Whole genome sequencing (WGS) is an advanced technology that the U.S. Food and Drug Administration is increasingly using to better understand foodborne pathogens, including identifying the nature and source of microbes that contaminate food and cause outbreaks of illness.
WGS essentially reveals the genetic fingerprint of a pathogen, by sequencing the chemical building blocks that make up its DNA. For example, it was recently used to help match samples of soft cheese to the genetic fingerprint of Listeria monocytogenes involved in a deadly foodborne illness outbreak in early March.
Eric Brown, Ph.D., the director of the Division of Microbiology at FDA’s Center for Food Safety and Applied Nutrition (CFSAN), and Marc Allard, Ph.D., the center’s senior biomedical research services officer for genomics, talk about how the agency is using WGS now and the future role of this technology in keeping consumers safe from contaminated foods.
Q: How is whole genome sequencing used by the FDA today?
Brown: Whole genome sequencing has been used regularly since about 2012-2013 to help safeguard the food supply. The way we use it is to augment investigations by our outbreak responders, to support them with better and more accurate information as they trace back contamination in the food supply to its source. We use it to support our Office of Compliance in its enforcement of food safety regulations and to help companies identify safety problems in their facilities. The goal in both instances is to keep contaminated food out of the food supply.
Q: For people who aren’t familiar with this technology, is this essentially a genetic fingerprint of bacteria? Is that the correct way to describe it?
Allard: Yes, it’s the whole genome of a bacterium. (A genome is an organism’s complete set of DNA, including all of its genes.) If you think about the human genome, with all of the genetic data that are present in a human cell, this is the equivalent in bacteria, although they have much smaller genomes. When you sequence a bacterium’s entire genome, you’ll have its complete genetic makeup. This provides the ability for a clear distinction in the characterization of bacteria.
Q: So would you say it is a faster and more clear way to identify bacteria involved in a foodborne illness?
Brown: Yes and I think the most important part of that statement is the clarity. That is, we can see if the bacterial genome of contaminated food matches that of people who have become sick from foodborne illness. The certainty is unprecedented, even though the food may have come from anywhere around the globe. It has always been a great challenge to try to track contamination of imported food because there are so many places where the food can come from. Since bacteria develop genetic traits in response to their specific geographic environment, it is now possible to obtain hints about their origin through sequencing. So to have this tool in our hands now and to localize contamination to specific parts of the world very quickly really goes a long way to help the inspectors that we have out in the field at any given time.
Q: Where is this technology in its development? Will it be advancing from here?
Allard: The technology continues to advance and one of the roles of our laboratory is to test the new genome sequencers and see if they are really faster, better, and cheaper or maybe more mobile. We are looking at some very small sequencers that could fit in the pocket. We could have a lab in a briefcase that could go out to the consumer safety officer and actually do field testing. This is the future vision and it will take time to test that equipment, but at the same time you have to decide when to get your feet wet and start using it.
Q: What has been the FDA’s role in spreading this technology, starting with state and federal labs across the country?
Brown: GenomeTrakr is the network we spearheaded in late 2012, first nationally and now internationally. We partnered with our federal counterparts, including the National Center for Biotechnology Information at the National Institutes of Health (NIH), where the data are housed and curated. We’ve worked with the Centers for Disease Control and Prevention, which is feeding clinical data (e.g., bacterial sequence data from people who became sick) from PulseNet into the database constantly, and our partners at the U.S. Department of Agriculture’s Food Safety and Inspection Service, who are uploading data from the foods that they regulate, such as meat and poultry. So starting in late 2012, the concept was born in that we could distribute desk-top sequencers in state and federal laboratories so that they could sequence foodborne pathogens collected during inspections, analyses of foods, and environmental sampling in food manufacturing facilities. We started seeing a real difference in our ability to pinpoint sources very quickly, almost instantly, as soon as an outbreak or contamination event would happen. So now we ask everyone to upload their bacterial sequences to the database over at NIH, which is publically available and easily accessible. The same data are there for regulators, public health experts, consumers, and industry to see in real time. This open-source availability has been one of the great innovations of the network, allowing everyone to have access to the data at any time.
Q: How is the technology being shared globally?
Allard: We have provided funding for one World Health Organization (WHO) laboratory, which delivers health care in the developing world, to set up a pilot program at the Malbran Institute in Buenos Aires and we continue to work with WHO to spread sequencing to more laboratories. The goal is to see genomic laboratories in many regions throughout the world. We are also working with WHO and the Food and Agriculture Organization (FAO) of the United Nations to help provide guidance for when countries should start getting involved in genomics, the best applications, and which parts of our system are easily adapted to bring more genomics to the global community.
Brown: We are excited to support WHO, FAO, and OIE (the World Organisation for Animal Health) in their efforts to learn how to best deploy whole genome sequencing to developing and more developed countries globally, not just here in the U.S. or in western Europe. We get our food from all over the world and we need to have good surveillance and good traceability to all points in the world where that food comes from.
Q: With other federal agencies doing whole genome sequencing, how do you coordinate your efforts?
Brown: Now that sequencing has permeated all the major public health agencies there is a good bit of coordination–we actually have formal steering committees between our agencies that involve management and some of the upper leadership to help develop policy decisions about who will sequence what, how we will share that data, and transfer that information not just to databases but to the public. When you have a database that’s populated with huge amounts of clinical data from sick people from CDC and combine that with many thousands of strains from environmental and food data from farms, factories, facilities, and contaminated foods from FDA and FSIS now you’ve got a recipe for real success.
Q: What are other uses for WGS beyond food safety?
Allard: There are other FDA programs that could benefit from this technology. For example, we are working with FDA’s Center for Veterinary Medicine to use WGS to monitor for the presence of bacteria resistant to antibiotics as part of FDA’s work with the National Antimicrobial Resistance Monitoring System. And, it isn’t just foodborne pathogens that are being collected and compared on a daily basis. NIH has a much broader mandate and they are comparing any pathogen that affects human health. So the basic tools that were set up for food safety are also now being used for global surveillance of human infectious diseases.
Q: What’s ahead in 2017 for WGS?
Brown: Most importantly, we want to continue to serve our own agency in its mission to protect consumers against contaminated food and bring whole genome sequencing around to the front line users like the people in compliance and our people in the outbreak response units, so that they can have these tools at their desktop. From my perspective, it’s been good to see how whole genome sequencing can serve as a single microbiological workflow tool that displaces numerous other separate tests that each cost a lot of money and take a long time. If we wanted to know about the virulence of a pathogen, if we wanted to know its serotype, if we wanted to know its drug-resistances, all of those were separate tests and very expensive. But genomics is providing one avenue, one workflow, so that with that sequence we can tell you if a bacterium has the genes for drug resistance to various antibiotics, what virulence factors and serotype (distinct variation) it has, and how we should classify it. All of this can be done now very quickly using computational tools.
Q: What is the most important thing for consumers to know about this technology and how it affects them?
Brown: One thing we’d like to tell the public is that we are leveraging this technology to further ensure and enhance the safety you have been accustomed to. Hopefully, if there is a (food contamination) event, we will find the source much more quickly and remove it from the food supply so that our consumers can be as safe as they can possibly be.
For example, in 2010 we had a massive shell-egg outbreak, one of the largest in the country. We weren’t online yet, but we did a retrospective analysis of that outbreak and we were able to show that not only could whole genome sequencing have pinpointed the two farms that were putting contaminated eggs into the food supply, but it could actually distinguish which farms were responsible for which illnesses.
We knew at that point the kind of power we had in our hands.