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The End of Plagues: The Global Battle Against Infectious Disease

The End of Plagues: The Global Battle Against Infectious Disease

by John Rhodes

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At the turn of the twentieth century, smallpox claimed the lives of two million people per year. By 1979, the disease had been eradicated and victory was declared across the globe. Yet the story of smallpox remains the exception, as today a host of deadly contagions, from polio to AIDS, continue to threaten human health around the world. Spanning three centuries,


At the turn of the twentieth century, smallpox claimed the lives of two million people per year. By 1979, the disease had been eradicated and victory was declared across the globe. Yet the story of smallpox remains the exception, as today a host of deadly contagions, from polio to AIDS, continue to threaten human health around the world. Spanning three centuries, The End of Plagues weaves together the discovery of vaccination, the birth and growth of immunology, and the fight to eradicate the world's most feared diseases. From Edward Jenner's discovery of vaccination in 1796, to the early nineteenth-century foundling voyages in which chains of orphans, vaccinated one by one, were sent to colonies around the globe, to the development of polio vaccines and the stockpiling of smallpox as a biological weapon in the Cold War, world-renown immunologist John Rhodes charts our fight against these plagues, and shows how vaccinations gave humanity the upper hand. Today, aid groups including the Bill and Melinda Gates Foundation and the World Health Organization have made the eradication of polio a priority, and Rhodes takes us behind the scenes to witness how soon we may be celebrating the eradication of polio.

Editorial Reviews

From the Publisher

“An engaging and expansive exploration of humankind's quest to defend itself against disease.” —History Today

“The historical tale of vaccination and the extraordinary achievements that have come from its implementation…this is a fascinating book.” —Cosmos Magazine

“An optimistic history of vaccinations and their underlying science…Rhodes also looks at vaccinations against tuberculosis and flu, HIV and malaria…the science behind these limited successes makes for some of the best chapters in the book, which is especially impressive given the difficulty of making immunology accessible to the lay reader” —Times Higher Education

“The remarkably clear voice of immunologist John Rhodes takes us through significant moments in man's battle against infectious disease… excellent and captivating.” —The Book Bag

The End of Plagues is a fascinating book and well worth a read for anyone interested in the history of medicine.” —LSE Review of Books

Library Journal
Immunologist Rhodes (fellow, Royal Coll. of Pathologists) has crafted an engaging and accessible history of vaccines, including those for smallpox, polio, and rabies. His timely discussion of the challenges of smallpox eradication (the disease was eradicated in 1979, though the threat of its use in bioterrorism remains) sheds light on the unfinished task of eradicating polio and malaria and the insufficient efforts at making HIV/AIDS and tuberculosis vaccines and treatments available. The more than 20 vaccines available today have reduced the incidence and fear of these once terrifying infectious diseases, particularly in first-world countries, but their threat to global health should not be underestimated. Rhodes's review of antivaccine protests (and riots) is helpful for understanding current events. Almost all medical treatments carry some risk, and populations rely on herd immunity (i.e., a critical mass of a community) for protection from infectious diseases. Related and complementary titles include Seth Mnookin's The Panic Virus and the 2013 reference work The History of Vaccines by Karie Youngdahl, et al. VERDICT This highly recommended work offers valuable, nuanced information to readers interested in public health policies and individual health decisions.—Mary Chitty, Cambridge Healthtech, Needham, MA
Kirkus Reviews
The end of at least one plague, smallpox, is the centerpiece in immunologist Rhodes' saga of humanity's attempts to overcome infectious disease. The author begins with the story of Edward Jenner (1749–1823), delivering a rich portrait that reveals Jenner as a gifted student befriended by members of the Royal Society, a doctor who was also an avid fossil hunter, botanist and student of bird migration. Most of all, he was a caring physician who wanted to bring the fruits of vaccination to the world--and at no cost to the poor. Vaccination in time would replace variolation, the procedure based on inoculating smallpox material under the skin to induce a mild case of disease in order to confer immunity. The danger was that variolation sometimes killed the patient and was also a source of contagion for those in contact. Rhodes makes clear that all the present-day controversies--the anti-vaccinationist advocates who declare vaccines as seeding autism or other plagues--were just as evident in the 19th century and probably with more reason, since vaccine material did not travel well, could lose potency and could become contaminated with other germs. The author goes on to provide a brief primer on immunology and the differences between killed and live attenuated vaccines. He then deals at length with the polio story and the bitter feud between Jonas Salk and Albert Sabin. His concluding chapters get bogged down in the country-by-country details of the conquest of smallpox and similar details in the up-and-down progress in eradicating polio. Nevertheless, Rhodes celebrates the work of thousands of volunteers as well as ongoing research to develop vaccines against new scourges. By no means the end of plagues, but a wonderful account of the end of smallpox and the man who deserves full credit for devising one of the safest and most effective means of prevention.

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The End of Plagues

The Global Battle Against Infectious Disease

By John Rhodes

Palgrave Macmillan

Copyright © 2013 John Rhodes
All rights reserved.
ISBN: 978-1-137-38131-6



"Of the causes of the Small-Pox; how it comes to pass that hardly anyone escapes the disease ... Now the Small Pox arises when the blood putrefies and ferments, so that the superfluous vapours are thrown out of it, and it is changed from the blood of infants, which is like must, into the blood of young men, which is like wine perfectly ripened."

Abu Bakr Mohammad Ibn Zakariya Al Rhazi, ca. 910 Translated from Arabic by W. A. Greenhill, 1848

Imagine a great city at sunrise. The trains are running from the outer suburbs and small towns, carrying commuters to their daily work. The highways glitter with an endless stream of cars, mass-transit systems ferry hordes of people packed in tight, each wrapped up in their private world. Picture an air traveler circling high above, eager to be on the ground, peering through the aircraft window at the city spread below. Not one among its millions is visible to him. But of course, he has no trouble believing in the invisible.

It's simply a matter of scale. In every big city there are millions of bodies. And in every human body there are trillions of microbes, outnumbering the body's cells by ten to one. Most are beneficial and essential to health. But plenty are our enemies and many can be fatal. Fortunately for us, an army is mustered against them, constantly on call, and the streaming traffic of these inner forces is no less teeming than the rush-hour traffic in the most crowded cities on earth.

Cities favor the invisible enemy: it's so much easier for him to pass between one person and the next when people live in close proximity, sharing their resources and encountering hundreds of other individuals every day. But generally the interior army, protected behind barriers of skin and membrane, remains effective.

It's hard for us in the twenty-first century to imagine the lives of our ancestors before the age of modern medicine, sanitation, and nutrition. Disease shaped and altered human history, dramatically changing the course of wars, the scale of empires, and the fundamental texture of everyday life. In medieval times, values and beliefs were formed by the daily reality of death in the midst of life. Children were lucky to survive to adulthood; in Britain the average life expectancy was 30 years. Bubonic plague (the Black Death), arriving in Europe along the Silk Road from China, killed more than one-third of the European population between 1348 and 1350, precipitating a series of religious, social, and economic upheavals and hastening the end of feudal society.

Bubonic plague, which killed half its victims within days, is one of three terrible manifestations of the bacterium Yersinia pestis.Transmitted most frequently by rat-flea bites, it spreads through the lymphatics, blackening the grossly swollen lymph nodes in the groin and armpits as it overwhelms them. The name bubonic plague refers to these dark swellings, or buboes. But plague also shows itself in septicemic and pneumonic forms, the latter easily transmitted through airborne droplets. It was Daniel Defoe, merchant, writer, pamphleteer, and secret agent, who wrote the most compelling account of the Great Plague of London, which raged in 1665 — 1666. Ostensibly an artless, sometimes stumbling eyewitness account by an ordinary London trader, it is in fact a cleverly crafted novel written decades after the devastation.

The face of London was now indeed strangely altered: I mean the whole mass of buildings, city, liberties, suburbs, Westminster, Southwark, and altogether; for as to the particular part called the city, or within the walls, that was not yet much infected. But in the whole the face of things, I say, was much altered; sorrow and sadness sat upon every face; and though some parts were not yet overwhelmed, yet all looked deeply concerned; and, as we saw it apparently coming on, so every one looked on himself and his family as in the utmost danger ... London might well be said to be all in tears; ... the shrieks of women and children at the windows and doors of their houses, where their dearest relations were perhaps dying, or just dead, were so frequent to be heard as we passed the streets, that it was enough to pierce the stoutest heart in the world to hear them. Tears and lamentations were seen almost in every house, especially in the first part of the visitation; for towards the latter end men's hearts were hardened, and death was so always before their eyes, that they did not so much concern themselves for the loss of their friends, expecting that themselves should be summoned the next hour.

Close to where I live in Cambridge is a natural monument to the plague, which tells a more domestic tale. The village of Clopton once had a market, water mills, a flint church, and two moated manor houses. When the Black Death swept through England, wealthy survivors enclosed the abandoned land for grazing, which needed little man power (the decimated workforce was demanding higher wages). Today the village is a hollow in the empty hillside, full of willow trees and waving grass.

After the depredations of the fourteenth century, the Black Death returned to Europe in the great plagues of Seville, London, Vienna, and Marseille. But then something changed. After the middle of the seventeenth century, another dreaded infection replaced bubonic plague as the most feared affliction in Europe. Smallpox, the speckled monster, brought death and disfigurement on a massive scale, attacking the young in particular, indiscriminately ravaging not just the poor, but the richest and most powerful in every kingdom. It blinded many of its victims, killing a half million in a single year.

The burgeoning cities were particularly vulnerable. Tens of thousands died in the epidemics in Paris in 1723 and Rome in 1746 and 1754. The sickness was unimaginably worse than chickenpox — a disease that still infects children today. Ten to 30 percent of all infected people died. The death was horrible, prompting Thomas Macaulay, the British poet and historian, to call it "the most terrible of all the ministers of death."

What was the illness like? About ten days after infection, the patient, whether child or adult, was struck with a sudden fever, splitting headache and often backache, and sometimes vomiting. The rash appeared two to three days later, the fever subsided, and the patient, who had been feeling extremely ill, began to feel better. Over the next two weeks the fever returned and the rash began to change. The smallpox rash started in the mouth and throat and on the face; it then spread to the upper parts of the limbs and to the trunk and finally to the hands and feet. In the course of the infection it evolved from flat spots, which gradually became raised and grew hard, "like embedded lead shots." The spots then softened and began to fill, first with a clear fluid, then with pus. These pustules gradually flattened, dried, and scabbed. The fever ebbed and departed, and within about three weeks of first appearance the dried scabs fell off, leaving fibrous, pitted scars — the pockmarks — particularly on the face.

In mild cases the rash remained sparse and scarring was limited. But in moderate cases it covered the body, and in severe cases the pustules could be so crowded that they fused together in an intense rash called confluent smallpox with a mortality rate around 60 percent.

Smallpox is restricted to humans (no other species gets infected); patients are infectious for only a couple of weeks, and those who recover are immune to further attacks for the rest of their lives. This means that in small, isolated communities the disease can't persist and soon runs out of potential victims as immunity becomes established. In contrast, cities favor the infection. In large communities, even if they're isolated, the supply of vulnerable children is sufficient to maintain the infection, though the number affected might fluctuate wildly, peaking only once every few years with troughs in between until the birth of more susceptible children. In this situation the disease is called endemic, and the majority of its victims are young. In societies never exposed to smallpox (or where it has been absent for several generations), the whole population is at risk, and entire nations can be devastated. In 1521 the Spanish conquistador Hernando Cortés, with an army of only 900 men, defeated the entire Aztec nation of 5 million, largely because it had been ravaged by smallpox, which the Spaniards brought with them. Smallpox was a formidable enemy.

To the Aztec nation and the Inca nation, which fell to an even smaller army a decade later, it must have seemed that the gods were on the Spanish side: their own people were ravaged by disease while the Spaniards remained miraculously untouched. The Aztec emperor Cuitláhuac and the Inca emperor Huayna Capac died of smallpox carried by the invaders.

Endemic smallpox in Europe had long conferred protection through immunity on adventurers setting out to colonize new lands, but the Old World origins of the disease remain uncertain. We can't be sure if Old Testament accounts of plague and pestilence include descriptions of smallpox, and we don't know for certain if smallpox corresponds with accounts in early Chinese and Indian texts. The first definitive evidence of its existence comes from studies of Egyptian mummies, especially Ramses V who died in 1157 BC. His face, neck, shoulders, and lower abdomen are covered in pockmarks.

The plague of Athens in 430 BC may well have been smallpox, although measles and typhus are possible candidates as well. The outbreak began in the second year of the Peloponnesian War. It killed more than 30,000 people and reduced the population by 20 percent. Thucydides, an Athenian aristocrat, wrote a vivid account, describing the dead lying unburied, the temples full of corpses, and the violation of funeral rituals. Thucydides himself had the disease, but survived to write his celebrated history. He noted the nature of immunity: "the sick and the dying were tended by the pitying care of those who had recovered, because they knew the course of the disease and were themselves free from apprehensions. For no one was ever attacked a second time, or not with a fatal result."

In the first millennium AD, outbreaks of smallpox regularly struck the great civilizations of Asia and the Middle East, changing the course of conflicts and influencing the spread of Islam, Christianity, and Buddhism. The first detailed description of the illness was written in 910 by Al Rhazi, an eminent scholar in the early Islamic world and the first to distinguish between smallpox and measles. He proposed that natural exudation of superfluous infant humors was the cause of disease (since smallpox was endemic in tenth-century Baghdad, adults were immune and children the main victims). Another contemporary view was that the symptoms were due to the necessary expulsion through the skin of poisons acquired in the womb, consistent with beliefs about the unclean nature of menstrual blood. Al Rhazi's view of the infection was informed by his knowledge of classical medicine, and he advocated highly specific treatments to rebalance the humors: bleeding and cooling in the early stages of illness, and heat treatment (steam and swaddling) when the rash was erupting, together with dietary measures.

But there seems to be a mystery here. How could the most gifted physician of his age liken a terrible disease, which killed so many of its victims, to a natural process like the maturation of fine wine (as in the quote that opens this chapter)? The answer may well be that the disease afflicting tenth-century Baghdad was a distinct variant of smallpox caused by a virus with low virulence (now known as Variola minor). This would also explain why Al Rhazi ranked smallpox as less serious than measles. Whatever the reason, two centuries later virulent smallpox afflicted the crusaders. And when they returned to Europe they carried this prince of pestilence home with them.



"The smallpox was always present, filling the churchyards with corpses, tormenting with constant fears all whom it had stricken, leaving on those whose lives it spared the hideous traces of its power, turning the babe into a changeling at which the mother shuddered, and making the eyes and cheeks of the bighearted maiden objects of horror to the lover."

Thomas Macaulay, The History of England, from the Accession of James II (Volume 4), 1848

Six hundred years after Al Rhazi, despite the understanding of contagion and immunity (the knowledge that infections struck only once in the lifetime of an individual), imbalances in the four vital humors, as characterized by the Hippocratic physicians of ancient Greece, were still blamed for most illness. Blood, phlegm, black bile, and yellow bile were said to correspond with the four elements of air, water, earth, and fire. Rebalancing the humors remained the purpose of treatments such as cooling or heating the body, diet, exercise, herbal medicines, vomiting, purging, blistering, and bloodletting, right up to the nineteenth century. A particularly strange treatment for smallpox began with a Portuguese physician in the fifteenth century who recommended wrapping patients in red or purple cloth. The practice caught on and in the sixteenth century, when Queen Elizabeth had smallpox, she was wrapped in a red blanket.

Whatever the degree of ignorance and mystery surrounding the disease, one thing was certain: its sources were invisible. What sort of agent might cause such dreadful sickness?

We now know that virulent smallpox is caused by a virus called Variola major,a large, brick-shaped virus much bigger than flu but too small to be seen clearly under the light microscope. The virus is spread by airborne droplets from blisters in the nose and mouth of an infected person across distances up to two meters (and by direct contact with body fluids and contaminated objects such as bedding and clothes, which may harbor active virus for weeks or even months). However, the nature of viruses was not understood until the twentieth century. Modern genetic-sequence studies suggest that the virulent virus (Variola major) appeared through mutations of the milder form (Variola minor) between 400 and 1,600 years ago. This would explain the absence of smallpox from ancient texts and histories. Variola minor, in turn, was probably produced by mutation in a rodent virus more than 16,000 years ago.

Variola major was the principle form of smallpox throughout the eighteenth century, when the sickness ravaged Europe. The strategy of quarantine (begun in fourteenth-century Venice when plague-infected ships were isolated for 40 days — quaranta being Italian for forty) was practiced in smallpox outbreaks. But apart from that there seemed no way to check the dread disease. As the new century dawned, smallpox ended the Stuart royal line with the death of James II's grandson William in 1700 (his two sisters had already died of smallpox).

By the mid-eighteenth century, smallpox was a major endemic disease across the world. In Europe the death toll reached hundreds of thousands each year. At the end of the eighteenth century, about a third of all cases of blindness are thought to have been caused by smallpox. The disease checked armies, decimated populations, and ruined economies.


Excerpted from The End of Plagues by John Rhodes. Copyright © 2013 John Rhodes. Excerpted by permission of Palgrave Macmillan.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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Meet the Author

John Rhodes is an international expert in immunology and vaccine discovery, and has held research fellowships at the US National Institutes of Health and the University of Cambridge. From 2001 to 2007 he was director of strategy in immunology at GlaxoSmithKline, a leading multinational healthcare company. He is a fellow of the Royal College of Pathologists, has served on UK government international vaccine missions and published numerous articles in leading journals such as Nature, Science and the Lancet. He lives and works in Cambridge, UK.

John Rhodes is an international expert in immunology and vaccine discovery, and has held research fellowships at the US National Institutes of Health and the University of Cambridge. He is the author of The End of Plagues. From 2001 to 2007 he was director of strategy in immunology at GlaxoSmithKline, a leading multinational healthcare company. He is a fellow of the Royal College of Pathologists, has served on UK government international vaccine missions and published numerous articles in leading journals such as Nature, Science and the Lancet. He lives and works in Cambridge, UK.

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