Team:SCU-WestChina/HP/Gold Integrated
This year, we've done a lot of works on human practices with painstaking effort. In addition, we consider seriously and extensively whether our project is safe, responsible and good for the world. Therefore, we designed and carried out numerous human practices around our project, and we integrate a lot of human practices considerations into every part of our project. Besides, we also conduct public engagement and education activities to have conversations with participates while inviting public input to shape the direction of our work and spreading synthetic biology and iGEM.
Based on the silver human practice, we've integrated all of the advices and suggestions we've obtained from them into our project. See how we integrate our human practice in our project in this page
1. 2016 Chengdu International Conference of Gastroenterology
Before determining what we will do this year, we made many alternative plans, and one choice was using intestinal probiotics to cure human diseases. However, for the lack of relevant knowledge, we decided to learn more before we made the final choice.
On 4th December 2016, the Chengdu International Conference of Gastroenterology was holding by the Gastroenterology department of West China Hospital, Sichuan University in Chengdu. As the students of Sichuan University, we were very lucky to have a chance to take part in this conference.
During the meeting, the report Intestinal Flora, Host Metabolism and Related diseases made by Shen Xizhong, professor of Zhongshan Hospital, Fudan University, attracted us a lot. Professor Shen gave a detailed introduction of the change of intestinal flora during the progress of host’s metabolism diseases and he mentioned some advance researches. What he introduced exactly was what we were interested in. Thus, we tried hard to gain a chance to communicate with him face to face, after the conference. We illuminated our project to him, which is using synthetic biology method to remold intestinal flora, and using these bacteria to metabolize some metabolite in the human body to cure some diseases. Professor Shen encouraged us, but he also pointed out some problems we need to take care of. Among those problems, microorganism colonization was what mentioned by Professor Shen as the most challengeable one, which usually influences the final cure effect. He suggested us to search more references to choice a suitable strain if we do want to develop a curable intestinal flora. Therefore, to solve the colonization problem, we made many effort, including choosing probiotics E. coli Nissle 1917 as the chassis, designing deficient strain and complementary plasmid to enforce the colonization ability, and we also use animal experiment to test whether the bacteria colonized as we expected.
In conclusion, attending the 2016 Chengdu International Conference of Gastroenterology is beneficial for optimizing our project.
2. Project Presentation for the 1st Time
On 22nd February 2017, After the rudiment of this project was determined, we invited our 6 instructors, professors from the State Key Laboratory of Biotherapy, Sichuan University, to give us some advice to our project. The professors are doing researches in different fields and we believe they can offer more diversified suggestions to our project. We made a presentation to introduce the whole design of our project to them. At that time our project contained 4 systems, which were related, progressive and all linked to the same theme, using reconstructive probiotics to cure metabolic diseases. The diseases we aimed to cure were phenylketonuria (PKU) and gout. The four systems were all related to reconstructive intestinal flora, but worked in different places, including gut, dialysis tube human being’s blood and artificial blood vessel.
After we introduced our project, professors asked many questions and had a fierce discussion with us. They mainly queried the safety and effectiveness of our project, especially the fourth part in which we planed to inject the remolded bacteria into a artificial blood vessel near the hepatic portal vein. They thought the immune reaction will do harm to the human body a lot. Their worry let us be more aware of the possible risk which our project contained, and let us thought twice before we made the final decision.
After this reply, we carefully collated and analyzed our instructors’ suggestion. Finally, we deleted the last two parts and started to focus on using reconstructive intestinal flora and dialysis devices to cure hyperuricemia and gout.
3. Project Presentation for the 2nd Time
Through the first reply, we gained many useful suggestion, adjusted our project, and concentrated on curing hyperuriemia and gout by remolding intestinal flora and using dialysis devices to let our project more feasible. After preparing enough, we invited our instructors to attend the 2nd reply. Compared with the last time, instructors’ attitude was more positive. They supported our whole idea and experimental design. The most inspiring thing is that we discussed the human immunity prob-lems with immunologist Hu Hongbo. He directly pointed out that although the bacteria in the dialysis device are indirectly contact with human being’s blood, once the bacteria debris or metabolite flow into blood, furious immune reaction will happen. He suggested we can try to avoid such risk by optimizing our dialysis device, increasing its leakproof ability and knocking out some gene of our engineering bacteria to decrease its toxicity. In addition, we can use animal experiment to mimic the leak of bacteria and find out the superior limit of the extent of immune reaction that we can accept.
Those valued opinions helped us to improve our project’s design in the parts of hardware, engineering bacteria and animal experiment. Human being’s immune reaction is always the biggest problem we confront, and professor Hu’s suggestions guided us to a brighter way. We do appreciate professor Hu and other instructors’ contribution.
1. West China Hospital Visiting for the 1st time With Dr. Yi Liu
After determining the main content and purpose of this project, we began to search for more related references to replenish our design. However, through this period, we found we shouldn’t only rely on references to design our subject. The data we researched on the Internet might not be real-time or specific enough, and a better way to know whether our design is meaningful to the clinic is getting close to it. Hence, we went to hospital and talked with doctors to get some first-hand clinic data and explore the real problems which they are facing with in the real clinical situation.
On 23rd April 2017, we went to rheumatology and immunology department, WestChina Hospital to visit Doctor Liu Yi. Doc. Liu introduced the cure situation of gout to us from many aspects, including patients’ condition, current clinical treatment methods, general drugs, etc. She also pointed out the argument on whether patients with hyperuricemia but no gout symptom should take medicine. Moreover, during the conversation, we knew that the biggest problem in the progress of decreasing patients’ uric acid level is that patients refuse to take medicine or can’t insist, for the cure progress is long and painful. Luckily, our design can be an alternative and suitable choice for patients, especially for those who are hyperuricemia but don’t have gout, as using the merit of intestinal flora, letting them colorize in patients’ gut can reduce the frequency of taking medicine. If our design can come true, then it will be a totally new and harmless method in the cure of hyperuricemia or gout.
The conversation with Dr. Liu benefited us a lot and gave us confidence to keep doing such research, as we had confirmed that what we aim to do has necessity and is valuable to the clinical circumstance. In addition, the supportive attitude and encouragement Dr. Liu gave us rendered us firmed our determination to make this year’s project as perfect as we can.
2. West China Hospital Visiting for the 2nd time With Dr. Yi Zhao, Dr. Chunyu Tan, Dr. Min Yang, Dr. Xiaomin Cen, Dr. Hua Zhao, Dr. Beibei Cui
After the last exchange with Dr. Yi Liu, we found that the direct communication with clinical doctor was very helpful and efficient for us to understand the status of clinical treatment and to improve our project. As a therapeutic project, doctor's advice was essential to us. Therefore, relying on the advantageous resources of West-China Hospital Sichuan University, we contacted Dr. Yi Zhao, Dr. Chunyu Tan, Dr. Min Yang, Dr. Xiaomin Cen, Dr. Hua Zhao, and Dr. Beibei Cui these six doctors, and we communicated directly with them face to face about what we wanted to know and what they suggested about our project.
We first asked the current situation and existing problems of clinical blood uric acid concentration lowering therapy for hyperuricemia and gout. The doctors' answers were basically similar. At present, the clinical use of blood uric acid concentration lowering drugs can basically reduce uric acid in patients and have less adverse reactions, but the biggest problem is the poor compliance of patients. Since the treatment cycle of acid lowering is very long, most patients stop taking medicine when they are not painful, so the treatment effect is difficult to achieve. At the same time, doctors tend to advise patients to control their diet and try to eat less-purine food, but patients are often unwilling to adhere to the doctor’s advice, causing the poor acid lowering effects. In addition, there is controversy over whether to use drugs on patients with hyperuricemia but without gout symptoms. On the one hand, the clinical endocrine guidelines are very strict and long-term hyperuricemia is bound to damage the body, so medication should be used; But on the other hand, if there is no symptom, it is very difficult for the patient to insist on taking medicine, and the drug is bound to cause certain damage to the body, so it is very difficult to solve this controversy. All of it give us with a very full clinical background, and we found out our project can provide a better solution to the above problems, which gives us great confidence. Because the colonization time of the bacteria is up to two weeks theoretically, it will reduce the number of taking medicine and improve the compliance of patients; Intestinal colonization can also reduce the degree of patient's dietary control, thereby reducing patient’s pain and improving their compliance; In addition, the intestinal colonization of engineering bacteria is different from the medication, it can solve the clinical controversy over whether to use drugs on patients with hyperuricemia but without gout symptoms.
We also inquired into the clinical treatment of refractory gout. Doctors said that there were indeed some clinically refractory gout patients with bad symptoms and even requiring dialysis, which allowed us to find the application objects for dialysis part project.
After that, we briefly introduced two parts of our project - the intestinal part and the dialysis part, and asked the doctors for their advices and suggestions. As for the intestinal part, the doctors agreed that our ideas were novel and feasible. Because the intestinal tract has always been a clinically neglected way to excrete uric acid, and if it is fully utilized, it must be a good method to reduce blood uric acid concentration. As for the dialysis part, there were differences among the teachers' opinions. Some doctors thought that this idea was radical, the effect was unknown, and there may be immune safety problems. The scope of clinical use was too small, it was better to concentrate on the intestinal part of the subject and make it better. There were also some doctors who believed that this was a new therapeutic strategy that was worth trying. It may be a ray of dawn for those patients in serious condition who currently had no treatment methods, but the problems of the safety and effectiveness must be paid attention to. In response to the doctor's feedback, we did a careful job of sorting out and absorbed the valuable suggestions.
Furthermore, some other advice also benefited us greatly. Dr. Hua Zhao told us that the clinical blood uric acid concentration lowering methods were very limited. At present, there are only three kinds of drugs allowed to be listed in China: allopurinol, benzyl bromide, and Malone. Therefore, it is very valuable to have other treatment methods, which can make the means of clinical uric acid lowering therapy more diverse. Dr. Yi Zhao advised us to pay attention to the coordination between the scientific significance and feasibility of the project, and suggested that we should focus on our intestinal part. In addition, as for the part of our animal experiments, he reminded us that the animal model of gout was different from that of hyperuricemia, and we must clearly consider to choose the correct model, besides the positive control group should be set up in animal experiments. We will integrate Dr. Zhao’s advice into the part of animal experiments, making the design more scientific and reasonable.
The interviews with the six doctors made us learn a lot. They let us realize that our subject was really meet the clinical needs, rather than indulged in empty talk, which brought the rich clinical background to the subject. We also got a lot of improvements on our project, we humbly absorbed and integrated them into the subject. Thank a lot to the doctors!
If you want to see the compete record of doctors’ Interviews, you can download it here!
Questionnaire for Patients with Hyperuricemia
As a therapeutic project, we believe that the patient's situation and their opinions on us are very important. Because our project ultimately serves the patients. Their needs are met and their pain is relieved even eliminated, which is the gold standard to evaluate our project. Therefore, we designed a questionnaire for patients with hyperuricemia, to investigate the patient's true situation and their views on the treatment of hyperuricemia.
This questionnaire included three parts, which were “basic information”, “basic living and treatment condition” and “views and opinions on new drugs or therapies”. “Basic information” included participants' age, sex, and blood uric acid concentration; “The basic living and treatment condition” included the degree of understanding for the harm of hyperuricemia, the degree of paying attention to hyperuricemia in daily life, whether on a diet, the feelings after the diet, reasons for the diet, whether use of drugs to control blood uric acid concentration, what drugs have been used and why to use them, etc. “Views and opinions on new drugs or therapies” were mainly to investigate the aspects of participants' attention on new drugs or new therapies.
We have widely disseminated through the Internet media, and received nearly 100 valid questionnaires. We conducted a statistical analysis of the questionnaire results, and we have got a lot of valuable information. The information worth discussing included the following four items:
Firstly, in the investigation of the degree of understanding for the harm of hyperuricemia, nearly fifty percent were not aware of it. Secondly, in the investigation of the degree of paying attention to hyperuricemia in daily life, nearly fifty percent of the participants did not pay attention to it. Integrated the previous two points, we found that the understanding degree and attention degree of the disease in patients with hyperuricemia were very scarce, which is the reason why we have published the Handbook of Hyperuricemia and held the Exhibition in Chengdu Public Library.
Thirdly, in the investigation of how they felt about dietary control in patients with hyperuricemia, over fifty percent of them felt painful, which also reflected dietary control had a great impact on the quality of life of patients, and reducing dietary control will be more appropriate to the needs of patients.
Fourthly, in the investigation of views and opinions on new drugs or new therapies for hyperuricemia patients that they were most concerned about, more than half of the patients believed that efficacy and safety were the most important. We attached great importance to these points, and we integrated the needs of patients into the improvement of our project. We will seriously consider the importance of improving the consuming efficiency of uric acid by engineering bacteria, prolonging the time of colonization, and reducing the adverse reactions such as immune rejection caused by engineering bacteria, so as to strengthen the efficacy and safety of intestinal part of our project.
If you want to see details of our questionnaire and the specific statistical analysis of the questionnaire, you can download it here!
Talking with General Product Designer of Sichuan Nigale Biomedical Ltd., Fei Li
Our project this year includes the design of analogous dialysis device, therefore we talked with Mr. Li Fei, who is product designer and engineering department section chief of hospital products division of Sichuan Nigale Biotechnology Co. Ltd. Nigale has extensive experience in design and production of devices related to dialysis equip, so we consulted Mr. Li Fei about the design, patent application, the later production promotion of our device.
We firstly introduced our project and the device in our project to Mr. Li Fei, and asked him for advice. He thought our idea and design is outstanding, but we should pay close attention to quality and security of our device. Because security is of critical importance, and the performance could be improved in the process of using. We posed a question that how to deal with problems could happen in the hemodialysis pipelines, such as infection, Mr. Li emphasized that the quality and the matching of products is the factor that should be consider primarily. Then we asked Mr. Li what we should take care while we were to apply for patent, He told us that the patent includes two kinds, one is patent of the method, one is patent of the device, the former is invisible while the later is tangible. We can try both parallel. Although the later can not get results quickly, as long as this method is feasible, patent of it can be applied firstly. The others could apply for another patent by changing something on the basis of our original design, which means the value of patent of device is limited. The method, nevertheless, is constant, and the application of patent of it could be better. At last, we asked Mr. Li if he had some suggestion for the promotion and going into market of our product. He pointed out that dialysis consumables are in great demand in China, and if our project is mature enough and possesses investment value, there must be companies purchasing our patent and putting the product into market. He thought our product has market potential.
Through the communication with Mr. Li, we got his affirmation of our device, and we also got suggestion that we should focus on the quality and matching problems of the device, and we should improve our device by miniaturization and ensuring safety. In addition, we learned about detailed methods, domestic status, laws and regulations, and strategies related to our later application for patent and promotion of product. Mr. Li answered our questions seriously and discussed with us on our doubts, which benefited us a lot.
Talking with Prof. Melinda Jones from Texas Tech University about Bioethical issues
Prof. Melinda Jones is the Associate Dean for Non-Traditional Undergraduate Studies in the School of Nursing of Texas Tech Univeristy. She currently teaches courses in health law and ethics. Dr. Jones is admitted to The Supreme Court of the United States, the State Bar of Texas, and is a member of the Lubbock Bar Association, The National Association of Nurse Attorneys, American Nurses Association, and Sigma Theta Tau International. She attended the “University Immersion Program” of Sichuan University and taught “Bioethics in Clinical Practice” for two weeks in West China Medical Center. We asked Prof. Melinda Jones several enthics questions for our project. Especailly the dialysis part of our project, which may cause risk in the clinical trails.
Prof. Melinda Jones stressed a few key aspects in the bioenthics we had to notice. She thought as for clinical trail, autonomy must be considered as the first thing. The patients should fully know the details about the project, what benefice it might bring and the risk the patients might take. Seperated from that, nonmaleficence is the also an important thing to consider, no matter for animal expriment or clinical trail of our dialysis device. For all these kinds of experiment, we should get the permission from the authority who is responsible for this to make sure to avoid the unnesscessary suffering for animals and harm to people. We don’t want our patients to get worse after the research.
Those principles play important roles in our animal experiment design. We compare many methods to establish the mouse model, but due to our lack of pracitce in gavage, we decided not to take risk to do this, according to the nonmaleficence principle. We replace the standard yeast extraction gavage method to the adenine feed method to establish the HUA mouse model to reduce the hurt as much as possible. And she suggested us to put our permisson of the Institutional Review Board for our animal experiment on the poster to clarify it. We adopoted this idea.
iSWU 2017
To strength the collaboration with other iGEM groups, we hosted the 2017 China iGEM Southwest Union (iSWU), and invited 4 groups in Southwest China to communicated each group’s project and exchange views.
On 8th April 2017, the invited 4 groups: SCU-China, SiCAU-iGEM, TMMU China and UESTC-China came to the WestChina campus of Sichuan university. We showed them around the campus and invited them to visit the laboratory where we do experiment. During the visit, we communicated a lot about the competition and experiment. In the afternoon, all the groups formally started to do presentation one by one. After each presentation the invited teachers asked questions and let iGEMers to think and express opinions. The discussion was heated and let each group gain precious suggestions. In terms of our own project, we were impressed of the valuable advice from TMMU-China. They suggested that we can change or chassis bacteria in the dialysis part from Bacterium typhimurium to Bacillus subtilis, and this kind of adjust can make the dialysis system safer and better. After careful consideration and weighing both advantages and disadvantages of those two chassis strains, we finally adopted their suggestion and chose Bacillus subtilis to be the chassis bacteria in the dialysis system. Thanks TMMU China for their valuable suggestion and we believe all the groups attending this conference have gotten some useful advice. All in all, collaborations let our opinions more diversified and let our projects more intact.
