Dr. Noam Sobel: How Smells Influence Our Hormones, Health & Behavior

Dr. Noam Sobel on Olfaction and Chemosensation

• Olfaction: sense of smell
• Chemosensation: ability to respond to chemicals in the environment
• Humans are incredibly good at sensing the chemical world around them
• We process information about other people’s chemicals (stress levels, hormone levels, etc.) subconsciously, impacting our emotions, decision making, and relationships
• Tears can impact our hormone levels
• We are always sensing our own odors, periodically smelling ourselves to change cognition and behavior

Components of Smelling

• Smelling through the nose (orthonasal olfaction) and mouth (retronasal olfaction)
• Retronasal olfaction: odorants come up through the back of the throat and out of the nose the reverse way, contributing to food and taste
• Orthonasal olfaction: sniffing in through the nose
• Airborne molecules travel up the nose and interact with about 6–7 million receptors in the olfactory epithelium
• Humans have about 350 different kinds of olfactory receptor subtypes
• Bloodhounds have a billion receptors in their nose, making them excellent at tracking scents
  Olfactory System and Loss of Smell
• Olfactory receptors in the epithelium undergo transduction 
  • Odorants dock at a receptor and turn into a neural signal
  • Action potentials propagate via the olfactory nerve
• Olfactory nerve synapses at the olfactory bulb 
  • Extreme case of convergence in the mammalian nervous system
  • Receptors of one subtype converge to one location in the bulb (glomerulus)
• Loss of smell due to trauma 
  • Contracu injury: brain movement in the skull can sever olfactory nerve
  • If completely severed, loss of smell is permanent
  • If partially severed or some recovery within a year to a year and a half, there’s a chance of recovery
• Olfactory training can help recover the sense of smell 
  • Keeping neurons active helps maintain connections
  • Smelling various items from the fridge or makeup cabinet can help
• Regeneration in the olfactory system 
  • Debate on the extent of neurogenesis in the human olfactory system compared to other mammals
  • Study using C‑14 levels in adults exposed to atomic bomb experiments to determine turnover in the human olfactory bulb
    Olfactory Abilities in Humans
• Humans have a remarkable sense of smell 
  • Detection threshold for Mercaptans (added to cooking gas for smell) is 0.2 parts per billion
  • Detection threshold for estratetraenol (odorant used in lab) is 10^-12 molar in the liquid phase 
    • Equivalent to detecting one drop in two Olympic-​​sized swimming pools
• Humans can improve their sense of smell 
  • Example: Tracking odors like a dog 
    • Started as a lab bet at UC Berkeley
    • Blindfolded participant successfully tracked a chocolate bar dragged across the grass
    • Turned into an experiment with naive participants 
      • Deprived participants of other sensory inputs (blocked eyes, ears, etc.)
      • Generated a consistent odor path in the grass for participants to track
      • Results showed that humans can indeed track odors effectively, even without prior practice
        Human Olfactory System and Nasal Cycle
• Odor trails created by burying twine under grass for consistency 
• Participants wore sensor packs to measure nasal airflow in each nostril
• RTK GPS used for tracking behavior with millimeter resolution
• People could scent track right away, improved with training
• Performance better with two nostrils than one centralized nostril

Nasal Cycle and Autonomic Nervous System

• Nasal cycle: alternating high and low flow between nostrils every 2.5 hours on average
• Linked to balance in autonomic nervous system (sympathetic and parasympathetic)
• Shift becomes more pronounced during sleep
• Nasal cycle overlooked in neuroscience, could be used as a marker for various diseases

Nasal Halter: Wearable Device for Measuring Nasal Airflow

• Measures airflow in each nostril separately and logs data for 24 hours
• Can be used as a disease marker, e.g., distinguishing between ADHD and non-​​ADHD adults
• Can also determine if an individual is on Ritalin or not

Yoga and Nasal Cycle Control

• Yoga practitioners claim to control the nasal cycle through breathing exercises
• Study with 14 yoga teachers found none could willfully switch between left and right nostril flow
• Unclear if the nasal cycle drives the shift in the autonomic nervous system or is merely reflective of it
• Ongoing experiments to determine the direction of causality, e.g., exposing participants to pain and measuring nasal cycle changes
  Alternating Nostril Airflow Phenomenon
• Not related to olfactory system 
• Nasal inhalation is timing and driving patterns of neural activity and cognitive processing 
  • Evolved from olfaction
  • Information processing linked to nasal inhalation
• Study led by Offer Peril 
  • Visual spatial processing compared on inhalation vs exhalation
  • Better performance on inhalation
• Nasal inhalation shapes cognition 
  • Other labs finding similar results (Christina Zelano, Yuan Lunstrom)

Olfactory System and Neurodegeneration

• Loss of sense of smell is an early sign of neurodegenerative diseases (e.g. Parkinson’s)
• Theory: Alzheimer’s may be the result of a pathogen entering the brain through the olfactory system
• Olfactory tests could potentially track neurodegeneration over time

Olfactory Tests

• Olfaction has not been effectively digitized 
  • Poor control of stimulus
• Standard clinical tests of olfaction: 
  • UPSIT (University of Pennsylvania Smell Identification Test) — scratch and sniff test
  • Sniffing Sticks — European version, pens with odors
• Olfaction not tested in newborns 
  • Congenital anosmia: being without the sense of smell from birth, affects 0.5% of the population
  • Average age of diagnosis is 29 years old
    Congenital Anosmia
• Affects 0.5% of the human population 
• Average age of diagnosis: 14 years old
• Social and health consequences: 
  • Reduced social contacts
  • Reduced romantic social contacts
  • Shorter lifespan (according to Ilona Croix’s research in Germany)
• Most individuals with congenital anosmia have remnants of olfactory bulbs or shriveled olfactory bulbs in adulthood

Link Between Olfaction and Reproduction

• Kalman’s syndrome: hypogonadic development in men, almost all individuals with this syndrome are anosmic
• Olfaction and reproduction are tightly linked in all mammals, including humans

Subconscious Olfactory Identification

• Humans subconsciously identify people by their smell
• Most of this processing is subconscious and not well understood

Handshaking and Olfactory Behavior

• Handshaking is a widespread behavior with unclear origins
• Study by Dan Frooming’s lab observed people touching their face and nose after handshaking
• Suggests that humans may subconsciously use handshaking as a way to gather olfactory information about others
  Handshake Study and Olfactory Behavior 
• Study on handshakes and hand-​​to-​​nose behavior 
  • Participants matched with experimenters of both genders
  • Handshake and no handshake conditions
  • Significant increase in hand-​​to-​​nose behavior after handshake
• Controls to verify olfactory behavior 
  • Measured nasal airflow — participants sniffed their hand after handshake
  • Manipulated odor on experimenter’s hand — drove self-​​sampling behavior up or down

Click Friendships and Body Odor

• Click friendships: people who instantly become close friends 
  • Poorly described in literature, but commonly experienced
• Study on click friends and body odor similarity 
  • Recruited click friends, sampled their body odor
  • Electronic nose used to analyze body odor similarity
  • Click friends had more similar body odors than random pairs
  • Participants also judged click friends’ odors as more similar
• Causality tested with strangers and electronic nose 
  • Strangers engaged in nonverbal social interaction (mirror game)
  • Odor similarity predicted friendship ratings and other positive traits

Smell and Romantic Attraction

• Mice choose mates with most distant immune composition (MHC)
  • Evolutionary advantage: broader immune gene array in offspring
• Humans also show romantic odor preferences influenced by body odor and MHC 
  • Not directly studied in the lab, but related research exists
• Reproduction and romanticism not always the same 
  • Mammalian reproductive behavior dominated by sense of smell
    Olfactory System and the Bruce Effect
• Main olfactory system: cranial nerve number one 
• Secondary olfactory system: 
  • Vomeronasal organ (VNO) or Jacobson’s organ
  • Present in most terrestrial mammals
  • Processes odorants called pheromones
• Bruce Effect:
  • Discovered by Margaret Bruce in 1959
  • Pregnant mice exposed to the odor of a non-​​stud male (not the father) will miscarry the pregnancy
  • Occurs in about 80% of exposures
  • Dependent on the vomeronasal organ
• Human Vomeronasal Organ: 
  • Considered vestigial and nonfunctional
  • Jury still out on its functionality
  • Humans have a high rate of spontaneous miscarriages, especially in the first trimester

Study on Unexplained Repeated Pregnancy Loss

• Participants: Couples experiencing unexplained repeated pregnancy loss
• Hypothesis: Possible Bruce effect-​​like phenomenon in humans
• Findings:
  • Women with repeated pregnancy loss could identify their spouse’s body odor with much greater accuracy than control women
  • No difference in detecting other odors
  • fMRI showed a difference in response to stranger male body odor between the two groups, specifically in the hypothalamus
• Currently seeking ethical approval for a causal experiment
  Pheromone Effects in Humans
• Chemosensory signaling between individuals 
  • Humans emit chemosignals that influence each other’s physiology and behavior
  • The term “pheromone” is problematic and mostly used for insect behavior
  • Researchers prefer to use the term “chemosignals” for humans
• Smell of fear 
  • Humans emit a specific body odor when in a state of fear
  • This odor increases autonomic arousal and sympathetic state in others
  • Fear can be considered contagious through the smell of fear
  • Dogs can also smell human fear
• Smell of safety 
  • Not just the absence of the odor corresponding to fear
  • Romantic partners often leave articles of clothing at each other’s homes, possibly for scent marking territory
  • Smelling a partner’s clothing can bring about positive connotations of the other partner
  • Mourning period post-​​breakup may involve olfactory unlearning
• Hexadecanal
  • A molecule studied in mice as a chemosignal that promotes social buffering
  • Mice emit hexadecanal in their feces
  • The receptor for hexadecanal is highly conserved throughout mammalian evolution, suggesting it may be a universal mammalian signal
    Hexadecanal and Social Buffering
• Hexadecanal promotes social buffering in mice 
  • Hypothesis: Hexadecanal may have similar effects in all mammals due to highly conserved receptor
• Study conducted using the Taylor Aggression Paradigm (TAP)
  • Participants played a game where they divided money with another “player” (actually a computer algorithm)
  • The computer algorithm was programmed to be unfair, provoking anger in the participant
  • In a second game, participants could blast the other “player” with loud noises as a measure of aggression
• Hexadecanal consistently reduced aggression in men, but increased aggression in women 
  • The effect size was quite meaningful and strong compared to other aggression studies
• fMRI study showed Hexadecanal increased activity in the left angular gyrus, an area involved in social appraisal, in both men and women 
  • Functional connectivity from the angular gyrus to aggression-​​related brain areas differed between men and women 
    • Hexadecanal increased functional connectivity in men (reducing aggression) and decreased it in women (increasing aggression)
• Insight: Hexadecanal’s effects make sense for mammalian offspring 
  • Paternal aggression is often directed at offspring, while maternal aggression is often protective
  • A molecule that makes mothers more aggressive and fathers less aggressive is beneficial for offspring
• Hexadecanal is the most abundant semi-​​volatile in baby heads 
  • Babies are reducing aggression in fathers/​​male figures and increasing aggression in mothers/​​female figures, which is beneficial for their survival

Menstrual Cycle Coordination

• Anecdotal evidence suggests that women’s menstrual cycles can become coordinated when they spend time together 
  • Scientific literature on this topic is unclear and possibly contradictory
• Early literature by Barbara McClintock discovered this phenomenon and published a paper in Nature as an undergraduate in 1971
  Menstrual Cycle Coordination and Olfaction
• Martha McClintock conducted a study in 1971 
  • Noticed menstrual cycle coordination among women in her dorm
  • Published findings in Nature
• Follow-​​up study in 1998 by Stern and McClintock 
  • Collected sweat from donor women and deposited it on recipient women’s upper lips
  • Found that sweat from follicular or ovulatory phase donors affected recipient’s cycle duration
  • Results called into question due to statistical complications
  • Majority in the field currently negative, but some researchers still on the fence

Odors, Hormones, and Crying

• Research on human social chemo signaling focuses on the smell of fear and sweat
• Collection of body odor from first-​​time skydivers to study fear 
  • Goal is to find fear molecules and develop potential treatments for anxiety
• Tears as a potential medium for social chemo signaling 
  • Emotional tears emitted in situations where nonverbal communication is key
  • Charles Darwin devoted a chapter to tears in his book on emotions but could not find a functional explanation for them
    Emotional Tears Study
• Study conducted to understand the function of emotional tears 
• Participants who cry easily were recruited
• Emotional tears were collected from participants while watching sad movie scenes
• Tears were odorless, but when sniffed by men, resulted in a 14% drop in free testosterone within 20–30 minutes
• Independent group from South Korea replicated the testosterone effect
• Emotional tears in mice were found to lower aggression in male adult mice towards them in a smell-​​dependent way
• Dogs emit emotional tears when they reunite with their owners, influencing oxytocin in humans

Oxytocin and Attachment to Dogs

• Oxytocin may play a role in the strong attachment humans have to their dogs
• Dogs may hijack the circuitry intended for child rearing through oxytocin
• People can become extremely attached to their dogs, experiencing strong emotions when they are separated or when the dog passes away
  Emotional Tears and Replication in Science
• Emotional tears in humans are not unique, dogs do not shed emotional tears 
• Failed replication of a study on arousal ratings in women 
  • Original researcher offered to collaborate and fund replication, but the other group refused
• Importance of replication in science, but it is rarely a pure replication of the study
• Ego and collaboration in scientific research

Smell and Nutrient Content of Foods

• Unclear if nutrient value of food is systematically encoded in odor
• Olfactory perceptual similarity in metabolic products
• Engineered meat companies seeking help to make their products smell like meat
• Nutrition topics on social media can be polarizing
  Olfactory Perception and Digitizing Smell
• Common misconception: olfactory perception is highly subjective 
  • Studies show humans are actually very similar in olfactory perception
  • Correlation in pleasantness estimates across humans is about 0.8
  • Outliers and poor application of language to olfaction contribute to misconception
• Digitizing smell is an active field of research 
  • Google and other companies working on digitizing smell
  • COVID-​​19 has increased awareness and interest in olfaction research
  • Goal: develop rules that link odor structure to odor perception 
    • Recent progress made by various labs (Leslie Voschall’s lab, Joel Mainland’s lab, etc.)
• Potential applications: search engines providing smells, richer sensory experiences, influencing decision-​​making
  Mini Breakthrough in Olfactory Research
• Paper led by ARN Ravia and Kobe Snitz published in Nature during the COVID pandemic 
• Developed an algorithmic framework to predict perceptual similarity of molecular mixtures 
  • Can predict how similar two mixtures will smell
  • Can design mixtures with known similarities
• Generated olfactory metamers (mixtures with no overlapping molecular structure but smell the same) 
  • Example: Created a Chanel No. 5 metamer with no components from the original perfume
• Publicly available website to generate metamers

Digitizing Smell

• Algorithm predicts similarity, which is enough to digitize smell
• Map of 4,000 molecules with known perceived smells 
  • Can predict the odor of any molecular mixture
• Working on finding a set of components (odor primaries) to mix any perceivable odor

First Odor Transmitted Over IP

• Collaboration with Jonathan Williams at Max Planck in Munich
• Measured odorants in Germany, transmitted information, and recreated them from a device that mixes primaries
• Proof of concept test with four different odorants: 
  • Rose (failed, perceived as bubble gum)
  • Anise (failed, perceived as cherry)
  • Gasoline (slightly better than chance)
  • Violets (15 of 16 people identified correctly)
• First odor ever transmitted over IP was violets
• Current device used for measuring is large and expensive ($1.5 million), but prediction is that size and cost will decrease over time