Integrated Human Practices

The Human-Centered SynBio Ethos of Team WLSA

Introduction

From its inception, Project LEGO was driven by a core belief: transformative science must be rooted in societal need and shaped by continuous dialogue. Our Human Practices (HP) journey was the central narrative strand, a dynamic and iterative process that intimately connected our lab work with the real world.

We moved beyond a mere checkbox exercise, embracing a philosophy of "Co-Creation and Responsive Innovation." This approach ensured that every aspect of LEGO—from the initial concept of a light-switchable dual-hormone system to its envisioned future as an implantable device—was scrutinized, validated, and refined through engagement with a diverse array of stakeholders. Our story is structured around four pillars—Inclusivity, Education, Entrepreneurship, and Sustainability—that together form a compelling chronicle of how we endeavored to make LEGO a responsible and impactful solution for the global challenge of diabetes and obesity.

Identifying the Problem: The Impetus for Project LEGO

Our journey began not in the laboratory, but with a critical examination of a global health crisis. Through an extensive review of the World Health Organization (WHO) reports and the International Diabetes Federation (IDF) Atlas, we were confronted by staggering figures: over 500 million people living with diabetes globally, a number projected to rise sharply, with Type 2 Diabetes (T2D) constituting the vast majority. We learned that T2D and obesity exist in a vicious cycle, each exacerbating the other, and together they significantly increase the risk of cardiovascular diseases, kidney failure, and blindness, placing an immense burden on healthcare systems and individuals' quality of life.

This desk research revealed the limitations of the current therapeutic landscape. While effective, medications like insulin and GLP-1 receptor agonists often operate in isolation—a single-target approach that fails to address the intertwined nature of dysregulated blood sugar and weight gain. We were particularly struck by the pervasive issue of low patient compliance, frequently cited in clinical literature as being driven by the invasiveness of injections, the complexity of multi-drug regimens, and the psychological burden of chronic disease management. The recent success of dual-action drugs like IDegLira,IGlarLixi and Soliqua confirmed a crucial insight: the market and patients were desperately seeking integrated solutions. This foundational research crystallized our mission: we needed to develop a therapy that was not only effective but also non-invasive, combinatory, and patient-centric. This was the genesis of Project LEGO—a direct response to a clearly defined and pressing global need.

Strategic Pivot Informed by Expert Consultation: From External Illumination to Endogenous Bioluminescence

In the earliest conceptual stages of Project LEGO, our initial design relied on an external blue light source to activate the optogenetic switch. To pressure-test this core premise for translational feasibility, we consulted Professor Xu, a specialist in biomedical optics and translational bioengineering at Zhejiang University. He immediately identified a fundamental biophysical constraint: the severe scattering and absorption of blue light in biological tissue would limit its effective penetration to mere millimeters, rendering an external light source impractical for illuminating deeply implanted therapeutic cells in a clinical setting. This critical expert insight served as a direct catalyst for a strategic pivot in our core system architecture. Acting on Professor Xu's guidance, we shifted from a hardware-dependent external illumination model to an internally triggered, bioluminescence-driven system. We integrated the NanoLuc (Nluc) luciferase, which produces intense blue light upon binding its small-molecule substrate, furimazine (FFz). This redesign replaced the cumbersome external hardware with a simple, non-invasive oral pill, fundamentally enhancing the project's clinical viability and patient-centricity from the outset.

Stakeholder Analysis: Mapping the Ecosystem for Impact

To ensure our solution was responsibly developed and widely adoptable, we proactively identified and engaged with key stakeholders throughout our project lifecycle. This analysis guided our outreach strategy, ensuring we incorporated diverse perspectives.

Phase 1: Foundation

Global Problem, Local Insights: Learning from International Exchanges

Our initial desk research highlighted the global prevalence of type 2 diabetes and obesity, with countries like the United States, India, and China bearing a significant and growing burden. Coincidentally, our team members had pre-planned educational exchanges to these very regions during the summer, providing a unique opportunity to gain on-the-ground, cross-cultural perspectives. We leveraged these trips to conduct informal interviews and observations, aiming to understand how this global health crisis manifests in different local contexts.

In the United States, a team member discussing dietary habits with a peer was told, "It's a constant battle. Healthy options are often expensive and time-consuming, while processed foods are cheap and everywhere. You can see why it's such a struggle for so many families." This highlighted the profound impact of food environment and socioeconomic factors on disease prevalence.

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In India, a conversation with a local student revealed a different dimension: "There's a cultural shift happening. Our traditional diets were plant-based, but now Western fast food is a status symbol for my generation. We're seeing more diabetes in younger people than ever before." This pointed to the complex interplay between rapid urbanization, cultural change, and health outcomes.

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Within China, our own community engagement echoed these concerns, confirming that the challenge is both universal and intensely local. These firsthand accounts, gathered outside a formal clinical setting, powerfully contextualized the statistical data. They reinforced that diabetes and obesity are not merely biological issues but are deeply embedded in societal, economic, and cultural fabrics. This global perspective solidified our conviction that a successful solution must be adaptable and patient-centric, capable of addressing needs that transcend national borders. It was with this nuanced understanding that we proceeded to structure our formal data collection within our home community.

HP Activity 1: The Patient Survey – From a Technical Idea to a Human Mission

Timeline & Logic (Aligning with Experimental Prep): Prior to our first wet-lab experiment (noted in our notebook as 5.12-5.20), we dedicated ourselves to understanding the problem space from the perspective of those most affected. Our "LEGO" concept—a non-invasive, dual-therapy system—was scientifically promising, but was it what people needed? To move from assumptions to evidence, we designed and launched a comprehensive survey in May.

Goal Specification: The global rise in T2D and obesity reflects not only a clinical issue but also the daily lived experience of millions, marked by management burdens and unmet needs. We believed a transformative therapy must go beyond biochemical efficacy to address holistic patient realities. Accordingly, our survey had two primary goals: first, to quantitatively identify key patient pain points and priorities in current treatment; and second, to raise public awareness of the disease interconnections and the potential of novel technologies like optogenetics to provide integrated, less invasive therapeutic options.

Questionnaire Design & Collection: We implemented a hybrid collection strategy to maximize reach and authenticity. We distributed surveys online via dedicated diabetes forums and WeChat groups, and crucially, conducted in-person surveys at the Zhejiang Hospital several times with the endocrinology department's agreement, engaging directly with authentic patients. This method yielded profound insights into the realities of long-term disease management.

We surveyed 427 individuals impacted by diabetes and obesity to understand treatment challenges and expectations for future therapies.

Age Distribution

Comprehensive coverage across age groups most affected by metabolic diseases.

Gender Representation

Balanced gender representation ensuring diverse perspectives.

Health Status

Substantial patient voice from individuals managing diabetes and/or obesity.

Injection Burden Dissatisfaction

81.5% of respondents expressed moderate to high dissatisfaction with injection-based regimens.

Combo-Therapy Need

72% concerned about weight, but only 34% felt current treatment adequately addressed both blood sugar and weight.

Innovation Openness & Safety Concerns

87% willing to consider novel therapy, but 65% voiced long-term safety concerns about new technologies.

Data-Driven Insight 1: Injection Burden

81.5% dissatisfaction with injections highlighted needle anxiety, social life disruption, and constant mental burden as major issues.

Data-Driven Insight 2: Unmet Combo-Therapy Need

Significant gap between patient concerns about weight (72%) and perception of adequate dual-treatment (34%) validated our dual-hormone strategy.

Data-Driven Insight 3: Innovation Readiness

Strong openness to innovation (87%) tempered by safety concerns (65%) pointed to need for transparent education about gene therapy safety features.

Headline Metrics from Patient Survey

Impact on Project LEGO: This data became our project's North Star, transforming LEGO from technical prototype to mission-driven solution. The overwhelming desire for non-invasiveness cemented our commitment to oral inducer and implantable device strategy. Clear demand for combo-therapy justified our complex scientific endeavor to co-express insulin and GLP-1.

Our Initial Design Solution: Translating Insights into Engineering Choices

Phase 2: Iteration

HP Activity 2: Expert Interviews – Pressure-Testing the Blueprint

Timeline & Logic: As we began building and testing our optogenetic switches (e.g., Confocal Microscopy experiments on Jun 29th and Jul 6th), we engaged in deep dialogues with experts. This corresponds to our planned hp 7.7-7.13.

Doctor Yu

Chief Endocrinologist, Zhejiang Hospital

"Your optogenetic switch is elegant, but clinical translation requires precision. How will you ensure personalized dosing? Bioluminescence intensity from an oral pill could vary greatly between patients based on metabolism and absorption. A one-size-fits-all 'light dose' is clinically irresponsible and potentially dangerous."

The Challenge: Having designed the core optogenetic switch, we needed to understand its clinical applicability. We approached Doctor Yu to pressure-test our system's feasibility for real-world patient care. The central question we posed was: "How can a light-based therapy be safely and effectively integrated into diabetes management?"

Our Direct Iteration (Engineering Response): This was a pivotal moment. The professor's insight exposed the inadequacy of a simplistic "on/off" model. In direct response, we conceptualized and designed a companion software application. This tool would act as an intelligent dose calculator, taking patient-specific inputs (weight, meal size, real-time glucose data from a CGM) to recommend a personalized amount of the oral inducer (FFz). This effectively translates a clinical dosing need into a precise physical input for our biological system. This step is a prime example of Entrepreneurship—thinking about the entire user experience and product ecosystem from the earliest stages.

Mr. Song

T2D Patient for 20+ years

"I don't just need a new drug; I need a system that fits into my life without making me feel like a patient all the time. The constant calculations, the injections, the planning—it's exhausting. A true solution would fade into the background of my life."

The Challenge: While our survey provided quantitative data, we sought deep, qualitative understanding of the patient experience. We spoke with Mr. Song, who has lived with T2D for over 20 years, to learn what "patient-centricity" truly means beyond the data points.

Our Reiteration: This human-centered feedback reinforced our focus on usability and minimal daily burden. It directly influenced our hardware design considerations for the future implant, emphasizing small size, long battery life, and ease of use. It also shaped our software design philosophy towards extreme simplicity and intuitiveness, ensuring the technology serves the patient, not the other way around.

Prof. He

Translational Science Expert

"Have you thought about how you would mass-produce these engineered cells in a GMP-compliant facility? And how will you rigorously characterize the potency and stability of your final product?"

The Challenge: As we looked beyond the lab, we recognized our lack of expertise in the path from a prototype to a product. We consulted Prof. He, an expert in growth factor formulations and translation, to understand the manufacturing and regulatory landscape.

Our Reiteration: This conversation pushed us to think about our project's long-term viability. We began preliminary research into cell encapsulation technologies and bioreactor systems, and we refined our experimental plans to include more rigorous, quantitative assays that would generate data suitable for future regulatory submissions, strengthening our Entrepreneurship and Sustainability pillars.

HP Activity 3: Cross-Team Collaboration with HiZJU-China

Detail & Learning: In July, we held a productive online exchange with the HiZJU-China iGEM team from Zhejiang University. The synergy was immediate, as their project also focused on GLP-1 therapeutics. This provided a unique opportunity for deep technical peer-review. During our discussion, they shared the significant challenges they had encountered regarding the molecular design of GLP-1 analogs, particularly in optimizing their in vivo stability against enzymatic degradation.

Our Direct Iteration (Scientific Response): This exchange directly influenced the details of our Cycle 3: Dual Hormone Expression Design. Inspired by their firsthand experience, we conducted a deeper literature review and ultimately introduced the Gly8 substitution into our own GLP-1(7-37) construct. This strategic modification was a direct result of peer collaboration, significantly enhancing our hormone's resistance to dipeptidyl peptidase-4 (DPP-IV) and thereby increasing its potential therapeutic longevity and efficacy.

Our Contribution: In the true spirit of iGEM, this was a two-way exchange. We detailed the core advantages of our optogenetic control system—its reversibility and spatiotemporal precision—to the HiZJU-China team. We brainstormed with them on the potential of applying such a precise, dynamic regulation platform to enhance their own project, offering them a new technological perspective for their future development. This exchange perfectly embodied the iGEM spirit: we are competitors, but more importantly, collaborators pushing the boundaries of science together.

Phase 3: Education & Engagement

HP Activity 4: Demystifying SynBio through Sustainable Outreach

Timeline & Logic (Aligning with Experimental Phase 2 and beyond): While conducting the critical experiments for dual-hormone expression (7.13-7.18), we recognized our responsibility to educate the public and build trust for emerging technologies like gene therapy.

Action 1: "The LEGO Block of Life" International High School Seminar

Detail: We organized an interactive workshop at WLSA Shanghai Academy, using the intuitive analogy of LEGO blocks to explain complex concepts: "iLID and sspB are like specialized magnetic bricks, and blue light is the invisible force that snaps them together to build a 'command center' (transcriptional activator) inside the cell."

Impact: Pre- and post-seminar quizzes showed a 55% increase in understanding of basic synthetic biology concepts. This direct engagement, a core part of Education, aimed to spark curiosity and demystify gene therapy for the next generation of scientists and citizens.

Action 2: Our Multi-Platform Science Communication Strategy

The Official WeChat Blog (Sustained Dialogue): We committed to a sustainable communication strategy, far beyond a one-off event. Our team's official account became a hub for nuanced science communication. We published a series of deeply researched articles, such as "Obesity and Diabetes: Two Sides of the Same Coin?" which explained the physiological link that our combo-therapy addresses, and "The Evolutionary History of Insulin," which provided context for our work. The cumulative playback volume exceeded 4,000, creating a lasting resource that fosters Inclusivity by making scientific knowledge accessible to a broad, non-specialist audience.

Xiaohongshu (Red Note) Account (Reaching New Audiences): To engage with a different and younger demographic, we established a presence on Xiaohongshu. Here, we translated our core messages into a more visual and engaging format, creating short, fun and interesting short videos that explained the dangers of diabetes and obesity in a relatable way. This platform allowed us to promote health literacy and our human-centered project philosophy to a community we would not have otherwise reached, further expanding our educational impact.

Public Feedback and Project Iteration: This two-pronged approach was not a monologue. The comments and questions we received on both platforms, particularly concerns about safety and ethics mirroring our survey results, directly reinforced our commitment to transparency. It motivated us to dedicate specific blog posts and video content to addressing these concerns head-on, explaining the safety features of our system (e.g., containment, reversibility) in an accessible manner. This public dialogue ensured our Education efforts were responsive and truly community-informed.

Phase 4：Implementation

HP Activity 5: The Genesis of Drylab

Our journey into Drylab began at the 2025 iGEM Exchange Summit. While presenting our foundational LEGO biological system, we were struck by a recurring theme from other top teams: the critical importance of the implementation bridge—the often-overlooked step that connects a brilliant lab prototype to a real-world application. We realized that our light-controlled therapeutic system, while scientifically elegant, would remain a conceptual novelty without a practical, user-centric method for control and delivery. This crucial insight, gained directly from the iGEM community, became the impetus for our Drylab component.

Market Research

To ground our Drylab development in concrete evidence, we conducted comprehensive market research.

Action 1: Analysis of Diabetes Management Applications
We scrutinized leading insulin dose calculators and glucose tracking apps, identifying common patterns:
Apps like "InsulinCalc" & "DoseHelper":
Weaknesses: Lacked numeric input validation, used ambiguous terminology, failed to reliably update outputs.
Apps like "SugarBalance":
Weakness: Functioned as passive logbooks, lacking active therapy management for combination regimens.

Action 2: Investigation of Optogenetic Hardware.
We researched commercial light stimulation devices (e.g., CoolLED, Thorlabs):
Weaknesses: Bulky, non-portable, prohibitively expensive, and lacked wearability.

Findings:
Our research revealed a significant market gap. Existing diabetes apps were largely passive or functionally unsafe, while laboratory optogenetic equipment was clinically impractical. Patients explicitly desired active, transparent, and personalized management tools. This analysis crystallized our core requirement: an active, trustworthy control unit that was wearable and integrated seamlessly into a patient's life.

HP Activity 6: The Initial Drylab Design

Our findings directly informed the initial design specifications:

This led to our first integrated Drylab prototype: the DíaPlan (Software) paired with the DiaLight (Hardware).

Expert Refinement with Dr. Xuelian Zhou

The Challenge: We presented our system to assess its clinical applicability, focusing on how its recommendations would be integrated into varied patient care scenarios.

Insight: Dr. Zhou affirmed our approach but identified a crucial limitation: "Your software demonstrates sound computational logic, but clinical practice demands flexibility. Treatment regimens must be adaptable to individual patient responses and evolving clinical guidelines. A rigid, automated system that doesn't allow for professional oversight and adjustment could be clinically unsafe and would not be adopted."

Iteration: This feedback was transformative. It prompted a fundamental enhancement to our software architecture that was not part of our initial blueprint:
We designed and implemented an Adaptive Rule Configurator. This module allows healthcare providers to view, adjust, and override key variables within the calculation formulas. For instance, the insulin sensitivity factor—initially auto-calculated from weight and age—can now be manually set to reflect a physician's clinical judgment or specific patient conditions.

Conclusion

Our Drylab development exemplifies a responsive engineering process, shaped by continuous external engagement. It began with broad inspiration from the iGEM community, was focused by rigorous market analysis, and was critically refined through clinical expertise. The creation of the Adaptive Rule Configurator, directly motivated by Dr. Zhou's feedback, stands as a testament to this process. This feature ensured that our system respects the crucial role of clinician judgment, making it not only technically sophisticated but also clinically viable. By meticulously designing this interface, we have ensured the LEGO therapy is grounded in real-world usability, safety, and a deep understanding of the clinical ecosystem, moving us decisively from a laboratory concept toward a future of implementable, patient-centered care.

5: Future Plan

HP Activity 7: Synthesizing HP into a Responsible Implementation Model

Timeline & Logic: In August, as we conducted final validation experiments (e.g., hormone bioactivity assays), we synthesized all HP insights into a cohesive and responsible pathway to impact.

Synthesis of Insights

• From Patients: Need for non-invasive, combo-therapy, and minimal life disruption.
• From Clinicians: Need for precise, personalized control, safety assurances, and simplified patient management.
• From Public Engagement: Need for transparency, education, and trust-building around advanced therapies.
• From the iGEM Ecosystem: Need for a practical, implementable device strategy and scalable manufacturing considerations.
• From Market Analysis: A clear opportunity for a solution that simplifies combo-therapy and improves quality of life.

The Integrated Outcome – A Holistic Vision for LEGO

The Product Ecosystem: Project LEGO evolved into an integrated solution: a subcutaneously implanted, encapsulated cell device containing our engineered HEK293T cells; activated by an orally administered, safe FFz pill; and personalized through a user-friendly mobile app and web platform (DíaPlan) that interfaces with the wearable hardware (DiaLight) and continuous glucose monitors.

Entrepreneurship in Action: We developed a preliminary Business Model Canvas and Value Proposition Canvas. We identified a B2B model, partnering with medical device companies for the implant and pharmaceutical firms for the inducer. Our value proposition centers on reducing long-term healthcare costs and improving patient outcomes compared to a lifetime of drug purchases and injections.

Commitment to Sustainability: This model promises a significant reduction in medical waste (syringes, pens, packaging). Economically, it aims for long-term sustainability for healthcare systems by potentially offering a durable treatment option versus chronic care costs.

Inclusivity by Design: The non-invasive oral administration, simplified software management, and discreet wearable device make the technology accessible to a broader demographic, including those with needle phobias or physical limitations.