The goals of the PACOmega project are generating an alternative EPA resource, raising public awareness of cardiovascular disease (CVD) prevention, and eliminating the prejudice against synthetic biology. To achieve these goals, we determined the original design for generating EPA through synthetic biology, and propagated our PACOmega project and synthetic biology on social media. However, soon after we implemented our naive PACOmega project, we learned that the scope and dimension of our project was far from enough.
To comprehend the needs for our PACOmega project, we first consulted a cardiologist (name withheld by request) to refine our design for generating an alternative EPA resource. The cardiologist also inspired us to remember that an excellent project could not ignore what society truly wants. Therefore, we performed street surveys to reach out to our target audience. We also invited a local pharmacist, Mr. Wu, to share his observations about the marketing of EPA supplements, and the attitude of local people toward nutrient supplements. To prepare our EPA product for the market, we consulted with Dr. Wu, the secretary general of the Health Food Society of Taiwan. Finally, through the activity of the “Taiwan Comprehensive University System (TCUS) entrepreneurship competition”, we contacted the CEO of TWBIO to learn how to promote our product. With these activities, we clarified the axis between EPA generation, product formulation, and future market.
Next, since taking EPA supplements is not the only way to prevent CVD, we sought help from a dietitian (Ms. Chen) and a professor (Dr. Lee) with expertise in exercise for the elderly. The dietitian informed us of the concept of a balanced life, in which diet and exercise are both important for any kind of disorder. The professor further pointed out that the frequency and intensity of exercise are also important factors for CVD prevention. Based on this precious feedback we developed an online recipe book to reduce the risk of CVD, and a campus walking activity (to encourage exercise). These activities raised the awareness of the CVD crisis and also showed the benefits of a balanced life.
From the street surveys, we found that the negative impression of synthetic biology is mostly fear of the unknown. After a detailed explanation, most people could accept the idea of using synthetic biology to make the world better. We are inspired that, in addition to linking the synthetic biology concept with activities promoting CVD prevention, we could hold activities more focused on synthetic biology. This idea led to the online web game, open lab activity, and TCUS entrepreneurship competition. Through the online web game, we shared the basic process of synthetic biology. In the open lab activity, we not only shared synthetic biology with teeangers, but also improved our presentation and pitch based on their feedback. Importantly, we witnessed the urban-rural gap directly, which inspired us to develop affordable laboratory equipment. In the TCUS entrepreneurship competition, we shared synthetic biology with freshmen.
In each aspect of our human practice work, we started off by pondering the problem that we needed to engage, and got feedback from consultants from different fields. We responded to the feedback and got feedback to our responses. These feedback loops brought us closer to the center of the problem, so we could answer the question in the right way. With the closing of the loop, we believe that PACOmega will show its value.
CVD is a rising crisis both in the world and Taiwan. The World Health Organization (WHO) estimated that 17.9 million people die from CVDs each year. Not surprisingly, CVD has been among the top three domestic causes of death for nearly thirty years.
To tackle the CVD crisis in Taiwan and worldwide, we contacted a cardiologist (name withheld by request) from National Taiwan University Hospital to talk about the concept of the PACOmega project and discuss possible improvements. He first pointed out that the growing number of CVD patients in Taiwan is mostly triggered by aging, the most important risk factor for CVD. The longer people live, the higher the risk of CVD. Next, he acknowledged the value of our idea of making pure and high concentration EPA supplements for CVD prevention, but also reminded us of the highly competitive nutritional supplement market.
The feedback from the cardiologist encouraged us to think more about what the elderly need, and what we can provide. Fortunately or not, MinXiong township, where our university is located, is the most aged region in Taiwan.
Therefore, we decided to perform a street survey, and consulted with a local pharmacist to gain more information about marketing EPA supplements, and how the customers think.
While it seemed like a brilliant idea to directly survey the opinions about EPA supplements and synthetic biology from the local people, we were hampered, seriously but not surprisingly, by the result of our market survey. People agreed that a pure, high concentration EPA supplement is attractive, but not if it came from E. coli. Importantly, however, the negative impression of synthetic biology could be reversed or mitigated after detailed explanation. Hence, to be responsible and reliable scientists, it is our duty to clarify the truth about synthetic biology.
Mr. Wu Chih Kai is a local pharmacist who has been working in a local drugstore for years. Not only does he possess proficiency in pharmaceutics, but also is familiar with the local market situation.
During the interview with Mr. Wu, he first reminded us to notice the drug interaction between EPA and other medications. For example, people taking anticoagulants cannot ingest EPA during their treatment due to the concern of synergism, causing the risk of massive hemorrhage.
When talking about the customers, Mr, Wu indicated that Taiwanese tend to overlook their health conditions. Therefore, a proper design of EPA supplement products that make it easy to use and store is necessary, and good propaganda through local media may be helpful for newly marketed products. Based on the suggestion from Mr. Wu, our plan is to sell future EPA supplement products in a quantity suitable for monthly consumption. The feedback from Mr. Wu provoked us to ponder the characteristics of our future product, including dosage, packaging, price, and any other information we would want to know when grabbing a bottle of nutrient supplement from the shelf in the pharmacy.
Dr. Chang-Jer Wu is currently a distinguished professor and the chairman of the Department of Food Science, National Taiwan Ocean University. He is also the secretary general of the Health Food Society of Taiwan.
To translate the lab product into the market, we consulted with Dr. Wu. He reminded us that the endotoxin problem should be considered when using a prokaryotic system. Endotoxin is a kind of lipopolysaccharide (LPS), composing the outer cell wall of all gram-negative bacteria, which are responsible for the organization and stability of the outer membrane. Ingesting endotoxins will cause the symptoms of high fever, vasodilation, diarrhea, and in extreme cases, fatal shock. Therefore, in separating the desired product from the other cell components, great care must be taken to remove all the endotoxin.
However, while endotoxin poses enormous threats to us, it would be our benefit if we could overcome this problem. Because if we make pure and high concentration EPA production a reality, we can shift our product from a nutritional supplement to a medical treatment, which generates far more profits.
Dr. Wu also reminded us of the laws we would face in the future when selling. To protect consumers’ health, there are many restrictions we have to follow to fulfill the goal. While this warning isn't directly relevant to our current projects, we should always make hay while the sun shines.
Dr. Lance Chang is the Chief Executive Officer of Trade Wind Biotech Co., Ltd. (TWBIO). TWBIO is the first biotech company in Taiwan with a fundamental interest in synthetic biology. They have made a lot of effort in preserving precious natural resources by designing a probiotic cell factory.
The interview with Dr. Chang was a problem-shooting discussion that focused on the unwelcome endotoxin. The outcome was very informative and constructive that enlightened us with not only a new development alternative, but also a realistic approach to its removal.
During the meeting, Dr. Chang first informed us that the E. coli Nissle guts microbiome, which has been approved by FDA, could be our best alternative because it can constantly generate EPA in our intestines. Hence, we could shift our prototype from ingesting EPA passively to cultivating EPA-producing probiotics gut microbiota to absorb EPA actively. This insight was a brand new idea that largely reversed our idea of EPA ingestion.
When it came to making our project more visible, Dr. Chang mentioned another fascinating option: vegetarian meat. Instead of packing the EPA into capsules, it would be very eye-catching if we extracted EPA from E. coli Nissle and incorporated it into vegan meat. This cutting-edge food innovation could not only make our product more competitive, but promote a new way of thinking about nutritional supplements.
During our experiments, we were often hindered during transformation because the genes we wanted to transform were too big to deal with. Dr. Chang suggested that using a Fusion kit to clone our target gene would be more efficient and the success rate would also rise. At the same time, Dr. Chang also suggested we compare the efficiency of different promoters, which might smooth our process of producing EPA.
As mentioned in the overview, prevention of CVD is our priority. Therefore, we looked for a more comprehensive answer for CVD prevention by reaching out to a dietitian, Dr. Chen. She told us that prevention of CVDs should begin with the optimization of daily routines, particularly daily exercise and diets.
Following the dietitian’s suggestion, our team came up with two ways to promote the two concepts of healthy diet and daily exercise:
We collaborated with worldwide iGEM teams to collect CVD-reducing recipes using local ingredients, and establish a CVD-reducing cookbook for people to get information on healthy eating more easily.
At the same time, we collaborated with the Center for Innovative Research on Aging Society in our university to hold a campus walking activity for hundreds of elderly living in nearby regions. In this activity, some participants shared their experience of fighting with CVDs, which greatly encouraged us.
However, since our target audiences are mostly elderly, the design of the exercise plan should take physical strength and endurance into consideration. Dr. Shuk-Fong Lee is the chair of the department of athletic sports of our own campus, Chung Cheng University. She is an expert not only in exercise psychology, but also has done research on exercise plans for the elderly specifically. Dr. Lee’s expertise happens to coincide with our needs. Therefore, we consulted her with some questions about how CVD patients or potential patients should exercise and how we could promote daily exercise to the public.
Dr. Lee reported that High Density Lipoprotein (HDL) increases in direct proportion with High Intensity Interval Training (HIIT), which is strenuous exercise for 30 seconds, followed by rest for 30 seconds, repeating the process for 3 minutes. In addition, she told us that the campus walking we held is effective but not efficient. It can achieve publicity about the importance of daily exercises, but isn’t the best choice to maintain health and prevent CVD. Instead, doing weight training, squats, and interval training with professional coaches will have a more significant effect.
As a result, this interview gave us a whole new perspective on doing exercise. “When you see a person with great skin and fair body, you're going to ask if that person used body care products or took nutritional supplements. Few will ask, what kind of exercise have you done?”, said Professor Lee. While we seek external care to improve bodily health, it is crucial for us not to leave any muscle, piece of bone, or inch of skin behind. Professor Lee not only brought us new knowledge about daily exercise, but also roused our consciousness of health care, not based on taking supplements, but caring for ourselves.
From the street survey, we learned that the negative impression of synthetic biology can be reversed or mitigated by education. Therefore, we tried to bridge the gap between science and society through activities. Accordingly, we designed a web game for all ages, an open lab activity for teenagers, and the TCUS entrepreneurship competition for university freshmen.
To fill the gap between science and society, and share the beauty of synthetic biology, we held an Open Lab science camp and invited high school students to get involved in synthetic biological experiments. We successfully left a positive impression of synthetic biology to high school students. However, we also learned an important truth from these students: not all high schools are fully funded in experimental equipment, especially those schools in rural regions. This truth made us wonder if we could do a little more to share our resources with others, the so-called USR.
Dr. Yan-Chang Lee, currently a postdoctoral fellow in the Research Center for Precision Molding, National Chung Cheng University.
In rural schools, it is impossible for teachers to have assistants to do preparation for laboratory activities. Therefore, we think that affordable, automatic, and remote lab equipment may encourage teachers in the rural schools to design more experimental courses to educate teenagers.
Since bacterial culture and gel electrophoresis are essential experimental techniques in synthetic biology, we decided to start by producing an automatic gel preparation machine and quantitative agar faucet. Accordingly, we ask for feedback from Dr. Lee.
Throughout the meeting, Dr. Lee emphasized the importance of knowing and meeting the user’s needs. He was interested in our design, pointing out that the potential clients for our quantitative agar faucet might probably be at institutions with limited learning resources. Being unable to afford fancy but costly utensils like electronic pipettes, our quantitative agar faucet could perfectly meet their needs, while electronic pipettes are too expensive to have.
Following our idea of the automatic gel preparation machine, Dr. Lee has observed the trend of introducing automation into experimentation. He then gave us many insights into possible enhancements of the machine, including applying a microchannel to the heating device, the concept of injection molding, and recommending other quantitative devices for better preparation of solution. Incorporating these suggestions, the process of making agarose gels by our machine will be conducted more smoothly and efficiently.
Throughout the entire IHP journey, we put a lot of emphasis on the human practice evaluation. Reflecting on the impacted communities, we showed our responsiveness in the way of “relieving the shortage, providing the necessary” to be connected to the wider world. However, the process of refining doesn’t stop here, but should be considered a long-term goal.
Therefore, to close the loop between our design and what is desired, we developed two values that should be followed thoroughly in the future work: (1) comprehensive perspectives on CVD prevention and (2) engaging with those impacted.
While our initial idea was to prevent CVD by producing EPA in our lab, it requires more than just ingesting good oil, but also staying away from bad oil. However, to meet the goal of having a balanced lifestyle, we should also value the importance of regular exercise and a healthy lifestyle.
One important component of our ultimate goal, advocating CVD prevention, is to introduce synthetic biological production EPA to society. Therefore, we should always stay in tune with public acceptance and discussion.
Keeping up with both negative and positive opinions should never be regarded as a transitional goal, but rather, a human practice that should be thoroughly implemented throughout all phases. Most importantly, we always remind ourselves of the importance of the opportunity of sharing between both scientific and general communities.