Revision as of 10:06, 17 October 2018

Overview
Silver Medal Criteria
- Education & Engagement
- Ethical, Social & Political Considerations
Integrated Human Practice
- Introduction
- Expert Views
Collaborations

Human Practices

"The essence of mathematics lies in its freedom."

Overview

"Technology is only a means, in itself it is neither good nor evil. Everything depends upon what man makes of it, for what purpose it serves him, under what conditions he places it." - Karl Theodor Jaspers

iGEMers should never be restricted in laboratory. To solve a real-life problem, STEP was created for cellular immunotherapy. But will it serve people in a responsible way? How can we perfect it by involving the world into our project? What shall we do for the public? Inspired by the idea of opening science, we delivered several lectures to students from kindergarten to college, from Shanghai to Canton. A video, a set of cartoon ‘tuanzi’ and a reportage were created to help the public better understand our project and the true living condition of sci-researchers in China. We contacted experts and stakeholders to help us add social, ethical and juristic considerations to our project. Professionals from synthetic biology, pharmaceutical industry and computer science also put touches into the design and application of STEP.

Silver Medal Criteria

Education & Engagement

Synthetic biology has its unique magic: every element works together for one purpose in the system we design, just like an imaginative idea can act as a magnet to draw people together. Involving the next generation stays on in our mind. In this spirit, we delivered a set of lectures and mini-labs to students of all ages to unlock a world of synthetic biology for juniors. Excitedly, vibrant students from High School Affiliated to Fudan University applauded the idea of synthetic biology and newly established an iGEM team on our instruction. In addition, inspired by the principle of opening science, we interviewed Ms. Shi, a doctoral student in pharmacy, revealing the true living and studying condition of common sci-researchers in China to people outside the industry. Finally, some artwork was created to help explain our STEP system to the public, saturated in the two-way constructing process of humanity and technology.

1. An image of sci-researchers in China

In our wildest dream of childhood, there always existed a profession named ‘scientist’. But only a few of us hold j nkkmnnnnon to it ultimately. Researchers are always a mystey to the public. In public mind they are a group of people burying themselves in labs and isolated from normal society. Nevertheless, the truth is far from that while the public has started to think differently. Rooted in China, we focus on three topics ‘Society, Research, Researchers’ to reveal the true living condition of sci-researchers in China today.

Reading1: A Tale of Two Cities

It was the best of times, it was the worst of times, it was the age of wisdom, it was the age offoolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness, it was the spring of hope, it was the winter of despair, we had everything before us, we had nothing before us, we were all going direct to Heaven, we were all going direct the other way--in short, the period was so. far like the present period, that some of its noisiest authorities insisted on its being received, for good or for evil, in the superlative degree of comparison only.

There were a king with a large jaw and a queen with a plain face, on the throne of England; there were a king with a large jaw and a queen with a fair face, on the throne of France. In both countries it was clearer than crystal to the lords of the State preserves of loaves and fishes, that things in general were settled for ever.

It was the year of Our Lord one thousand seven hundred and seventy-five. Spiritual revelations were conceded to England at that favoured period, a sat this. Mrs. Southcott had recently attained her five-and-twentieth blessed birthday, of whom a prophetic private in the Life Guards had heralded the sublime appearance by announcing that arrangements were made for the swallowing up of London and Westminster. Even the Cock-lane ghost had been laid only a round dozen of years, after rapping out its messages, as the spirits of this very year last past (supernaturally deficient in originality) rapped out theirs. Mere messages in the earthly order of events had lately come to the English Crown and People, from a congress of British subjects in America: which, strange to relate, have proved more important to the human race than any communications yet received through any of the chickens of the Cock-lane brood.

France, less favoured on the whole as to matters spiritual than her sister of the shield and trident, rolled with exceeding smoothness down hill, making paper money and spending it. Under the guidance of her Christian pastors, she entertained herself besides, with such humane achievements as sentencing a youth to have his hands cut off, his tongue torn out with pincers, and his body burned alive, because he had not kneeled down in the rain to do honour to a dirty procession of monks which passed within his view, at a distance of some fifty or sixty yards. It is likely enough that, rooted in the woods of France and Norway, there were growing trees, when that sufferer was put to death, already marked by the Woodman, Fate, to comedown and be sawn into boards, to make a certain movable framework with a sack and a knife in it, terrible in history. It is likely enough that in the rough outhouses old some tillers of the heavy lands adjacent to Paris, there were sheltered from the weather that very day, rude carts, be spattered with rustic mire, snuffed about by pigs, and roosted in by poultry, which the Farmer, Death, had already set apart to be his tumbrils of the Revolution. But that Woodman and that Farmer, though they work unceasingly, work silently, and no one heard them as they went about with muffled tread: the rather, for as much as to entertain any suspicion that they were awake, was to be atheistical and traitorous.

In England, there was scarcely an amount of order and protection to justify much national boasting. Daring burglaries by armed men, and highway robberies, took place in the capital itself every night; families were publicly cautioned not to go out of town without removing their furniture to upholsterers' warehouses for security; the highwayman in the dark was a City tradesman in the light, and, being recognised and challenged by his fellow-tradesman whom he stopped in his character of `the Captain, 'gallantly shot him through the head and rode away; the mail was waylaid by seven robbers, and the guard shot three dead, and then got shot dead himself by the other four, `in consequence of the failure of his ammunition: after which the mail was robbed in Peace; that magnificent potentate, the Lord Mayor of London, was made to stand and deliver on Turnham Green, by one highwayman, who despoiled the illustrious creature insight of all his retinue; prisoners in London gaols fought battles with their turnkeys, and the majesty of the law fired blunderbusses in among them, loaded with rounds of shot and ball; thieves snipped off diamond crosses from the necks of noble lords at Court drawing-rooms; musketeers went into St. Giles's, to search for contraband goods, and the mob fired on the musketeers, and the musketeers fired on the mob, and nobody thought any of these occurrences much out of the common way. In the midst of them, the hangman, ever busy and ever worse than useless, was in constant requisition; now, stringing up long rows of miscellaneous criminals; now, hanging a house-breaker on Saturday who had been taken on Tuesday; now, burning people in the hand at Newgate by the dozen, and now burning pamphlets at the door of Westminster Hall; to-day, taking the life of an atrocious murderer, and to-morrow of a wretched pilferer who had robbed a farmer's boy of sixpence.

All these things, and a thousand like them, came to pass in and close upon the dear old year one thousand seven hundred and seventy-five. Environed by them, while the Woodman and the Farmer worked unheeded, those two of the large jaws, and those other two of the plain and the fair laces, trod with stir enough, and carried their divine rights with a high hand. Thus did the year one thousand seven hundred and seventy-five conduct their Greatnesses, and myriads of small creatures--the creatures of this chronicle among the rest--along the roads that lay before them.

In the meeting with Shi, a typical doctoral student of pharmacy, we discover the change of public attitude towards the field of research. What’s their working pattern? How do they step into this field? What do their future look like? Her one-step-at-a-time experience gave the answer.

2. Future scientists — from kindergarten to college

To propagate synthetic biology and share the fun of iGEM with future synthetic biologists, we organized a series of activities and lectures to students of all ages. Kindergarten: A mini-lab For kids in kindergarten, we host a mini-biolab to introduce some basic concepts regarding microorganisms in an interesting way. Moreover, we helped the lovely children cultivate their interest in synthetic biology as well as inform them of the significance of keeping personal hygiene. PS: Safety is guaranteed during this activity.

Canton primary school: Volunteer teaching When our team is working as volunteer teacher in rural areas of Canton, we also always bear the responsibility of sharing the idea of iGEM to more people. In Canton, to broaden their horizon to a grander world, our deliver introduced our project and some basic situations of iGEM to hundreds of seated students from primary school and junior high school. Though due to the limit of equipment and knowledge, they could not be iGEMers now, we have planted seeds of synthetic biology in their naïve heart which might grow up to a glorious tree one day in the future.

Senior High School: A newly set-up iGEM team

As for senior high school, we organized some lectures to introduce synthetic biology and our project. Firstly, we held a lecture in High School Affiliated to Fudan University (FDFZ). And this lecture gave us unexpected pleasure.

FDFZ is a well-known high school in Shanghai having a long history. And thanks to the abundant resource of Fudan University, the students of FDFZ can get easy access to top theory and technology in the science field and the atmosphere of exploring is really thick there. Thus, we reached a biology teacher in FDFZ discussing about holding a lecture in FDFZ and the possibility of establishing an iGEM high school team to help them participate in this creative competition. To attract more students to our lecture, we prepared beautiful posters for every classroom and made sufficient plans. The outcome is more than fantastic. The number of students that came to our lecture is far over our expectation, and they were all eager to know iGEM and how to take part in it. Thus, we organized two interviews together with a teacher of FDFZ to select suitable students for future competition. In the interview, we asked about lots of things such as their basic knowledge of modern biology, experience in laboratory, the understanding of iGEM and their current ideas. To our surprise, some had attended the John Hopkins Summer Camp and had the experience of PCR, Western Blot and etc. And some had learned pharmacodynamic evaluation, mice emergency immunization, flow cytometry, labeling fluorescent antibody and so on. And their ideas were also innovative concerning Chinese traditional herb, malaria, controlling blood pressure, and regulation of K+. As for the division of labor, they also have their considerations. Some prefer wet laboratory, and others would like to major in modeling or visual designing…… We not only shared basic knowledge of synthetic biology, lab skills and safety rules with them in our mini-class, but also achieved a lot from them- discussing ethic and law issues in regard to advanced technology. What impressed us most is their passion on practice with their own hands. The knowledge they’ve learnt in class inspired fantastic ideas, while we provide a stage to help them realize. Welcome, new iGEMers!

It’s a really successful try, and we did help our next generation not only know about iGEM and synthetic biology but assist them to become one of us, to make them enjoy the interest of it. Now, a promising iGEM team is coming into formation and we will also support them theoretically and practically. The world is changing. Except this, we were also invited to Shanghai Shixi High School, a famous high school to deliver a lecture named Synthesis + Biology = Synthetic Biology to expand their view. University: iGEM club During our summer vacation, we attended a sharing meeting with BIOS (Biology Intensive Orientation Summer) students who were learning basic biological technique to discuss our project and absorb positive opinion to polish our STEP system. Despite their relatively poor experience in research, but their fancy thoughts did inspire us and make our project more charming.

In Fudan University, iGEM exists as a club. In this semester’s giant meeting of all clubs, iGEM has attracted much attention from students of all majors and some showed great interest in iGEM. Through our introduction, they had a deeper understanding of iGEM and synthetic biology and got deeply fascinated by the idea. It’s predictable that next year, there will be more students fond of synthetic biology taking part in iGEM to share the fun.

3. STEP into Art

Are you attracted by our mascot on the poster? It’s a set of "Tuanzi"（团子）！Really cute , aren’t they? Each represents one of our team member and instructor. Pipette, protein, E.coli, culture medium, camera, computer engineering… As part of our team culture, Tuanzi are our little bonus, for us and for other iGEMers. They were printed on sweaters and key rings, delivered to friends, instructors and others who gave us a hand during our preparation. Also we will bring them to Giant Jamboree. Thanks to them, more and more people come to know our team, realizing that iGEM involves more than wet-lab students. No matter what you are responsible for- human practice, modeling, art design and so on- we wish to express gratitude to every member’s effort in iGEM.

As a cutting-edge therapy, cellular immunology is really a hot spot. Mostly people only know it by the media, but hardly understand how it works. To make the public get acquaintance with the STEP system and how it comes to our mind, an animated video was created. Producing a video helps us reflect on the whole project design as well as plays an educational role.

Watch Project Video

Because I could not stop for death, he kindly stopped for me. The carriage held but just ourselves and immortality.

What’s the connection between porcelain and STEP? We came to a workshop and made a STEP plate with our own hands. As a traditional Chinese art, it contains philosophy from our ancestor. Round and smooth, the porcelain plate serves people as a container, while it would easily hurt us when broken into pieces. Just like our system, it’s never easy to create one and make it serve the public for the right purpose.

Ethical, Social and Political Considerations

When developing a therapeutic project for cancer, it’s not only the technical issues that need to concern about, but also ethical and political issues. Though China have earned a large number of research achievements in the field of cellular immunotherapy, till now, none has been approved or applied in clinical treatment. The question stays on in our mind- why there is a lack of ethical and political considerations in China, regarding this new therapy? What can we do to make a change? For this purpose, we stepped out of the lab, contacting professionals in the field of ethic and policy, to find out the answer. Also, Dr. Xu, an oncologist of Fudan Univ. Cancer Hospital, explained the approving process of current clinical trial of cellular immunotherapy to us. What’s more, we received a phone call from National Health Commission of the People’s Republic of China, after contacting them by e-mail, which explains the regulations we concerned about. In our meeting with Dr. Jie Yin(link), an expert in medical ethic, she admitted that the main issue concerned with our project is safety, considering its high cost and risk. Thus the government will give top priority to its approval. For the particularity of cancer patients who are at the end of their life, cellular immunotherapy served as a last resort. Patients flooded into it, striving for a chance to survive. We were reminded that there are certain clinical indications that need to be satisfied before a clinical trial, which made us reflect on a fairer distribution of medical resources. In China, collective consciousness always plays the leading role on the historical and social stage, covering the light of Spirituality Concern on the value of individual life. Compared with the unprecedented hot market, the lack of ethical consciousness should receive more attention. We called for the existence of humanity in this “technology & market first” society, truly benefiting every single patient.

Just in early October, we received an official phone call from National Health Commission, answering our concerns in the e-mail. Its official firmly declared, till now, no institute or enterprise is permitted to apply a clinical treatment with cellular immunotherapy, while several clinical trials have been approved. Through our research on policies in the field of cellular immunotherapy in China, we discovered that the attitude of government is quite vague. For years, regulations concerned have swung chaotically from encouraging drug-innovation to strengthening supervision. Yao, an expert in law of health, showed his worries towards the lack of a special committee responsible for cellular immunotherapy. He analyzed the deriving history of regulations concerned, optimistic about its application prospects in China. It would be a good idea to have an outline of the current ethical and political situation in China, he suggested.

Reading2: A Tale of Two Cities

It was the best of times, it was the worst of times, it was the age of wisdom, it was the age offoolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness, it was the spring of hope, it was the winter of despair, we had everything before us, we had nothing before us, we were all going direct to Heaven, we were all going direct the other way--in short, the period was so. far like the present period, that some of its noisiest authorities insisted on its being received, for good or for evil, in the superlative degree of comparison only.

There were a king with a large jaw and a queen with a plain face, on the throne of England; there were a king with a large jaw and a queen with a fair face, on the throne of France. In both countries it was clearer than crystal to the lords of the State preserves of loaves and fishes, that things in general were settled for ever.

It was the year of Our Lord one thousand seven hundred and seventy-five. Spiritual revelations were conceded to England at that favoured period, a sat this. Mrs. Southcott had recently attained her five-and-twentieth blessed birthday, of whom a prophetic private in the Life Guards had heralded the sublime appearance by announcing that arrangements were made for the swallowing up of London and Westminster. Even the Cock-lane ghost had been laid only a round dozen of years, after rapping out its messages, as the spirits of this very year last past (supernaturally deficient in originality) rapped out theirs. Mere messages in the earthly order of events had lately come to the English Crown and People, from a congress of British subjects in America: which, strange to relate, have proved more important to the human race than any communications yet received through any of the chickens of the Cock-lane brood.

France, less favoured on the whole as to matters spiritual than her sister of the shield and trident, rolled with exceeding smoothness down hill, making paper money and spending it. Under the guidance of her Christian pastors, she entertained herself besides, with such humane achievements as sentencing a youth to have his hands cut off, his tongue torn out with pincers, and his body burned alive, because he had not kneeled down in the rain to do honour to a dirty procession of monks which passed within his view, at a distance of some fifty or sixty yards. It is likely enough that, rooted in the woods of France and Norway, there were growing trees, when that sufferer was put to death, already marked by the Woodman, Fate, to comedown and be sawn into boards, to make a certain movable framework with a sack and a knife in it, terrible in history. It is likely enough that in the rough outhouses old some tillers of the heavy lands adjacent to Paris, there were sheltered from the weather that very day, rude carts, be spattered with rustic mire, snuffed about by pigs, and roosted in by poultry, which the Farmer, Death, had already set apart to be his tumbrils of the Revolution. But that Woodman and that Farmer, though they work unceasingly, work silently, and no one heard them as they went about with muffled tread: the rather, for as much as to entertain any suspicion that they were awake, was to be atheistical and traitorous.

In England, there was scarcely an amount of order and protection to justify much national boasting. Daring burglaries by armed men, and highway robberies, took place in the capital itself every night; families were publicly cautioned not to go out of town without removing their furniture to upholsterers' warehouses for security; the highwayman in the dark was a City tradesman in the light, and, being recognised and challenged by his fellow-tradesman whom he stopped in his character of `the Captain, 'gallantly shot him through the head and rode away; the mail was waylaid by seven robbers, and the guard shot three dead, and then got shot dead himself by the other four, `in consequence of the failure of his ammunition: after which the mail was robbed in Peace; that magnificent potentate, the Lord Mayor of London, was made to stand and deliver on Turnham Green, by one highwayman, who despoiled the illustrious creature insight of all his retinue; prisoners in London gaols fought battles with their turnkeys, and the majesty of the law fired blunderbusses in among them, loaded with rounds of shot and ball; thieves snipped off diamond crosses from the necks of noble lords at Court drawing-rooms; musketeers went into St. Giles's, to search for contraband goods, and the mob fired on the musketeers, and the musketeers fired on the mob, and nobody thought any of these occurrences much out of the common way. In the midst of them, the hangman, ever busy and ever worse than useless, was in constant requisition; now, stringing up long rows of miscellaneous criminals; now, hanging a house-breaker on Saturday who had been taken on Tuesday; now, burning people in the hand at Newgate by the dozen, and now burning pamphlets at the door of Westminster Hall; to-day, taking the life of an atrocious murderer, and to-morrow of a wretched pilferer who had robbed a farmer's boy of sixpence.

All these things, and a thousand like them, came to pass in and close upon the dear old year one thousand seven hundred and seventy-five. Environed by them, while the Woodman and the Farmer worked unheeded, those two of the large jaws, and those other two of the plain and the fair laces, trod with stir enough, and carried their divine rights with a high hand. Thus did the year one thousand seven hundred and seventy-five conduct their Greatnesses, and myriads of small creatures--the creatures of this chronicle among the rest--along the roads that lay before them.

In this paper, we discussed current ethical and political problems in the field of cellular immunotherapy, comparing regulations concerned in China with the ones in other developed countries. It is important for people in the field to be aware that only with refined legal system and ethical instructions can this advanced therapy truly work. This kind of insight into thinking about national conditions and the function of interdisciplinary communication was essential to our project design and execution.

Integrated Human Practice

Introduction

Through our Bench-to-Bed approach, we take every effort to make our STEP system perfect and responsible for the world, involving experts in different field into our project. Initially, it was created for cellular immunotherapy. After contacting pathologists and experts from pharmaceutical industry, we paid close attention to cancer treatment. Under the conduction from Prof. Huang and other computational biology experts, we intensify our modeling and develop a distinct and persuasive model on molecular interaction and system output. What’s more, response from ethicists, jurists, hospital administrators and National Health Commission helped us add ethical and juristic considerations to our STEP system, leading to a paper investigating the major interest of cellular immunotherapy in China. An Oncologist responsible for clinical trials of immunotherapy also provided a precious view on our target identification in anti-tumor molecule work. Professionals from Shanghai iDrug Center and pharmaceutical industry proved the application prospects of STEP.

Expert Views

1. Project Design

Dr. Xiaoming Ding Associate Professor, Department of Microorganism School of life sciences, Fudan University

What kind of cells should we use in experiment? Prof. Ding's research interest is microbial molecular genetics and synthetic biology. In the early design of the project, we consulted Pro.f Ding about the carrier built by the system. He gave us suggestions in this direction, holding that the system is more suitable to be built in eukaryotic cells and will have a higher prospect of success and application. Therefore, we chose 293T and Hela cells to build STEP system.

Prof. Dr. Jiang Zhong Executive Director of Department of Microbiology and Microbiology Engineering School of life sciences, Fudan University

Which track should STEP be applied to, therapy or diagnositics? In the early design of the project, we considered using our core receptor system to detect cancer or thrombotic diseases. Prof. Zhong believes that the current methods for the detection of common diseases are mostly based on colloidal gold test paper. For specific diseases such as cancer, blood is usually drawn for blood test. The relevant technology has been mature and the detection cost is low. If such a receptor system is only to used to detect the occurrence of a disease, it's overqualified. Therefore, he suggested that it would be more promising for us to apply our STEP system into a therapeutic project, but not a diagnostic one.

Prof. Dr. Li Chen Distinguished Professor of Fudan University Inventor of first rapid detection kit for salivary-oral pathogens Former technical supervisor of Japan GC Company

After we introduced our project design and execution, Prof. Chen considered that the basic idea of STEP system is innovated and can enrich the tools for research. Meanwhile he recommended that we may focus the STEP system on a more specific and clinical situation to make it more attractive to those potential investors. Prof. Chen initially studied in biology, then worked in pharmaceutical company and now he is doing research for clinical medicine. From his perspective, a reliable solution of one single problem might be more worthy than a hazy answer to a universal question. Thanks for his working experience in medicine industry, we turned our attention to a specific disease, Non-Small Cell Lung Cancer, as the concentration of D-Dimer and VEGF in blood has a strong correlation with it.

Dr. Wei Mo Associate Professor, Department of Biochemistry and Molecular Biology School of Basic medical sciences, Fudan University

Mo gave us relevant advice when we chose small molecules that our receptors can target. We initially selected VEGF and d-dimer to target cancer, and Prof. Mo thinks that's a viable idea. He introduced to us the significance of d-dimer in postoperative diagnosis of non-small cell lung cancer has been reported in the literature, and believed that the application of this molecule in tumor targeting and treatment is a new and meaningful idea, linking cardiovascular diseases and tumors, two diseases closely related to each other.

2. Wet Lab

Prof. Dr. Roman Jerala Synthetic biologist Head of Department of Synthetic Biology and Immunology National Institute of Chemistry

It is a great honor to have a breakfast meeting with Prof. Roman Jerala. As an expert in the field of synthetic biology, he had led the Slovenian team to participate in iGEM for many years, achieving remarkable results. We talked about our project design and details of protein design in our experiment. He suggested that our two-chain system can be improved and simplified to one. Inspired by this imaginative idea, we evaluated the possibility of a flexible linker and its cutting another chain. Prof. Roman Jerala provided a unique view on our project, improving STEP system with its protein structure and gene expression.

Honghai Tang PhD student in Department od Biostatistics & Computational Biology School of life sciences, Fudan University

How to gain more protein? In the process of purification of KDR, we still could not obtain a higher concentration of protein after several attempts. Tang devotes herself to the study of protein structure and has rich experience. He proposed it was not appropriate to simply follow the old protocol, and suggested that we screen out the best conditions for protein expression by changing the formula of the medium, such as adding glycerin or NaHPO4. His input was integrated in our practice. We obtained more target proteins by changing the temperature of culture, the formulation of culture medium and the concentration of induction.

Dr. Jiaxue Wu Principal Investigator, State Key Laboratory of Genetic Engineering School of life sciences, Fudan University

We ran into many problems testing our STEP system on 293T cells and Hela cells. For example, when testing the activation of STEP system, we found that the response of the system was very noisy. Wu, a researcher specializing in the field of cells at the national key laboratory of genetic engineering, suggested reducing the problem of system noise by reducing the transfection concentration of the whole two chains of the system. He argued that the number of cell membranes capable of accommodating the artificial receptors we have constructed is limited, and if the number of plasmids transfected into the cell is large enough to express two strands, it is likely that some of the artificial receptors are not located on the cell membrane. Because of the nuclear localization sequence (NLS) on the transcription factor we designed, the expression of the downstream gene circuit is directly activated. Therefore, it is possible to solve this problem by reducing the amount of transfection.

Hui Li Hospital Administrator Shanghai Anda Hospital

Li’s experience is quite unique- expert in medical disputes for decades, he now works on management in the biggest private hospital of Shanghai, after serving the army as a surgeon. Thus, he analyzed the application prospects of a new medicine in three aspects for us: clinical doctor, hospital management and patient. When we wondered whether a clinical trial would cause any medical disputes in China, Li admitted that the lack of effective communication between doctors and patients is to blame for. Clinical trials should never be permitted without informed consent, concerning its high risk. After all, patients are living people, just like us, but not a simple data in the research. At Li’s advice, we reached out to a broader audience by making a video which explained our STEP system in plain language for potential users.

3. Dry Lab

Prof. Dr. Qiang Huang Professor, Department of Molecular Biophysics Engineering Research Center of Gene Technology, Ministry of Education Fudan University

When we consider reengineering vegf-scfv to obtain better protein binding capacity, Prof. Huang has given us great help. Based on his knowledge of medical genetics and structural bioinformatics, he guided us in the molecular design of cancer drugs and used computers to carry out theoretical and simulation of biological molecular structure and interaction. At first, we intended to simulate the receptor movement on the cell membrane to directly study the output level of the STEP system. Afterwards, Prof. Huang suggested that the movement of the receptor on the cell membrane was not completely random, and the differences in different regions on the membrane were not convincing enough. So then we turned to the probabilistic model, to study the relationship between the parameters of the wet experiment and the model by simulating the motion of the membrane receptor.

Dr. Yi Shi Associate Professor, Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine, Ministry of Education Shanghai Jiaotong University

How to build up a STEP system with the computer’s power? To make research on whether the Protein ligand we have designed has a better combination ability, we came to Shanghai Jiaotong University， where is located the Key Laboratory of Systems Biomedicine established by the Ministry of Education. Expert in Computational Biology and Tumor Genetics ，Shi was strongly interested in our platform. After listening our program introduction, he emphasized the importance of the math modeling in the whole system. “Only the framework with rich logic will possess a better sense of instruction to the wet lab”. Taking Shi’s suggestions, we justified the rationality of simulation by using Rosetta， and, at the same time, considered the spontaneous rotation problem happened on TC\PC chain of cell membrane. Furthermore, he also advised us to compare the STEP system with current Car-T therapy in the background in order to highlight our originality.

Haotian Guo Judge PhD student in The Center for Research and Interdisplinarity Leader of 2013 Fudan iGEM Team

We invited Guo, who has led the Chinese and French teams to participate in iGEM several times and has rich experience in the competition. In his opinion, the basic assumptions of our dry experiment could be refined, so we further considered the reaction mechanism of STEP system completely in the model, and improved the integrity and authenticity of the model. In addition, he suggested that we should use more intuitive images as a result when introducing projects to the outside world, so that people without professional knowledge can understand meanings. Therefore, while making statistical explanation of the data, we also directly showed the molecular structure diagram to make intuitive comparison.

4. Ethic and Law

Dr. Jie Yin Associate Professor, School of Philosophy Fudan University

How ethical issues are involved in cellular immunotherapy? In China, no medical institution has received clinical application approval for tumor immunotherapy as there are major ethical issues. As a result, we are very curious about which ethical issues are involved in our research and how to make our research more ethical. Dr. Yin, who graduated from Shanghai medical university, turned to philosophy after graduation as a clinical undergraduate. She majored in medical philosophy and Kantian philosophy. Her dual background in medicine and ethics, therefore, has greatly helped us in the field of research ethics and clinical ethics. She says that unlike the embryonic ethical issue facing stem cell therapy, safety is the major ethical controversies facing our STEP system. Tumor immunotherapy is expensive, but it can have serious side effects and fatality. She stressed that among the four principles of bioethics, the principle of no harm is pivotal. It is crucial for us to consider how the technology and drugs that are still in clinical trials can protect the rights and interests of the subjects. Therefore, we tried to solve the problem of cytokine storm through the cooperation between wet lab and dry lab in subsequent experiments, thereby making our platform more secure. Dr. Yin introduced us to the history, composition and approval process of the Chinese Hospital Ethics Committee. When we talk about the current ethical situation in China, we find that the lack of cross-disciplinary talents is one of the major reasons leading to issues in medical ethics. Humanists shows their ignorance of medical knowledge, and physicians lack ethical literacy and critical thinking. While law is the lowest bottom line for developing technology, ethics makes the ever-changing technology responsible for the world. We take this opportunity to review the purpose, design and execution of our project through an ethical perspective. The STEP system is designed to treat tumor, which is the second leading cause of death in the world; we hope that our system can be good for the world. In the experiments, we think that cell and molecular cloning experiments are not mature enough to reach phase where use of mice is possible as we don't want to hurt innocent mice just to produce good-looking data. We hope that the input of scientific research resources can bring real results. Medical ethics have been neglected for too long in China. Under the guidance of Dr. Yin, we improved experimental design and execution and wrote a paper on the ethical issues of Chinese tumor immunotherapy, hoping to arouse more ethical awareness of scientific and clinical researchers to make our investigation more responsible for the world.

Jun Yao Associate Professor, Law school of Fudan University Expert in Health Regulations

Yao graduated from Shanghai Medical College and later changed his major into law. He has years of experience in dealing with law problems with hospitals, patients and the health administrative department. He was just compiling the book Medical Law when we arrived at his office. After consulting literature, we found that there are still problems about the cellular immunotherapy in China, such as undefined supervisor, ineffective measures of standardization and so on. And that's why we are here to consult him. According to Yao, there is not a single organization that has gained permission for the clinical application of cellular immunotherapy, and all are still at the stage of clinical trial. Therefore, as far as medical organizations are concerned, they are obligated to report their cases to the health administrative department and obtain permission, inform patients of the potential risk and outcome of their experiment without charge. As for China Food and Drug Administration(CFDA)and National Health Commission，they should establish a sound legal system to supervise the whole process from research and development to industrial production and clinical application comprehensively. In addition, he also called for the emergence of cross-disciplinary talents in medicine and law. Yao made compliments about our attention we had paid to relevant laws and regulations and he answered the questions we were concerned about. He made us realize when we formulated and enforced the laws, we should take the complex commercial benefit and the national overall background into account. We found out the contradiction of innovation and strict control. When China encourages “Mass entrepreneurship and innovation”, the law may not keep up with the innovation of the new medicines. Therefore, we hope to draw the attention of departments concerned by summarizing these questions and suggestions. Finally, Yao emphasized, no matter how much benefit were involved, we should always put the right to life in top priority. Behind the laws and regulations, living lives were what our projects were truly facing.

5. Industry and Clinic

Dr. Li Ye Associate Professor, Microbiology and Biochemical Pharmacy Fudan University

How is a laboratory project transformed into industrialization? Prof. Ye is dedicated to the research of tumor immunotherapy drugs, owning multiple patents, and is involved in many enterprise technology development projects. We come to Zhangjiang pharmaceutical valley, which is not only the location of the school of pharmacy, but also the base of biomedical science and technology industry gathering a large number of pharmaceutical companies. Ye introduced the current limitations of car-t therapy, and proposed that if our cell therapy could be universal, it would greatly reduce the cost of treatment. She made us realize that safety and targeting are two sides of tumor immunotherapy. Therefore, in the later experiment purpose and implementation, we not only improved the work efficiency of STEP system, but also strengthened the attention to security In addition, Ye stressed that a new drug cannot be popularized by a single medical or scientific institution and must be linked to the industry. Therefore, we went to Shanghai pharmaceutical r&d collaborative innovation center to participate in the Open Day for consultation services on new drug development.

Dr. Litao Xu Oncologist, Expert in Liver Cancer Fudan University Cancer Hospital

Half of our team members are from medical school, and we were lucky enough to have an appointment with Dr. Xu, who also from Shanghai medical college. He greeted us kindly and gave a hearty laugh from time to time. He has rich experience in the treatment of liver cancer. He led the trial of immunotherapy in tumor hospital and handled nearly 60 patients. He showed us the procedures and specifications of clinical trials, and introduced two cases with excellent results. Previously, we were concerned about the clinical possibilities of the free molecules chosen for the project. In the interview, he affirmed the clinical application value of VEGF as a target in our project, and indicated that in clinical diagnosis, small and medium molecules in blood are often used as diagnostic indicators.

Shanghai Center iDrug Discovery & Development

On Oct.9, 2018, we arrived at the Shanghai Drug Research and Development Collaborative Innovation Center where a open day for advisory services on new drug research and development is held here on Tuesdays on the first week every month. On the open day, diagnosis and consultation on projects are provided freely, which are promoted to develop in the pattern people expected, and it will also bring contacts with the projects’ transformation. The professors from the center and the college of pharmacy gave us professional instructions scientifically and reasonably, as well as reference opinions from the industrialized angle. He commended the integrity of our project and the meaningful directions to wet lab from dry lab. Also, he pointed that the problems of the high prime cost and low safety of the current cell therapy, and wish us to make considerations on the choice of the cell type for transformation. In iDurg, we gained a more solid understanding of the current situation of Chinese Pharmaceutical Industry. We deeply appreciate this platform , which integrated the resources of high institution, government and enterprises effectively, can bring contacts for our project from lab into the transformation to industry. During the visit, we found that, as for 2016, Anticancer and immune-related drugs took 7 places among the top 10 drugs in the world by retail sales. Thus, we may see that the market size of tumor immunotherapy will be inestimable in the future.

Collaborations

During the visit, we found that, as for 2016, Anticancer and immune-related drugs took 7 places among the top 10 drugs in the world by retail sales. Thus, we may see that the market size of tumor immunotherapy will be inestimable in the future. View Our Collaborations!

Useful Links

iGEM Main Page
iGEM Special Pages

Email

igem@fudan.edu.cn
kfjin16@fudan.edu.cn

Address

G604, School of Life Sciences, Fudan University
2005 Songhu Road, Yangpu, Shanghai, China