Team:SEHS-China/Human Practices
Inspiration
Every spring, my second uncle decks out in a thick mask. The culprit? A hay fever so bad that even with a mask, he still suffers greatly. Every day, his nose would cause massive discomforts for him — he found it hard to breath, he couldn’t sleep at night, and he sneezed consistently. I wondered: could syn bio be a possible way out of his misery?
Our initial idea was to address the pollen allergy that he suffers from. We thought about potential ways to destroy the pollen, for bacteria to destroy the bacteria in the nasal cavity. However, after further research, we found that to be unpractical; there were too many kinds of allergens, and each specific allergen would require a different bacteria to destroy.
At this stage, we were stuck. Fortunately, our teacher gave us some advice: he told us that most allergic reactions are a result of high histamine content in our body. That gave us an idea: what if we can engineer bacteria that can detect histamine, break down histamine, and alert the patient to high concentrations of histamine?
Thus, our final idea is born. A two part project that involves making a test paper capable of detecting histamine levels and an allergy cream that can slow down and alert the patient to allergic reactions.
The test paper would measure the histamine content of food in order to determine how fresh the food is, since histamine content would be higher in more stale food.
In high histamine levels, the LAC-Z gene would be expressed, causing a change in color that can be measured.
The allergy cream would be engineered E.coli that produces histamine oxidase and beta-ionone, both of which can degrade histamine. Another function of beta-ionone is to give off an aroma in the nose, which alerts the patient to elevated histamine levels and an imminent allergic reaction. We intend to put the bacteria in a liposome. When the histamine content around the liposome increases, lipase inside the liposome will be expressed and destroy the liposome, thus releasing the bacteria inside.
Abstract
At the beginning of the project, after a series of literature study and offline investigation, we determined to treat allergic symptoms with histamine degradation as the subject. But as the project progressed, we realized: We didn't have a complete idea, and we weren't sure if our idea would really meet the needs. In order to verify the feasibility and promotion of our project and get effective Suggestions for product improvement, we conducted the following investigations, including questionnaires, pharmacies surveys, doctor interviews and pharmaceutical factory interviews.
The feedback we got from interviews with doctors and pharmacies provided us with the following important information. Firstly, the treatment of histamine degradation is feasible and can be widely promoted.
Secondly, at the patient level, allergy patients' expectations of our products are much higher than we imagined, and we should improve the quality of our products, including side effects, portability and other aspects.
Finally, the forms of products can be diverse, and we are constantly trying and exploring to improve the most suitable products for most people's needs. The pharmaceutical industry has provided us with a variety of options for making drugs, which are very useful to us.
introduction
When our project faltered and we didn't know whether our ideas could meet the needs of most people, the Human Practice group started offline research to promote the development and improvement of the project. So we divided the research into four parts.
We interviewed two doctors for advice on how to treat allergies specifically; Then we set ten questions about allergy and invited 500 allergy sufferers to answer them; After understanding patients' demands for antihistamines, we went to pharmacies for field investigation and analyzed the advantages and disadvantages of our products for existing antihistamines on the market. Finally, we contacted the experience of the pharmaceutical factory for an interview to understand the process from pharmacy to drug distribution, and obtained the manufacturing methods of different types of drugs.
Our research received good feedback, so our project can be further promoted and improved in terms of the research results.
Interview of the doctor
Talking to our doctors, we were advised that we should target allergy prevention by investigating the proteins in pollen that cause allergies and then degrading them accordingly. Starting from a young age, we can investigate the green plants in Jinan city to degrade protein. In fact, the first thing we thought about was this possibility. However, as the project continued, we rejected this plan in the subsequent investigation. Because each pollen has its own unique protein, it's impossible to find an enzyme that breaks down all the proteins. So, we adjusted the Angle and started with histamine.
By the way of histamine, it's more direct and more sensitive. We can degrade histamine directly and thus relieve allergies. The main reason is that the existing drugs are convenient enough without obvious side effects, so we must have some advantages over the current allergy drugs. In addition, doctors say that allergy treatment regimens are already well established, so we need to make certain advantages, such as early warning. So we plan to introduce warning strips or ointments that can give off an early warning if histamine is elevated.
Survey of patients
Our questionnaire for allergy patients did not start with hay fever, but directly surveyed the allergy status of citizens with allergy as the theme. This is because the audience of hay fever is so small that it is difficult for us to obtain a large amount of data to support our hypotheses and ideas. At the same time, allergies and hay fever are both caused by histamine overexpression, and our project is also focused on the degradation of histamine.
We investigated the prevalence of allergies through questionnaires, identified the needs of patients, understood the severity, and the urgency of addressing allergies. At the same time, the demand of many city residents for allergy treatment was investigated, and the popularity of the project was confirmed.
We distributed the questionnaire widely in different cities, collected more than 500 samples, and carried out case analysis on the questionnaire. The majority of respondents indicated that their expectations for the quality of the product were greater than their expectations for the price. This project is of great significance for allergy patients. At the same time, we also learned about the current drugs used by allergy patients. In order to further understand these drugs, we went to pharmacies for field research and contacted doctors for more detailed inquiries.
Survey of the pharmacies
We did field studies of antihistamines on the market and learned about their potency and characteristics, but we realized that there are many effective antihistamines on the market, so our project should have originality.
Compared to these antihistamine medicine, here are our product’s strengths and weaknesses:
First of all, our project develops a preventive drug, which can effectively inhibit anaphylaxis before the onset of the disease. Secondly, the product is for external use and only need to be applied in the nasal cavity, which can significantly avoid adverse reactions of patients with small side effects. Finally, there is still a lot of room for improvement in our project. For example, the application type medicine can be changed into the spray type medicine, which is more convenient to use and enables patients to obtain better medication experience.
However, due to the uncertainty of the specific time of the onset of allergies, completely timely treatment is almost impossible, and we can not thoroughly eradicate allergies from patients' daily life. On the other hand, like some other general antihistamines on the market, our products still have the limitations of being slow to take effect and unable to relieve other allergic symptoms caused by non-histamines.
Interview of Pharmaceutical Factory
We asked about the approximate time and process needed to get from the lab to the clinic. We know that it takes 2-10 years of research and development, 3-6 years of pre-clinical animal testing, and 6-7 years of clinical testing. Clinical trials are divided into three stages: safety evaluation of healthy subjects, efficacy evaluation of patients, and further evaluation of patients. After the completion of clinical trials, new drug marketing approval is required, clinical monitoring phase: phase IV clinical, and approval after marketing (generally 4-10 years after marketing). This is the most basic of a new drug from the approval of research to the market must go through. In the interview with the pharmaceutical factory, we asked questions about the process of making spray medicine and daubing medicine, and understood the different preparation methods and the process that the medicine have to go through from laboratory to clinic. API is the effective part of the preparation, its preparation and selection is a very important part. The development of new medicine is a complex process that requires a lot of human and financial resources.
Conclusion
After establishing the project of histamine degradation in the treatment of allergies, we issued two rounds of questionnaires aiming at patients’ expectation and demand, and both obtained universal and effective information. In order to investigate the feasibility, the production prospects and market value of the products, we conducted further interviews with professional doctors, pharmaceutical companies and pharmacies. After the live investigations we analyzed the advantages and disadvantages of existing antihistamines in the market. Then we are advised to give full play to the advantages of drugs in early warning of histamine.
In the future, if sufficient data are obtained, we will switch to preclinical animal experiments to test drug safety, dosage, activity, and side effects of rats or mice. With the guarantee of successful animal experiments, medicine development and human clinical trials will begin. If the safety and efficacy meet the expectations, the next step is to contact the manufacturer to put into production and apply for listing. Different types of drugs have diverse R & D trials and production lines, which is bound to be a long process. But it is predicted that the product will eventually enter the market, and the probability will be favored by the patient group, also providing a new idea for the treatment of histamine allergy.