Human Practices

Cycle of Reflections

• Introduce and explain the Gibb’s Reflective Cycle and its components
  
• Impetus ~ The driving force for us to reach out to people
  
• Two-Way Communication ~ Have both the team and stakeholders be able to ask questions and voice concerns
  
• Analysis ~ Process information from stakeholders to better our project
  
• Implementation ~ Change and evolve our project to become better suited for the needs of our stakeholders

General Use In our project:
The Gibbs Reflective Cycle is a structured framework designed to support reflective learning in both individuals and groups. Its six phases—description, feelings, assessment, analysis, conclusion, and action plan—allow experiences to be systematically investigated in order to achieve meaningful advancement. In our iGEM project on Triple-Negative Breast Cancer (TNBC), we used this reflective model to make sure that our design process remained highly responsive to the needs of patients, clinicians, and the larger community.

Impetus:
Our motivation stemmed from the urgent need to address the limitations of the current TNBC treatments. Treatment options for TNBC are frequently restricted to aggressive chemotherapy, which has serious side effects and limited efficacy, because it lacks the hormonal receptors that other breast cancers rely on for targeted therapy. In order to make sure our project addressed actual gaps in care, we felt compelled to contact oncologists, researchers, patients, and advocacy groups after realizing these difficulties. The “Description” and “Feelings” phases of Gibbs’ cycle are reflected in this motivation and we started with a well-defined issue and a sympathetic understanding of its effects on people with TNBC.

Two Way Communication:
The foundation of our project’s stakeholder engagement was two-way communication. We invited patients to share their lived experiences, advocacy groups to voice concerns about communication, safety, and accessibility, and oncologists to question the viability of our methods, rather than just sharing what we were developing. For example, clinicians encouraged us to consider scalability and integration into existing treatment protocols, while patients stressed the significance of treatments that minimize side effects and maintain quality of life. The “Evaluation Phase” of Gibbs’ cycle states that this reciprocal communication enabled goals and concerns from various viewpoints to actively influence the course of our project.

Analysis:
Following feedback collection, our team moved on to the analysis stage. We examined recurring themes like affordability, accessibility, and safety and contrasted the input with our current project framework. For example, after stakeholders raised the issue of ensuring equitable access to innovative cancer treatments, we found that our design needed to consider both biological efficacy and implementation in different healthcare contexts. This reflective analysis helped us see the broader implications of our work: a successful TNBC therapy must be both innovative and beneficial for patients and healthcare providers.

Implementation:
Converting insights into real change was the last stage of reflection. We modified parts of our design and communication plan in accordance with Gibbs’ “Conclusion” and “Action Plan” phases. In addition to taking into account pathways to make the therapy scalable and accessible, we improved our suggested model to highlight specificity in targeting TNBC cells. Regarding human practices, we created educational resources that directly addressed patient concerns and explained complicated science in an understandable manner. Every one of these adjustments showed our dedication to developing the project in light of reflection, guaranteeing that our TNBC initiative is both a scientific breakthrough and a socially responsible solution.
Identification of Stakeholders: Our main stakeholders were Triple Negative Breast Cancer doctors, patients and survivors, researchers, and current medical manufacturing companies.

Expert profiles:

• Dr. Cesar Augusto Santa-Maria

  Dr. Cesar Augusto Santa-Maria, a medical oncologist and Associate Professor of Oncology at the Johns Hopkins University School of Medicine, specializes in treating and researching breast cancer. The goal of his research and clinical work, which is supported by the Breast Cancer Research Foundation, is to develop more specialized treatments for breast cancer, particularly immunotherapy and strategies for triple-negative breast cancer (TNBC). During our meeting, Dr. Santa-Maria provided our iGEM team with valuable information regarding the clinical and translational aspects of our TNBC diagnostic project. In reference to the uniqueness of our approach, he emphasized the importance of identifying clear gaps in current diagnostics and modifying our work to fill them, particularly in the areas of accessibility and patient-centered care.

  He pointed out that patients are concerned about breast cancer biopsies and that advancements in detection and diagnostic effectiveness could have a big impact on patient satisfaction and doctor-patient relationships.

  Technically speaking, Dr. Santa-Maria suggested that we deepen our comprehension of toehold switch-based diagnostics by directing us to particular studies on cell-free systems, like the Zika virus detection model. He urged us to examine more specialized literature on the subject and posed the question of whether post-transcriptional changes to miRNAs, such as 3’ methylation, could obstruct their binding to toehold switches. Additionally, he suggested that we carefully evaluate whether it would be more efficient to start with DNA transcription in the mixture or to rehydrate freeze-dried toehold systems for direct blood sample input, keeping in mind that this decision would have an impact on our kit’s design. He also emphasized how crucial it is to comprehend the advantages and disadvantages of cell-free systems in comparison to cell-based systems, guiding us to read reviews that dissect any potential benefits and drawbacks.

  Dr. Santa-Maria offered ways to improve the quantitativeity of our system’s execution, like equipping plate readers with colorimetric or fluorescent outputs for accurate measurements. Regarding implementation, Dr. Santa-Maria recommended ways to increase the quantitative nature of our system, like incorporating colorimetric or fluorescent outputs into plate readers to ensure accurate measurements. Additionally, he offered a practical viewpoint on the cost of scaling up, reminding us that although reagents might be cheap, labor, packaging, branding, and distribution are significant obstacles to product development. He illustrated how collaborating with well-established businesses can aid in overcoming these obstacles by using his experience with BioBits. All things considered, his criticism pushed our group to strengthen the project’s technical underpinnings while maintaining patient needs, budget, and viability as our top priorities.

• Zimmerman:
  Zimmerman, a specialist consultant for our TNBC miRNA diagnostic, suggested that we clearly identify a niche: instead of using the test for general screening, it should be used for patients who have a confirmed diagnosis to track recurrence and minimal residual disease. He stressed that quantitative tracking (relative changes, patient-specific baselines) is more clinically useful than a simple yes/no and suggested specifying use at predetermined intervals (roughly every three to six months). He recommended creating a new baseline and using longitudinal trends to direct care for patients whose tests never come back negative.

  Zimmerman outlined the following significant technical difficulties: Due to their short length, low abundance, and potential for post-transcriptional modifications that could impact toehold binding, miRNAs may require pre-amplification and meticulous probe design. Prioritize specificity to TNBC (be cautious of markers like miR-21 that rise in inflammation) and confirm the universality of the selected miRNAs across TNBC subtypes to avoid an excessively large panel, he advised. He backed colorimetric or fluorescent outputs for quantification, which can be read by plate readers or a calibrated app to generate thresholds and monitor changes over time.

  Zimmerman made several recommendations for implementation and validation, including coordinating testing with imaging/clinical follow-up, conducting systematic validation experiments (stage/recurrence mixes, negative controls, healthy controls, and graded TNBC-level samples) to establish thresholds, and concentrating on demonstrating the scientific justification for selected miRNAs rather than developing new hardware. In order to clearly demonstrate patient value, he suggested that branding emphasize the noninvasive nature and earlier-detection benefit.

• Emily Hernstein:
  The 48-year-old Caucasian TNBC survivor Emily Hernstein, who is in her first year of remission, met with Adelaide McMurray on August 4. Because she has the BRCA1 gene, Emily has been getting screenings every six months. Her breast cancer developed and was discovered months later in spite of this vigilance, necessitating surgery, chemotherapy, and continued care for remission. She highlighted the strain that many TNBC patients endure by describing the experience as emotionally and physically exhausting.

  Emily emphasized that if a noninvasive blood test for TNBC detection had been available, she would have used it once a month. She believed that this could have prevented the severe treatment she endured and enabled early detection. She also underlined the cost of routine imaging screenings, noting that even with insurance, the costs were high and that the six-month intervals allowed cancer to spread undetected for extended periods of time.

  Emily saw our project as promising and potentially life-changing for TNBC patients, especially for monitoring remission and recurrence, even though she has not had a recurrence. She also kindly offered to help us with our outreach by sharing a survey with her online support group for breast cancer and putting us in touch with people who might be interested in doing interviews for the project. Her testimony reaffirmed the significance of frequent monitoring, affordability, and accessibility in determining the course of our diagnostic tool.

• Ally Huang:
  The expert who reviewed our TNBC diagnostic concept said that while the high-level idea makes sense, more information about the experimental setup is required before the feasibility of the idea can be fully evaluated. To gain a better understanding of the sequential validation process, they suggested investigating current diagnostics that employ toehold switches, such as Zika virus detection in cell-free systems. Additionally, a deeper understanding of cell-free systems in general was suggested.

  Technically speaking, they prompted additional literature review and suggested that post-transcriptional changes of miRNAs (such as 3′ methylation) might impact binding to toehold switches. They also highlighted a crucial design choice: whether to incorporate DNA transcription machinery into the mix or directly rehydrate freeze-dried toehold switches for blood sample testing, both of which call for distinct experimental considerations. They recommended reading reviews and published research contrasting cell-free and cell-based systems to help direct this.

  For quantification, they recommended using colorimetric or fluorescent outputs, which can be measured using a plate reader to generate precise absorbance or fluorescence units that can then be adjusted for a colorimeter application. Finally, they stressed that while raw materials may seem inexpensive, the true costs of implementing such a diagnostic would be labor, plastics, packaging, branding, distribution, and marketing. They suggested considering partnering with established companies to handle infrastructure and scale-up, based on their own experience with BioBits.

• Mary Passini:
  After a lump was discovered during a yearly checkup, the patient was diagnosed with Stage 4 TNBC. She didn’t initially have a biopsy or ultrasound because of her dense breast tissue. She started treatment, which included 12 rounds of Taxol, a second round of chemotherapy, acupuncture, and red-light therapy, following additional testing and visits to an oncologist. During treatment, she also lost hair.

  In response to a question about our project, she called it a “good idea” and stressed the value of any tool that gives patients greater assurance about whether they have cancer, particularly for tracking remission. She claimed that she would be quite at ease utilizing such technology, preferably in the form of a straightforward blood prick test. She emphasized the value of accuracy and ease of use but had no serious privacy concerns. “The better the diagnosis and treatment plan, the more information you have,” she said. Lastly, she urged researchers to keep asking patients about their experiences and viewpoints during the development process in order to involve them.

  Overview Explain who the Baltimore Biocrew is, our mission, our values, and why we have an emphasis on Human Practices.

The Baltimore Biocrew’s project was shaped by our goals to improve accessibility and reduce inequality in healthcare by creating an improved remission detection technology for Triple Negative Breast Cancer (TNBC). We aimed to help support post-breast cancer individuals, promote early, non-invasive cancer diagnostics, and ensure accuracy in tests using ethical and sustainable methods with our project. Our project is based on the fact that there are limited opportunities for recurrence monitoring as women receive very expensive standard mammograms every year after treatment. Oftentimes, because of how infrequent the mammograms are, the breast cancer has time to develop and become severe without the patient’s notice. This was our call to action and why we chose this project–we support the development of a rapid test meant to identify breast cancer mRNA that is cheap and can be done at home. Then we needed to inform the community about our project for support, so our human practices group surveyed and interviewed doctors, researchers, and patients to guarantee a positive impact produced by our project. The results were widely supportive, and past and current patients, as well as doctors and experts, gave us suggestions about how we might improve our project to meet its full potential.