The American Anti-Vivisection Society (AAVS) petitioned the National Institutes of Health (NIH) on April 23, 1997, to prohibit the use of animals in the production of mAb. On September 18, 1997, NIH declined to prohibit the use of mice in mAb production, stating that "the ascites method of mAb production is scientifically appropriate for some research projects and cannot be replaced." On March 26, 1998, AAVS submitted a second petition, stating that "NIH failed to provide valid scientific reasons for not supporting a proposed ban." The office of the NIH director asked the National Research Council to conduct a study of methods of producing mAb. In response to that request, the Research Council appointed the Committee on Methods of Producing Monoclonal Antibodies, to act on behalf of the Institute for Laboratory Animal Research of the Commission on Life Sciences, to conduct the study. The 11 expert members of the committee had extensive experience in biomedical research, laboratory animal medicine, animal welfare, pain research, and patient advocacy (Appendix B). The committee was asked to determine whether there was a scientific necessity for the mouse ascites method; if so, whether the method caused pain or distress; and, if so, what could be done to minimize the pain or distress. The committee was also asked to comment on available in vitro methods; to suggest what acceptable scientific rationale, if any, there was for using the mouse ascites method; and to identify regulatory requirements for the continued use of the mouse ascites method. The committee held an open data-gathering meeting during which its members summarized data bearing on those questions. A 1-day workshop (Appendix A) was attended by 34 participants, 14 of whom made formal presentations. A second meeting was held to finalize the report. The present report was written on the basis of information in the literature and information presented at the meeting and the workshop.

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The last decade has witnessed remarkable developments in antibody research and its therapeutic applications. With the methods of molecular biology it is now possible to manipulate the specificities and activities of antibody molecules to generate an almost limitless array of structures for both basic investigations and the clinical setting. The contributions to this volume cover all three domains of the antibody: the variable regions, the relatively neglected but crucial hinge, and the constant region. These studies provide critical structural and functional information about antibodies, while also pointing the way to the construction of molecules with enhanced or even novel properties. Bringing together major experts on antibody engineering, this book is highly recommended to faculty, postdoctoral fellows and graduate students in molecular biology, microbiology, immunology, cancer research and genetics.

Over the last ten years, much effort has been devoted to improving the biophysical techniques used in the study of viruses. This has resulted in the visualization of these large macromolecular assemblages at atomic level, thus providing the platform for functional interpretation and therapeutic design. Structural Virology covers a wide range of topics and is split into three sections. The first discusses the vast biophysical methodologies used in structural virology, including sample production and purification, confocal microscopy, mass spectrometry, negative-stain and cryo-electron microscopy, X-ray crystallography and nuclear magnetic resonance spectroscopy. The second discusses the role of virus capsid protein structures in determining the functional roles required for receptor recognition, cellular entry, capsid assembly, genome packaging and mechanisms of host immune system evasion. The last section discusses therapeutic strategies based on virus protein structures, including the design of antiviral drugs and the development of viral capsids as vehicles for foreign gene delivery. Each topic covered will begin with a review of the current literature followed by a more detailed discussion of experimental procedures, a step in the viral life cycle, or strategies for therapeutic development. With contributions from experts in the field of structural biology and virology this exceptional monograph will appeal to biomedical scientists involved in basic and /or applied research on viruses. It also provides up-to-date reference material for students entering the field of structural virology as well as scientists already familiar with the area.

Coronaviruses were recognized as a group of enveloped, RNA viruses in 1968 and accepted by the International Committee on the Taxonomy of Viruses as a separate family, the Coronaviridae, in 1975. By 1978, it had become evident that the coronavirus genomic RNA was infectious (i. e. , positive strand), and by 1983, at least the framework of the coronavirus replication strategy had been per ceived. Subsequently, with the application of recombinant DNA techniques, there have been remarkable advances in our understanding of the molecular biology of coronaviruses, and a mass of structural data concerning coronavirus genomes, mRNAs, and pro teins now exists. More recently, attention has been focused on the role of essential and accessory gene products in the coronavirus replication cyde and a molecular analysis of the structure-function relation ships of coronavirus proteins. Nevertheless, there are still large gaps in our knowledge, for instance, in areas such as the genesis of coronavirus subgenomic mRNAs or the function of the coronavirus RNA-dependent RNA polymerase. The diseases caused by coronaviruses have been known for much longer than the agents themselves. Possibly the first coronavirus-related disease to be recorded was feline infectious peritonitis, as early as 1912. The diseases associ ated with infectious bronchitis virus, transmissible gastroenteritis virus, and murine hepatitis virus were all well known before 1950.

A respected resource for decades, the Guide for the Care and Use of Laboratory Animals has been updated by a committee of experts, taking into consideration input from the scientific and laboratory animal communities and the public at large. The Guide incorporates new scientific information on common laboratory animals, including aquatic species, and includes extensive references. It is organized around major components of animal use: Key concepts of animal care and use. The Guide sets the framework for the humane care and use of laboratory animals. Animal care and use program. The Guide discusses the concept of a broad Program of Animal Care and Use, including roles and responsibilities of the Institutional Official, Attending Veterinarian and the Institutional Animal Care and Use Committee. Animal environment, husbandry, and management. A chapter on this topic is now divided into sections on terrestrial and aquatic animals and provides recommendations for housing and environment, husbandry, behavioral and population management, and more. Veterinary care. The Guide discusses veterinary care and the responsibilities of the Attending Veterinarian. It includes recommendations on animal procurement and transportation, preventive medicine (including animal biosecurity), and clinical care and management. The Guide addresses distress and pain recognition and relief, and issues surrounding euthanasia. Physical plant. The Guide identifies design issues, providing construction guidelines for functional areas; considerations such as drainage, vibration and noise control, and environmental monitoring; and specialized facilities for animal housing and research needs. The Guide for the Care and Use of Laboratory Animals provides a framework for the judgments required in the management of animal facilities. This updated and expanded resource of proven value will be important to scientists and researchers, veterinarians, animal care personnel, facilities managers, institutional administrators, policy makers involved in research issues, and animal welfare advocates.