Our Integrated Human Practice work this year helped us have a better understanding of our project from different aspects, not only the synthetic biology experiments, but also our potential development. We manufactured our bio-sunscreen product to obtain economic benefits and to protect our coral ecosystem as well. From our HP experience, we even found the public ignorance of the danger faced by coral and the legal loopholes in our home country, which urged us to take the responsibility of scientific education and legislative suggestion.
Most important factors influenced by Human Practice work:
1. Selection of natural UV absorbent considering environmental effects;
2. Selection of original strain considering current regulations and production cost;
3. Necessity of product evaluation;
Some future work guided by Human Practice work:
1. Priority to guarantee product safety to coral reefs;
2. Commercialization and large-scale production;
3. Cooperation with NGO to promote perfection of related laws.
COVID-19 has been undoubtedly a hot topic in recent years. In the early days after building the iGEM team, we discussed many issues around the epidemic, from health care to the economy, wishing to find some topics for the project this year. COVID-19 has brought various negative influences, such as poor health conditions, employment difficulty, and economic recession. But we found an interesting phenomenon: the sales of sunscreen products increased during the epidemic while most cosmetics and skin-care products decreased a lot (Fig.1). This finding made us so curious about the sunscreen market.
Fig.1 Sales Data Of Cosmetics During The Epidemic
Through our market interview, most products are chemical sunscreens with high sun protection factors (Fig.2). After further research, we found that this may result from the increasing public understanding of skin cancer and awareness of UV protection. Although this product can effectively protect people from UV radiation, it has seriously affected the marine ecology, especially the coral reefs.
Fig.2 Sunscreen Products On Sales
There are many potential ways for us to protect the coral reefs from chemical pollution caused by sunscreen, and here are some of our ideas:
1. Completely ban sunscreen products;
2. Engineer zooxanthellae to increase its resistance to environmental pollution and change;
3. Produce coral-friendly sunscreen components.
Purpose : To better understand people's needs and attitudes towards sunscreen products to help us decide the specific method to solve the environmental problem, we did a preliminary questionnaire.
HP Result : Based on the data from our questionnaire, we found that most people know nothing or know very little about the harmful pollution to coral reefs caused by chemical sunscreens (Fig.3). What's more, most interviewees were only willing to use less after we told them the relationship between sunscreen usage and coral bleaching, and 12% of interviewees even totally didn't accept the absence of sunscreen. Only 8% of interviewees would like to give up sunscreen products after knowing the relationship (Fig.4). In addition, through reviewing the literature, we have also found that some scholars have questioned the laws of banning sunscreen in some countries and regions, believing that such measures will raise the risk of skin cancer and melanoma in humans.
Fig.3&4 Preliminary Questionnaire
Analysis : After conducting this questionnaire, we found that sunscreen products are necessary and challenging to be banned entirely. Thus, we began to have the initial idea of producing a coral-friendly sunscreen component as a substitute for current chemical elements.
Reason 1 : Through our preliminary questionnaire, we learned the necessity of sunscreen and the real needs of users. Thus, entirely banning sunscreen is not a reasonable means of coral protection;
Reason 2 : Through our interview with the diver Miss Su and Prof. Liu, we were aware of the difficulty to cultivate and transplant artificial coral reefs and then gave up engineering zooxanthellae to increase its resistance to environmental pollution;
Fig.5 Decision Of Bio-sunscreen Project
HP Result : Considering the vast market consumption demand of sunscreen products and the goal of coral protection, we finally decided to produce a coral-friendly bio-sunscreen to save corals and create some economic benefit at the same time.
Impact : There are many natural UV absorbers from totally different species, including flavonoids in plants, mycosporin amino acids (MAA) in algae and bacteria, and hipposudoric from hippo. The above compounds have the potential to make bio-sunscreens indeed. However, after seriously considering the suggestion from Miss Su, we believed that natural components of plants, algae, and mammalian may be potentially risky to species in the marine ecosystem and may not be able to be truly environmentally friendly. Therefore, we finally chose a natural UV absorber, gadusol, which comes from zebrafish eggs and is widely present in other species living in coral reefs, as the main component of bio-sunscreen products through microbial synthesis.
Purpose : To deeply understand the current status of coral reefs and related issues of coral protection, we turned to the most prominent environmental NGO in the area of coral protection, Better Blue.
HP Result : From their introduction, we learned about the current situation of coral declining and the pessimistic trend of future development, which further strengthened our determination to protect corals through this project. Our team also reached a cooperation agreement with Better Blue to make joint efforts in science popularization and education.
Useful Future Interviewee Information : During our cooperation with Better Blue, we learned that they had just carried out an annual coral reef check. We believed that we might gain some valuable information by interviewing divers who took part in the coral reef check project. After knowing that, Aria Yu, Public Advocacy Program Officer of Better Blue, willingly helped us contact the diver, Miss Su. Besides, we also got in touch with Professor Liu Sheng, who is involved in coral conservation research with the help of Better Blue.
Introduction : Miss Su started diving in 2011 and participated in coral reef checks many times. She is an experienced diver for coral reef protection and coral data collection(Fig.6).
Fig.6 Diver Su & Her Coral Reef Check Experience
HP Result : Miss Su said that the scale of coral reefs is relatively small in Guangdong province. Most coral reefs grow in clusters and are scattered, and most of their bleaching conditions are also on a small scale. In addition, from the data point of view, the number of corals in Guangdong is increasing year by year. Apart from artificial cultivation, another reasonable explanation considering global climate change is the coral belts moving to high-latitude seas: Although tropical waters are no longer suitable for corals, subtropical waters may become new homes for them. This conclusion reflects the long-term value of our project. Some measures to transplant corals may not conform to the natural living conditions of corals and may cause damage to their diversity as well as ecological balance.
Su told us this vital information: On February 5th of 2021, more than 500 corals distributed in China became second-class animals under state protection. Moreover, there was even news that someone got punished for destroying corals, which shows that the general public awareness of coral conservation is fragile, not to mention asking the public to understand the relationship between sunscreen and coral bleaching.
In addition to that, we accidentally learned that Su has tried to promote some so-called environmentally friendly sunscreen to her colleagues. However, such products were rejected and questioned by them. They commented: A real environmentally friendly sunscreen should not only be harmless to coral reefs but, more importantly, ensure harmless to more marine species in marine ecosystems. This story raised more considerations in the selection and determination of our target products.
Analysis : This interview conveyed the urgency of coral conservation, the need for education & communication. We also knew that we should consider more about the environmental influence on the whole marine ecosystem when selecting our bio-functional component.
Introduction : With the help of Better Blue, we interviewed Prof. Liu Sheng from the South China Sea Institute of Oceanology, Chinese Academy of Sciences (Fig.7). He focused on coral protection by artificial cultivation and transplant.
Fig.7 Interview With Prof. Liu
HP Result : During our interview, we learned that he insisted on doing his research without sunscreen to avoid environmental problems. Prof. Liu said that the technology for artificial cultivation and transplant of corals was maturing. Still, such an approach would not protect the endangered coral reefs on a large scale, and the current protection method treats the symptom rather than the cause. Moreover, large-scale coral cultivation requires a lot of money without much economic return, which means that artificial coral cultivation will not be smooth sailing in the future. In short, the significance of preventing pollution is far greater than repair through artificial cultivation.
Impact : From this interview, we were aware of the difficulty of engineering zooxanthellae to increase resistance to environmental pollution and change, considering the long artificial transplant time and low return of financial benefits. Finally, we decided to produce coral-friendly sunscreen components as a prevention method to solve the chemical pollution problem from the source.
Purpose : Through our Partnership team, GXU-China, we got in touch with Prof. Jiayuan Liang from the School of Marine Science of Guangxi University and China Coral Reef Research Center to discuss our bio-sunscreen project with his research group (Fig.8). We wanted to get more advice from marine scientists.
Fig.8 Discussion With Prof. Liang's Group
HP Result : A.P Liang thought highly of our project and made some constructive comments to develop our bio-sunscreen product. He said that although gadusol originates from zebrafish embryos and is a common component in many fish species in the coral ecosystem, the total concentration of gadusol in nature is still deficient. Thus, we need to consider whether the accumulation of gadusol bio-sunscreens will cause some adverse effects after large-scale application. Impact : In the end, our team has reached a consensus with A.P Liang that we will carry out experiments under the guidance of the Coral Reef Research Center of China to test the influence of high concentration gadusol products on coral reefs.
Purpose : Given the future market situation of our project's bio-sunscreen products, we made a questionnaire to confirm that consumers can accept our future products.
HP Result : We found that most people are very optimistic about the emerging bio-sunscreen product and are very willing to try it out. The fact that genetically modified organisms synthesize our product didn't trigger their resistance.
Fig.9 Market Questionnaire
Analysis : This result of market consumption intention fully showed the development potential and market demand of our future bio-sunscreen products, which demonstrated the feasibility of our project.
Purpose : Guangzhou Longhui Trading Co., Ltd. is a cosmetics raw material supplier focusing on the research, development, and sales of special cosmetics raw materials. We asked Hu Peng, the sales manager of Longhui Company, about the current situation of the cosmetics industry and the needs of customers.
HP Result : He told us that people nowadays tend to favor natural biological sources when choosing cosmetic products. For enterprises, they should pay more attention to the scarcity of raw materials and building a green brand image. He showed us some common types of cosmetics during the interview, such as spray, gel, shake lotion, etc. It is worth noting that sunscreens belong to a particular category of cosmetics, which are stricter than ordinary cosmetics in the legal filing. In addition, we also discussed the matters that need attention in the selection of raw materials for different cosmetics companies. Hu Peng thinks it is necessary to set up a negative list to eliminate some cosmetic raw materials harmful to the environment.
Conclusion : We gained deep insight into the current popularity of synthetic biology-derived products in the cosmetics industry through this interview, which increased our confidence to carry out the project. We also learned many related legal and normative issues, which provided help for the production and marketing preparation of our future bio-sunscreen product.
Fig.10 Interview With Manager Hu
Purpose : To unveil the secret of environmental-friendly raw materials in the cosmetics industry, we went to Lubrizol Management (Shanghai) Co., Ltd. Guangzhou Branch to communicate with their regional sales manager Wu Guanhua. We learned more about the promotion and use of these materials and cosmetics companies' attitudes towards relevant regulations.
HP Result : During the communication, he introduced some methods of selecting green raw materials implemented at present, including the evaluation of RCI, the backtracking of raw material sources, and so on. At the same time, he also said that the cosmetics industry had already adopted some products produced by synthetic biology. Still, unfortunately, product evaluation is generally the company's behavior, and there is no unified standard at present for synthetic biology-derived products.
Conclusion : Manager Wu expressed his opinion on the current regulations of cosmetics. He believed that the increasingly strict rules were conducive to the final formalization of the industry. However, the enterprises may face the problems of rising testing costs, becoming difficult to declare, etc.
Fig.11 Interview With Manager Wu
Analysis : Through these two interviews, we were greatly inspired and realized that the development of cosmetics derived from synthetic biology has just started and has excellent prospects for the future. However, at the same time, we found that there may be some potential legal loopholes in applying synthetic biology in cosmetics.
Purpose : To further understand the application of synthetic biology in cosmetics, we visited Ruiting Biotechnology Co., LTD., a research company specializing in developing synthetic biology-derived cosmetics.
HP Result : Through communication with cosmetics research staff, we learned that yeast, as the most common model organism, can be directly added to cosmetics in the form of yeast lysate. That will be a wise choice to eliminate pollution caused by chemical extraction and save considerable production costs.
Impact : We finally decided to select the food-grade strain Saccharomyces cerevisiae as the chassis organism for the biosynthesis of gadusol and add our functional gadusol ingredients in the form of yeast lysates in our final bio-sunscreen products.
Purpose : Given the legal issues that may exist in the production and marketing process of bio-sunscreen products known from the companies, we interviewed government staff of the Market Supervision Administration for help (Fig.12).
Fig.12 Interview With Government Staff From MSA
HP Result : We know that, at present, our daily supervision, which includes the production and sales of cosmetics, is carried out by the regulations on the Supervision and Administration of Cosmetics effective from January 1, 2021. There are requirements for cosmetic efficacy, quality and safety level, production process, stability, adverse reactions, and so on. However, there are no specific regulations on the supervision of environmental hazards related to cosmetics.
As far as we know, before the registration of general cosmetics new raw materials, the data and some results of the test phase must be retained. If other institutions in the country are not doing the substance you extract, you can take it out and apply for a patent separately. Then you take this patent to the Food and Drug Administration (FDA), which has production qualification supervision authority, and you let them figure out whether this ingredient can be a raw material or not. The FDA would issue a written reply, and you can only carry out the production after receiving this reply from FDA. It would help to determine whether the substance you produce is toxic to the human body. If it is not harmful, you can go to the quality inspection department to find whether the substance meets the national standard.
Conclusion : We have roughly understood the relevant laws and regulations on new raw material registration and product production, which is of guiding significance to our gadusol product registration in the later period. At the same time, we found problems in the regulation of cosmetics in China, particularly in assessing environmental hazards, which reflected legal loopholes.
Impact : We will conduct further research on the specific registration progress and analyze relevant legal loopholes. We hope to fill this legal loophole and promote the advance of assessment standards from environmental aspects through our team's efforts.
Purpose : We interviewed relevant staff of the State Food and Drug Administration (SFDA) about the registration of gadusol for a functional sunscreen ingredient and its production (Fig.13).
Fig.13 Interview With Government Staff From SFDA
HP Result : From this interview, we learned that the whole standardized registration and the testing process involves the Market Supervision Administration, the State Food and Drug Administration, the Environmental Protection Bureau, and other departments, which is tedious and complicated. In addition, for products produced by genetically engineered strains, there are more detailed specifications that need to refer to documents of other departments.
Impact : It took us a lot of time and effort to understand the process thoroughly. Such registration problems are inevitable for companies hoping to use synthetic biology to produce cosmetics and could be the biggest obstacle to the commercialization of many innovative companies. This cumbersome process makes it even more difficult for foreign companies to enter the Chinese market. Thus, we decided to collate a Guidance for Bio-cosmetics to provide some help and reference for future synthetic biology cosmetics enterprises.
Purpose : We asked Prof. Yunxin Li from NMPA Key Lab (Fig.14) for Cosmetics Monitoring & Evaluation for help to have a better knowledge about the specific experiments we need to carry out for our product to enter the market.
Fig.14 Interview With Prof. Li From NMPA
HP Result : From this interview, we learned that we could do some of the testings ourselves so that third parties could later evaluate us. We also learned that the current SPF/PA indicators used in sunscreen evaluation are not reasonable. However, the film formation of sunscreen is the essential factor in deciding whether the sunscreen can effectively protect us against UV rays. Film formation is closely related to the sunscreen formula. We will ask Prof. Wang to customize a suitable procedure for our gadusol bio-sunscreen in the future to achieve better performance.
Impact : Under the guidance of Prof. Li, we have decided to use the software first to simulate the UV absorption spectra of gadusol and several similar chemical sunscreen components on the market. Besides, we will also conduct cytotoxicity tests on gadusol crude samples to demonstrate the safety of our product's core ingredients.
Purpose : After finding the potential legal loopholes in the area of assessment standards for cosmetics from the environmental aspect, we turned to lawyers Ms. Guan to know better about possibility to promote the perfection of current laws and regulations.
HP Result : We knew from Ms. Guan that we can prepare a comprehensive proposal and make some related legislative suggestions to our local National People's Congress (NPC) member. If the NPC member help us table our legislative proposal on next NPC, the law will be promoted.
Purpose : As the biggest environmental NGO and our partner in education work this year, Friends of Nature has a professional group of lawyers focused on environmental public litigation. Thus, we wanted to cooperate with them to help our country have better laws and regulations related to the environmental safety evaluation on cosmetics.
Future Work : Because of the time limit, we only collated some related legal documents and have not finished our legislative proposal. However, we have reached a long-term cooperation with Friends of Nature and we will pursue a social responsibility together as environmentalists by promoting the perfection of current laws.
Problems : Failure of Gibson Assembly, False positive of transformants, Failure of PCR reactions, Product extraction optimization & Fermentation optimization.
Solutions : We consulted PhD candidate Jianing Zhang, MSc student Jiaheng Liu and MSc student Kejia Ye and MSc student Wanqi Cheng for the above questions. You can see the detailed information and their specific efforts for the wet lab experiments promotion here.
Problems : Difficulty in making sure which model to choose, Difficulty in finding data we need, Difficulty in estimating the feasibility of different models in this project.
Solutions : We discussed with PhD candidate Jianing Zhang, borrowed relevant books and documents from Jie Liu, and we also discussed with Qingli Chen from iGEM team BUCT about MFA.
Purpose : Large-scale production is the main issue for our bio-sunscreen products to the reality, from lab to plant. Thus, we visited our pilot scale test workshop(Fig.15) to have a better understanding of the preparation and factors we need to consider before we begin large-scale fermentation work to reduce trial and error costs.
Fig.15 Preparation For Large-scale Production
HP Result : We had a visit around the pilot scale test workshop which is designed for technical identification before large-scale fermentation in real plants. Through this visit, we knew that we had to take pH, dissolved oxygen, ventilatory capacity, temperature, defoamer, fed-batch method and many other detailed factors into account in order to make sure our test in a smooth going.
Purpose : To find our potential investment helping us produce and promote bio-sunscreens, we decided to take part in some business conferences and chat with potential investors.
HP Result : We finally took part in Synbiopunk hosted in Shanghai by Ailurus Biotech, Miracleplus, 5Y Capital, iGEM EPIC and Amazon and won the early-stage financial support (Fig.16) from Synbiopunk members. We will have future negotiation with potential investors we knew from Synbiopunk and try our best tofinally transition the technology to full commercialization. We also made some preliminary business negotiation with L'OREAL, Source Code Capital, Shang Finance and Lvye Investment (Fig.17).
Fig.16 Financial Support From Synbiopunk
Fig.17 Business Negotiation With Potential Investors
Problems : After our visit to NMPA Key Lab and our interview with Prof. Yunxin Li, we knew the importance of doing some preliminary experiments by ourselves to evaluate our core component before large-scale production and registration.
Safety problem is the priority of our product. Based on Prof. Li's advice, we decided to do some experiments to evaluate the cytotoxicity effect of gadusol.
Besides, we also need to consider the quality of gadusol, especially the ultraviolet absorption capacity which is the most important factor for gadusol to be an UV absorber.
To evaluate gadusol's cytotoxicity effect, we cooperated with iGEM team Shanghai_Tech China and consulted their team leader R. Su and then did the cytotoxicity evaluation experiment in their lab.
To compare gadusol with some current chemical UV absorbers and reduce the difficulty of obtaining these substances, we decided to simulate ultraviolet absorption spectrum based on their molecular structure.
You can find results of the above experiment and simulation in our Proof Of Concept page.