Team:ASIJ Tokyo/Human Practices

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Integrated Human Practices

The concept of integrated human practice involves communication between our potential users and our team. Therefore, in our work for integrated human practice this season, we showed how the different activities we conducted helped “close the loop” and inform various aspects of our project such as its design and outreach, showing how our project is beneficial and helpful to our community.

General Purpose of Breast Cancer Detection

The purpose of breast cancer detection is to identify patients with breast cancer as early as possible in their onset such that efficient treatment methods can be administered. Early detection of breast cancer is a way to control and treat breast cancer (Priyanka, 2021). From the various research, interviews, and surveys we conducted, we recognized that creating an accessible, at-home testing kit for breast cancer would help with the lack of testing in Japan and high prevalence of breast cancer mortality.

Project Inspiration

Interviews with Ms. Saki Suzuki
From our interview with Ms. Saki Suzuki, leader of RFTC Japan: Hana-me, an organization that educates men and women in Japan on basic information about breast cancer, there is a lack of awareness of breast cancer in Japan. In fact, Ms. Suzuki mentioned that in Japan, individuals know more about earthquake drills than breast cancer as there is a lack of urgency regarding breast cancer despite its prevalence (breast cancer is the fifth leading cause of cancer-related death among Japanese women, according to the Japanese Ministry of Health, Labor and Welfare). When we asked Ms. Suzuki regarding reasons for the lack of testing and awareness, she mentioned that possible causes include the resistance to getting tested and the assumption that breast cancer is not prevalent until old age. Therefore, with the information provided by Ms.Suzuki, we decided to make an informational pamphlet on basic information regarding breast cancer that was advertised in our school and passed out around the city.
Additionally, Ms. Suzuki also emphasized that a lot of misconceptions regarding breast cancer are from unreliable or inaccurate sources. This misinformation has caused people to fel unsafe and uncomfortable with getting tested. She recommended taking a friendly approach that respects the ideologies of individuals while encouraging them to try testing when trying to raise awareness of our cause. In addition to our informational pamphlet, we also compiled a list of reliable sources to inform individuals in Japan about breast cancer.
Figure 1: Interview with Ms. Saki Suzuki
Finally, Ms. Suzuki also mentioned that educating individuals at a young age is important to make change. She recommended that creating an education curriculum or health program in school is needed in Japan as schools do not educate students enough on prevalent disorders. Taking her suggestions, we spoke to students at our school regarding breast cancer to make a start and will hopefully extend this to other Japanese schools
A transcript of our interview can be found here.
[Lemon Project Interview conducted by Eva L, Sage F, Sophia S, Noe T, and Aditi P]


Interview with Helen Yoon
We had the opportunity to interview Helen Yoon, a breast cancer survivor. She shared her experience about getting diagnosed for breast cancer, specifically how mammograms “hurt so badly”. She mentioned that less painful tests such as blood tests were not as accurate as the mammograms, and her regret in not getting a mammogram earlier. She also highlighted the importance of how people need to be more educated about breast cancer and breast cancer testing. From our interview, we became inspired to develop a more accurate testing procedure that is non-invasive compared to the current diagnostic methods. This helped inform our research on biomarkers that could be detected through non-invasive means.
[Interview conducted by Eva L]


Interview with a Community Member
We interviewed a community member in her fifties, who shared her experience with getting tested for breast cancer and her knowledge on the influence many companies have on breast cancer testing in Japan.
Like many other interviewees, she clarified that one of the most common reasons for not frequently getting tested with mammograms is because of the pain associated with it. She also mentioned that in Japan specifically, many families are not comfortable with talking about it, too busy with work, or assume that “eating healthy and going to the gym” is fine.
Additionally, she mentioned that in many corporations, all employees are required to go to an annual checkup that may include a screening for breast cancer, however, the results get submitted to the company, and many women are expected to pay out of pocket for such tests. After the checkup, the company doesn’t mention how frequently women should get tested, and no further information is provided. This information added to the many reasons our team wanted to have a more convenient test for breast cancer, and why we wanted to focus on education during breast cancer awareness month, and towards the outside community through our educational videos on YouTube.
Finally, she inspired our design of the testing kit by verifying that she would want it to not be as painful as mammograms are, and are more available in developing countries. This pushed us to make our testing kit noninvasive and portable through the lateral flow strip, making it more accessible and painless.
[Interview conducted by Eva L]


Interview with Dr. Sangai
We had the opportunity to interview Dr. Sangai, a breast cancer doctor and professor at Kitasato University in Kanagawa. He answered questions we had regarding breast cancer detection and treatment, as well as sharing his experience and the stigma he’s noticed around the disease working in the field.
He noted that early detection is crucial in tackling breast cancer. Although technology has been steadily improving, there is still no definite way to detect breast cancer at a minimal level. According to him, finding the cancer at stage 1, although it may seem early, can still be dangerous. He hopes that less invasive, more accurate detection methods accessible to all are developed, perhaps with the use of biomarkers, which is why we decided to focus on detecting them for our iGEM project. Additionally, he emphasized that the earlier the detection, the higher the chance of survival and curing the disease.
Finally, he shared information on a patient-led support network at his hospital. To tackle the fear and misunderstandings that arise within patients, especially recently diagnosed patients, he connects them to other breast cancer patients, past and present, so they can share their experiences with one another. Through these talks, patients are able to relieve some of their stress and find ways to work through their condition one step at a time.
Based on the interview with Dr. Sangai, we realized the stigma that exists with breast cancer patients in Japan and tried to raise awareness for this stigma through our breast cancer awareness month events and educational videos.
[Interview conducted by Koharu M]


Interview with Breast Cancer Surgeon
On behalf of ASIJ_Tokyo, NTU-Singapore had the opportunity to interview a breast cancer surgeon in Singapore, who shared insights on the screening rates, treatment methods, and limitations of detection that she has encountered in her work. She mentioned that in Singapore, there is a program to promote screening, where women over 50 years old are sent a letter of reminder to get screened every 2 years. However, only 30 - 40% of women actually receive screening from public hospitals. This may be because some do not use public health services and use private appointments instead, but she also mentioned the many limitations that currently exist in screening methods. For example, mammograms can be very painful, and many women “do it once, but never do it again”.
In her interview, she described her opinion on how to make our design more effective. She mentioned that the test should be convenient and accurate, and should give patients “no pain”, specifying that “that would be the easiest”. This supports our use of a small, portable, at home test that is noninvasive. She also described the tough balance between high accuracy and convenience, emphasizing how important it is to test molecules that are present in high amounts in blood, urine, or serum. This supports our use of Mucin and Mammoglobin, which are both molecules present in high levels in sweat, and tears.
[Interview Conducted by NTU Singapore]

Student Interviews
We had the opportunity to interview a number of junior and senior students from the American School in Japan, including Nico Sawaki, Jon Jon Wang, Christina Sarukos, and Kalyn Ouk. All of the interviewees confirmed that they would be more willing to screen for breast cancer if a testing method similar in design to a pregnancy test was offered. This shows the appeal of a test that is small, convenient, and noninvasive—all qualities we aimed at including in our design.
Additionally, all interviewees agreed that there is a lack of discussion around breast cancer in their community due to lack of knowledge about the topic and the stigma associated with getting tested and treated. This consensus among all interviewees emphasized the importance of educating the community about breast cancer, and inspired us to organize interactive activities, presentations, posters and pamphlets aimed towards people of all ages during Breast Cancer Awareness Month (October).
[Interviews conducted by Eva L, Sophia S, Akika A]

Public Surveys Analysis

As part of our effort to increase awareness about breast cancer, we sent out an international survey (in Japanese and English) via Instagram, Twitter and Facebook and gathered over sixty responses. We gathered information on how much people knew about testing for breast cancer and conducted followup interviews with several of the individuals who responded.
Through the survey, we were able to identify several trends with respondents’ basic knowledge regarding breast cancer and breast cancer screening. Despite nearly half (45.9%) of our respondents having at least one close acquaintance or family member with breast cancer, only 23% of respondents ever received breast cancer screening in their lifetime. With regards to knowledge about breast cancer screening, only 27.9% correctly replied that breast cancer testing should occur after around 40 years of age, while only 29.5% of respondents knew that breast cancer testing should occur about once every 2 years.
Figure 2: Prevalence of Breast Cancer
Figure 3: Prevalence of Breast Cancer Testing
When given multiple choices for what factors have prevented or would prevent respondents from getting screened for breast cancer, “Cost” and being “Too busy” were selected as the most common responses (44.3% and 42.6% respectively), followed by “Inconvenience” and “Lack of understanding of the risks of breast cancer screening” (both 39.3%). Other factors repeatedly mentioned in the free response section of the survey included the pain associated with breast cancer screening, as well as a reluctance to engage with the Japanese medical system (in some cases, due to bad past experiences with government-sponsored screenings).
Figure 4: Inconveniences for Breast Cancer Testing
Finally, in order to determine if there would be a demand for an easy at-home breast cancer detection test, we asked respondents whether they would be more willing to test frequently, or at all, if there were such a test. The answers to this question were overwhelmingly positive, with 95.1% responding “yes”. Therefore, we realized the importance of crafting a more convenient testing system, and made this the focus of our iGEM project.
Figure 5: Testing Kit User Input

Experimental Design

For our 2021 iGEM Project, we worked with mentor Rengwei Liu, a PhD student of Kyoto University majoring in biological chemistry who has had iGEM experience. Based on our interest in breast cancer and selected biomarkers, Rengwei suggested we use an aptamer based approach instead of an inducible promoter due to the difficulty in finding inducible promoters that already exist for our specific biomarker. Rengwei also put us in contact with his former team XMU-China, where we learned valuable information regarding amplification of the biomarker-aptamer complex via the use of Cas-12a.
Our team thanks Rengwei for his valuable contributions and advice he has given to our team.
[Communication with Rengwei was managed by Matthew K]
Interview with Mr. Serita
Figure 6: Interview with Mr.Serita
When looking into detection methods for breast cancer, we came across a paper by Professor Tonouchi and Mr. Okada from Osaka University that explained the use of terahertz waves as a method to detect breast cancer. We contacted Professor Tonouchi and spoke to a member of his lab Mr. Serita regarding their physics-based method and advice regarding biomarker detection. From the interview, we learned that this method was not for early detection, but rather for use during surgery to accurately predict the location of the cancer tumor.
[Interview conducted by Koharu M, Aree L, Kai H, Annmarie H]
Tokyo University of Agriculture and Technology(TUAT) Meetup
Figure 7: TUAT Meetup with Dr.Ikebukuro
When looking into aptamer-protein modeling and determining which aptamers to use for our project, we asked Dr. Ikebukuro for help because he specializes in modeling and he helped our team in 2019. We visited the Tokyo University of Agriculture and Technology to meet with him, and he introduced us to Dr. Hiraka who also works on protein modeling. We talked with the two of them as well as university students about our project, and they agreed to help us with modeling our aptamer-protein complex. We also discussed with the university students about iGEM and how our iGEM team runs, as they are working to restart iGEM at the Tokyo University of Agriculture and Technology next year.
During the meeting, Dr Ikebukuro also gave us advice on the design and marketing of our testing kit, and posed questions regarding our collection method for biomarkers and methods to troubleshoot for false positives. His advice played a crucial role in the development of the framework for our proposed implementation.
After our meeting, we kept contact through email, and Dr. Hiraka introduced us to servers to help us with protein docking. He also helped identify a process and servers to help predict 3D models of our aptamers from our DNA sequences, and we double checked to make sure our process of visualizing the protein docking on PyMol was accurate. Please see our modeling page here.
[Interview conducted by Matthew K, Seeun K, Kai H, Annmarie H]

Conference

We were invited by Professor Haruhiko Siomi of Keio University to participate and present at the 44th Annual Meeting of the Molecular Biology Society of Japan on 12/3/2021.
The event will be attended by professors and researchers, and is open to the public. At the event, we plan on presenting our iGEM project, and hope to receive advice and guidance for the second phase of our project next year. In addition, we plan on again raising the importance of early breast cancer testing and awareness for breast cancer.

Summary

Our integrated human practices, which involved interviews with students, former breast cancer patients, and doctors, communicated heavily with stakeholders in our project. From our project ideation, design, experimental work, and outreach to the community, we integrated and acted upon the feedback and opinions that were provided to us to connect our community and our project together.
Our initial goal was to create a system to detect breast cancer, and the first problem we encountered was designing a method that would be better than the existing clinical procedures. We decided to speak to former breast cancer patients to receive their input on limitations of clinical procedures and realized that current detection methods are costly, invasive, and uncomfortable. This sentiment, which was shared by many of our interviewees, let us realize that an at-home testing kit was required as an alternative.
We decided to model the design of our testing device like a pregnancy test strip after interviewing students at our school. As young adults and one of the most important populations that need to get tested for breast cancer, the input from students informed the design of our testing strip, which aimed to address the qualities we wanted to include in our device.
Upon deciding that we wanted to create an at-home testing kit, we consulted with former iGEM participants and professors on methods for detection. From our consultations, we realized the importance of detecting biomarkers, and specifically, the use of aptamers to detect for our biomarkers. We combined our lab experiments and modeling with advice from experts to help justify our detection methodology.
Finally, we closed the loop by recognizing the importance of the lack of detection of breast cancer in Japan and the need for a better alternative. We did this by sending a survey to a global audience and seeing their opinions and response towards our solution that acted on the feedback of our community.
Please see our Education pages for our engagement with the community and our Proposed Implementation page for the application of our testing device in the community.

References

Priyanka, K. S. (2021). A Review Paper on Breast Cancer Detection Using Deep Learning. IOP Conference Series: Materials Science and Engineering, 1022(1), 012071.