s Herbal, Chapters VIII, XVII, XIX. (Ne w York: Putnam, 1972) ISBN: 0-399-50944-5. (Not suitable for children!)*

* Includes selections of period recipes.

Period sources:

An Herbal, 1525. Also known as Banckes’ Herbal. Author unknown, published 1525. Facsimile & transcripted edition ed. by Larkey & Pyles. (NY: Scholars’ Facsimiles and Reprints, 1941)
A Medieval Home Companion: Housekeeping in the fourteenth century. (from  Le menagier de Paris) Trans. & edited by Tania Bayard. (NY: HarperCollins, 1991)
Culpeper, Nicholas. Culpeper’s Complete Herbal. Published by W. Foulsham & Co, New York. ISBN: 0-572-00203-3.
Culpeper, Nicholas. The English Physitian, online through Yale Medical Library:
Dioscorides Pedanius, of Anazarbos. The Greek Herbal of Dioscorides: illustrated by a Byzantine, A. D. 512; Englished by John Goodyer, A. D. 1655; edited and first printed, A. D. 1933, by Robert T. Gunther … with three hundred and ninety-six illustrations.
Hildegarde of  Bingen. Hildegard von Bingen’s Physica: the complete English translation of her classic work on Health and Healing. Trans. from the Latin by Patricia Throop. (Rochester, VT: Healing Arts, 1998). ISBN 0-89281-661-9
Gerard, John. Leaves from Gerard’s Herball: arranged for garden lovers. edited by Marcus Woodward (Peter Smith, 1990). ISBN: 0844609714 (also available from Dover in paperback, ISBN: 0486223434). Note: any Gerard’s Herbal edited by Woodward is actually an abridgement.

Hill, Thomas. The Gardener’s Labyrinth[: The first English Gardening Book]. ed. Richard Mabey. (NY: Oxford University Press, 1987) ISBN: 0-19-217763-X. Illustrated with reproductions of woodcuts & paintings from a wide variety of sources.

Markham, Gervase. The English Housewife: containing the inward and outward virtues which ought to be in a complete woman…, Chapter III: “Of distillations and their virtues, and of perfuming.” first printed 1615. Published 1986 by McGill-Queen’s University Press, Montreal; edited by Michael R. Best. ISBN: 0-7735-0582-2.

Le Menagier de Paris. translation of cookbook sections by Janet Hinson:

Nostradamus, The Elixirs of Nostradamus: Nostradamus’ original recipes for elixirs, scented water, beauty potions and sweetmeats. edited by Knut Boeser. (Wakefield, RI: Moyer Bell, 1996) ISBN: 1-55921-155-5

“De Ornatu Mulierum /On Women’s Cosmetics.” in The Trotula : A Medieval Compendium of Women’s Medicine . edited and translated by Monica H. Green. (Philadelphia: University of Pennsylvania, 2001)>

Parkinson, John. A Garden of Pleasant Flowers: Paradisi in Sole. (NY: Dover Publications, 1991.) ISBN: 048626758X

Pepys 1047, in Stere htt Well: Medieval Recipes and Remedies from a manuscript in Samuel Pepys’s Library. Modern English version by G.A.J. Hodgett. (Adelaide: Mary Martin Books, s.d.)

Plat, Hugh. Delightes for Ladies. 1594. (Herrin, Ill., Trovillion Private Press, 1942) Note: here are a selection of rosewater recipes from it.

Strabo, Walafrid. Hortulus. Translated by Raef Payne. Commentary by Wilfrid Blunt. (Pittsburgh: Hunt Botanical Library, 1966)

Tusser, Thomas. His Good Points of Husbandry, “Of Herbs and Flowers.” 1557. Published 1931 by Country Life Limited, London; edited by Dorothy Hartley.

A few web resources:

TGSC fragrance information site: (information on various fragrance ingredients)
A History of Fragrance, by Kathi Keville and Mindy Green

Modern safety information can be found in
Julia Lawless, The illustrated encyclopedia of essential oils: the complete guide to the use of oils in aromatherapy and herbalism. (NY: Barnes & Noble, 1995) ISBN: 1-56619-990-5

1998-2004. Last updated July 13, 2004

Copyright Jennifer A. Heise. Contact me via email for permission to reprint:
Permission is explicitly granted for limited reproduction as a printed handout for classes in schools, herb society meetings, or classes or guild meetings in the Society for Creative Anachronism (except to corporate officers and board members of the SCA, Inc.), as long as I am notified and credited and the entire handout is used.
Jadwiga’s herbs homepage:

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Flower Aroma Is a Honeybee’s Chill Pill

by Christopher Wanjek

Aggressive honeybees sting an "intruder" (a leather flag).

Music has charms to soothe a savage breast. And, it seems, flowers can calm an aggressive honeybee.

Scientists in France and Australia have found that angry honey bees are less likely to attack when exposed to certain floral scents, such as lavender, associated with the promise of food. This occurs even when the bees are provoked into releasing odorous pheromones that recruit other bees into a stinging attack.

The reason appears to be that the bees would rather feast than fight, the researchers said. The bees respond more strongly to the smells related to gathering food than to pheromones calling for war. [Images Reveal Honeybee Scouts Searching for Food]

The research provides insight into how chemical signals affecthoneybees’ decision-making, and may also have a practical application in helping beekeepers maintain calm in their hives.

Social bees

The complex social organization and elaborate communication system of honeybees are well-known. Any given hive, or colony, will have a single queen bee, many drone bees that mate with the queen, and a multitude of worker bees assigned very specific tasks, such as foraging, cleaning the hive and protecting the hive.

The worker bees that guard the hive tend to be the most aggressive of the colony, research has shown. When threatened, perhaps by an invading wasp or an intruding human hand reaching for honey, these bees will emit a scent called a sting-alarm pheromone. When other bees in the immediate area catch whiff of this pheromone, they, too, become agitated and prepare to attack the intruder.

But aggression can come at a cost. The worker honeybee will die after using its stinger on a fleshy animal such as a bear or human, because the stinger is torn loose from the bee’s body during the attack.

Angry bees?

To better understand this decision to sting, scientists created an experiment that exposed honeybees to various kinds of odors while a rotating, feathery object agitated the insects. The research was led by Martin Giurfa at the University of Toulouse in France and Judith Reinhard of the University of Queensland in Brisbane, Australia.

As expected, when the bees caught whiff of the attack pheromone, they stung the feathery object. Yet, when exposed to scents such as lavender — even in combination with the sting-alarm pheromone and with the menacing feather constantly brushing them — the bees restrained themselves from attack. The soothing effect of “flower power” was directly related to the appeal of the odor: The more appetizing the odor, the greater its ability to thwart or postpone an attack. [Video: Watch Angry Honeybees Calm Down from Flowery Scents]

Most surprising, Giurfa said, was that newly emerged bees that were raised in different environments — in France and in Australia — responded similarly to odors. This implies that the calming affect is an innate characteristic, he said. Other floral odors used in the experiment were linalool and 2-phenylethanol. [Beautiful Begonias: See Amazing Photos of Flowers]

The power of scents

While the result is important for understanding the effects of chemical signaling at a neurological level, the finding may have direct value for beekeepers.

“We certainly see great potential for applications to beekeeping,” said Morgane Nouvian, first author on the report published today (Dec. 22) in the journal Nature Communications, and a graduate student at the University of Queensland and at the Paul Sabatier University, part of the University of Toulouse.

“Developing a product based on our results — for example a scented hand spray [or] cream, or an odor-releasing device to place at the hive entrance — could certainly help reduce the number of bees stinging while [beekeepers are] handling the hives. This method would be a great alternative to the current use of smoke and repellents, because we would be tricking the bees with something that they actually ‘like,’ and it would thus likely be less stressful for them,” Nouvian added.

Giurfa said his research team subsequently tested these results in the field, applying odors to the front of a beehive. The calming odors reduced the aggressiveness of the bees, which had been agitated by a jiggling flag at the hive entrance.

The researchers said the results cannot translate directly to the effect of odors on humans. There is anecdotal evidence that lavender has a calming effect on people, but this is likely coincidental to the discovery in bees and, if the effect is real, relies on a different biological mechanism, the scientists said.

“The question of whether humans really have a pheromone communication system remains open, in my opinion,” Giurfa told Live Science.

Posted in Biology, Fragrance, In The Garden, Perfumery, Uncategorized, Under the Tree | Tagged , , , , | Leave a comment