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    by Peggy Thomas

    Bacteria and

    Viruses

    San Diego Detroit New York San Francisco Clevel and New Haven, Conn. Watervil le, Maine London Munich

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    2004 by Lucent Books . Lucent Books is an imprint of Thomson Gale, a part of the Thomson

    Corporation.

    Thomson is a trademark and Gale [and Lucent Books] are registered trademarks used herein underlicense.

    For more information, contact

    Lucent Books

    27500 Drake Rd.

    Farmington Hills, MI 48331-3535

    Or you can visit our Internet site at http://www.gale.com

    ALL RIGHTS RESERVED.

    No part of this work covered by the copyright hereon may be reproduced or used in any form or by

    any meansgraphic, electronic, or mechanical, including photocopying, recording, taping, Web dis-

    tribution, or information storage retrieval systemswithout the written permission of the publisher.

    Thomas, Peggy.Bacteria and Viruses / by Peggy Thomas.v. cm. (Lucent library of science and technology)

    Includes bibliographical references and index.Summary: Discusses various types of bacteria and viruses, methods of fighting diseases,and how bacteria and viruses can be used to benefit people and the environment.

    ISBN: 1-59018-438-6

    LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA

    Printed in the United States of America

    On cover: E.coli bacteria

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    Foreword 4

    Introduction 7Swimming in a Sea of Microbes

    Chapter 1 10We Are Surrounded

    Chapter 2 25

    Early DiscoveriesChapter 3 39

    Fighting an Invisible Enemy

    Chapter 4 54Emerging Microbes

    Chapter 5 67Harnessing Invisible Power

    Chapter 6 81The Future Under a Microscope

    Notes 95

    Glossary 97

    For Further Reading 99

    Works Consulted 101Index 105

    Picture Credits 111

    About the Author 112

    Table of Contents

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    4

    The world has changed far more in the past 100 yearsthan in any other century in history. The reason is notpolitical or economic, but technologicaltechnologiesthat flowed directly from advances in basic science.

    Stephen Hawking, A Brief Historyof Relativity, Time, 2000

    The twentieth-century scientific and technological

    revolution that British physicist Stephen Hawkingdescribes in the above quote has transformed virtuallyevery aspect of human life at an unprecedented pace.Inventions unimaginable a century ago have not onlybecome commonplace but are now considered necessi-ties of daily life. As science historian James Burke writes,We live surrounded by objects and systems that we takefor granted, but which profoundly affect the way we be-have, think, work, play, and in general conduct our

    lives.For example, in just one hundred years, transporta-

    tion systems have dramatically changed. In 1900 thefirst gasoline-powered motorcar had just been intro-duced, and only 144 miles of U.S. roads were hard-surfaced. Horse-drawn trolleys still filled the streets ofAmerican cities. The airplane had yet to be invented.Today 217 million vehicles speed along 4 million milesof U.S. roads. Humans have flown to the moon and

    commercial aircraft are capable of transporting passen-gers across the Atlantic Ocean in less than three hours.

    The transformation of communications has been justas dramatic. In 1900 most Americans lived and workedon farms without electricity or mail delivery. Few peo-ple had ever heard a radio or spoken on a telephone. Ahundred years later, 98 percent of American homes have

    Foreword

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    Foreword 5

    telephones and televisions and more than 50 percenthave personal computers. Some families even have morethan one television and computer, and cell phones are

    now commonplace, even among the young. Databeamed from communication satellites routinely pre-dict global weather conditions and fiber-optic cable, e-mail, and the Internet have made worldwide telecom-munication instantaneous.

    Perhaps the most striking measure of scientific andtechnological change can be seen in medicine and pub-lic health. At the beginning of the twentieth century, theaverage American life span was forty-seven years. By the

    end of the century the average life span was approach-ing eighty years, thanks to advances in medicine in-cluding the development of vaccines and antibiotics, thediscovery of powerful diagnostic tools such as X rays, thelife-saving technology of cardiac and neonatal care, andimprovements in nutrition and the control of infectiousdisease.

    Rapid change is likely to continue throughout thetwenty-first century as science reveals more about phys-

    ical and biological processes such as global warming, vi-ral replication, and electrical conductivity, and as peopleapply that new knowledge to personal decisions and gov-ernment policy. Already, for example, an internationaltreaty calls for immediate reductions in industrial andautomobile emissions in response to studies that showa potentially dangerous rise in global temperatures iscaused by human activity. Taking an active role in de-termining the direction of future changes depends on

    education; people must understand the possible uses ofscientific research and the effects of the technology thatsurrounds them.

    The Lucent Books Library of Science and Technologyprofiles key innovations and discoveries that have trans-formed the modern world. Each title strives to make acomplex scientific discovery, technology, or phenome-non understandable and relevant to the reader. Becausescientific discovery is rarely straightforward, each title

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    6 Bacteria and Viruses

    explains the dead ends, fortunate accidents, and basic sci-entific methods by which the research into the subjectproceeded. And every book examines the practical appli-cations of an invention, branch of science, or scientificprinciple in industry, public health, and personal life, aswell as potential future uses and effects based on ongoingresearch. Fully documented quotations, annotated bib-liographies that include both print and electronic sources,glossaries, indexes, and technical illustrations are amongthe supplemental features designed to point researchersto further exploration of the subject.

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    7

    Swimming in aSea of Microbes

    Introduction

    People do not realize how often they come into con-

    tact with bacteria and viruses. These microscopicorganisms are in the air, on the surface of this book,and inside peoples bodies digesting their last meal.Most people do not fully appreciate that microbes areresponsible for the oxygen they breathe, the healthyvegetables on the kitchen table, the pungent cheese inthe refrigerator, the clean clothes in the closet, and theclean water coming through the plumbing. Every as-pect of peoples lives and every part of the natural

    world is affected, for better or worse, by the actions ofbacteria and viruses.

    And the worst comes in the form of disease. Eventhough the overwhelming majority of the encounterswith microbes go unnoticed, people are quick to re-spond when a run-in gives them a runny nose, fever,upset stomach, or more severe symptoms. Some bac-teria and viruses cause such pain and devastation thatthey become headline news. Every year novel microbes

    are discovered and new infectious diseases emerge. Itis not big news when a new bacterium is discoveredliving harmlessly in the soil, but it is broadcast whena virus mysteriously crops up out of nowhere and killsunsuspecting victims.

    The first new disease-causing organism to emerge inthe twenty-first century was a virus that appeared in a

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    remote village in China. Researchers may never knowhow or why the paths of man and microbe crossed,but that fateful event led to the global outbreak in 2003of SARS (severe acute respiratory syndrome).

    Researchers believe the viruss story started inside awildcat called a civet. Through the natural process of ge-netic change, the virus gained the ability to infect hu-mans and may have seized the opportunity to do just

    that when the civet was captured by a hunter or perhapsbought in a marketplace. Whatever the encounter was,it took only days for the first symptoms to appear. Atfirst just a few people came down with a fever and haddifficulty breathing. Soon dozens of others in the vil-lage grew ill. A doctor treated the patients as best hecould, but the mysterious illness would not respond totypical treatments. He had never seen anything like it.It was similar to the flu or pneumonia, but it hit hard

    8 Bacteria and Viruses

    Patients in a Singaporehospital wait to betested for SARS. TheSARS virus was thefirst new disease-causing organism to bediscovered in thetwenty-first century.

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    and was deadly. Mysteriously the virus avoided childrenand attacked otherwise healthy adults.

    Health officials do know that the doctor traveled toHong Kong, infecting many of the guests on the ninthfloor of a four-star hotel. One of those guests left the ho-tel and boarded an overseas flight to Toronto, Canada.Along with her luggage, she carried with her the SARSvirus. The microorganism proved to be an eager trav-eler. It unwittingly hitched rides inside its victims toTaiwan, Singapore, Vietnam, and dozens of other coun-tries.

    In reaction to this outbreak, the medical community

    and organizations such as the Centers for DiseaseControl and the World Health Organization mountedone of the fastest and largest responses in medical his-tory. Even so, in China alone, SARS infected more thanfive thousand people. It closed schools and businessesand threatened the lives of thousands of people wholanguished for weeks in quarantine. Outside of China,the virus weakened thousands of people and killed morethan eight hundred people worldwide. Economic ex-

    perts estimated that SARS cost Asian countries morethan $30 billion. Toronto, the largest city in Canada,lost $30 million a day because tourists and businesstravelers were warned to stay away.

    When a microbe kills and causes the global panic thatSARS did, it is not difficult to imagine it as a malevo-lent microorganism out to get us. But disease is just theawful side effect of living in a sea of microbes, whichare as vital to the planets web of life as we are. The

    emergence of a new disease should remind people howinterconnected human society is with these invisibleorganisms. Most of the time people are not aware thatthey exist. And unlike the clash with the SARS virus,the overwhelming majority of the encounters with mi-crobes are actually good for us.

    Swimming in a Sea of Microbes 9

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    We AreSurrounded

    10

    Chapter 1

    We are not alone. No matter how clean we are or

    how healthy we feel, we carry around on ourbodies billions of microbesmicroscopic one-celledorganisms called bacteria and viruses. Although theycannot be seen, microbes hide under fingernails, lurkbetween teeth, and live in hair. There are more than sixhundred thousand bacteria living on just one squareinch of skin, and an average person has about a quarterof a pound of bacteria in and on his or her body at anygiven time. There are more microbes on a persons body

    than there are humans on Earth.Viruses and bacteria are responsible for some of the

    deadliest diseases in history, such as AIDS, the plague,and flu. And yet bacteria perform the most importantroles in maintaining life on this planet. They [bacte-ria] protect us and feed us, says Abigail Salyers, formerpresident of the American Society for Microbiology. Alllife on Earth depends on their activities.1 Bacteria arethe planets recyclers, plant nurturers, and undertakers.

    Microbes have been found in almost every type ofenvironment. Some thrive in subzero Arctic ice, whileothers live in boiling undersea volcanoes. Bacteria havebeen found inside oil-drilling cores pulled from morethan a thousand feet down in the earths crust, and ithas been estimated that there may be as much as 100trillion tons of bacteria deep beneath the surface of the

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    earth. If all the subterranean microbes were broughtto the surface, they would cover the planet with a layerfive feet deep. Microbes have been discovered six milesbeneath the Pacific Ocean, where the pressure is equiv-alent to being squashed by fifty jumbo jets, as well asnineteen miles out in space.

    Professor Adrian Gibbs of the Australian NationalUniversity asserts, You can increase the probability offinding new things by looking in interesting places,like deep sea vents or thermal pools, but you can alsofind them in your own backyard.2 One teaspoon ofordinary soil contains 10 million bacteria, and one acre

    of soil can hold up to five hundred pounds of micro-scopic life. There is more unseen life than seen. Themass of all microbes on the planet is twenty-five timesmore than the mass of all other animals combined.The human race may believe it is at the top of the foodchain, but microbes are the food chain.

    We Are Surrounded 11

    Microbes can thrive inalmost anyenvironment, fromsubzero Arctic ice toboiling underwatervolcanoes.

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    Ancient Microbes

    How did these organisms become so widespread? Theanswer lies in the fossil record. Scientist J. William

    Schopf found evidence of ancient microbes in rock sam-ples collected in western Australia in the 1980s. Theserocks proved that bacteria had been on Earth for morethan 3.5 billion years, long enough to adapt to nearlyevery type of environment. In his book Cradle of Life,Schopf notes, These organisms are not only extremelyancient but surprisingly advanced, and show that earlyevolution proceeded faster and faster than anyone imag-ined. 3 Scientists have even discovered a strain of bac-

    teria that can survive blasts of radiation one thousandtimes greater than the amount needed to kill a humanbeing.

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    Bacteria and viruseshave infected humansfor thousands of

    years. Some Egyptian

    mummies bear scarsor other evidence ofviral disease.

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    Scientists have not found fossil evidence of ancientviruses and may never do so because viruses are sosmall. But researchers believe that viruses have beenaround just as long as bacteria have, or even longer.Deadly viruses may have played a part in the extinc-tion of the dinosaurs and are thought to have con-tributed to human evolution.

    Historians do know that bacteria and viruses infectedhuman civilizations as far back as three thousand yearsago. The mummy of Egyptian pharaoh Ramses V hasthe telltale signs of scars caused by the deadly small-pox virus. The shriveled arms and legs of other mum-

    mies suggest that these people suffered from the poliovirus. And the Bible describes an ancient plague, rem-iniscent of anthrax, which caused sores that breakinto pustules on man and beast. 4

    Bacteria

    One reason scientists believe that microbes have sur-vived for so long is their simple structure. A bacteriumis a primitive one-celled organism. Like all living things,it grows, uses energy, makes waste, and reproduces allwithin one cell. A hard cell wall made of cellulose pro-vides support and protects the bacteria from antibioticsubstances, such as medicines, tears, and saliva. An in-ner lining, called the cell membrane, acts as the gate-keeper controlling what goes in and out. Some bacte-ria also have a sticky outer coat, called a capsule, thatallows the bacteria to stick to other cells.

    Bacteria come in three basic shapes: Cocci (pro-nounced cox-eye) are shaped like little round balls;bacilli (buh-sill-eye) are rod- or stick-shaped; and spirilla (spy-rill-uh) form a spiral. Scientists estimate thatthere may be a million species of bacteria in the worldand more than five thousand different viruses, but onlya small fraction of these has ever been studied.

    Some bacteria exist as individual cells floating ontheir own, while others cluster together to form pairsthat scientists call diplo. Several bacteria strung together

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    in a chain are called strepto, and when bacteria stick to-gether in clusters, they are referred to as staphylo.

    Bacteria have a wide-ranging diet. Some bacteria arecapable of photosynthesis, just like plants. They maketheir own food from sunlight and give off oxygen.These bacteria are called cyanobacteria. Although theseaquatic organisms are often referred to as blue-greenalgae, that name is misleading because they are not re-lated to other types of algae.

    Other bacteria absorb nutrients from the materialsthat surround them. There are bacteria that feed off ofwood, glue, paint, and anything dripped, dribbled, or

    left out on the kitchen counter too long. Others eat iron,sulfur, petroleum, a variety of toxic chemicals, and evenradioactive plutonium. The bacteria that live in a per-sons stomach absorb the nutrients from ingested food.A rotten spot on an apple is evidence that bacteria areeating. The sour smell of old milk is a clue that bacteriaare there. And the feeling of fuzzy teeth in the morningis evidence that bacteria are at work.

    Although most bacteria cannot move about their en-

    vironment on their own, some have flagella, long whip-like tails that propel bacteria through a drop of liquid.One bacteriums flagellum was recorded moving twenty-four hundred beats per minute. Other bacteria are notas speedy. They secrete a slime that allows them to slideover surfaces like a slug, or they move with the help ofcilia, tiny hairlike structures that beat wildly.

    Bacteria move in response to their environment.While studyingEscherichia coli (the bacteria that live

    in human intestines and can sometimes cause diar-rhea), researchers identified special structures callednose spots. These nose spots allow the bacterium tosense the presence of food and move toward it. Theyalso detect toxins and move away from them. Thesenose spots are extremely sensitive and can perceivetiny changes in the surrounding environment. It is thesame degree of sensitivity that would allow a personto detect the difference between a jar with 9,999 pen-

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    nies and one with 10,000 pennies. When food is de-tected, the receptors send a message to the flagella,which then beat rhythmically, carrying the bacteriatoward the increased concentration of food.

    When food is not available, bacteria are capable of ly-ing dormant for many years in the form of a spore. Sporesof anthrax have been found in eighty-year-old museumdisplays; other bacterial spores have been brought back

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    to an active state from cans of meat that were 118 yearsold and beer that was 166 years old. Russian scientistseven claim to have brought back to life bacteria that wasfrozen in Arctic ice for a million years.

    Spores are hard to find because they are microscopic.All bacteria are measured in nanometers. One nanome-ter is one-billionth of a meter. The period at the endof this sentence is about 1 million nanometers in di-ameter. The average bacterium, in comparison, is onlyone thousand nanometers across.

    Bacteria are small, but viruses are even smaller. Toget an idea of their size, imagine one human cell the

    size of a baseball diamond. In that cell, an average bac-terium would be the size of the pitchers mound. Buta single virus would be the size of a baseball. Scientistsneed to use a powerful piece of equipment called anelectron microscope to enter the world of the virus.

    Viruses

    Bacteria and viruses are often grouped together underthe heading of microbes, but there are vast differencesbetween them, and size is just one of those differences.While bacteria perform all of the functions necessary tobe considered a life form, scientists debate whether virusesare alive at all. For something to be alive it must eat, grow,make waste, and reproduce. When a virus is floatingaround in the air or sitting undisturbed in soil, it is nomore alive than a rock. But if that same virus comes incontact with a suitable animal, plant, or bacterium cell,it suddenly becomes active. A virus does not eat, but it

    gets its energy from the host cell it infects. It does notgrow in the sense that it gets larger, but it does reproduce.In fact, a viruss sole purpose seems to be reproduction,and it cannot do that without the help of a living cell.

    A virus is not even considered a true cell. It is sim-ply a tiny bundle of genetic material, DNA (deoxyri-bonucleic acid) or RNA (ribonucleic acid), surroundedby a protein coat. Both DNA and RNA are the mole-cules that contain coded genetic information. They

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    make up genes that determine what an organismlooks like and how it behaves. Unlike the DNA in ananimal or plant cell that is contained in a nucleus,

    viral DNA floats loosely within the protein coat, orcapsid.Like bacteria, viruses come in many shapes and sizes.

    Many are multisided and look like a cut diamond.Other viruses are shaped like sticks, ovals with spikes,or tiny sausages. The deadly Ebola virus looks like apiece of looped string. Viruses that attack bacteria arecalled bacteriophages and resemble tiny lunar land-ing modules or alien spaceships.

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    Microbial MultiplicationMicrobes are experts at mass production. Bacteria re-produce through a process called binary fission. One

    cell divides into two cells, each of which then divideinto two more. Each cell is identical to the mother cell.Most bacteria divide every two or three hours, somewait as long as sixteen hours, and others are capable

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    of dividing every fifteen minutes. One researcher esti-mated that if one bacterium reproduced every twentyminutes without running out of food or encounteringany toxins, it would grow into a colony of 2 millionbacteria within seven hours.

    Viruses are just as productive, but they cannot do italone. Viruses need the reproductive mechanisms of aliving cell in order to multiply, but first the virus mustget inside the cell. A cells membrane is made out ofprotein molecules, and some molecules have speciallyshaped receptors, or landing sites, where other mole-cules with matching shapes can land and dock. This

    lock-and-key system allows the entry of only certainmolecules that are necessary for normal cell function.For example, essential nutrients such as oxygen are al-lowed to pass through the membrane to one of manyof the cells powerhouses, the mitochondria. Nitrogenis received at different sites on the membrane and shut-tled through to be used in the assembly of various pro-teins.

    But viruses have also acquired the key to specific

    cells. For example, the pneumonia virus is capable oflatching on to a human lung cell. The virus that causeshepatitis can infect human liver cells. The human im-munodeficiency virus (HIV) that causes AIDS is capa-ble of landing on white blood cells.

    Once a virus attaches to a host cell, it inserts its ge-netic material in one of three ways. Some host cells arefooled into thinking that the virus is food. These cellspull the genetic material in just as they would pull in

    other nutrients. Other viruses have a sticky coat thatfuses with the cells membrane, and the genetic mate-rial enters that way. Other viruses forcibly pierce thecells membrane and inject their DNA into the host.

    The genetic material from the virus hijacks the re-productive machinery of the host cell and provides itwith a new set of instructions to follow. The cell isnow programmed to make hundreds of copies of theviruss DNA or RNA instead of its own.

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    The virus then uses the cells enzymes, which aremolecules that control chemical changes, to build newcapsids and other proteins it needs to survive. Like agenetic factory, the host cell churns out viral parts thatare assembled into brand-new identical viruses. Allother cell functions are shut down to conserve energyfor producing as many viruses as the cell can stand.Some cells simply fall apart from exhaustion, andviruses tumble free. But other viruses actively dissolvethe cell membrane to get out. Stronger cells will fill upwith viruses until they burst like an overfilled waterballoon. The new viruses are free to infect other host

    cells, a process that spreads the disease. This continuesuntil the virus is stopped or the host dies.

    Microbes at Work

    Other microbes can cause the death of their hosts too,but the vast majority of bacteria play a vital role inEarths ecosystem. All life on Earth is connected in aweb of relationships. Every creature, no matter howsmall, has a job to do, and microbes are the workhorsesof the living world.

    Bacteria keep the planets life cycles turning. It is animportant job because the earth is a closed system.There is only a limited amount of the materials thatsustain all living things, and these elementsoxygen,carbon, hydrogen, nitrogen, phosphorus, and so onhave to be recycled again and again. Microbes are thekey players, chemists building, breaking down, and re-building chemical compounds for both animal and

    plant use. For example, animals breathe in oxygen andexhale carbon dioxide (CO2). Plants take in that CO2and release oxygen that will be taken up again by an-imals. Microbes beneath the sea pump out about 150billion kilograms of oxygen every year, producing one-half of all the oxygen we breathe. This recycling processseems simplistic on the surface, but scientists are awedby the complexity of this assembly-line efficiency thatis required to keep the earths ecosystem cycling. If that

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    system were to stop, all the oxygen in the air would beexhausted within twenty years.

    A similarly complex cycle occurs for nitrogen.Nitrogen exists in every living cell and is necessary forbuilding proteins. Although nitrogen is the most com-mon gas in the atmosphere, animals cannot use it inthat form. Animals get their nitrogen from eatingplants or eating plant eaters. Most plants are also un-able to take nitrogen from the air; they get their cell-building nitrogen from the soil. But most plants can-not get the nitrogen they need without the help ofnitrogen-fixing bacteria. These bacteria fix the ni-

    trogen by combining the nitrogen in the atmospherewith other elements to form organic compounds inliving cells. When these cells later die, the nitrogen,now in a fixed form, is readily available to the plantsthrough their root systems with the help of other bac-teria in the soil. In return, the plant supplies the mi-crobes with nutrients for their growth. Some bacteriasimply live in the soil surrounding the roots, but otherkinds of bacteria actually live inside the roots of plants.

    Farmers rejuvenate their fields by planting nitrogen-fixing crops such as the pea plant. These plants havea powerful partnership with a bacterium called Rhizo-bium. As a young pea plant sends out its roots, it alsosends out a signal to willing bacteria. The bacteria inthe soil migrate to the roots, where they are surroundedby and eventually become part of the roots. An up-rooted pea or clover plant reveals tiny nodules or bumpswhere the bacteria are working to fix nitrogen for the

    plant. In return, the plant provides the bacteria with asafe home and the nutrients they need to live. This sys-tem is very effective. Researchers estimate that the bac-teria living in Asian rice paddies are capable of fixingmore than six hundred pounds of nitrogen per acre.

    DecompositionAnother job of the microbial chemists is to free up theessential chemical compounds that are trapped in

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    plants and animals and would otherwise remaintrapped after death. Bacteria (along with fungi) are theundertakers of the microbial world. Bacteria help break

    down the dead matter in a process called decomposi-tion. If all the microbes were wiped out suddenly,nothing would rot. We would eventually be knee-deepin dead organisms.

    All living things only borrow their atoms. They mustbe continually rotated and returned to the soil so thatother plants and animals can grow. The fertilizers thatpeople put on their lawns are nothing more than mix-tures of chemical compounds of phosphorus, nitro-

    gen, sulfur, and potassium, the same elements that arereleased into the soil by the decomposing activities ofmicrobes.

    The Bacterial Buddy SystemJust as some bacteria form partnerships with plants,other bacteria form partnerships with animals. Oneof the most common relationships involves bacteriadigesting other animals food.

    Ruminant animals like cattle, sheep, goats, giraffes,and camels are incapable of digesting cellulose, a tough,protective structural substance that forms plant cellwalls. Yet leafy greens are their prime food source. Theonly creatures known to digest cellulose are microbes,so the only way ruminant animals can get any nutri-tion from plants is to harbor a healthy amount of bac-teria in two of their four stomachs. The first two stom-achs in the digestive system of a cow contain billions

    of bacteria that break down the cellulose into glucose,which the cows cells can use.Humans rely on bacteria to digest the cellulose in

    food too. When babies are born, their mouths and di-gestive tracts are sterile; there are no microbes livingthere yet. Newborns have been protected from all in-fection, including beneficial microbes, by the placenta.But the first time babies are fed, they get the bacteriathey need to digest food for the rest of their lives.

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    Besides breaking down tough cellulose in a personsdiet, the bacteria that live in the large intestine also pro-duce essential vitamins (K, B12, thiamine, and riboflavin)that humans could not make themselves. Studies of an-

    imals born and raised in a sterile environment showhow vital microbes are to survival. Without them a per-son would have a whole host of problems. Without vi-tamin K, which is necessary in the clotting process ofblood, a person would be prone to uncontrolled bleed-ing. Without vitamin B12, a person would suffer from ablood disorder called pernicious anemia. Scientists didnot realize the importance of bacteria in our digestivesystem until the development of antibiotics. They were

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    An electronmicrograph showsbacteria at workbreaking down food

    in the humandigestive tract.

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    surprised to find that people developed digestive prob-lems when taking an antibiotic. The drug killed thegood bacteria in the intestines as well as the badbacteria that made them sick.

    Viruses and Evolution

    Microbiologists are discovering new information everyday about the important roles bacteria play in theworlds ecosystem. But no one has yet discovered ifviruses have a beneficial function. Recent studies sug-gest that viruses may play some part in the adaptationsthat change species over time. Geneticists have foundbits and pieces of viral DNA inside animal cells. Thesesmall fragments were probably left behind from a timewhen that animal was infected with the virus. Whilethe host cells were reproducing the viruss DNA parts,the genetic material was pulled into the hosts genes.There they survived in the hosts cells and were passeddown to the animals offspring.

    Geneticists discovered that this junk DNA accountsfor nearly half of a persons genetic material, or genome.People started to seriously consider that they [viruses]might contribute to evolution, 5 says John McDonald,a molecular evolutionist at the University of Georgia.Certain viral genes may have caused significant changesin human looks and behavior or even the branchingoff of man from ape 6 million years ago.

    Bacteria and viruses have inhabited the earth muchlonger than humans have and were performing im-portant tasks long before we arrived. Microbiologistsare still learning the intricate connections that link themicrobes existence with our own. The smallest or-ganisms on Earth have had a powerful effect. Theyhave even altered the course of human history.

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    Early Discoveries

    25

    Chapter 2

    It is impossible for the human tongue to recountthe awful truth. . . . The victims died almost im-mediately. They would swell beneath the armpitsand in the groin and fall over while talking. Fatherabandoned child, wife husband, one brother an-other; for this illness seemed to strike throughbreath and sight. . . . In many places . . . great pitswere dug and piled deep with the multitude ofdead. And they died by the hundreds, both day andnight. 6

    Agnolo di Tura chronicled this tragic yet commonoccurrence in Siena, Italy, in 1348. Called the GreatPestilence, the disease was later known as the BlackDeath or bubonic plague, and it swept through Europewith frightening speed. Spread by the bite of an in-fected flea, the Yersinia pestis bacteria caused the mostdevastation recorded in human history. Within fouryears it killed one-third of the population of Europe,more than 25 million people.

    The first symptom to strike a plague victim was a se-vere headache. The victim would grow weaker and even-

    tually too tired to walk. After about three days the lymphnodes in the victims armpits and groin swelled to thesize of goose eggs. These swellings, called buboes, gavethe disease its namethe bubonic plague. The victimsheart would futilely try to pump blood throughout theswollen areas. Blood vessels broke, causing widespreadhemorrhaging that blackened the skin. Soon the patient

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    would cough up blood and the nervous system wouldcollapse, causing their limbs to jerk in fits of pain.

    Once the lungs became infected, the disease couldbe transmittable from person to person through theair. At that stage, it was called pneumonic plague, andit swept through villages like wildfire. Within a weekthe patient was dead.

    I, Agnolo di Tura, buried my five children with myown hands. . . . And so many died that all believed itwas the end of the world. 7

    The world did not end, but it did change drastically.With more than a third of the population gone, la-

    borers were in high demand. Large tracts of land weresuddenly available for those once too poor to own

    26 Bacteria and Viruses

    A nineteenth-centurypainting depicts theagony of plaguevictims. The Black

    Death of the 1340s,the worst outbreak of

    plague in history,

    decimated Europespopulation.

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    property. The wealthy became wealthier still, as theyaccumulated the riches of their dead relatives. Thosewho survived the epidemic experienced a time of re-juvenation.

    They also experienced a time of doubt and inquiry.The methods for dealing with the plague had failedmiserably. Many physicians began questioning the va-lidity of the ancient Roman medical philosophies thathad been the foundation of all their knowledge. Somebegan to study the human anatomy and develop newmethods of treating the sick. Rather than relying ontraditional methods, scientists began proposing new

    theories of disease and experimenting to prove or dis-prove their theories. An invisible bacterium capableof killing millions changed history and opened thedoor to an era known for its startling new ideastheRenaissance.

    Smallpox and the New WorldMicrobes had an impact on history in the Americas aswell. The Caribbean island of Hispaniola had more thana million inhabitants when Christopher Columbuslanded there in 1492. Within twenty years, more than athird of the population was dead. Some died at the handsof cruel Spanish masters, others starved to death, but themajority of native islanders died from an epidemic dis-ease they had never seen beforesmallpox.

    Breathing in the invisible virus particles from an in-fected persons sneeze or cough spread the smallpox virusfrom person to person. A week after inhaling these par-ticles, an infected person came down with a high fever,body aches, a headache, and chills. Soon the victim brokeout in a flame-red rash that grew fiery, raised, and blis-tered. These sores or pustules gave the virus its name,variola, derived from the Latin word for spotted. A per-son who survived might have scars or be permanentlyblinded. More severe cases that attacked the internal or-gans resulted in death. This devastating disease spreadquickly through a population that had no resistance.

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    The same thing happened when Hernn Corts in-vaded the Aztec city of Tenochtitln, where he and hissoldiers were soundly defeated by the Aztec army. Butas the Spaniards fled, they unwittingly left behind atime bomb in the form of a dead Spanish soldier in-fected with smallpox. Within weeks, the entire capi-tal was under siege by the smallpox virus, which killedone-fourth of the citys inhabitants. According to oneSpanish priest, In many places it happened thateveryone in a house died and, as it was impossible tobury the great number of dead, they pulled down thehouses over them so that their homes became their

    tombs.

    8

    The smallpox epidemic spread throughout Mexicoand helped the Spaniards defeat the Inca Empire aswell. Without the help of the deadly smallpox virusand other epidemics, the Europeans might not haveso easily conquered the New World. Smallpox also trav-eled to Brazil with the Portuguese, killing tens of thou-sands of Indians there, and marched north to NorthAmerica with the British, French, and Danish explor-

    ers, wiping out scores of Native American villages andentire tribes. The terror was universal. According toone French missionary stationed in Canada, The con-tagion increased as autumn advanced; and when win-ter came . . . its ravages were appalling. The season ofHuron festivity was turned to a season of mourning.9

    Other infectious diseases caused by bacteria andviruses may not have had such a profound effect on theworld order as the bubonic plague and smallpox, but

    they also weakened armies, wiped out villages, attackedthe poor, and cast blame on those who were different.

    Punishment from the Gods

    Where could these horrific diseases come from? Theymysteriously came upon a person, gripping him or herwith terrible symptoms and then quickly spread througha community. Ethnic and religious groups were oftenblamed for the disease.

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    Prior to the 1800s most people believed that epi-demics like the plague and smallpox were punishmentsfrom God. Describing the plague that hit Italy in 1347,the Italian writer Giovanni Boccaccio suggested thatthe plague signified Gods anger at peoples wicked way

    of life. And when the Black Death ravaged England threeyears later, the archbishop of York said, This surelymust be caused by the sins of men.10

    In India, people worshipped Sitala, the goddess of small-pox. Known as the cool one, she had the power to re-lieve raging fevers. In paintings and sculptures Sitala isportrayed dressed in red, riding a donkey. She carries acup of water to cool a victims wilting thirst and a broomto sweep away the disease. Although people bestowed

    Early Discoveries 29

    English nurses tend tosmallpox patients inthis nineteenth-century illustration.

    Although a vaccineexists today, deadly

    outbreaks of smallpoxhave been commonthroughout history.

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    her with offerings of cool drinks and chilled food, theyalso feared her, for Sitala could inflict the disease on theundeserving as well. It seemed only reasonable to blamethe mysterious illness on a higher power. After all, noone could see another cause.

    The earliest written record suggesting that invisibleliving things might cause illness came from the Romanwriter Marcus Terentius Varro. In the first century A.D.he wrote, Care should be taken where there areswamps in the neighborhood, because certain tinycreatures which cannot be seen by the eyes breedthere. These float through the air and enter the body

    by the mouth and nose and cause serious disease.

    11

    Microbes Come into View

    Perhaps Varro was not the only one who suspected thata living organism invisible to the naked eye could ex-ist, let alone cause the deadly destruction that plaguedhumankind. But it was not a popular thought. Therewas no evidence that these tiny creatures inhabited theworld until a curious amateur scientist named Antonivan Leeuwenhoek saw them for the first time in 1676.

    By profession, Leeuwenhoek was a draper (a clothdealer) who examined threads for flaws with a magni-fying glass. His fascination with magnifying lenses andthe world they brought into view led him to experi-ment with single-lens microscopes he made himself.While others used microscopes that enlarged objectsonly ten times their size, Leeuwenhoeks microscopecould magnify up to 270 times. His lenses were so

    finely made that experts today still are not sure howthey were constructed given the technology of the sev-enteenth century.

    What Leeuwenhoek saw under his microscope wouldopen up a new field of science called microbiology. Afterlooking at the matter he picked from between his teeth,Leeuwenhoek recorded for the first time the presenceof what are now known as bacteria. He described themas animacules, very prettily a-moving. The biggest sort

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    had a very strong and swift motion, and shot throughthe water like a pike does through the water; mostlythese were of small numbers.12

    Although Leeuwenhoek was the first person to de-scribe bacteria, the scientific community did not takehis observations seriously. In 1676 the secretary of theRoyal Society in London, wrote to Leeu-wenhoek: Your letter . . . has been receivedhere with amusement. Your account of myr-iad little animals seen swimming in rain-water, with the aid of your so-called mi-croscope, caused the members of the

    society considerable merriment when readat our most recent meeting. 13 The mem-bers of the Royal Society declined to pub-lish Leeuwenhoeks observations until 1683,when they received more evidence. In themeantime, Leeuwenhoek continued to studypond water, spittle from an old man, in-sect larvae, and even the spermatozoa insemen. Leeuwenhoek brought the world

    beneath the microscope into view, but itwould take one hundred years before theseinvisible creatures would be linked withdisease.

    Putting It All TogetherThroughout the 1860s, two scientists, LouisPasteur of France and Robert Koch ofGermany, working independently, collectedconvincing evidence that infectious diseaseswere caused by microbes and not by evilspirits or the wrath of God.

    Pasteur was a chemist and microbiologistworking in France. In his studies of winemaking for the wine industry, he learnedthat microscopic bacteria and yeast organ-isms caused fermentation, the chemicalbreakdown of carbohydrates into carbon

    Early Discoveries 31

    In the seventeenthcentury, Antoni van

    Leeuwenhoek inventedthis powerful single-lens microscope.

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    dioxide and alcohol. He went on to identify the mi-croorganisms that caused food to spoil and decompose.Before his discovery, people assumed that spoilage was

    the natural result of chemical breakdown over time.Pasteur found the microbes in milk that caused it to spoiland also devised pasteurizationthe process of heatingmilk to a certain temperature at which harmful bacte-ria are killed.

    After Pasteurs success in the wine industry, the silkmanufacturers of France consulted him about the mys-terious deaths of their prized silkworms. Pasteur iden-tified two different bacteria that caused the deadly silk-

    worm disease. Pasteurs work provided the world with

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    Anthrax bacteriainfect lung tissue. In aseries of laboratoryexperiments withmice, Robert Kochwas able to isolate thedeadly anthraxbacterium.

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    convincing evidence that microorganisms cause dis-ease, a concept that became known as the germ the-ory. Around the same time in Germany, medical doc-tor and researcher Robert Koch was also putting someof the pieces of the bacterial puzzle together.

    Robert Koch

    Koch was experimenting with ways to grow bacteriain the lab when he developed the process for growingbacteria that is still followed today. By using a gelatin-like substance called agar, which is made from seaweed,rather than blood or tissue from an animal, pure bac-terial cultures could be grown without contaminationfrom other blood or tissue cells. Kochs assistant, JuliusPetri, created a covered shallow glass dish to hold theagar and the growing culture. Today this commonlyused piece of lab equipment bears his namea petridish.

    Another problem Koch struggled with was makingbacteria more visible under a microscope. Some bac-teria are very difficult to see, especially if they aremixed with other cells. Through experimentationKoch found that bacteria absorbed a dye made fromcoal tar, called aniline dye, which made them easierto see under the microscope.

    At the time Koch was perfecting his lab techniques,anthrax was a common and debilitating disease that at-tacked cattle and sheep throughout Europe. Parts ofGermany were hard hit by the disease, and Koch set outto isolate the bacterium that caused it. He injected mice

    with blood taken from the spleens of infected animalsand observed how the disease worked as he transferredit from one mouse to another. His study of disease ledhim to write the criteria that are still used to determineif a microorganism is the cause of a disease. CalledKochs postulates, these criteria state that a pathogenic(disease-causing) organism must be present in everycase of the disease. This organism can then be grown,or cultured, outside the body. An animal inoculated

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    with the culture would develop the same disease. Theorganism could then be taken from that infected ani-mal and cultured again.

    Koch went on to isolate the bacteria that caused tu-berculosis and chicken cholera, and Pasteur used Kochslab methods to expand on his work with anthrax. Inorder to create a vaccine for sheep, Pasteur weakenedthe anthrax bacterium by growing it in the lab athigher temperatures than normal. When this weak-ened bacteria was injected into a healthy animal, itprevented infection from the virulent anthrax bacte-ria and became an effective vaccine. Pasteur went onto create a vaccine for chicken cholera and rabies.

    By the end of the nineteenth century the germ the-ory was accepted as a scientific principle. Only oneproblem remained. For some diseases, no microor-ganisms could be found.

    What Could Be Smaller than Bacteria?

    Although Pasteur created a vaccine for rabies, he neversaw the organism that caused this dreaded disease.Many other scientists who worked on plant and ani-

    mal infections assumed they were looking for bacte-ria, but they would never find them. What they didfind was something smaller and more puzzling.

    In 1886 Adolf Mayer, a German scientist, was re-searching the tobacco mosaic disease, so called becauseit left the leaves of the tobacco plant shriveled andmottled. Mayer believed that the disease was causedby a bacterium, but he failed to isolate the elusive or-ganism. In 1892 Russian scientist Dmitri Ivanovski

    ruled out the possibility that a bacterium caused allthe damage to the tobacco plant. He suggested that asmaller pathogen must be at work, possibly a toxin.It was not until six years later that Martinus Beijerinck,a scientist from the Netherlands, showed that the dis-ease was indeed caused by an infectious agent smallerthan any other life-form known.

    Ivanovski and Beijerinck performed similar experi-ments. They pressed juice from infected plants through

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    filters so fine that they removed all bacteria. When thisfiltered liquid was rubbed onto a healthy plant, itcaused the leaves to shrivel and discolor. Both scien-tists discovered that the plant juice could be dilutedmany, many times and still cause disease. And althoughthey suspected a bacteria-like organism might be atwork, it could not be grown separately in a petri dish.

    Where Ivanovski and Beijerinck differed was in theirconclusions. Beijerinck believed that whatever passedthrough his filters was some kind of an infective agent

    Early Discoveries 35

    Dutch botanistMartinus Beijerinckwas the first scientistto identify viruses,infectious microbesthat are even smallerthan bacteria.

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    other than bacteria. He did not believe it was simplya toxin, as Ivanovski suggested. Beijerinck filtered anddiluted the infective liquid again and again until hewas left with such a weak substance that if it were atoxin, it would no longer harm the plant. But whenthis diluted substance was rubbed onto a healthy to-bacco leaf, it shriveled and the disease spread to otherparts of the plant. Attempts to grow the organism inthe lab failed. Whatever it was, the infective agentwould grow and spread only inside plant cells.

    In 1898 Beijerinck wrote his conclusions. Using theLatin term for poison, he called the elusive particle a

    filterable virus. He showed that although it could notbe seen, the virus was an infective agent that was notconducive to being cultured in a lab. In his paper heobserved, The contagion, to reproduce itself mustbe incorporated into the living cytoplasm of the cellinto whose multiplication it is, as it were, passivelydrawn. 14

    Building on Beijerincks virus theory, new discover-ies were made in rapid succession. That same year,

    Friedrich Loeffler and Paul Frosch discovered the virusthat caused foot-and-mouth disease, which had beenkilling cattle throughout Europe. They collected pusfrom the sores of infected cattle and passed it througha filter. They did not find a bacterium, but they did dis-cover that when the so-called filterable virus was in-jected into a healthy animal, it caused the disease.

    It was not until 1900 that a filterable virus was dis-covered to cause human disease. Yellow fever had been

    rampant and troublesome throughout Central andSouth America. It caused almost insurmountable prob-lems for the builders of the Panama Canal. Cuban doc-tor Carlos Juan Finlay suspected that a mosquito, Aedesaegypti, spread the disease. But this idea did not receivemuch attention until U.S. Army doctor Major WalterReed traveled to Cuba and conducted medical experi-ments. He discovered that the disease was caused by afilterable virus and confirmed that a mosquito was in-

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    deed the vector (it carried the virus from person to per-son).

    Fifteen years later brought the discovery of a virus thatinfected bacteria. It was called a bacteriophage (bacteriaeater). The definition of a virus was taking shapeanorganism that could be passed through the finest filterand still cause an infectious disease in plants, animals,humans, or bacteria. The organism, however, could not

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    be seen and could not be grown in a laboratory. It wasnot until the 1930s that scientists got their first glimpseof their smallest enemy.

    Viruses Come into ViewImprovements in microscope manufacturing did nothelp the search for viruses until a revolutionary ma-chine was invented. In the 1930s German researchersMax Knott and Ernst Ruska created the electron mi-croscope.

    Instead of using an ordinary beam of light to illu-minate an object, the electron microscope uses elec-trons, which are accelerated in a vacuum until theirwavelength is extremely short. The beams of these fast-moving electrons are then focused on cells. The elec-trons are absorbed or scattered by the cells parts andform an image on an electrosensitive photographic plate.This technique allows the microscope to magnify an im-age up to 1 million times.

    For the first time scientists could see the shape ofviruses. But the electron microscope still did not revealwhat a virus was made of or how it was constructed.That breakthrough came in 1932, when chemist WendellStanley used a technique called X-ray crystallography totransform the tobacco mosaic virus into a crystal. Thiswas an amazing feat. Because crystallization is a charac-teristic of a mineral, a nonliving thing, Stanleys achieve-ment proved that a virus is not a typical living organism.It is essentially a chemical molecule, a protein, withminute bits of genetic material. This discovery won

    Stanley the Nobel Prize in Chemistry.The bulk of what was discovered about microbes inthe early years of microbiology was through the studyof disease and disease-causing bacteria and viruses.One prime goal was finding a way to destroy them.

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    Fighting anInvisible Enemy

    39

    Chapter 3

    Humans have evolved along with bacteria and

    viruses for millions of years, so it should be nosurprise that the human body has developed a systemof keeping the harmful microbes out. The first line ofdefense is the skin, which is a sheath of closely inter-locking cells. Sweat and oil glands under the skin se-crete acids that prevent the growth of microbes, andharmless bacteria that normally live on the body de-fend their territories against foreign bacteria.

    The nose, mouth, and throat are common sites of at-tack, but fragile membranes and layers of sticky mucusthat are toxic to harmful microbes protect them. Tearsand saliva also contain antiseptic substances. Bacteriaand viruses are sneezed out, coughed up, and cried outof the body. If microbes make it through these barriers,they are swallowed. Most will not survive in the stom-achs acid environment or the toxic world of the in-testines. The beneficial bacteria that reside there willfight off potential competitors.

    Our Internal ArmyA cut on the skin is a way in for some opportunistic mi-crobes, but the body quickly fights back with an in-flammatory response. Injured cells release histamine, achemical that causes blood vessels near a wound to swell,which brings more blood to the area to aid healing.

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    Blood quickly clots to seal off the cut and prevent morebacteria from getting into the bloodstream and spread-ing further into the body.

    Injured cells also release a chemical that attractsbacteria-eating white cells called phagocytes. Phagocytesengulf any bacteria they encounter until they are sofull they die. Any bacteria that manage to get pastthe phagocytes will be carried to other parts of thebody. The bodys immune system is alerted and sendsout lymphocytes, or white cells. There are about 2trillion lymphocytes patrolling a persons bloodstreamand lymph system at any given time. They stand

    guard in the spleen, tonsils, and lymph nodes and de-tect all foreign invaders such as bacteria, viruses,fungi, and transplanted organs.

    When a foreign invader is detected, the lymphocytesdivide and create antibodies to kill or neutralize the in-vaders. Antibodies are chemicals that target and destroyonly one type of invader. For example, an antibody sentout to fight against the pneumonia bacterium cannotfight a salmonella bacterium. It takes about a week to

    generate enough antibodies to fight a disease. In thattime, it is a race for survival between man and microbe.The immune system has an ingenious way of re-

    membering past battles so that this life-and-death strug-gle does not happen again. Lymphocytes create mem-ory cells that circulate through the body ready to battlethe old enemy. If a person comes down with the samestrain of pneumonia a second time, the memory cellskick into maximum production immediately. Some

    memory cells last a lifetime, which provides immunityagainst that disease for the rest of a persons life. Thatis why a person who has had chicken pox will not getit again. This amazing immune response is the princi-ple behind vaccinations.

    Ancient Asian Secrets

    Smallpox ravaged Asia for generations, yet as early asthe eleventh century there was a method of fighting

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    smallpox called ingrafting. No one knows how it wasdeveloped, but over time, a treatment was devisedwhere pus from the sore of a person with a mild caseof smallpox was smeared into a scratch on the arm ofa healthy person. The person who was ingrafted usu-ally developed mild symptoms but recovered quickly.They never caught smallpox again.

    This technique spread to Europe with the help ofLady Mary Wortley Montagu, the wife of the British

    Fighting an Invisible Enemy 41

    Bacterium

    Antigen

    Lymphocytes

    Lymphocytelocks ontoantigen.

    Lymphocytemultipliesrapidly.

    Antibodylocks ontobacterium,marking itfor destruction.

    Memory cell

    B cell

    The surface of germs such as bacteriacarry markers called antigens, whichenable lymphocytes to identify invadinggerms. Each lymphocyte recognizes aspecific antigen, just as a key fits a lock.

    When the lymphocyte recognizes bacteria by their antigens, it divides againand again to produce memory cells and B cells. Memory cells memorizethe antigen, so that in any future invasion the body can react quickly.B cells make and release chemicals called antibodies. These target newinvaders, locking onto their antigens. In this way they disable the invadingbacterium and mark it for destruction by other cells.

    Antibody

    The Immune Response

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    ambassador living in Turkey in 1716. After witnessingthis procedure, she had her three-year-old son ingrafted.She brought news of the technique back to England,where it was called inoculation. The procedure was notwidely used because, although it was successful, therewas a risk that the patient could develop a severe caseof the disease.

    The First Vaccine

    One boy who was inoculated was eight-year-old EdwardJenner. He survived the painful procedure and grew upto be a country doctor whose keen observations led tothe first vaccinations.

    In 1796 Jenner noticed that young women whomilked cows sometimes became infected with cowpox,a disease that caused sores on a cows udders. The girlswould get painful sores on their hands, but the diseasewas not fatal. Once the girls caught cowpox, they neverbecame infected with smallpox.

    In May of that year Jenner performed his first cow-pox experiment. He took fluid from a sore on the handof dairymaid Sarah Nelmes and inoculated a healthyeight-year-old boy named James Phipps. Within a fewdays James came down with a fever and a small sore.On July 1, believing that the cowpox inoculation wouldprevent the development of smallpox, Jenner inoculated

    James with matter from a smallpox patient. Nineteendays later Jenner wrote, The Boy has since been inoc-ulated for the Smallpox which as I ventured to predictproduced no effects. I shall now pursue my Experiments

    with redoubled ardor.

    15

    Jenner went on to repeat his experiments and pub-lished his results, calling his technique vaccination andthe matter taken from the cowpox sore a vaccine (de-rived from vacca, the Latin word for cow). In a letter writ-ten to a friend, Jenner predicted, The annihilation ofsmallpoxthe most dreadful scourge of the humanracewill be the final result of this practice. 16Jennerwould never know how accurate his prediction would

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    become. He also would never know how his vaccineworked or even what kind of organism he was actuallyfighting against. That information would not come for

    many more years.How Vaccines Work

    Vaccines work by using our own natural defenses. Aninjection of a weakened virus or a part of a virus is justenough to trigger the lymphocytes to create memorycells. If the virus invades again, the body is able to fightit with ready-made antibodies before a serious infectiontakes hold. Vaccines may be made with dead microbesor parts of dead viruses. Some are made with living mi-crobes that are weakened and rendered harmless butare still able to elicit an immune response.

    Rabies Vaccine

    Louis Pasteur had created a successful vaccine forchickens, another for sheep, and he had been exper-imenting on a rabies vaccine for dogs, but he had notdeveloped a safe vaccine for humans. But that did notmatter to the mother of nine-year-old Joseph Meister,who took her son to Pasteurs office in 1885. A maddog had bitten Joseph. Rabies is a horrible disease thatinfects only mammals. The virus attacks the nervoussystem and infects the brain, causing a difficult andpainful death.

    Pasteur knew that a weakened germ worked as a vac-cine against other diseases in animals and believedthat a similar treatment for humans should work

    against rabies. He injected Joseph with the weakenedvaccine and increased the dose daily. After fourteendays Joseph Meister was stronger and had made his-tory. He became the first person to survive rabies.

    More Vaccines

    Pasteurs success inspired a concerted effort to develop

    vaccines for other dreadful diseases, but it did not happen

    quickly. Max Theiler created a vaccine against yellow

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    fever in the 1920s, and Jonas Salk and Albert Sabin pro-

    duced polio vaccines in the 1950s.

    Today, there are vaccines for mumps, rubella,measles, tetanus, chicken pox, flu, and other once dan-gerous diseases. But there are many viral infectionsthat the medical community cannot prevent with aninjection. For example, there are too many strains ofthe common cold to create an effective vaccine, andother viruses mutate too quickly. A virus can alter itsouter protein coat so that antibodies and vaccines thatonce worked on the virus are no longer effective. Even

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    Vaccine Skin

    Harmlessgerm

    Injecting vaccineA person is injected with aharmless form of the germ,which does not cause the disease.

    Antibodies are madeAlthough the germ is harmless,

    the body still recognizes it andmakes antibodies against it.

    Fighting infectionIf the body is invaded by the disease-causing form of the germ, the immunesystem responds immediately withhuge numbers of antibodies to destroythe germ.

    This type of immunization uses a form of the disease-causing germ that has been slightly altered to stop it fromcausing the disease. The person receiving it will not become ill, but he or she will produce antibodies againstthe pathogen that does cause disease. The body will do this every time it is threatened by that germ.

    Antibody locksonto germ

    Antibodiesfighting disease

    The Vaccination Process

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    a slight difference can mean that a persons memorycells would not recognize the virus, and the antibod-ies that a persons immune system created in the pastwould be powerless against this new strain.

    The First Antibiotics

    It seems ironic that medical researchers were success-ful in developing a preventive medicine for viruses,which were unknown to science and unseen by man,but were not able to fight off known bacterial infec-tions. The key was finding a way to kill a bacteriumcell without harming human cells.

    The first breakthrough came in 1910, when PaulEhrlich, a German scientist, discovered that an arseniccompound killed a spiral-shaped bacterium called aspirochete that caused syphilis. His discovery was in-spired by Robert Kochs work with aniline dye. In ameeting in Berlin, Ehrlich heard Koch describe howhe used the dye to identify the tuberculosis bacterium.When Koch applied the dye, it stained the bacteriacells, making them easier to see under a microscope,but it also killed the microbes.

    Ehrlich experimented with many other dyes andchemical compounds before he achieved success witharsenic compound 606, which was dubbed the magicbullet.

    How Antibiotics Work

    Ehrlichs compound was called a magic bullet because,like other antibiotic agents, it specifically targeted thesyphilis spirochete. Antibiotics are simply chemicalsthat react with other chemicals. Every cell, whether itis human or bacterium, is also made up of chemicals.The cells membranes are covered with receptor sitesthat allow the cell to react with or take in other chem-icals. In order for an antibiotic to work, it must havethe right chemical makeup, or key, to fit the chemi-cal makeup, or lock, at the receptor site on the bac-terium. But the antibiotics chemical key must not fit

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    the receptor sites of other cells in the patients body.If it does, then it would cause adverse side effects.

    Each kind of antibiotic attacks a bacterium in a dif-ferent way. Some, like penicillin, stop the bacteria fromforming a cell wall. Other antibiotics interfere withthe bacterias ability to make essential nutrients, suchas folic acid and other proteins, while others stop thebacterias DNA replication.

    Penicillin

    The power of microorganisms can be harnessed to healas well as harm. This was discovered by chance whenAlexander Fleming observed a yellowish mold grow-ing on a bacterial culture in his lab. It was 1928, andFleming had been studying staphylococcus, which isa common bacterium on skin. He noticed that wher-ever the mold grew, an area of clear liquid surround-ing it was free of bacteria. Wherever Fleming spreadthe mold juice, which Fleming called penicillin, bac-terial growth was stopped dead. Although penicillinworked wonders, Fleming was unable to present it to

    the public. Apparently people were not ready to ac-cept a microorganism that could make an effective an-tibiotic.

    Twelve years later, a young Australian doctor namedHoward Walter Florey, along with his colleagues ErnstBoris Chain and Dr. Norman G. Heatley, showed theworld that penicillin was indeed a miracle drug. Itkilled the bacteria that caused scarlet fever, pneumo-nia, diphtheria, and meningitis, as well as other com-

    mon bacterial infections.The discovery of penicillin was so important thatAmerican soldiers were sent to collect soil samples fromIndia, China, Africa, and South America so that it couldbe tested for other miracle molds. Employees of theU.S. Department of Agriculture laboratory in Peoria,Illinois, were instructed to collect any unusual moldsas well. One employee, Mary Hunt, earned the nick-name Moldy Mary because she searched through peo-

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    ples garbage cans and litter. While poking through aneighbors trash, Mary found a rotting cantaloupe thathad a golden mold growing on it. When the melon

    mold was tested, it produced twice as much penicillinas Flemings mold, and it grew easily in large quanti-ties. It was namedPenicillium chrysogenum, and it re-placed Flemings mold for use in penicillin productionuntil researchers learned to make the drug synthetically.

    Drugs Dug from the EarthEvery pharmaceutical company raced to find new an-tibiotic compounds. Bristol-Meyers Pharmaceuticals

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    sent envelopes to all of its stockholders with instruc-tions to collect soil samples from their neighborhoods.Other companies contacted missionaries in far-offplaces, foreign news correspondents, airline pilots, anddeep-sea divers in their search for a mold that mightlead to a new treatment.

    In 1943 Dr. Paul Burkholder at Yale University sentout plastic mailing tubes to everyone he knew and re-ceived more than seven thousand soil samples in re-turn. One soil sample sent from Venezuela containeda powerful antibiotic that was eventually developedinto the drug called Chloromycetin. It killed manydifferent kinds of microbes, including the deadly bac-teria that caused Rocky Mountain spotted fever andtyphus.

    48 Bacteria and Viruses

    In the wake ofAlexander Flemingsdiscovery of penicillinin 1928, the U.S.

    Department ofAgriculture discoveredthat mold growing onrotting fruit produceslarge amounts of theantibiotic.

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    Dr. Selman Waksman at Rutgers University workedfor the pharmaceutical firm Merck & Company. Hetested the mold found in the throat of a New Jerseychicken. It contained a compound called streptomycinthat killed the tuberculosis bacillussomething peni-cillin could not do.

    Man over Microbes

    With the development of antibiotics, common infec-tious diseases lost their grip on the world. People be-lieved that man had conquered harmful bacteria andviruses. The medical community even fulfilled Jennersprediction of annihilating smallpox.

    By the end of the 1800s, many European countrieshad enacted laws requiring its citizens to be vaccinatedagainst smallpox. In short order, the virus disappearedfrom many countries. Surprisingly one of the lastWestern countries to eradicate smallpox from withinits borders was the United States, in the late 1940s.

    The success of mandatory vaccination inspired officialsat the United Nations to adopt a resolution to eradicatesmallpox from the forty-four countries that still reported

    its occurrence. The World Health Organization (WHO),which is part of the United Nations, set a deadline of

    January 1, 1977.Teams of medical workers searched for outbreaks of

    smallpox in poor pockets of major cities and remotevillages. Wherever an outbreak occurred, the teamswooped in to vaccinate all the inhabitants, creating aring of containment around the victims in a particulararea. Those who were infected were put into quaran-

    tine. Defusing each epidemic case by case and countryby country, the WHO successfully snuffed out the onceraging flames of smallpox.

    By 1979 the WHO declared the project a success. Theonly places on Earth where smallpox existed were inlaboratory test tubes. One question remained: Whatshould be done with the stored virus? Some nationsvoluntarily destroyed their supplies, and others handedthem over to research centers in the Soviet Union or

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    the United States. There are now about four hundredvials of frozen virus securely stored at the U.S. Centersfor Disease Control in Atlanta, Georgia, and anothertwo hundred stored in a lab in Moscow. Although theWHO ordered the destruction of all smallpox samplesin 1993, the order was not carried out. Scientists stilldebate the validity of destroying a virus species. Someargue that more study could provide clues to fightingother deadly microbes.

    50 Bacteria and Viruses

    A Nigerian womanreceives a smallpoxvaccination in 1969

    during the WorldHealth Organizationseffort to wipe outsmallpox. By 1979the virus had beeneradicated.

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    Fighting BackThe elimination of smallpox and the availability of so

    many antibiotics lulled the world into believing that

    infectious diseases were a thing of the past. The U.S.surgeon general William H. Steward even declared be-

    fore Congress in 1969 that he was ready to close the

    book 17 on infectious disease. The development of an-

    tibiotics was put on the back burner.

    But as quickly as man could manufacture antibiotics

    and vaccines, bacteria and viruses were faster to develop

    resistance to the drugs. In an interview with Newsweek,

    Dr. Richard Wenzel of the University of Iowa said, Ever

    since 1928, when Alexander Fleming discovered peni-cillin, man and microbe have been in a footrace. Right

    now the microorganisms are winning. Theyre so much

    older than we are . . . and wiser. 18

    Microbes MutateThe wisdom of a microbe lies in its ability to change.

    They are able to reproduce much faster than their hu-

    man competitors. A new generation can come along as

    quickly as every fifteen minutes, and each time a bac-terium divides, there is a chance for error. A random

    change in the genetic makeup of a cell that becomes apermanent inherited characteristic is called a mutation.

    And a mutation that increases a microbes chance of

    survival is passed on to the next generation.Bacteria can also trade or share parts of their DNA

    through a process called horizontal gene transfer. In ad-dition to strands of DNA, bacteria have rings of DNAcalled plasmids. These plasmids give the bacteria cer-tain survival skills, such as being resistant to a type ofantibiotic. This means that bacteria in the same gener-ation can potentially share advantageous plasmids, justas easily as two friends exchange phone numbers. Twobacteria can exchange a gene or genes that allow themto inhabit a new species of animal, thrive in a new cli-mate, or protect them against a certain drug.

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    Growing ResistanceThe use of antibiotics creates a situation in which thefittest microbes survive. Each time someone uses an

    antibiotic, the majority of the bacteria are killed butnot all. These heartier microbes are left to multiplyand spread their resistance to the next generation.Within four years of the widespread use of penicillinin the 1940s, doctors saw evidence of microbes thathad grown resistant to it. Even Alexander Fleminghimself warned the public in a New York Times inter-view of the dangers of taking antibiotics. The mi-crobes are educated to resist penicillin and a host ofpenicillin-fast [resistant] organisms is bred out whichcan be passed to other individuals and from them toothers until they reach someone who gets a septicemiaor a pneumonia which penicillin cannot save. 19

    As each new antibiotic came on the market, a mi-crobe came along that could withstand the toxic ef-fects. Today doctors are encouraged to stop prescrib-ing antibiotics for viral infections, because they haveno power over a virus. And when patients are pre-scribed an antibiotic, they need to take the entire dose.

    After two days on an antibiotic, a patient usually startsto feel better, but that is only because the antibiotichas killed off a significant number of bacteria. Theminute treatment is stopped, the surviving bacteriabegin to multiply. It takes only one drug-resistant bac-terium to multiply into millions.

    The Bacteria EatersOne treatment that may prove to be a solution to the

    problem of antibiotic resistance comes from an un-likely sourceviruses. It is a method developed inRussia before Fleming discovered penicillin. To mod-ern mentality it seems bizarre, for it pits microbesagainst each other.

    Phage therapy harnesses specific kinds of virusesthat attack only certain harmful bacteria. Discoveredand named by Felix dHerelle in 1917, bacteriophages(bacteria-eating viruses) were soon used by doctors to

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    cure cholera and typhoid fever. Although the treat-ment never caught on in the West, research contin-ues, particularly in the Republic of Georgia. Today theworlds foremost center for the development of phagetherapy is at the Eliava Institute in Tbilisi, Georgia.Doctors at the institute study a wide range of virusescollected from nature. The viruses that are active

    against harmful bacteria are then cultivated and usedfor treatment. A patient suffering from an antibiotic-resistant bacterial infection is injected with a solutionthat contains the proper bacteriophages. The virusesseek out the larger harmful bacteria and inject theirgenetic material into the cell, where it hijacks the bac-terias reproductive machinery. Only one hundred bac-teriophages placed on an infected wound is enoughto destroy more than 100 million bacteria. Once the

    bacteria are eliminated, the viruses also die out. Theyhave no cells to infect and are washed harmlessly outof the patients body.

    More than twenty companies in the United States arenow studying and testing phage therapy in the lab andwill seek future government approval to conduct clini-cal trials on humans. In the meantime, dozens of ex-otic, mysterious illnesses are cropping up all over theworld.

    Staphylococcusbacteria are destroyedby antibiotics.

    Although antibioticsare extremely effective,their use over timeresults in heartier,drug-resistant strains

    of bacteria.

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    EmergingMicrobes

    54

    Chapter 4

    Many infectious diseases, like smallpox, polio, and

    anthrax, are ancient and have plagued humankindfor thousands of years. But new strains of bacteria and

    viruses continue to emerge seemingly out of nowhere

    to cause mysterious new ailments.

    In Wisconsin in May 2003, three-year-old Schyan

    Kautzer came down with symptoms vaguely reminis-

    cent of smallpox. Eileen Whitmarsh, a forty-two-year-

    old pet store owner, developed flulike symptoms along

    with blisters on her head and under her arms. Two em-

    ployees at a veterinary clinic also became sick. The one

    thing they all had in common was a close encounter

    with prairie dogs. The three-year-old had received a prairie

    dog for a pet, the pet store owner had had the animals

    in stock, and the workers at the clinic had recently treated

    a sick prairie dog.

    Blood samples taken from all the victims revealed

    startling news: They had a disease never encountered

    before in the Western Hemispherea virus called mon-keypox, a less severe cousin to smallpox. At one time

    the virus infected only rodents in Africa, but it had

    jumped species and was now known to have infected

    fewer than one hundred people in Africa. But how did

    it travel five thousand miles across an ocean to a small

    town in Wisconsin?

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    A Global VillageMicrobes are opportunists. They take advantage of likelyand unlikely hosts. The virus that was carried to the

    United States inside an African rodent seized the op-portunity to inhabit a new species when the animal washoused in a small, tightly packed cage next to prairiedogs in a pet store warehouse. The virus mutated, orchanged its genetic code, so that it was able to infect anew species. From a Gambian rat to an American prairiedog, it then jumped to a little girl.

    Emerging Microbes 55

    Crowded cities andthe ease ofintercontinental travefacilitate the spread omicrobes throughoutthe world.

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    Humans live in a global society, and our actions af-fect the microscopic community around us. We dothings as part of progress, which we dont recognize as

    changing the microbial environment,

    20

    says G. RichardOlds, the chairman of medicine at the Medical Collegeof Wisconsin and the former head of the TropicalDisease and Travel Medicine Center in New England.Everything a person does affects the microscopic world:traveling in airplanes, eating foreign foods, and livingin crowded cities. As Olds says, Nothing happens onthis planet that doesnt impact us. Were wearingclothes that were made in China. Were eating foods

    that were grown in Chile.21

    Infective agents cancome from anywhere, and frequently do. Monkeypoxappeared in this country because of peoples passionfor exotic pets.

    But the connection between man and microbe wasnot always so apparent. Disease was something thatjust happened to a person, and there was little thoughtas to why or how a persons behavior or activities con-tributed to their illness. It took hundreds of years be-

    fore someone thought to look at our own behaviorand modify it in an attempt to prevent the spread ofdisease.

    The First Disease Detective

    In 1854, during the Industrial Revolution, living con-ditions in many parts of urban England were poor.Factories belched black smoke, and slums were over-crowded and unsanitarythe perfect conditions for

    bacteria and viruses. An outbreak of cholera occurredin a small area near Broad Street in London. Cholerais contracted by drinking water infected with thecholera bacterium or eating food contaminated by it.Cholera causes severe diarrhea, vomiting, fever, anddeath.

    When physician John Snow began questioning peo-ple in the neighborhood, he noticed that of the seventy-seven households infected with cholera, fifty-nine used

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    the hand pump on Broad Street. Families that remainedhealthy used a water pump farther away.

    Near the Broad Street well was a cesspool that con-tained the waste and garbage of the neighborhood.Snow believed that sewage from the cesspool had con-taminated the drinking water. He begged the board oftrustees of the St. James Parish to remove the handlefrom the pump to prevent people from collecting thecontaminated water. Although no other physicianagreed with Snows assessment, the men on the boarddid as he advised. The handle was removed and thecases of cholera declined. Later Snow learned that the

    bricks lining the cesspool were indeed old and broken,and sewage had leaked into the well.

    Disease Detectives TodayThe same kind of detective work that Snow con-ducted in the 1800s is carried out today by scientistsat the Centers for Disease Control and Prevention(CDC) headquartered in Atlanta, Georgia, and theDivision for Emerging and Other CommunicableDiseases Surveillance and Control at the WorldHealth Organization (WHO). More properly calledepidemiologists, these scientists study the spread ofinfectious illnesses and respond to outbreaks any-where in the world.

    They watch for the emergence of a new disease oran old microbial adversary using a network of doctorsand high-tech equipment like satellites and theInternet. The WHO is continuously monitoring theWorld Wide Web with a customized search enginecalled the Global Public Health Intelligence Network,listening for rumors and reports of suspicious disease-related events. Online eavesdropping led to the earlydetection of the 2003 outbreak of SARS (severe acuterespiratory syndrome).

    When a suspicious event is detected or when epi-demiologists are consulted by local authorities, these sci-entists use some of the same skills that police detectives

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    use when trying to solve a crime. They interview the pa-tients, their friends, and family to pinpoint the initialsigns of illness. They ask patients what they may have

    eaten, what animals or animal products they may havecome in contact with, and where they may have trav-eled. As each person is interviewed, patterns of the dis-ease emerge. Are the victims all children, or are they alladults? Are they mostly male or female? Knowing whenan outbreak began, who it affected, and when it endedgives epidemiologists an idea of the kind of disease thatcould have occurred within that time frame.

    Epidemiologists also track each patients activities to

    narrow down the possible source of infection and ploteach incident on a map to see if there is a geographi-cal element. They search the area for evidence of ani-mal activity, insects, or contaminated water or food.Doctors take samples of blood or tissue and send themto their lab in Georgia, where microbiologists will iden-tify the microbes involved in the incident.

    58 Bacteria and Viruses

    Epidemiologists fromthe World HealthOrganization conductresearch on the Ebolavirus. Epidemiologistsstudy the incidence,spread, and control ofinfectious diseases.

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    Suspect infectious agents are examined in a labcalled a biocontainment unit. There are four levels ofsecurity and safety features in the labs. The most

    deadly infectious agents are examined in biocontain-ment unit level 4, which is as airtight as a space shut-tle. Air locks and a ventilation system that sucks airinward prevent dangerous bacteria or viruses fromdrifting out. Microbiologists suit up in astronaut-likeblue suits complete with their own air supply. Atthe end of the day, the workers are decontaminatedin chemical showers. The evidence found in the labcombined with the information gathered in the field

    will lead to the cause and hopefully the treatment ofthe infection.

    Microbes on the MoveEpidemiologists respond to outbreaks all around theworld, but today our world is more mobile than everbefore, and that mobility means that microbes are onthe move too. One of the most important means ofspreading diseases around the globe is air travel, 22

    says David Heymann, the director of communicablediseases for the World Health Organization.Every day, more than 500 million people travel

    across international borders, and tens of billions ofbacteria and viruses hitch a ride. In 2003, within sixmonths of the first reported case of SARS in China,the disease was spread by air travel to twenty-sevenother countries. All the victims who came down withSARS in Toronto, Canada, could be traced directly back

    to one woman who had traveled from Hong Kong.And shortly after the Toronto outbreak, the WorldHealth Organization warned travelers not to visit thecity and effectively prevented the virus from spread-ing further.

    Changing the EnvironmentPeople not only get around faster than ever before,but they change the environment more easily too.

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    Every day, in some part of the world, whole tracts ofrain forests are bulldozed, rivers are dammed, and newroads are paved into the wilderness. This disrupts thebalance and distribution of plants and animals, in-cluding microbes. It may cut off a virus from its hostso that the virus must seek another means of survival.

    The story of Lyme disease, which causes arthritis-likeaches and pains, provides an example of this process.In the 1800s settlers in Old Lyme, Connecticut, clear-cut the old growth forests, which led to a decline inthe deer population. A hundred years later, when theagricultural production in that area ceased, the forests

    returned, along with a burgeoning deer population.But the human population grew too. Housing devel-opments in forested areas put man, deer, and microbes