In the fight against COVID-19

In just a few short months, COVID-19 has upended daily life around the globe. However, one thing that hasn't changed is the scientific community’s drive to find answers and solutions to big problems. And right now, there's no bigger problem than COVID-19. In this episode, you'll hear from ORNL researchers who are applying their expertise in computational science, advanced manufacturing, data science and neutron science to combat the novel coronavirus.

[THEME MUSIC]

LONNIE LOVE: This is our best moonshot. This is what we were made for addressing these challenging problems that are that are facing our nation.

MARTI HEAD: And it does need all of us from all of the different sectors and all of the different countries working together to tackle it. 

BUDHU BHADURI: If we cannot make a difference today -- I don't know when we will get another opportunity in our lifetime.  

[MUSIC]

JENNY: Hello everyone and welcome to the Sound of Science, the podcast highlighting the voices behind the breakthroughs at Oak Ridge National Laboratory.

MORGAN/JENNY: We’re your hosts, Morgan McCorkle and Jenny Woodbery.

JENNY: In just a few short months, COVID-19 has upended daily life around the globe.

MORGAN: The devastating virus has changed how we work, get our groceries and interact with one another.

JENNY: It’s even changed the way we produce this podcast. Instead of being in our regular recording studio, I’m in my clothes closet.

MORGAN: And I’m in a blanket fort in my living room.

JENNY: However, what it hasn’t changed is the scientific community’s drive to find answers and solutions to big problems. And right now, there’s no bigger problem than COVID-19.

MORGAN: Researchers and scientists in a range of fields are pitching their knowledge and expertise into the fight.

JENNY: At ORNL, projects in computational science, data science, neutron science and advanced manufacturing are underway to help combat the virus as quickly as possible.

MORGAN: Whether it’s through identifying potential drug therapies, understanding the structure of the virus, tracking its transmission, or accelerating the production of life-saving healthcare equipment.

JENNY: Through socially-distant video calls, we talked to a few of the scientists and researchers working on COVID-19 projects at the lab.

[Music transition]

MORGAN: Unlike viruses such as the seasonal flu that we typically face, COVID-19 is completely new to the scene, which means no one has immunity to it and there aren’t any proven therapies to treat it.

JENNY: Discovering new therapeutic treatments can be a very long process, and when you’re dealing with a global pandemic, every second counts.

MORGAN: Scientists are turning to high-performance computing to help accelerate the process.

JENNY: Jeremy Smith is a Governor's Chair at the University of Tennessee and ORNL and directs the Center for Molecular Biophysics. In January, he and his team began using Summit, the world’s fastest supercomputer, to screen drug compounds that might effectively treat the virus.

JEREMY SMITH: A few years ago we developed an interest in early stage drug discovery, that's when people come to you with something called a target, which is normally a protein molecule, a specific protein in the human body, and that they have reasons to suspect if one binds a chemical, a compound to it, that it will modify the behavior of the target in a way that would have interesting physiological effects that could potentially be of relevance in diseases.

MORGAN: Jeremy and his team were interested in simulating targets of the novel coronavirus to see what compounds might bind to it and stop it from infecting host cells.

JENNY: By now, we’ve all seen renderings that depict the virus as spherical with points sticking out of it. Those points are called “spike” proteins.

SMITH: The two types of calculations that we do are simulations of the proteins and then docking compounds to the simulations. So, we started off with the spike protein, which is the first one that's this protein gives the coronavirus its name: the corona. And one of my postdocs quickly did a computational simulation of the spike protein and docked a database of compounds.

MORGAN: The initial simulation screened 8,000 existing compounds and their ability to “dock” or bind with the spike protein. It revealed 77 compounds, ranked in order, that could be potentially effective against the virus. Experimentalists outside of ORNL are now working on testing the compounds Jeremy’s team has identified on the live virus.

JENNY: Because of Summit’s massive compute power, this simulation took hours rather than months on a traditional computer.

SMITH: We’ve now done that for 10 different targets on the virus. We’ve done these simulation models and used these simulation models to dock millions of compounds and we’re now gearing up to dock 1 billion compounds. So, thousand million to some of these targets, hopefully all of them in the end with our special simulation method. Not only that, but we're going to dock them in 24 hours, so that we get really quickly to the computational solution.

JENNY: In March, the White House announced the COVID-19 High Performance Computing Consortium, which is allowing more researchers to gain access to supercomputing resources like Summit.

BRONSON MESSER: ORNL is a founding member of the so-called COVID-19 HPC Consortium, which is a collection of resources and people coming together, offering up a set of computational resources, including expertise, and a lot of ways to researchers that want to be able to attack the COVID pandemic problem as quickly as possible, and they have a need for high-end computing resources. 

MORGAN: That’s Bronson Messer. He’s the director of science at the Oak Ridge Leadership Computing Facility, which is home to Summit.

JENNY: There are currently about a dozen projects running on Summit as a part of the consortium.

MESSER: Where Summit can really provide benefit is in two separate, but related areas. One is the pure computational power of each node enables you to do things like molecular dynamics simulations and docking simulations that you probably couldn't do on a regular laptop. We want to be able to accelerate the way that we explore the whole space of solutions, if you will, where we try to look at all the possibilities of ways to attack the virus from either a vaccination or a treatment standpoint, and try to whittle that down so the wet labs can take that data and actually use it. The other part of it is, it's not enough to enable one single simulation to go really fast. In fact, you have to do many, many, many simulations. And that's a place where the sheer volume the sheer size of Summit really comes into play.

MORGAN: At 200-petaflops, Summit can perform 200 quadrillion floating-point operations per second.

JENNY: You’re probably thinking that sounds impressive, but what exactly does that mean? Well if every person on Earth completed one calculation per second, it would take the world population 305 days to do what Summit can do in 1 second.

MORGAN: It’s this kind of speed that makes Summit an ideal tool to use when looking for solutions to COVID-19.

MESSER: The thing to remember about Summit is that yeah, it's just a big computer. But in a lot of ways, it's a very unique scientific instrument and in that sense, it has a lot more in common with something like the Hubble Space Telescope with the Large Hadron Collider than it does with a laptop or the desktop on your desk. Well, what makes it very special even in that exclusive club, is that it's good for a lot of different things. And the fact that we were able to pivot our focus so quickly to this is really part and parcel of what Summit's all about. It's a general-purpose supercomputer and therefore it can attack a multitude of scientific problems.

JENNY: High performance computing is also playing a role in another consortium called Accelerating Therapeutics for Opportunities in Medicine, or ATOM.

MORGAN: ATOM is a public-private partnership focused on dramatically reducing the time it takes to discover and develop new medicines through the application of leading-edge technologies like machine learning and artificial intelligence.

MARTI HEAD: What's unique about ATOM is that it's an integrated approach, bringing together high-performance computing, artificial intelligence, and a tightly coupled engineering approach to chemical synthesis, and biological assays. So that we can think about all of the aspects that are important for making a drug in one tightly coupled, integrated platform.

JENNY: Marti Head is the director of the Joint Institute for Biological Sciences at ORNL, and she was a co-creator of ATOM when she was working in research and development at GlaxoSmithKline Pharmaceuticals.

HEAD: The purpose of the collaboration is to build a platform that allows us to start with a lead molecule and get to something suitable for clinical trials as quickly and as reliably as possible. That part of the drug discovery process takes five to seven years on average. And of all of the projects that we start at the very beginning in the pharmaceutical industry, 95 to 98 of them will fail.

MORGAN: The hope is that ATOM will not only speed up the drug discovery process, but also significantly improve its success rate of therapies that make it to clinical trials.

HEAD: The national labs have a unique role to play with other partners and other government agencies, in the pharmaceutical industry and in universities in generating knowledge and potential small molecule tools that would be useful, not just now in this current crisis, but that would set us up to be able to have a rapid response the next time this happens. Because this will happen again.

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JENNY: With so much unknown about COVID-19, scientists are using a range of techniques to find answers.

MORGAN: At ORNL, scientists are using neutrons to gain insight into the structure of the virus.

HUGH O’NEILL: By studying the structures of the individual viral proteins and understanding how they form complexes with each other, and also, in the viral RNA, that will give us clues on how to develop therapeutics that we can then disrupt the lifecycle of the virus and essentially stop it in its tracks.

JENNY: Hugh O’Neill is the team lead for the bio-labs within ORNL’s Neutron Sciences Directorate.

MORGAN: Hugh and his team are studying COVID-19 proteins constructed from synthetic DNA. Those genes are then inserted into bacteria to produce proteins of the virus and studied using a suite of neutron scattering instruments to gain a better understanding of the structure and function of the disease. 

O’NEILL: We'll use our neutron scattering techniques to look at the structures of the individual protein complexes and how they assemble to replicate the virus. Then we will use the information that we get from neutron scattering to inform computational calculations that then we will be able to carry out using Summit to get more in-depth information from our neutron scattering experiments on the molecular details of how these complexes assemble, disassemble, interact with RNA and also bind potential therapeutics as well.

JENNY: Neutrons are able to provide unique information at the atomic scale that researchers wouldn’t be able to get with other techniques.

O’NEILL: Neutrons in particular are ideal to study that system, because using neutron crystallography, we can see where all the hydrogen atoms are in the protein crystal. And then that way we can understand the mechanism of how the drugs bind.

MORGAN: The lab is also offering rapid, remote access to its neutron facilities for scientists pursuing novel coronavirus research.

JENNY: This program makes it possible for scientists to have beam time at the Spallation Neutron Source or the High Flux Isotope Reactor in a matter of days.

O’NEILL: So that's been sent out to the research community. And we're starting to see some proposals come in. We're making all our instruments available to carry out research related to COVID-19.

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MORGAN: In December, news of a new respiratory virus in Wuhan, China, began to emerge. 

JENNY: Just a few weeks later, cases of the virus began cropping up in different parts of the world.

MORGAN: By March, the virus had rapidly spread across the globe, prompting the World Health Organization to officially declare COVID-19 a pandemic.

BUDHU BHADURI: Our effort for the Department of Energy is to understand how this pandemic has unfolded across the planet, and particularly in the United States.

JENNY: That’s Budhu Bhaduri. He leads the National Security Emerging Technologies Division at ORNL.

MORGAN: Budhu and a team of scientists from Argonne, Los Alamos, and Sandia national laboratories are working together to develop an integrated capability to monitor, model and analyze COVID-19 pandemic, leveraging the labs’ collective scalable data and computing resources.

BHADURI: The main objective is to understand the trends and patterns of disease transmission and the impact on local infrastructure, healthcare infrastructure and population, and also to understand the geographic variability. So, we can really provide some insights into how what we call the non-pharmaceutical interventions, which are minimizing travel, stay at home, closing schools, closing non-essential businesses. How do those measures make an impact in terms of reducing and controlling the number of infections that are going through the population? And how soon can we get a good grip on understanding what sort of measures should we take that will allow us to go back to life as we knew it.

JENNY: This kind of data would give a better understanding of what mitigation strategies are effective in decreasing the number of coronavirus cases.

BHADURI: I think one of the key aspects that the DOE national labs are trying to build for the community is a very robust data and modeling infrastructure that will not only help the nation in dealing with COVID-19, but also get prepared for COVID-20 or COVID-21. Assuming that these sorts of diseases have a tendency to come back around every year. So, we want to be better prepared for the future as well and not just be in a situation to deal with the current crisis.

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MORGAN: The pandemic has created some supply chain issues in the production of critical healthcare equipment for medical professionals.

JENNY: ORNL is using innovations in advanced manufacturing to develop tools that industry can use to rapidly produce items like face shields, masks and test kit tubes.

LONNIE LOVE: The strength of Oak Ridge is being able to catalyze industry and move at an extremely fast pace. And there's a number of areas where we're helping industry to address some of the supply chain issues due to the pandemic.

JENNY: That’s Lonnie Love. He’s spearheading ORNL’s COVID-related advanced manufacturing initiative.

MORGAN: N95 masks have been in high demand for healthcare workers because they’re the most effective at filtering virus particles.

LOVE: We’re using the Carbon Fiber Technology Facility and we're working with Dr. Peter Tsai, the inventor of the N95, to show how we can scale up the process. And then we're transferring that, transitioning that technology to a number of industrial partners so they can scale up and manufacture the fabrics.

JENNY: In addition to helping ramp up the production of traditional N95 masks, the team is looking new options as well.

LOVE: We're developing new reusable N95 masks, using the latest advancements in additive manufacturing to print the molds and then giving those molds to industry to injection mold and go into mass production of these respirators.

MORGAN: With these molds, industry partners could easily make 300,000 reusable masks per week.

JENNY: Lonnie and his team have also 3D-printed metal molds that industry can use to make millions of face shields. 

LOVE: Everything we're doing is to get tooling into the hands of industry in hours and days rather than weeks and months. So, we can address some of these supply chain issues immediately.

MORGAN: ORNL is also helping companies envision new uses for existing products. When the lab was asked to help address a shortage of collection tubes for COVID-19 test kits, staff quickly realized the perfect solution was something used to contain a liquid known around the world – Coca-Cola.

JENNY: The small preform bottles that are usually blown up to make 20-ounce plastic Coca-Cola bottles will instead serve as test tubes in COVID-19 kits.

MORGAN: ORNL worked with a diagnostic company and Sandia National Laboratories to confirm the existing preforms would meet the requirements of the test tube kits.  

JENNY: A Coca-Cola bottling cooperative will convert a portion of its production line to manufacture over a million test tubes per week.

LOVE: So, this is a great success story. Others are coming just like this where we're working with companies that have massive manufacturing capabilities that are not directly used in the healthcare industry, but they can be turned on very quickly.

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JENNY: You’ve heard about some of the incredible ways that ORNL is using big science to solve one of the most challenging problems of our time.

MORGAN: Scientists from a variety of fields at the lab have jumped in to make a difference in this pandemic.

JENNY: We asked what it’s been like, from a researcher’s perspective, to try and tackle this massive scientific challenge.

O’NEILL: We don't necessarily have people working on these types of problems under normal work life, but they have, you know, technical skills and experience that they can apply to make some real contributions when asked and in a very rapid way. So, we can go from doing nothing in the field to actually, you know, producing and characterizing materials in a very short period of time.

LOVE: So, the hallmark of the MDF is speed. And, and one of the things that we've been very good at are what we call “moonshots” where we have outrageous schedules, very challenging problems to solve. It started with the printed cars, the Cobra, all the way up through to hypersonic vehicles. The team is used to working under extremely high-pressure, solving problems real-time and this is our best moonshot. This is what we were made for.

BUDHU: Just like we are dealing with an unprecedented situation in the world, this is also an unprecedented opportunity for us as scientists to make us count and make our science count. If we cannot make a difference today, I don't know when we will get another opportunity in our lifetime. So, it's very exciting for the entire team and that's why they keep working every day and trying to make a difference.

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Morgan: Thank you for listening to this episode of “The Sound of Science.”

Jenny: We hope everyone is staying safe and healthy.

Morgan: If you’d like more updates on ORNL’s COVID-19 research efforts, follow us on Twitter, Facebook or Instagram.

Jenny: Until next time!