INTRODUCTION

Although microbiology and immunology are fundamentally separate areas of biology and medicine, they combine to provide a powerful understanding of human health and disease—especially with regard to infectious disease, disease prevention, and tragically, of the growing awareness that bioterrorism is a real and present worldwide danger.

World of Microbiology and Immunology is a collection of 600 entries on topics covering a range of interests—from biographies of the pioneers of microbiology and immunology to explanations of the fundamental scientific concepts and latest research developments. In many universities, students in the biological sciences are not exposed to microbiology or immunology courses until the later half of their undergraduate studies. In fact, many medical students do not receive their first formal training in these subjects until medical school. Despite the complexities of terminology and advanced knowledge of biochemistry and genetics needed to fully explore some of the topics in microbiology and immunology, every effort has been made to set forth entries in everyday language and to provide accurate and generous explanations of the most important terms. The editors intend World of Microbiology and Immunology for a wide range of readers. Accordingly, the articles are designed to instruct, challenge, and excite less experienced students, while providing a solid foundation and reference for more advanced students. The editors also intend that World of Microbiology and Immunology be a valuable resource to the general reader seeking information fundamental to understanding current events.

Throughout history, microorganisms have spread deadly diseases and caused widespread epidemics that threatened and altered human civilization. In the modern era, civic sanitation, water purification, immunization, and antibiotics have dramatically reduced the overall morbidity and the mortality of disease in advanced nations. Yet much of the world is still ravaged by disease and epidemics, and new threats constantly appear to challenge the most advanced medical and public health systems. For all our science and technology, we are far from mastering the microbial world.

During the early part of the twentieth century, the science of microbiology developed somewhat independently of other biological disciplines. Although for many years it did not exist as a separate discipline at all—being an "off-shoot" of chemistry (fermentation science) or medicine—with advances in techniques such as microscopy and pure culturing methodologies, as well as with the establishment of the germ theory of disease and the rudiments of vaccination, microbiology suddenly exploded as a separate discipline. Whereas other biological disciplines were concerned with such topics as cell structure and function, the ecology of plants and animals, the reproduction and development of organisms, the nature of heredity and the mechanisms of evolution, microbiology had a very different focus. It was concerned primarily with the agents of infectious disease, the immune response, the search for chemotherapeutic agents and bacterial metabolism. Thus, from the very beginning, microbiology as a science had social applications. A more detailed historical perspective of the development of the field may be found in the article "History of Microbiology" in this volume.

Microbiology established a closer relationship with other biological disciplines in the 1940s because of its association with genetics and biochemistry. This association also laid the foundations for the subsequent and still rapidly developing field of genetic engineering, which holds promise of profound impact on science and medicine.

Microorganisms are extremely useful experimental subjects because they are relatively simple, grow rapidly, and can be cultured in large quantities. George W. Beadle and Edward L. Tatum studied the relationship between genes and enzymes in 1941 using mutants of the bread mold Neurospora. In 1943 Salvador Luria and Max Delbrück used bacterial mutants to show that gene mutations were apparently spontaneous and not directed by the environment. Subsequently, Oswald Avery, Colin M. MacLeod, and Maclyn McCarty provided strong evidence that DNA was the genetic material and carried genetic information during transformation. The interactions between microbiology, genetics, and biochemistry soon led to the development of modern, molecularly oriented genetics.

Recently microbiology has been a major contributor to the rise of molecular biology, the branch of biology dealing with the physical and chemical bases of living matter and its function. Microbiologists have been deeply involved in studies of the genetic code and the mechanisms of DNA, RNA, and protein synthesis. Microorganisms were used in many of the early studies on the regulation of gene expression and the control of enzyme activity. In the 1970s new discoveries in microbiology led to the development of recombinant gene technology and genetic engineering. One indication of the importance of microbiology today is the number of Nobel Prizes awarded for work in physiology and medicine during the twentieth century; about a third of these were awarded to scientists working on microbiological problems.

Microorganisms are exceptionally diverse, are found almost everywhere, and affect human society in countless ways. The modern study of microbiology is very different from the chemically and medically oriented discipline pioneered by Louis Pasteur and Robert Koch. Today it is a large discipline with many specialities. It has impact on medicine, agricultural and food sciences, ecology, genetics, biochemistry, and many other fields. Today it clearly has both basic and applied aspects.

Many microbiologists are interested in the biology of the microorganisms themselves. They may focus on a specific group of microorganisms and be called virologists (scientists who study viruses), bacteriologists (scientists who study bacteria), phycologists or algologists (scientists who study algae), mycologists (scientists who study fungi), or protozoologists (scientists who study protozoa). Others may be interested in microbial morphology or particular functional processes and work in fields such as microbial cytology, physiology, ecology, genetics, taxonomy, and molecular biology. Some microbiologists may have a more applied orientation and work on problems in fields such as medical microbiology, food and dairy microbiology, or public health. Because the various fields of microbiology are interrelated, an applied microbiologist must always be familiar with basic microbiology. For example, a medical microbiologist must have a good understanding of microbial taxonomy, genetics, immunology, and physiology to identify and properly respond to the pathogen of concern.

It is clear that scientists study the microbial world in much the same way as they studied the world of multicellular organisms at the beginning of the twentieth century, when microbiology was a young discipline. This is in part due to the huge developments and refinements of techniques, which now allow scientists to more closely and fully investigate the world of bacteria and viruses.

One of the focuses of this book is the field of medical microbiology and its connection with immunology. Medical microbiology developed between the years 1875 and 1918, during which time many disease-causing bacteria were identified and the early work on viruses begun. Once people realized that these invisible agents could cause disease, efforts were made to prevent their spread from sick to healthy people. The great successes that have taken place in the area of human health in the past 100 years have resulted largely from advances in the prevention and treatment of infectious disease. We can consider the eradication of smallpox, a viral disease, as a prime example. The agent that causes this disease is one of the greatest killers the world has ever known—and was probably the greatest single incentive towards the formalization of the specialized study of immunology. Research into the mechanism of Edward Jenner's "vaccination" discovery—he found that of a patient injected with cow-pox produces immunity to smallpox—laid the foundations for the understanding of the immune system and the possibility of dealing with other diseases in a similar way. Because of an active worldwide vaccination program, no cases of smallpox have been reported since 1977. (This does not mean, however, that the disease cannot reappear, whether by natural processes or bioterror.)

Another disease that had a huge social impact was bubonic plague, a bacterial disease. Its effects were devastating in the Middle Ages. Between 1346 and 1350, one third of the entire population of Europe died of bubonic plague. Now generally less than 100 people die each year from this disease. The discovery of antibiotics in the early twentieth century provided an increasingly important weapon against bacterial diseases, and they have been instrumental in preventing similar plague epidemics.

Although progress in the application of immunological research has been impressive, a great deal still remains to be done, especially in the treatment of viral diseases (which do not respond to antibiotics) and of the diseases prevalent in developing countries. Also, seemingly "new" diseases continue to arise. Indeed, there has been much media coverage in the past twenty years in the U.S. of several "new" diseases, including Legionnaires' disease, toxic shock syndrome, Lyme disease, and acquired immunodeficiency syndrome (AIDS). Three other diseases emerged in 1993. In the summer of that year a mysterious flu-like disease struck the Southwest, resulting in 33 deaths. The causative agent was identified as a virus, hantavirus, carried by deer mice and spread in their droppings. In the same year, more than 500 residents of the state of Washington became ill with a strain of Escherichia coli present in undercooked beef prepared at a fast-food restaurant. The organism synthesized a potent toxin and caused haemolyticuremic syndrome. Three children died. In 1993, 400,000 people in Milwaukee became ill with a diarrheal disease, cryptosporidiosis, that resulted from the improper chlorination of the water supply.

It is a great credit to the biomedical research community that the causative agents for all these diseases were identified very soon after the outbreaks. The bacteria causing Legionnaires' disease and Lyme disease have only been isolated in the past few decades, as have the viruses that cause AIDS. A number of factors account for the fact that seemingly "new" diseases arise almost spontaneously, even in industrially advanced countries. As people live longer, their ability to ward off infectious agents is impaired and, as a result, the organisms that usually are unable to cause disease become potentially deadly agents. Also, lifestyles change and new opportunities arise for deadly agents. For example, the use of vaginal tampons by women has resulted in an environment in which the Staphylococcus bacterium can grow and produce a toxin causing toxic shock syndrome. New diseases can also emerge because some agents have the ability to change abruptly and thereby gain the opportunity to infect new hosts. It is possible that one of the agents that causes AIDS arose from a virus that at one time could only infect other animals.

Not only are new diseases appearing but many infectious diseases that were on the wane in the U.S. have started to increase again. One reason for this resurgence is that thousands of U.S. citizens and foreign visitors enter the country daily. About one in five visitors now come from a country where diseases such as malaria, cholera, plague, and yellow fever still exist. In developed countries these diseases have been largely eliminated through sanitation, vaccination, and quarantine. Ironically, another reason why certain diseases are on the rise is the very success of past vaccination programs: because many childhood diseases (including measles, mumps, whooping cough, and diphtheria) have been effectively controlled in both developed and developing countries, some parents now opt not to vaccinate their children. Thus if the disease suddenly appears, many more children are susceptible.

A third reason for the rise of infectious diseases is that the increasing use of medications that prolong the life of the elderly, and of treatments that lower the disease resistance of patients, generally weaken the ability of the immune system to fight diseases. People infected with human immunodeficiency virus (HIV), the virus responsible for AIDS, are a high-risk group for infections that their immune systems would normally resist. For this reason, tuberculosis (TB) has increased in the U.S. and worldwide. Nearly half the world's population is infected with the bacterium causing TB, though for most people the infection is inactive. However, many thousands of new cases of TB are reported in the U.S. alone, primarily among the elderly, minority groups, and people infected with HIV. Furthermore, the organism causing these new cases of TB is resistant to the antibiotics that were once effective in treating the disease. This phenomenon is the result of the uncontrolled overuse of antibiotics over the last 70 years.

Until a few years ago, it seemed possible that the terrible loss of life associated with the plagues of the Middle Ages or with the pandemic influenza outbreak of 1918 and 1919 would never recur. However, the emergence of AIDS dramatizes the fact that microorganisms can still cause serious, incurable, life-threatening diseases. With respect to disease control, there is still much microbiological research to be done, especially in relation to the fields of immunology and chemotherapy.

Recent advances in laboratory equipment and techniques have allowed rapid progress in the articulation and understanding of the human immune system and of the elegance of the immune response. In addition, rapidly developing knowledge of the human genome offers hope for treatments designed to effectively fight disease and debilitation both by directly attacking the causative pathogens, and by strengthening the body's own immune response.

Because information in immunology often moves rapidly from the laboratory to the clinical setting, it is increasingly important that scientifically literate citizens—those able to participate in making critical decisions regarding their own health care—hold a fundamental understanding of the essential concepts in both microbiology and immunology.

Alas, as if the challenges of nature were not sufficient, the evolution of political realities in the last half of the twentieth century clearly points toward the probability that, within the first half of the twenty-first century, biological weapons will surpass nuclear and chemical weapons as a threat to civilization. Accordingly, informed public policy debates on issues of biological warfare and bioterrorism can only take place when there is a fundamental understanding of the science underpinning competing arguments.

The editors hope that World of Microbiology and Immunology inspires a new generation of scientists who will join in the exciting worlds of microbiological and immunological research. It is also our modest wish that this book provide valuable information to students and readers regarding topics that play an increasingly prominent role in our civic debates, and an increasingly urgent part of our everyday lives.

K. Lee Lerner & Brenda Wilmoth Lerner, editors

St. Remy, France

June 2002

Editor's note: World of Microbiology and Immunology is not intended to be a guide to personal medical treatment or emergency procedures. Readers desiring information related to personal issues should always consult with their physician. The editors respectfully suggest and recommend that readers desiring current information related to emergency protocols—especially with regard to issues and incidents related to bioterrorism—consult the United States Centers for Disease Control and Prevention (CDC) website at http://www.cdc.gov/.

Acknowledgments

In addition to our academic and contributing advisors, it has been our privilege and honor to work with the following contributing writers, and scientists: Sherri Chasin Calvo; Sandra Galeotti, M.S.; Adrienne Wilmoth Lerner; Jill Liske, M.Ed.; and Susan Thorpe-Vargas, Ph.D.

Many of the advisors for World of Microbiology and Immunology authored specially commissioned articles within their field of expertise. The editors would like to specifically acknowledge the following contributing advisors for their special contributions:

Robert G. Best, Ph.D.

Immunodeficiency disease syndromes
Immunodeficiency diseases, genetic

Antonio Farina, M.D., Ph.D.

Reproductive immunology

Brian D. Hoyle, Ph.D.

Anthrax, terrorist use of as a biological weapon

Eric v.d. Luft, Ph.D., M.L.S.

The biography of Dr. Harry Alfred Feldman

Danila Morano, M.D.

Rh and Rh incompatibility

Judyth Sassoon, Ph.D.

BSE and CJD disease, ethical issues and socio-economic impact

Constance K. Stein, Ph.D.

Genetic identification of microorganisms

Susan Thorpe-Vargas, Ph.D

Immunology, nutritional aspects

The editors would like to extend special thanks Dr. Judyth Sassoon for her contributions to the introduction to World of Microbiology and Immunology. The editors also wish to acknowledge Dr. Eric v.d. Luft for his diligent and extensive research related to the preparation of many difficult biographies. The editors owe a great debt of thanks to Dr. Brian Hoyle for his fortitude and expertise in the preparation and review of a substantial number of articles appearing in World of Microbiology and Immunology.

The editors gratefully acknowledge the assistance of many at Gale for their help in preparing World of Microbiology and Immunology. The editors thank Ms. Christine Jeryan and Ms. Meggin Condino for their faith in this project. Special thanks are offered to Ms. Robyn Young and the Gale Imaging Team for their guidance through the complexities and difficulties related to graphics. Most directly, the editors wish to acknowledge and thank the Project Editor, Mr. Brigham Narins for his good nature, goods eyes, and intelligent sculptings of World of Microbiology and Immunology.

The editors dedicate this book to Leslie Moore, M.D., James T. Boyd, M.D., E.M. Toler, M.D., and to the memory of Robert Moore, M.D. Their professional skills and care provided a safe start in life for generations of children, including our own.

The editors and authors also dedicate this book to the countless scientists, physicians, and nurses who labor under the most dangerous and difficult of field conditions to bring both humanitarian assistance to those in need, and to advance the frontiers of microbiology and immunology.

INTRODUCTION

How to Use the Book

Advisory Board

Acknowledgments