Difference between revisions of "Team:Shanghai HS ID/Human Practices"

During our project, we focused on two parties: professional researchers (such as pharmaceutical manufacturers and companies) and the general public. We wanted to quantify the demand of companies and manufacturers for this new strain of L casei bacteria our group was creating. At the same time, we kept in mind that the mainly conservative public might not embrace GM products smoothly without educating them how beneficial transgenic technology could be. At the dawn of our investigation, we created surveys targeting the general public to elucidate their stance on GM products. To achieve better product positioning, our team interviewed five excerpts from different fields, ranging from diary industry to pharmaceutical industry. Each of them gave precious insights on how our project can bring huge benefits to not only the people around us, but on a world-wide scale.

On the first day of our intensive conversation, with Professor Zhiqiang Wen (Associate Professor, School of Food Science and Pharmaceutical Engineering) states that “we are currently experiencing a bottleneck since the tool bacteria (L.casei)'s conversion rate is too slow”. This confirms our hypothesis that a strain of L.casei with more proficient transformation efficiency is needed. He points out that our method of removing the restriction endonuclease to increase the transformation efficiently has competitive advantage over other traditional methods such as methylation.

Afterward, we continued our interview trip with Ms. Yangyang Kong (Graduate Alumna of Key Laboratory of Synthetic Biology, Chinese Academy of Sciences), who is currently working at Shanghai Xuhui Siqiao Science & Technology Research Center, expressed her eagerness to obtain a genetically modified strand of L.casei. She points out that demands for the technology to genetically engineer L casei are concentrated in companies and corporations, mainly to reduce production costs. She also postulated that different companies will demand this technology in various ways. Dairy companies would demand this technology to become more efficient in their production lines. On the other hand, scientific companies have a more intimate relationship with the production of the new strain of L casei bacteria. "Your predicted product – the modified strain of L.casei is like the chassis of a car" she says, "while by itself, partially decides the efficacy of the medicine, the rest is dependent on the additional components constructed upon the foundation. If we want to construct a sports car, we need to apply a powerful engine; if we want L. casei to help alleviate diabetes, we need to apply plasmids containing cures for diabetes into the cell".

In our third interview, our team discussed the topics "transgenetic products" and :"GM food" with Dr. Yicong Chen (Ph.D Candidate, Cornell University, Research Assistant, The Institut Pasteur Shanghai (IPS), Chinese Academy of Sciences). Dr. Chen clarifies that, although CRISPR has been widely used in animal husbandry and the production of animal vaccines, the regulations of using CRISPR in medicines for humans have stricter regulations. Despite this, pharmaceutical companies are supportive of transgenics because it can solve many practical medical problems, such as the production of insulin, genistein, and recombinant cytokines. Transgenic technology is now commonly found in the R&D of pharmaceutical companies. Almost every microbial research, bioengineering research, and immune system research uses transgenic technology.

To get a better glance at the general public's opinion on transgenetic food, we conducted a survey on this topic. Throughout our surveys, we realized that most respondents are either skeptical of genetically modified food products or blatantly against it. 56% of respondents choose to withhold opinions regarding genetic modifications. These respondents mainly concerned about the safety of GM technology. Most importantly, will GM technology positively or negatively influence human health? Many respondents wonder. They believe that there has not yet been sufficient research and data to conclude genetic modifications have no ill effect on humans health. Others also believe that genetic modifications do not fulfill their purposes, such as improving the agricultural yield.

To have a deeper and more comprehensive understanding of CRISPR and GM tools, we invited Professor Yibei Xiao to give us some guidance. Prof. Xiao completed his postdoctoral research at Cornell University, and currently works as professor, principal investigator at China Pharmaceutical University. He has 6 papers published on Cell, Nature, Science. His research expertise includes CRISPR, anti-virus drug development and transcription & reproduction mechanism of RNA virus.

Prof. Xiao states that labs and companies have no biased views against GM foods, and will fully accept this technique if it can reduce current expenses. Nonetheless, from the perspective of the general public, the professor believes that Eastern culture accepts genetic modifications better than the Western background. He gave the example of a genetically modified infant in China. While the eastern culture considered it a scientific advancement, the western culture took it as taboo since it deviated from their ethical standards. This drew our attention to the ethical backgrounds of genetic modifications. We designed lectures in our school – Shanghai High School International Division, and published informative articles on our WeChat official account.Targeting both the young and the old, we gathered their opinions on GM foods and tried to debunk the misperceptions of GM technology, such as those claiming that GM technology can turn human beings into octopuses. However, we still asked ourselves whether using genetically modified strains of bacteria in foods and pharmaceuticals will be commonly acceptable. Would it be an overly risky, audacious attempt to improve our market? Our interviewees gave us the answer: the benefits of having this technology and the demand seen could out-competed the alternatives, revealing that this is a necessary step to take to advance the fields of medicine and scientific research.

We indeed saw a deviation in demands as Ms. Kong predicted. Bright Food & Diary Co.,Ltd, the dairy company we interviewed would be glad to utilize the CRISPR technology if we could provide data showing how much time and effort could be saved by using our new strain of L.casei. The director of the R&D department of Bright Food & Diary Co., Ltd claimed that she is more concerned about the results instead of the actual process, while many of the other scientific researchers were curious of the process of cultivating the new strain of bacteria. Bright conceded that they are currently still utilizing the traditional methods to incorporate plasmids into L casei. They have encountered the same hardships that many of our interviewees confronted:increasingly unprofitable costs and lengthy development times.

While we are certain that the new method would save both time and money, we did not yet find an exact conclusive figure. In this interview, we realized the importance of having a specific comparison between the two types of technologies and prompted us to ask these questions in future interviews. Keeping this in mind, we continued investigation by interviewing Professor Xiao. He explained that even though there are only limited studies related to the improvement of the conversion rate using CRISPR compared to traditional methods, it is unquestionable that CRISPR is indeed the fastest and cheapest technique in the current medical world. CRISPR takes only 7 days and costs as few as couple hundred dollars. In contrast, in clinical applications,traditional methods could be lengthy and is much less profitable due to high fixed costs. Additionally, the research and development can averagely cost millions of dollars, and can take longer than a decade. CRISPR, in comparison, is much faster and efficient.

This inspired us to also design an experiment as the end of our transformations. After silencing the LSEI 2094 gene in L casei, we designed another experiment to compare the expression rate of foreign DNA in the original strain and the new strain we created. We discovered that the strain that we have obtained has a much higher transformation rate than wild ones. (For details, please refer to our Results page) Considering the time and financial input we invested into the project, we were able to obtain the prototype of a new strain with high transformation rate of foreign DNA in 2 months, using 10000 RMB. Comparing this to the time and money we need to obtain a similar strain using the traditional methods, our project is much more efficient and economical.

Bright Dairy uses distinct types of bacteria in various products. Each species of bacteria produces unique metabolites, which have discrete effects in the human body. People of age groups possess a variety of gut-bacteria populations and thus demand different types of bacteria to improve their health. This functions by changing the composition of the bacteria in the gastrointestinal tracts. In Bright Diary, individual products target a wide range of different social groups. Just as Prof. Wen said, Bright Dairy identified their customers' needs and strove to solve their issues. Every corner of our society can receive maximum aid that exactly suit their personal conditions. This shows that there is a wide variety of dairy products in the market, many of which people regard them as the same. This hypothesis is supported by our survey questions investigating the types of dairy products our respondents notice in their daily life. Most answered milk, yogurt and cheese. we realized that there were a lot more other unnoticed dairy products.

This inspired us to consider a wider variety of products. Giving each food a ranking and a short description, we realized that many products actually do not contain LAB while their advertisements said so. Within the other products, only a few contained L casei. Most contained the other types of LAB, such as L.bulgaricus, Bifidobacterium lactis, L.acidophilus, as the head of Bright Dairy explained. Moreover, many products are untasty (for example, one LAB drink taste like rotten apples). Social demand and awareness for healthier drinks show us that while there's a promising in incorporating LAB into more foods, the taste and cost also need more considerations. There remains a need to incorporate L casei into the more products, given its immense health benefits and its lack of presence in our current market.

Despite all these challenges, we are determined in the propitious future for our product. According to our interview with Dr. Chen, similar technologies, such as the genetic modification of E. coli to modify it into an effective carrier, had already proven effective in animal vaccines. We could eventually extrapolate these uses to be more beneficial for human health. A positive sign is how genetic modifications were proved to be successful in many other medications, such as the production of insulin and certain vaccines. Just like Prof. Xiao encouraged us, we should envision an ideal scientific world where L casei is universally applied to optimize carrier proteins. Scientific data and stats already proved the pivotal role genetic modifications display in the world of scientific world. We have already organized lectures in schools and community centers, and planned to interview more professionals on their position on the safety of GM products. We firmly believe that through our efforts, the public will gradually proceed to accept GM products, and factories and diary products companies would gladly pursue our product.

Short Conclusion:
Both expert interviews and online questionnaire survey have provided us with great insights about our project and its future direction.
1) Since L. casei could be used in a broad range of areas, both scholars and diary firm professionals will be interested in our CRISPR-Cas9 edited L. casei as long as it does users’ costs and time;
2) Safety concerns have caused challenges to gene-editing, thus in our future experiments, we must be very cautious about these issues and we also need to launch education activities to proliferate impact of gene-editing for the long-term development of our project