by Shane Elliott, Rod Chalk and Jonathan Epstein
If 2020 is remembered for one thing, it will be the year COVID-19 sent the world into lockdown and completely changed the way we live and interact day to day. As we begin 2021, the world is searching for answers to questions posed by the virus’s rapid spread across the world. With vaccines now being administered in certain parts of the world, we are still working hard to better understand the virus and its origin, as well as reflecting on where we are now, how we responded and how to move forward as a society in a way that will protect against a future pandemic.
Based on a podcast of the same name, this article takes a closer look at “the new normal” and how we can resist and adapt to infectious diseases, interviewing three experts from various backgrounds to share their unique perspectives and ongoing work.
First, Rod Chalk, Head of Mass Spectrometry at The Centre for Medicines Discovery, University of Oxford, speaks about the R&D behind developing a vaccine so quickly. Next, Jonathan Epstein, DVM, MPH, PhD, Vice President for Science and Outreach, EcoHealth Alliance, speaks about ways to prevent pandemics in the future. Lastly, Shane Elliott, Vice President, Global Laboratory Solutions Marketing division at Agilent Technologies addresses how Agilent handled adjusting to business in 2020.
Developing a Vaccine
While businesses and the workforce were adjusting to ‘the new normal’ and working hard to find novel ways to work together and help customers remotely, academics and research scientists have been looking for answers to some of our unanswered questions on the new virus. Here, Chalk discusses the science behind vaccine R&D, and shares insights on the collaboration between The Centre for Medicines Discovery’s collaboration at Oxford University and Agilent to develop robust and reliable methods to analyze the SARS-CoV-2 spike protein.
Q: You have a particular focus on what’s known as spike proteins when it comes to supporting research against viruses such as SARS-CoV-2 that’s responsible for causing COVID-19. Can you tell us a little about their importance to the virus?
Chalk: We believe the spike protein has two essential functions for the virus. The first one is it allows the virus to dock. The virus needs to be able to recognize a suitable host cell and dock onto it, in order for the viral replication cycle to start. The second is that the spike protein is covered with these complex glycan sugars, this is the thing that hides the virus from the immune system. We believe this is the thing that makes the virus such a deadly disease.
Q: There must be challenges when you have to suddenly work to such scale and with such high stakes. What kind of variables do you have to manage in your work?
Chalk: The quality of the protein that we produce is absolutely paramount. Our own work has been involved in looking at how we can manage that quality. What we've found is that different batches of spike protein that we make are not identical. We have batch-to-batch variation. That variation is not in the primary sequence of the protein, which remains constant. What we see is, these glycans, these sugars that are on the surface of spike, they vary, so we see slightly different characteristics each time we make it. To characterize it, we need to chop the spike protein up into peptides, and then examine them. Some of the peptides will be without a glycan, some peptides will be with a glycan, and the idea is that we can separate these, and then characterize them. The second thing we do is, separate the glycans, these glycopeptides, so that we can then characterize them by mass spectrometry. With this information we have been able to build a database. This workflow and the database have allowed us to do very rapid and very simple quality control on each batch of spike protein that is made.
Q: And more quality control means better output, which means more research?
Chalk: I believe the more we know about spike glycans, how they're made, where the glycans occur, their profile and how that profile varies, the better we can produce improved antibody diagnostics. I believe it will allow us to generate better therapeutic antibodies, maybe even better vaccines. There's also a possibility of developing better drugs.
Interventions to prevent pandemics
The work of research scientists like Chalk is crucial to enhancing our understanding of viral diseases like COVID-19. But in addition to understanding the virus on a molecular level, it’s also important to look at the virus from an epidemiological standpoint to understand its origins and gain perspective on how to prevent future outbreaks. Here, Epstein, a veterinarian and ecologist working to better understand and prevent zoonotic disease emergence like Ebola, SARS, and MERS, talks about how he has helped to shed some light on how diseases, such as COVID-19, are introduced to humans and how to protect against them.
Q: As an expert in animal-to-human disease transmission, how much do we understand about how COVID-19 changed from being an animal disease into a global human pandemic?
Epstein: We don’t know exactly how COVID-19 started or where the first human cases occurred. The idea that COVID-19 began in a wet market just like SARS isn’t necessarily true and certainly isn’t likely to have happened in Wuhan as originally thought. These are questions that remain unanswered but that need to be answered for us to truly understand how COVID-19 began. We can be relatively sure that it is a bat virus - the question is: how did it emerge?
Q: Would you say that in cases like this, animals are to blame for the cause and spread of viruses?
Epstein: The fact that these viruses tend to originate in wild animal populations is not the fault of wildlife. This is not a matter of we need to eradicate or remove wildlife so that we can live a safer life, that is absolutely the wrong way to think of this. The number one reason that pandemics happen is because of us, human activities, things that we do to the environment around us, whether it’s deforestation, agricultural expansion, land conversion, travel and trade. If we could focus on those behaviours and the places on the planet where they most frequently occur, we could start to put in interventions that would reduce the risk of spill over happening, that would limit opportunities for viruses to make that jump from wildlife into people. One of the keys to limiting the risk for diseases to emerge is protecting ecosystems, protecting biodiversity because if we limit the impact we have, we limit the damage we do and the alteration we do to some of these environments that we know are incredibly biodiverse and therefore also potential sources for zoonotic pathogens, like viruses.
Q: So, by fixing some of humanities’ more destructive tendencies we can also limit the risk of future pandemics?
Jonathan Epstein: It’s a win-win. If we avoid damaging these ecosystems it will protect human health by reducing the risk that a virus will emerge from those forests.
Rise of Digital Business
A smooth transition to conducting business virtually, was important for many companies globally. It was not only crucial for companies to provide their own employees with stability in an uncertain time, but also to retain the confidence and trust of its customers. Here, Elliott talks about how Agilent handled adjusting to business in 2020 and some of the obstacle’s businesses faced in 2020.
Q: How has Agilent responded to the COVID-19 pandemic?
Elliott: COVID-19 has affected almost everybody on the planet and Agilent is not immune to that. Our focus as we headed into lockdown, remote work and this very unusual time with COVID-19 was to keep the health and wellbeing of our employees as our number one priority. Our senior leaders, including our CEO, came out very early on and made a commitment that no one at Agilent would lose their jobs or take a base salary cut due to COVID-19. It really allowed our employees to knuckle down and feel safer in terms of their job security – understanding that they'd be able to support their families and really get to work in supporting our customers.
Q: That’s within Agilent’s walls, but outside of your control, I imagine you’ve seen customers dramatically affected by the pandemic?
Elliott: Markets like academia were hit hard. The labs closed, schools and institutes closed, and we saw that in our engagement with those parts of the market. In other cases, though, markets like biopharma and even food are bouncing back and showing resilience. Also, some markets that are more directly involved in infectious disease research, testing and treatment have ramped significantly.
Q: So, 2020 at Agilent has been all about adapting to the circumstances, both inside and outside its own walls?
Elliott: We can't change the direction of the wind, but you can adjust your sails and that's exactly what we have done. We're looking at our customers, their preferences, their changing desires and we're adjusting our model to align with that new need. That said, our fundamental mission hasn't changed. We still are focused on delivering trusted answers and insights to advance the quality of life at Agilent and for our customers.
As a global community, we still have a lot of work to do to unravel the puzzle of 2020, but through the struggle we have proven that we can continue moving forward, despite what seem to be insurmountable obstacles. Leading experts across disciplines, like those featured in this episode of the Agilent podcast, are dedicating their time and energy to supporting us through this pandemic and increasing our understanding of infectious diseases like, COVID-19, all with the hope that their efforts will bring us closer to finding better solutions to protect us today and tomorrow.