The European Food Safety Authority (EFSA) and EU Commission’s Inter-European Union Reference Laboratories (EURL) Working Group on Next Genome Sequencing (NGS) organized the second Science Meets Policy conference this week. More than 100 people from 20 countries attended in-person while online viewers peaked at 257.

Stefano Morabito, from the Italian National Institute of Health (ISS); George Haringhuizen, at the Dutch National Institute for Public Health and the Environment (RIVM); João André Carriço, of bioMérieux; Katja Alt, from the German Federal Ministry of Food and Agriculture and Coen van der Weijden, from the Netherlands Food and Consumer Product Safety Authority (NVWA) were featured on a panel discussion.

Panelists highlighted the need for flexibility, especially as there are 27 countries in Europe at different stages in use of Whole Genome Sequencing and as outbreaks can involve nations outside the EU. They discussed the types of data needed, data quality and comparability, resource issues, how to build trust and the role of different parties including regulators and industry.

EFSA and ECDC’s One Health WGS system has been operating since July 2022 and while things are going well, not all member states are contributing equally.

Data sharing dilemmas

Bernhard Url, EFSA’s executive director, said genomic data sharing is now at a turning point.

“We believe that from a technological and methodological point of view we are ready to use WGS data more widely and with more impact. Many of the problems have been solved and the technical infrastructure has been built. There is no doubt, at least within the community, that data sharing adds value, because it leads to faster outbreak detection and better tracing. It increases the likelihood of connecting sporadic cases to clusters and to detect outbreaks and there is measurable economic impact,” he said.

However, despite the knowledge that sharing data helps, there are still some obstacles that prevent wider use, said Url.

“There are technological gaps as not all member states or organizations use WGS on a routine basis. There is also a worry that people and countries say we don’t have a robust legal basis to share data. There is a fear that people lose control of data, they produce the data, share it but don’t know what happens afterwards. There is a concern that if this technology would be used widely, many more clusters would be detected, which is good from a public health point of view, but it also would increase the workload of national authorities to follow-up and deal with these clusters.”

Url said it would be “unwise” to wait for legislators to define the rules of the game.

“The WGS community must do our part to create the conditions for success. We think there is a lot we can do to move data sharing forward in the current legislative framework. We still have to work on creating a mutual understanding about benefits and limitations of this technology. We have to agree on common guidelines, processes and procedures, otherwise we wouldn’t know how to compare different outcomes,” he said.  

“We want to act as openly as possible but as confidential as needed, there is a fine line that we have to find. EFSA has invested resources in creating a technological infrastructure for enabling WGS data sharing, mainly to tackle foodborne threats. We will continue to do our part to move genomic data sharing forward.”

United States perspective

Eric Stevens, from the U.S. Food and Drug Administration, said the GenomeTrakr network is the result of 12 years of work. At the end of 2021, there were 600,000 genomes in the public database, today it is more than 1,000,000 sequences.

“After more than a decade of experience, it is not the sequencing that is the challenge when transitioning to this data, it is how you are going to analyze it, train staff, gain the skills and enable the entire system to utilize it effectively,” he said.  

“Metadata helps to tell a complete picture, without it you have a DNA sequence, which can only tell you some stuff. Contextual data gives that data life, it tells you where those bacteria came from, how they were living and when we are starting to think about the interventions we can make, we need that information to understand the complete picture.

“For us, the best use is making it open data available to anyone because somebody maybe interested in Salmonella, somebody else in E. coli and sometimes they overlap with interventions you can make for preventive controls and reducing contamination.”

Stevens said once data is in the database, a variety of things can be looked at.

“When you start thinking of the global food chain you can think where do we need more data from and start doing some projects to tackle those problems to better understand how food becomes contaminated in the first place. You wouldn’t know any of this unless you had the data that can help point the way,” he said.

“GenomeTrakr is responsible for almost 100,000 food and environmental isolates to tell a more complete picture of linking clinical isolates back to their sources, so we can not only respond to foodborne outbreaks but then try to prevent them. When you start looking at where your sources of food and environmental isolates linked to human illnesses come from, you can start doing source attribution and more preventive targeting. If we can get to a point where we can upload data in real time we can start to make those connections as early as possible to get a contaminated product out of the market.”

It can also help in moving from responding to outbreaks to trying to prevent contamination occurring.

“In a facility for example, you are not going to do WGS to identify a pathogen, you can do a quick culture method to see presence or absence. But if you have a facility that is concerned about whether they have a resident pathogen you would 100 percent like this information from WGS. You could expand that further to farms and potential water sources,” said Stevens.  

“When you start doing projects in different parts of the world you start understanding that everybody has issues that maybe aren’t issues for you. We’ve done a lot of work in Latin America and the big problem in getting started in sequencing is availability of reagents. We hear it costs five to seven times more than what we pay. When we talk about this being utilized by the world we have to start focusing on those issues that are going to make the most impact.”

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 By 2019 the program was already estimated at providing nearly $500 million in annual health benefits, compared to an approximately $22 million investment by public health agencies. 

The FDA created the WGS Network in 2013, as a tool to improve food safety. The network has grown to include federal, state, hospital and other labs in the United States and other nations that use WGS for pathogen identification.

 The FDA study presents an analysis of whole genome source tracking implementation on potential food contamination and related illnesses through theoretical, empirical and cost benefit analyses. Specifically, the study examined FDA regulated food commodity outbreaks from 1999 through 2019 and looked at the effect of the National Center for Biotechnology Information (NCBI) Pathogen detection program.

 The results of the study also suggest that each additional 1,000 WGS isolates added to the public NCBI database is associated with a reduction of about 6 illnesses per WGS pathogen, per year.  

 Even under conservative assumptions, the program likely broke even in its second year of implementation and could produce increasing public health benefits as the GenomeTrakr network matures, according to officials.

Currently, the FDA continues to facilitate opportunities to speed the adoption of WGS by public and private laboratories. WGS and the GenomeTrakr also have roles in advancing the goals set out in the FDA’s New Era of Smarter Food Safety Blueprint, which include facilitating opportunities to speed the sequencing of pathogens.

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Such a system is a platform for storing whole genome sequencing (WGS) data on the full genomes of investigated microorganisms such as bacteria, viruses and parasites, providing quick characterization and treatment options of such organisms when they are detected in sick patients or food.

In the United States the federal Centers for Disease  Control and Prevention works with states to collect sequences of pathogens in the PulseNet database. It has been credited with helping to detect outbreaks and assisting investigations.

More than 250 scientists and experts from 40 countries met at Nanyang Technological University in June to discuss strategies to combat foodborne disease and food poisoning outbreaks. The 12th meeting of the Global Microbial Identifier (GMI) conference was organized by the NTU Food Technology Centre.

Seize the opportunity
Joergen Schlundt, professor Food Science at Nanyang Technological University Food Technology Centre (NAFTEC), said the GMI suggested such a database be created but it needs political agreement among all countries.

“I think the main takeaway is that a lot of scientists and technical people see a giant opportunity for scientists and countries to work together to build science in this microbiological area with the new technology because this is one of the first times where if we connect all our data together in one or several big databases, researchers all over the world will gain from that,” he told Food Safety News.

“If the system was functioning, public, animal and plant health would benefit because you would end up having a system that could always answer what your microorganism is, what is the name, where it comes from, how you can treat it and maybe also if it is causing foodborne outbreaks.

“It is a huge resource that we could build if we wanted to, technically it is not a big deal, but we need countries to discuss whether it makes sense, whether they want to share their data and whether they want to fund it collectively. Optimal use is dependent on policies and the willingness and ability of countries to share genomic sequences across borders and in real-time.”

Databases on DNA sequences already exist such as those run by the National Center for Biotechnology Information (NCBI) and European Nucleotide Archive (ENA) but Schlundt said these are passive.

“It would be an active system that would give you an answer as soon as you send your sequence. So you have your microorganism, you put it through the sequencer, you get a sequence so four million letters in an excel or another file, you send that off to the machine and five minutes later it will give you the answer, so it is like searching on Google. The answer is the species, subtype and resistance of the microorganism and there could be other information.”

Improve outbreak response
Sharing of sequencing results would allow early detection of emerging threats and rapid identification, investigation, and prevention of national, regional and global disease outbreaks. Equal access and implementation of such sequencing technology between countries could reduce the global burden of disease by enabling real-time surveillance of animal and human diseases and food safety risks.

Schlundt said if most countries take up the idea then there would be an almost perfect standardized real-time surveillance system for diseases.

“It could be there is a foodborne outbreak in a number of different European countries and it is the same Salmonella typhimurium subtype, the system would see the one that is in Berlin is the same strain that is in Marseille and Rome so it can link it together like that. They are starting to do something like this in the U.S. with their system so they find many more national outbreaks than before because they used this type of methodology.”

Data privacy and anonymity could be protected as there are already ways to separate metadata from the four million letters that is the sequence.

“In that system where you can go in and look you cannot see this strain number, or any details about the patient, or the animal or food this comes from. That would be hidden. You would only be able to get that metadata through a special route, for instance if there was an outbreak. So there would be safeguards against privacy concerns in relation to the single patient and so on,” said Schlundt.

Letters sent to agencies worldwide
One of the reasons GMI was founded was to include developing countries in discussions on new techniques and technology.

Schlundt said the organization sent letters in 2018 to 186 countries to push for such a database and got answers back from 15 of them.

“We sent a second round of letters at the beginning of 2019 to 30 countries, the 15 countries that answered us and some other countries we know are interested in this area. From that second round, we have received six or seven replies. They don’t go into any detail but most of them say they agree it is an important issue and there needs to be international discussions about it,” he said.

“We’re hopeful France, Germany or the U.S. might bring it up in connection with G20 Health. If you want to have big movement in things like this you need to get nation states involved. The whole thing is predicated upon an agreement that you want to share this data and that has to be an inter-governmental discussion, it cannot be only between scientists.”

GMI will keep pushing on the issue through the “friendly” countries and international organizations, said Schlundt but while he would like it to happen in the next few years it may take decades.

“In my opinion, international organizations should take their own initiative on this. The World Health Organization (WHO) especially but also the Food and Agriculture Organization (FAO). They are agreeing with us but they are not actively pursuing this. We have to rely on member states that might be interested in this as a major potential for public health and all microbiology.”

GMI 13 will take place June 8 to 11, 2020 in Vancouver, Canada.

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Researchers found while some countries lack the capacity to collect and analyse the data generated from whole genome sequencing (WGS), the main technical gap in most developing nations is in data interpretation using bioinformatics. The study was published in the Foodborne Pathogens and Disease journal.

A scoping review and a focus group session helped understand the use of WGS for foodborne disease surveillance and food monitoring globally and identify limitations for developing countries in adopting WGS for their food control systems. Experts from Ghana, Iran, the Philippines, Sudan, Tanzania, and Thailand were part of the focus group.

Underreporting of foodborne diseases and microbial contamination cases is common in developed and developing countries; however, the extremely low number of outbreaks reported by developing nations likely does not reflect the actual situation in these countries.

Differences between developed and developing nations
Results showed some developed nations routinely use WGS in food surveillance systems resulting in more precise understanding of outbreak causes. In developing nations, knowledge of WGS exists in the academic and research sectors; however, there is limited understanding at government level on the usefulness of it for food safety regulatory activities.

Gaps in knowledge and capacities between developed and developing nations regarding use of WGS will likely introduce an inequality in international food trade. International organizations and countries already proficient in WGS have significant roles in assisting developing nations to fully benefit from the technology and its applications in food safety management, said researchers.

The scoping review identified that more than 10 countries are using WGS for regulatory purposes compared to four that used it for food safety management in 2016. However, it also found these additional countries are developed nations. There were no data that any developing country had started using WGS in the government system and this was confirmed by the focus group.

All focus group participants said they are ready to use the technology to contribute to their national food control systems, but lack of commitment at higher levels of government has been a barrier to use.

While focus group members said well-equipped in-country labs are available for analysis of isolates, WGS needs to be conducted routinely if it is used as the basis for food surveillance systems, according to the study.

Is WGS cost-effective?
Some research institutes, such as the Pasteur Institute in France, have conducted WGS-related studies in developing countries to promote the technology. Before introducing WGS, it is essential for countries to have a systematic mechanism to collect isolates and metadata from clinical and food/environment samples.

“Assuming that it is already costly for developing countries to fully implement traditional methodologies to detect foodborne outbreaks, it is necessary to question whether incorporating WGS would be cost-effective in improving outbreak detection/reporting situations,” according to the study.

Universality of WGS has a benefit in efficiency and cost-per-sample has been decreasing. Although it could contribute to cost savings for identification of foodborne pathogens, overall cost may still be high as WGS requires relevant infrastructures and functioning equipment/personnel.

As of July 2018, between 11,000 and 18,000 scientific articles discuss the use of genomic technologies for identification, investigation, and/or prevention of foodborne disease outbreaks.

Case studies from the United States, Denmark, and England have shown how WGS can be incorporated into the food safety regulatory system for outbreak investigations with benefits, such as specificity, allowing improved case definition to enhance outbreak management; sensitivity, enabling linkage of apparently sporadic diseases occurring under the outbreak surveillance radar; and precision, determining the root cause of complex outbreaks.

Introduction of WGS in Kenya drew attention of decision makers to the importance of food safety and provided the basis for development of a national food control system. The Kenya Medical Research Institute introduced WGS to sequence strains from selected pathogens from clinical samples and the government was able to map disease hotspots to revise existing systems and identify high-risk foods.

Databases and platforms for WGS-data sharing include the U.S. FDA GenomeTrakr, European Nucleotide Archive, and deoxyribonucleic acid (DNA) Data Bank of Japan. Some initiatives, such as the Global Microbial Identifier (GMI), are trying to boost global data sharing.

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Editor’s note: This column by FDA’s Steven Musser and Eric L. Stevens was originally published on the agency’s blog.

FDA is laying the foundation for the use of whole genome sequencing (WGS) to protect consumers from foodborne illness in countries all over the world.

We recently traveled to Geneva to join a meeting of the Codex Alimentarius Commission, an international organization that works to protect consumer health and promote fair practices in food trade. There, we participated in a panel discussion on how best to share WGS globally to fight foodborne illnesses and elicit support from the world’s governments in this effort.

There’s no time to waste.

The World Health Organization (WHO) estimates that as many as 600 million people in the world fall ill every year after eating contaminated food and 420,000 of these people die.

FDA has been a leader in the use of WGS to identify the nature and source of bacteria that contaminate food and cause outbreaks of foodborne disease. By sequencing the chemical building blocks that make up the DNA of these pathogens, WGS reveals their genetic fingerprint, offering clues about their geographic source, antimicrobial resistance, and other key markers that help scientists respond more effectively to food contamination, preventing illnesses.

In the last few years, WGS has fundamentally changed the way that we detect, identify and monitor microbiological food safety hazards within the United States. This technology is rapid, precise, cost-effective, easy-to-use, and can be applied universally to all foodborne pathogens.

The GenomeTrakr is an international network of laboratories sequencing microbial foodborne pathogens and uploading the data to a common public database in real time.

The goal of GenomeTrakr is simple: to assemble a large, freely accessible database of genetic sequence information and accompanying metadata, e.g. geographic location and date, from food, environmental and human clinical isolates of bacterial pathogens. This information can be used by scientists on the trail of disease-causing bacteria, unmasking each contaminant’s identity and offering clues to where and how it got into the food supply.

Recently, public health institutions, including FDA, WHO and FAO (the Food and Agriculture Organization of the United Nations), have been working to raise awareness about the importance of WGS and the benefits of sharing both sequence information and metadata.

In Geneva we talked about how this technology is being utilized in some countries to support their foodborne disease surveillance system or outbreak investigation activities. We all understand that food is a global commodity, with complex shipping and distribution networks that can easily result in contaminated food being sold in more than one country. Thus, the most effective use of WGS in foodborne disease surveillance requires coordination and collaboration, and the panel emphasized the global health benefit of every country sharing their data. One approach would be sharing the data through FDA’s GenomeTrakr.

We are certain that the public health benefit of WGS will only become more evident with every foodborne pathogen’s genomic sequence that is shared. Already, GenomeTrakr has collected more than 142,000 sequenced strains, has made them freely available to anyone in the world, and continues to demonstrate how a large database of this kind is being used effectively for food safety within the United States, and throughout the world.

As the food supply becomes increasingly global, the use of WGS in a way that crosses national borders will ultimately help keep us all safe from foodborne illness.

About the authors: Steven Musser, Ph.D., is the Deputy Director for Scientific Operations in FDA’s Center for Food Safety and Applied Nutrition (CFSAN). Eric L. Stevens, Ph.D., is a Staff Fellow in FDA’s Division of Microbiology at CFSAN.

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• determine which illnesses are part of an outbreak and which are not;
• determine which ingredient in a multi-ingredient food is responsible for the outbreak;
• differentiate sources of contamination, even within the same outbreak; and
• link small numbers of illnesses, including geographically diverse illnesses occurring across multiple states, that might not otherwise have been identified as a common outbreak.

Once a bacterium is sequenced, the generic information can be used indefinitely. The “evidence” doesn’t get used up, and scientists can continue to match strains from years past. Brown says the FDA is pushing the whole genome sequencing technology out to the frontlines of food safety “as quickly and completely as it can.” What does this mean for future tracking of food-borne illnesses? Industry is starting to recognize and use whole genome sequencing as a way to monitor ingredient supplies, determine the effectiveness of preventive and sanitary controls, and determine the persistence of pathogens within the factory environment, Brown says. If a food production facility finds a pathogen during testing, it can use the GenomeTrakr database to help identify the source of bacterial contamination and take whatever corrective steps are necessary to make sure the food it produces is safe to eat. Allard adds that the FDA is working with like-minded food industry specialists who are examining the value of whole genome sequencing for food safety as they work to produce the safest food possible. “We’re helping to raise the bar for food safety around the world,” Brown says. (To sign up for a free subscription to Food Safety News, click here.)