What is Whole Genome Sequencing?

Whole-genome sequencing (WGS) has proven to be very effective at identifying where resident Listeria strains may be found in a food facility. To date, however, it has also been proven to be equally effective at ensuring that only a few food companies want to use the technology.

WGS as a Technology

For the most part, scientists, such as molecular biologists, and regulators, such as FDA, view WGS as an evolving state of the art. Using these methods has repeatedly helped regulators identify resident strains in a food facility before the strains can cause significant public health issues. If the strains end up on manufacturing equipment and/or in food, WGS is very
useful at identifying the association between the original source, retail distribution, and public consumption of that food.

WGS is, in essence, an upgrade from its precursor technologies such as pulse-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and multiple-locus VNTR analysis (MLVA).

As has been demonstrated in recent years, the science of identifying genes, bacteria, and food-related organisms keeps progressing, and always will. As many people have stated in published articles and speeches, WGS technology has probably outpaced the food industry‘s ability to keep up with it at the moment. But surprisingly, industry has been reluctant to embrace the technology, in large part because of fear that their products will be linked to human illness and the potential resulting regulatory enforcement actions.

Keeping Up with the Technology

Grabbing any new technology and putting it to work in a manufacturing plant is rarely straightforward, is difficult to mandate, and must be done with careful consideration. This is because new technologies come with baggage, some of which include significantly higher costs initially (compared with past/current technologies), longer lead times initially, and higher alpha- and beta-risks (i.e., chances of false results).

These are all good reasons why the food industry in general has not embraced WGS as a routine tool. And this is in spite of the fact that FDA will sequence any positive it finds during a “swab-a-thon.” In fact, the food industry has barely even embraced WGS as a problem-solving tool.

WGS as a Problem-Solving Tool

One of the best uses of WGS in a food production plant is increasing the odds of finding the root source of a strain of Listeria that is resident. For example, positive WGS findings (i.e., matching gene sequences with an extremely high probability) can help a company identify a regularly incoming raw material as the source of a Zone 3 recurring contamination (e.g., on pallets).

FDA takes this same approach in attempting to link a specific Listeria strain sequence found in a clinical isolate or food product with an identical strain found in a food plant.

Using WGS in this manner takes a lot of time (and money), and it is at the moment a best practice for identifying Listeria strains that have resided in given locations over time. This allows discovery of “hot spots” and certainly helps in identifying external sources (e.g., a supplier issue). Hence, a regular use of WGS testing of strategic samples around a food facility can pay huge dividends in identifying, and then eradicating, resident Listeria strains.

By contrast, WGS is a poor tool to use to identify transient strains of Listeria and/or when results are needed quickly to be able to respond to an issue or corrective action. This is primarily because of the fact that by the time the WGS results come back, the transient organism is long gone. And although the cost of WGS testing has dropped by orders of magnitude over the years (as happens with new technologies that become mainstream—look at wide-screen TVs), simply churning out WGS samples to try to locate Listeria in a food facility can become extraordinarily expensive.

Other techniques are far quicker and can be equally effective at the end game. For example, there is still value in using some of the older techniques such as PFGE and MLVA. Even easier and cheaper, although less informative, is using well-proven standard microbiological techniques to assay for Listeria (e.g., FDA BAM Chap 10). These standard micro tests have widespread proven use in environmental monitoring programs to “seek out and destroy” pathogens in a food facility, regardless of whether those organisms are transient or resident. WGS can then be used sparingly as a means of continued surveillance, ensuring that strains are or are not taking up residency.

The “time and cost” value equation of WGS, however, is still a reason why food companies do not routinely use WGS. Do note that over the past two years, turn around time and costs have been significantly reduced (e.g., a five-business day turn for Listeria WGS is about $500). However, this value equation is either still not good enough, and/or companies are still saying that the tests are “too long and too costly” as a shield for not wanting to enter FDA’s territory.

FDA and WGS

Clearly, FDA sees WGS as a savior; euphemistically speaking, if use of the technology prevents even one illness, then its use is warranted. And, since the technology is available, an informed public would most likely want FDA to use it. So, it may be that as time progresses, public and political pressure may push WGS forward independent of food safety professionals wanting to do so or not.

Having WGS in its toolkit also allows FDA to trumpet what it is doing: WGS is a well-defined technology, and the public can understand it (especially when the public watches crime shows that use DNA testing, or consumers use DNA sequencing for ancestry determination purposes). FDA will continue to use these tools to find organisms, such as Listeria monocytogenes, which can cause significant adverse health consequences or death to the small populations that are highly susceptible to the organism’s effects.

This is also why FDA continues to maintain a “zero tolerance” policy for
Listeria monocytogenes. This is not the case worldwide (e.g., Canada and Australia), but it is the position FDA has taken. Granted, the rationale for this is to protect the public health, but it also allows FDA to conduct deeper investigations into a food company’s practices and, when resident pathogens are detected and linked to human illness, initiate the enforcement actions the public would expect them to take.