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11 November
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Whole Genome Sequencing: Affirmative or Adverse Outcomes for Food Safety Management--or a Bit of Both?

Whole Genome Sequencing—a scientific breakthrough we first thought would remain confined to the halls of medical science for the treatment of human diseases such as cancer and previously undiagnosed ailments. Nevertheless, it has quickly entered and impacted the realm of microbiologists, food safety managers, risk managers, lawyers and CEOs in the food industry. For better or for worse?

Not to get overly scientific and risk lose readers at the second paragraph, but a short primer on Whole Genome Sequencing (WGS) is important to put the rest of the article in context. WGS is figuring out the order of DNA nucleotides, also called bases in a genome, which we know has now been performed for the entire human genome (aka The Human Genome Project). These DNA bases are known as As, Cs, Gs, and Ts and WGS is to identify and order these to determine the make up an organism's DNA. No small task either. The human genome is made up of over 3 billion of these little genetic letters!

For example, if in the sequencing process “ATGCC” was determined, it means that in that piece of DNA, an adenine (A) is followed by a thymine (T) is followed by a guanine (G) which is followed by a cytosine (C) and then again another cytosine (C).

How Does WGS Impact Food? WGS provides rapid identification and characterization of micro-organisms, with a level of precision not previously possible. When it was first discovered, the use of WGS was cost prohibitive to apply to the food industry. At first application, this technology had proved useful in areas such as antimicrobial resistance (AMR); however, it was still cost prohibitive. Seeing its value continued investment was made in this technology and as such it is rapidly advancing—and as as result costs are declining quickly.

Therefore, the “mainstream” application to the food industry occurred swiftly; especially the regulatory and surveillance arenas at the intersection of public and patient health (for both humans and animals). Consequently, WGS is being leveraged as the future key consumer protection tool used by regulatory agencies and the Centers for Disease Control and Prevention (CDC). This tool is now almost fully implemented in many regulatory laboratories in many states. For example, those who did not implement WGS in 2016 have plans to do so in 2017-2018 at the latest. This change will mean laboratories will be moving from its current PFGE (Pulsed Field Gel Electrophoresis) technology, which has some limits, compared to WGS.

CDC Surveillance/Regulatory Use

The CDC uses a tool to detect foodborne illness outbreaks called PulseNet. It is a national laboratory network whose goal is to connect foodborne illness cases early to identify outbreaks. This allows investigators to quickly find the source, alert the public sooner, and identify gaps in our food safety systems that would not otherwise be recognized. PulseNet uses the patterns of bacteria that make people ill—known as “DNA fingerprinting”—to detect local and multi-state outbreaks. PulseNet has been using PFGE technology to perform this “fingerprinting” service; however, it is now using WGS much more often due to its precision.

What is the impact? Imagine an episode of CSI (Crime Scene Investigation). PFGE was like leaving a partial fingerprint behind at the crime scene. There may be a way for a lawyer to possibly defend against it arguing that it was not the Defendant’s print because only a partial print was discovered or there was variation—it was smeared so somehow maybe it could belong to another source (a.k.a. another food). Nonetheless, with WGS it is like leaving your entire handprint or your whole DNA as evidence at the crime scene. It’s a bit of a “smoking gun” theory.

The CDC describes this specificity best on its website by explaining the difference between WGS and PFGE, stating:

“Whole genome sequencing provides more detailed and precise data for identifying outbreaks than the current standard technique that PulseNet uses, pulsed-field gel electrophoresis (PFGE). Instead of only having the ability to compare bacterial genomes using 15-30 bands that appear in a PFGE pattern, we now have millions of bases to compare. That is like comparing all of the words in a book (WGS), instead of just the number of chapters (PFGE), to see if the books are the same or different. Using whole genome sequencing, we have found that some bacteria that appeared to be different using PFGE are actually from the same source. This has helped solve some outbreaks sooner.”

WGS provides the entire genome—which facilitates targeted exchange and comparison of its data. Since the data is comprised of the genetic code—WGS results can be used for more than one purpose simultaneously, such as identification, subtyping, virulence marker detection, AMR predictions, and genome-wide association studies. This information can be analyzed and then stored for many years in PulseNet. Then, in the future, this data can be mined or reanalyzed at any time. This is admittedly useful to respond to a subsequent outbreak. Additionally, this data can now often make it possible to detect—and even solve—outbreak clusters or prevent additional cases from otherwise occurring. Because of this high-resolution sequencing data, matches between human clinical isolates and food/production environments often provide stronger hypotheses than those provided by matches using older methods. In food monitoring, WGS is used as forensic evidence for traceback (source) identification and to inform regulatory action.

On top of PulseNet, the Food and Drug Administration (FDA) has GenomeTrakr. This is a distributed network of laboratories that uses WGS for pathogen identification, which consists of public health and university laboratories that collect and share genomic and geographic data relating to foodborne pathogens. The information is accessible by researchers and public health officials for immediate comparison and analysis during and after an outbreak which is meant to speed up investigations and reduce foodborne illnesses and deaths. This network helps piece together outbreaks originating in certain regions, for example.

 

What Could the Potential Problems be with WGS?

With all the benefits that WGS appears to offer, there are also some challenges presented with its use, or maybe more in the application of the information.  A few are summarized below:

Potential Trade Issues—some countries exporting to the U.S. have not yet adopted WGS due to its cost or lack of trained microbiologists—or both. Thus, if Suppliers are performing less sophisticated testing methods and then shipping into the U.S.; there may not be an even playing field in terms of the Supply Chain players applying the same level of food safety management systems. As such, all trading partners—regardless of geographic location—should commit to using WGS. The reason why is that then the same tests (and more important); the same test results are used and relied upon within the global food supply chain.

Legal Severity? Double Jeopardy?

Data Ownership and Use: Some people have raised issues around such topics as the legal ownership of publicly available WGS data and/or privacy laws that still need clarity. For example, who owns the data once collected and in a central database like PulseNet?

Case Closed or Not? To some, WGS has become analogous to double jeopardy. Consider the power of WGS by reviewing this 2013 Denmark Case Study of human infections of listeria monocytogenes (LM):

For the first cluster of illnesses, epidemiological investigations were initiated when a cluster of four cases over a period of eight months was identified by WGS. Although a few more cases with the same WGS subtype were found in the following months—the investigation was closed with no source identified. Case Closed. (Insert sound of gavel here folks). Then, almost two years after the first case—one more case was detected. Environmental samples were taken at “Company X” (the suspect company) and were found by WGS to match the cases from years’ past. A review of case interviews supported a hypothesis that the outbreak source was Ready-to-Eat (RTE) products from Company X sold in a supermarket chain. The food authorities investigated Company X’s production facility and found several production lines implicated with different RTE products produced by Company X likely to be the cause of the listeria monocytogenes (LM) outbreak.

Look at another example a bit closer to home:

An outbreak between May 2015 and January 2016 of approximately 19 ill people in the U.S. and Canada involving bagged salad (1 person died per the CDC information). On January 21st, 2016—the Ohio Department of Agriculture took a random sample of bagged salad and tested it for LM. It was positive and the isolate from that food was uploaded to CDC’s PulseNet and it matched the same strain that caused the illnesses. The FDA then later visited the facility where the salad was made. The facility, equipment, and surfaces were all swabbed and the same strain was found. Thus, WGS linked the ill people, product, and facility. The smoking gun—but wait…in the records review, it was discovered that the company had also found LM in 2014 in the same facility and was still producing product. This revealing fact received a lot of press and therefore, during the investigation, it was questioned whether the company should be imputed with criminal charges for knowledge of an ongoing, previous LM problem that it knew about and didn’t correct. Read this sentence again. Because it can be interpreted to mean a very distinct, powerful concept in legal terms: willful or intentional distribution of contaminated product. Really? Fortunately, that potential claim slipped quietly into the night and we did not see this allegation in the final resolution of the outbreak or the recall. Still, it is occurring and it could recur.

Undoubtedly, the two examples above proved the use of WGS to correctly identify the source of the outbreak. Therefore, it did its job, right? So, how could this technology possibly be problematic? Well, WGS can resurrect cases the food industry may otherwise think were closed. A company may have had a pathogen finding in 2013—conducted an appropriate investigation and couldn’t determine the root cause—so they did the best they could with a proper corrective action and called the cased closed. However, if this was part of an “outbreak” (foodborne illness ‘outbreaks’ being defined by the CDC as, “an incident in which two or more persons experience a similar illness resulting from the ingestion of a common food”); then such unresolved outbreaks are never closed. Instead, they are filed as “cold cases” and these cases can be reopened with no regard to a statute of limitations by leveraging Whole Genome Sequencing and PulseNet’s and GenomeTrakr’s databases.

In short, WGS can take information from an environmental swab taken from your plant in 2013 and store the isolate information in the CDC database indefinitely. For example, a consumer in Arizona in 2017 may become ill with a Salmonella strain that is the same strain that your plant had in the environmental sample in 2013 and the consumer’s human clinical isolate matches your environmental isolate. If the consumer ate a product made from your facility (the epi data); you are done. The trifecta of linkages has already occurred and your once unresolved 2013 cold case could rise like a phoenix out of the ashes and come back to haunt you causing a recall, product liability claims, financial losses, negative PR, and a possible willful or intentional distribution claim.  

This shows the robust power of WGS. That WGS-typing of clinical-to-food-to-environmental isolates are often useful to identify a source of contamination and pinpoint a source to guide formerly inconclusive investigations based on epidemiological data only. The question remains, is it a form of double jeopardy if the investigation was previously closed?

The Fifth Amendment, in relevant part, reads “no person shall be subject to the same offense…to be twice put in jeopardy of life or limb.” Stated another way, it is considered a second prosecution for the same offense after one was convicted or acquitted for the same offense—some food for thought.

Several More Positives

Clearly, there are many positives to using more advanced science and technology, such as Whole Genome Sequencing in the quest to improve food safety management systems. Two key benefits that immediately come to mind are:

  • 1. Specificity: WGS significantly improves specificity and sensitivity when diseases occur over long periods of time to identify the actual company/product/ farm/source responsible for the outbreak. Thus, it greatly reduces the likelihood that a commodity crop will be completely decimated. For instance, tomatoes were blamed for a multi-state outbreak of Salmonella Saintpaul in Southeast U.S. and the tomato growers sued the USFDA for falsely warning consumers to not consume tomatoes costing that market over $100M in lost sales. In actuality, raw peppers grown in Mexico were to blame[1]. While it appears the USFDA could quash most claims by the tomato growers, it doesn’t take away the substantial loss suffered by that commodity and the fact that the USFDA didn’t have science as specific as it does now with WGS to identify the root cause of an outbreak. Hopefully, a commodity catastrophe like this doesn’t have to occur again.
  • 2. Protection: The obvious benefit to the sensitivity, the specificity, and the level of granularity that WGS brings is consumer protection. This way, we all win. Regulators, the scientific community, the food and beverage industry, and most important, the consumers.

 

Conclusion: From a public policy perspective, it seems these benefits will always outweigh the apparent challenges that WGS may pose. Its reliable, efficient, and one test yields information about resistance, serotype, virulence factors, and more. With that, I suggest the food industry learn as much as it can about this new technology, adopt and embrace it—as it is here to stay. Review your testing and sampling programs, as well as other policies and procedures as they relate to the new era of WGS. Ask yourself whether anything should change?

Likewise, ask yourself whether the findings from WGS should be used “against” the food industry from a legal liability standpoint to impute “knowledge” of an ongoing outbreak as severely as it may be beginning to be.   Many in the industry have a “seek and destroy” approach to environmental monitoring programs--an approach toward looking for pathogens, wanting to find them, and eradicating them. If WGS can be used against industry years later to impute knowledge of a systemic problem and resident strain, could this take the industry backwards in its thinking around environmental monitoring—back to doing the bare minimum? Could WGS whittle away the very public policy objective around consumer health and safety that it meant to protect?  

You be the judge. Do you feel WGS could open the food industry to excessively harsh legal exposure?

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