Team:ShanghaiTechChina B/Integrated Practices
Introduction
IGEM encourages participants to conduct human practice, to see the world, and to exchange experience with other people. We love this idea because it offers us a chance to get inspired by the society, allows us to better understand the meaning of our scientific research, and constantly reminds us how and why we should contribute back to the society. Therefore, we strived to integrate human practice activity closely into our project advancement.
We began by surveying the public knowledge of intestinal diseases and by interviewing three leading professionals (doctors and researcher) to get a vivid understanding of the severity and incidence of intestinal diseases. We realized intestinal diseases including IBD, are big threats to human health, yet without a cure and without sufficient public acquaintance. We therefore decided to tangle IBD by engineered bacteria and succeeded in proof-of-concept experiment in using bacteria produced therapeutic agent (EGF) to alleviate IBD symptoms. During the communications with other teams , we received concerns on safety issues that we must deal with. So we upgraded our biosafety strategies by not only using two types of kill switches, but also using a 'warship' (which limits bacteria spreading and still allows nutrient and chemical exchanging). In addition, in the spirit of raising public interests, we established an IGEM Day for Public Interests (IDPI) to advertise the beauty of synthetic biology to the community. Meanwhile, we used posters and popular social media to introduce intestinal bowel disease and our work to the society.
Interviews
At the beginning of our project design, we thought of many possible treatments but during the process of reasoning we encountered some difficulties. In the spring of 2016, at National Center for Protein Science Shanghai, we interviewed Professor Pengfei Lu who was a researcher at the Paterson Institute for Cancer Research in the University of Manchester. He specializes in development and proliferation.
When he got to know that we wanted to fight IBD, he pointed out to us that Epidermal Growth Factor (EGF), which is an important factor of his ongoing research, is a molecule that has the ability to promote regeneration of cells in the inflammatory regions. Prof. Lu introduced us detailed mechanisms of this growth factor and emphasized that in different human tissues, EGF will have different effects. Therefore, as a growth-promoting factor, EGF may bring about the risk of over-proliferation and even cancer. He reminded us that we have to pay great attention to safety issues.
In the end, Prof. Lu encouraged us to be ambitious and have a try. It turns out that this interview became the foundation of our project!
In our project, we chose intestinal bowel disease as our object of study. To have a better understanding of IBD and obtain the first view of the current situation of patients, we contacted two doctors and set up an interview with them.
One is Ge Wensong, who comes from Shanghai Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The other is Zhang Shengyu, who is from Beijing Xiehe Hospital Affiliated to School of Medicine,Tsinghua University.
Here is the summary of the interview script. (Q= question, A= answear)
Q: Human diseases include not only intestinal diseases, but also many other diseases which threaten human health seriously. So what’s the reason that made you choose to do the research in the field of intestinal diseases?
A1: Diseases involved in gastroenterology are complicated. One of the most prominent disease is intestinal diseases. There are so many different types of intestinal diseases and a major part of them consists of inflammatory bowel disease and intestinal tumors. Studies of intestinal disease are the core research of intestinal diseases nowadays. Personally, I’m very interested in the field of intestinal tumor.
A2: There are three reasons:
Upon the development of social economy and the change of life styles, disease spectrum of digestive system also has been changing. For example, the occurrence of inflammatory bowel disease is closely related to the the process of industrialization in Europe and America. And I antipate that intestinal diseases will be one of the most common diseases of digestive system in the 21st century in our country. And the obvious increase of the occurrence of inflammatory bowel disease in our country in recent years proves this opinion.
During my years of clinical training, I truly understand the influence brought by intestinal diseases to our patients. For example, the recurrence of the disease seriously affects people's health and lives and aggravates their economic conditions.
Intestinal microecology is the research hotspot in recent years. However many pathogenesy of intestinal diseases is still vague. I’m greatly interested in studying inflammatory bowel disease from the perspective of intestinal microecology.
Q: We really hope to learn more about the classification of intestinal lesions from the perspective of medicine.
A1: The first classification of lesions in digestive system is mainly based on dissection, including esophageal diseases, gastroduodenal diseases, small intestinal diseases, colon diseases, anorectal diseases, liver diseases and biliary and pancreatic diseases.
Actually, each disease from different splanchna can make a sub-classification, like congenital disease or genetic disease, inflammatory diseases, tumor diseases, infectious diseases, metabolic diseases, etc. Also there are other symptoms of gastrointestinal involvement caused by some certain disease. For example, immune disease can cause the gastrointestinal involvement.
A2: There are four types of lesions in digestive system : esophageal and gastric diseases, intestinal disease, liver diseases and biliary and pancreatic diseases. Intestinal disease includes infectious intestinal disease, inflammatory bowel disease, ischemic bowel disease, autoimmune enteropathy, medical bowel disease and tumor enteropathy.
Q: As an outstanding doctor, you must have participated in many major discussions of operations on patients and intractable cases. We would appreciate it if you can offer us some details about some cases caused by inflammatory intestinal disease and patients’ following development.
A1: Inflammatory intestinal diseases is an important type of intestinal disease, which is one of the priorities of our work here at Department of Gastroenterology. There are mainly two types of inflammatory intestinal diseases: ulcerative colitis and Crohn's disease.
The target organ of ulcerative colitis(UC) is colorectal mucosa mostly, which means that inflammation is limited in mucous layer. The main clinical symptoms are abdominal pain, diarrhea and blood stool with mucus and pus. Most of cases are chronic and recurrent, and a little of them is fulminant. We treat mild-moderate patients with 5-aminosalicylic acid(5-ASA) preparation. If the patient is not sensitive to 5-ASA, we give them glucocorticoid. If the patient is also resistant to glucocorticoid, we add imuran(AZA) or 6-mercaptopurine(6-MP). Note that patients with severe lesions should use intravenous corticosteroid, and for nonresponder , we consider to use intravenous cyclosporine or to operate, which remove the whole colon and rectal mucous membrane. Some foreign countries use infliximab or adalimumab to induce and maintain remission. But this treatment is not widely used in our country.
Crohn's disease(CD) may involve the whole digestive tract, any place from oral cavity to crissum, typically at the terminal of small intestine, which is ileum and ileocecus. It is an inflammation covered the whole layer. The general pathology of CD is fissuring ulcers and changes in mucus pattern, which will make intestinal tract become narrow and induce the formation of internal/external fistula, characterized by bellyache, fever, abdominal mass and hematochezia/ melaena. We mainly use glucocorticoid to induce remission, supplemented with 5-ASA preparation. To maintain the remission, we mainly use AZA or 6-MP. If it is difficult for glucocorticoid to induce remission, we can try the methotrexate(MTX), cyclosporine(CsA) and infliximab. The latter applies more but there exists the primary/secondary drug resistance problems.
Ulcerative colitis is less difficult to treat relatively. Patients with poor therapeutic effect can choose to have a operation, which is considered to be a radical cure of disease. ( Of course, not every patient in our country will accept the fistulization at the end of ileum. However, PORCH operation is not spread widely currently. ) Patients who have had ulcerative colitis over 10 years has an increased risk of colon cancer. It is more difficult to treat Crohn's disease, because recurrence tendency always exists throughout one's life. Operation can only deal with the problem that intestinal tract become narrow, get block or bleeding. What’s more, it often brings up anastomotic recurrence, thus we mainly consider medicine as a treatment. However, many CD patients require to undergo surgery once or twice all their life, facing the risk of short bowel syndrome.
Actually I think that particular case is not the key point, and learning some common sense about the disease is more meaningful than individual cases.
A2: Nowadays, treating Inflammatory intestinal diseases is still a difficult problem over the whole world, mainly in terms of poor response to drug therapy for some patients, recurrence after treatment and serious adverse reactions after a long-term drug therapy. Of course, some patients still have to undergo an operation because of the bowel obstruction, intestinal perforation, intestinal fistula, hemorrhoea, etc. And some patients die from various complications.
Q: We hope to understand the common methods of treating intestinal diseases, especially the inflammatory intestinal diseases
A: Now the methods of treating inflammatory intestinal diseases mainly include drug therapy (5-aminosalicylic acid, hormone, immunization drug, antibiotics, biologics), operative treatment, stool transplantation, stem cell transplantation and leukocyte elution adsorption treatment.
Q: Now the cure rate of inflammatory intestinal diseases, especially chronic diseases and severe diseases, is still low. We hope to know the disadvantage of current methods and techniques of treating inflammatory intestinal diseases, from the perspective of a clinical doctor.
A1: Treatment is mainly based on the drug therapy, because 5-ASA preparation has poor tolerance and glucocorticoid has several side effects (hypertension, hyperglycaemia, osteoporosis, etc.). Chinese people have a case of a certain proportion of metabolic enzyme deficiency that may cause the bone marrow depression. And biologics has a high risk of infection and may exists the probability of drug resistance.
A2: Disadvantage of current methods and techniques of treating inflammatory intestinal diseases is mainly about: 1. lack of effective drugs for all patients, even if the biological agents which is researched and developed in recent years and whose efficacy is only about 50%. 2. There are concerns about the drug for long term use existing serious adverse reactions. 3. Some drugs have problems with secondary failure. 4. Expenses.
Q: The leading edge of biological sciences is about the direction of the intestinal ecosystem. However, there is a big gap between the theoretical research and practice. So what’s your opinion about this current situation?
A1: Intestinal micro ecosystem (intestinal flora) is a hot topic in recent years. Actually, inflammatory intestinal disease is a pathogenesis with genetic background, which involves environment, immunity and infection.
Maybe it is not because of a certain bacteria, instead, because of the change of the proportion of some bacteria or the change of metabolites. These factors can initiate or accelerate diseases, but they are not the determinants.
For children, probiotics are the important method to maintain remission. But for adult patients, it is still hard to observe this effect. Actually, intestinal flora is in large quantities and very complicated. Therapeutic mechanism of supplementary micro ecological preparation (probiotics, prebiotics, synbiotics, etc.) is not clear and sometimes it is hard to determine the clinical effects.
A2: Intestinal microecology is one of the factor causing inflammatory bowel disease. Treating inflammatory bowel disease completely through changing intestinal microecology still have a long way to go. For example, fecal bacteria transplantation is effective only in a few patients. (But for the inflammatory bowel disease with the concurrency of infection of clostridium, it is the first-line therapy.) Personally, treating inflammatory bowel disease in the direction of intestinal microecology is very promising.
Survey
This survey consists of three major parts: intestinal diseases, gut flora and synthetic biology. As people know life-related diseases, i.e. intestinal tract diseases, better than merely intestinal diseases, the survey is needed to start from a boarder aspect and be narrowed to intestinal diseases.
363 shares of answers are received, with 81.82% of which have no idea about iGEM. People above 40 years old contribute to 46.55% of all answers and people from 26~40 take up 15.43%. People below 26 account for 15.43%. Participants come from all walks of life, with only 36.36% of them being students.
In the first part we investigated people’s cognition in intestinal diseases. People believe that cancer and AIDS are the most severe diseases. Heart attack ranked the third, followed by Parkinson’s disease and Alzheimer’s, then the pneumonia. Intestinal tract diseases are among the least severe common diseases, as expected. However, 84.3% of participants have witnessed the suffering of intestinal tract diseases, with the cost of treatment covers a long range. 8.82% cost is below ¥100, 29.41% ¥100~500, 24.18% ¥500~1000 and 23.2% beyond ¥2000 . Only 6.21% participants claim that 1~2 days are needed to cure the disease, while different people suffer from various intestinal tract diseases, with the time required to cure ranging from days to more than half a year. Furthermore, 50% people get the diseases once or twice, while the rest suffer more often. Among all the intestinal tract diseases, diarrhea, bellyache and stomachache are the most common ones. In this part of survey, we mixed intestinal diseases and tract diseases intentionally, and we are surprised to see that only 50.69% of participants can distinguish one from another. However, people know about detailed intestinal diseases, i.e. 70.6% heard about IBD . They also know about common treatments of these diseases. 60.44% know about dietotherapy, 66.21% know the Chinese traditional treatment. Medicine and operation are the most known. 26.37% are conscious of fecal bacteria transplantation, along with the strict test it needs to run, which could be considered a disadvantage. The other advantages of tradition treatments mentioned by participants are pain (58.52%), immune system disorder (53.57%), drug allergy (52.2%) and others (i.e. slow effect). 64.19% of participants never came into contact with any propaganda or advertisement on intestinal diseases, and most (95.87%) of them feel it important to strengthen people’s comprehension of intestinal diseases.
In the second part we asked about gut flora. Most of participants believe the relationship between gut flora and intestinal to be symbiotic. Nearly all of them heard about Escherichia coli, while 49.18% knows Enterococcus faecalis.
In the third part we started propagating our project and gain feedbacks.
In conclusion, the result gives a proof of our initial conjecture that people are unconsciousness of the severeness of intestinal diseases, while they have been suffering from such things greatly. Besides propagating our project, we managed to make respondents aware of the differences between tract diseases and intestinal diseases and the detailed treatments to these. Consequently, we keep popularizing the knowledge in this field, as we always do.
Social Media
People nowadays spend a lot of time on social media, gaining information fragment by fragment. Subscription account on WeChat is a very popular form of social media in China. In the previous survey, our team found out that most Chinese know little about intestianl diseases and much more superficial about synthetic biology, many of whom having no idea what it is.
In order to create a window for our team to communicate with the world, our team applied and managed a WeChat subscription account, trying to share the knowledge of synthetic biology and trending news about medical treatment responsibly. This account recorded our progress and interesting comments about synthetic biology. The articles were written by our team members and were published regularly. The number of Subscribers are increasing as we speak.
HUST_Cheering
On July 7th, members of team ShanghaitechChina_B attended HUST-CHEERING seminar hosted by Huazhong University of Science and Technology in Wuhan, China. After several days of heavy rains, the city suffered serious water-logging. Power supply was damaged in HUST. Organizers and participants had to move from the hall to the teaching building to continue our seminar. The classrooms were not spacious but were big enough for passionate IGEMers.
Because ShanghaitechChina_B is a newly founded team, we gave a presentation about our project and received many pieces of valuable advice. Experienced IGEMers also gave their encouragement to our team. Our team gained a more comprehensive understanding of IGEM competition through this event and became much more interested in synthetic biology. It was quite an experience to establish friendships with other IGEM teams.
iDPI
Owing to one of the purposes of IGEM that is to improve public awareness and knowledge of synthetic biology, as the first team founded in ShanghaiTech IGEM, we decided to establish an IGEM Day for Public Interests (IDPI). This year, the IDPI invited students and teachers from Shanghai Concordia International High School and held an IGEM Open-Lab Day on Sep 3rd, 2016. Along with another IGEM team at Shanghaitech, we warmly welcomed the visiting delegation from Concordia. Their delegation included two major science teachers and eight students from different grades. We delivered two introduction speeches about and synthetic biology and the IGEM on behalf of two ShanghaiTech IGEM teams respectively. One was done by Haolong Zhu, a member of ShanghaitechChina Team, another was by Shenjian Ai, one of our team member. We introduced our IGEM project Gutrio to these curious visitors. To explain the design of our project, we made analogy of engineered bacteria to trained agents who carried secret weapons to terminate their targets. Thus, we described our potentially complicated experimental system in an understandable manner - an amazing adventure. Those high school students were all cheered up: “It was really cool!”. Our provocative speeches did stimulate their interests to synthetic biology.
After that, we held an open discussion session, where we witnessed the curiosity and passion of these high school students towards synthetic biology and IGEM. We shared many details of the IGEM competition. Besides IGEM, we also discussed many frontier life science progress and appreciated their unique views.
We then showed them our lab space and facilities, including cell sonicators, ultra-centrifuges and flow cytometry. We explained the principles using analogies and metaphors. The IDPI ended around 6 pm and we can see through their eyes and faces that these high students were reluctant to leave. As one of the visiting students commented, this tour was 'so impressive and amazing'. We believed that the one day IDPI truly delivered the IGEM core value by arousing their curiosity to explore the secrets of nature. A few days after the visit, the teachers contacted us to consult us for building a biology lab. We really hope that this is the beginning of another amazing adventure!
Poster
During the investigation of intestinal diseases, we realized that IBD is a world-wide threat to human health with a great morbidity and severity. And we found that, unfortunately, public awareness intestinal diseases like IBD is insufficient.
Thus, we decided to introduce IBD and its hazard to the public. The symptoms, diagnosis and related information about IBD were collected.
A poster was designed by our team to show the public that IBD is threating our health, and we need basic knowledge about it. The poster includes the definition, morbidity, diagnosis, symptoms and potential causes about IBD. Our IGEM project Gutrio and the idea to utilize synthetic biology to treat IBD were also introduced.
We have introduced IBD to many communities, and wish more and more people to realize the severity of IBD.
