This article was originally published in October 2020 and has since been updated with the latest in the biosecurity space.
Synthetic biology has made it easier than ever to engineer organisms to serve our needs. But as the technology becomes widespread, concerns about its potential misuse arise. How can we ensure biosecurity without hindering the advance of synthetic biology?
Biosecurity consists of the prevention of and response to the release of potentially harmful organisms. Now that genetic engineering and synthetic biology are available to users outside established labs, biosecurity measures are becoming more important than ever.
However, ensuring biosecurity without preventing technological advances is a gray area with many unresolved questions. Who can do bioengineering? Which applications are allowed and which are prohibited? How can regulations adapt to new technological developments?
The legal framework that governs synthetic biology and bioengineering in the European Union was established in the ‘90s as a response to genetically modified crops coming to the market. These technologies are mainly regulated by the European Medicines Agency (EMA) and the European Food Safety Authority (EFSA). In the U.S., meanwhile, the equivalent regulators include the Food and Drug Administration (FDA), Environmental Protection Agency (EPA) and Department of Agriculture (USDA).
Different countries have different rules on what is permitted, but most of these regulations address cases where a gene from one organism is transferred to another. This approach is problematic when applied to new synthetic biology applications such as precision gene editing or cell-free synthetic biology.
Andreas Meyer, former CEO of the Basel-based biopharma company FGen and now bioworker at Gingko Bioworks, dismisses any major concerns about whether the lack of clear regulation around synthetic biology may discourage companies from adopting new technologies. “[We] just need updated regulatory guidelines regarding modern technologies such as CRISPR.”
“The regulatory authorities in the EU, in particular the European Food Safety Authority, which deals with the approval of genetically modified organisms, are still trying to figure out the differences between genetic engineering and synthetic biology,” said Victor de Lorenzo, group leader at the CNB-CSIC research institute in Madrid.
The EFSA is currently evaluating its existing guidelines, focusing on synthetic biology products that could reach the European market within the next decade. The EFSA proposes introducing the concept of ‘safe-by-design’ by taking into account all safety aspects during the development process. This could lead to faster approval compared to the current approach, where every product is evaluated from scratch, regardless of whether it is very similar to another approved product or process. However, a challenge that remains is that policymakers are still focused on how an engineered organism is made rather than what it does, an approach likely to result in blanket bans and discourage innovation.
A question of accountability
When it comes to risk from synthetic biology applications, one source of concern is the community of DIY biologists and biohackers using bioengineering technologies outside of certified laboratories.
DIY biologists have attracted negative attention when it comes to biosecurity. Due to the wide availability of cheap custom-made DNA, it is in theory easy even for lone individuals to produce pathogenic agents. “I can order gene fragments for any biological toxin and if I want, I can create the strain in my basement,” Meyer noted.
However, de Lorenzo is skeptical that this will become a big problem for the field. “My impression is that in quantitative terms [DIY biology] will not be very important,” he said.
Whether the danger comes from lone biohackers, synthetic biology researchers or multinational corporations, the DNA synthesis companies that supply them are developing safeguards. These providers screen the sequences of their clients’ orders for matches with pathogens and potentially hazardous genes, though shorter sequences remain challenging. In addition, as benchtop DNA synthesizers drop in cost, individuals could make their own DNA, circumventing any quality controls.
“We are working on an active solution to [DNA] screening that would allow shorter pieces of DNA to be screened routinely,” said Emily Leproust, CEO of Twist Bioscience. “We encourage all benchtop synthesis providers to ensure that these machines will not print DNA that is a controlled sequence – similar to how a Xerox machine will not copy U.S. dollars.”
A major concern for regulators – and the general public – is unintentional release. What if bioengineered organisms escape into the environment or what if they start spreading in areas they were not intended to? According to Natalie Curach, former president of the non-profit organization Synthetic Biology Australasia and now in senior roles at Ginkgo Bioworks, HydGene Renewables and Eden Brew, the community is working on solutions for such eventualities.
“Physical containment, integrated kill switches and metabolic dependencies, for instance, provide technical control measures. Upskilling genome foundries and equipping them for rapid responses in the event of biosecurity threats, as we have seen in the Covid response, is also a way of containing biosecurity risks and implementing countermeasures,” she explained.
However, de Lorenzo is skeptical about biocontainment methods. “I have no faith at all in containment; bugs will always escape.” As a solution, he suggests the implementation of chassis organisms. The idea is that the synthetic biology community will be using a set of defined microorganisms to develop new applications. This concept is borrowed from mechanical engineering, where manufacturers can add different components to a standard frame of a car to design the final vehicle.
These organisms will be barcoded, meaning that the regulators can track exactly where they came from and how they are modified through a simple DNA analysis. This method would also make the approval of new applications speedier, as the chassis would be already proven safe for environmental release.
Biosecurity as an investment, not a burden
“We need to think carefully about the context in which we use tools like synthetic biology. We have a responsibility to maximize these benefits, in part at least by helping to manage any risks,” said Piers Millett, vice president for safety and security at iGEM, a global student competition of synthetic biology projects.
One of the iGEM partners is the U.S. Federal Bureau of Investigation (FBI), which every year uses the opportunity to raise biosecurity awareness among the competitors. “When you engage with them on biosecurity issues, iGEMers find the topic interesting and can see how it relates to their projects and future ambitions,” Millett added.
What the iGEM experience has shown is that synthetic biology practitioners are very eager to internalize security concerns and work with or around any societal concerns. “All the synthetic biologists I know are driven by the potential of their work to contribute to a more sustainable and equitable world and that’s a pretty good start,” said Curach.
We should see biosecurity awareness and preparations to confront potential risks as an investment, not a burden. Biosecurity, as well as cybersecurity, should be seen as a necessary part of the development process of any synthetic biology product from the start. This will then assure that the effort put into developing synthetic biology solutions will reach the industry, the market and the consumers. And it is the only way to avoid the sterile debates that dominate the synthetic biology field.