Ethics and Safety

Overview

Our program began with a clear and ambitious scientific vision: to create a precise and effective therapeutic for patients with colorectal cancer. Along this journey we came to realize that the end point of truly meaningful innovation is not a flawless curve on a laboratory plot, but whether it can gently reach—and comfort—people living with illness. This is not an engineering project with a predetermined route; it is a record of growth in which ongoing resonance with patients, clinicians, and the wider world keeps reshaping who we are.

From Assumption to Grounded Practice

At conception, we were captivated by the possibilities of synthetic biology. When we asked the basic question of how to deliver a therapy, orally administered engineered bacteria seemed, at first glance, the "optimal" solution—cutting-edge and convenient, and in principle least disruptive to daily life. We envisioned an appealing scenario: patients completing treatment at home, much like taking a daily probiotic. That vision appeared to align perfectly with a patient-first ethos, and with that confidence we moved rapidly into early experiments and formulation work.

The first crossroads arrived quietly during a conversation with Dr. Wang at Zhongshan Hospital. Expecting confirmation of technical feasibility, we instead heard a few sentences that shifted our gaze from Petri dishes to the complex, individual faces in the clinic—reminding us that real-world care is richer, messier, and more humbling than any bench-top ideal.

Figure 1. Discussion with Dr. Wang at Zhongshan Hospital

Dr. Wang (Zhongshan Hospital) reminded us that the principal challenge for our original concept is the wide variation in patients' health literacy and cultural frames, which complicates communication. For an older patient with limited formal education, a targeted agent may be misconstrued as a "poison that can track me," provoking fear and resistance. In many people's mental models, "swallowing live bacteria to cure disease" can sound more frightening than chemotherapy. This is not a gap that simple popularization can close; it touches deep-seated fear of the unknown and culturally shaped habits of acceptance.

Our conversation with Prof. Wang Ran (Hebei Medical University) underscored the point. He emphasized, repeatedly, that patients must have the right to know the composition and use of such a therapy. In other words, patients will—and should—understand the mechanism and use conditions; this cannot be sidestepped or obscured. Reflecting on that, we realized our plan might unintentionally add a psychological hurdle for patients to clear.

This prompted a long pause for self-examination. We recognized a classic error of techno-optimism: equating what we perceive as "convenient" with what patients actually experience as convenient. We had underestimated human complexity—people's cultural backgrounds, knowledge structures, and emotional states. That assumption, in itself, was a form of insufficient respect.

Soon after, our own experiments corroborated—at a physiological level—the rough terrain ahead: orally administered 5-FU was readily degraded by gastric acid, and first-pass metabolism was substantial, sharply blunting efficacy. From a clinical-development perspective, converting the therapy to an oral route would also entail long timelines and high costs to satisfy FDA requirements and run trials, making it an ill-suited path for an iGEM project.

We therefore acknowledged that our initial route was not feasible to pursue. For a time the team felt adrift; some proposed reverting to standard intravenous administration. But renewed listening sessions with patient communities led us to reject that option as well. Interviewees spoke not only of hair loss and nausea but also of the weekly commute for infusions, needle anxiety, and a steep decline in quality of life. Our mission, we realized, is not merely to extend life, but to safeguard its quality and dignity. Rather than oscillate between two imperfect, familiar options, we chose to open a new path—one grounded in empathy.

Lesson learned: From "assumed convenience" to humble respect for lived experience—that was our first and most important lesson.

Why We Pivoted to Microneedles

Microneedle delivery, initially a backup, became our core platform and a concrete expression of our commitment to patients.

Painless microinvasion soothes bodily suffering. At-home self-application helps people step out of the entrenched "patient" role and re-enter family and everyday life.

Figure 2. Flexible Bioelectronic Microneedle Patch (FBMP)

Our team's flexible bioelectronic microneedle patch (FBMP) integrates a responsive materials system and embedded sensing on top of a microneedle array to exert precise control of drug release—a design that embodies our patient-first ethos. The patch connects to a smartphone via Bluetooth; a flexible printed circuit board (FPCB) provides PWM-controlled heating to modulate film temperature and thereby tune the release rate. Through the companion app, users can set timing, temperature, and pulsing frequency; once parameters are configured, the system initiates heating and release automatically and displays real-time status. Operation logs are stored and may be uploaded to the cloud for clinical follow-up and individualized treatment assessment.

Unlike conventional microneedles or patches that deliver in a single burst, FBMP's remote control and data capture greatly enhance dosing precision and flexibility, making it well suited to home therapy, post-operative management, and long-term chronic care. The system's intelligent, customizable, and lightweight design reduces discomfort and mitigates the practical constraints of traditional modalities—an expression of our commitment to humane, patient-centered engineering.

We deliberately selected biodegradable polylactic acid (PLA) as the microneedle substrate. After use, the tips dissolve within skin or fracture, eliminating needle retrieval and cross-infection risks, and reducing sharps waste. This choice advances cost containment and coverage goals while reflecting our environmental stewardship as early-career scientists.

"Guarded Intelligence": Redesigning ACPP for Control and Safety

With delivery solved, we advanced to activatable cell-penetrating peptides (ACPPs)—and, following further dialogue with clinicians, re-examined risk. As Dr. Wang emphasized, targeted agents may be safer than chemotherapy but not risk-free; off-target effects arise from target biology and can affect normal cells. If our ACPP achieved exceptional penetration without discriminating friend from foe, it would still risk non-selective injury—a violation of the ethical imperative to first, do no harm. Power demands wisdom and constraint.

Guided by these principles—and with input from Prof. Li Yong (ethics) and technical advice from Prof. Wang Qi on histidine protonation—we overhauled the design:

These revisions raised the hemolysis-toxicity threshold from 25 µM to 200 µM—an eight-fold improvement—transforming a mere boost in metrics into a design philosophy: from the mechanics of killing to the ethics of safeguarding the host.

Reassuring Companionship: System-Level Privacy and Governance

When molecules and device converged, the FBMP intelligent therapy system took shape. Feedback from a joint forum with the Tsinghua and Beijing Normal University iGEM teams highlighted a dimension we had not fully addressed: data privacy. If therapy can be app-monitored and app-controlled, who owns the data and who can see it?

Our final iteration closes not only the technical loop but the ethical loop:

In sum, our pathway—from delivery hardware to molecular logic to data governance—reflects a single throughline: patients first, safety foremost.

Figure 3. Discussion with Professor Chong Zhang of Tsinghua University

Our proposed risk-mitigation safeguard was affirmed in conversations with Professor Chong Zhang of Tsinghua University. In these exchanges, Professor Zhang repeatedly underscored the primacy of patients' privacy in the era of big data and reminded our iGEM team that personal information must be protected with rigor.

Figure 4. Continued discussion on data protection measures

After hearing our plan for data-privacy protections, he expressed support and urged us to think more deeply—about where residual risks to patients might still arise and about what more our project could do to serve their interests.

Looking back, we realize that the project's final form has already moved beyond our initial scientific conception. It has been shaped by the voices of patients, refined by the judgment of clinicians, and corrected by the thoughtful cautions of our peers. We are no longer merely creators of technology; we are also attentive listeners and stewards of shared values. We believe this is the most compelling promise of synthetic biology: that, with code and cells, we may help author a warmer future—one grounded in life, respect, and hope.