Team:HZAU-China/Human Practices
As the Chinese saying goes, “know the enemy and know yourself, and you can fight a hundred battles with no danger of defeat”. In the battle with cancer, we have gained great knowledge about the “enemy”, as well as our own immune system. However, despite the success in curing early and middle stage cancers we have made, the lack of public comprehension is still likely to cause panic. We sensed that our mission is to help the public learn more about cancer and its treatment, as well as the difference that synthetic biology can make in future approach. To accomplish that, we held a live seminar to share our idea and then started to blog newly emerged cancer therapies, basic aspects of synthetic biology and our project. Meanwhile, letting the public know that their voices have been heard is also very important, so we collected their opinions carefully through public survey, designed new circuits for their safety concerns, and invited them for discussion on our team blog. To explore the further application and the potential risk, we also communicated with some cancer experts. We want to be a communicating bridge during this battle where information is accessible to everyone who needs it.
This year, we have done a lot of work in order to meet the requirement of biosafety. After collecting opinions from experts and the public, we learned that the general concerns are about: How is it safe to apply bacteriotherapy against cancer without causing unexpected damage or infection? We took these concerns seriously and have found some practical solutions.
Professor Jin He has given us a lot of useful suggestions and instructions. As an expert in microbes, he points out that Salmonella is a kind of safe bacterium which is widely used in researches around the world. After knocking out a series of genes, the harm of Salmonella is acceptable. He also points out that Salmonella has very common with E.coli on behalf that both bacteria are in Enterobacteriaceae. This means that we can incubate Salmonella on the same condition and cultivation with E. coli. In addition, Salmonella is very similar to E. coli in genetics, which means many metabolic reactions happen in E. coli would also happen in Salmonella. Besides, he tells us that there are many intracellular parasites well studied such as Listeria , so we have many choices in the future. In conclusion, his indispensable instructions have made up our minds to engineer on Salmonella.
Doctor Qike Jia is a young doctor works in Hubei Tumor Hospital and has some experience in tumor treatment. He is familiar with all popular tumor therapies in China and has given us an overview of tumor treatments. When asked about what the most used therapy at present is, the doctor directly pointed out that it is surgery without hesitate. He thinks that operating on patients is always the first thing to do when a doctor is facing a tumor in medium or late stage. After cutting off tumor issues, radiation and chemical therapies can be carried out for further clearance of tumor cells. When asked about the opinion to our project, he encouraged us with a big smile on his face. He said our project is quite good and expectable, although we may have faced some trouble. Cell cultivation is a really hard work taking a lot of time and spirits. Even if we could complete the project, we still need an enormous amount of efforts to push our therapy to the market. He hoped that we could overcome all the difficulties and gain the final success.
In July, we had a nice symposium with Cao. At that time, our team didn’t come up with a mature project. Since Cao is major in Biomedical, we asked him for help and he responded us warmly. In a special symposium, He pointed the weakness is our naïve thoughts and helped us strengthen the advantages. He taught us tremendous things about pyroptosis, including it’s pathway and recent researches in that field, and encouraged us to march on. Cao is so enthusiastic about our project and willing to give us a helping hand.
After attending meetings and analyzing questionnaires, we learned that there are many concerns about the use of bacteria to treat cancer. We thought people's scruple is largely because they know little about bacterial therapy and synthetic biology. So, we not only set up a blog for popularizing science about synthetic biology and our project, but also gave lectures to freshmen in our university about our work to get more feedback. Through above activities, we expanded the scope of our survey. By making people more aware of synthetic biology and bacterial therapy, they became more receptive to our project. In the survey results and discussion on our blog, we realized that more knowledge can significantly reduce peoples’ worries. During our education engagement, we also had more safety thinking and better performance in our experimental design.
Pyroptosis therapy, as a new approach derived from cell natural defense mechanism, can only make positive effect on human health with our rightful use. We all know that one day synthetic biologists will develop artificial life forms as vehicles. At that point, pyroptosis carried out by these excellent tools will release its enormous potential, work just like the nanorobots in science fiction movies, leaving cancer cells nowhere to hide. Within the right hands, it can provide us with new opportunities of making the world a better place.
For a new treatment, a person or institution cannot represent all human beings to define it. Therefore, our integrated human practice aims to hear voices from both experts and the public, in order to analyze and improve our project. At the beginning, we participated in two conference meetings in mainland China, and had an in-depth communication with the teams who had conducted the tumor treatment related projects like us. Then, we consulted several experts from Hubei Cancer Hospital and professors of microbiology and biomedical in our school for their professional advice. Besides the communications, we have done an insightful social survey, to gain better understanding about what people concern about cancer, as well as their attitude towards our project. The social survey results inspired us to reconsider the security level and the future application of our project. Meanwhile, we sensed that other mission for us is to help the public learn more about cancer and its treatment, as well as the difference that synthetic biology can make in future approach. To accomplish that, we held a live seminar to share our idea and then started to blog newly emerged cancer therapies, basic aspects of synthetic biology and our project. We also established a science blog, in which we can keep offerring people cancer-related information with a more lucid way to express. We also answered their questions in person for the best effects at comment area.
We carried out our project with full compliance with the safety policies and safety rules (see also Safety for details). In analyzing the results of expert consultation and public investigation (see also Education for details), we concluded that an enhancement of safe properties nevertheless should be considered as a first priority. After a careful reconsideration, we introduced two major safety improvement. First, we knocked out the sifA gene from Salmonella Typhimurium str. SL1344 genome by conjugation transfer, in order to weaken its pathogenicity. Although Salmonella has already been used in some cancer therapy research, its pathogenic bacteria identity had limited its anticancer application. After collecting opinions from experts, we decided to perform this gene knock-out. Then we demonstrated the effect of this change by using macrophage assay, where ΔsifA strain cannot replicate effectively in the host cell after infection, in contrast with the control group (see also Design and Results for more information). This effect means the ΔsifA strain can be easily cleaned by human macrophage, which can prevent unexpected infection from occurring. On the other hand, even though Salmonella have natural taxis towards tumor microenvironment and attack tumor cells selectively, any destructions done to the non-tumor tissue remain unacceptable. For the purpose of an accurate attack, we displayed RGD motif on the bacteria surface to demonstrate an enhanced targeting specificity towards tumor cells covered by αvβ3 integrin (see also Design and Results for more information).
