Team:RDFZ-China/Human Practices

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Overview

In our early design of the project, the intended influence is to focus on the development of alternative therapy for depression patients, which can be influential to people who are affected by similar diseases. However, we would need to acknowledge the more practical difficulties that our clients might face, so that we can improve our project and make plans for our second year for further development. As it is hard to experience the medical treatments of a depression patient or the production of related medicines, we talked with related experts and summarized feedbacks on specific aspects. Also, considering the implementation of our therapy, which involves the intake of catechin, we did the investigation on the general public of our school and obtained the result of the general preference on the selection of different kinds of tea. This result will be put into use when we introduce real tea to our experiment.

Psychotherapist

We visited Yang Rui, the psychotherapist, who is also a lifetime member of the U.S. National Psychology Honor Society, to acknowledge the first-hand experience from the contact with the student patients. She is also the author of Understanding the immigrant paradox in youth: Developmental and contextual considerations. New York: Cambridge University Press (2013). She was fond of our project and suggested its possible application in the treatment of mental diseases.


"Many patients do not receive effective treatment in the first place...Your treatment can contribute to alleviative therapies for patients with mild symptoms"

We were concerned about to what extent our development of TEA-HEE can be useful to the patients since the traditional therapies are hard to be replaced. However, Ms. Yang suggested a way that our products do not have to be the intended replacement for SSRI.

According to Ms. Yang, our engineered bacteria can be used as a kind of prescription medicine that helps patients with mild symptoms to intervene in the worsening condition. Since these patients won't be treated with therapies that involve actual drugs and TEA-HEE is somehow milder than SSRI but more effective than simply letting the illness develop, our product can be an alternative therapy that alleviates the state of depression.

However, it's also important to note that the process of using our product is rather complicated, which can reduce patients' motivation to cooperate in the therapy. Additionally, many patients that suffered from depression also have symptoms of insomnia, so we need to choose the types of tea carefully.

Clinical Doctors

At the early stage of our program, we try to investigate more about depression and the current treatments for the disease. Therefore we had an interview with several psychiatrists working in Shijitan Hospital in Beijing. During the interview, the doctor introduced the pathogenesis of depression and the current existing treatments, which provide detailed background information for our project.


"Serotonin has many effects in the brain, including regulating mood, sleep, appetite, pain, body temperature, and sexual function."

The conversation with Mrs.Wang reminded us to pay attention to the important role serotonin plays in regulating not only the mood but also other body functions. When we increase the amount of 5-HTP, we should be concerned about how much of it transform into other hormones besides serotonin and the side effects it might bring. We plan to monitor different physiological responses when giving a different concentration of the 5HTP, therefore we can reduce the risk of our product to some extent.

TEA-HEE aims to find an alleviative therapy for depressed people who is afraid of taking medicine. Based on our previous research, some patients report severe secondary actions when they take drugs. Therefore our team is curious about the side effects of the major antidepressant drugs, which include: SSRI, SNRI.

Apart from the side effects, the reoccurrence and inappropriate schedules of taking medicines are also contributing to the insignificant effect of the traditional antidepressant treatments.

Our conversation with the experts clears up a misunderstanding we previously held, which is the secondary reaction is tense and can not be alleviated. The comments made by patients online might have been exaggerated because of their negative emotions, therefore we should probably consider the experienced doctors' perspective more when considering the side effects of drugs. However, in the second year, our team plans to have a face-to-face interview with patients and their family members. We want to get first-hand data and think thoroughly from the patients' point of view.

Lv Xueyu is an attending physician in the psychology department and sleeps medicine clinic at Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine, with a doctorate in the direction of Chinese psychology in acupuncture and massage and a master's degree in the clinical direction of sleep disorders in Chinese internal medicine; a bachelor's degree in applied psychology from Shandong University of Traditional Chinese Medicine; and is qualified as a psychologist, psychotherapist, and TCM psychologist. We asked some questions about the patients and hope to get some feedback on the clinical application of our project through this interview. And Dr. Lv's feedback pointed us to a problem with the product.


"All treatment modalities have serious residual recurrence problems."

From Dr. Lv's point of view, mental illness is induced by family education, major life events, and a weak social support system. The causes of these triggers are difficult to pinpoint and summarize, so treatment options are varied.

Dr. Lv mentioned that taking medication is officially approved, but patient rejection is high. Some side effects are less influential but can cause some distress to the patient. Also, therapeutic drugs are expensive, although they are taken in smaller doses. And all the treatment modalities have a serious problem of relapse.


"The issue of direct ingestion of serotonin has yet to be addressed."

Dr. Lv praised that the existing treatment did not involve engineered bacteria, which is a good idea. But one loophole in the program is the direct ingestion of serotonin. This involves its synthesis, and the amino acids are likely broken down making it ineffective.


Pharmaceutical companies


Xie Guanfang, Ph.D. of Wuhan University Department of Microbiology. Yang Di, Ph.D. in Nutrition and Molecular Sciences, Berkeley, California, now a scientist at a biotechnology company. Cui Kui, a postdoctoral fellow at Harvard Medical School. Tu Fei, postdoctoral fellow of the University of Pittsburgh School of Medicine. Zhang Nan, M.S. in Food Microbiology, now a scientist in a biotechnology company. We wanted to interview a panel of experts from this biopharmaceutical company to explore the feasibility of this project becoming a drug.


"It is a key question of whether the microflora can be implanted well."

The experts point out that the capsules we place may affect the normal ecology of intestinal flora. Intestinal flora varies from person to person, and adhesion protein affects each person differently. If the individual's intestinal flora is well established, it is highly exclusive. It is a key question of whether the microflora can be implanted well. Because the microbiome has effects on other things, like proteins, we want it to have no other effects on the rest of the body. Individual variation had the greatest influence, and food-grade bacteria had little influence on the intestinal tract. But we also have to consider whether the balance of the post-implantation flora is disrupted and if it is disrupted, whether the flora can remain. It is difficult to control the stability and effective conversion rate of stable expression in vitro and in vivo. How to control the strain in the body and how to achieve the corresponding blood concentration with the oral drug are problems to be solved.


"There are still some uncontrollable factors in your project that need to be further improved."

Experts agree that more or less controllable factors, such as the reaction to drinking more or less tea and how much of it reaches a given concentration, need to be set within a strict range. Besides, if bacterial reproduction dominates and production concentration changes, the method to control this variable still needs to be considered. In general, how to deal with or control the imbalance of intestinal flora.

Dr. Yang said further research was needed into the effects of different teas, such as black and green tea, and eventually standards. To be specific, after the strain is made, all the tea on the domestic market should be bought to stimulate the strain. The content of tea polyphenols was measured after different kinds of tea were metabolized. Currently, it is relatively easy to construct intestinal stable proteins, but more literature needs to be consulted for practical problems such as the control of production. Also, the significance of the subject is too large, and experts point out that the significance of the subject needs to be reduced.

Tea culture expert

After choosing tea as the substance that stimulates the system, we interviewed Ms. Ma who is experienced in the basic facts of tea and is willing to provide support for our projects. We need to recognize the possible risks in this whole system.

"Black tea nourishes the stomach, promotes blood circulation and is almost harmless to the body"

After we introduced our project, Ms. Ma suggested black tea, which contains more trace elements and has less stomach irritation. For patients, the naturally heavy and rich taste of black tea is more friendly. Besides, as world-renown drinking, the use of black tea expands the target audience of our project.

"Although tea is a relatively mild drink, there are still some precautions when drinking it."

After Ms. Ma's explanation, we understood that tea should be drink half an hour after meals. Besides, one should drink as little tea as possible after 5 p.m according to traditional Chinese habits. Ms. Ma gave a very professional explanation of the physiological deficiencies of drinking tea which is an important supplement to our overall program. To better achieve the effect of our project. We plan to do some mathematical modeling to determine the most appropriate amount of tea one should ingest at different times.

Although we confirmed the feasibility of using tea as a primary stimulation in our therapy, relating to the visit to the psychotherapist, it's still necessary to suggest not to take in tea at night.


Conclusion

In-depth communication with several experts made us aware of the development and improvement of our project. We characterized the suggestions made by experts into three categories, including the tea itself, the feasibility of implant engineering bacteria, and the effectiveness of our treatment methods.

Based on previous investigations and expert interviews, we believe that the use of tea as a medium for the treatment of depression has great physiological benefits and is easy to be accepted and promoted. However, the potential problems related to drinking tea also required further consideration. We are already investigating the levels of caffeine and theophylline in different teas. We are also planning tea tasting activities based on expert advice. For our second year experiment, we plan to test the number of nutrients in different tea products and concentrations and their effects on the human body.

Some experts have raised questions about the safety issues of engineered gut bacteria. The Technique of enteric implantation of engineered bacteria is still immature, and many questions need to be explored. We plan to seek experts in the field of gut microbiota and further investigate the intestinal microenvironment and the problems caused by the imbalance of bacterial flora. In the subsequent experiments, we will simulate the intestinal tract in vitro and test the feasibility and safety of the attachment and shedding of our engineered bacteria.

The experts' suggestions made us realize that there are still many areas to be improved in our project. To make our project more feasible, we will interview depressed patients and solicit their opinions on our project. Although it is difficult for our project to turn into a clinical drug, it is still our goal to turn our idea into reality.