Biosafety Considerations of Synthetic Biology: Lessons Learned from Transgenic Technology

Abstract

The commercialization of transgenic crops has expanded rapidly in the past decade. However, there are still debates and concerns about the safety issues of these crops for human health and their environmental impact. Debates have also focused on the socioeconomic consequences of the monopoly of seed production of a few companies. While adhering to national and international regulations to ensure the health of people and the environment, the broad applications of this technology would be difficult without addressing the public concerns of biosafety and other related issues, including social and ethical considerations. Golden rice has been developed based on transgenic technology with aims to prevent blindness and reduce malnutrition from vitamin A deficiencies by reintroducing the biosynthesis pathway of beta-carotene into the rice. However, it is still stuck in the lab after its invention nearly 15 years ago due to public resistance and skepticism of this product [1]. Synthetic biology is a new and rapidly growing field that is building on experiences in genetic engineering, bioinformatics, system biology, and the principles of engineering science [2,3]. Its development and biosafety management should also build on the previous experiences of transgenic technology. In contrast to traditional genetic engineering, synthetic biology attempts to introduce a large number of heterogeneous genetic circuits into host cells by designing and constructing new biological parts, devices, and systems. Even synthetic forms of life can be constructed [4]. Synthetic biology brings new opportunities to life sciences research and industrial production [3]. With its successful applications in the biomass-based productions of biofuels, pharmaceuticals, and bulk chemicals, its potential contribution to sustainable development is highly expected. However, there are also concerns on its impacts on society and the environment, and these should be addressed in order to enable further development of this technology. Scientific knowledge is the determinant of attitudes toward science [5]. Thus, it is crucial to communicate with the public on the benefits and risk management of synthetic biology while trying to implement appropriate measures to eliminate, reduce, and manage the risks. The current research activities in synthetic biology are mainly focused on microorganisms, such as bacteria, viruses, and yeasts, which leads to concerns on the creation of novel pathogens that may result in biosafety and biosecurity problems. For example, scientists have successfully synthesized several viruses that could lead to fatal diseases, such as poliovirus [6] and the 1918 Spanish influenza virus [7]. Although antibiotics and vaccines have played important roles in combating the infectious diseases caused by microorganisms, many pathogens still pose great challenges to public health. These pathogens range from multiple drug-resistant bacteria to lethal viruses (bird flu virus, HIV, Ebola virus, etc.). The situation may become worse if the revival of lethal pathogens, such as synthetic Spanish flu virus, can be achieved with the development of modern biotechnology, such as synthetic biology that can synthesize the whole genome of the virus and revive it. Currently, it is also possible to enhance the virulence of known pathogens with new traits that can contribute to their competence and resistance to existing treatments. It is believed that new pathogens can be created with technologies that have been developed for synthetic biology. For example, a novel type of avian flu virus with enhanced infectivity in mammalian animals may be created, and the H5N1 virus can be modified to evolve into a dangerous human virus [8]. The International Genetically Engineered Machines (IGEM) competition since 2004 is an event that attracts university students from around the world who represent their interest in the technology and who may become key players in the field of synthetic biology in the near future. One of the aims of the competition is to attempt to build simple biological systems from standard, interchangeable parts and operate them in living cells. In recent years, the organizers requested the participants to respond to biosafety issues and questions about their synthetic biology projects as a standard procedure in the competition. The most important issue that the participants were concerned about was laboratory biosafety [9]. The biosafety concerns raised by the IGEM teams mainly focused on physical and biological containment in routine laboratories of universities (normally below biosafety level 2). The risk assessments of DNA materials (or biobricks) and pathogens were considered the priority for safety management. There is a possibility that synthetic biology research and the products (organisms/molecules) that are derived by this technology will pose higher risks than the traditional transgenic ones because synthetic biology employs genetic elements from various sources (even completely new designs). However, concerns about risk assessment and management of synthetic biology are based on traditional transgenic organisms because they both involve DNA recombination and genetic engineering technologies [10]. Thus, the precaution principle, a case-by-case approach, and the use of other related methodologies for the risk assessment of transgenic technology may still be valid for synthetic biology. For example, biosafety containment guidance from the fifth edition of Biosafety in Microbiological and Biomedical Laboratories is applied in synthetic biology research. NIH Guidelines for Research Involving Recombinant Molecules have been slightly revised to include synthetic nucleic acid molecules [10].