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 living 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.
Thus, we visited places like dialysis centers, laboratories, biotech companies and also IPO (Intellectual Property Office) to learn from experts in their fields, and understand more on how to improve our project.
Winston Medical Supply Co.
GeneFerm Biotechnology Co., LTD.
GenMont Biotech Inc.
NARLabs (National Applied Research Laboratories)
Synbio Tech Inc.
TFDA (Taiwan Food and Drugs Administrations)
IPO (Intellectual Property Office)
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.
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. Li-Hui Huang 7/11
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. Li-Hui Huang. 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.
Ms. Yu-Chen Kuo 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.
Feng Dian United Dialysis Center
We visited Tainan Dialysis Center to learn more about patients undergoing dialysis treatments. and to find out whether CreSense can be a good fit if placed in dialysis centers. We also met with Dr. Shun-Jie Hsu and Dr. Kuan Wen Chen who gave us plenty of advice for our device. They agreed that there was currently a gap in the market for a p-Cresol reader, or any other kind of uremic toxin readers. However, they warned us that especially in small dialysis centers like this, the cost of the device and treatments need to be considered.
We also talked about the mindset of patients undergoing dialysis. Not many know the connection of p-Cresol or other uremic toxins with CKD, and only 10% of patients know about gut bacteria. We talked to one CKD patient undergoing dialysis, and he mentioned that his CKD had developed from diabetes - which is considered quite common. Despite not knowing about uremic toxins, he does know that 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 acrylic chip. From this discussion, we then decided to use 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.
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 Biotechnology Co., LTD.
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:
- Quality control of a living cell on a medication
- Food Industry Research and Development (FIRDI) help in inspection of the supplement
- Comparison between food and medication process and regulation
- The risks if we do not apply patent for our drug or medical device
Moreover, they suggested us three things:
- Determine the usage of product like the age group and delivering product
- Take into account the law and regulations since Taiwan does not have proper gene-editing regulations especially toward the biotherapeutic drug
- 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. Also, because of them, we also planned to pay a visit to IPO (Intellectual Property Office) to learn more about patents.
GenMont Biotech Inc.
Genmont is a leading probiotic company in Taiwan, where we had our first enterprise visit and we were fortunate enough to meet Genmont’s Miss Tsai, Wan-Hua, Miss Mei-Ling Wang, Miss Janette Chen. As this enterprise visit was made when we still wanted our product to be a probiotic, our main purpose of visiting GenMont is to learn about how probiotic is made, how quality management is done and regulations we need to obey in applying this product to the market.
They were kind enough to give a short talk about how their company works and how their research and development works. They also talked about their process in entering their product into the market. This way, we were able to get a glimpse of how the company is able to build from the ground up, and inspired us to create a business plan for our products.
Through this visit, we received a lot of feedback and realized we need to much more research, not only on developing our product, but also more research on many other fields. We need to start thinking about how to apply this project into a real life situation. We need to consider the regulations and consider adding our product into the National Health Insurance.They also mentioned about the safety assay on how our engineered E.coli is and by their suggestions, we optimized our kill switch plan and run a functional check to make sure that our engineered E.coli is safe.
Synbio Tech Inc.
Synbio Tech Inc., 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 on how we are going to market the product and manufacture process. We implemented the marketing suggestion from Synbio Tech to expand our products marketing and business plan. It was an enlightenment meeting, we received a lot of suggestions on how we should market our products:
- Establish the key points of the products
- 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):
- Join medical conferences to meet potential business partners and auiliences
- The website design must be appealing and have a clear description
- White paper to attract investors
- Proper and effective advertisements
- Drug must fulfill cGMP requirements, and have their form. They told us that from powder, liquid and tablets form of the drug, the most popular one is the powder sachet but to determine which one is suitable for us, we need to conduct a survey for prices and forms. By their suggestions, we started our survey about public opinions.
Winston Medical Supply Co.
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 Yu-Cheng Wang, CEO of the company and also Yi-Ching Chen, Marketing Director of Winston. 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 Can 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 CreSolve living therapeutic drug flowchart that includes the few steps we need to take in order to make our living therapeutic 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 a new flowchart of our CreSolve living therapeutic drug:
We also asked whether they can be our potential partners regarding drug manufacturing in the future, they said it is possible as long we can show them the final prototype of our CreSolve living therapeutic drug accompanied by government approval and research data.
NARLabs (National Applied Research Laboratories)
Founded by the government, NARLabs is one of the leading research centers in Taiwan. We had the opportunity to visit the lab and consulted our business model with NARLabs’ startup team, which is aimed at helping new startups 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 quite strict and there are still some laws under discussion. So, we should pay more attention to the laws and make sure we are always up-to-date with the latest news.
- 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 that has to be met in order to survive.
- When developing the business model, sometimes it is also important to consider users’ experiences into the model. For example, where will the sensing device best serve our patient and if the device is safe enough to let the patients operate it by themselves.
Laws and regulations set by the government, especially when it comes to GMO products, can sometimes be tricky. In addition to the fact that we wanted to potentially launch our own start-up based on this project, we needed to make sure that we are not breaking any rules. To make sure we are on the right track, we contacted several government agencies.
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 the “invention” patent for our living therapeutic drug. As for our CreSense sensing device, it’s suitable to apply for a utility model patent because the device has new features and new testing projects after our team’s improvement.
TFDA (Taiwan Food and Drugs Administration)
By phone call:
Through GenMont’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.
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).
Fig. 1. Age distribution
Fig. 2. Highest education level
Fig. 3. Background
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)
Fig. 4. Have you heard of CKD?
Fig. 5. What is your understanding of CKD? (5 being an expert on CKD)
Fig. 6. What are the current treatments for CKD?
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.
Fig. 7. What is your level of support for ‘Genetic Engineering’ or ‘Genetic Modification’?
Fig. 8. What is your level of support for the development of "gene-edited" bacterial drugs?
Fig. 9. Will you agree to use "gene edited" bacterial drugs?