A Planet of Viruses

A Planet of VIRUSES Carl Zimmer The University of Chicago Press Chicago and London CARL ZIMMER writes about science for the New York Times and other publications and is the author of eight books, including Parasite Rex, Soul Made Flesh, and Microcosm. He is a lecturer at Yale University, where he teaches writing about science and the environment, and visiting scholar at the Science, Health, and Environment Reporting Program at New York University’s Arthur L. Carter Journalism Institute. The University of Chicago Press, Chicago 60637 The University of Chicago Press, Ltd., London © 2011 by The Board of Regents of the University of Nebraska All rights reserved. Published 2011. Printed in the United States of America 20 19 18 17 16 15 14 13 12 11 1 2 3 4 5 ISBN-13: 978-0-226-98335-6 (cloth) ISBN-10: 0-226-98335-8 (cloth) The essays in this book were written for the World of Viruses project, funded by the National Center for Research Resources at the National Institutes of Health through the Science Education Partnership Award (SEPA) Grant No. R25 RR024267 (2007–2012). Its content is solely the responsibility of the authors and does not necessarily represent the official views of NCRR or NIH. Visit http://www.worldofviruses.unl.edu for more information and free educational materials about viruses. World of Viruses is a project of the University of Nebraska–Lincoln. Library of Congress Cataloging-in-Publication Data Zimmer, Carl, 1966– A planet of viruses / Carl Zimmer. p. cm. Includes bibliographical references and index. ISBN-13: 978-0-226-98335-6 (cloth : alk. paper) ISBN-10: 0-226-98335-8 (cloth : alk. paper) 1. Viruses. I. Title. QR360.Z65 2011 362.196’9—dc22 2010036742 This paper meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper). ISBN 978-0-226-98333-2 (electronic) To Grace, my favorite host Contents Foreword by Judy Diamond and Charles Wood INTRODUCTION “A Contagious Living Fluid”: Tobacco Mosaic Virus OLD COMPANIONS The Uncommon Cold Rhinovirus Looking Down from the Stars Influenza Virus Rabbits with Horns Human Papillomavirus EVERYWHERE, IN ALL THINGS The Enemy of Our Enemy Bacteriophages The Infected Ocean Marine Phages Our Inner Parasites Endogenous Retroviruses THE VIRAL FUTURE The Young Scourge Human Immunodeficiency Virus Becoming an American West Nile Virus Predicting the Next Plague Severe Acute Respiratory Syndrome and Ebola The Long Goodbye Smallpox EPILOGUE The Alien in the Watercooler: Mimivirus Acknowledgments Selected references Credits Index Foreword Viruses wreak chaos on human welfare, affecting the lives of almost a billion people. They have also played major roles in the remarkable biological advances of the past century. The smallpox virus was humanity’s greatest killer, and yet it is now one of the only diseases to have been eradicated from the globe. New viruses, such as HIV, continue to pose new threats and challenges. Viruses are unseen but dynamic players in the ecology of Earth. They move DNA between species, provide new genetic material for evolution, and regulate vast populations of organisms. Every species, from tiny microbes to large mammals, is influenced by the actions of viruses. Viruses extend their impact beyond species to affect climate, soil, the oceans, and fresh water. When you consider how every animal, plant, and microbe has been shaped through the course of evolution, one has to consider the influential role played by the tiny and powerful viruses that share this planet. Carl Zimmer wrote these essays for the World of Viruses project as part of a Science Education Partnership Award (SEPA) from the National Center for Research Resources (NCRR) at the National Institutes of Health (NIH). World of Viruses was created to help people understand more about viruses and virology research through radio documentaries, graphic stories, teacher professional development, mobile phone and iPad applications, and other materials. For more information about World of Viruses, visit http://www.worldofviruses.unl.edu. JUDY DIAMOND, PhD Professor and Curator, University of Nebraska State Museum Director of the World of Viruses Project CHARLES WOOD, PhD Lewis L. Lehr University Professor of Biological Sciences and Biochemistry Director of the Nebraska Center for Virology Introduction “A Contagious Living Fluid” Tobacco Mosaic Virus Fifty miles southeast of the Mexican city of Chihuahua is a dry, bare mountain range called Sierra de Naica. In 2000, miners worked their way down through a network of caves below the mountains. When they got a thousand feet underground, they found themselves in a place that seemed to belong to another world. They were standing in a chamber measuring thirty feet wide and ninety feet long. The ceiling, walls, and floor were lined with smooth-faced, translucent crystals of gypsum. Many caves contain crystals, but not like the ones in Sierra de Naica. They measured up to thirty-six feet long apiece and weighed as much as fifty-five tons. These were not crystals to hang from a necklace. These were crystals to climb like hills. Since its discovery, a few scientists have been granted permission to visit this extraordinary chamber, known now as the Cave of Crystals. Juan Manuel García- Ruiz, a geologist at the University of Granada, made the journey and figured out that the crystals formed when volcanoes began to form the mountains 26 million years ago. Subterranean chambers took shape and filled with hot mineral-laced water. The heat of the volcanic magma kept the water at around 136 degrees, the ideal temperature for the minerals to settle out of the water and form crystals. Somehow the water stayed at that perfect temperature for hundreds of thousands of years, allowing the crystals to grow to surreal sizes. In 2009, another scientist, Curtis Suttle, paid a visit to the Cave of Crystals. Suttle and his colleagues scooped up water from the chamber’s pools and brought it back to their laboratory at the University of British Columbia to analyze. When you consider Suttle’s line of work, his journey might seem like a fool’s errand. Suttle has no professional interest in crystals, or minerals, or any rocks at all for that matter. He studies viruses. There are no people in the Cave of Crystals for the viruses to infect. There are not even any fish. The cave has been effectively cut off from the biology of the outside world for millions of years. Yet Suttle’s trip was well worth the effort. After he prepared his samples of crystal water, he put them under a microscope and saw protein shells loaded with genes. Each drop of cave water may hold two hundred million viruses. Just about wherever scientists look—deep within the earth, on grains of sand blown off of the Sahara Desert, under mile-thick layers of Antarctic ice—they find viruses. And when they look in familiar places, they find new ones. In 2009, Dana Willner, a biologist at San Diego State University, led a virus-hunting expedition into the human body. The scientists had ten people cough up sputum and spit it into a cup. Five of the people were sick with cystic fibrosis, and five were healthy. Out of that fluid, Willner and her team fished out fragments of DNA, which they compared to databases of the tens of millions of genes already known to science. Before Willner’s study, the lungs of healthy people were believed to be sterile. But Willner and her colleagues discovered that all their subjects, sick and healthy alike, carried viral menageries in their chests. On average, each person had 174 species of viruses in the lungs. But only 10 percent of those species bore any close kinship to any virus ever found before. The other 90 percent were as strange as anything lurking in the Cave of Crystals. The science of virology is still in its early, wild days. Scientists are discovering viruses faster than they can make sense of them. And yet this is a late-blooming youth, for we have known about viruses for thousands of years. We have known them from their effects, in our sicknesses and our deaths. But for centuries we did not know how to join those effects to their cause. The very word virus began as a contradiction. We inherited the word from the Roman Empire, where it meant, at once, the venom of a snake or the semen of a man. Creation and destruction in one word. Over the centuries, virus took on another meaning: it signified any contagious substance that could spread disease. It might be a fluid, like the discharge from a sore. It might be a substance that traveled mysteriously through the air. It might even impregnate a piece of paper, spreading disease with the touch of a finger. Virus only began to take on its modern meaning as the nineteenth century came to a close, thanks to an agricultural catastrophe. In the Netherlands, tobacco farms were swept by a disease that left plants stunted, their leaves a mosaic of dead and live patches of tissue. Entire farms had to be abandoned. In 1879, Dutch farmers came to Adolph Mayer, a young agricultural chemist, to beg for help. Mayer carefully studied the scourge, which he dubbed tobacco mosaic disease. He investigated the environment in which the plants grew—the soil, the temperature, the sunlight. He could find nothing to distinguish the healthy plants from the sick ones. Perhaps, he thought, the plants were suffering from an invisible infection. Plant scientists had already demonstrated that fungi could infect potatoes and other plants, so Mayer looked for fungus on the tobacco plants. He found none. He looked for parasitic worms that might be infesting the leaves. Nothing. Finally Mayer extracted the sap from sick plants and injected drops into healthy tobacco. The healthy plants, Mayer discovered, turned sick as well. Some microscopic pathogen must be multiplying inside the plants. Mayer took sap from sick plants and incubated it in his laboratory. Colonies of bacteria began to grow and became large enough that Mayer could see them with his naked eye. Mayer applied the bacteria to healthy plants to see if it would trigger tobacco mosaic disease. It failed. And with that failure, Mayer’s research ground to a halt. A few years later, another Dutch scientist named Martinus Beijerinck picked up where Mayer left off. He wondered if something other than bacteria was responsible for tobacco mosaic disease, something far smaller. He ground up diseased plants and passed the fluid through a fine filter that blocked both plant cells and bacteria. When he injected the clear fluid into healthy plants, they became sick. Beijerinck filtered the juice from the newly infected plants and found that he could infect still more tobacco. Something in the sap of the infected plants— something smaller than bacteria— could replicate itself and could spread disease. Beijerinck called it a “contagious living fluid.” Whatever that contagious living fluid carried was different from any other kind of life biologists knew about. It was not only inconceivably small but also remarkably tough. Beijerinck could add alcohol to the filtered fluid, and it would remain infective. Heating the fluid to near boiling did it no harm. Beijerinck soaked filter paper in the infectious sap and let it dry. Three months later, he could dip the paper in water and use the solution to sicken new plants. Beijerinck used the word virus to describe the mysterious agent in his contagious living fluid. It was the first time anyone used the word the way we do today. But in a sense, Beijerinck simply used it to define viruses by what they were not. They were not animals, plants, fungi, or bacteria. What exactly they were, Beijerinck could not say. He had reached the limits of what nineteenth-century science could reveal. A deeper understanding of viruses would have to wait for better tools and better ideas. Electron microscopes allowed scientists to see viruses for what they are: particles of a nearly inconceivably small size. For comparison, tap out a single grain of salt from a shaker. You could line up about ten skin cells along one side of it. You could line up about a hundred bacteria. Compared to viruses, however, bacteria are giants. You could line up a thousand viruses alongside that same grain of salt. Despite the small size of viruses, scientists discovered ways to dissect them and peer inside. A human cell is stuffed with millions of different molecules that it uses to sense its surroundings, crawl hither and yon, take in food, grow, and decide whether to divide in two or kill itself for the good of its fellow cells. Virologists found that many of the viruses they studied were just protein shells holding a few genes. They discovered that viruses can replicate themselves, despite their paltry genetic instructions, by hijacking other forms of life. They could see viruses inject their genes and proteins into a host cell, which they manipulated into producing new copies of the virus. One virus might go into a cell, and within a day a thousand viruses came out. Virologists had grasped these fundamental facts by the 1950s. But virology did not come to a halt. For one thing, virologists knew little about the many different ways in which viruses make us sick. They didn’t know why papillomaviruses can cause horns to grow on rabbits and cause hundreds of thousands of cases of cervical cancer each year. They didn’t know what made some viruses deadly and others relatively harmless. They had yet to learn how viruses evade the defenses of their hosts and how they evolve faster than anything else on the planet. In the 1950s they did not know that a virus that would later be named HIV had already spread from chimpanzees into our own species, or that thirty years later it would become one of the greatest killers in history. They could not have dreamed of the vast numbers of viruses that exist on Earth; they could not have guessed that most of the genetic diversity of life can be found in virus genes. They did not know that viruses help produce much of the oxygen we breathe and help control the planet’s thermostat. And they certainly would not have guessed that the human genome is partly composed from thousands of viruses that infected our distant ancestors, or that life as we know it may have gotten its start four billion years ago from viruses. Now scientists know these things—or, to be more precise, they know of these things. They now recognize that from the Cave of Crystals to the inner world of the human body, this is a planet of viruses. Their understanding is still rough, but it is a start. So let us start as well. OLD COMPANIONS The Uncommon Cold Rhinovirus Around 3,500 years ago, an Egyptian scholar sat down and wrote the oldest known medical text. Among the diseases he described in the so-called Ebers Papyrus was something called resh. Even with that strange sounding name, its symptoms—a cough and a flowing of mucus from the nose—are immediately familiar to us all. Resh is the common cold. Some viruses are new to humanity. Other viruses are obscure and exotic. But human rhinoviruses—the chief cause of the common cold, as well as asthma attacks— are old, cosmopolitan companions. It’s been estimated that every human being will spend a year of his or her life lying in bed, sick with colds. The human rhinovirus is, in other words, one of the most successful viruses of all. Hippocrates, the ancient Greek physician, believed that colds were caused by an imbalance of the humors. Two thousand years later, the physiologist Leonard Hill argued in the 1920s that they were caused by walking outside in the morning, from warm to cold air. The first clue to the true cause of colds came when Walter Kruse, a German microbiologist, had a snuffly assistant blow his nose and mix the mucus into a salt solution. Kruse and his assistant purified the fluid through a filter and then put a few drops into the noses of twelve of their colleagues. Four of them came down with colds. Later, Kruse did the same thing to thirty-six students. Fifteen of them got sick. Kruse compared their outcomes to thirty-five people who didn’t get the drops. Only one of the drop-free individuals came down with a cold. Kruse’s experiments made it clear that some tiny pathogen was responsible for the cold. At first, many experts believed it was some kind of bacteria, but Alphonse Dochez ruled that out in 1927. He filtered the mucus from people with colds, the same way Beijerinck had filtered tobacco plant sap thirty years before, and discovered that the bacteria-free fluid could make people sick. Only a virus could have slipped through Dochez’s filters. It took another three decades before scientists figured out exactly which viruses had slipped through. Known as human rhinoviruses (rhino means nose), they are remarkably simple, with only ten genes apiece. (We have twenty thousand.) And yet that haiku of genetic information is enough to let the human rhinovirus invade our bodies, outwit our immune system, and give us colds. The human rhinovirus spreads by making noses run. People with colds wipe their noses, get the virus on their hands, and then spread the virus onto door knobs and other surfaces they touch. The virus hitches onto the skin of other people who touch those surfaces and then slips into their body, usually though their nose. Rhinoviruses can invade the cells that line the interior of the nose, throat, or lungs. They trigger the cells to open up a trapdoor through which they slip. Over the next few hours, a rhinovirus will use its host cells to make copies of its genetic material and protein shells to hold them. The host cell then rips apart, and the new virus escapes. Rhinoviruses infect relatively few cells, causing little real harm. So why can they cause such miserable experiences? We have only ourselves to blame. Infected cells release special signaling molecules, called cytokines, which attract nearby immune cells. Those immune cells then make us feel awful. They create inflammation that triggers a scratchy feeling in the throat and leads to the production of a lot of mucus around the site of the infection. In order to recover from a cold, we have to wait not only for the immune system to wipe out the virus but also to calm itself down. The Egyptian author of the Ebers papyrus wrote that the cure for resh was to dab a mixture of honey, herbs, and incense around the nose. In seventeenth-century England, cures included a blend of gunpowder and eggs and of fried cow dung and suet. Leonard Hill, the physiologist who believed a change of temperature caused colds, recommended that children start their day with a cold shower. Today, doctors don’t have much more to offer people who get colds. There is no vaccine. There is no drug that has consistently shown signs of killing the virus. Some studies have suggested that taking zinc can slow the growth of human rhinoviruses, but later studies failed to replicate their results. In fact, some treatments for the cold may be worse than the disease itself. Parents often give their children cough syrup for colds, despite the fact that studies show it doesn’t make people get better faster. But cough syrup also poses a wide variety of rare yet serious side effects, such as convulsions, rapid heart rate, and even death. In 2008, the Food and Drug Administration warned that children under the age of two—the people who get colds the most—should not take cough syrup. Another popular treatment for the cold is antibiotics, despite the fact that they only work on bacteria and are useless again viruses. In some cases, doctors prescribe antibiotics because they’re not sure whether a patient has a cold or a bacterial infection. In other cases, they may be responding