Team:CPU CHINA/HP/Gold Integrated
summary
We conducted our human practice with the purpose of evaluating whether our novel “immune like cells” would be practically plausible and of importance in the field of tuberculosis treatment. First we got in touch with Center for Disease Control (CDC) and researched on literature about this disease so that the idea of using innate immune system arose. Then we interviewed several professors and doctors to add all the parts to our original frame. We also communicated with loads of entrepreneurs and policy related experts, providing us with insights of what to do if we want to make our project a real product, during which we thoroughly considered the current market, our competition and our strength. We further communicated with experts from CDC and doctors again to make sure our design meets the needs of society. Last, we took a survey among patients which helps us understand the importance of disease management and eventually leads to our new APP. Our human practice is well integrated throughout with our project, and significantly broadened our horizon on this specific topic, and more importantly, improved our iGEM project by considering the views of different stakeholders.
The event of tuberculosis in schools
We learned that a school was temporarily closed because of the outbreak of tuberculosis. At the same time, a incident that many young children were infected with tuberculosis, also indicated that tuberculosis was not far away from our lives.
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CDC
Poor compliance is one of major problems in the process of long-term medication (the basic course of treatment of tuberculosis is about 6-9 months). We have learned that patients must take more than three kinds of drugs a day, which is very inconvenience and will lead to the patients' unauthorized suspension of medication once the symptoms become not obvious.
Conclusion :
Different departments have diffract division of labor, to obtain clinically relevant information, we need to visit a local tuberculosis hospital; if long-life cell therapy is employed, the presence of Mycobacterium tuberculosis in the patient can be detected and constantly damaged, avoiding discontinuation of treatment or a recurrence of tuberculosis caused by a false negative diagnosis result.
Detian Li and Yuqi Wang interviewed the consultants of the Nanjing Municipal Center for Disease Control and Control (Nanjing CDC) to learn about the current status of diagnosis and treatment of tuberculosis.
Through this interview, we got aware of current status of tuberculosis diagnosis and treatment, which gave us a lot of insights of project design.
One of the problems is the difficulties of tuberculosis detection. As we all know, tuberculosis patients are infected with Mycobacterium tuberculosis (Mtb). However, there is no obvious symptoms for the early period patients which makes this disease sometimes hard to diagnose. When tuberculosis develop, the symptoms may become more obvious, like fever, fatigue, upset, poor appetite, long-term weight loss which make the patients very suffering. Currently, the main detection method is molecular examination carried out by hospitals. This method is efficient but cannot cover all infected people due to limited resources. Normally, it can only be applied on a part of high exposure populations who are generally considered to have higher risk to get this disease, for example, close contacts of tuberculosis patients. Obliviously, this scope of usage of this method is not sufficient compared to the population infected with Mtb, so we are wondering if we could endow our immune-like cells with other functions to simplify the detection methods, reduce the cost of diagnosis and realize precise early diagnosis (For more details please visit here).
Another problem is the compliance of patients (or we can say the acceptance of patients). The treatment period of tuberculosis is relatively long, which could last for 6 to 9 months. Therefore we tend to make a long cycle therapeutic strategy, to be more precisely, a strategy can be efficient for a long time after single administration to improve the compliance. What’s more, we learned that the patients tend to stop taking medicine when their symptoms relieve which, however, usually leads to the relapse of tuberculosis. Because although the symptoms seem to be less severe, the bacteria is not eliminated. So we came up with the idea to set up a system like this (For more details please visit here), capable of treatment and surveillance during a relatively long period after just a single injection, thus to improve the compliance of patients.
From the interview and the publication[1]，we learned that all drugs used on tuberculosis patients are chemical drugs, like rifampicin and isoniazid. There are two problems of chemical drugs, side effects and drug resistance. First, most existing drugs can result in liver and kidney damage, and the damage can be even more severe with long-term drug administration which is commonly required for patients. So we decided to develop a project which utilizes the body's own immune system to fight against pathogens. Furthermore, Some drugs have fought the Mtb for more than 50 years, and this bacteria have evolved to resist them. Some patients may even come up with multidrug-resistant tuberculosis (MDR-TB) with resistance to at least 2 powerful first-line anti-TB drugs, which means they may have no drugs to use! However, if we can take advantage of immune systems to fight against Mtb, it is not that likely to render resistance due to the quite different functional mechanism. So, we are aiming to develop a new strategy by activating the immune system to fight against Mtb that is quite difficult to render resistance, totally different from the existing anti-Mtb methods.
Others：
1. Children having BCG as a preventive measure for severe tuberculosis get rid of significant risk of death, but may still be infected with tuberculosis.
2. Adults are susceptible to tuberculosis, and often tuberculosis patients will also have pleurisy, meningitis and other related diseases.
3. There is a certain latent period after a healthy person being infected with Mycobacterium tuberculosis, and a healthy person who has no symptom may also be a carrier of this bacterium.
4. For TB patients, different departments have diffract division of labor. CDC is responsible for the prevention and control of diseases, and the hospital is responsible for the containment and treatment of patients.
5. The drug resistance of tuberculosis becomes increasingly severe year by year. Patients who end the course of treatment for some reasons may also lead to the recurrence of tuberculosis.
[1] Mabhula, A., and Singh, V. (2019). Drug-resistance in Mycobacterium tuberculosis: where we stand. Medchemcomm 10, 1342-1360
CDC specialists pointed out that not every hospital is eligible for TB patients, and introduced us to the designated hospital for tuberculosis
Questionnaire to the public
After visiting the CDC, we suspect that perhaps not only is our attention and understanding of tuberculosis insufficient, but so is the public. Therefore, we have put forward a questionnaire on tuberculosis common sense. While investigating the society's attention to tuberculosis, we promoted tuberculosis-related knowledge among the public.
Conclusion:
As expected, the public is not very familiar with tuberculosis and does not pay much attention to it. Therefore, we try to add relevant information related to tuberculosis in public engagement and education to disseminate knowledge about tuberculosis and synthetic biology, raise everyone's attention to prevent on tuberculosis.
In our survey, we found that more than 77 percent of people do not understand the tuberculosis. At the same time they do not know anything about the existing TB therapies. About more than three percent of the people have been suffering from tuberculosis，and most people do not have basic medical knowledge of diagnosis and treatment on tuberculosis. Despite of the Chinese policy of free treatment for tuberculosis, many people do not know the policies like free TB. Not many people know more AIDS patients at higher risk of infection combined. At the same time, only a small number of people know how to properly protect themselves against TB. （准备替换）
Mr. Michael Levitt
We had the opportunity to interview Mr. Levitt, who had won the Nobel Prize in Chemistry. He explained to us how to make science simple and interesting, which provides valuable ideas for our public engagement and education.
Conclusion:
We are piloting young people in the form of comics, in order to explain the knowledge in a simple way, so that children can understand the most basic common sense.
Professor Yu liu, our PI
In our original design, we used granule enzyme B and perforin to kill Mtb , but our PI suggested us to use granulysin instead since granule enzyme B and perforin are not safe and effective, and granzyme is more suitable for killing tumor cells rather than Mycobacterium tuberculosis.
Conclusion:
We used granulysin instead of a combination of granzyme B and perforin, which directly kills Mtb and does not affect the function of normal cells.
Yu liu, Professor. She is focusing on the development of monoclonal antibody drugs and the biochemical drug activity and mechanism of action.
Doctor Chen
Doctors tell us that if you want to fight tuberculosis through the body's innate immunity, you must consider the inhibition of macrophages by Mtb.
Conclusion:
So we decided to add a system to kill the bacteria inside the macrophages by using miRNAs delivered by exosomes.
Jiangning Hospital is one of the designated hospitals for tuberculosis in Nanjing. It has established a tuberculosis clinic and is qualified to treat tuberculosis patients.
Professor Jun Zhou
Prof. Zhou raised the problem of excessive cell overload and transfection stability. She believes that if our artificial cells need to identify and kill the bacteria at the same time, the cell burden is relatively heavy, and the success rate and stability of expression is uncertain, which can be further improved in the future.
She also gave us the following suggestions:
a. TLR1/2 have a membrane protein detection problem, because membrane protein has both intracellular and extracellular segments. These receptors participated in a series of reactions which may results in some difficulties in the detection. She hopes us can refer to other publications and clear our experimental methods.
b. She also mentioned the stability of TLR1, TLR2 expression might be a problem since the experimental process is only instantaneous transfection. After a period, it might be hard to determine whether these receptors will still exist on the cell membrane.
Although our idea is valid, it is necessary to find more relevant documentary evidence.
Dr. Haoqian Zhang
At The 3rd Nanjing iGEM Regional Meetup, when Dr. Zhang commenting on our design, he mentioned that NF-κB may not respond strongly.
Conclusion:
We searched the literature and found that there is a positive feedback mechanism between let-7f and NF-κB, but the specific situation requires further experimental exploration.
(For more details, please visit here!
Karen Wang
We interviewed Ms. Karen's views on drug ethics and safety. As a drug management manager, she explained to us that drug ethics and safety are actually the ethics of every detail in the process of production and use. Safe, legal compliance, so as the experiment or preparation, you need to ensure that every detail is safe and effective, so that the safety of the drug are guaranteed.
Conclusion:
Safety
Frank Lim
Frank told us some people with tuberculosis in the Philippines are not going to see a doctor because they are worried about the cost of medical treatment. But in fact, such inspections in the Philippines are as free as China, so we are trying to raise local awareness of tuberculosis related policies.
Conclusion:
Analogous to China, we conducted research, through comics and other ways to enhance public understanding of policies, and we began to think about how to use modern network tools to help people better understand tuberculosis.
Questionnaire to patients
Based on the information obtained by doctors and CDC, we designed a questionnaire to investigate the impact of tuberculosis on patients' lives and the inconvenience.
The survey showed that patients do not dare to communicate with others, because they afraid to transmit the bacteria to others.At the same time, the supervision and care of the patients by the community doctors were mostly 1-2 times a week, and there was also a phenomenon of half a month.
Conclusion:
So we designed an app: NCDS, which is convenient for online consultation of doctors and patients, daily automatic supervision and medication, etc. This app can also avoid tuberculosis patients entering the crowds to reduce the risk of tuberculosis transmission.
(The survey also shows that the drug price of the patient is very expensive in the case of multi-drug treatment, which leads us to think of including this fee in the medical relief policy and asking the CDC again for help.)
China artificial Intelligence summit 2019，Most potential award
We participated in the 2019 China Artificial Intelligence Summit with our app, and won the Most Potential award. The judges commented on our thoughts and told us that we should start with the management of infectious diseases, so that we can solve two problems.
The second is that the tuberculosis patients can effectively isolate the source of infection in the case of reducing contact with the outside world.
Conclusion:
In order to improve patient compliance and access to doctors, we designed daily program recommendations, including diet and online counseling. The concept of the user community has been added, which can enhance the user's stickiness and achieve the purposes.
The first is that the compliance of patients with tuberculosis can be improved.
The second is that the tuberculosis patients may effectively isolate the source of infection in the case of reducing contact with the outside world.
The second college student innovation competition in Nanjing，Excellent award
We participated in the second college student innovation competition in Nanjing with our app. The judges expressed their affirmation on the management status of patients who wish to improve chronic diseases, but they also pointed out that we should invest more energy in the online inquiry system, and doctors should be more inclined to retirees.
Conclusion:
We contacted the doctors of Nanjing Drum Tower Hospital, The affiliated Hospital of Nanjing University Medical School, the tuberculosis department of Nanjing Jiangning Hospital, the Affiliated Jiangning Hospital of Naning Medical University. They said that if there is such an app, they are willing to try as online doctors.
United Kingdom and China Entrepreneur Association ; global fourth prize
We participated in the United Kingdom and China Entrepreneur Association with our app. Investors say that our app has taken shape and has great prospects, but in UK, it can be more convenient if you can combine medical insurance with an online store, but you need to pay attention to safety and policy issues.
Conclusion:
Therefore, we have come up with the idea of visiting the CDC again to understand the relevant policies, and put it into practice soon.
Yangtze River Pharmaceutical Group
In order to further understand how to industrialize the products, we got in touch with the Taizhou Municipal Government and went to visit the China Medical City. After learning about the local government's planning for the vaccine industry, we went to Yangzijiang Pharmaceutical.
After learning about the local government's planning for the vaccine industry, we went to Yangzijiang Pharmaceutical.
Conclusion:
In Yangzijiang Pharmaceuticals, we visiting factories and museums, which gives us a better understanding of how to refrigerate and manage biological cell vaccines. The release rate and hemorheology parameters of our vaccines containing microencapsulated cells after injection into the body remain to be considered. (For more details please visit here.)
He Wang
When marketing a product, we need to have a sound supervision mechanism. At the same time, we need to know more about the product. For each audience's acceptance and price, when we are doing “to business and to customers.” We must pay attention to the health of every patient. We believe that people-oriented vaccines will produce many social benefits.
Conclusion:
His philosophy coincides with us. When we try to use synthetic biology to benefit the majority of TB patients, we must consider the price of our products.
Doctor Chen
If our treatment plan is put into use, although it is cheaper than cell therapies like CAR-T, it will still be more expensive than most traditional drugs. Therefore, we seek help from clinicians to ask how we should reduce the cost of patients and improve the market competitiveness of our programs.
Conclusion:
The doctor said that our therapeutic can compare to the MDR-TB treatment drug bedaquiline, which is currently undergoing clinical research. He suggested that we can also cooperate with the government to try to include our treatment plan in the scope of medical insurance to reduce the patient's treatment burden.
Mr Min Luo, Marketing Manager, Bank of China Insurance Department
He explained to us that critical diseases insurance in China does not cover tuberculosis, but the Chinese government has made a great relief policy for the free use of first-line drugs for non-resistant tuberculosis infections.
However, with the emergence of multi drug resistant Mycobacterium tuberculosis, a increasing number of patients are required to use second-line drugs and they have to bear the cost on their own, so relevant commercial insurance can also become a promising solution.
Conclusion:
At the same time, the questionnaires distributed to patients also showed that in the case of multi-drug treatment, the patient's drug price is very expensive, which makes us consider including it in the medical assistance policy. In this case, we decided to seek help from the CDC once again.
CDC again
This time, we revisited the CDC with the ideas of other experts. This time we have a policy understanding of the reform of the medical insurance structure and try to incorporate our treatment plan into the national health insurance policy. The CDC said that the current development of TB drugs is not very fast, and the country will quite welcome us to provide new ideas for the treatment of tuberculosis.
Conclusion:
Under the guidance of the CDC, we have wrote a proposal to suggest including vaccines for the prevention of major infectious diseases into health insurance.
