Team:NCKU Tainan/Human Practices
Overview
Sometimes as scientists, we tend to forget the world outside the lab. Innovations succeed inside the laboratory doesn’t mean it can be applied to the real world. An important aspect we need to consider is how our technology can be applied in society. Thus, human practice became one of the major pillars of our project, to test our project against the challenges in the real world. We believe that only through working with both professionals and consumers can we ensure that our product is beneficial to all. Our approach to human practices involved working with both professionals and the general public to understand their opinions and tailoring our project to meeting their demands. Through our interactions, we get to explore different aspects of the project that we would otherwise ignore, including intellectual property, sustainability, laws, and regulations.
The world is changing daily, and with it, talents, skills and experience needs to be a part of that growth cycle too. With the growing controversy on GMOs and live therapeutics, we realized our iGEM project is at the heart of this discussion. The research and results on live therapeutics are few and far between, with it only being brought to attention these past few years. There are still so many challenges and obstacles live therapeutics have to face before it is widely accepted as a treatment method. We realized that no matter how much research we do, we ended with more questions unanswered than answered. Can we make it out onto the market, and survive in the harsh and competitive environment? How do we ensure our product’s viability in the market? What is the current stance of the world when it comes to live therapeutics? To ensure we are able to finalize the different aspects of our products, we decided to turn to different aspects of society, engaging with doctors, nurses, researchers, professionals involved in the legal and business side of drug and device development, patients, students and the general public.
Expert Visit
Healthcare experts Visit
Dialysis center
Dry & HP labs visit
Enterprise Visit
Winston
Geneferm
Genemont
NAR LABs
Synbio Tech
Government Association
TFDA
IPO
(Intellectual Property Office)
Survey
OMG Survey
Expert visit
Before we are able to get started on developing our idea into a product, we need to make sure that our idea is as close to perfect as possible, and that means tons of research and experiments. But, the real problem with many ideas, and perhaps the reason why many fail to become a success, is a lack of expertise. No matter how much time and effort we put into research, there will always be an expert who knows the topic or even industry much better than we do. So, to help further verify and improve our ideas, we visited several experts in different fields.
Dr. Te-Hui Kuo 4/15
Attending Physician, Division of Nephrology, National Cheng Kung University Hospital
We met with Dr. Te-Hui Kuo to gain knowledge about Chronic Kidney Disease. He provided us with invaluable insight into the connection between p-Cresol and Chronic Kidney Disease. We met with him during the early stages of the project, and he advised us to keep expanding on the idea of using blood measurement for uremic toxins. He also warned us that the public, and even doctors don’t pay much attention to uremic toxins, which encouraged us to design activities to spread awareness, which you can find in our public engagement page.
Dr. Junne-Ming Sung 6/25
Director and Attending Physician, Division of Nephrology, National Cheng Kung University Hospital
We met with Dr. Junne-Ming Sung to talk more about the viability of our device in the market. He guided us to think about the future of our device, highlighting several questions we had never thought of. His valuable insight allowed us to begin shifting the trajectory of our device to have a more functional role in the market. Instead of just being able to prove our biotherapeutic works, our device now has the potential to become a cornerstone in the diagnosis of Chronic Kidney Disease.
Ms. Huang Li-Hui 8/11
Nurse, Chia Yi Chang Gung Memorial Hospital Dialysis Center
In an activity hosted by Taiwan Chronic Kidney Disease Foundation, we had the opportunity to meet Ms. Huang Li-Hui. As someone who interacts with CKD patients on a daily basis, she was able to give us more insight on a CKD patient’s needs and wants. She talked us through the treatments that CKD patients undergo, mentioning that dialysis was often used as a prevention method for CKD patients, and they need to undergo dialysis three times a week. While uremic toxins and uric protein checks are important for CKD patients, they do not do routine checks on it - and even if they do, they only do creatinine checks once a month. Another interesting tidbit is that patients tend to favor chewing candy rather than injections or capsules.
Ms. Guo Yu-Zhen 8/29
Chronic Kidney Disease Nurse Specialist, National Cheng Kung University Hospital
As a CKD Nurse Specialist, she periodically give lectures on how to handle CKD patients and background knowledge on the disease, and thus, knows the disease very well. She taught us quite a lot about the disease, especially about the treatments. While there is no current treatment that can fully cure the patients, she does admit that the patients will sometimes take Chinese Herbal medicine or even go for acupuncture to give themselves a peace of mind. When we mentioned our project, she mentioned a current drug currently insured by National Health Insurance (NHI) that could be our market competitor. In order to make it in the Taiwanese market, she advised us to consider our drug being insured by NHI, as the government has policies regarding CKD in Taiwan, and thus insured most CKD treatments.
Tainan Dialysis Center
Purpose: to learn more about dialysis and whether our p-Cresol device is suitable and can be put in the dialysis center , we met Dr. blabla to learn more about CKD patients who are doing dialysis , Dr. Xu said to have p-Cresol reader is a good idea but we need to consider the cost of the device and treatment since in small clinic of dialysis center , if it is expensive and inconvenient , they will not apply the method or device. When we went there , we were still proposing having probiotic to reduce p-Cresol ,he told us probiotic can not be included in the NHI because it is considered as “healthy supplement” but usually this “healthy food” will be recommended by Doctor.We were wondering whether uremic toxin is harmful for CKD patients are known by them but Dr. Xu said usually patients don’t have uremic toxin awareness since they mostly are only following doctor’s suggestion. Currently, only 1/10 of patients understanding intestinal bacteria. By our talks , we can summarized :
- CKD patients do dialysis 3 times a week and it takes 4 hours per treatment
- ESRD Patients in Taiwan are usually treated by 95% Hemodialysis , 4% Peritoneal dialysis and 1% Renal transplant
- Taiwan CKD patients do dialysis but small percentage of them do kidney transplant.
We also got permissionWe also got permission from doctor and one CKD patient who was dialysing that time to be interviewed , our questions were more about how they got CKD and do they know uremic toxins accumulation in CKD which can lead to CVD? Patient replied us he was developed from diabetes and he thought the diets for CKD are based on the patient’s condition itself , he doesn't really know about uremic toxin but he does know CKD can lead to cardiovascular disease.
Professor Yi-Je Juang
Professor, Department of Chemical Engineering, National Cheng Kung University
While we were testing PDMS chip, we encountered a problem. When we injected whole blood into the blood separation chamber, the blood would flow into the reaction chamber instantly, causing impureness of the plasma. We hope to stop this from happening so we went to Professor Juang to ask suggestions toward our microfluidic wafer. He suggested us to apply a passive valve on the channel between the whole blood chamber and the reaction chamber. The passive valve can stop the flow of the blood without incurring any additional operation, which improved the purity of the plasma we gained significantly. Furthermore, He told us to retry on the PDMS spinning test (the PDMS would burst during centrifuge at that time) since theoretically, PDMS layers should strongly adhere together and it should be inseparable. Also, he suggested us to use double-sided tape in the combination of the acrylic disc, which is proved to be effective. By having a fruitful meeting with him, we restored our faith in PDMS and improved our project by applying passive valve and double-sided tape in the microfluidic disc.
Professor Chia-Yuan Chen
Associate Professor, Department of Mechanical Engineering, National Cheng Kung University
We proposed our idea about creating a device using microfluidic chips in mind, however we were not exactly sure how to apply the chip into our device. Professor Chen was very helpful as he discussed with us about the type of microfluidic chip that can be used in our device, how the chip will integrate with other parts of the device, and whether our chip is reusable or not. He told us to try using PDMS chip because it’s affordable and it has the same performance as the acrylic chip. From this discussion, we then decided to use a PDMS-based microfluidic chip. Professor Chen then provided us with resources in his lab and taught us the required PDMS chip fabrication skills. By his help, we successfully made a few version of PDMS microfluidic chips.
Professor Ruey-Jen Yang
Chair Professor, Department of Engineering Science, National Cheng Kung University
We consulted Professor Yang when we kept failing on creating the PDMS microfluidic chip as the runner joint made of PDMS will rupture during centrifugation process. Although the third version of the wafer is reinforced at the joint, we still hope to find an alternative before the third version of the wafer comes out. Since Professor Yang has done low-cost paper-based chip development and micro-flow channel design, we hoped to get help and his advice in this regard.
After asking and briefly describing what we wanted to do, he suggested us to find his student who was doing a PDMS-related study. He told us that the bond between PDMS and PDMS is weaker than the bond between PDMS and glass and acrylic. It is recommended that we try to use PDMS and acrylic binding to test whether the strength could have a higher performance. Other problems also include the parameters of the oxygen plasma during binding that will also affect the binding effect (the pressure and time of the binding). Professor Yang then suggested that we make the whole acrylic disc into a microfluidic disc, which will save some space and fixed processes and introduced Ph.D. Weng to us. By his suggestion, we went to Ph.D. Weng and tested acrylic materials for bonding in our third version of the device.
Ph.D. Chen-Hsun Weng
Chief of Industry-Academic Collaboration in Medical Device Innovation Center, Tainan
We went to Ph.D. Weng to learn about paper-based microfluidic chip and how to use acrylic engraving machine and we also consulted about what type of microfluidic chip suit us the best. We had tested our device parts and found some troubles regarding the chip we used. Our first version uses PDMS microfluidic chip but apparently when we tested it in our centrifuge, it burst. Therefore we went to Ph.D. Chen-Hsun Weng who suggested us to use paper-based chip because it can do blood separation. He also said PDMS is harder to customize and is quite inefficient. He then taught us to use the engraving machine for the acrylic disk.
Enterprise visit
Just because an idea is good does not always mean it will sell well in the market. Our product may be designed and modified in the laboratory and adjusted to maximize its performance. However, we needed advice from potential stakeholders to ensure our product will meet real- world demands. We need to interact with industries to understand more about the industrial environment and current market situation. So, in order to refine our idea into a product suitable for the market, we visited several enterprises.
Geneferm
Geneferm is a leading fermentation company, that focuses on fermented fungi, microbes and also probiotics. We visited Geneferm to learn more about the criteria we need to meet before our product can enter the market. At this stage, we were still considering whether to market our product as a drug or probiotic.
From our meeting with Miss Erin Wu and Mr Eugene Wu, we learned the criteria for quality control of a living cell on a medication. We also realized we need the help of Food Industry Research and Development (FIRDI) in inspection of the supplement. They advised us to compare the differences between food and medication processes and regulations. They also reminded us of the risks if we do not apply patent for our drug or medical device.Moreover, they suggested us three things. First, we need to determine the targeted consumers of our product like the age group. Second, we need to take into account the law and regulations since Taiwan does not have proper gene-editing regulations especially toward the biotherapeutic drugs. Third, education toward GMO usage. By their suggestions, we conducted survey for our drug method delivery and classified approximate age of ESRD patients who will consume our biotherapeutic drug (Data can be seen in our entrepreneurship part. Also, because of them, we also planned to pay a visit to IPO (Intellectual Property Office) to learn more about patents.
Genemont
Genemont is a leading probiotic company in Taiwan , we had our first enterprise visit with Genemont’s Miss Tsai, Wan-Hua, Miss Mei-Ling Wang, Miss Janette Chen, our purpose is to learn about how probiotic is made , quality management and law regulation in applying this product to the market we proposed our project to Genemont , but before that they presented about how their company works and how they usually manage to have new probiotic and their process to reach the market. By this visit , we received a lot of feedback and realized we got many bugs and homework to do ,helping to shape our views in many terms such as law & regulation , not only just we need to go through National Health Insurance or Taiwan Food and Drugs Administration but they suggested us to apply for European Union and American Law to have worldwide approval , they also mentioned about safety assay on how our engineered E.coli is and by their suggestions , we optimized our kill switch a plan and run a functional check to make sure that engineered E.coli is safe. They suggested to use Lactobacillus since it’s more common in probiotic world
Synbio Tech
Synbio Tech , a company focusing on probiotic powder and healthcare products. We got a chance to meet Mr Jin-Seng Lin , Miss I-Ju Chang and Miss Erica Chang from Synbio Tech.Our purpose is to have valuable insights in how we are going to market the product and manufacture process . It was an enlightenment meeting ,we received a lot of suggestions on how we should market our products :
1. Establish the key points of the products
2. Marketing Promotion has to be different since our products are different and have a specific target. They also mentioned our drug marketing is also limited as we have target consumers. However, they did mention B2B (Business to Business):
i. Join medical conferences to meet potential business partners and audiences
ii. Website design must be appealing and have a clear description
iii. White paper to attract investors
iv. Proper and effective advertisements
We implemented the marketing suggestion from synbiotech to expand our products marketing and business plan (hyperlink to “Entrepreneurship” Business Plan)
v. Drug must fulfill cGMP requirements, and have their form. They told us that from powder, liquid and tablets form of drug, the most popular one is thepowder sachet but to determine which one is suitable for us, we need to conduct survey for prices and forms. By their suggestions , we started our survey about public opinions (Hyperlink to “Entrepreneurship” Method to deliver)
Winston
We went to Winston Medical Supply Co. to learn about the drugs market and the steps needed to be taken for a drug to be in the market. We were able to meet with Wang blabla, CEO of the company and also Yi-Ching Chen, Marketing Director.We received a lot of feedback toward our wet and entrepreneurship part. He agreed that CKD is a serious problem in Taiwan and uses up a lot of money to deal with the treatments, but they were concerned about how we are going to maintain the effectiveness of yadF gene knockout, but after we showed them how we did a functional test, they then suggested it needs to be optimized later when we already finished with the fermentation and packaging part in the future.
Moving on to the marketing part, we showed them our biotherapeutic drug flowchart that includes the few steps we need to take in order to make our biotherapeutic successful in the market. Wang CEO emphasized that we need to start from API (Active Pharmaceutical Ingredients), and it needs to be divided into 4 parts which are Regulation, API, Formulation and Preclinical. After that we then can develop our drug more precisely. Through their recommendations, we came up with new flowchart of our CreSolve living therapeutic drug:
College X
Founded by the government, Narlabs is one of the leading research center in Taiwan. We were really appreciated to be able to visit the lab and the consulted our business model with the Narlabs’ startup base, aim to help new startup to build better business model and also provide fundings to potential startups. During the visit, we talked about the overall project of OMG and also showed them the current business model we had.
The meeting was successful and we gained a lot from Narlabs, mostly from the business part:
- Currently laws in Taiwan on engineered bacteria are strict and some laws are still under discussion, we should pay more attention on the laws and make sure to follow them.
- Coating the sensing bacteria on PDMS chips may be a good idea, but we need to be extra careful about the bacteria because most bacteria have a certain condition to survive.
- When developing the business model, sometimes it is also important to consider user experiences into the whole model. For example, where can the sensing device best serve our patient and if the device is safe enough to let the patients run by themselves.
Government Association
This has been called "one of the best-known sentences in the English language",[7] containing "the most potent and consequential words in American history".[8] The passage came to represent a moral standard to which the United States should strive. This view was notably promoted by Lincoln, who considered the Declaration to be the foundation of his political philosophy and argued that it is a statement of principles through which the United States Constitution should be interpreted.[9]The Declaration of Independence inspired many similar documents in other countries, the first being the 1789 Declaration of United Belgian States issued during the Brabant Revolution in the Austrian Netherlands. It also served as the primary model for numerous declarations of independence in Europe and Latin America, as well as Africa (Liberia) and Oceania (New Zealand) during the first half of the 19th century.
IPO (Intellectual Property Office)
Due to a suggestion made by Geneferm, we visited the Intellectual Property Office. We wanted to consult the expert and commissioner about the procedure of the patent application. We also wanted to know if there will be more regulations and laws to ensure the uniqueness and specificity of our product after the living therapeutic drug is marketed. In addition, we also wanted to understand why there are so many bio-related restrictions.
The director of IPO Tainan Branch gave us a patent-related course. He taught us the query skills of our patent search mechanism. The expert also reminded us to pay attention to the relevant application procedures. From category, item, objects to cost, they all have clear explanations. Even the years, nationality, and method of application have different regulations, too. Due to its unique operations and novel ideas, the director recommended us to apply “invention” patent for our living therapeutic drug. As for our p-cresol reader, it’s suitable to apply “new type” patent because the device has new features and new testing projects after our team’s improvement.
TFDA
By phone call:
Through Genemont’s suggestion, we contacted Taiwan Foods & Drugs Administration to propose our project. They were very clear in the difference between a probiotic and drug. They said that because we wanted to say our product has pharmacological effects, we need to market CreSense as a drug instead of a probiotic.
2019 NCKU iGEM OMG Survey
Genetically Modified Organisms (GMOs) are becoming more and more prevalent in our society due to its potential in many different fields, including pharmaceutical field. There is a large amount of misconceptions and controversies surrounding GMOs. Despite the majority of scientists and researchers pushing for GMOs, it seems like the public are getting more and more wary about it.
In order to have a better idea of how the public perceives GMOs in the context of our Oh My Gut project, we developed an opinion survey about GMOs and their use in the treatment of CKD. We were fortunate enough to be able to spread this survey to international citizens. We received responses from Singapore, Malaysia, Indonesia, Japan, the Netherlands, Germany, Ukraine, Spain, Mexico, China, Canada, India and Greece.
Population Sample
From the responses we got, we know that nearly 80% of responses were comprised of those aged 18 - 25 and 41 - 65 (see Fig. 1). It was relieving to know that a large majority has received high school-level education at the very least (see Fig. 2), although only 19% were of scientific backgrounds (see Fig 3.).
Knowledge on CKD
First, we wanted to assess the sample population’s general knowledge of Chronic Kidney Disease. Thus, we established several questions to learn more about their level of information. It was quite a surprise to us that only 47% of them had heard of CKD (see Fig. 4) and only 10% admits to being quite knowledgeable about CKD (see Fig. 5). When asked about current treatments for CKD (see Fig. 6), 58% admitted to knowing nothing. The most well known method was dialysis and kidney transplant, with 22% and 11% responses respectively. Other responses include medicine, diet control, controlling blood pressure/sugar and active charcoal.
From these responses, we could deduce that there is still a lack of education and knowledge when it comes to Chronic Kidney Disease. The responses inspired us to launch a workshop aimed at elementary students, to educate them about kidneys with a hands-on approach. (See Public Engagement Hyperlink to Public Engagement)
Living therapeutic Acceptance
Second, we wanted to assess the sample population’s acceptance when it comes to living therapeutic. Thus, we established a few questions to understand more about their stance on living therapeutic (engineered bacteria used as medical treatments). Only 37% were supportive of genetic engineering, while 31% were considerably neutral (see Fig. 7). 39% approved the development of ‘gene-edited’ bacterial drugs, while only 34% agreed to use said bacterial drugs.
From these responses, we could deduce that there is still a large percentage of people who do not fully support or are neutral about gene editing, especially when it comes to gene-edited bacterial drugs. As such, we can conclude that there is still a long way to go before gene-edited pharmaceutical products like CreSolve (our live therapeutic drug) is able to hit the market. However, we are still optimistic that given enough time and education, live therapeutics can become a staple in medical treatments.
p-Cresol Detector Acceptance
Last, we wanted to assess the sample population’s acceptance when it comes to utilising a p-Cresol Detector. Thus, we established a few questions first to understand the current situation and whether or not there is a need for this detector. 38% have ever done a kidney function test (see Fig.10), but only a mere 9% has ever done a self paid uremic toxin test (see Fig. 11). However, we cannot know for sure if the reason there is only a small percentage of people doing uremic toxin tests is because of lack of knowledge or lack of need.
We performed this survey to understand more about what the public wants and needs when it comes to a uremic toxin detector, to further understand CreSense, our blood p-Cresol quantification device’s value in the market. Most are concerned about the accuracy and cost of the device, with 67% only accepting the device if the price-tag is below 50 USD. That being said, we are happy to say that each CreSense test will cost less than $2, which is much lower than the public’s estimation.
