Andrew Huberman - Dr. Noam Sobel

1) Dr. Noam Sobel discusses the concept of smart drugs and how there is no neural circuit in the brain for being smart, only circuits for things like focus, memory, creativity, and task-switching. Sobel explains that nootropics are designed to enhance specific brain states by targeting different neural circuits, and he directs listeners to take a quiz on the Thesis website to receive a personalized starter kit. Sobel goes on to explain how the olfactory system works, including the role of receptors in the olfactory epithelium and the process of retro-nasal olfaction.

2) Dr. Noam Sobel discusses the number of olfactory receptors in the nose and an amusing story about how the number of receptors in Bloodhounds was drastically exaggerated to a billion in numerous textbooks. This highlights the propagation of incorrect scientific information in the field. He then explains how odors interact with these receptors through transduction, which produces a neural signal that travels via the olfactory nerve to the olfactory bulb in humans. The olfactory nerve's passage through the cribriform plate presents a point of sensitivity as a hit on the back of the head cans hear the olfactory nerve and lead to loss of smell permanently.

3) Noam discusses the possibility of recovery for individuals who have lost their sense of smell due to injuries or viruses such as COVID-19. If the sense of smell is completely severed, there is no chance of recovery, but partial damage or something showing up soon after the injury means there is a good chance of recovery. The rule of thumb is that if the sense of smell is not recovered within a year to a year and a half, it is unlikely to return. Dr. Sobel also mentioned the use of alpha lipoic acid as an over-the-counter remedy that can accelerate the recovery of sense of smell.However, he emphasizes that olfaction is a "use it or lose it" system and that olfactory training programs, which involve constantly and intentionally smelling different scents to keep olfactory neurons electrically active, have proven to be more successful than the use of alpha lipoic acid.

4) Noam discusses neuroregeneration in the olfactory system, noting that olfactory neurons are the only neurons to consistently do so in adult mammalian brains. While there is debate regarding whether the human olfactory system shows the same level of regeneration as other mammals, a study using postmortem analysis of adult brains exposed to atomic bomb experiments suggested there is not as much turnover in the human olfactory bulb. Sobel delves into the extreme case of convergence in the mammalian nervous system and how receptors of one subtype converge to one location in the bulb called a glomerulus, reflecting its receptor identity in its map.

5) Noam discusses the close link between smell and memory, as well as the direct route that olfaction takes to the memory centers compared to other sensory stimuli such as sound waves. Sobel's lab published a study on the privileged representation of early olfacturers associations, which found that the first exposure to a smell generates a particularly robust representation that etches it into our being. There appears to be something special about olfaction and first olfactory experiences that creates strong memories, although this does not discount the uniqueness and importance of other senses such as vision or audition.

6) Noam discusses humans' remarkable sense of smell capabilities and the example of tracking odors like a dog. He explains how humans have a detection threshold of 0.2 parts per billion, which is remarkable in the mammalian world, and how participants in his lab were able to detect an odorant mixed at 10 to the negative 12 molar in the liquid phase. Additionally, he shares the story of the lab picnic where they blindfolded a graduate student and had her track the path of a chocolate bar across the grass, which she did very effectively.

7) Noam discusses an experiment that he conducted where participants were blindfolded, their ears were blocked, and they were wearing heavy gloves while following an odor trail. The trail was generated by burying odor impregnated twine under the grass to create a consistent odor path. Participants also wore a sensor pack that measured nasal airflow in real-time and RTK GPS was used for millimeter resolution tracking of behavior. They found that people could track the odor trail, and when they were trained, the speed at which they crawled became the rate-limiting factor. They also investigated the effects of having two nostrils versus one big nostril by constructing a nasal prosthesis, and found that people performed better with two nostrils.

8) Noam discusses his experiments examining yoga teachers' abilities to control the airflow in each nostril by thought. He found that none of the 14 yoga teachers in the study could willfully switch between left and right nostril airflow. They believed they could, but Sobel suggests they were not intentionally lying. Sobel's experiments are exploring why the alternating nostril airflow phenomenon occurs and whether it has anything to do with preferential processing of olfactory information on either side of the brain.

9) Noam discusses the "sniffing brain approach," which suggests that nasal inhalation has a significant impact on neural activity and cognitive processing. The theory is founded on the fact that the mammalian brain evolved from olfaction and is dependent on sniffing. Thus, information processing is inextricably linked to nasal inhalation, which can influence brain processing beyond olfactory information processing. Sobel cites a study that tested visual spatial processing on inhalation versus exhalation and found that people performed significantly better on inhalation.

10) Noam discusses how loss of the sense of smell is one of the earliest signs of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Although olfactory loss is an early sign of neurodegeneration, it is not a diagnostic tool due to its non-specific nature since individuals can lose their sense of smell for many reasons. Sobel also explains a theory that suggests Alzheimer's disease may be the result of a pathogen that enters the brain through the olfactory system. However, olfaction has not been effectively digitized, which has prevented olfactory tasks from becoming standard clinical tests. While a test called the University of Pennsylvania smell identification test exists, it has its limitations and has not been digitized to the same precision as visual or auditory stimuli.

11) Noam discusses his research on handshaking and the olfactory behavior that follows it. He explains that there is still no good evidence for the belief that handshaking is meant to show that one is not holding a weapon. Through a study published in E-life, Sobel and his team discovered that people tend to touch their noses and faces more frequently after handshaking compared to a control group that did not shake hands. The results showed that this was an olfactory behavior, proven through a James Bond-like device with pleasant and unpleasant odors. This research provides insight into an everyday behavior that has gone unexplained until now.

12) Noam discusses a study on the phenomenon of "click friendships," where people immediately become close friends upon meeting. The study hypothesized that similarity in body odor may contribute to this phenomenon. Researchers recruited same-sex, non-romantic pairs of click friends and found that their body odor was more similar to each other than expected by chance. To address causality, total strangers were also recruited, and although the hypothesis that people who smell more similar would perform better in a mirror game did not pan out, the study did confirm that click friends' body odor was more similar to each other than to non-clickfriends or strangers.

13) Noam discusses an experiment where people were not allowed to speak to each other, but played a round-robin game and ranked each other on how much they think they would want to be friends with each other, and how nice and affectionate they think the other person is. The results showed that people who smell more similar to each other are more likely to think of the other person as their friend or as a nice person. Dr. Sobel explains that this plays into the causal elements of building friendship, and reveals that people are constantly smelling themselves and others, which he calls the "low effect."

14) Noam describes the importance of the secondary olfactory system in mammals, which is used for reproductive and aggressive behavior. The system is linked to the accessory olfactory bulb and then to the limbic system, which controls such behavior. He then introduces the Bruce effect, which occurs when a pregnant mouse is exposed to the odor of a non-stud male and causes her to abort the pregnancy. This effect is mediated by chemosensation, and experiments show that it is completely dependent on the vomeronasal organ.

15) Noam talks about the Jacobson's organ, or the formerly known as organ, that is considered vestigial and non-functional. However, there is a suspicion that humans may experience something similar to the Bruce effect, wherein humans may have a Remnant Bruce effect due to the enormous number of miscarriages that occur in the first trimester. A study was conducted on couples experiencing unexplained repeated pregnancy loss, and the results showed that male partners had a decrease in testosterone levels when smelling the shirt of their partner during ovulation, which suggests that smells do influence our hormones, health, and behavior.

16) Noam discusses his research on unexplained repeated pregnancy loss and how olfaction may play a crucial role. He hypothesized that there may be a Bruce effect, which implies that the female must have a pronounced olfactory memory to know whether the fetus is non-father to prevent a miscarriage. Dr. Sobel's study found that women who experience repeated pregnancy loss can identify their spouse's body odor with much greater accuracy than the typical person.

17) Noam discusses the challenges of defining pheromone effects in humans and how chemosensory signaling between individuals can affect each other's physiology and behavior. Although there is debate among "mouse people" and "insect people" over whether humans exhibit pheromone effects, humans emit chemical signals from their bodies, referred to as chemo-signals, that can influence each other. One example of this is the "smell of fear," emitted by humans in a state of fear that can influence other humans, increasing their autonomic arousal and sympathetic state. Dogs can also smell human fear, as shown in a study about a year and a half ago. Additionally, romantic partners leaving articles of clothing with each other's scent is common in marking territory, and smelling the article of clothing can bring about positive connotations of the other partner.

18) Noam shares personal experiences of how the sense of smell has influenced his behavior, such as his preference for certain body odors over perfumes. He also highlights how losing the sense of smell for even a short period of time can cause intense fear and grief. The sense of smell plays a crucial role in basic behaviors that sustain us, such as choosing what to eat and picking romantic partners. The importance of the sense of smell is further discussed in relation to children, the breath of romantic partners, and how smells can influence our emotions during a breakup.

19) Noam discusses an experiment involving a game in which participants can blast their opponent with a loud noise. This game was used to quantify aggression in participants while they were exposed to hexadecanal, a semi-volatile compound that has a very weak smell and is difficult to detect. The results of the experiment showed that hexadecanal consistently reduced aggression in men, but increased aggression in women.

20) Dr. Noam discusses Martha McClintock's study on whether menstrual cycles become coordinated among women who spend time together and the role of olfaction in this. McClintock noticed that her menstrual cycle and her co-inhabitants in her dorm room were coordinated in time. She conducted a study in which she collected sweat from donor women and deposited it on the upper lip of recipient women, and found that the sweat taken from the follicular or ovulatory phase of the donors extended the cycle in recipients and one shortened the cycle in recipients, indicating a chemosignaling effect.

21) Noam discusses his interest in replicating a study on the influence of smells on hormones, health, and behavior. He explains the uniqueness of olfactory effects in humans, indicating that they could produce a real biological phenomenon compared to the arbitrary associations made by people with oxytocin. The conversation moves on to discuss sobel's lab paradigm of creating fear by throwing people off airplanes and the media they use which is sweat. They are working on generating fear as part of a collaboration with the Israeli paratrooper brigade and collecting body odor from first-time jumpers.

22) Noam discusses the challenge of studying fear and bodily media in humans, which could provide insight into social chemosignaling. While urine is a common bodily fluid used for communication among terrestrial mammals, experimenting with smelling urine in humans is not feasible. Therefore, Sobel and his team turned to researching emotional tears as a potential chemical signal. They collected emotional tears from volunteers, and to their surprise, there was a gender bias with only one male participant. Sobel believes that this is due to a cultural stigma around men crying easily. They hypothesize that the function of emotional tears may be a chemical signal and are researching further.

23) Noam discusses his lab's study on the effect of tears on hormones in men. The lab screened volunteers who could easily cry and ultimately found six women who could consistently shed tears in the lab. The lab collected a full mL of tears in 15 minutes from these women, focusing on the tears' effect on testosterone levels. The study found that within 20-30 minutes of sniffing the tears, there was a 14 drop in free testosterone, the active form of testosterone. The tears were completely odorless, yet they still had a pronounced effect on hormone levels when men sniffed them.

24) Noam talks about a study he conducted on how smelling tears can affect testosterone levels, brain activity, and behavior. The study found that smelling tears can lower testosterone and dampen brain activity in under an arousing state. Additionally, the team discovered that the chemo-sensory system pathways of smelling tears can lower aggression in men. Sobel discusses the challenges of replicating studies and how a lab in Holland did not like their original tear story. However, he also notes that after they did some work, more or less identical effects were discovered in rodents.

25) Noam discusses how tears can lower aggression in male adult mice and how scientists have found the actual component in tears that lowers aggression. He compares tears to a chemical blanket that animals use to protect themselves against aggression. The conversation then shifts to the topic of tears and oxytocin in dogs, and how dog owners often feel attached to their pets in the same way that they do to their children. Dr. Sobel also talks about a study that claimed to show the effect of tears on human arousal, but he notes that it was not replicated successfully, and he offers to fund a new study to replicate the findings, but the authors decline.

26) Noam talks about his experience publishing a rebuttal to a study on the effect of testosterone, which had supposedly failed a replication on behavior. Despite advice from a colleague not to publish the rebuttal, Sobel reanalyzed the data and uncovered something that had been hidden. He shares his thoughts on the sociology of science, where egos are strongly woven into the game of seeking facts. Sobel also discusses the role of smell in signaling the nutrient contents of foods, as well as the importance of collaboration and his experience living above the Cheeseboard in Berkeley.

27) Huberman and Sobel discuss whether there are subconscious signals that the olfactory system has learned to seek for nutrient value in smells. They mention how the scent of food can increase the likelihood of ingesting important nutrients and the potential for this idea to be applied to highly processed foods. Sobel admits that he doesn't have a good answer for this, but it's a good idea that should be looked into. He also mentions an anecdote where two companies approached his lab asking for help to make engineered meat smell like real meat.

28) Noam discusses how similarity is the most crucial factor in measuring sensory systems. By rating pairwise similarity between odorants, a similarity matrix can be created to describe an individual's perception of smell regardless of the name or order of odorants presented. Sobel explains that humans are most dissimilar in color vision, but in olfaction and audition, we are all fairly similar. Furthermore, Sobel explores the possibility of generating smells in silico through computers, which could lead to richer sensory experiences and drive decision making. Although Google had previously released an April Fool’s joke about "Googlesmell," the company has been trying to create an interface for generating smells, and Sobel believes it is something that will be achievable in thefuture.

29) Sobel discusses the development of a startup called Osmo, which aims to digitize smell, and the importance of the awareness of the sense of smell due to COVID-19. He explains the efforts of his lab in developing a set of rules that link odor structure to odor perception and theirrecent break through on this front, where they could predict the perceptual similarity of any two molecular mixtures with very high accuracy using an algorithmic framework. The result highlighted the generation of olfactory metameres or mixtures with zero molecules in common but smell exactly the same.