Why Do Some Organizations Screen DNA Voluntarily?

DNA screening is a vital component of an effective biosecurity program. Certain stakeholders in the biotechnology community screen DNA sequences voluntarily because they want to ensure that the technology is used responsibly and that the broader ecosystems around them are protected.

Professionals in the fields of gene editing and synthetic biology voluntarily screen DNA sequences in part because they are aware of the consequences of the accidental or nefarious use of biological materials, especially pathogens. Additionally, these professionals realize the potential business risk and liability they face if their products are ever used intentionally in a bioterror attack. Fortunately, those involved in this sector have the benefit of seeing how cybersecurity protocols have evolved over time to protect computer networks from increasingly sophisticated and malicious hacks. As a result, they can incorporate these learnings into biosecurity protocols by considering early on how biotechnology advancements can potentially be used both for the greater good and malicious purposes. 

What is DNA Biosecurity Screening?

In the context of DNA, screening is the use of specific criteria to assess the integrity of a sale to a customer in terms of the risk associated with a transaction involving DNA sequences or research equipment that can be used to produce DNA sequences. Some aspects of the criteria may vary with the type of sequence or equipment, and there may be some variation in the information screened, but the core information required for a sale is generally uniform across the industry. This overall consistency is due to the fact that most screening programs follow guidelines outlined in the U.S. HHS 2010 Screening Framework Guidance that recommends screening at three levels: customer screening, sequence screening, and flag and follow-up if needed.

Three Parts of Biosecurity Screening

Customers - Customer screening is intended to authenticate customer-provided information as well as that the purchase is being made for legitimate research or commercial use. Per the HHS guidelines, customer screening should include several essential pieces of information that answer the following questions:

• Who is making the purchase?

• Is the customer the ultimate user?

• What is the purpose of the purchase?

• Is the customer on any warning or watch lists?

Sequences

Certain pathogens have been identified as threats and are therefore included on one or more of the control lists created and maintained by governments and agencies around the world. Screening for DNA sequences from these pathogens is necessary to ensure those sequences are either not produced or if they are, that they are only delivered to customers authorized to work with them. However, there can be many challenges in determining whether or not a sequence is a high risk. For example, some sequences are not yet known to be dangerous or will not be dangerous unless they are manipulated in yet unknown ways. Also, there are sequences in known pathogens such as anthrax, that are not themselves pathogenic sequences. 

The HHS Screening Framework Guidance recommends the identification of sequences that are associated with pathogens on the Select Agents and Toxins list, the Commerce Control List (CCL), and The Australia Group (AG)’s three pathogen lists for the purposes of:

• identifying “unique” Select Agents and Toxins and CCL-listed entities;

• determining whether or not a nucleotide sequence “is derived from or encodes a ‘sequence or agent of concern’” through the use of six-frame screens of translation polypeptides; and

• detecting any sequences of concern in order through the use of overlapping screenings. This can be done by comparing “overlapping 200 bp (base pair) nucleotide segments … and corresponding 66 amino acid sequences, over the length of the dsDNA (double-stranded DNA) to a public sequence database… using a sequence alignment tool.”

Flag and Follow-up

The screening itself would be meaningless without follow-up for nonconforming customers or sequences. The recommended protocol is straightforward.

• Verify the information in hand.

• Contact the customer involved or rescreen the sequence.

• Decide whether or not to ship based upon the outcome of the contact and rescreening.

• Consult law enforcement when appropriate.

Stakeholders large and small should recognize that it’s in their best interest to secure the industry for the protection of all. To that extent, some gene synthesis companies have developed in-house screening applications of their own.

Companies like Battelle have developed cloud-based solutions for sequence screening. UltraSEQ™ Advanced DNA Sequencing Threat Analysis is updated on a regular basis and includes metadata for “sequences of concern” that provides the evidence and literature citations to support classifying a sequence as a threat.

Whether through the use of an in-house system that flags customers and sequences, or a commercial cloud-based sequence screening solution that augments a company’s customer screening procedures, the identification, and flagging of customers and sequences of concern before orders ship should be an imperative.