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Microbiology, Fifth Edition
Microbiology, 5/e
Lansing M Prescott, Augustana College
Donald A Klein, Colorado State University
John P Harley, Eastern Kentucky University


Preface

Microbiology is an exceptionally broad discipline encompassing specialties as diverse as biochemistry, cell biology, genetics, taxonomy, pathogenic bacteriology, food and industrial microbiology, and ecology.

Microbiology is an exceptionally broad discipline encompassing specialties as diverse as biochemistry, cell biology, genetics, taxonomy, pathogenic bacteriology, food and industrial microbiology, and ecology. A microbiologist must be acquainted with many biological disciplines and with all major groups of microorganisms: viruses, bacteria, fungi, algae, and protozoa. The key is balance. Students new to the subject need an introduction to the whole before concentrating on those parts of greatest interest to them. This text provides a balanced introduction to all major areas of microbiology for a variety of students. Because of this balance, the book is suitable for courses with orientations ranging from basic microbiology to medical and applied microbiology. Students preparing for careers in medicine, dentistry, nursing, and allied health professions will find the text just as useful as those aiming for careers in research, teaching, and industry. Two quarters/semesters each of biology and chemistry are assumed, and an overview of relevant chemistry is also provided in appendix I.

Organization and Approach

The book is organized flexibly so that chapters and topics may be arranged in almost any order. Each chapter has been made as self-contained as possible to promote this flexibility. Some topics are essential to microbiology and have been given more extensive treatment.

The book is divided into 11 parts. The first 6 parts introduce the foundations of microbiology: the development of microbiology, the structure of microorganisms, microbial growth and its control, metabolism, molecular biology and genetics, DNA technology and genomics, and the nature of viruses. Part Seven is a survey of the microbial world. In the fifth edition, the bacterial survey closely follows the general organization of the forthcoming second edition of Bergey's Manual of Systematic Bacteriology. Although principal attention is devoted to bacteria, eucaryotic microorganisms receive more than usual coverage. Fungi, algae, and protozoa are important in their own right. The introduction to their biology in chapters 25-27 is essential to understanding topics as diverse as clinical microbiology and microbial ecology. Part Eight focuses on the relationships of microorganisms to other organisms and the environment (microbial ecology). It also introduces aquatic and terrestrial microbiology. Chapter 28 presents the general principles underlying microbial ecology and environmental microbiology so that the subsequent chapters on aquatic and terrestrial habitats can be used without excessive redundancy. The chapter also describes various types of microbial interactions such as mutualism, protocooperation, commensalism, and predation that occur in the environment. Parts Nine and Ten are concerned with pathogenicity, resistance, and disease. The three chapters in Part Nine describe normal microbiota, nonspecific host resistance, the major aspects of the immune response, and medical immunology. Part Ten first covers such essential topics as microbial pathogenicity, antimicrobial chemotherapy, and epidemiology. Then chapters 38-40 survey the major human microbial diseases. The disease survey is primarily organized taxonomically on the chapter level; within each chapter diseases are covered according to mode of transmission. This approach provides flexibility and allows the student easy access to information concerning any disease of interest. The survey is not a simple catalog of diseases; diseases are included because of their medical importance and their ability to illuminate the basic principles of disease and resistance. Part Eleven concludes the text with an introduction to food and industrial microbiology. Five appendices aid the student with a review of some basic chemical concepts and with extra information about important topics not completely covered in the text.

This text is designed to be an effective teaching tool. A text is only as easy for a student to use as it is easy to read. Readability has been enhanced by using a relatively simple, direct writing style, many section headings, and an organized outline format within each chapter. The level of difficulty has been carefully set with the target audience in mind. During preparation of the fifth edition, every sentence was carefully checked for clarity and revised when necessary. The American Society for Microbiology's ASM Style Manual conventions for nomenclature and abbreviations have been followed as consistently as possible.

The many new terms encountered in studying microbiology are a major stumbling block for students. This text lessens the problem by addressing and reinforcing a student's vocabulary development in three ways: (1) no new term is used without being clearly defined (often derivations also are given)--a student does not have to be familiar with the terminology of microbiology to use this text; (2) the most important terms are printed in boldface when first used; and (3) a very extensive, up-to-date, page-referenced glossary is included at the end of the text.

Because illustrations are critical to a student's learning and enjoyment of microbiology, all illustrations are full-color, and many excellent color photographs have been used. Color not only enhances the text's attractiveness but also increases each figure's teaching effectiveness. Considerable effort has gone into making the art as attractive and useful as possible. Much of the art in the fourth edition has been revised and improved for use in the fifth edition. All new line art has been produced under the direct supervision of an art editor and the authors, and designed to illustrate and reinforce specific points in the text. Consequently every illustration is directly related to the narrative and specifically cited where appropriate. Great care has been taken to position illustrations as close as possible to the places where they are cited. Illustrations and captions have been reviewed for accuracy and clarity.

Themes in the Book

At least seven themes permeate the text, though a particular one may be more obvious at some points than are others. These themes or emphases are the following:

1. The development of microbiology as a science

2. The nature and importance of the techniques used to isolate, culture, observe, and identify microorganisms

3. The control of microorganisms and reduction of their detrimental effects

4. The importance of molecular biology for microbiology

5. The medical significance of microbiology

6. The ways in which microorganisms interact with their environments and the practical consequences of these interactions

7. The influences that microorganisms and microbiological applications have on everyday life

These themes help unify the text and enhance continuity. The student should get a feeling for what microbiologists do and for how their activities affect society.

What's New in the Fifth Edition

Many substantial changes and improvements have been made in the fifth edition, including the following:

1. The general organization of the text has been modified to provide a more logical flow of topics and give greater emphasis to microbial ecology. Treatment of nucleic acid and protein synthesis has been moved to the genetics chapters to integrate the discussion of gene structure, replication, expression, and regulation. Recombinant DNA technology has been moved to a separate section, which also contains a new chapter on microbial genomics. The three-chapter introduction to microbial ecology now follows the survey of microbial diversity. This places it earlier in the text where basic principles of microbiology are introduced. Part Nine now contains a description of nonspecific host resistance as well as an introduction to the fundamentals of immunology. Symbiotic associations are discussed in the context of microbial ecology. The treatment of microbial pathogenesis has been expanded into a full chapter and placed with other medical topics in Part Ten.

2. Pedagogical aids have been expanded. A new Critical Thinking Questions section with two or more questions follows the Questions for Thought and Review. Section numbers have been given to all major chapter sections in order to make cross references more precise. The summary now contains boldfaced references to tables and figures that will be useful in reviewing the chapter.

3. New illustrations have been added to almost every chapter. In addition, all figures have been carefully reviewed by our art editor, and many have been revised to improve their appearance and usefulness.

4. All reference sections have been revised and updated.

Besides these broader changes in the text, every chapter has been updated and often substantially revised. Some of the more important improvements are the following:

Chapter 1--A box on molecular Koch's postulates and a new section on the future of microbiology have been added.

Chapter 2--Differential interference contrast microscopy and confocal microscopy are described.

Chapter 3--More details on the mechanism of flagellar motion are provided.

Chapter 5--Phosphate uptake and ABC transporters are described.

Chapter 6--The chapter has new material on starvation proteins, growth limitation by environmental factors, viable but nonculturable procaryotes, and quorum sensing.

Chapter 8--The discussions of metabolic regulation and control of enzyme activity have been combined with the introduction to energy and enzymes.

Chapter 9--The metabolic overview has been rewritten to aid in understanding. The sections on electron transport, oxidative phosphorylation, and anaerobic respiration have been updated and expanded.

Chapter 11--The chapter now focuses on nucleic acid and gene structure, mutations, and DNA repair. New material on DNA methylation has been added.

Chapter 12--Material on gene expression (transcription and protein synthesis) has been moved here and combined with an extensive discussion of the regulation of gene expression. New sections on global regulatory systems and two-component phosphorelay systems have been added.

Chapter 15--This new chapter provides a brief introduction to microbial genomics, including genome sequencing, bioinformatics, general characteristics of microbial genomes, and functional genomics.

Chapter 18--Virus taxonomy has been updated and new life cycle diagrams added.

Chapter 19--Material on polyphasic taxonomy and the effects of horizontal gene transfer on phylogenetic trees has been added. The introduction to the second edition of Bergey's Manual has been revised and updated.

Chapters 20-24--The procaryotic survey chapters have been further revised to conform to the forthcoming second edition of Bergey's Manual.

Chapter 28--This chapter, formerly chapter 40, has been substantially rewritten and now includes a treatment of symbiosis and microbial interactions (e.g., mutualism, protocooperation, commensalism, predation, amensalism, competition, etc.). A discussion of microbial movement between ecosystems has been added, and the treatment of biofilms and microbial mats has been expanded.

Chapter 29--The chapter on microorganisms in aquatic environments has new material on such topics as oxygen fluxes in water, the microbial loops, Thiomargarita namibiensis, microorganisms in freshwater ice, and current drinking water standards.

Chapter 30--Microorganisms in cold moist area soils, desert soils, and geologically heated hyperthermal soils are discussed. The effects of nitrogen, phosphorus, and atmospheric gases on plants and soils are described more extensively. There is a new section on the subsurface biosphere.

Chapter 31--This reorganized chapter discusses normal microbiota and nonspecific resistance. An overview of host resistance; a discussion of the cells, tissues, and organs of the immune system; an introduction to the alternative and lectin complement pathways; and a summary of cytokine properties and functions have been included.

Chapter 32--All aspects of specific immunity have been moved to this chapter in order to provide a more clear and coherent discussion. The chapter contains an overview of specific immunity, a discussion of antigens and antibodies, T-cell and B-cell biology, a discussion of the action of antibodies, the classical complement pathway, and a section on acquired immune tolerance. It ends with a summary of the role of antibodies and lymphocytes in resistance.

Chapter 33--The new chapter on medical immunology contains topics more directly related to the practical aspects of health and clinical microbiology: vaccines and immunizations, immune disorders, and in vitro antigen-antibody interactions. Previously these were scattered over three chapters. The treatment of vaccines has been greatly expanded.

Chapter 34--The treatment of microbial pathogenicity has been greatly enlarged and made into a separate chapter. Several topics have been expanded or added: regulation of bacterial virulence factors and pathogenicity islands, the mechanisms of exotoxin action, and microbial mechanisms for escaping host defenses.

Chapter 37--In the epidemiology chapter, the treatment of emerging diseases has been expanded. New sections on bioterrorism and the effect of global travel on health have been added.

Chapters 38-40--The disease survey chapters have been brought up-to-date, and bacterial diseases are now covered in one chapter rather than two. New material has been added on genital herpes, listeriosis, the use of clostridial toxins in therapy, and other topics. A new table describing common sexually transmitted diseases and their treatment is provided.

Chapter 41--New aspects of food microbiology include discussions of modified atmosphere packaging, algal toxins, bacteriocins as preservatives, new variant Creutzfeldt-Jakob disease, food poisoning by uncooked foods, new techniques in tracing outbreaks of food-related diseases, and the use of probiotics in the diet.

Chapter 42--The chapter on industrial microbiology and biotechnology has been revised to include current advances due to new molecular techniques. A section on developing and choosing microorganisms for use in industry has been added. Other topics that have been added or substantially revised include the synthesis of products for medical use, biodegradation of pesticides and other pollutants, the addition of microorganisms to the environment, and the use of microarray technology.

Aids to the Student

It is hard to overemphasize the importance of pedagogical aids for the student. Accuracy is most important, but if a text is not clear, readable, and attractive, up-to-dateness and accuracy are wasted because students will not read it. Students must be able to understand the material being presented, effectively use the text as a learning tool, and enjoy reading the book.

To be an effective teaching tool, a text must present the science of microbiology in a way that can be clearly taught and easily learned. Therefore many aids are included to make the task of learning more efficient and enjoyable. Following the preface a special section addressed to the student user reviews the principles of effective learning, including the SQ4R (survey, question, read, revise, record, and review) study technique. Specific chapter aids are described in the special Visual Preview section.

Besides the chapter aids the text also contains a glossary, an index, and five appendices. The extensive glossary defines the most important terms from each chapter and includes page references. Where desirable, phonetic pronunciations also are given. Most of the glossary definitions have not been taken directly from the text but have been rewritten to give the student further understanding of the item. To improve ease of use, the fifth edition has a large, detailed index. It has been carefully designed to make text material more accessible. The appendices aid the student with extra review of chemical principles and metabolic pathways and provide further details about the taxonomy of bacteria and viruses. To aid the student in following the rapidly changing field of procaryotic taxonomy, appendix III provides the classification of procaryotes according to the first edition of Bergey's Manual of Systematic Bacteriology, and appendix IV gives the classification used by the upcoming second edition of Bergey's Manual.

Supplementary Materials

Rich supplementary materials are available for students and instructors to assist learning and course management.

For the Student

1. A Student Study Guide by Linda Sherwood of Montana State University is a valuable resource that provides learning objectives, study outlines, learning activities, and self-testing material to help students master course content.

2. The third edition of Microbes in Motion by Gloria Delisle and Lewis Tomalty is an interactive CD-ROM that brings microbiology to life. A correlation guide on the CD links this exciting resource directly to your textbook. This easy to use tutorial can go from the classroom to the resource center to student's own personal computers. Microbes in Motion brings discovery back into the learning and education process through interactive screens, animations, video, audio, and hyperlinking questions. The applications of this CD-ROM are only as limited as your good ideas.

3. The second edition of Hyperclinic by Lewis Tomalty and Gloria Delisle is packed with over 100 case studies and over 100 case studies and over 200 pathogens supported with audio, video, and interactive screens. Students will have fun and gain confidence as they learn valuable concepts and gain practical experience in clinical microbiology.

4. The fifth edition of Laboratory Exercises in Microbiology by John P. Harley and Lansing M. Prescott has been prepared to accompany the text. Like the text, the laboratory manual provides a balanced introduction to laboratory techniques and principles that are important in each area of microbiology. The class-tested exercises are modular and short so that an instructor can easily choose only those exercises that fit his or her course. The fifth edition contains recipes for all reagents and media. New exercises in biotechnology have been added to this edition. A new appendix provides practice in solving dilution problems.

5. A set of 305 Microbiology Study Cards prepared by Kent M. Van De Graaff, F. Brent Johnson, Brigham Young University, and Christopher H. Creek features complete descriptions of terms, clearly labeled drawings, clinical information on diseases, and much more.

For the Instructor

1. A Testing CD is offered free on request to adopters of the text. This cross-platform CD provides a database of over 2,500 objective questions for preparing exams and a grade-recording program.

2. A set of 250 full-color acetate transparencies is available to supplement classroom lectures. These have been enhanced for projection and are available to adopters of the fifth edition.

3. The Visual Resource Library CD-ROM contains virtually all of the images from Microbiology, Fifth Edition, as well as the tables that appear in the text. This presentation software allows you to create your own multimedia presentations or export images into other programs. Images may be sorted by a number of criteria. Features include an Interactive Slide Show and a Slide Editor.

4. A set of 50 Projection Slides provides clinical examples of diseases and pathogens to supplement the illustrations in the text.

5. Your McGraw-Hill representative may arrange a Customized Laboratory Manual combining your own material with exercises from Laboratory Exercises in Microbiology, Fifth Edition, by John Harley and Lansing Prescott. Contact your McGraw-Hill representative for details about this custom publishing service.

6. Designed specifically to help you with your individual course needs, PageOut and McGraw-Hill Course Solutions will assist you in integrating your syllabus with the fifth edition's state-of-the-art media tools. Create your own course-specific web page supported by McGraw-Hill's extensive electronic resources, set up a class message board or chat room online, provide online testing opportunities for your students, and more!

Online Resources

Through the Prescott 2002 Online Learning Center, everything you need for effective, interactive teaching and learning is at your fingertips. Moreover, this vast McGraw-Hill resource is easily loaded into course management systems such as WebCT or Blackboard. Through the Online Learning Center, you will also link to McGraw-Hill's new Biocourse.com site with a huge dynamic array of resources to supplement your learning experience in microbiology.

Some of the online features you will find to support your use of Microbiology by Prescott, Harley, and Klein include:

For the Student

* Additional multiple-choice questions in a self-quizzing interactive format

* Electronic flashcards to review key vocabulary

* Study Outlines

* Web Links and Exercises

* Clinical Case Studies

* An Interactive Time Line detailing events and highlighting personalities critical to the development of microbiology

* Study Tips

* Student Tutorial Service

For the Instructor

* A complete Instructor’s Manual containing chapter overviews and objectives, chapter resource guides, correlation guides, and more.

* A comprehensive Test Item File, written by David Mullin of Tulane University is available through Page Out. The Test Item File containing over 2500 questions, and password protected, provides a powerful instructional tool.

* The Laboratory Resource Guide provides answers to all exercises in Laboratory Exercises in Microbiology, Fifth Edition, by John Harley and Lansing Prescott.

* All images and tables from the text in a downloadable format for classroom presentation.

* Correlation guides for use of all resources available with the text and correlations of text material with the ASM Guidelines.

* Answers to Critical Thinking Questions in the text.

* Web Links to active microbiology sites and to other sites with teaching resources.

* A Course Consultant to answer your specific questions about using McGraw-Hill resources with your syllabus.

Acknowledgments

The authors wish to thank the reviewers, who provided detailed criticism and analysis. Their suggestions greatly improved the final product.

Reviewers for the First and Second Editions

Richard J. Alperin, Community College of Philadelphia

Susan T. Bagley, Michigan Technological University

Dwight Baker, Yale University

R. A. Bender, University of Michigan

Hans P. Blaschek, University of Illinois

Dennis Bryant, University of Illinois

Douglas E. Caldwell, University of Saskatchewan

Arnold L. Demain, Massachusetts Institute of Technology

A. S. Dhaliwal, Loyola University of Chicago

Donald P. Durand, Iowa State University

John Hare, Linfield College

Robert B. Helling, University of Michigan-Ann Arbor

Barbara Bruff Hemmingsen, San Diego State University

R. D. Hinsdill, University of Wisconsin-Madison

John G. Holt, Michigan State University

Robert L. Jones, Colorado State University

Martha M. Kory, University of Akron

Robert I. Krasner, Providence College

Ron W. Leavitt, Brigham Young University

David Mardon, Eastern Kentucky University

Glendon R. Miller, Wichita State University

Richard L. Myers, Southwest Missouri State University

G. A. O'Donovan, North Texas State University

Pattle P. T. Pun, Wheaton College

Ralph J. Rascati, Kennesaw State College

Albert D. Robinson, SUNY-Potsdam

Ronald Wayne Roncadori, University of Georgia-Athens

Ivan Roth, University of Georgia-Athens

Thomas Santoro, SUNY-New Paltz

Ann C. Smith, University of Maryland, College Park

David W. Smith, University of Delaware

Paul Smith, University of South Dakota

James F. Steenbergen, San Diego State University

Henry O. Stone, Jr., East Carolina University

James E. Struble, North Dakota State University

Kathleen Talaro, Pasadena City College

Thomas M. Terry, The University of Connecticut

Michael J. Timmons, Moraine Valley Community College

John Tudor, St. Joseph's University

Robert Twarog, University of North Carolina

Blake Whitaker, Bates College

Oscar Will, Augustana College

Calvin Young, California State University-Fullerton

Reviewers for the Third and Fourth Editions

Laurie A. Achenbach, Southern Illinois University

Gary Armour, MacMurray College

Russell C. Baskett, Germanna Community College

George N. Bennett, Rice University

Prakash H. Bhuta, Eastern Washington University

James L. Botsford, New Mexico State University

Alfred E. Brown, Auburn University

Mary Burke, Oregon State University

David P. Clark, Southern Illinois University

William H. Coleman, University of Hartford

Donald C. Cox, Miami University

Phillip Cunningham, Wayne State University

Richard P. Cunningham, SUNY at Albany

James Daly, Purchase College, SUNY

Frank B. Dazzo, Michigan State University

Valdis A. Dzelzkalns, Case Western Reserve University

Richard J. Ellis, Bucknell University

Merrill Emmett, University of Colorado at Denver

Linda E. Fisher, University of Michigan-Dearborn

John Fitzgerald, University of Georgia

Harold F. Foerster, Sam Houston State University

B. G. Foster, Texas A&M University

Bernard Frye, University of Texas at Arlington

Katharine B. Gregg, West Virginia Wesleyan College

Eileen Gregory, Rollins College

Van H. Grosse, Columbus College-Georgia

Maria A. Guerrero, Florida International University

Robert Gunsalus, UCLA

Barbara B. Hemmingsen, San Diego State University

Joan Henson, Montana State University

William G. Hixon, St. Ambrose University

John G. Holt, Michigan State University

Ronald E. Hurlbert, Washington State University

Robert J. Kearns, University of Dayton

Henry Keil, Brunel University

Tim Knight, Oachita Baptist University

Robert Krasner, Providence College

Michael J. Lemke, Kent State University

Lynn O. Lewis, Mary Washington College

B. T. Lingappa, College of the Holy Cross

Vicky McKinley, Roosevelt University

Billie Jo Mello, Mount Marty College

James E. Miller, Delaware Valley College

David A. Mullin, Tulane University

Penelope J. Padgett, Shippensburg University

Richard A. Patrick, Summit Editorial Group

Bobbie Pettriess, Wichita State University

Thomas Punnett, Temple University

Jo Anne Quinlivan, Holy Names College

K. J. Reddy, SUNY-Binghamton

David C. Reff, Middle Georgia College

Jackie S. Reynolds, Richland College

Deborah Rochefort, Shepherd College

Allen C. Rogerson, St. Lawrence University

Michael J. San Francisco, Texas Tech University

Phillip Scheverman, East Tennessee University

Michael Shiaris, University of Massachusetts at Boston

Carl Sillman, Penn State University

Ann C. Smith, University of Maryland

David W. Smith, University of Delaware

Garriet W. Smith, University of South Carolina at Aiken

John Stolz, Duquesne University

Mary L. Taylor, Portland State University

Thomas M. Terry, University of Connecticut

Thomas M. Walker, University of Central Arkansas

Patrick M. Weir, Felician College

Jill M. Williams, University of Glamorgan

Heman Witmer, University of Illinois at Chicago

Elizabeth D. Wolfinger, Meredith College

Robert Zdor, Andrews University

Reviewers for the Fifth Edition

Stephen Aley, University of Texas at El Paso

Susan Bagley, Michigan Technological University

Robert Benoit, Virginia Polytechnic Institute and State University

Dennis Bazylinski, Iowa State University

Richard Bernstein, San Francisco State University

Paul Blum, University of Nebraska

Matthew Buechner, University of Kansas

Mary Burke, Oregon State University

James Champine, Southeast Missouri State University

John Clausz, Carroll College

James Cooper, University of California at Santa Barbara

Daniel DiMaio, Yale University

Leanne Field, University of Texas

Philip Johnson, Grande Prairie Regional College

Duncan Krause, University of Georgia

Diane Lavett, Georgia Institute of Technology

Ed Leadbetter, University of Connecticut

Donald Lehman, University of Delaware

Mark Maloney, Spelman College

Maura Meade-Callahan, Allegheny College

Ruslan Medzhitov, Yale University School of Medicine

Al Mikell, University of Mississippi

Craig Moyer, Western Washington University

Rita Moyes, Texas A&M University

David Mullin, Tulane University

Richard Myers, Southwest Missouri State University

Anthony Newsome, Middle Tennessee State University

Wade Nichols, Illinois State University

Ronald Porter, Pennsylvania State University

Sabine Rech, San Jose State University

Anna-Louise Reysenbach, Portland State University

Thomas Schmidt, Michigan State University

Linda Sherwood, Montana State University

Michele Shuster, University of Pittsburgh

Joan Slonczewski, Kenyon College

Daniel Smith, Seattle University

Kathleen C. Smith, Emory University

James Snyder, University of Louisville School of Medicine

William Staddon, Eastern Kentucky University

John Stolz, DuQuesne University

Thomas Terry, University of Connecticut

James VandenBosch, Eastern Michigan University

Publication of a textbook requires effort of many people besides the authors. We wish to express special appreciation to the editorial and production staffs of McGraw-Hill for their excellent work. In particular, we would like to thank Deborah Allen, our senior developmental editor, for her guidance, patience, prodding, and support. Our project manager, Vicki Krug, supervised production of this very complex project with commendable attention to detail. Liz Rudder, our art editor, worked hard to revise and improve both old and new art for this edition. Beatrice Sussman, our copy editor for the second through fourth editions, once again corrected our errors and contributed immensely to the text's clarity, consistency, and readability.

Each of us wishes to extend our appreciation to people who assisted us individually in completion of this project. Lansing Prescott wants to thank George M. Garrity, the editor-in-chief of Bergey's Manual, for his aid in the preparation of the fifth edition. Revision of the material on procaryotic classification would not have been possible without his assistance. We also much appreciate Amy Cheng Vollmer's contribution of critical thinking questions for each chapter. They will significantly enrich the student's learning experience. John Harley was greatly helped with the section on bioterrorism by James Snyder. Donald Klein wishes to acknowledge the aid of Jeffrey O. Dawson, Frank B. Dazzo, Arnold L. Demain, Frank G. Ethridge, Zoila R. Flores-Bustamente, Michael P. Shiaris, Donald B. Tait, and Jean K. Whelan.

Finally, but most important, we wish to extend appreciation to our families for their patience and encouragement, especially to our wives, Linda Prescott, Jane Harley, and Sandra Klein. To them, we dedicate this book.

Lansing M. Prescott

John P. Harley

Donald A. Klein