Team:ZJU-China/Integrated Human Practice
Integrated Human Practices
In order to make our project responsible and good for society and have it optimized, human practice was supposed to play a supporting role in every step of project implementation. Not only would we thoroughly consider the influence our project might have on the world, but we also were intended to talk to the public, stakeholders, experts and patients through interviews or questionnaires, reflect the results in our daily meeting, modify and improve our project according to that. Also, remember to look at how we carried out Human Practices into our project.
Integrated Human Practices
Back in May, Dr. Wu Mengchao, "Father of Chinese Hepatobiliary Surgery" and who was awarded China's highest scientific prize, died in Shanghai. Mengchao Wu originated a new operation using intermittent interruption of the porta hepatis at room temperature, and completed the first middle lobectomy of the liver worldwide. And besides from Wu, millions of medical staffs has contributed to improving health care for the society. His death reminded us of the responsibility that we undertook to our society and the world as an iGEM team. ZJU_China this year made the health management and quality of life of HCC patients as our priority. To make Viruguard up to patients’ expectations, we considered the actual need of real patients from design to execution to engineer a user friendly, staff friendly and environmental friendly product.
Defining responsibility and service as our core value, throughout this year, feeling the particular burden of obligation, we always set high standards for ourselves. Viruguard has been specifically and pointedly improved according to the drawbacks of current virus treatment to better meet the demand of patients including quick immunal clearance, low efficiency of infect, low specificity, and weak transmission capacity. And we also built an app containing the patient’s version and doctor’s version to better serve our customers. See Hardware and Engineering for more information.
Questionnaire
From the questionnaire that we delivered, we got a basic insight into the knowledge about virus therapy of the public, experts and clinical doctors and their expectation of Viruguard. Specific efforts were paid based on the feedback that we got from our questionnaire, from which we discovered that the prevalence of synthetic biology related cancer treatment was still quite low even among medical staff and academic subjects. Among 11 clinical physicians and surgeons, only 4 of them have heard of virus therapy, reasoning from the lack of bio-therapy approved and used in clinical trial. Thus public and professional education were greatly needed in the future, several related lectures were given by ZJU_China 2021 for education. And patients who received our questionnaires were required to tell if there were any aspects they were not satisfied about the treatment they received. We have received 18 replies from HCC patients, and after analyzing their appeal, we made several improvements to our project design including make our therapy effective with single administration and decreasing the expenditure of Viruguard manufacture.
Also, some experts have put forward many expectations that we are not capable of adapting to our project, many of which can be subjects of iGEM teams and other researchers. We believe that these visions which are listed below can be realized one day in the future by the combined efforts of everyone involved
Interview
Stakeholders
We interviewed several medical staff in the department of hepatobiliary surgery and gastroenterology of the first affiliated hospital of Zhejiang university.
Associate director in gastroenterology Mosang Yu gave us a synopsis of etiology, pathology, morphology, clinical symptoms, diagnosis, differential diagnosis, staging and treatment of HCC. He highlighted the important role played by Child-Pugh grading in staging and further directing the selection of therapy including surgical resection and TACE (Transarterial chemoembolization). Thus he recommended us to identify the specific indications (staging) for our Viruguard. Though, due to iGEM limitations on clinical trials and animal experiments and lack of evidence-based medicine support, we couldn’t figure out the accurate indication for Viruguard, we were inspired to build a software platform for preliminary screening, in which the positive result prompted the need for further treatment including biopsy, radiology etc. And when diagnosis was definitive, it came to the selection of different therapies. In the future, we can compare the efficiency, side effects of Viruguard to other therapies in different stages.
Different from internal medicine, director Yiwen Chen raised up his suggestions from the surgery aspects. He told us the blood supply for the liver is complicated, in which two different circulation systems are involved, including portal vein and hepatic artery. Thus the metabolism rate of Viruguard should be prudently regarded to make sure the concentration of Viruguard in situ can reach the treating threshold. Initially, we were intended to inject engineered adenovirus into blood to make it transport to liver through our circulation, but we found the treating effect could be significantly affected by blood dilution and spread, unknown catalytic reaction in liver, possible enterohepatic circulation and possible ramus communicans because of HCC induced cirrhosis. After Dr. Yiwen’s support, we decided to administer Viruguard by intratumoral injection. And to ensure that Viruguard can cover all the HCC cells, we adjusted siRNA-targeted protein in HCC killing from one to two with the design of VEGF siRNA which has the potential to promote the lysis of tumor cells and facilitate intratumoral transmission of Viruguard.
To be responsible and good for society, we attached great importance to those advice from clinical doctors to assure the feasibility of our project in the real world. Both two directors spoke highly of our Viruguard project after we adjusted the design based on their suggestions. Since then, most of the project improvements we made to Viruguard have been reviewed by Mosang and Yiwen. We would like to give our devout acknowledgment for their generous help.
Experts
Knowing the expectation and appreciation of clinicians, we were motivated to ameliorate the specificity and killing potency of Viruguard ulteriorly. We thus managed to seek help from professors in our uni. As experts in their research area, professional advice could be given especially in the experimental principle and design viability. Before our interview, we presented our project thoroughly to all the professors invited and answered any question they may have about Viruguard to make sure all the suggestions we received were unbiased and based on understanding of our project.
Prof. Xiao Chen, studying the effect of miR199a on inducing osteogenesis through HIF-1α pathway, proposed the design of miRNA sponge to boost cell specificity in viral replication. He said that though miRNA content in different cell types was significant but might not be enough to induce the conspicuous difference in protein expression, which made it necessary to enlarge the discrepancy of miRNA level between HCC cells and normal cells. Team ZJU pitched a blueprint of miRNA sponge under the control of HCC-specific promoter to absorb the excessive miRNA in HCC cells, consequently elevate viral titer in HCC cells. Our conception was then presented to and rechecked by Prof Chen. He appraised us for the initial plan and wondered if we could tell the miRNA that function most effectively, based on which we added three different tandem miRNA sequences to the 3’UTR of E1A and miRNA sponge. The efficiency of different miRNA types were illustrated in follow-up experiments.
Meanwhile, Prof Qingjun Liu raised interest in our screening system, he introduced us to the electrode embellished by different flag molecules that were able to especially combined with substances that we were intended to detect which can possibly be used for AFP or GPC3 detection. According to his recommendation, we detected the variance of impedance before and after the binding of antigen to the electrode's surface. And our experiments showed a linear relationship between the substances detected and the impedance. Because of our lack of experience during this experiment, Prof. Qingjun has offered abundant experimental equipment and instruction for us without which we couldn’t verify the effectiveness of our hardware.
Stakeholders feedback
After our discussion and communication with experts of different fields, we embarked on our pre-experiment which basically showed positive results. Therefore, we informed our stakeholders and they were willing to further assess our project. This time Mosang focused on the safety of Viruguard, with several FDA approved virus therapies, it can never be too cautious for us to improve the safety of Viruguard. And he had high praise for the Viruguard, and he said if we wanted to put Viruguard into the market, the legitimate factors should be considered. We then consulted our schoolfellow who majored in law in ZJU, but only to find the legal deficiency in virus treatment. And Mosang said that only after 4 phases of clinical trials which verify the efficiency and little side effects of Viruguard, can we put Viruguard into real-world medicine. This reminded us that laboratory work was only the preparatory job for the market, while more emphasis should be put on the drug application and trial.
Patients
With lack of medical knowledge for most of the patients, we tried to use the plainest words to explain Viruguard to our patients, and comics were also made to help patients understand how Viruguard might improve their life quality. 72% (13 out of 18) of patients were willing to accept and use our therapy if successfully manufactured. Patients have been our best teachers from the beginning of our project, it was their expectation and wish that helped us to understand problems that urgently needed to be solved in our Viruguard, and shape our lab work.
Conclusion
After our human practice, we generally recognized that the combination of different fields and perspectives in real-world could solve actual problems we came across in researching. We are glad to see that the rudiment of Viruguard finally fits people’s expectations on it with our continuous devotion to it. It can be anticipated that, in the near future, virus therapy can develop rapidly with the support of humans, society, and the world, and eventually be applied to clinical practices for curing.
-
February 2021
Team building session
Nice to meet you,guys. We together will sure have an unforgetable journey.We all are important.
-
League construction
-
March 2021
Brainstorming
each team member voted for one of the candidate projects and the winner was...
-
Apirl 2021
Questionnaires delivered
-
Stakeholders interview
-
Overall design
-
May 2021
First look with NJU
-
Pre-experiment started
-
CCiC Eastern China Conference
ZJU_China shared our initial design to other iGEM teams. The idea exchanging has been quite inspired for us to modify our Viruguard design.
-
Communication with Dr. Xiao Chen, and Qingjun Liu and other professors
Xiao Chen and Qingjun Liu helped us with the design of miRNA sponge and constrction of software platform.
-
June 2021
Deep discussion with PI and our supervisor
miRNA sponge were modified according to their advice
-
Hangzhou meetup planning
-
July 2021
General education
-
Hangzhou meetup
Hangzhou meetup was successfully held in July, 7 teams in Hangzhou participated in it.
-
HUST_China visit
HUST_China was invited to visit us, and we have communicated deeply about each other’s design. The collision of ideas helped both team to work better.
-
The intense lab work
Tiring but fulfilling
-
August 2021
CCiC8
-
Stakeholders feedback
-
The launching of user manual
ZJU_China this year launched out a user manual to better serve our future customers and helped others to better understand how Viruguard can work.
-
September 2021
Patients feedback
-
Wiki construction
Nearly the end
-
October 2021
Presentation video
Jiangchu wrote the draft of presentation video. Haoran, Yongyin and Jiangchu participated in the recording of presentation video.
-
Giant
Jamboree
2021!
Human Pratice
Collaborations
Public engagement
Integrated human practice
Inclusivity
Real world implementation
References
[1] Chiovato, L., Magri, F. & Carlé, A. (2019) Hypothyroidism in Context: Where We’ve Been and Where We’re Going. Adv Ther 36, 47–58. DOI:10.1007/s12325-019-01080-8
[2] Fliers, E., Demeneix, B., Bhaseen, A., & Brix, T. H. (2018). European Thyroid Association (ETA) and Thyroid Federation International (TFI) Joint Position Statement on the Interchangeability of Levothyroxine Products in EU Countries. European thyroid journal, 7(5), 238–242
[3] Ernst, F., Barr, P., Elmor, R., Sandulli, W., Thevathasan, L., & Sterman, A. et al. (2016). The Economic Impact of Levothyroxine Dose Adjustments: the CONTROL HE Study. Clinical Drug Investigation, 37(1), 71-83. doi: 10.1007/s40261-016-0462-3
[4] Gorgojo Martínez, J., Zugasti Murillo, A., Rubio Herrera, M. and Bretón Lesmes, I., 2020. TELECONSULTA En Endocrinología Y Nutrición En Tiempos De La Pandemia COVID-19 Y Más Allá. [online] Seen.es. Available at: https://www.seen.es/ModulGEX/workspace/publico/modulos/web/docs/apartados/1433/160620_105727_7128864936.pdf [Accessed 22 October 2020].
FOLLOW US
