Synthetic biology: how to screen for DNA danger now and for the future

Curiosity propels scientists and engineers to drive progress. As we start to build the bioeconomy (using biology instead of electronics to solve problems including DNA-based computational platforms) we must maintain a rigorous curiosity – not just about what we can create, but about what we could inadvertently unleash.

One of the most important questions is: how do we ensure that advancements in synthetic biology do not come at the expense of safety?

We typically think of the bio economy’s use of DNA in a life sciences context, such as developing new pharmaceuticals or medical treatments. However, new industries including DNA-based computing offer tremendous advantages compared to traditional computers on processing some workloads. DNA computation platforms use very little energy and occupy significantly less space. This could usher in a world where more synthetic DNA is created for computation than for life sciences purposes.

Consider this comparison: the human body has 3 Giga-base pairs of DNA in our genomes, but the phones we carry around in our pockets have hundreds of gigabytes of digital data. Despite the opportunities, we have to stay vigilant about the potential unintended impact of these new technologies if used by nefarious actors.

Responsible stewardship dictates a need for proactive approaches to biosafety and biosecurity. This includes the entire industry adopting a standard protocol for screening synthetic DNA against known pathogens and toxins and maintaining an active database to capture new and emerging threats to public health and safety.

Specifically, as we create new DNA molecules, it is essential that we rigorously screen for high-risk sequence patterns (specific sequences of DNA that overlap with those known to be harmful). The challenge here lies in the sheer scale of what we are working with. All the information stored in football-field-sized data centres can be converted into a small vial of synthetic DNA. This necessitates a robust strategy to ensure that every combination we produce remains safe.

One approach used to convert digital data DNA is synthesis, which creates new strands of DNA with binary data stored inside. With synthesis, an infinite amount of DNA strands are created to convert new information into DNA, each of which represents a potential point of exposure.

To address this problem, our company CATALOG is pioneering the use of a “clean library” in all of our DNA data encodings. This library includes 30-50 base pair DNA components that are combined in different ways to represent different digital information. Think of this library like letters in an alphabet. The Oxford English Dictionary contains more than 600,000 words based on combinations of just 26 letters.

The advantage of CATALOG’s approach is that each base pair of DNA strands in the library has undergone rigorous screening and has been certified to be biologically safe. These base pairs can be combined in an unlimited number of ways without the need for additional screening. With synthesis, every time a new piece of information in stored inside DNA it must be screened for bio-risk flags.

CATALOG's systematic approach ensures that as we expand our libraries, we can remain assured that no dangers are introduced in accordance with the screening recommendations established by the US Department of Health and Human Services.

In our screening efforts, we have used the open-source software suite The Common Mechanism developed by the The International Biosecurity and Biosafety Initiative for Science (IBBIS), designed to scan DNA sequences against a set of four risk databases. As a result, all future DNA encodings using our validated set of components are deemed safe to the current IBBIS standards of pathogen and toxin screening until new sequences are added to the corresponding databases. Updates are made available as necessary and can be easily downloaded locally.

Looking ahead, creators should not be left to their own devices to continuously monitor and adapt the tools needed to keep their creations safe. In fact, current synthetic DNA companies engaged in active monitoring for harmful sequences are doing so voluntarily with no standardized practices in place. Many often have an economic incentive or even a fiduciary duty to take the shortest path to profit that does not align with the long-term benefits of society.

In addition, bad actors continue to evolve new strategies to circumvent the existing biosafety screening tools to synthesize DNA for nefarious purposes. How we identify these individuals and alert the proper authorities of their intent adds an additional layer of responsibility to our industry.

Our discussions with world leaders in Geneva in September at an event hosted by the World Economic Forum, IBBIS and the Coalition for Epidemic Preparedness Innovations (CEPI) underscore the complex, global nature of this challenge. The bioeconomy is a collaborative endeavour, transcending borders and disciplines. Incentives for the industry to take action in the call for biosafety and biosecurity, however, lag behind the incentives for innovation.

We must engage with scientists, policymakers and industry leaders alike to ensure we build a robust system of checks and balances that continues to scale and evolve alongside the emerging technical capabilities being realized in the DNA economy.