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.
目前美国FDA正在广泛使用全基因组测序（WGS）技术，用于更好的了解那些食源性病原体，包括查明污染食品和引起疾病暴发的微生物的特性和来源。
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.
WGS从根本上揭示了病原体的遗传密码，通过化学测序模块展示其DNA。
举个例子，它最近被用来帮助我们从一些干酪样品中寻找与3月初爆发的单核细胞增生李斯特氏菌污染事件相关的基因图谱。
The FDA has been a leader in spreading the use of this technology in government labs at the state, federal, and international levels.
In 2012, the agency started GenomeTrakr, a network of laboratories that use WGS to identify pathogens. The sequence data are housed in a publically available database and the network now includes FDA’s federal and state public health partners.
美国食品和药品管理局(FDA)一直是在国家、联邦和国际各级政府实验室推广这种技术的领导者。
2012年，该机构启动了GenomeTrakr，这是一个实验室网络，使用WGS来识别病原体。数据被安置在一个网络共享的数据库中，方便包括FDA的各个联邦和州的公共卫生合作伙伴共享。
Initially, the GenomeTrakr network consisted of 10 FDA and four state laboratories. Since 2012, the network has seen rapid growth to its current level of more than 60 domestic and international laboratories. Recently, FDA included three more laboratories across the country and has been instrumental in developing additional software tools to augment analysis of WGS data by GenomeTrakr partners. And the agency is now turning its attention to the power of WGS globally, working with the World Health Organization (WHO) and the United Nations’ Food and Agriculture Organization (FAO) to make this technology available to developing nations.
最初，GenomeTrakr网络由10个FDA实验室和4个洲际实验室组成。自2012年以来，该网络已迅速增长到目前的60多家国内外实验室。最近，FDA在全国范围内又增加了3个实验室，并开发了更多的软件工具，以增强GenomeTrakr合作伙伴对WGS数据的分析能力。该机构现在正将注意力转向全球卫生组织的力量，与世界卫生组织(世卫组织)和联合国粮食和农业组织(粮农组织)合作，向发展中国家提供这项技术。
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. To hear their complete remarks, listen to this podcast.
美国食品和药物管理局的食品安全和应用营养中心(CFSAN) 微生物部门主任 埃里克?布朗博士和,生物医学研究中心的基因组学高级服务官 马克?阿拉德博士 讨论如何使用WGS技术保护消费者食用安全无污染的食品。
Q & A
Q: How is whole genome sequencing used by the FDA today?
问：FDA现今如何使用全基因组测序技术？
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.
布朗：从2012年到2013年，WGS技术一直在被使用，以帮助保护食品的供应。我们使用它的方式是加强对暴发疾病的调查，用更好更准确的信息来支持风险监测，因为WGS技术可以追溯到食物供应中的污染源头。我们用它来指导我们的执法部门执行食品安全法规，并帮助相关公司识别其设备中的安全问题。
这两种情况的目标都是将受污染的食物从食品供应链中排除出去。
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?
问：对于那些不熟悉这项技术的人来说，这本质上是细菌的遗传基因吗?这是正确的描述方式吗?
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.
阿拉德：是的，这是一种细菌的全基因组测序技术。
（基因组是生物体的一整套DNA，包括它所有的基因）好比大家熟悉的人类基因组，它拥有人类细胞中所有的遗传数据，这在细菌中是一样的，尽管它们的基因组更少。你对一个细菌的整个基因组进行分析时，你就会有完整的基因组成序列。这为细菌的鉴定提供了明确的区分能力。
Q: So would you say it is a faster and more clear way to identify bacteria involved in a foodborne illness?
问：所以你说这是一个更快、更明确的方式确定是什么细菌导致食源性疾病吗？
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.
布朗：是的，我想这句话最重要的部分是明确的。也就是说，我们可以看到受污染的食物的细菌基因组是否与食源性疾病患者的基因组相匹配。尽管食物可能来自全球任何地方，但最终结果是前所未有的准确。追踪进口食品的污染一直是一个巨大的挑战，因为有这么多的食物可以从任何地方过来。但是由于细菌在特定地理环境下产生的遗传特性，现在可以通过测序获得其来源的提示。
因此，我们利用这种新技术，可以迅速将污染定位到世界的特定地区，对我们现场核查工作非常有帮助。
Q: Where is this technology in its development? Will it be advancing from here?
问：这项技术的未来发展是什么？它会提高吗？
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.
阿拉德：这项技术还在继续发展，我们实验室的一个任务就是研发新的基因组测序仪，看看它们是否真的更快、更好、更便宜，或者更容易移动。我们正在研究一些非常小的测序器，可以放进口袋里。我们可以在一个公文包里有一个实验室，可以到消费者那里做实地测试。这是未来的愿景，需要时间来测试设备，但同时你必须决定何时让你开始使用它。
Q: What has been the FDA’s role in spreading this technology, starting with state and federal labs across the country?
问： FDA在从全国各地的州和联邦实验室开始推广这项技术的过程中扮演了什么角色?
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.
布朗：GenomeTrakr是我们在2012年末发起的，首先是在全国范围内，现在在国际上推广。我们与我们的联邦同行合作，包括国家卫生研究院(NIH)的国家生物技术信息中心(NCBI)，在那里数据被保存和管理。我们已经与疾病控制和预防中心（CDC）合作，他们正在提供临床数据。在美国，我们的合作伙伴不断地从PulseNet病毒中获取细菌序列数据。美国农业部食品安全与检验服务部(Department of Agriculture ' s Food Safety and Inspection Service)，他们正在从他们监管的食品(如肉类和家禽)上上传数据。
所以从2012年末开始，自这个概念诞生起，我们可以在州和联邦的实验室里分发desk - top测序仪，这样他们就可以在检查、分析食物和食品制造设施的环境取样时，对收集到的食源性病原体进行分析。我们开始看到，一旦爆发或污染事件发生，我们很快就能迅速找到污染来源。所以现在我们要求合作伙伴都把他们的细菌序列上传到国家卫生研究院的数据库，这是公开的，很容易获得的。监管机构、公共卫生专家、消费者和行业机构也可实时查看数据。这种开放是网络的一大创新，允许每个人在任何时候都能访问数据。
Q: How is the technology being shared globally?
问：技术是如何被全球共享？
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.
阿拉德：我们为在发展中国家提供医疗保健的世界卫生组织(世卫组织)实验室提供资助，在布宜诺斯艾利斯的Malbran研究所建立一个试点项目，将测序技术推广到更多的实验室。我们的目标是在世界上许多地区看到基因组实验室。我们还与世卫组织和联合国粮食及农业组织(粮农组织)合作，为各国应何时开始参与基因组学提供指导和最好的应用。
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.
布朗：我们很高兴能够支持WHO，联合国粮农组织和世界动物卫生组织（世界卫生组织）在他们的努力下可以学习如何最好地将整个基因组测序部署到全球发展和更发达的国家，不仅仅是在美国或西方欧洲。我们从世界各地获得食物，我们需要对世界上所有食物来源的地方进行良好的监测和溯源。
Q: With other federal agencies doing whole genome sequencing, how do you coordinate your efforts?
问:与其他联邦机构做全基因组测序，你如何协调你的工作?
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.
布朗：现在测序已经渗透到所有主要的公共卫生机构所以协调起来很容易--我们的机构之间实际上有正式的指导委员会，包括管理层和一些高层领导来帮助制定政策决定谁将负责，我们将如何分享这些数据，把这些信息传递给公众，而不仅仅是数据库。当你有一个数据库，里面有大量来自疾病控制中心的病人的临床数据，并将这些数据与来自食品和药物管理局和FSIS的来自农场、工厂、设施和受污染食品的环境和食物数据结合在一起，你就有了真正成功的秘诀。
Q: What are other uses for WGS beyond food safety?
问：对WGS在食品安全以外的其他方面的用途是什么？
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.
阿拉德：还有FDA其他项目可以从该技术中获益。例如，做为FDA的工作部分在国家抗生素耐药性监控系统的监控中心，我们正在和FDA的兽药检测中心合作，使用WGS监测细菌对抗生素的耐药性。所以，我们每天正在收集比对的不只是食源性细菌。美国国立卫生研究院获得授权比对任何影响人类健康的病原体。
因此，用于食品安全的基本工具现在也被用于监测全球人类传染病。
Q: What’s ahead in 2017 for WGS?
问：2017 WGS的未来是什么？
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.
布朗：最重要的是，我们要继续服务我们的消费者使之免受食品污染和把整个基因组测序带到检测前线使用，比如现场工作人员和我们在疫情应对部门的人，这样他们就可以在他们的桌面上拥有这些工具。从我的角度来看，很高兴看到全基因组测序可以作为一个单一的微生物工作流程工具，取代了那些花费了大量的金钱和很长的时间的单独测试。如果我们想知道病原体的毒性，如果我们想知道它的血清型，如果我们想知道它的耐药性，所有这些都需要独立测试而且很昂贵。但是基因组学提供了一个途径，一个工作流程，我们可以告诉你这个序列，如果是一个细菌，它的抗药性的基因，它有什么毒性因子和血清型(不同的变异)，以及我们应该如何对它进行分类。所有这些都可以用计算工具快速完成。
Q: What is the most important thing for consumers to know about this technology and how it affects them?
问：对消费者来说了解这项技术的重要性是什么？以及它是如何影响他们的？
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.
布朗：有一件事我们想告诉公众的是，我们正在利用这一技术来进一步确保和提高您所认可的安全性。未来，如果有一个（食品污染）事件，我们会从食品供应链中迅速发现，并保证我们的消费者是尽可能安全的。
例如，在2010，在全国最大的城市之一爆发的大规模shell-egg。我们不在现场，但在爆发后做的回顾性分析表明，全基因组测序不仅可以发现了两个农场把受污染的鸡蛋流入食物供应链，而且可以区分疾病来自哪些农场。
那时我们知道我们手中掌握了什么力量了！
