Viruses, Pandemics, and Immunity
Viruses, Pandemics, and Immunity
Arup K. Chakraborty and Andrey S. Shaw
illustrated by Philip J. S. Stork
The MIT Press
Cambridge, Massachusetts
London, England
© 2020 Massachusetts Institute of Technology
All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means (including photocopying, recording, or information storage and retrieval) without permission in writing from the publisher.
Library of Congress Cataloging-in-Publication Data
Names: Chakraborty, Arup, author. | Shaw, Andrey S., author.
Title: Viruses, pandemics, and immunity / Arup K. Chakraborty and Andrey S. Shaw.
Other titles: MIT Press first reads.
Description: Cambridge, Massachusetts : The MIT Press, [2021] | Includes index.
Identifiers: LCCN 2020033971 | ISBN 9780262542388 (paperback)
Subjects: MESH: Pandemics | Viruses--pathogenicity | Immunity | Vaccines | Virus Diseases--drug therapy
Classification: LCC RA644.V55 | NLM WA 105 | DDC 614.5/8--dc23
LC record available at https://lccn.loc.gov/2020033971
10 9 8 7 6 5 4 3 2 1
d_r0
To the victims and heroes of the COVID-19 pandemic
Contents
Prologue
1Conquering a Pandemic That Raged from Antiquity to the Eighteenth Century
2Discovery of Infectious Disease-Causing Microbes and the Dawn of the Modern Era of Vaccines
3Viruses and the Emergence of Pandemics
4Immunity
5Spread and Mitigation of Pandemics
6Antiviral Therapies
7Vaccines
Epilogue
Acknowledgments
Suggested Reading
Prologue
Throughout history humans have contended with pandemics, and the written record since antiquity is replete with references to plagues, pestilence, and contagion. The end of the Middle Ages through the beginning of the Renaissance, a period of heightened creativity, was accompanied by a new freedom of movement around the Mediterranean and between Europe and Asia. But this increase in mobility was also linked to the spread of the plague. The great bubonic plague of the fourteenth century occurred from 1347 to 1352. It spread throughout Europe and the Middle East, killing about 100 million people. The plague likely started in China and then passed into Eastern Europe through the Silk Road. Once in Italy, it was able to spread widely across Europe and eventually crossed the Mediterranean to the Middle East.
This was not the first or last time the world suffered because of the plague. In AD 541, a pandemic began in Constantinople, the heart of the Byzantine Roman Empire, resulting in deaths equivalent to half the European population. The plague pandemic of the nineteenth century began in China in 1855 and first spread to India, where it killed over 10 million people. It would eventually spread across the world with famous outbreaks in Hong Kong, San Francisco, Mecca, Glasgow, and Cuba. It was during this pandemic that scientists were first able to identify that a certain kind of bacterium causes the plague. It has the official name Yersinia pestis, after its discoverer, Alexandre Yersin. Black rats were discovered to be the hosts of this bacterium, and fleas from these rats infected humans with the disease. These discoveries led to public health measures aimed at reducing rat infestation and the development of insecticides to control fleas. Combined with the subsequent development of a vaccine, the plague gradually became a thing of the past in most countries, and now only small outbreaks resulting in a few thousand cases are reported each year.
World War I saw one of the largest mobilizations of people around the world in history, with over 70 million troops involved. By 1917, many of these troops were mired in horrific conditions, sheltering in crowded trenches in northern France. This would prove to be a perfect breeding ground for a new pandemic that would kill 20–50 million people, many more than were killed in four years of war (about 15 million, including 6 million civilian casualties). The huge loss of life due to the pandemic that began in early 1918 almost certainly contributed to ending the war on November 11, a day now remembered as Armistice Day, or in the United States as Veterans Day. The 1918 influenza pandemic was caused by a virus from the same family as the ones that cause the seasonal flu. Influenza viruses also caused pandemics in 1957, 1968, and 2009.
In addition to the flu pandemics, in the twentieth century, pandemics and epidemics caused by cholera, smallpox, tuberculosis, measles, leprosy, malaria, and human immunodeficiency virus (HIV) resulted in a staggeringly large number of deaths around the globe. Because of dramatic improvements in sanitation and modern medicine (vaccines, antibiotics, and antiviral drugs) the devastation wrought by pandemics was largely forgotten by us, the inhabitants of the twenty-first century.
But our perpetual battle with infectious disease-causing organisms and devastating pandemics is an integral part of the human story, and this war is not over. The enormous human and economic toll exacted by the COVID-19 disease vividly reminds us that infectious disease pandemics are one of the greatest existential threats to humanity. Most of us lack an understanding of the conceptual frameworks and facts necessary to critically consider issues that have suddenly become pertinent. The goal of this book is to provide readers with a description of how viruses function and emerge to cause pandemics; how our immune system combats them; how diagnostic tests, vaccines, and antiviral therapies work; and how these concepts are a foundation for our public health policies. The narratives interweave scientific principles and ongoing efforts to combat COVID-19 with stories of the people behind the science. After reading this short book, we hope you will be an informed participant in debates about what we can do to safeguard the future by creating a more pandemic-resilient world. As we note in the concluding chapter, it does not have to be the way it has been with COVID-19 again. With the right investments and scientific advances, we could have the knowledge and tools that will help prevent such devastation in the future.
1 Conquering a Pandemic That Raged from Antiquity to the Eighteenth Century
In the history of the war between pathogens and humans, there are two eras. In the first era, the subject of this chapter, humans were suffering from the misery of infectious disease but didn’t know what caused them or how to mitigate their effects. Our ancestors observed, however, that individuals who recovered from these diseases did not get the same disease again, and thus could serve as caregivers during an outbreak. We will begin by briefly describing the earliest ideas regarding the origins of this observation, which we now understand to be acquired immunity. The attempt to harness this observation for human good is the history of vaccines. We will describe how the first era of our eternal battle with infectious diseases ended with one of the major achievements of medicine, the vaccine against smallpox. We will tell the tale here of how this procedure, which ultimately eradicated the scourge of smallpox from the planet, was developed slowly by several cultures on different continents in an empirical way without any understanding of how or why it worked. The following chapters will describe the second era when we learned about the origins of infectious diseases and how to combat them.
The Earliest Ideas
Spirits, Demons, and Divine Punishment
We are an inherently curious species. So, the observation that once someone recovers from a disease like smallpox they are not afflicted again led to ideas attempting to explain what was going on. In ancient civilizations (e.g., India, Egypt, and Mesopotamia) diseases were considered to be a punishment
from God for sins that a person had committed. In India, upon being afflicted with smallpox, people prayed to a specific incarnation of God called Sitala. This custom is still followed in India when someone in the family has chicken pox or measles, presumably because these diseases also result in skin rashes and pustules that look like liquid-filled raised bumps on the skin.
Not surprisingly, it was speculated in ancient times that individuals who recovered from a serious illness had sinned less than those who succumbed. The reason why one was protected from a disease after recovering from it was because the sufferer had been sufficiently punished. The reason for subsequently being afflicted with other diseases was presumably that the person must have gone on to commit other sins.
Spirits, demons, and celestial objects were also considered to cause diseases. The name “influenza” is derived from the Italian word for influence because the disease was thought to be caused by the influence of stars. Similarly, in Europe, syphilis was supposed to have been caused by an evil conjugation of planets. One implication of the idea that spirits and demons caused diseases was that one could be protected from them by practicing the right rituals. One of the authors (AC) had firsthand experience with such practices. After AC’s infant sister died of pneumonia in 1968, his educated but distraught mother visited a “Man of God.” This man provided her with an amulet that AC was made to wear to protect him from disease-causing spirits. AC does not remember when in college he stopped wearing it or whether he was admonished by his mother for this action. He has not been struck with terrible illnesses since he stopped wearing the amulet!
Spirits, demons, celestial objects, and divine punishment are not the causes of infectious diseases. The appeal of these earliest ideas regarding the origins of disease and acquired immunity is their simplicity and the peace of mind that comes from taking action to prevent disease. This is why similar ideas persist to present times in some segments of society.
Expulsion or Depletion
Physicians had also started thinking about why people were not usually infected by smallpox after recovering from illness. One type of explanation is the expulsion theory. An example is one attributed to the great Persian physician and scientist Abu Bekr Mohammed ibn Zakariya al-Razi, who lived in the ninth and tenth centuries AD. His name, al-Razi, means that he came from a city, Rey, near Tehran. During his lifetime, he achieved great fame as a physician with his evidence-based approach to examining disease and evaluating various therapies. He was the first to distinguish between smallpox and another skin disease, measles. Besides his many seminal contributions to medicine, he was also a scholar of grammar and other diverse fields. His work in medicine was influential throughout the Islamic world and beyond.
In al-Razi’s view, smallpox afflicted young people because they had too much moisture and this led to fermentation of blood. The products of this fermentation process caused pustules to form, and when they burst the liquid that was expelled was the excess moisture. Given this explanation, it was also clear why smallpox did not recur; people who recovered no longer had excess moisture.
Many other explanations of a similar vein were proposed over the years. Girolamo Fracastoro (1478–1553), proposed that seeds (or seminaria) that arose spontaneously in a person, earth, or water were the cause of diseases like smallpox. The disease was transmitted from one person to another by transfer of seeds. To explain acquired immunity to smallpox, he posited that all humans were “contaminated” with menstrual blood during birth. When seeds emerged in a person, it caused this contaminant to putrefy or decay. After recovery, one could not be afflicted by smallpox again because the putrefied menstrual blood was expelled in the smallpox pustules. Variants of this theory included ones where, instead of menstrual blood, other fluids from the birth process were considered to be the contaminants that putrefied and were expelled upon infection with smallpox seminaria. It is interesting to speculate on why the birth process had such a powerful influence on the worldview of some early physicians.
Girolamo Mercuriale (1530–1606), a contemporary of Fracastoro, pointed out several problems with the expulsion theory. If the need for expulsion of menstrual blood contamination was the cause for smallpox, why were only humans, and not other mammals, afflicted with smallpox? Why did smallpox not exist in Indigenous populations before the Europeans brought it to the Americas? Since the menstrual blood contaminant had been expelled by smallpox, why was there not protection from all diseases after recovery from smallpox? Mercuriale was logically testing the expulsion model to see if it made sense and whether it was consistent with all the data, and found it wanting.
By the way, this is a good example of how science progresses. A model is proposed to explain certain observations. The model is then found to be inadequate for describing new observations. The model is then modified to accommodate the new data, leading to newer predictions. This is exactly what we witnessed in real time when epidemiological models continually revised estimates of deaths due to COVID-19 as new data became available and lockdown measures started to take effect.
New models that were proposed in the seventeenth and eighteenth centuries to account for observations not explained by the expulsion theory continued to rely on disease-causing seeds, but proposed a different function for the seeds. This class of models was called depletion theories. One version of this type of theory, proposed by the English physician, Thomas Fuller (1654–1734), posited that individuals were born with various kinds of “ovula” (like seeds) and that each corresponded to a particular disease. When the appropriate seed was germinated, it gave rise to a specific disease. Upon recovery from the disease, this seed was depleted, and one could not subsequently be afflicted by the same disease. But the seeds for other diseases remained. This model builds on the seed idea and now easily explains why we are protected only from diseases from which we have recovered.
As new observations became available, the depletion idea also became untenable. When a scientific model cannot be modified further to account for new information, there is a crisis because the old model has to be completely abandoned. Then, in what the philosopher Thomas Kuhn referred to as a paradigm shift, a new model is put forth. In later chapters, we will describe the paradigm shifts that led to our modern understanding of infectious diseases and immunity. For now, let us turn to the history of the devastation caused by smallpox, and how it was vanquished by human ingenuity and informed public policy.
A Brief History of Smallpox
From Antiquity to the Early Eighteenth Century
Smallpox is a viral infection that was not only lethal but also horrifying for the patient. It usually began with a high fever, malaise, and muscle and headaches. That would last for 3–4 days. Then a rash and pustules would develop in the mouth, tongue, and throat. Over the next 24 hours, the rash would then progress to cover other parts of the body. Over a few days, the pustules would increase in size and eventually burst. During this second phase, about 30 percent of those infected would die. Those who survived were often left with a disfigured appearance because of severe scarring of the skin and a loss of skin pigment. Their appearance was proof that they had recovered from the disease and would not be afflicted by smallpox again. Thus, they could safely care for the sick. Fortunately, the COVID-19 disease does not leave visible scars, but this means that scientific tests are required to prove that one has been exposed to the disease and is protected for some time.
It is believed that smallpox started to afflict humans in about 10,000 BC. Concrete evidence for its existence in humans 3,000 years ago is provided by Egyptian mummies with signs of the disease. A medical book written in roughly AD 400 in India describes the classic symptoms of the disease, the appearance of pustules on the skin of patients. The first description of smallpox in Europe is in the writings of Bishop Gregory of Tours around AD 580. With the start of European exploration in the fourteenth century, smallpox was spread to Africa and Asia. By the seventeenth century, smallpox was among the top two killer diseases
in Europe. In 1849, 13 percent of all deaths in the Indian city of Calcutta (where one of us was born) were due to smallpox, and between 1868 and 1907 over 4 million people in India died of the disease. Globally, it is estimated that, just in the twentieth century, smallpox caused 300 to 500 million deaths, with roughly 50 million people afflicted every year as recently as the 1950s. These numbers indicate a level of devastation greater than the enormous damage already caused by the COVID-19 pandemic.
Smallpox was brought to the Americas by the Spanish in about 1520 with devastating consequences. It is estimated that between 60 and 90 percent of the population of the New World was decimated by the virus. The extremely high mortality rate in the Americas was probably due to the simultaneous introduction of other highly infectious viruses like measles that the native population had never seen. Smallpox also influenced the outcome of wars. Infected with smallpox, the Aztec armies had no chance against the invading armies of Cortes.
Smallpox epidemics occurred regularly in American cities. Between 1636 and 1698, Boston had six epidemics. The Boston epidemic in 1721 was so severe that many fled to other colonies, thus spreading the epidemic. The epidemics in Boston and New York in the early twentieth century (1900–1903) led to the establishment of government quarantine facilities and mandatory vaccination programs.
The devastating smallpox and plague epidemics led our ancestors to make an important observation. In 430 BC, during the plague of Athens, the Greek historian Thucydides noted that those who recovered from the disease could become caregivers to the sick without consequence. Throughout history, there are many other references to individuals being protected or exempt from a disease after recovering from it. People who had recovered began to be referred to as “immune,” derived from the Latin word immunis for “exempt.”
Viruses, Pandemics, and Immunity Page 1