A Q&A with Arup K. Chakraborty and Andrey S. Shaw, authors of Viruses, Pandemics, and Immunity

Experts in immunology discuss the current pandemic

Arup K. Chakraborty and Andrey S. Shaw, experts in immunology and authors of Viruses, Pandemics, and Immunity, have a more intimate understanding than most about the current COVID-19 pandemic. Shaw is Staff Scientist in Immunology and Oncology at Genentech, where his research focuses on immunology, oncology and cancer immunology. Meanwhile, Chakraborty is the Robert T. Haslam Professor of Chemical Engineering and Professor of Physics and Chemistry at MIT. For over two decades, Chakraborty’s work has largely focused on bringing together approaches from immunology, physics, and engineering.

Their book, Viruses, Pandemics, and Immunity, focuses on how viruses emerge to cause pandemics, how our immune system combats them, and how diagnostic tests, vaccines, and antiviral therapies work. We spoke to them about their book as well as their understanding of the current crisis at hand.

"Viruses, Pandemics, and Immunity by Arup K. Chakraborty and Andrey S. Shaw" The MIT Press: How does our modern COVID-19 pandemic compare to the pandemics of history? What is similar, and what is different?

Chakraborty and Shaw: Pandemics occur when a pathogen that did not previously circulate in humans emerges to become capable of infecting humans. This usually happens when a virus circulating in animals undergoes changes that allow it to infect humans. Few, if any, people have immunity to this new pathogen, and if the pathogen can be easily transmitted to others by casual contact, it can spread rapidly through the population. In this sense, the COVID-19 pandemic is just the latest example of many such scourges that have come before.  There are, however, many differences between our experience with COVID-19 and pandemics past.

A few of the differences are:

  1. A much larger share of the world’s population lives in urban areas compared to when the 1918 influenza pandemic was raging. For example, in the US, the fraction of the population that lived in urban areas passed 50% in 1920, and today it is estimated to be over 80%. Viruses like SARS-CoV-2 or influenza that can be transmitted by casual contact spread more readily in dense populations. Rapid and easy ways to travel around our interconnected globe today also made it easier for the virus to quickly spread globally.
  2. Establishing that a new virus has emerged, and developing vaccines and therapies that can combat it, requires that we first identify it. HIV was identified about two years after the first reports of a new disease. New methods for rapid isolation of viruses and routine fast ways to sequence their genomes enabled identification of the SARS-CoV-2 virus that causes the COVID-19 disease about a month after the first reports of the disease. So, compared to past pandemics, scientists got a much earlier start on developing medical interventions. This is an important reason why effective vaccines have been developed so rapidly. The 1918 influenza pandemic caused roughly 50 Million deaths before it faded away without the protective effects of a vaccine.
  3. Another difference is our current standards of medical care, which can mitigate some of the more serious problems caused by infection. The death toll from COVID-19 would be much worse without the advances in health care and associated technologies that are available in the 21st century.
  4. COVID-19 infection and the virus that causes it is being studied at a level of depth and breadth that is unprecedented. We are currently acquiring enormous amounts of knowledge and data that when properly analyzed and understood will potentially pave the way for creating a more pandemic-resilient world.

The MIT Press: In your book you discuss how the eradication of smallpox was made possible by close international coordination between nations. Do you think this kind of coordination is possible for COVID-19?

Chakraborty and Shaw: Indeed, the eradication of smallpox required a coordinated international vaccination drive without which eradication would not be possible. We are witnessing the beginning of major COVID-19 vaccination drives across the world right now. Until the global population acquires herd immunity aided by vaccination, life will not return to complete normalcy anywhere. So, ending the pandemic is an international problem. Global coordination right now is beginning to develop, but is sub-optimal. Vaccination rates in poorer countries is projected to be much lower than in wealthier nations. Hopefully, global coordination by world leaders will soon address such questions. We should point out that the smallpox virus primarily infected humans. So, by vaccinating the human population, we could eradicate this disease. Coronaviruses circulate in animals, like bats and other animals. As we describe in our book, the animal viruses can change by various mechanisms to become capable of infecting humans. After that there are opportunities for exchanges of the virus between humans and animals. So, vaccinating against the virus that causes COVID-19 will likely not allow us to eradicate the possibility of future pandemics caused by ever changing coronaviruses. The same is true for influenza. So, should we start thinking about how to create pan-coronavirus vaccines like we are doing for influenza?

The MIT Press: Why do you feel it is important for readers today to learn about previous outbreaks and treatments for illnesses like measles, polio, and smallpox?

Chakraborty and Shaw: We wanted to remind people that pandemics have occurred frequently throughout human history. Having a sense of the arc of history as it pertains to our perpetual war with infectious diseases provides context for the COVID-19 pandemic, and reminds us that this war will not be over after COVID-19. Equally importantly, we have much to learn from how past outbreaks were overcome. The fact that the severity of the 1918 influenza pandemic came in waves taught us to expect something similar for COVID-19. As we describe in the book, the non-pharmaceutical mitigation policies we put in place during COVID-19 were based on lessons learned from what was done in 1918 in St. Louis. Gertrude Elion’s work on developing antiviral therapies, and the successes we have had with HIV and HCV in this regard taught us about the challenges associated with developing therapies and how they can be overcome. Polio is also an important example of what can be learned from the past. The logistical challenges of manufacturing and distributing millions of doses of Salk’s vaccine quickly were harbingers of what we face today. Indeed, based on lessons past and modern scientific advances, we have accomplished miraculous things with regard to developing and manufacturing multiple effective vaccines. All these vaccines are necessary to end the pandemic quickly. Which ones are the best? Here, the polio example provides some lessons too. When the Salk vaccine was shown to be efficacious in 1954, we thought we had defeated the virus. Fortunately, Sabin continued working on his vaccine, which ultimately proved to be more effective and his vaccine was deployed world-wide. For reasons that we describe in the book, today we have gone back to the Salk vaccine. This teaches us that we need to have multiple vaccines as different ones may be better in different contexts. The recent measles outbreaks vividly illustrate what happens when vaccine coverage for an infectious disease falls below a threshold.

The MIT Press: Why do you think vaccines cause such controversies, both in our modern times and in the past?

Chakraborty and Shaw: There has always been trepidation about the use of vaccines, and our book discusses examples. This is because vaccination involves administering some form of a dangerous pathogen into healthy people. It is natural to be apprehensive. Indeed, as we describe in our book, variolation that aimed to protect against smallpox was often dangerous. In the 19th century, most families lost a child to infectious diseases, and millions of people still died of smallpox and other infectious diseases in the twentieth century. An inhabitant of past times would find a transformed world today. This is because vaccines, antibiotics and better sanitation have been transformative. In some sense the fear and controversies about vaccines today are partly a product of the success of vaccines. If we do not have to always worry about the perils of infectious diseases, we turn our attention to the possible perils of vaccination. No vaccine can be guaranteed to be 100 % safe. But, data collected by the National Vaccine Injury Compensation program in the US show that between 2006 – 2013 there was only one report of an adverse reaction for every million vaccine doses administered. So, vaccines are very safe. The fear of vaccines is exacerbated by mis-information. A great example is the one we describe in our book concerning a completely debunked and retracted study that suggested that there was a connection between autism and vaccination. So, the natural trepidation about vaccines is amplified by lack of information. The concerns about the COVID-19 vaccines largely concern three issues: One, how could a vaccine be developed so quickly, when scientists have not succeeded in producing a vaccine against HIV in so long? They must have cut corners, and so the vaccine may not be safe. Two, the new vaccines use genomic material (RNA, DNA introduced into adenoviruses). Will they alter my genes? And three, how do I know that the vaccine will not create problems in the long-term future? The first two issues can be addressed in clear scientific terms to alleviate concerns. For the third issue, no such effect is anticipated, but this cannot be definitively proven with data.

The MIT Press: What are the most common misconceptions about coronaviruses, including COVID-19? How can readers better educate themselves?

Chakraborty and Shaw:

  1. All viruses mutate, and indeed the SARS-CoV-2 virus has begun to mutate into strains that appear to be more effective at infecting people and spreading the disease more rapidly. But, coronaviruses do not mutate as fast as many other viruses (for reasons that we describe in our book). This is a saving grace.
  2. While coronaviruses have caused three deadly diseases recently, SARS, MERS, and COVID-19, there are several coronaviruses that are relatively harmless. For example, some cause the common cold.
  3. Why, unlike COVID-19, the SARS and MERS epidemics could be controlled before a global pandemic resulted.
  4. The risk to an individual that is under the age of 65, is relatively low. That doesn’t mean that it is benign, but most young people can expect a relatively mild response to the infection. So, assessing risk for a particular individual is difficult. However, everyone can potentially transmit the disease.

We hope that our book provides the necessary facts and concepts that can inform readers.

The MIT Press: What is some of the most important information about viruses, vaccines, and pandemics that is left out of mainstream discussions of our current crisis?

Chakraborty and Shaw: Most discussions focus on a particular aspect of a complex problem. We wrote our book with the hope of providing the reader with a holistic perspective on viruses, vaccines, pandemics, and other associated issues. This will enable people to understand various issues themselves – issues that are pertinent immediately and beyond the COVID crisis. This will allow individuals to participate in discussions about the current crisis and how to build pandemic-resilience in the future. Here are a few examples of facts and concepts that are largely left out in mainstream discussions: 1] A basic knowledge of how viruses function. 2] How antiviral therapies like Remdesivir and monoclonal antibodies or treatments like dexamethasone work. What are their limitations?  3] Decline of antibody levels does not mean that immunity is necessarily lost. 4] How long a vaccine can be protective varies greatly with disease, and we really do not know why. 5] Vaccines protect against disease through mechanisms that are not restricted to antibodies. 6] How and why mutations arise, the potential effects of these mutations on the efficacy of the current vaccines, and the kinds of mutations that may arise after the whole world is vaccinated. 7] The nature of immune responses to a viral infection, and how our immune system can get out of control to cause severe patient distress. 8] Political polarization has prevented honest and in-depth discussions about balancing the effects of mitigation policies aimed to save lives and their socio-economic effects.

The MIT Press: What have been some of the most concerning developments you have seen in the current pandemic? What has given you the most hope?

Chakraborty and Shaw: Some of our biggest concerns include:

  1. That the complex science underlying viruses, pandemics, immunity, vaccines and therapies was not presented in a way that was simple for the general public to understand.
  2. The nature of the mutants that are emerging and may emerge in the future, and their potential impact.
  3. Global cooperation was not optimal. Viruses do not respect borders.
  4. That our political polarization led to different views on issues such as whether masks could be protective, how treatments are determined to be effective, etc.

We find hope in a few key places:

  1. The amount of information that we have collected on this virus will help us better address and mitigate the effects of future pandemics caused by viruses.
  2. The speed with which totally new technologies led to such effective vaccines so quickly. These technologies will have an impact far beyond the current pandemic.
  3. The whole world is now paying attention to biomedical science, especially young people. Could this be a Sputnik like moment for the world, and young people will turn to how they can impact human health through approaches from diverse disciplines (much like they turned to math and science after Sputnik)?
  4. The vivid reminder that infectious disease-causing viruses are an existential threat to humanity will motivate us to work toward creating a more pandemic-resilient world.

The MIT Press: Human beings have learned plenty from the previous pandemics and plagues that have ravaged the globe. What do you think will ultimately be the key learnings we will gain from COVID-19?

Chakraborty and Shaw: First of all, we, the inhabitants of the 21st century have learned that infectious disease-causing viruses are an existential threat to humanity. They can exact an enormous toll in terms of lives lost and causing economic carnage. We are learning more about viral infections and our immune response to them at a level of detail that is unprecedented. We are also collecting enormous amount of data on the epidemiology of this virus. When these data are translated into knowledge, the advances in science that will result will prepare us better for the next pandemic. For example, perhaps we are likely to learn how to better treat viral infections and develop epidemiological models that can balance public health concerns and the enormous toll of death and disease with the economic and social toll. We are also learning so much about the development, deployment and manufacturing of vaccines that use technologies that have never been deployed before. The development of new vaccines and therapies will greatly benefit from this knowledge. Finally, we hope that we need to be vigilant about the need to be better prepared to test for a new virus in ways that can be rapidly deployed at scale. This is essential for containing an outbreak of a deadly disease and potentially eradicating the causative agent.

The MIT Press: You write that you hope readers will be better equipped to participate in discussions around viruses, vaccinations, and the current pandemic after reading Viruses, Pandemics, and Immunity. What is the most important takeaway that you wish readers will glean from your book?

Chakraborty and Shaw: There are a few important takeaways. We hope that readers will obtain an understanding of how viruses function, how our immune system responds to them, and why viruses are such a challenge to human life. We hope that readers will see that a long history of scientific advances created by dedicated people underlay our ability to address medical needs and develop vaccines so rapidly. Most importantly, directed investments in advancing some areas of science and technology can help us build a more pandemic-resilient world – we hope that the readers of our book will be armed with the knowledge necessary to be informed and avid participants in the debates that will hopefully ensue in this regard.

Learn more about the book