Running customer and sequence information through the screening process is just the first step.
The theory behind biosecurity screening and the methodology for screening is not difficult. The U.S. HHS 2010 Screening Framework Guidance is thorough and clear about both. The willingness to screen is also clear, given that the IGSC Harmonized Screening Protocol is followed by companies accounting for about 80% of the commercial gene synthesis capacity worldwide. With workable protocols in hand and the will to utilize these protocols, it seems that all companies need to do is put the recommendations in place. The truth, however, is that implementing and maintaining an effective screening program is more difficult than it seems.
The Gray Area
Customers and sequences can be flagged for a variety of reasons. A simple “error” in an address can be just that. Then again, it can also be an attempt by an entity with ill intent to avoid identification. The same is true with a sequence of concern. Genes, for example, from viruses that are otherwise considered pathogenic could be used for beneficial purposes such as drug delivery. It can be tough to determine what the ultimate end-use for a sequence of concern might be. When the response to a flag is ambiguous and those responsible for follow-up find themselves in the troubling gray area, it requires a greater commitment of time and expertise to clear that flag.
More to Consider
Expertise in the form of those with a Ph.D. and the requisite expertise in the field for correctly interpreting a flagged sequence of concern is one of the most costly components of an effective DNA sequence screening program. If orders come in irregularly, or if there are spikes and valleys in the level of orders, it may not be economically feasible to have experts dedicated to sequence screening, which is an overhead cost, when their talents could instead be used on other revenue-generating work. At a minimum, it would be inefficient to have such high-value talent sitting idle.
Leaps in Scale Engender Additional Complications
The need for the required expertise and experience at the time of greatest need is one complication. When an enterprise is growing in size and scaling their systems to meet a steady increase in demand as the market for synthetic DNA sequences grows, it is even more complicated. What works at one scale and output level may not work at the next, or the one after that. When the mix of expertise and technology is not directly scalable to an increase in sales, it’s not always feasible to maintain the quality required without slowing down order fulfillment.
Advancing Technology Creates New Issues
Advances in technology also create new issues for companies fulfilling orders for synthetic DNA sequences. As it becomes possible to “stitch” together smaller portions of DNA to create a required sequence, the question of screening sequences with fewer base pairs and determining if a certain combination of the short sequences could be concerning becomes more pressing. It’s also possible that customers will order novel sequences that don’t match with sequences in any reference database yet have pathogenic potential. Additionally, new benchtop DNA synthesis technology introduces new biosecurity challenges that will affect screening protocols in an as yet unknown manner.
If all that was required was a screening protocol and the necessary hardware, DNA sequence screening programs would be easy to implement, easy to run, and easy to maintain. Since biosecurity screening depends upon a fragile balance of expertise and technology in the face of a changing environment, there is much to appreciate about the inherent difficulties.