Human Practices

With COVID spreading even more rapidly across the world, 2021 has been a hard year for the iGEM community, which sets a higher requirement for each iGEM team to collaborate with other teams and communicate with the world. However the severe and grim pandemic situation, instead of abating our enthusiasm, reminded us of the role of synthetic biology can play in public health from time to time. Therefore, considering the responsiveness and goodness that our project was supposed to shoulder, engagement with real-world and our laboratory work interacted and reinforced each other throughout the whole course of our project to make sure that the Viruguard has the potential to benefit the world one day in the future.

Conception

ZJU_China this year built a diverse and powerful team in February, composing of 13 members from 10 different majors and different places in China. Before determining the topic of our project, the members of ZJU China had a one-month brainstorm, with complete understanding of the requirements of iGEM, which indicated that our project should be good and responsible for society and the world. Our team happened to share the same view with the iGEM community and decided that the project we were going to work on must be closely related with the problems that plagued our society or country and waited to be solved. Therefore, during the brainstorm, our team members pitched different ideas including pest control, resource regeneration, disease treatment, hair dyeing, etc.

Right In February 2021, a famous Hong Kong actor Mengda Wu confirmed that he suffered from liver cancer and had been undergoing chemotherapy and surgical resection, but his condition had turned critical during recuperation. As a famous comedy actor, who had brought happiness to generations of people, his health condition tugged at our heartstrings. Unfortunately, Mengda passed away in the end of February.

The tragedy of this comic star drew our attention to liver cancer. The majority of primary liver tumors are HCC, with cholangiocarcinoma comprising most of the remaining cases. Hepatocellular carcinoma (HCC) is a primary liver malignant tumor that typically develops in the setting of chronic liver disease, especially in those with hepatic cirrhosis or infected by HBV. The worldwide incidence of HCC shows a geographic variation which stands consistent with HBV infection. It was estimated that 72 percent of HCC cases occur in Asia, among which a great number of people are from China[1]. With over 756,000 new cases of HCC diagnosed each year globally, and over 353,000 in China, the HCC treatment has been a huge challenge to the medical institution and staff. Therefore, we were inspired to use synthetic biology to create an effective and affordable treatment for HCC. Moreover, in May, Dr. Wu Mengchao, an academician at the Chinese Academy of Sciences, considered as the "Father of Chinese Hepatobiliary Surgery" and awarded China's highest scientific prize, died in Shanghai. This news further strengthened our intention to put our effort into the development of a novel treatment.

Questionnaire

Before selecting the treating method with the biggest prospect for development, the first thing we wanted to learn about was how much attention did the academic public and patients pay to HCC treatment? Therefore, we made a simple questionnaire and delivered them to the academic public including bio-majored professors, scholars and students, through different social media or face-to-face. We had also specifically send our questionnaire to HCC patients with the support of the first affiliated hospital of Zhejiang university and department of hepatobiliary surgery.

We had then received many effective replies from the public, and several from the iGEMers. We found that there were a wide range of iGEMers, scholars and professors involved in our survey, which indicated that our survey was quite representative of different communities and had significance.

A succinct introduction to our initial conception was presented in the cover of our questionnaire to help subjects understand our rudimentary product, and in order to ensure compatibility and accuracy of our result, exclusion criteria was set including major, age, academic experience, etc.

And in order to analyze our results, participants were grouped according to their major which meant the collection of private information was necessary and inevitable. All the privacy was protected by a third-party app and by our sincere effort. The questionnaire is listed here.

According to the questionnaire collected, the low CR (complete recovery) rate, high cost, severe side effects, and long course of treatment remained to be the main concern and complaint of HCC patients and their families. Considering the safety and efficiency of the treatment method, we decided to improve a currently approved virus treatment and eliminate its drawbacks to make it first-line treatment for HCC in the future.

Interview

Since Virugaurd would be a novel product to treat HCC, we believed that its impact in the medical and pharmaceutical practice would be worth being discussed. And only after learning about the current role virus therapy play, can we consider viruguard potential influence in an appropriate manner.

Stakeholder

We intended to learn about the current situation about viral treatment from the stakeholders, especially those who worked in related fields and were well-known for their academic success. The interviewees we found were from different departments in the hospital, which made sure that we could receive professional recommendations from several different perspectives. Our selection of subjects participated was fair without bias. The subjects were required by us for a relatively experienced career in terms of our project related work which means we could hopefully get specialized knowledge and highly professional suggestions for improvement.

In order to avoid misleading the interviewees and get real feedback from our stakeholders, instead of using questionnaires, we chose to communicate with the interviewees face to face in person. Before the interviews, we had explained to them about the background and basic design of our project, how the results of the interview would be used, and our interviews were recorded under the permission of interviewees. We had made interviewees anonymous if required and made sure that all questions asked were neutral and had open-ended answers.

We visited the department of hepatobiliary surgery and gastroenterology of the first affiliated hospital of Zhejiang university. The recommendations that we got from medical staff and clinical researchers were sincerely adapted and applied to amend our Viruguard design.

Fig.1 Consulting Yiwen about how the clinical practice of HCC patients worked

Experts

Realizing our stakeholders had quite high expectations of our Viruguard, we found that great effort should be put into the product. Since our initial design was intended to build an engineering virus which can be applied to clinical trials, there were still several problems that we would need to solve before experimental conduction, including low efficiency and specificity, and ambiguous indications etc. Therefore, we carried on further interviews with the professors in our university discussing the problems we were confronted with in our project design. We also requested professors to evaluate our project and raise some opinions on how to improve it considering the suggestion given by our stakeholder, apart from our concerns about the value of our project. Professors proficient in different areas were invited according to problems we were confronted with. Similar disciplines with those that we set during stakeholder interviews were applied.

Listed below were two professors that gave us cordial advice, our team would like to express our sincere acknowledgement to them. According to the answers we get from the interviews, we further modified our project design.

Name：Xiao Chen

Reasons for interview: Expert at miRNA (mir199a) induced stem cell differentiation3

Recommendation: miRNA sponge design

Institute: Center of stem cell and regenerative medicine, Zhejiang University

Name: Qingjun Liu

Reasons for interview: Expert at medical biosensor design and development Recommendation: Detection device design

Institute: School of Biomedical Engineering and Instrument science, Zhejiang University

Fig.2 Inviting Prof. Wentao to our lab to examine our design.

Stakeholders’ feedback

After our preliminary experiment to verify the feasibility of our design, we were eager and excited to figure out an intact plan for our future laboratory work. For this part, we notified the stakeholders of the primary results of our work and we would like the stakeholders to imagine the role Viruguard could play in their job, and its performance if it could come to the market. Different visions were proposed and it could be pretty helpful for us to develop future products based on that. Terms mentioned above in the interview were applied. Stakeholders were informed if their ideas were intended to be implemented, and their permissions were solicited before our work.

This feedback gave us an insight into how precise therapy would benefit the world in the future, and inspired us to continuously ameliorate our Viruguard to satisfy the urgent need of HCC patients. The medicine related to synthetic biology showed brilliant and limitless prospects and our design can never be too good.

Patients

Curing is the final goal of medicine and with synthetic biology emerging and developing rapidly, more and more patients can benefit from various novel therapies. As our future target audience, it was important for us to know how HCC patients reflect on our Viruguard which indicated the future market of Viruguard, and if there were any drawbacks that they would like to improve. We explained our Viruguard to patients in the form of comics, which was relatively superficial. Their proposal made us realize the requirement of real patients in a comprehensive way, and we would be devoted to achieving it.

Fig.3 Patients examination under the instruction of our tutor. Shown in this photo is a patient dignosed with HCC, and secondary hepatopulmonary syndrome. The permission from patients was obtained before we took and posted the photo.

Conclusion

In a gesture to make our project responsible and good for society and have it optimized, human practice is supposed to play a supporting role in every step of project implementation. Not only did we thoroughly consider the implications our project would have on the real world, but we also managed to talk to the public, stakeholders, experts and patients through interviews, questionnaires, or social medical, reflect the results in our group meeting, and modify our project based on that. Also remember to look at how we integrated Human Practices into our project.

References

[1] https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf (Accessed on January 27, 2020).

[2] Llovet, J. M., Kelley, R. K., Villanueva, A., Singal, A. G., Pikarsky, E., Roayaie, S., ... & Finn, R. S. (2021). Hepatocellular carcinoma. Nat Rev Dis Primers, 6-6

[3] Nanoparticle delivery of stable miR-199a-5p agomir improves the osteogenesis of human mesenchymal stem cells via the HIF1a pathway. Biomaterials, 53, 239-250.