As with any new technological advance, Synthetic Biology has been subject to a number of ethical and regulatory procedures to ensure that research in this area is done in a responsible and safe manner. The iGEM Tec-Monterrey team takes the issue of safety very seriously and we conducted a thorough research to understand the underlying ethical, toxicological and pathological risks that are commonly associated with Synthetic Biology. As part of our project, we analyzed each of our procedures and biological parts in order to ensure that everything was done under the safest conditions possible. We also discussed the issue of biosafety legislation in our institution and our community and we decided to propose a series of new methods that could help to reduce the risk of any security breach when working in this discipline. We invite other iGEM teams to join us in the conversation of Biosafety and together define the path the scientific community should take in these issues.
In order to discuss Biosafety, it is important to understand the concept. Biosafety refers to the prevention of unintentional outbrakes of pathogens, toxins due to accidents or lack of knowledge. It is important to distinguish the concept of Biosafety from Biosecurity. Biosecurity deals with issues of theft, misuse, diversion or any intentional release of dangerous biological material or pathogens (Schmidt, Chapter 6: Do I undestand what I can create? Biosafety issues in synthetic biology, 2009).
Although Biosecurity is an important concept, especially when dealing with issues such as bioterrorism and national security, it’s mostly managed by the government and international regulatory agencies. The scientific community can do little or nothing with respect to Biosecurity in the same manner it can only make small contributions to solve problems such as terrorism or organized crime. Most of the times, researchers can limit themselves to denounce irregularities they detect so that a law enforcement agency can assess if it can be considered a Biosecurity breach. However, the issue of Biosafety is almost entirely in the hands of scientists and their research teams. Without the cooperation of the scientific community, governments will have a hard time preventing accidents that can have possible repercussions in public health.
In an emerging discipline such as Synthetic Biology, the issue of safety is always front and center because most of the times, even scientists are not sure of potential hazards that can arise from their experiments. However, it has been determined that it is the ethical responsibility of the scientific team to determine possible risks and safety issues that can arise from their projects, and it is expected that they do everything in their power to prevent those risks from materializing into real biological crisis.
In current years, there has been an effort to streamline the process of manipulating genes to create synthetic organisms and biological systems. New tools such as the BioBrick standard have made it possible for people without a high degree of specialization to develop new and innovative uses for biological systems. This has led to a series of challenges in the subject of biosafety that need to be addressed immediately since more and more people outside of the traditional scientific community will begin to create self-replicating organisms that will be used in civil and defense applications (Schmidt, Difussion of synthetic biology: a challenge to biosafety, 2008). The situation has become even more critical with the emergence of the so-called biohacker community, a group of people that have begun to lead biological projects from within their own garages and homemade molecular biology laboratories (Ledford, 2010).
The international community has begun to respond to this new challenge by signing accords such as The Cartagena Protocol on Biosafety that has enabled countries to regulate the transfers of Genetically Modified Organisms through their borders. This treaty, signed by the leading nations as well as many developing countries (such as Mexico) was applied for the first time in the year 2003 (Gupta & Falkner, 2006). However, for many biosecurity experts, this agreement was too little too late and therefore, future regulations must be addressed immediately. This has prompted many institutions to launch biosecurity panels as well as investing in research in order to engineer security measures to prevent any accidents that could put public health in jeopardy.
To this date, there have been no serious accidents in the area of Synthetic Biology, however it is foolish to assume that it will continue to be this way if we don’t do anything to prevent outbreaks. This is especially true since there are still many mechanisms we don’t understand about biological systems and things can get out of control really fast. Therefore, it has become the responsibility of every person involved in the area of Synthetic Biology to contribute and analyze the risks and hazards associated with their projects, in order to prevent any involuntary release of toxins and potentially pathogenic organisms.
As we mentioned previously, at the Tecnológico de Monterrey we take the issue of Biosafety very seriously. That’s why when we finally decided on which project we would pursue for the iGEM competition, we began to analyze the potential safety issues that would arise from this experiment. We focused mainly on three aspects: our own safety (researcher safety), the safety of our community (public safety) and the safety of our local ecosystem (environmental safety).
We began by analyzing the potential hazards our project could have for the research team. Because this team would be in direct contact with the synthetic microorganisms it was extremely important to assess any hazards from the beginning to prevent any involuntary security breach. Fortunately, our project dealt with very few toxic chemicals and there were no pathogenic organisms involved. Therefore, by attaining to the basic rules of laboratory work, we could prevent most expositions. The use of latex gloves during the manipulation of bacteria and toxic chemicals, sterilization of all material before and after their use, the strict prohibition of any ingestion of foods inside the laboratory and the disinfection of all working zones before and after laboratory sessions are examples of the rules that we established since the beginning of our work in the wet lab. Thanks to the observance of these rules, we prevented accidents within our lab and fortunately, there were no biosecurity accidents during the span of our project.
Secondly, we had to ensure that we weren’t putting our community under any unnecessary risk of exposure to a dangerous microorganism. Even though we never used any pathogenic organism, we did create certain antibiotic resistant strains of E. coli. This can be considered a hazard because even though the bacteria we used were reported to be innocuous, we couldn’t have the certainty that they would remain that way forever. Therefore, disposal of all biological material that was in contact with any of the strains of E. coli we used in the laboratory was autoclaved before its disposal in clearly marked red biohazard bags. The same applied for all liquid residues, especially growth media. We did not dispose of liquids through the drain under any circumstance. All of our liquid residues were collected in containers that were clearly marked as biological residues. Afterwards, these biological residues were handed over to a specialized waste disposal enterprise that was in charge of responsibly dumping the wastes according to the Mexican Sanitary Law.
The FEMSA Biotechnology Center is undergoing a process of accreditation that will identify it as a responsible and safety conscious institution. As part of that accreditation, the Center must demonstrate it has a series of safety protocols for laboratory procedures and waste disposal. Most of these safety protocols are developed in order to prevent social and environmental damage. The iGEM team also adhered to these rules and protocols, so we can assure all of our procedures were done with a conscious attempt to reduce environmental damage and contamination.
Each of our BioBricks were thoroughly analyzed with the help of our Instructors and Advisors to assess if it posed any type of Biosafety hazard. We came to the conclusion that, since most of our parts are related to the amplification of PoPS within a bacterium and most of them don’t involve the secretion of any substance, there weren’t any important biosafety issues to consider when compared to other BioBricks of this type.
It is important, however, to consider the basic safety rules for all handling of BioBricks. This means that special care should be taken to prevent mutations that could lead to the development of dangerous biological parts. It is also important to avoid unnecessary exposition of microorganisms to DNA samples in order to prevent cross contamination that could lead to the creation of antibiotic resistant microorganisms with pathogenic properties.
Mexico is a country that is still in the process of regulating biosafety issues. This means that most of the aspects involved in our project are not directly mentioned in the law. This creates a great amount of uncertainty that leads to a lack of standardization in laboratory procedures throughout the country. It also means that there is no regulatory or biosafety group that could supervise our project. Therefore we had to rely on the mentorship of our advisors to make sure that our biosafety practices were thorough and sufficient to prevent any undesirable result.
We based our laboratory biosafety procedures on international standards, specifically those proposed by the United States Health and Safety Executive in The SACGM Compendium of Guidance for the Risk Assessment of Genetically Modified Microorganisms (Scientific Advisory Committee on Genetic Modification [SACGM], 2009). When in doubt we consulted with specialists from the FEMSA Biotechnolgy Center and the Center for Sustainable Development of our institution to make sure that we could minimize risk of involuntary exposure to hazardous substances as much as possible.
One thing we think that would be useful to ensure that all teams follow biosafety measures in future iGEM competitions is to create a checklist in the style of a flowchart. This flowchart would include a series of questions pertaining to the different type of projects that can be developed in the area of synthetic biology. Before starting wet-lab work, teams could consult the flowchart in order to know which type of safety measures apply to their specific needs.
For example, the first question that the flowchart would ask is if the project would concern eukaryotic cells or prokaryotic cells. Depending on the answer, the team would be asked other questions such as if any of the microorganisms used are known pathogens or if they are GRAS organisms. Again, the answers will continue to guide the team until they reach the “end” of the flowchart, and in that dead end they will find a set of important guidelines to consider for their project. These guidelines would be custom made depending on their project and would therefore be easier to apply and follow.
All teams could contribute to the construction of the flowchart and the guidelines. However, a team of specialists would supervise the collaboration and make sure that the final guidelines are sufficient to prevent any involuntary outbreaks. Special care should be given to projects that manipulate pathogenic microorganisms or toxic substances. In theory, the flowchart would be updated in each iGEM competition so that it is up to date with the latest information pertaining to the areas of biosafety and biosafety engineering.
ReferencesGupta, A., & Falkner, R. (2006). The Influence of the Cartagena Protocol on Biosafety: Comparing Mexico, China and South Africa. Global Environmental Politics, 23-55.
Ledford, H. (2010). Lifehackers. Nature, 650-652.
Schmidt, M. (2008). Difussion of synthetic biology: a challenge to biosafety. Systems and Synthetic Biology, 1-6.
Schmidt, M. (2009). Chapter 6: Do I undestand what I can create? Biosafety issues in synthetic biology. In M. Schmidt, A. Kelle, A. Ganguli, & H. de Vriend, Synthetic Biology. The Technoscience and its Societal Consequences (pp. 81-100). Springer Academic Publishing.
Scientific Advisory Committee on Genetic Modification [SACGM]. (2009). The SACGM Compendium of guidance. Part 2: Risk assesment of genetically modified microorganisms (other than those associated with plants). Health and Safety Executive Books.