Hidden Messages in DNA Could Reduce Biosecurity Risks

Synthetic nucleic acid sequences are a staple in modern biology these days. Whether it is cell and gene therapies, biofuels, or foods like the Impossible Burger, products using synthetic DNA are everywhere. Over the last two decades, synthesizing DNA has become faster and easier, but researchers worry that this will make it easier for people to access potentially dangerous products. While many experts call for more federal guidance and regulation over the production of synthetic nucleic acid sequences, others have drawn focus to biosecurity concerns that are a little closer to home: in research labs. Jean Peccoud, a synthetic biologist at Colorado State University, and Casey-Tyler Berezin, a molecular biologist on Peccoud’s team, discussed the biggest biosecurity issue facing research, approaches for encrypting messages into DNA sequences, and the importance of sequencing technologies for mitigating biosecurity risks.



How do you define biosecurity in the context of DNA?

Peccoud: An internet search for biosecurity will return stories about security measures aimed at preventing pests or infectious agents from entering the country. However, what gene synthesis has done in terms of transforming biosecurity is that now you can have an infectious agent coming through the computer network. What I mean by that is that countries can build walls across their borders, fill airports with dogs, and introduce more screening of passengers, but an infectious agent can come from a database and then get sequenced. However, the topic has evolved significantly; rather than solely focusing on whether someone can use a benchtop DNA printer to create Ebola in the lab, it's much more interesting to broaden the scope of risks that we’re exposed to. Some of the problems that people are starting to pay attention to with respect to the biosecurity of gene synthesis are way too narrow. The life sciences enterprises need to develop more awareness of what they're actually doing: How do we know that what we have in our labs is what we think it is? The community would really benefit from more security awareness.


For example, every research sample, such as a tube with a DNA plasmid, has two facets: a computer record that contains information about the sequence or provides a plasmid map and then there's the content of the tube. When the two don't match, there are all sorts of potential problems that arise. This may not be a biosecurity problem in the regular sense because you're not dealing with infectious agents, but people are spending millions of dollars on research that they cannot reproduce because they don't know what they have in their flasks. It's a security problem that comes from the fact that what you're working with is not what you think it is. That's something that is happening in every lab, every day, and we have very few tools to figure out what's going on in our own lab.

How did you become interested in studying biosecurity in the lab?

Berezin: When it comes to biosecurity with respect to synthetic DNA sequences, the onus is really on the gene synthesis companies that are making the sequences, but these security efforts are limited in scope and can't protect against other events that can come up later in the life of the product, whether it’s the intentional manipulation of a sequence or plasmid mutations that naturally occur over time. Biosecurity is not something that was part of my PhD training, nor something that ever came up in any of the labs that I worked in. That is really a missed opportunity to educate people on these potential security issues. I became interested in the topic when I joined Peccoud’s synthetic biology team. I realized that a lot of the methods that we’re using, such as polymerase chain reaction (PCR) and bacterial transformations, are methods I had used before but never wondered where the DNA sequences came from or how I would know if something had changed in the sequences. This is the status quo—we work with DNA and take for granted that it's going to be what we think it is. Once you are aware of the biosecurity issues, it's something you can't turn your back on. Now, I see those issues everywhere.


How can DNA sequencing prevent potential biosecurity events?

Berezin: Initial screenings of DNA products may not be enough to prevent problems from arising years down the line. DNA is going to mutate. That's what it likes to do. It likes to replicate and sometimes that doesn't go perfectly. So even if you might have something safe in a tube in your lab, after you propagate it 100 times or 1,000 times, you might not have what you think you do. Whether that's dangerous or not really depends on the specific scenario, but that uncertainty of not knowing what you have, is very prevalent across academic research labs. It takes a lot of work on the part of the user to ensure that they're tracking all the sequences that they have and that they are sequencing their plasmids as they go on.

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