Three months ago, few of us gave much thought to the threat posed by coronavirus. But being prepared as a nation to respond to potential biological threats is part of PNNL’s mission. As we are all learning, infectious disease can be a threat to the security of the nation. Scientists at PNNL are working along several lines of research to combat emerging viruses like the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 disease. PNNL scientists have been leading the national and international conversation on a number of important fronts related to biological defense, risk reduction, and prevention strategies. As part of that effort, biodefense expert Kristin Omberg and biochemist Katrina Waters talked about research on biological threats at the annual meeting of the American Association for the Advancement of Science in Seattle.
Pods of Science | Episode 7 | How to Stay Safe from Biothreats
JW: Welcome. I’m your host, Jess Wisse. Today I want to share something a little different with you.
Let me introduce you to my friend Nick Hennen. He’ll be co-hosting of Pods of Science for us today. This episode was recorded live at the 2020 AAAS meeting.
Take it away, Nick.
NH: I’m Nick Hennen, Media Relations Advisor for the Pacific Northwest National Laboratory. And I’m here today with Katrina Waters who represents the Biological Division of our laboratory and Kristin Omberg, representing Chemical and Biosignatures Science at PNNL.
Today we’ll talk about how increasing globalization is fueling the spread of novel natural biological threats, and advances in biotechnology that could be used to engineer new threats are constantly emerging. Frameworks for assessing unknown biological agents can enable rapid risk profiling and mitigation. This includes applying novel data analysis methods to host-pathogen interaction data to help predict, at early exposure times, whether a patient can be expected to recover from a disease such as Ebola without major interventions.
Please introduce yourself and describe what you do at PNNL and why you do it.
KW: Hi. So I’m Katrina Waters. I’m a Biochemist and Laboratory Fellow at PNNL. I manage the basic science organization for biology at the lab and work as a researcher in the area of infectious disease and public health. So the reason that I do it is that I get to work with really awesome people who contribute in a lot of different ways and it’s just been a lot of fun.
KO: I’m Kristin Omberg. I am the manager of the Chemical and Biological Signatures Group at PNNL which is in the National Security Directorate. I’m a chemist by training and in 1999 I was doing a post-doc at Los Alamos National Laboratory, which is a sister laboratory. And my post-doc didn’t go very well so I started looking for jobs and I got a couple of offers.
One was in accelerator production of Tritium and one was in biothreats—so, looking at preparing a system to detect a biological threat in the future. And I talked to my father who happens to be a Nuclear Engineer at PNNL and he said, “I feel kind of good about that counter terrorism stuff.” So I took the job and I started the job in December of 2000.
NH: Oh, wow. That’s wonderful.
KO: And since then, the 2001 anthrax attacks on the United States, it’s just been a constant sprint.
NH: Thanks, Dad.
KO: Yeah, thanks, Dad.
NH: Tell us briefly about the nature of biothreats and what does that word mean?
KO: That is a really interesting question because the way we use biothreat has actually changed in all of our lifetimes. A lot of people don’t realize that up until 1969, the United States had a bioweapons program. So they weaponized Bacillus anthracis, Yersinia pestis and other human pathogens for use in war. The former Soviet Union also had a biological weapons program and they weaponized many of the same pathogens. So at that time biothreat was used to describe a deliberate act of war by a state program using a weaponized pathogen.
In 1975, the Biological Weapons Convention came into force and we became less concerned about a state program, both the Soviet Union and the United States ratified that convention. In the 1990s though, we started becoming concerned about terrorist groups. We started worrying about terrorist groups overseas who started using biological agents, and then we saw that in 2001. So we started being concerned about the biothreat by a state actor, terrorist, or a lone actor.
But since 2001, we’ve so many outbreaks of diseases that are zoonotic diseases that jump from animals to humans. We’ve had avian influenza, we’ve seen a couple of rounds of Ebola, SARS, MERS and the current coronavirus. And they’ve all demonstrated that they can really be equally devastating in a globalized world. So, in the last decade we’ve started to worry about emerging disease, as well as the health of other populations, so the populations of animals and plants that share our world. Because the health of those populations also impact human health.
And we’ve also become more concerned about lab accidents. If we had an accident and if a pathogen were to escape from a laboratory, it could potentially become disruptive. So, in 2018, the U.S. government released the biodefense strategy and they define biological threats as natural, accidental, or deliberate outbreaks of disease, whether in the human, animal, or plant population. So it’s a much more broad definition that we have today that incorporates natural, accidental events and deliberate events, as well as all the populations of the world.
NH: Thank you. So I want to talk about outbreaks. What makes an outbreak happen, anyway? Is there a typical timeline that happens with an outbreak? Do most pretty much die off eventually? Or are they here to stay?
KW: Yeah, that’s a really great question. So predicting when an outbreak will emerge, or what will emerge is a really complicated task. There are a lot of different factors that play into that, dozens of factors as we heard at one of the sessions yesterday at AAAS on infectious disease forecasting. Pathogens adapt to their changing environment. So right now we have climate change, we have changes in farming practices, migrations of populations closer to animal species, migrations of species closer to humans. And all of this human to other species, or animal vector contact increases the chances for the emergence of a pathogen to jump from their host species to a new host species.
So when an outbreak happens, typically what that means is that not only does a primary human host get infected, but that pathogen changes to become human to human transmissible. So as we’ve seen with the current coronavirus, once that happened it spread pretty rapidly, that human to human transmission. The timelines can really vary.
So one of the things we saw in our session yesterday was the Dengue virus outbreaks that happen in Puerto Rico tend to be very seasonal based on weather changes, whereas Ebola outbreaks that came from local animal populations tend to have really irregular frequency but they’ve been increasing in frequency since the 1970s.
So I think outbreaks will continue to happen but predicting them is really more of a challenge of us understanding where they come from, what is causing that transmission and then how quickly they die off is influenced by a lot of different factors. Some of those things could be the nature of the pathogen itself, how infectious it is or how lethal it is to the human host. How we as a community or response agencies respond to that in terms of medications available, or vaccines, quarantine efforts.
And then finally, the other thing is really is the natural reservoir of the pathogen. Is it existing in a reservoir where people are going to continue to get reinfected no matter what we do? All of those things will influence the timeline for an outbreak.
NH: That’s quite complex, isn’t it? Is there anything very different or surprising about the current outbreak compared to these past outbreaks?
KO: The thing I’ve been surprised about, and there’s been a nice focus on it at this meeting, is that we’re getting data in a lot faster than what we typically see. AAAS pulled together a nice session at the beginning of the meeting where they discussed, in part, some of the genomic sequence data that’s been collected and disseminated. And they’ve done a nice analysis of what that tells us about animal to human vs human to human transmission.
I don’t ever remember having this many sequences available in such a short time following the identification of a disease. It really speaks to how ubiquitous sequencing machines have become. They have sequencers that can actually plug into a laptop and we’re deploying those all over the world. So people can sequence more than they ever could before.
The other thing that I’m seeing that’s really remarkable is really the international effort to control the spread has been a lot more proactive and thorough that we’ve seen in the past. I was astonished, although in a good way, for example when Starbucks shut down stores in China. One of the big things that drives person to person transmission is the number of contacts a person has throughout the day. So a place like a Starbucks, a place like a school that's why you often see these public spaces, like a market for example in the current one, that's why you often see these public spaces associated with epidemics. It's because that's where people get together and that's where they end up sharing germs.
NH: What’s tricky about identifying patients quickly during an outbreak? Walk us through what typically happens.
KW: One of the things that's really tricky about these, about many of these outbreaks, is that the symptoms that people come down with sound a lot like the flu. Or a common cold, right? So even during the Ebola outbreak, some of the initial symptoms were fever, fatigue, body aches, chills, things that would normally be seen during any kind of similar endemic infection that people are accustomed to. And so right now, for example with coronavirus outbreak in the middle flu season, the symptoms are very similar to influenza. And so it's hard for the doctors to really notice, or for even the patients themselves to notice there's something different going on with them from what they would see in a typical flu season.
So in the case of a doctor’s office or emergency room, really what's going to happen is somebody's going to walk in, they're going to say I have these symptoms, I have breathing problems, and the doctors are really going to be looking at the symptoms to try to determine what is there, but it could take hours if not days for the results of the tests that they need to find out if they're infected with something, if they have asthma, do they have COPD? Do they have pneumonia? What is it really that you're trying to treat?
And many times what happens is that in the middle of the identification process, they're still focusing on getting that patient to breathe. And that will often include the administration of bronchodilators, steroids, or in really severe cases, putting people on a ventilator. And all of those treatments can drive the viral infection much deeper into the lung and make it worse.
And so really, the need is for rapid diagnosis that can provide clues to physicians about how to treat a patient based on their physiology and the symptoms. While in the process we're trying to identify what caused it, but really be able to treat them appropriately right out of the gate.
NH: I want to talk about biological threats. Tell me a little bit, about I definitely want to talk about biological agents. Can you tell me a bit about how are emerging biological agents or potential threats identified today?
KO: In the strict deliberate threat space, we identify them based on a list that currently stands at 67 agents that were defined back in 1997 originally as a list of things that we wanted to keep out of the hands of terrorists or lone actors.
NH: So 67?
KO: 67 today. It was actually 47 when they originally defined it, but there have been diseases that have been added to it like pandemic influenza. So we have that list of things and in many cases we identify it through either an environmental sample if we can get a sample of it or a clinical case. And the clinical cases are the same problem that Katrina described.
I actually had a friend when I lived in New Mexico who got plague. He got it golfing. Plague is endemic in the southwest part of the United States. When he first came in, plague manifests as a respiratory problem, so he came in and they thought he had a bad cold. It wasn't flu season fortunately, but they sent him home to rest. And it progressively got worse, so then they started testing him for other respiratory pathogens. But it took about two weeks before they got around to using the tests for plague because plague looks a lot like a lot of other respiratory diseases. So in many cases what we do is we try our diagnostics to see if we can find something in a clinical case. If we can't identify what it is based on things we've already identified, we can do DNA sequencing and that is one of the things we're seeing coming out of the current outbreak is a lot of sequences of this corona virus.
If we have sequences available we can also do something called real-time polymerase chain reaction or RT-PCR, which is a DNA matching technique. Unfortunately, whether you're sequencing or whether you're doing RT-PCR, both of those techniques rely on matching the nucleic acid sequence to a known database of sequences. So we are really primarily looking for things that we've already seen before. When we have something that hasn't been seen before, if it hasn't been entered into the database, we can say that it's close to something in many cases, but we can't say exactly what it is. And even when you can't identify that sequence the nucleic acid tells you what the microbe is capable of doing. But it doesn't always tell you what it is doing.
Microbes adapt to their environment. I like to actually think of them like my cats. My cats have a lot of functions they could do, but they choose not to because they don't have to. And so microbes adapt and they use the functions that they need to survive and they turn off the ones that they don't. So when you have a sequence, it may not tell you, for example what antibiotics you would use to treat something, it won't tell you often times how lethal it might be. It only will have limited applicability to determining person-to-person transmissibility and usually you just tell that by how quickly it mutates.
So for example, with the current outbreak of corona virus the first DNA sequences didn't tell us if it was transmitting from human to human. It was only when we got enough clinical cases and enough sequences that we were able to compare the similarity and say it was human to human transmission. And that's true of all new diseases. And in 2020 we have all these data sharing techniques, we have a lot more data gathering techniques but in a lot of cases we still just wait and watch a disease play out in a human population.
NH: What are some of the tools you're using to address these challenges?
KW: So one of the things we're trying to do at the Pacific Northwest National Laboratory is to focus more on the host response and the actual biological response of the pathogen when it gets into a human host. And we can use the gene sequencing and we can use the transcribed RNA that comes out of those systems to study them.
But we're also focusing at PNNL on the development of advanced mass spectrometry measurement approaches so that we can look at the proteins and the small molecules and the lipids within a biological system and see how are they functionally responding, these pathogens in their new environment and how is the host responding to that pathogen so that we can get a better sense of what is the severity of that infection. What does the disease actually look like physiologically within the human? And even give us clues for how to treat that.
If we know that there's a specific kind of metabolic shutdown is there a drug, or a specific kind of treatment that can focus on the treatment of that while we went through the process that Kristin just described for identifying, developing a vaccine—figuring out what antibiotics or antivirals might be effective—we can really focus more on that treatment of the physiological condition of the human.
NH: That's great. Are such measurements brand new? Or have they been used before?
KW: So they have been used before and at PNNL we've been developing these technologies for several decades, but it's really only been in the recent history that they've become more and more sensitive. Now we can identify more molecules in smaller samples with greater quantitative precision to know what is there, how much of it is there, and whether it's really specific for one condition or another.
And so in addition to the mass spectrometry for the identification, we also are developing a lot of computational approaches to make sense of all of that data so that we know with what precision we've done the identification and made that quantitative measurement. And so really it's the advances in the past few years that have given us the ability to get much better precision.
And one of the things we talked about at our AAAS session on Friday was how we've applied this to the Ebola outbreak from 2014 and we could identify a set of biomolecules that were really indicative of the survival of patients that came down with the infections. And we've applied similar approaches to study cancer from military populations to get a sense of early cancer diagnosis and treatment, as well as to study the human microbiome and its influence on human health.
NH: Is this as simple as measuring one or two things in a patient's blood?
KW: That would be great, but it's really unlikely. So the reality is that there are hundreds of factors that contribute to disease and they might vary from person to person. So the genetic makeup of our population is so diverse that our individual susceptibilities to things is very different, and how they express physiologically.
So we're working to get the needed measurements down to just a handful so that it could be used realistically in a clinical diagnostic. And at the same time, allow for an accurate prediction of somebody's risk or how you would want to treat them. And one of the really key tools that we have that we're applying to this is machine learning. So machine learning really helps us apply that to the big data problem, the complexity of the data that we collect and the huge amounts of data that we accumulate to use machine learning to help us identify those factors that are the most predictive in combination to be used in a clinical assay.
NH: And what would you say is the biggest need right now in our response to an emerging bio threat?
KO: I think there are two needs right now and one is an immediate need and one's a longer-term need. Right now, we need clear information and we need it as early as possible. That was one of the subjects that was brought up at the AAAS meeting in the session on coronavirus was the difficulty of getting clear, high-quality information out. Particularly when there is a lot of information coming out that is sensationalist, or only partially true. But in the longer run, I think what we really need is better science. And we're working on that science but it's going to take a little while to get there.
What we really need is we need to apply the science techniques that we have developed over the last ten years, like the ones that Katrina talked about, like artificial intelligence, to try to figure out if we can do something while we're waiting around to identify a disease. So instead of asking, as was the case with my friend with plague, what does he have and then how will we treat it can we really get the right treatment first while we're figuring out what someone has. So can we understand what's going on with the host? Can we understand more about the pathogen without having to be able to match the DNA sequence?
I think we can. I think it's not very far away right now. I think we couldn't have done it back in the 1970s when we stopped our biological weapons programs, but I think that we have the science now that in the next couple of decades we will be able to really be proactive in treating the disease as well as identifying it.
NH: It's exciting. What can people listening to this podcast right now do to protect themselves from bio threats? I mean or do they even need to protect themselves? Should they be concerned?
KW: So I think for the general population they don't need to be concerned about bio threats from a deliberate release. But when we think about these natural emerging agents that will continue to come up, the single most important thing people can do on a day-to-day basis is washing their hands. It is the most effective way of preventing people catching, as well as spreading, infections of any kind.
The second thing people can do is get vaccines when they are available. People have forgotten that at the turn of the century 6,000 people died every year from measles. And vaccines really are a miracle of modern medicine as they’ve been applied, and childhood mortality rates have dropped from greater than 20% when before childhood vaccines were available in the 60s, to less than 5% today. And deaths attributed to childhood diseases have dropped by 99%.
And so what people can do is get those vaccines that are available, including the influenza vaccine because even if they get the strains wrong it will often result in a less severe infection for the people who've had the vaccine. And particularly for the young, or for the older and compromised immune systems, getting influenza can be very, very serious or deadly. And so getting the vaccines where available is very important.
KO: I think there's an interesting risk perception issue when we have something spectacular in the news, and there's an interesting risk perception for issue with the biological threat. While I personally believe that those are all very important, I believe that we lose perspective on the fact that between thirty and forty thousand people every single year die of flu in the United States.
I was very proud of that recently, I tell my daughter that every single year when I'm trying to convince her that the flu vaccine is worth it and when some of her friends got upset the other day about coronavirus in her class my daughter's spouted up with, “Every year 30 to 40 thousand people in the U.S. die from the flu!”
NH: She remembered it!
KO: So proud. But we tend to think that these things or measles because they're more commonplace are not as serious, but they are. And in many cases the things that we use to protect ourselves against influenza, like handwashing, and really good sanitation, and hygiene practices. And I always tell my family to make sure you get a good night's sleep and you're eating your vegetables and you have a generally good health system.
NH: Yeah and that's definitely an important thing to take care of your body, to eat right, wash your hands. It’s a defense against everything. Right well this has been really interesting. Thank you both so much for being a part of Pods of Science!
KW: You're very welcome.
JW:Thanks for listening to Pods of Science. Want to learn more? Follow us on social media at PNNLab. We're on Twitter, Instagram, Facebook, and LinkedIn. You can also visit our website at pnnl.gov. Thanks for listening.