Flavor and fragrance influences the quality of life in a wide range of settings. However, compared to the other senses, namely the visual and auditory senses, their use is relatively unexplored. Professor Kazushige Touhara of the Graduate School of Agricultural and Life Sciences at the University of Tokyo, is a pioneer in flavor and fragrance research. He has been conducting research to establish technology for predicting how people perceive them and for designing flavor and fragrance at will. He is working in industry-academia collaboration to realize people-friendly services and implement the results of his research in society.
Professor, Graduate School of Agricultural and Life Sciences, the University of Tokyo.
Project Leader for the JST-Mirai program since 2017.
Approximately 400 different olfactory receptors: Objective evaluation is a challenge for industrial applications
Flavor and fragrance affect people's psychology, physiology, emotions, and behavior and influence the quality of life in various settings, such as eating, bathing, and sleeping. For example, lavender and chamomile are known to have relaxing and stress-relieving effects. As a result, flavor and fragrance can contribute to fostering a sense of security and enriching the mind by passing on food culture and creating a sense of excitement, among other uses. Nevertheless, its use remains unexplored because the olfactory sense is more complex than the other senses.
While humans have only four different light-sensing receptors, humans have as many as about 400 different olfactory receptors that sense flavor and fragrance. In addition, hundreds of thousands of odorants have been reported. The responses of olfactory receptors to these numerous odorants differ substantially among individuals. For example, the same flavors and fragrances are liked by some people and disliked by others due to "genetic polymorphisms," which are differences in genes. Moreover, experience, culture, physical condition, and other factors affect the perception and preference for different flavors and fragrances. Due to the complexity of the olfactory sense, objective evaluation of the concept of flavor and fragrance is a challenge for industrial applications.
"To effectively utilize the functions of flavor and fragrance, we need to develop technologies for designing and controlling them based on the mechanism of olfactory perception in humans and for evaluating their effects on people," said Professor Kazushige Touhara of the Graduate School of Agricultural and Life Sciences at the University of Tokyo. He has been a leading researcher in the analysis of olfactory receptor functions since his success in measuring the odor responses of olfactory receptors in mice, which had not been demonstrated for many years. To date, he has revealed many mechanisms by which flavor, fragrance and pheromones affect the brain and behavior, including the discovery of pheromones involved in sexual behavior in mice and the elucidation of the mechanism of sex pheromone receptors in insects.
However, Touhara did not intend to study flavor and fragrance from the beginning. When he first entered the University of Tokyo, he wanted to pursue a career in architecture. However, he ultimately selected the Department of Agricultural Chemistry in the Faculty of Agriculture. Then, he became interested in the functions of receptors and hormones. After graduating from the university, he made a bold decision to attend graduate school in the United States. During that time, Dr. Richard Axel and Dr. Linda Buck of Columbia University in the U.S. discovered olfactory receptor genes, and research on odor perception and signal transmission to the brain made big strides. Touhara was so impressed by this discovery that he proceeded with full-scale research on flavor and fragrance as soon as he returned to Japan.
The unique way humans use their olfactory sense: Effective use of functions
Animals and insects use odors and pheromones for communication. Therefore, studying these is important for understanding ecosystems. While many organisms use olfactory sensations for their survival, humans use it more often to make themselves happy with good food and to relax with pleasant flavors and fragrances. Touhara discussed the uniqueness of the human olfactory sense, "Instead of the original way that animals use it, humans mainly use it for wellbeing, or for getting a sense of satisfaction, and that is the clue to effective utilization of the effects of flavor and fragrance."
Since 2012, Touhara has been conducting basic research on odors and pheromones in humans as well as animals as the research director of the "Touhara Chemosensory Signal Project" under the JST's ERATO program. Based on the research results and knowledge gained from this project, "Providing humane services by expanding the function of flavor and fragrance" was launched in 2017 as a JST-Mirai project to realize social implementation through focused research in humans. He envisions "Olfactory DX," which aims to effectively utilize the effects of flavor and fragrance based on evidence using big data and machine learning (Figure 1).
Figure 1:Examples of olfactory DX applications
This project took a composite approach to research on flavor and fragrance, with five Proof of Concept (PoC) goals, including analysis of olfactory receptor responses, deciphering flavor and fragrance information by measuring brain activity, and clarifying their effect on the human mind. Currently, research on aroma and odors covers various fields, from molecular-level research to behavioral change, and covers a variety of issues. Thus, the project has five pillars (Figure 2). Touhara recalls, "As a result, individual projects were closely interlinked and synergistically produced the results."
Figure 2:Five pillars of the project toward PoC and the results
A large-scale questionnaire survey was conducted — Visualization and prediction tools created
Various individual research results on "human body odor" were obtained. One of them concerns the role of body odor in mother−child communication. Touhara and his colleagues analyzed odorants collected from the heads of mothers and children and found that some components were discharged more by the babies than by the mothers. When these components mixed at the same ratios as the discharge from the baby's head were smelled by the mothers, it was found that the secretion of "oxytocin," a hormone related to affection increased.
Other results are related to body odor between men and women. Men find the armpit fragrance of women produced during ovulation pleasant; however, there were issues, such as non-reproducibility of the results. Therefore, Touhara and his colleagues analyzed the axillary odors of women during different phases of a menstrual cycle and confirmed that the fragrance during the ovulation phase, during which the female hormone estrogen is at its peak, had positive psychological effects on men. "We have found that certain fragrances have positive effects on communication. The findings may promote family bonding and a sense of security."
Genetic polymorphisms influence the perception of flavor and fragrance. To determine whether genetic polymorphisms found in many people have effects on the olfactory receptor activity, Touhara and his colleagues extracted the genetic polymorphisms and actually exposed them to odorants to observe the activity. Simultaneously, in cooperation with the NTT Data Institute of Management Consulting, they conducted a questionnaire survey to ask approximately 1,000 people in their 20s or older in Japan "how they felt about the flavor/fragrance," and found multiple new genetic polymorphisms related to their perception. Thereafter, they combined a database of flavor and fragrance and human information to create a tool for visualizing and predicting responses (Figure 3).
Figure 3:Visualization and prediction tool for flavor and fragrance responses
Prediction of flavor and fragrance from brain activity is difficult — Successful measurement with electroencephalography and "fMRI"
Touhara and his colleagues also established a decoding model for predicting flavor and fragrance from brain activity. "Decoding" refers to a technique that measures brain activity and uses measured signals to deduce perception, thought, and other functions. This technique is often used in visual and auditory perception research, and research on decoding has recently advanced. Although accurate presumption has become possible in visual perception, decoding olfactory perception is difficult, and research has not advanced.
In response to this, Touhara and his colleagues combined electroencephalography with functional magnetic resonance imaging (fMRI) to measure brain activity during the perception of flavor and fragrance. The results suggested that the type of flavor and fragrance being smelled could be decoded from the electroencephalogram recorded while the subject smelled it for one second, and that the signal sources were the middle temporal gyrus in the right brain, the inferior frontal gyrus in the left brain, and other brain regions such as the insula. These results provide new insights into the process of conversion from flavor and fragrance information to perception. This is because abnormalities in the olfactory sense have attracted attention as one of the signs preceding Parkinson's disease, a neurological disorder, and there is a need for a non-invasive method to evaluate olfactory processing in the human brain.
Moreover, measurements using fMRI revealed that when a flavor/fragrance was presented at the same time with words to evoke them, the activity pattern in the primary olfactory cortex changed depending on the words presented, even though the flavor/fragrance presented was the same. If these changes in the activity pattern can be clarified, including what happens when words alone are presented and when something other than words is presented, it may be possible in the future to virtually perceive flavor and fragrance in the absence of odorants (Figure 4).
Figure 4:Brain activity in response to flavor and fragrance
A study group established to exchange ideas: Progressing toward social implementation
Regarding food flavor and fragrance, Ajinomoto has played a central role in constructing an "olfactory database" based on fragrance components and the olfactory receptors that responds to them since before the start of the JST-Mirai project. In this project, they constructed a map to visualize flavor and fragrance for improving the usability of the olfactory database. Furthermore, they developed a flavor and fragrance prediction algorithm to enable prediction based on receptor activity information. The digitization of a series of flavor and fragrance is expected to be implemented for efficient flavor development in the future.
When the full-scale research for this project began in 2019, Touhara and his colleagues launched the "Flavor and Fragrance 4.0 Study Group," bringing together researchers and planners from companies. This is a forum for people with expectations of, and an interest in, the effective use of flavor and fragrance to share knowledge and information and to exchange ideas across industries and fields. For some time now, companies have consulted with them about the use of flavor and fragrance; however, many topics of consultation were vague and were not followed through. However, a concrete idea of what the issues are was drawn out through participation in the study group. As a result, joint research projects with many companies have been initiated, and further progress has been made toward social implementation.
Touhara was initially interested in architecture and space design when he entered university, but he chose agriculture, which is a completely different field of study. He pointed out that understanding the odors and pheromones that control animal ecosystems and designing comfortable flavor and fragrance spaces for people are consistent with the goals of agriculture, such as promoting positivity towards nature and wellbeing. "In fact, there are many points in common with architecture that is about designing spaces, which was my interest when I was in college, and I think my research is in line with my thoughts at that time. Moving forward, I want to expand my work to cross modal research, particularly on the senses" (Figure 5). We look forward to Touhara's future research activities.
Figure 5:Objectification of the senses aimed for by Touhara and colleagues
(Article: Sachiko Ito, Photography: Hideki Ishihara)
