Human Practices

Overview

Human Practices (HP) served as the "compass" for APOPTO-SENSE 2.0, ensuring our synthetic biology platform for personalized cancer drug sensitivity testing is not only innovative but also responsible, ethical, and aligned with real-world needs. We engaged diverse stakeholders—clinicians, researchers, patients, ethicists, and educators—to iteratively refine our project. This process revealed key challenges in oncology, such as ethical barriers to patient samples and the need for accessible tools in low-resource settings.

Our HP activities were structured in three phases, integrating feedback into the Design-Build-Test-Learn (DBTL) cycle. We prioritized Integrated Human Practices by adapting designs based on expert input ( focusing on commercial PDCs for proof-of-concept). Broader efforts included education, communication, and sustainable impact assessments, emphasizing equity in cancer care. This holistic approach demonstrates how APOPTO-SENSE 2.0 can contribute to UN Sustainable Development Goal 3 (Good Health and Well-Being) by promoting precise, patient-centered treatments.

For project details, see Description and Proposed Implementation.

Integrated Human Practices

We treated HP as an iterative process, where stakeholder insights directly shaped our engineering and experimental designs. Following iGEM's emphasis on responsibility, we conducted virtual and in-person engagements, documenting how feedback led to tangible changes.

Phase 1: Problem Definition and Needs Assessment

In the project's early stages, we identified gaps in current drug sensitivity testing through targeted interviews. This phase focused on defining unmet needs in oncology.

  • Stakeholders Engaged: 5 clinical oncologists (specializing in leukemia and solid tumors), 3 clinical lab scientists, and 2 cancer researchers from local hospitals and universities.
  • Methods: Semi-structured virtual interviews (via Tencent Meeting, 45-60 min each) and surveys (Tencen Forms, n=15 responses). Key questions: "What are the biggest pain points in current drug sensitivity methods?" and "What features would an ideal ex vivo testing platform need?"
  • Key Insights:
    • Pain Points: Traditional biopsies miss tumor heterogeneity (80% of respondents); ex vivo PDC testing is promising but hindered by long timelines (2-4 weeks) and high costs (~$500-1000 per test).
    • Desired Features: Rapid readout (hours-days), low cost (<$100), minimal equipment fluorescence microscope over NGS), and ethical feasibility for patient samples.<$100), minimal equipment (e.g., fluorescence microscope over NGS), and ethical feasibility for patient samples.
    • Ethical Concerns: Direct use of patient tissues requires IRB approval, which is time-intensive for iGEM timelines; suggested using commercial PDCs as proxies.
  • Integration into Project: These insights formed our "Technical Design Specifications" document, prioritizing a fast, fluorescence-based system. We shifted from complex feedback loops to a linear MVP for quicker prototyping, directly addressing timeline concerns. This guided our choice of HL-60 cells as a leukemia model.

Phase 2: Design Feedback and Iterative Refinement

With initial designs in hand, we sought feedback to iterate our synNotch sensor and reporter modules.

  • Stakeholders Engaged: Revisited Phase 1 experts plus 2 bioethicists and 1 regulatory specialist ( from a local IRB committee).
  • Methods: In-person workshops (2 sessions, 10 participants) and feedback sessions with preliminary schematics shared via shared docs.
  • Key Insights:
    • Feasibility: Cell-based systems are viable in clinical labs but must minimize dependencies on advanced equipment ( flow cytometers); ratiometric fluorescence is practical for bedside use.
    • Iterations Needed: Experts recommended normalizing outputs ( TagBFP/mCherry ratio) to account for variability; concerns about synNotch's potential off-target activation led us to emphasize orthogonality (Gal4 system).
    • Regulatory Path: For future clinical translation, start with PDCs to bypass immediate ethical hurdles; discuss FDA-like pathways for diagnostic devices.
  • Integration into Project: Feedback prompted DBTL Cycle 2: We added constitutive mCherry for normalization and tested specificity with controls ( non-apoptotic cells). This reduced variability from 20% to <10% in wet lab tests (see Engineering). We also pivoted to commercial PDCs for concept validation, avoiding direct patient sample ethics in iGEM timeframe.

Phase 3: Societal Impact, Ethics, and Feasibility

We explored broader implications, focusing on ethics, accessibility, and long-term vision.

  • Stakeholders Engaged: Patient advocacy groups ( local cancer support network, n=20 participants), 2 policymakers, and underrepresented community representatives from rural areas).
  • Methods: Online webinars (3 sessions, 50+ attendees) and focus groups; distributed plain-language project summaries.
  • Key Insights:
    • Societal Hopes: Patients emphasized hope for reduced side effects via personalization; concerns about access in low-income regions ( cost barriers).
    • Ethical Discussions: Touched on informed consent for PDC use, data privacy in multiplexing, and equity ( avoiding biases in AI predictions from dry lab models).
    • Feasibility Validation: Clinicians confirmed PDCs as a strong proxy for proof-of-concept; long-term path includes multi-center trials for real patient samples.
  • Integration into Project: This led to ethical safeguards in our proposed implementation ( opt-in data sharing) and expansions like portable readers for global use. We incorporated diversity by designing for low-cost reagents, aligning with inclusion goals.

Overall Impact on DBTL: HP feedback reduced project risks ( ethical pivots saved 2 months) and enhanced relevance, turning APOPTO-SENSE 2.0 into a clinically viable tool.

Education & Communication

We extended HP through outreach to inspire the next generation and raise awareness of synthetic biology in oncology.

  • School Workshops: Conducted 4 sessions for 150 high school students, using interactive demos ( DIY fluorescence models) to explain apoptosis detection. Feedback: 90% reported increased interest in biotech.
  • Public Webinars and Social Media: Hosted 2 online events (200+ views) on personalized medicine; shared project updates on Instagram/Twitter (500+ engagements). Collaborated with iGEM teams for cross-cultural exchanges.
  • Patient Education Materials: Created infographics and videos (in English/Chinese) explaining APOPTO-SENSE, distributed via advocacy groups. Emphasized ethical aspects to build trust.
  • Inclusivity Efforts: Translated materials for non-English speakers; partnered with underrepresented groups to discuss biotech access.

Sustainable Development Impact

APOPTO-SENSE 2.0 aligns with SDG 3 by promoting health equity through affordable diagnostics. Sustainability assessments:

  • Environmental: Low-waste design (reusable cell lines); modeled carbon footprint ( <1 kg CO2 per test vs. 5 kg for NGS).
  • Economic: Reduces ineffective treatments (potential $10B global savings in oncology costs).
  • Social: Addresses disparities by enabling testing in resource-limited settings; ethical framework ensures inclusive benefits.

Future iterations will incorporate life-cycle analysis for greener reagents.