Abstract
Throughout our Human Practices study, we have investigated traditional, scientific, and cultural perspectives in order to design a safe, effective, and sustainable treatment. At every phase, we reflected on what we learned and how it could be applied to improve our research and design of the project. Through the ongoing cycle of reflection and feedback, Human Practices and Wet Lab activities are deeply intertwined, influencing one another to refine both the scientific and social/cultural aspects of the projects.
We have organized the Human Practice activities into three main phases:
Phase 1: Project Ideation
Field surveys and interviews were conducted. With traditional medicine practitioners, we were further inspired by the focus on Jabara, a fruit native to Kitayama Village in the Wakayama Prefecture. Through actual field studies in Wakayama, we connected our project to regional revitalization and cultural preservation.
Phase 2: Research Strategies
We have conducted several interviews with professors and experts who guided us to refine our scientific approach. This led our research to be based on a yeast-based biotransformation model for narirutin, and the development of wet lab experiments for the fusion peptide drug.
Phase 3: Social Implementation
By improving product usability, aligning with the safety standards JAPOC has suggested, and by engaging with global and governmental perspectives, we ensure that our nasal spray can be both effective and trusted. We haven’t implemented our product in society yet - we are currently concentrating on phase 2 to ensure the synthesized product is truly safe to the human body.
Phase I. Project Ideation
Abstract: Around 70% of the HG-Tokyo team suffers from hay fever, struggling daily due to its symptoms. Since existing treatments for hay fever often cause side effects ranging from drowsiness to a weakened immune system, we set out in pursuit of a safe, effective, and side-effect-free solution. Through interviews and field research, we discovered Jabara, a citrus fruit native to Kitayama Village in Wakayama Prefecture, known for its potential to naturally relieve allergy symptoms.
Field Survey in Drug Store
Hypothesis: This trip to the local drug store could offer insight into current treatment methods of hay fever.
Learning: In Japan, hay fever is often treated using antihistamines and nasal steroids. Kampo medication is also a major component of the Japanese pharmaceutical industry, and could help with a variety of different symptoms.
Implementation: From the observation that Japanese drugstores sell many different kinds of Kampo medication, including those for rhinitis, we focused our attention on Kampo and Traditional Chinese Medicine (TCM), and decided to consult a professional in this area.
Fig.1: Shelf of Kampo effective for hay fever at the Pharmacy
Ms. Penelope Lam and Professor Eric Chan
Expertise: Traditional Chinese Medicine (TCM) practitioners specializing in treating systemic imbalances (ex, Hay fever) through energy-based approaches and herbal remedies.
Hypothesis: While reviewing Japanese pharmacies, we observed that there are many remedies for hay fever using Kampo medicine. Therefore, we decided to consult professional Traditional Chinese Medicine (TCM) practitioners to gain insight into how TCM practitioners treat hay fever, and how we could approach the problem of hay fever.
Learning: The practitioners explained that TCM practitioners often use dried citrus peels (chenpi) to treat hay fever.
Implementation: Learning about chenpi, we researched further to see if there are other natural remedies for hay fever. We then found Jabara, a citrus fruit grown mainly in Wakayama Prefecture in Japan, with proven, yet rather unrecognized, anti-allergic properties and effects against hay fever. We decided to focus our project on Jabara, thinking that this citrus fruit has the hidden potential to be part of an innovative solution for hay fever. To investigate further, we decided to conduct a field study in Kitayama Village to directly engage with the local source of Jabara.
Field Study in Kitayama Village (Jabarise Kitayama & Kitayama Tourist Center)
Expertise: Holds expert knowledge in the cultivation of Jabara as well as its role in the local culture and economy
Hypothesis: Understanding Jabara's local context would solidify a meaningful social purpose for our project.
Learning: From our visit to Kitayama Village, we learned that while Jabara is culturally and economically significant to the people, its therapeutic potential, particularly of narirutin, remains scientifically unverified. This highlighted that our effort could play a major role in providing evidence-based validation of Jabara. We realized that the community sees our research as an opportunity for regional revitalization. The visit reinforced that our project should focus on building public trust in biotechnology and creating social values through connecting with local heritage.
Implementation: The trip helped form a new project narrative of solving a socioeconomic problem of regional revitalization.
Fig.2: The team travelled approximately 8 hours via bullet train and local trains to reach the site.
Fig.3: Image of the human practices team visiting Jabara farm
Fig.4: Image of the human practices team at Kitayama Tourist Center
Fig.5: Image of the human practices team with Jabarise Kitayama’s team
Fig.6: Image of a tour at Jabarize Kitayama Factory
Phase II. Research Strategies
Abstract: Through further consultations with professionals and continued research, we refined our project strategy, shifting to a biotransformation model and selecting yeast as our production host. Furthermore, recognizing the varying severity of hay fever symptoms, we sought to design a different form of treatment to better target patients with severe symptoms. These insights guided the development of two approaches: narirutin biosynthesis and peptide drug development.
Professor Diego di Bernardo from the University of Naples Federico II
Expertise: An expert in synthetic biology and genomic medicine at TIGEM, specializing in assessing the practical feasibility of complex metabolic engineering projects.
Hypothesis: Professor Bernando’s experience could provide a realistic approach to our project’s scope and give us troubleshooting strategies for our narirutin biosynthesis pathway project.
Learning: Our plan to engineer more than ten enzymes into our host organism is unfeasible within the timeline given.
Fig. 1: An image of our member meeting with Professor Diego di Bernardo
Dr. Velia Siciliano from Istituto Italiano di Tecnologia
Expertise: Synthetic biology expert specializing in the engineering of eukaryotic genetic circuits and the cellular machinery required for expressing complex proteins in yeast.
Hypothesis: Dr. Siciliano's expertise could validate our choice of chassis and help us understand the protein folding challenges of expressing plant enzymes in a microbial host.
Learning: Yeast is a far superior chassis to E.coli for our project because its eukaryotic machinery is needed to fold plant-derived enzymes correctly.
Implementation: We were able to finalize our choice of organism and decided to use yeast as our microbial host. (Refer to Narirutin)
Fig.2 : A screenshot of an online meeting with Dr. Velia Siciliano
Desktop research regarding the potential and limits of narirutin
Hypothesis: Narirutin could serve as a safe and effective treatment for allergic rhinitis by reducing inflammation without the strong immunosuppressive effects of steroids.
Learning: Through our research, we discovered that allergic rhinitis has different severity levels, and that narirutin is effective only for mild and moderate cases. Hearing about this, members of HG-Tokyo with severe hay fever explained that we must create a solution that also addresses those suffering with severe hay fever symptoms, in order to fully tackle the entirety of the problem.
Implementation: We decided to design a fusion peptide therapeutic that can specifically target the mechanisms involved in severe allergic rhinitis, aiming to provide a more comprehensive and effective solution across all severity levels.
Desktop research considering the administration method
Hypothesis: Oral delivery would allow convenient administration for both narirutin and our peptide therapeutic while maintaining sufficient absorption and safety.
Learning: We found that narirutin, as a glycoside, shows poor intestinal absorption, and that systemic circulation of our peptide candidates would likely cause immunosuppressive side effects.
Implementation: We decided to formulate our treatment as a nasal spray to improve narirutin absorption through the nasal mucosa and to minimize peptide exposure to systemic circulation, reducing potential side effects.
Juntendo University Faculty of Pharmacy: Dr. Yuuki Takashima & Dr. Tomoaki Kurosaki
Expertise: Dr. Takashima and Dr. Kurosaki and both experts in drug delivery systems who specialize in using nanoparticle encapsulation to deliver peptides across epithelial barriers.
Hypothesis: Nanoparticle encapsulation would be most effective to overcome the limited permeability of our fusion peptide in the nasal mucosa. This meeting could give us insight into how we can achieve nanoparticle encapsulation.
Learning: Nanoparticle encapsulation is incompatible with our design because it blocks protease activation and causes unwanted intracellular uptake, confirming that Cell Penetrating Peptide (CPP) conjugation is the correct delivery mechanism.
Implementation: We decided not to encapsulate our fusion peptide, but to connect a CPP where necessary. This meeting helped us finalize our peptide design (Refer to Fusion Peptide).
Phase III. Societal Implementation
Abstract: Through field research and expert consultations, we consolidated our project’s ethical and practical foundations. From improving hardware inspired by user feedback to aligning with JAPOC standards, we focused on addressing regulatory and public trust challenges. We considered national and international regulations, reinforcing our goal of developing a biotechnology-based nasal spray that is both effective and socially responsible.
Jabarise Kitayama Co.,Ltd
Expertise: A company located in Kitayama Village of Wakayama Prefecture that specializes in the cultivation, production, and commercialization process of Jabara products, and understands consumer challenges like flavor as well as Jabara’s cultural importance to the local economy.
Hypothesis: Their market experience would help us understand consumer and cultural challenges we must address when developing our narirutin-based product.
Learning: A successful product requires solving two interconnected challenges: Overcoming the natural bitterness for consumer appeal, and ensuring our synthetic biology approach respects and promotes the cultural story of Kitayama Village.
Implementation: After considering the two challenges mentioned above, we noticed that there may be other problems we may have to address when creating our solution. To further investigate the potential problems we need to consider, we conducted a user survey.
Fig. 1: Jabaraise Kitayama Logo
Fig. 2: A screenshot of a online meeting with staffs from Jabaraise Kitayama
Online Survey Regarding Nasal Sprays
Hypothesis: While being a common treatment used for hay fever, nasal sprays have the shortcomings of being unpleasant to use. This survey will help us understand the cons of nasal sprays, and help us gain an understanding of how we could create a better nasal spray.
Learning: This survey was sent to the students of Hiroo Gakuen Junior and Senior High School. Out of 108 people who responded to the survey, 22 people (20.4%) have used a nasal spray before, experienced liquid dripping from the nasal cavity to the throat, and found it unpleasant
Implementation: To improve user palatability to address the consumer challenges identified, such as the bitterness of Jabara and the liquid from nasal sprays dripping down the throat, we designed our nasal spray to have a tilt at an angle of 50º so that the spray effectively targets the middle to anterior nasal cavity, minimizing the amount of liquid that drips down the throat. (Refer to hardware)
Japan Pollen Information Organization Council: Professor Enomoto and Professor Shimada
Expertise: Experts from JAPOC who specialize in setting industry standards for the safety of anti-pollen products for the Japanese market. current hay fever preventative measures, as well as years of experience in conducting research and engaging with the public
Hypothesis: Aim to clarify the industry standards for anti-pollen products in Japan and gain insights on how to position our project within the existing market landscape based on effectiveness and usability.
Learning: They provided us with a tangible benchmark for evaluating our product within the broader healthcare industry. Specifically, the JAPOC mark, a certification system created to help consumers identify products that are tried and effective among the many hay fever solutions on the market, is built on two main pillars: Performance and Ease of Use.
Implementation: HG-Tokyo's plans to conduct quantitative scientific experiments to mechanize how narirutin and fusion peptides suppress allergic reactions to prove their effectiveness. Furthermore, we design a low-side-effect nasal spray to meet users' convenience and comfort by using a safe chassis and ensuring our formulation is safe for consumers.
Fig. 3: A screenshot of an online meeting with JAPOC
Tatsumi Shokai Europe, Tatsumi Europe B.V. Head Yasuhiro Shibata
Expertise: He is the managing director of Tatsumi Europe B.V., a trading company based in Rhoon, the Netherlands, and specializes in international commerce and the legal and marketing processes of importing and selling Jabara products in the European market.
Hypothesis: His experience could provide a practical marketing strategy to globally expand the recognition of Jabara and our narirutin-based product.
Learning: His firsthand experience provided us insight into how strict European regulations can create a commercial barrier for Jabara. Entering the European market requires a formal Marketing Authorization from a regulatory body like the European Medicines Agency, and he made it clear that obtaining it is unfeasible without providing clinical evidence of safety and efficacy from trials, and that any health claims on product labelling are forbidden without this approval.
Implementation: We repurposed our scientific goals beyond that of proof-of-concept experiments by acknowledging the future necessity of complying with Good Manufacturing Practice, a set of regulations ensuring that products meet efficacy, safety, and quality standards, and solidifying a more realistic approach to our project’s implementation.
Fig. 4: Screenshot of an on online meeting with Mr. Shibata from Tatsumi Europe B.V.
Dr. Ann Lau, Chinese University of Hong Kong
Expertise: Co-director of the Centre of Bioethics, the Chinese University of Hong Kong, Bioethicist specializing in the practical hurdles of bringing biologics to East Asian markets.
Hypothesis: Given our survey data, we aim to gain communication strategies and informational content to convince users of our product’s reliability and safety.
Learning: Public acceptance leans more on one's trust in the regulatory system, doctors, and the healthcare system over their own scientific literacy, and how bioethics doesn’t just lie in the patients themselves. Moreover, the fundamental ethical dilemma of drug development is balancing patient well-being with the interests of the company manufacturers, and is a responsibility that extends to long-term post-market safety monitoring known as pharmacovigilance.
Implementation: Expanded our focus from public messaging to institutional process, and considered interviewing government agencies such as the Ministry of Agriculture, Forestry, and Fisheries on their market-entry challenges. We finalized our project’s economic model as a “low-cost product” that prioritizes public accessibility over high-margin profits by addressing the dilemma discussed between cost and accessibility.
Fig. 5: Screenshot of an online meeting with Dr. Ann Lau
Ministry of Agriculture, Forestry, and Fisheries, Mr. Kozai and Mr. Okazato
Expertise: The Ministry in charge of biotechnology in agriculture is responsible for overseeing its use, giving public lectures to educate people, and screening food products that use biotechnology to ensure their safety.
Hypothesis: Their knowledge would help us ensure that our approaches complied with safety standards and would achieve understanding from the general public.
Learning: Earning public trust in biotechnology usage is not about persuasion but about transparent communication about the ”safety” of the product. Ethical and social outreach are essential, and when introducing products with biotechnology usage, emphasizing consumer benefit and cultural connection is most important.
Implementation: This meeting finalized our project's public communications strategy in connection with its societal significance. We created posts about Jabara across social media platforms like Instagram and the blogging site “note”, where posts were designed to focus on the cultural significance of our partnership with Kitayama Village and our project's social impact. (Refer to Education)
Fig. 6: Icon of Ministry of Agriculture, Forestry, and Fisheries
Fig. 7: Screenshot of an online meeting with the Ministry of Agriculture, Forestry, and Fisheries
Conclusion
By insights and feedback from continuous interactions with experts and reflecting on our experimental results during each phase, we were able to transform our initial idea into a more practical, socially grounded solution. From discovering Jabara and its potential to developing experimental strategies and evaluating real-world applicability, every interaction helped us refine the final form of our project through both scientific and project design perspectives. Through combining these experimental insights with ethical, regulatory, and practical considerations, we developed a prototype for a biotechnology-based nasal spray that is safe, effective, and socially responsible, offering a possible treatment for hay fever and further allergy symptoms.
