Posted on 22 July 2021 by Andrei Mihai

The Nobel-Winning Research That Helped Us Mount an Effective Pandemic Response

Different ways of microscopy have led to a better understanding of biological processes. Photo/Credit: FroggyFrogg/iStockphoto

When the World Health Organization declared COVID-19 a pandemic on 11 March 2020, few people thought we’d have a vaccine in nine months. But by early 2021, several working vaccines had already been produced and distributed in various countries.

This wasn’t a fluke, nor was it something that just emerged naturally and simply. It took countless hours of work by research teams from all around the world – and a series of previous innovations that made it all possible. Here are just a few of them.

Seeing the Unseen

Seeing what you’re doing is usually important, but when you’re working at the micro- or even nanoscale, it’s all the more important. To image and understand key reactions and processes, researchers often use electron microscopes. Instead of using light (photons) as a source of information, electron microscopes use a flow of accelerated electrons.

As the wavelengths of electrons can be up to 100,000 times shorter than that of photons, electron microscopes have a higher resolution than a conventional microscope and can reveal the structure of much smaller objects. For their fundamental work in electron microscopes, Ernst Ruska, Gerd Binnig, and Heinrich Rohrer were awarded the 1986 Nobel Prize in Physics.

But things haven’t stayed still since, and two other key advancements in the field were recently awarded the Nobel Prize. In 2014, Eric Betzig, Stefan W. Hell, and William E. Moerner were awarded the Nobel Prize in Chemistry for the development of super-resolved fluorescence microscopy, surpassing the limits of optical microscopy.

Richard Henderson about Electron Cryomicroscopy
Richard Henderson about Electron Cryomicroscopy during #LINO70

Another breakthrough came from Richard Henderson, Jacques Dubochet and Joachim Frank, whose work pioneered cryo-electron microscopy, which is essentially applying electron microscopy on samples cooled to cryogenic temperatures, which improved the visualisation technique even further.

Over the past year and a half, these techniques have been used intensively to study the virus itself, its interaction with human cells, and its reaction to various treatments or substances of interest. At the 70th Lindau Nobel meeting in 2021, Stefan Hell and Joachim Frank discussed pushing the limits of microscopy and what more can still be accomplished – but for now, we’ve already seen just how crucial these visualisation techniques can be in mounting a quick response to a pandemic.

Pushing the Immune System

Your body is the best doctor – that´s a (often misused) medicine adage. But oftentimes, medical treatments are less about directly fighting a disease, and more about teaching and helping our bodies fight pathogens.

The first-ever Nobel Prize in Medicine and Physiology (in 1901) was awarded to Emil von Behring for the discovery of a diphtheria antitoxin. Von Behring figured out that animals that survived diphtheria and became immune could pass blood on to other animals and make them immune as well. He called this blood an “antitoxin” – now known to contain antibodies. This approach (of transferring plasma from people who were cured of COVID-19) has been tried in this pandemic, and results have been mixed – but Behring’s work was helpful in other ways.

B Cell Rendering
A 3D rendering of a B cell. Photo/Credit: Blausen Medical (CC BY 4.0).

By the 1970s, researchers were well aware of antibodies, but they had other problems: How do you get the right antibodies from one person to another? Antibodies were known to be produced by a special lymphocyte called “B cells”, with each B cell only making one type of antibody. But B cells don’t really survive long outside the human body, so how do you produce cell cultures to use and study them?

César Milstein and Georges Köhler found a way around this problem, which they presented in a landmark paper in 1975. A solution, they went on, is to fuse B cells with cancer cells. The resulting mass produced a single type of antibody – a so-called monoclonal antibody. The two, along with Niels Kaj Jerne shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery.

Surprisingly or not, many drugs are monoclonal antibodies – including a drug called Tocilizumab, which was first developed as a drug for arthritis. Tocilizumab, which suppresses parts of the immune system, was found to also be effective against COVID-19. A recent systematic review found that the drug “may have substantial effectiveness in reducing mortality among COVID-19 patients, especially among critical cases.” Two other monoclonal antibody drugs (casirivimab/imdevimab and bamlanivimab/etesevimab) have also shown effectiveness against the disease.

Antibodies, however, can only do so much at protecting the body; once a virus enters inside human cells, antibodies are essentially blind to it. But the body has another line of defense: T cells. T cells are a crucial line of defense in our immune system and play a central role in the adaptive immune response. Rolf Zinkernagel and Peter C. Doherty discovered a key mechanism that enhanced our understanding of T cells, and eventually paved the way for COVID-19 treatments and vaccines. For their work, they were awarded the 1996 Nobel Prize for Medicine or Physiology.

T cells recognise COVID-19 variants, and they are stimulated by vaccines to fight SARS-CoV-2. These cells are also an essential part of our body’s memory – this is why the second shot of some COVID-19 vaccines is so important, it triggers a long-lasting immune response. The mRNA vaccines in particular seem to elicit a strong T cell response.

In Lindau, Doherty spoke about T cells and the “killer defense”, as well as the promise and pitfalls of science communication – two sessions well worth checking out.

Slow and Steady Wins the Race

When the pandemic kicked off, we had the virus sequenced in a matter of weeks. Testing became available quickly and vaccines that are normally developed in a decade turned up in a year or so. None of this would have been possible without advancements in basic science. From Behring’s research at the turn of the century to the mRNA vaccines that were only pioneered in this pandemic, there is a long list of advancements that helped us mount such a robust (and yet imperfect) response to COVID-19.

Just look at advancements in gene sequencing and PCR, which are essential for understanding the virus, testing for it and creating treatments and vaccines. Without this work, which was awarded the 1993 Nobel Prize in Chemistry, this response wouldn’t have been possible. Neither would it have been without our understanding of antibodies, DNA or optics. It may not be flashy, but all this (and many, many more discoveries) scientific progress helped us navigate the pandemic and have not one, but several responses to it.

Scientific progress is often slow, but it can help us lead better lives and be prepared against grand challenges such as the COVID-19 pandemic. It’s hard to tell exactly where the apple will fall, and sometimes, research in one field leads to advancements in another. Simple questions can sometimes go a long way towards solving grand problems and the best way to be prepared for future crises is to answer as many questions as possible.

Andrei Mihai

Andrei is a science communicator and a PhD candidate in geophysics. He co-founded ZME Science, where he tries to make science accessible and interesting to everyone and has written over 2.000 pieces on various topics – though he generally prefers writing about physics and the environment. Andrei tries to blend two of the things he loves (science and good stories) to make the world a better place – one article at a time.