Team:Jilin China/Integrated Practices

Particles

Human Practices

To improve the feasibility of our project and stimulate public interests in our work, we did the following human practices. First, we held meetings with experts in cancer-therapy research to get academic advices on our project. After finishing a sketch of our project plan, we made surveys among faculties in cancer research and attend a cancer summit in Changchun to get suggestions and comment about the feasibility and safety of our plan. Next, we discussed with some professors in law to understand better the potential biosafety issues of our project. All these work helped us make great improvement of our project. To help people understand more about cancer therapies and our project, we attended a HUST-Cheering meeting, did a TED presentation and were interviewed by some local TV programs, including the Jilin University Television. Furthermore, we made online games, established a public Wechat platform and a twitter account to get feedback from the general public on the internet. To stimulate the interests in science among high school students, we gave a seminar on synthetic biology and our project in a local high school.

Human Practices - Overview

Professional Advice: 1. Meetings With Expert: Professor Ying Xu;2. Law & Regulation

Social Influence: 3.Changchun International forum of Oncobiology and Translational Medicine; 4.TEDxJLU; 5.HUST-Cheering Meeting; 6.Survey; 7.Social Network Platforms; 8.Newslatter; 9.The iGEM Booklet; 10.TV Interviews; 11.iGEM Alliance

Education: 12. Youth Education & 13.Illuminating Little Game

How our human practices have been integrated into the project?

1.Meetings With Expert: Professor Ying Xu

Ying Xu: Chronic Inflammation and Tumor

1.Meetings With Expert: Professor Ying Xu

Lecture: Chronic Inflammation and Tumor

Place: Computer Building A521 Auditorium

Professor Xu, got a bachelor's and master's degree from Jilin University in 1982 and 1985 respectively, and received a doctor's degree from the department of Computer Science at the university of Colorado in 1991. Now he is in the board of University of Georgia and a famous scholar in science and technology, the director of the center for systems biology research at the University of Georgia. In 2009 he was awarded as a "Changjiang Scholar", the chair professor at Jilin University. In 2012, he was recruited as a Jilin university professor in "one thousand plan". Professor Xu is a world-class expert in computational biologist, bioinformatics, cancer research and so on. He has made quite a few significant contributions in the field of bioinformatics, for example: (a) biological pathways and the calculation method of networks and model research (b) cancer of bioinformatics (c) comparative genome analysis (d) Protein structure prediction and modeling. The papers he published had more than 40 H-Index. He got the Distinguished Scholar of Georgia at 2003, and was selected as American Association for Advancement of Science Fellow.

In the lecture, professor Xu introduced their recent research progress. They investigated the transcriptomes of different tumor tissue and make big data analysis. They made two major discoveries. One is that all the tumors went through the process of chronic inflammation, but not all of the chronic inflammation can lead to cancer; and the other is that the basis of tumor proliferation is Fenton reaction.

Finally, professor Xu suggested some useful suggestions to prevent cancers:

First: Stay away from meat, red meat have higher iron content, which is the main force of Fenton reaction;

Second: Stay away from alcohol, especially the person who would show red face after drinking, the body is telling you not to drink;

Third: Male should make regular blood donation to help prevent accumulation of iron in the body; women don't have to bother before menopause.

1.Meetings With Expert: Professor Zhe Li

Meeting with professor Zhe Li,
a tumor research scholar

1.Meetings With Expert: Professor Zhe Li

On December 17, 2015, professor Zhe Li was invited to give a seminar at the 13, 14 Tang Class forum at the Life Sciences Building.

Professor Li got his bachelor degree from the department of genetics at Fudan University in 1992, went to the United States in 1995 and got his Ph. D. training at the laboratory of Nancy A. Speck, a world-class expert at the research field of blood and transcription factors. In 2003, he got his Ph. D. degree in molecular and cell biology at the Dartmouth College, school of medicine. During his Ph. D. training, he made a systematic study of hematopoietic differentiation, GATA 1 transcription factor and leukemia, and published many research articles at high-impact journals, such as Nature Genetics, Blood, Cancer Cell and Genes Dev. In 2009, he became an assistant professor at Harvard Medical School, Brigham and Women’s Hospital, and continued his research at the differentiation of hematopoietic system and the molecular mechanism of leukemia and cancer biology. He has established a variety of animal models, made outstanding contributions at the pathogenesis of cancer research and treatment, and he has received many national funds in the United States, so that his research has been well funded.

Professor Li introduced the current research trends of tumor prevention and treatment, made in-depth discussions for cancer stem cells, tumor biomarker, the relationships between the tumor and inflammation. In addition, professor Li also talked about his expectations for good students, which are “motivation”, “detail”, and “attitude”. Professor Li is an excellent scientist, and we would like to follow his path and make our contribution to the scientific research.

2.Law & Regulation

Law & Regulation about gene science and technology

For this project, we modified some genes using techniques of synthetic biology and constructed a recombinant plasmid. The Bifidobacterium transformed with this plasmid can settle in the tumor regions, and secret the apoptin protein, and kill tumor cells. This could potentially be developed into a novel therapy method for the treatment of tumors. To a certain extent, gene modification is gene therapy, and our project is about gene therapy to tumor cells, imperceptibly we may put ourselves in the center storm of ethical and juristical issues. Therefore, to have a deeper perspective about the ethical and juristical issues in China, as well as to better understand the potential biosafety issues of our project, we discussed some questions with two experts in law, Ms. Fang Ruan, a judge from the People's Court of Jinjiang, China, and Professor Zhipeng He, Jilin University School of Law. They shared with us their insights and a great critical thinking of moral and ethical issues. Thanks for their generous help and assistance; we get a complete result in the Human Practice.

Dialogues with law expert, Ms. Fang Ruan

We want to have a better understanding about law and regulation actuality in China. Meanwhile, We have great interest and also are concerned what will happen if synthetic biology is applied to human being. Sooner or later, based on the development of gene therapy, the technique used to modified human being will come true. However, what should we do to guarantee the safety? And is there any law about gene technology? Based on our concern, we have a talk with Ms. Fang Ruan, a judge from the People's Court of Jinjiang, China. She has great experience in judicial work in Intellectual Property Law. In the conversation between Jilin_China and Ms. Fang Ruan, she provided us with a full-scale perspective of gene technology law in China.

The following 4 questions are answered based on our conversation.

1. In China, what are the existing laws concerning gene technology?

The legal aspects of gene technology in our country, embodied in science and technology law,which is an important part of our legal system. Science and technology law refers to the state of science and technology activities arising from the various social relations to adjust the legal norms.

China has developed a number of technical and legal norms on encouraging innovation, safeguarding inventions and patent rights. In the Constitution, we mentioned that science and technology are part of the productive forces, in addition, the state has also formulated the " Science and Technology Progress Law of the People's Republic of China", " Patent Law of the People's Republic of China " and so on, all of these have a great impact on gene science and technology.

"Science and Technology Progress Law of the People's Republic of China" is the basic law of our country, however, there are the protection of intellectual property rights and scientific and technological achievements reward of the laws and regulations related to gene technology,, such as " Patent Law", the legislation of scientific and technological research institutions and the management of science and technology associations, such as the "Natural Science Research Institutions to establish, adjust and approve the pilot scheme", there are also some international scientific and technological exchanges provisions, international treaties and agreements.

2. How popular is the law on gene science and technology nowadays? Whether it is necessary to increase the publicity?

The concept of scientific and technological law is first proposed by the Chinese people. But our development is extremely slow. In recent years, the United States has established more than 100 research centers of various types of technology, published dozens of specialized magazines, nearly a thousand kinds of monographs. Taiwan in recent years has also set up seven research centers of science and technology, and some universities also specifically recruit graduate students in science and technology, science and technology enterprises specializing in the recruitment of legal and technical director. At the same time, many countries are also strengthening the research and legislation of science and technology. Science and technology legislation, scientific research and specialized personnel training has become a global boom.

China also adopted the Popularization of science and technology in People's Republic of China in 2002, which shows that China is also attaching importance to the popularization of science and technology law. It has established a new mechanism from the angle of legislation and social promotion. It has also formed an atmosphere of popularization.

In my opinion, there is still a long way to go for the promotion of science and technology law, in which scientific research and technology development institutions, institutions of higher learning should become the main force of propaganda, such as through popular science activities, popular science publicity , held lectures and other measures to further expand the public understanding of science and technology work and support.

3. What legal developments have been made so far? What are the existing deficiencies, and if there any suggestion for Legislation in China?

So far, in the Constitution, civil law, administrative law, criminal law and other traditional jurisdictions had establish a large number of technical and legal norms in the legislation, but also carried out special legislation in the field of science and technology. Its main legal system can be divided into several aspects, such as scientific and technological progress law, science and technology contract system, scientific and technological achievement right protection and so on.

With the development of the times, China's science and technology legislation also need to improve. Such as legal gaps, some legislation is too principled and lack of operability, and some regulations are ineffective, many laws and regulations are issued in different departments in the process of reform, and therefore there are contradictory and repeated too much. Therefore, China's scientific and technological legal system construction should also continue to strengthen and perfect.

My proposal for this is: Our country should further speed up the process of scientific and technological legislation, targeted and complementary legal gaps, and further refine the relevant implementation details, make scientific and technological legislation more systematic, standardized, and adapt to the times.

4. Whether the genetically modified bacteria can be applied to human disease treatment?If so, what are the legal considerations?

With the advances in modern DNA manipulation technology, humans can modify bacterial DNA, thus affecting human health. Many bacteria have been modified to synthesize molecules needed by humans, such as hormones, interferon, and antibodies. So we can say that after the transformation, bacteria can become a cure for disease medicine, to make greater contributions to human health.

The reasons why biotechnology companies have such high risk is that there are many biotechnology industry-related regulatory laws and regulations. Common legal risks in the biotechnology industry are the risk of intellectual property right and the risk of daily business activities.

Intellectual property rights are the basis for the survival and development of biotechnology enterprises. Relevant legal risks often occur in areas such as: early R & D contractual agreement, rights attribution, patent and trademark acquisition, use, maintenance, transfer, license, infringement, cyber squatting, fraudulent use and so on.

Risks of business activities. The biotechnology industry is heavily regulated. For example, individual consumers of the product efficacy and side effects of different reactions, easily lead to product liability complaints, litigation and claims, and even lead to public relations events, improper handling will lead to significant losses.

Critical Thinking about Law Related to Gene Technology from Professor Zhipeng He.

Zhipeng He, an excellent professor of Jilin University School of Law, who has written books in law, and is good at teaching and scientific research of Law, shared with us three law principles.

From his perspective, which is profound and thought-provoking, firstly, while there are phenomena in the society, it is not to say that there must be some law concerning the very kind of phenomena. It is the maturity of the society and the consensus we reached contribute to the forming of law. Any kind of radical law is not mature response to the society phenomenon.

Secondly, it is the development of life that leads the development of law. No vice. Thirdly, genetic research is a matter of hot dispute, however, the focus of law should be concerning relevant technology and social more. All in all, the law is passive.

Who can tell how the law will be in the future? We guess no one. However, Chinese scientific research needs a more effective ethical regulation urgently. The more we human being have in technology, the more we are exposed to danger. We need the law so that we prevent mistakes happening again after we have done something wrong. But only the practice and real situation in the near future can better promote the development of law of gene technology. And when that day comes, the development in gene editing and therapy techniques may have greater breakthrough. We will be not dare to welcome that day, and with our efforts, the gene therapy/technology can make progress in law.

3.Changchun International forum of Oncobiology and Translational Medicine

On June.19th, 2016, Jilin_China Team attended Changchun International forum of Oncobiology and Translational Medicine. We interviewed the experts in cancer biology about the current trends and newly developed methods of treating solid tumors. In addition, we also asked their advices on our project.

3.International Forum

Professor Yun Dai from Jilin University gave a lecture about precise targeted therapy and drug-resistance in hematologic malignancies. We consulted him about drug-resistance. He told us there are two kinds of drug-resistance: primary resistance and long-term resistance. He also used one repressor named HDAC as example. It has curative effect to treat neoplastic hematologic disorder, but it has unsatisfactory result to treat solid tumors. Although HDAC is effective in vitro, it still needs more experiments to be verified. He also mentioned that if we want to develop a real drug, we should consider safety tests, pharmacology researches and clinical trials as well.

3.International Forum

Professor Cheshi Chen from Kunming Institute Of Zoology, CAS, gave a lecture about the development of new animal models for breast cancers. He discussed four kinds of common animal models: spontaneous animal model, experimental animal model, implanted tumor model and PDX model. He also mentioned some alternative animal models of breast cancers in addition to these commonly used laboratory mice.


Assistant Professor Boyi Gan from the University of Texas MD discussed energy metabolism and sensing in cancer. We asked him some questions about current cancer therapies. He told us that although radiotherapy and chemotherapy have low targeting, these two therapies are still major treatments in clinic application. Some new methods, such as targeted therapy and immunization therapy, may demonstrate better targeting effects, but they still have many weaknesses. Targeted therapy is designed to treat patients with specific mutations, so the rates of mutation largely determine the efficacy of the treatment. Immunization therapy can educate patient’s own immune system to cure cancer, and it is now widely used in clinic. He suggested that our group should verify whether bifidobacterium could educate human immune system.

3.International Forum

Assistant Professor Xiangwei Wu from the University of Texas MD gave a lecture about early-disseminated tumor cells as a biomarker for colorectal cancer early detection. A specific feature of the apoptin used in our project is that it only enters into nucleus of solid tumors but stay in cytoplasm of normal cells. We consulted him whether the apoptin could be used as a biomarker as well. He said that we should first use nude mice to figure out whether MCF-7 cells can multiply in vivo by subcutaneous injection. Next, we should use CTC cellular immunostaining to figure whether the apoptin could work well.

Professor Songyang Zhou from Sun Yat-sen University mainly discussed about telomere signaling networks in aging and cancer. Associate Professor Yong Xu, Professor Sheng Zhang, Professor Hui Zheng discussed human obesity, huntingtin and Alzheimer’s Diseases with us.

4.TEDxJLU

TEDxJLU Conference was held in Jilin University in October 19th, 2016. We found it is a good opportunity to let people know synthetic biology and iGEM, so we gave a very good talk for this conference.

Our team was the third one to give the talk and the team member, Tingtao Wu, took the responsibility. Firstly, he introduced synthetic biology by giving the examples of the synthesis of artemisnin and the work of Jeff, which used the method of synthetic biology to assist in curing cancer. Then, Luwei Huang briefly introduced the definition of synthetic biology and its advantages. Subsequently, some problems were discussed and many potential resolutions were proposed.

4.TEDxJLU

TEDxJLU Conference was held in Jilin University in October 19th, 2016. We found it is a good opportunity to let people know synthetic biology and iGEM, so we gave a very good talk for this conference.

Our team was the third one to give the talk and the team member, Tingtao Wu, took the responsibility. Firstly, he introduced synthetic biology by giving the examples of the synthesis of artemisnin and the work of Jeff, which used the method of synthetic biology to assist in curing cancer. Then, Luwei Huang briefly introduced the definition of synthetic biology and its advantages. Subsequently, some problems were discussed and many potential resolutions were proposed.

Secondly, Yuwei Huang started to introduce iGEM to the audience, which was also the most important part of this talk. He started with the history of iGEM and its recent development. Then, Mingjun Zhang introduceed the primary responsibillities of members who want to participate in the competition. After that, some main contributions that iGEM has made to the development of synthetic biology were also introduced, including the construction of RSBP and some novel ideas raised from the competition. In addition, some achievements that the previous teams made were also included in this part.

At last, this speech was concluded with the introduction of our own project. Since the time was limited, we just introduced the basic ideas and the important progresses of our project. We also illustrated some of our results from experiments, human practice and wiki.

The talk was a big success, since the audience showed great interests in synthetic biology and the treatment of solid tumors. It also promoted the public awareness of iGEM among universities in Northeast region of China.

5.HUST-Cheering Meeting

5.HUST-Cheering Meeting

We always wanted to have a chance to communicate with iGEMers from other teams. During July 7th. – July 9th. , we attended a HUST-Cheering meeting in Wuhan. We were glad to have an opportunity to change our thinking about iGEM with other brilliant iGEMers in China.

The HUST-China team gave an excellent presentation. Their project focused on a new type of biological filter. They designed two ingenious plasmids that can work in prokaryote and eukaryon. This excellent team is also the sponsor of the meeting. They also held many other meetings to introduce the ideas of iGEM.

NCTU-iGEM team talked about a new protein they produced. They named it Pantide and it could be used as an alternative option as an insecticide by decreasing the efficacy of ion channels in lepidopterous larvae. Their presentation was really flawless, and they also talked about two biobricks they made.

NJU-iGEM team mainly introduced a plasmid that could produce hydrogen in prokaryote. The team members were very experienced researchers and we consulted a lot from them.

We also presented our project and many iGEMers gave us advices. They think our project is really interesting, and our modeling is really good. They gave us some advices on improving our experiment, and we are very grateful about that.

6.Survey

With the aim of helping people understand solid tumors and synthetic biology, we did a survey with related questions in August 2016.Among 179 people completing the questionnaire, about 79% of them were between 18~30 years old, and most of them have bachelor’s degrees. However, most of them knew almost nothing about solid tumors.

6.Survey

Besides, more than half of them knew nothing about the therapies to treat solid tumors and only 10% of them know something about novel therapies, such as immunotherapy or therapies with the assistance of modified microbes. To the potential application of synthetic biology in the treatment of solid tumors, people’s opinions were uncertain.

6.Survey

Because their knowledge about solid tumors and the new achievements was very limited, many people worried the behavior of the microbes inside human body. They thought that it was difficult to control the proliferation of microbes in vivo, which might cause some side effects. Many people held the belief that there were many other severe problems that remained unknown if the microbes were introduced into human bodies. Some people also thought that the efficacy of using protein drugs to cure solid tumors was limited.

In conclusion, even in the well-educated population, the knowledge of solid tumors was not widespread. About curing solid tumors by the means of synthetic biology, many people questioned the risk of the introduction of bacteria into the bodies and the efficiency of this approach. We could learn from the results that it is important to raise public awareness of the threat of solid tumors, and it will be very helpful if we could promote the public interest in curing solid tumors with the aids of synthetic biology.

7.Social Network Platforms

WeChat and Twitter

Though social network platforms, such as Wechat and Twitter, we shared our experience and enthusiasm with others. By recording the on-going events, we shared our failure or success and everybody could look at our growth. Sometimes we posted our lab-notes and our efforts in laboratory can be seen by our fans. We also promoted external communication, interacted with other iGEM Groups. Most importantly, we used these platforms for educational purposes. With our fan page, people who are interested in our project and the iGEM competition can follow us all the time. By doing that, they can learn basic information of synthetic biology, and get further knowledge in frontiers of this field.

Our fans give us support and encouragement, and they make our promotions no end at all. When operating these platforms, we saw a lot of support or accompany from our fans. Each response is the hopes, and they make us to know that there is always a group behind us. We are just a small group, but with our efforts, we are confident to take a try and solve social problems. A refueling let us have motivation to continue efforts. The Internet will help the knowledge and our enthusiasm cross all the boundaries.

8.Newslatter

On Aug 16th 2016, we were invited by XMU-China to delivered them an article to introduce our project and our experiment results. We are very glad to share our project to iGEMers all around the world, and we wrote our article. On Sep 5th 2016, XMU-China published our article on Newsletter magazine.

9.The iGEM Booklet

To spread public awareness of our project, we completed a iGEM booklet to introduce "What is Synthetic Biology?" and "What is solid tumor and how to treat it". As an educational booklet, knowledge is carefully summarized. Background information, social situation, and critical learning questions are all included so that people with limited Biology background could easily learn something from the booklet.

We have already shared our booklet with teachers all over the city, the country, and even the world! Here in Jilin University, we joined a TED JLU talk and our booklets were present as a gift to the teachers and students. In addition, we have given our booklet to students, teachers, and people from other walks of life all over the state. In the HUST-Cheering Meeting,we provided our booklet to other iGEM teams and exchanged ideas with them. Two students helped bring some booklets to Los Angeles, America, as well as Stockholm, Sweden. And in Boston, during the Gaint Jamboree, we will hand out our booklet to others as well.

Three Different edited version of the booklet have been printed, better and better. And we are still working on fulfilling the information for our booklet. Currently, we are working on providing the some updated statistics so that people can have a bigger view of tumor.

The information we provided and taught to students and adults will inspire them to look into Synthetic Biology. We have already received many positive responses and we feel certain that this enthusiasm for Synthetic Biology will carry them into the future. Additionally, people learn about tumor and a healthy style of life will be pursued. Our educational synthetic biology activities booklet will be available online for anyone to use for free as soon as we get our final edition.

10.TV Interviews

Our iGEM project gets high attention and positive responses from all life sciences teachers and even directors of the Academic Affairs Division Office at Jilin University.

To support our project and spread the influence of iGEM, our Jilin University News Network interviewed our Jilin_China 2016 iGEM Team early in 2016. Through this educational TV exhibition, we shared our project idea as well as basic synthetic biology concepts with the public. We are informed that the interview about us reached a vast audience throughout the whole University.

11.iGEM Alliance

The construction of iGEMUnion was initialized this year with the aim of providing the stage for different groups from all over China to communicate with each other. There were five teams in the iGEMUnion (BIT-China, Tianjin, Jilin_China, CGU and BIT teams), and gradually teams including Peking, NCTU-Formosa and UCAS also participated in the iGEMUnion. We constructed a WeChat group number (iGEM-Union) together and updated our progress and results in it. We also propagandized synthetic biology and iGEM. Through iGEMUnion, all teams are able to communicate their own problems and it is a good stage for teams to collaborate with each other.

12.Youth Education

We always care about the young generation, and we hope our project will have a positive influence on high school students. Therefore, we introduced our project to students at the High School Affiliated to Jilin University. They do not know much about the Synthetic Biology, so we gave a brief introduction about Synthetic Biology and the iGEM competition at the beginning. Then we gave a detailed description about our project. The possibility of using bacteriotherapy to cure cancer was the major topic of our talk, as the major approaches to treat cancer have been radiotherapy, chemotherapy and surgery. We told the students how we designed our genes and how we electrotransfered them into bifidobacteriums. We also explained how our system worked. We also invited them to visit our lab. Not many students showed much interests in our presentation at the beginning of our presentation. However, more and more students showed great interest about our project during our presentation. After we finished our speech, we gave them the e-mail address of our team. Those who are interested in our project could contact our team and get more detailed information about our project and synthetic biology.

12.Youth Education

We think our presentation stimulate their interest in science. We want to introduce more about biological science to those high school students in the future, and we hope some of them will be iGEMers latter!

13.Illuminating Little Game

How our human practices have been integrated into the project

HP into the design of our project

In our iGEM Booklet, we gathered background knowledge about "What is solid tumor and how to treat it". As an educational booklet, knowledge is carefully summarized, including background information, social situation, and critical learning questions. Therefore people with limited Biology background could easily learn something from the booklet. But more importantly, when we gathered information for this handbook, we were also enriched with the knowledge, which helped us design our project at the very beginning more rationally.

For example, by making the booklet, we knew that bifidobacterium, an anaerobic gram positive bacterium, and has been validated on anti-aging, anti infection, relieving constipation, and improving lactose which is not resistant to disease and nutritional immunity. In addition, it has an inhibitory effect on the occurrence and development of a variety of tumors. The characteristics of bifidobacterium impressed us, therefore we decided to make bifidobacterium a part of our design.

Other information we got when we make the booklet are also important and then be integrated into the design of our project. Such as the application of plasmid pMB – 1, the design of adding HU-promoter to improve the expression level of apoptin. More information can be found in our booklet and the website.

How our human practices have been integrated into the project

HP into the execution of our project

1. After introducing our iGEM project in HUST-Cheering meeting, some experts and members from other teams showed great interest in our project, and had a very long discussion. Among all the people we talked to, some of them gave us valuable suggestions, and Professor Kang Ning's suggestion about animal experiments, the in-situ injection method, was applied in our execution of the experiments. Professor Kang was also generous for contributing the experience about in-situ injection. Thanks to Prof. Kang, our experiments were able to progress smoothly.

2. We interviewed Assistant Professor Xiangwei Wu from the University of Texas MD after his lecture about early-disseminated tumor cells as a biomarker for colorectal cancer early detection, during an international Forum. From him, we know that a specific feature of the apoptin used in our project is that it only enters into nucleus of solid tumors but stay in cytoplasm of normal cells. We consulted him whether the apoptin could be used as a biomarker as well. He said that we should first use nude mice to figure out whether SMMC-7721 cells can multiply in vivo by subcutaneous injection. This part is really inspiring and actually made us changed previous experiment design and we changed to use the nude mice. The result turns out to be very good. Without HP, the interview with him, we cannot imagine how ridiculous our result would be.

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