Viruses, Pandemics, and Immunity
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© 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,
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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
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To the victims and heroes of the COVID-19 pandemic
Contents
Prologue ix
1 Conquering a Pandemic That Raged from Antiquity to
the Eighteenth Century 1
2 Discovery of Infectious Disease-Causing Microbes and
the Dawn of the Modern Era of Vaccines 19
3 Viruses and the Emergence of Pandemics 35
4 Immunity 67
5 Spread and Mitigation of Pandemics 103
6 Antiviral Therapies 135
7 Vaccines 153
Epilogue 181
Acknowledgments 189
Suggested Reading 191
Index 195
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 pan-
demic 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
x Prologue
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 peo-
ple 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 pan-
demic 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, tuber-
culosis, measles, leprosy, malaria, and human immunodefi-
ciency virus (HIV) resulted in a staggeringly large number of
deaths around the globe. Because of dramatic improvements in
Prologue xi
sanitation and modern medicine (vaccines, antibiotics, and anti-
viral 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 exis-
tential threats to humanity. Most of us lack an understanding of
the conceptual frameworks and facts necessary to critically con-
sider 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 sys-
tem 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 prin-
ciples 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 immu-
nity. 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 ulti-
mately 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.
2 Chapter 1
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 Mes-
opotamia) 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 indi-
viduals 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 sup-
posed 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 prac-
ticing 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
Conquering a Pandemic 3
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
4 Chapter 1
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 trans-
fer 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 men-
strual 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 Fracas-
toro, 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.
