No one whose opinion deserves a moment's consideration can doubt that most of the great positive evils of the world are in themselves removable, and will, if human affairs continue to improve, be in the end reduced to narrow limits. J. S. Mill, Utilitarianism, II, 1863 Mill was not writing about herpesviruses, but had he known them as we do, he would have included them among the great positive evils of the world. They cause disease and premature death, and are very costly to our society. There is no loftier aim than to cure or prevent human infections with these viruses. The objective of much of the current research on herpesviruses is directed toward an understanding of the molecular mechanisms involved in initiation of infection, establish ment and termination of latent state, virus multiplication, and the destruction of cells which ultimately is the basis of the diseases caused by these viruses. At no time during the past 80 years, since members of the herpesvirus family were first discovered, has there been so much progress in our understanding of the biology of these viruses as in the past few years. Along with the development of a greater understanding of the molecular biol ogy of the well-known herpesviruses we have witnessed the isolation of new human herpes viruses.

All but one* of the following articles represent comprehensive reports on a workshop held between 7 and 9 May 1981 at the Institute of Virology and Immunobiology, University of Wfuzburg, Federal Republic of Germany. The title of the workshop was "The Involvement of Endogenous Retroviruses inN ormalFunction and Pathological Growth of Lymphocytes." Rather than collecting and printing manuscripts of the individual communications, the organizers asked selected parti cipants to write, after the workshop, concise articles each compris ing several contributions and discussions on major topics. In so doing, we hope to present to a larger audience a synopsis of the various information and views exchanged at the meeting. Such a procedure seemed the more appropriate as the workshop was intended to bring together specialists from two rather diverse fields: RNA-tumor virology and immunobiology. While this created some initial problems of terminology, it was quite effective in making representatives of one field more aware of the significance and the contributions ofthe other. It also great ly contributed to realization of the complexity of the problems involved in virus-induced leukemogenesis."

The first volume of Antibiotics was published in 1967 and contained a series of review papers on antibiotic actions. The editors, Drs. GOTTLIEB and SHAW, were aware of the rapid development of this field of study and provided a number of addenda in an effort to keep knowledge up to date while the book was in production. One year after the publication of Antibiotics I, this editor had a conference with Dr. KONRAD F. SPRINGER in which it became clear that another volume on actions of antibiotics would be necessary. For a variety of reasons, this was delayed until 1975 and became Antibiotics III. It did not contain addenda since it was recognized by the editors, Drs. CORCORAN and HAHN, that still another volume would have to follow and that in a moving field, such as the study of the actions of antibacterial drugs, no publication can be definitive or remain current, except for a limited period of time. The editors of Volume III grouped the contributions into sections: 1. Inter ference with nucleic acid biosyntheses, 2. Interference with protein biosynthesis, and 3. Interference with cell wall/membrane biosynthesis, specific enzyme sys tems, and those in which the mode of action was not known with certainty."

This volume in the Monographs in Evolutionary Biology series addresses issues that are part of an emerging area of research loosely called "mo lecular evolution. " Its practitioners include both molecular biologists cu rious about the evolutionary implications of their data and evolutionary biologists pushing their analyses to the molecular level. The union of these fields of molecular and organismal biology has been turbulent at times, and, as shall be seen, this dialectic has led to some very serious challenges to long-held notions about the role of natural selection in evolution and the economy of genome organization in eukaryotes. As an inevitable outgrowth of molecular biology, molecular evolution is necessarily a young discipline, but it can already point proudly to two major discoveries. The first, is the molecular clock, a concept that has emerged from the analysis of at least four data sets-amino acid sequences, immunologic data, DNA renaturation studies, and, recently, analyses of DNA sequences. The reality of a strong stochastic component in the evolution of nucleotide sequences can no longer be doubted, although the accuracy of the clock with regard to particular sequences and within particular groups of or ganisms should be independently measured each time it is used. Never theless, molecular clocks will assume increasingly important roles in phy logenetic reconstructions, especially since the fossil record is so fragmentary. The second major discovery of molecular evolution has been the incredible complexity of the eukaryotic genome."

The basis for the effective treatment and cure of a patient is the rapid diagnosis of the disease and its causative agent, which is based on the analysis of the clinical symptoms coupled with laboratory tests. Although rapid advance ments have been made in the laboratory diagnosis of virus diseases, the neces sary isolation of the causative virus from the clinical specimens is a relatively long procedure. Viruses which integrate into the cellular DNA (such as human immunodeficiency virus, HIV -1, or hepatitis B virus) are difficult to identify by molecular techniques, while viruses which exist in the clinical material in low concentrations are even more formidable to identify. Recently, the application of the polymerase chain reaction (peR) technique developed by K. D. Mullis and detailed in the study by Saiki et al. (1985) led to a revolution in virus diagnosis. The peR technique was rapidly applied to the diagnosis of viruses in clinical material. Volume 1 of Frontiers of Virology provides new information on the advan tages of the use of the peR for the diagnosis of many human disease-causing viruses, as well as on some problems with its use."

In recent years, biotechnology research and development (R&D) in China has been receiving increasing attention from the world. With the open-door policy of the Chinese government, many international publications (for academia) and large market potential (for industry) constitute the two big reasons for the above phen- enon. Biotechnology has become one of the priorities in Mainland China for so- ing many important problems, such as food supply, health care, environment protection, and even energy. The central government has been implementing a c- ple of programs which cover a wide spectrum in basic research, high-tech devel- ment and industrialization, such as Basic Research Program (973 Plan), Hi-Tech R&D Program (863 Plan), Key Science & Technology Problem Solving Program (Gong-guan Plan), as well as the establishment of centers of excellence - Key Laboratories and Engineering Centers, etc. The funding from various local gove- ments and industry for R&D has also been increasing continuously. Biotechnology centers in Shenzhen, Shanghai and Beijing have been established. There are more than 400 universities, research institutes and companies and a total of over 20,000 researchers involved in biotechnology in the Mainland. The number of research papers published internationally and patent applications is also increasing rapidly. In addition, the huge market potential with about 1. 4 billion population, which is already open to the outside world, has provided numerous opportunities for int- national and domestic companies to invest in biotechnology, which pushes forward the biotechnology industrialization in China.

Antiviral chemotherapy has come of age, and, after an initial slow pro gress, the development of new antiviral agents has proceeded at a more rapid pace and the perspectives for their clinical use have increased considerably. Now, 25 years after the first antiviral assay (idoxuridine) was introduced in the clinic, it is fitting to commemorate the beginning of the antivirals' era. In its introductory chapter B.E. Juel-Jensen touches on what may be con sidered as five of the most fundamental requirements of an antiviral drug: efficacy, relative non-toxicity, easy solubility, ready availability and rea sonable cost. Surely, the antiviral drugs that have so far been used in the clinic could still be improved upon as one or more of these five essential demands are concerned. How is all began is narrated by W.H. Prusoff. The first antiviral drugs to be used in humans were methisazone and idoxuridine, the former, which is now of archival interest, in the prevention of smallpox, the latter, which was approved for clinical use in the United States in 1962, for the topical treatment of herpetic keratitis. In terms of potency, also because of solubility reasons, idoxuridine has been superseded by trifluridine in the topical treatment of herpes simplex epithelial keratitis. H.E. Kaufman did not find trifluridine or acyclovir ef fective in the treatment of deep stromal keratitis or iritis and he reckons that other antiviral drugs (i.e. bromovinyldeoxyuridine) would not be effec tive either."

Scientific research on dengue has a long and rich history. The literature has been touched by famous names in medicine- Benjamin Rush, Walter Reed, and Albert Sabin, to name a very few- and has been fertile ground for medical historians . The advances made in those early investigations are all the more remarkable for the limited tools available at the time. The demonstration of a viral etiology for dengue fever, the recognition of mosquitoes as the vector for transmission to humans, and the existence of multiple viral variants (serotypes) with only partial cross-protection were all accomplished prior to the ability to culture and characterize the etiologic agent. Research on dengue in this period was typically driven by circumstances. Epidemics of dengue created public health crises, although these were relatively short-lived in any one location, as the population of susceptible individuals quickly shrank. Military considerations became as a major driving force for research. With the introduction of large numbers of non-immune individuals into endemic areas, dengue could cripple military readiness, taking more soldiers out of action than hostile fire. Dengue and dengue hemorrhagic fever, which assumed pandemic proportions during the latter half of the last century, have shown no indication of slowing their growth during this first decade of the twenty-first century. Challenges remain in understanding the basic mechanisms of viral replication and disease pathogenesis, in clinical management of patients, and in control of dengue viral transmission. Nevertheless, new tools and insights have led to major recent scientific advances. As the first candidate vaccines enter large-scale efficacy trials, there is reason to hope that we may soon "turn the corner" on this disease.

When phagocytes are exposed to a number of different stimuli, they undergo dra matic changes in the way they process oxygen. Oxygen uptake increases markedly, frequently more than 50-fold; the phagocytes begin to produce large quantities of superoxide and hydrogen peroxide; and they immediately begin to metabolize large amounts of glucose by way of the hexose monophosphate shunt. This series of changes has become known as the respiratory burst. It was first believed that the major function of this respiratory burst was to generate powerful antibacterial agents by the partial reduction of oxygen. It is becoming apparent that the respiratory burst has much wider application, and its physiological function in many different biolog ical areas is clear. In this volume, we have attempted to bring together the work of experts who have published extensively on the involvement of the respiratory burst in different physiological functions. In the first three chapters, Dr. Borregaard and Dr. Berton and co-workers and Dr. Roos and co-workers bring together what is known about the respiratory burst. They present up-to-date versions of the biochemical and metabolic activities associ ated with the burst. In Chapter 4, Dr. Styrt and Dr. Klempner discuss the respiratory burst as it affects cellular ion homeostasis. Dr. Cohen and Dr. Britigan (Chapter 5) present some interesting data on the competition between the respiratory burst and bacteria for oxygen. Dr. Dobrina and Dr."

Those who have had the privilege to visit the Sistine Chapel may remember the fres co painting of Jesus curing the leper (Marcus 1, 40-45). It seems that leprosy was not only known 2000 years ago but was also recognized as an important problem. Unfortunately, little has changed since then. Although leprosy is mainly known as an "import" disease in Europe and North America, in the greater part of the world it remains the problem it has always been, one of a stigmatizing disease comparable to the modern day pestilence, namely AIDS. Who could forget Durer's etch of a leper walking with a clapper to an nounce his presence, or the heartbreaking stories of patients, especially those with lepromatous leprosy, ousted by their own families to become social outcasts forced to beg for their food. This attitude is slowly changing and with this change the name of Mahatma Ghandi will always be connected and remembered."

JAMES L. MCGAUGH Understanding of the nature and functions of neurotransmitter systems in the brain has increased enormously in recent decades. Lack of knowledge required us, not too long ago, to use the adjective "putative" when discussing transmitters. Such caution is no longer essential (at least for a number of transmitters). Impressive progress has been achieved in understanding the pharmacology, biochemistry and anatomy of transmitter systems. There has, however, been relatively less progress in understanding the functioning of brain transmitters in regulating and mediating behavior. A simple and certainly correct explanation for this is, of course, that understanding of neurotransmitter functions requires prior detailed knowledge of basic pharmacology, biochemistry and anatomy. Beyond that, it now seems likely that progress in understanding the functions of brain neurotransmitters will proceed only as we examine the interactions of neurotransmitter systems in regulating behavioral functions. This premise is, of course, suggested by the findings of studies of the chemical neuroanatomy of the brain: Neurotransmitter systems are influenced by other neurotransmitter systems and, in tum, influence the same as well as other systems. No system works alone. The chapters in this book explicitly examine the interactions of neurotransmitter systems involved in the regulation of cognitive processes. The facts and interpretations offered provide compelling support for the premise that cognitive processes are orchestrated by interactions among neurotransmitter systems. And, they offer promise that understanding of such interactions will be of critical importance in the develop ment of treatments for brain diseases affecting cognitive functioning."

The use of biotechnical processes in control of environmental pollution and in haz ardous waste treatment is viewed as an advantageous alternative or adduct to phys ical chemical treatment technologies. Yet, the development and implementation of both conventional and advanced biotechnologies in predictable and efficacious field applications suffer from numerous technical, regulatory, and societal uncertainties. With the application of modern molecular biology and genetic engineering, there is clear potential for biotechnical developments that will lead to breakthroughs in controlled and optimized hazardous waste treatment for in situ and unit process use. There is, however, great concern that the development of these technologies may be needlessly hindered in their applications and that the fundamental research base may not be able to sustain continued technology development. Some of these issues have been discussed in a fragmented fashion within the research and development community. A basic research agenda has been established to promote a sustainable cross-disciplinary technology base. This agenda includes developing new and improved strains for biodegradation, improving bioanalytical methods to measure strain and biodegradation performance, and providing an in tegrated environmental and reactor systems analysis approach for process control and optimization."

This book is a collection of critical reviews about a diverse group of virus families with two features in common: the stable repository of genetic information in each virus is RNA, and each virus modifies and appropriates a particular patch of the eukaryotic cell membrane system to complete its structure. The reviews take the reader from the level of virus genome structure and expression through the quaternary interactions between virus-specified elements and cellular components that cooperate to produce virus particles. There are spectacular illustrations in this volume, but it is much more than a picture gallery. Reading widely in this book can be an effective antidote to overspecialization: in these pages, you are likely to learn much about viruses and about cells that you didn't know before; you'll discover illuminating parallels between diverse virus families; you'll come away with a sharpened awareness of important things that are still to be learned. Memphis, Tenn. , Summer 1984 David W. Kingsbury Preface This book was written at the suggestion of Dr. David W. Kingsbury made at a work shop on viruses organized by the Multiple Sclerosis Society in Aspen, Colorado, U. S. A. , three years ago. Originally, we had thought to focus on the morphological aspects of viral assembly. Later, during our discussions on the process of budding of enveloped RNA viruses, it became evident that we should include biochemical data in our review and correlate them with the structural aspects of virus maturation.

Presented here are recent achievements in molecular biology of non-pathogenic yeast and filamenous fungi as well as of human pathogens. Thebook is diveded into 4 sections: - Molecular Biology of Yeast; - Molecular Biology of Filamenous Fungi; - New Tools and Prospectives for Medical Mycology; - Fungal Morphogenesis. It focuses on aspects of medical mycology, namely isolation of specific genes and strategies for developing new targets for antifungal therapy.

A sample of the most exciting developments in the cloning, manipulation, expression and application of genetically-engineered monoclonal antibodies. This rapidly-evolving field has witnessed the PCR combinatorial cloning of vast immunological diversity, in vitro mutagenesis of MAbs, MAbs created by transgenic animals, novel expression systems in plants, animals and lower systems, as well as a rich variety of genetically modified MAbs as potential therapeutic agents. Leading scientists from academia and industry present their own findings as well as short reviews of these research areas.

Mter the discoveryof the tobacco mosaic virus by D. I. Ivanov skU in 1892 14], the new science of virology was born and began to develop rapidly. The number of viruses now known is enormous and they can infect nearly all animal and plant organisms. Microorganisms themselves are no exception to this rule. Despite intensive study of Vlruses, their origin and nature are still a subject for speculation and hypothesis. The general concept of viruses embraces a wide group of biologically active structures occupying an intermediate position between living and nonliving matter. The dual character of viruses is determined by the fact that, while they do not possess an inde pendent system of metabolism, which is a characteristic feature of every living being, they nevertheless carry within themselves all the necessary information for autoreproduction. A striking feature of the virus is that it consists essentially of two components: a protein envelope and the nucleic acid con tained within it. In contrast to the elementary structural unit of the living or ganism, the cell, which contains two types of nucleic acid (DNA and RNA), the virus particle contains only one type of nucleic acid - either DNA or RNA. It is perhaps this which is responsible for the imperfection of the virus as a living organism."

William Trager has been an avid student of parasites for over 50 years at the Rockefeller University. Around the turn of this century, parasitology enjoyed a certain vogue, inspired by colonial responsibilities of the technically ad vanced countries, and by the exciting etiological and therapeutic discoveries of Ross, Manson, Ehrlich, and others. For some decades, the Western hemi sphere's interest in animal parasites has been eclipsed by concern for bacteria and viruses as agents of transmissible disease. Only very recently, initiatives like the Tropical Disease Research programs of WHO-World Bank-UNDP, and the Great Neglected Disease networks of the Rockefeller and MacArthur Foundations have begun to compensate for the neglect of these problems by United States federal health research agencies. Throughout that period, how ever, the Rockefeller Institute (later University) has given high priority to the challenges of parasitism, corresponding during a formidable period with Dr. Trager's own career. The present work then, is a distillation of the insight collected by our principal doyen of parasite biology, informed but by no means confined to his own research. It is addressed to the reader of broad biological interest and training, not to the specialist. The disarmingly unpretentious style makes the work readily accessible to college undergraduates or even to gifted high school students; but do not be deceived thereby, as it has an enormous range of factual information and theoretical insight, familiar to few, but potentially important to most biologists."

The advancement of science is ever more contingent upon the interaction of experts vast amount of scientific information being gathered every day that exceeds the ability of any one scientist to acquire. As an illustration of the frantic pace of scientific disc- more acute in the case of scientific fields at the interface of different and seemingly distant areas of study. Amidst these, the field of cell encapsulation brings together an array of diverse disciplines such as molecular biology and biopolymers, gene therapy and inorganic membranes, stem cell biology and physicochemistry, immunology and nanotechnology. Clearly, such range of topics is too broad for any individual scientist the state-of-the-art in the field of cell encapsulation. At the core of this technology, there is an interaction of physicochemical and biological elements forming three distinct layers of complexity. First, the chemistry of the biopolymer dictates the degree of protein adsorption, vascularization, tox- ity and biocompatibility of the microcapsules. Advances in biopolymer science are providing solutions to overcome existing challenges and to improve microcapsules as delivery vehicles. Second, the choice of cells, and more precisely the plethora of in determining the immune response elicited by the host to implanted microcapsules.

nomenon [26]. Indeed, Krieg et al. [21] showed that the elimination of the CpG in a particular ODN invariably abolished immune stimulation, but changes in the ODN sequences that did not affect the CpG or the flanking bases did not alter the immuno- stimulatory (IS) effect. Furthermore, they extended the initial observations of the IS effects to non-palindromic CpG-enriched ODN [21]. Subsequent studies showed that CpG-enriched ODN also induce the secretion of IL-6 and IL-12 [19] and IFN-a [6, 27]. By adding or deleting various IS sequences (ISS)-ODN to or from different pDNAs, it was demonstrated that the ISS have a pivotal role in the induction of the subsequent immune response to the gene product in gene-vaccinated animals. The enhanced Thl immune response induced by gene vaccination is the consequence of the activation of the innate immune response by the ISS in the pDNA backbone [30, 31], rather than the low dose of intracellularly produced antigen. The cell activation products induced by the ISS, i. e. , IFN-a [3], IFN-~ [43], IL-12 [37], and IL-18 [25], are established inducers of IFN-y synthesis and promote the differentiation of naive T helper cells to Thl lym- phocytes. Thus, the ISS activate the precise innate cytokine network required to pro- mote Thl differentiation (see Fig. 1). In a recent study it was demonstrated that this ap- proach is also applicable to a protein antigen.

Almost 50 million persons visit another continent each year. It is mainly those 15-18 million travelers from industrialized nations who visit or reside in developing countries that are at increased health risk. To develop effective health protection advice, the health risks of travel and the benefits of prophylaxis (vaccines, new and old drugs, behaviour modification, etc.) should be assessed systematically. The purpose of this book is to improve the protection of the travelers' health by more effective and more uniform recommendations. It contains many data on recent research and represents the first comprehensive account on travel medicine for professionals.

We are most gratified by the response to the initiation of this series of volumes presenting recent developments and new concepts in microbial ecology. Favorable reactions have been expressed in both oral and written communication, and Ad vances in Microbial Ecology thus seems to be providing a worthwhile outlet in a rapidly growing field of microbiology and environmental sciences. The growing importance of microbial ecology is evident in many ways. Uni versity personnel are expanding their programs and increasing the number of research topics and publications. Substantial numbers of industrial scientists have likewise entered this field as they consider the microbial transformation of chemicals in waters and soils and the effects of synthetic compounds on natural microbial communities. Agricultural, medical, dental, and veterinary practitioners and scientists have also been increasing their activity in microbial ecology because of the importance of the discipline to their own professions. In addition, govern mental agencies have expanded regulatory and research activities concerned with microbial ecology owing to the importance of information and regulations fo cused on the interactions between microorganisms in nature and particular en vironmental stresses."

Given the continuing high level of concern among health professionals and the general public about issues related to AIDS, this volume on testing for AIDS and related viruses is extremely timely. The book has been written by experts in the area of AIDS testing, many of whom are at the Centers for Disease Control. The book includes several chapters which compare the different laboratory tests available for detecting the AIDS virus (HIV). It also addresses such topics as ethical considerations in AIDS testing, HIV infection in children, testing for other human viruses related to HIV, safety practices in HIV-testing laboratories, and managing occupational exposure to HIV. The book is intended for public health officials involved in HIV testing, hospital administrators and clinical laboratory directors responsible for setting up HIV testing programs, and physicians concerned with testing for AIDS.

Study of parasitology, like any other branch of biological science, has in recent years been increasingly revealing and rewarding with enrichment and embellishment by basic sciences, specially with application of spectacular advances in molecular biology and biotechnology. Such a fruitful fusion of more than one discipline has now come to characterise more than ever before our approach to the subject. This volume of helminthology with contributions from a galaxy of distinguished scientists in specific areas, bears an eloquent testimony to the gratifying yield that accrues from cross fertilisation of multiple disciplines and able support from basic sciences. Matazoan parasites, helminths, living in more than one host in different stages of development, present an intricate spectrum of host-parasite relationship, which has evolved through diverse frame and flow of ecologic circumstances. The situation is further complicated, as elaborated here, by genotypic and phenotypic variations, which profoundly influence the dynamic interaction between hosts and parasites and determine consequently survival and propagation of the latter. Indeed, one of the important messages upheld in this book is that genetic endowment of parasites plays a pivotal role in their immunogenicity, pathogenicity, response to variable environmental composition, including drug response and also their transmission dynamics and epidemiology. Evolution of parasitic helminths with concomitant physiologic and morphologic alterations have been traced from free-living stage to development of host-specificity of different degrees and parasitic speciation.

The eighth workshop in this series on Mechanisms in B-Cell Neoplasia 1990 was held in Wilson Hall at the National Institutes of Health, Bethesda, Maryland on March 28-30. Five major topics formed the basis for the discussions: 1) progress in experimental models of B-cell tumorigenesis, 2) the role of IL-6 in plasma cell tumor formation with particular emphasis on human myeloma, 3) immortaliza tion and regulation of mitosis in B-cells, 4) the mYQ gene in B-cell neoplasia, and 5) the role of EBV and other oncogenes in transforma tion of human B-Iymphocytes. A meeting on the Epidemiology of Myeloma was held at the N. I. H. on the preceding day, and many of those interested in the clinical aspects of myeloma were also participants at the workshop. Experimental Models of B-Cell Tumor Development We have seen in the last eight years the steady growth of model experimental systems, many of which have been designed to be counter parts of the major forms of human B cell tumors, e. g., follicular lymphomas, Burkitt's lymphomas, acute B-cell leukemia and multiple myeloma. A variety of novel ways of inducing these tumors has been described. Advantage has been taken of the "experiments in nature" to identify critical genes that playa role in tumor pathogenesis. These genes have been identified by being near to viral insertion and chromosomal translocation sites, or by having been incorporated or transduced into a defective transforming retrovirus."

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having passed only recently through its descriptive phase of naming and numbering, has probably reached that stage at which relatively few new-truly new-viruses will be discovered. Triggered by the intellectual probes and techniques of molecular biology, genetics, bio chemical cytology, and high resolution microscopy and spectroscopy, the field has experienced a genuine information explosion. Few serious attempts have been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of 19 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed, and scattered throughout a wide literature. In this way, we hope to place the entire field in perspective, and to develop an invaluable reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered any where, but which also provides a logical progression of developing facts and integrated concepts."