Safety is one of the core concepts of iGEM and synthetic biology, and it is also the foundation of engineering biology towards practical applications. In 2021, through multiple efforts, NDNF_China aims to integrate "safety" in every aspect of this project.
Firstly, we have designed "Hidro" in our project to ensure that genetically engineered organisms can be safely applied in the real environment. Secondly, we carried out diverse activities to promote biosafety through human practice including Biosafety Education and Biosafety Law Revision Proposal. Finally, we emphasized the importance of safety in the laboratories where the project was conducted.
With the integrated safety setup, we have created a comprehensive safety system that will be of use to any future iGEM team or research team (Figure 1). We will describe this in more detail in the following sections.
Figure 1: Integrated safety system built by NDNF_China 2021 team
As more and more advanced technologies are being invented, we could say without exaggeration that we are stepping into the era of synthetic biology. However, there is still a long way to go for engineered bacterial strains to function outside the laboratory (For more detailed information, please visit the Description page).
To solve these challenges, we designed Hidro. Hidro aims to promote synbio applications to transcend laboratory restrictions. Hidro system can easily achieve escape efficiency lower than 10^-9, which has met the NIH biosafety standard, so we can help engineered strains truly step out of the lab and into real-life application scenarios.
To further ensure safety when engineered strains are applied into the environment beyond the lab, we have also designed a Trace and Control system in Hidro. By designing a customizable DNA barcode & CRISPR-Cas12a and genetic kill switch system, we can dynamically track and effectively control escaped organisms when the escape event occurs (though the possibility is extremely low).
The Hidro system designed by NDNF_China could be a promising platform to promote bioengineered products safely applied in the environment beyond the lab, such as rivera, soil, food, human gut, and so on. (For more detailed information, please visit Proof-Of-Concept & Proposed Implementation).
Figure 2: The different subsystems in Hidro to ensure synthetic biology products applied beyond lab in a safe, stable and traceable way.
「Safety」Promotion in HP
We believe that in addition to technically achieving higher biosafety, we should go beyond the laboratory and make more general public or government agencies pay attention to biosafety through Human Practice. In this regard, we have taken the following two main actions.
Biosafety by focusing on Tianjin Biosecurity Guidelines
First, we started with education. We held a number of online and onsite events during iGEM 2021.(See more information here, please visit Communication) At each of these events, safety was one of our core themes.
Besides promoting biosecurity knowledge, we focused on the Tianjin Biosecurity Guidelines for Codes of Conduct for Scientists. The aim of the Tianjin Biosecurity Guidelines is to promote a culture of responsibility and guard against biotechnology misuse, which is an international consensus achieved in 2021 by the IAP organization. In a world where distrust of biotechnology continues to grow, we believe it is our responsibility to popularize this international consensus. We think both individual scientists and institutions active in biological research are expected to follow. At each event or in a public article or video, we have disseminated these guidelines to more than thousands of people, raising awareness of the importance of biosafety and making people aware of specific actions that bioscientists can take for self-regulation.
Figure 3: Education activities focusing on biosafety. A: Poster for a high-school "Biosafety and Synthetic Biology" meetup at Beijing National Day School; B: Tianjin Biosecurity Guidelines for Codes of Conduct for Scientists was the main focus of each online and onsite events.
focusing on Biosafey law in China
Second, we believe that government agencies need to respond in a timely and appropriate manner not only in terms of science education for the general public but also in terms of safety regulation on synthetic biology. We analyzed China's biosafety laws and discussed them with several experts, resulting in a law proposal to optimize biosafety laws in China.
In this proposal, we proposed changes to more than 10 regulations and suggested that "biosafety laws should follow the rapid development of synthetic biology in a timely manner and take appropriate measures to control the risks that synthetic biology may bring". In addition, we also made suggestions for regulators to optimize the biosafety law at the technical level, such as establishing a barcode tracking system and installing a suicide switch in engineered organisms, etc.
Upon completion of our report, we contacted a professor in a think tank related to the Chinese government and received positive feedback. We also have subsequently submitted a corresponding law proposal through government online channels. We hope that in the future we can have a positive impact that will drive progress on biosecurity legislation in China.
We believe that regulatory optimization at the legal level will be able to promote the safety of engineering biology and further facilitate the rapid development of synthetic biology. See our law proposal, please visit Integrated Human Practice.
Figure 4: The law proposal proposed by NDNF_China iGEM 2021 Team
「Safety」Working in Lab
Creating a safe laboratory working environment is also a responsibility that NDNF_China is committed to. At iGEM 2021, we have taken several measures to ensure a safe environment for every team member to conduct engineering biology research.
Given the importance of laboratory safety, we have received training on standard experimental procedures and common operation rules of bio-lab including the prohibition actions in the lab, the emergency safety measures, laboratory fire safety, the storage and use of hazardous chemicals, the disposal of laboratory waste, the daily management of the laboratory, and the notes for the use of laboratory instruments. In addition, each of us was given a laboratory notebook informing us on some basic experiment protocols and guidance. Furthermore, each team member had to pass the test of Safety Operating Rules for BSL-1 laboratories, which ensured we were all familiar with what we had previously been taught.
Figure 5: The laboratory notebook contains important information and guidance for safe experiments in lab
Specific Safety Problems
During the preparation of the hydrogel material, we used mercuric nitrate, acrylamide, and TEMED, all of which are toxic. So, in relevant experimental procedures, we strictly abided by the laboratory’s dress requirements such as wearing protective gloves and masks all the time to fully prevent exposure to toxins and carried out the experiments in a well-ventilated environment. Our team instructors, who have rich experimental experiences and are well educated, supervised us when we conducted experiments that involved toxic materials (for example, she helped us add mercuric nitrate herself to the medium instead of team members), and gave us necessary instructions to prevent any potential accidents. Furthermore, we strictly followed the safety rules and avoided contamination of clean areas by restricting the handling of the above chemicals to a specified zone.
Everyone in our team takes COVID seriously, ensuring their own safety while being responsible for the health of others.
Our temperature was taken before we entered the lab building and we also scanned a QR code using "Health Kit" (a WeChat Mini-program that can record your visit to certain public places). We were also asked to wear our masks all the time when we were in the lab. A negative COVID test result and letter of assurance signed by parents were also required.
In summary, our team integrated biosafety in three ways throughout every detail of the project. Our synthetic biology design enables the safe deployment of engineered modified bacteria in real-world environments. Our HP education activities and legal activities impact biosafety to a wider audience and government agencies. We also take steps to ensure the safety of everyone at work.
The different safety measures ensured that the NDNF_China project ran successfully and could be an example for future iGEM teams.
In explanation to the videos showing plasticity of the hydrogel shell on our engineering page:
I. No risks were involved during our handling process in the video due to the following reasons
1. Preparation of the hydrogel material was for exploring optimum conditions only, no microorganisms had been involved at this stage.
2. The major shell component --- polyacrylamide is not toxic.
3. It takes 12 hours for complete formation of the hydrogel material from its components. At the time of our experiment, this had already fully taken place. In addition, before direct contact with the hydrogel, the material was thoroughly rinsed with water multiple times to ensure that all possible remains of acrylamide and TEMED were washed off, thus eliminating any possible safety hazards.
4. As stated throughout our webpage, safety was a paramount part of our project. Integrating it during the competition season was critical towards leading us to our achievements. We have and will continue to strictly abide by all biosafety rules of iGEM.
II. For further clarifications, handling the gel would be inconvenient if gloves were worn since peeling and pulling of the material would be extremely difficult