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Progress in Medical Virology, Vol. 33
exemplary in highlighting the important classical experiments with yellow fever virus and also including very recent nucleotide sequence data which will be invaluable in at last elucidating the replication strategy of the flaviviruses. The chapters dealing with the epidemiology of the disease and clinical diagnosis are clearly written with several most useful tables and should thus enable the educated but inexperienced worker in the field to recognize the disease, assess the extent of epidemics and understand the importance of the control measures which must be taken. The chapter on control and prevention contains several tables which will be a useful source of reference to all field workers. Those dealing with the suitability, resistance and spraying conditions for insecticides will be a valuable ready reference for those involved in vector control. The chapter also contains a fairly comprehensive account of vaccination procedures as well as a relatively detailed description of the contraindications and complications which can arise through mass vaccination programmes. The final chapter in this book deals with national and regional strategies for combating vector-borne diseases. The
principles laid out here should enable the public health administrators to appreciate and implement a comprehensive control strategy and should also enable the worker in the field to appreciate the part they play in the overall eradication strategy. In conclusion I found the book a clear and concise account of the many diverse political and scientific procedures which must be implemented in order to control yellow fever. The book obviously has gained a great deal by combining the expertise and experience of a number of recognized experts in yellow fever, and the 'rapporteur' must be congratulated in integrating these diverse skills to produce a clear and precise final product. My only critisisms are first that I doubt if only 64 references are adequate to represent the large and diverse field of yellow fever research. Secondly, although the book is attractively produced and clearly printed, the relatively poor quality of paper and binding would be a disadvantage. This problem could be particularly enhanced as the book is clearly intended to be a frequently used handbook by workers in the field in tropical countries.
J.R. Stephenson
Vaccine Supply and Innovation Committee on Public-Private Sector Relations in Vaccine Innovation, Institute of Medicine, National Academy of Sciences National Academy Press, Washington, DC, 1985, 210 pp., ISBN 0-309035449 As stated by Dr J.P. Sanford (Chairman) in the preface, 'vaccines are an elegant solution to one of the perennial problems of the human race - infectious disease'. Though the potential savings in dollars and human misery are phenomenal, the ultimate possibilities have been far from realized. This is especially distressing at the dawn of a new era in biotechnology that provides approaches and solutions to problems that, until
recently, were considered intractable. The shortfall in development and utilization of vaccines is explicable in a maze of interrelating problems and circumstances that may only be resolved slowly and in stepwise progression. These problems are focused principally on a triumvirate of institutions and workers that include (a) basic research creators (usually academia and government but sometimes industry), (b)
Progress in Medical Virology, Vol. 33 Editor: J.L. Melnick, S. Karger AG, Basel, 1986, 182 pp., £58.50. ISBN 3-8055-4155-4 This series is consistent in providing high quality reviews covering all aspects of virology. Volume 33 is no exception and contains an interesting blend of subjects including human papillomaviruses, herpes simplex latency, cytomegalovirus, transmissable encephalopathy agents (e.g. scrapie and CreutzfeldtJakob disease) and persistent autonomous parvovirus infection (Aleutian disease). In addition there is an excellent review on virus vaccines which succinctly describes the present status and future developments of over 17 human vaccines. The section on future prospects for vaccination covers administr-
254 Vaccine,Vol. 5, September1987
ation routes, live (including genetically attenuated strains), inactivated, subunit, recombinant, synthetic and antiidiotype vaccines. This is both an interesting and readable summary and, aided by well tabulated data, a useful reference work. It is intended as a status report, thus the sections on individual vaccines are, of necessity, short and succinct summaries and not in depth studies. Papillomaviruses are DNA viruses and, except for bovine types, are species specific. They replicate in epidermal cells during keratinization. The human types are of interest because as well as
industrial research and development and production laboratories, and (c) health care providers including policy makers. The incentives, disincentives and motivations for this triple complex are multiple and include such matters as resource allocation for research, economic incentives for vaccine development and production, vaccine-caused injury and liability and compensation issues, marketability and extent of vaccine use, public information and public acceptance, and the lack of precedent and strong orientation in medical practice, aside from paediatrics, to disease prevention by vaccination. The committee's report is exemplary in its analysis of problems and proposals for solving this multifactorial complex of barriers to innovation in vaccine development and supply. The Committee recognized the difficulty of maintaining any coordinated and continuing activity in vaccine development and use and recommended, as did previous committees, that a non-governmental or quasi-governmental National Vaccine Commission be established. This commission would report to the President and the Congress, and the objectives would be '(1) to advance the control of infectious disease by promoting the continued innovation, production, and use of vaccines, and (2) to ensure that this goal is achieved in a socially responsible and just manner'. One aspect of report is, in a sense, outdated by the recent enactment of the omnibus health package (S. 1744) that contains vaccine injury compensation reforms. The committee may take credit, in part at least, for bringing about this favourable development. The report should be considered required reading for anyone engaged in development or delivery of vaccines. Dr Jay Sanford and his committee, and study director Dr Roy Widdus can be justifiably proud of what they have wrought.
Maurice R. Hilleman being responsible for warts, and benign tumours (papillomas), they are also associated with genital tumours. The review very thoroughly covers all aspects of their role in human disease, their interaction with the body's immune surveillance system, and therapeutic and prophylactic aspects. Aleutian disease is caused by an autonomous and persistent parvovirus infection of mink and has serious economic consequences. This chapter summarizes recent data on the postimmune response to the infection and its effect on initiating the disease. The chapter on herpes virus latency and recurrence addresses a problem that is still not fully understood and is of great importance to the development of safe herpes simplex virus vaccines. The
classical belief that recurrent disease arises from latent virus in the neuroganglia is now questionable with the discovery of other latent sites (e.g. footpad, genital skin, cervix). Whilst still admitting to many gaps in our knowledge of the mechanisms involved in latent and recurrent infections the author does put forward a full hypothesis of this phenomenon. The transmissable spongiform encephalopathy diseases, such as scrapie and Creutzfeldt-Jakob disease, are unconventional and poorly understood. The agents are filterable, have high resistance to inactivating agents such as heat, formalin and irradiation, and no virion-like particles or nucleic acids have been identified. This review de-
scribes recent biochemical and biological studies which have led to partial purification of the agents (protein component). The chapter on the structure of human cytomegalovirus and transcription data is very detailed and provides a full analysis of the genomic structure of the virus. It serves as a useful reference for studying genetic variation and for analysing the individual genes and their role in pathogenesis. In conclusion, a worthwhile addition to the series with new information on both well known and some not so well known diseases, with a high standard of presentation.
J.B. Griffiths
Life with the Pneumococcus. Notes from the Bedside, Laboratory and Library R. Austrian, University of Pennsylvania Press, Philadelphia, Pennsylvania, USA, 1985, 168 pp., US$25 This book can be viewed from several perspectives. It is a collection of essays by a physician and reputed medical scientist. The essays have all been previously published in journals, and therefore they vary in subject and literary intent, but they are sufficiently related to form a coherent picture. In these pages one finds clinical pearls, historical perspective and modern science on the subject of Streptococcus pneumoniae. For example, there are chapters concerning the discovery of pneumococcus and pneumococcal pneumonia; the syndrome of pneumococcal endocarditis, meningitis and rupture of the aortic valve; and the role of toxaemia in pneumococcal meningitis. The book is also a sort of autobiography of one who has built his career on the study of one microorganism. The autobiographical material has :o be gleaned from the facts presented, for with characteristic modesty Austrian has not added a curriculum vitae to the book. Nevertheless, by reading the essays one learns that he took up the study of the pneumococcus at an early age, when he was still at John Hopkins; that he continued these studies in New York from 1952 to 1962, where he showed that pneumococcal pneumonia was deadly despite the use of antibiotics; and that as Professor of Research Medicine at the University of Pennsylvania he designed pneumococcal vaccines to prevent bacteraemic disease. Lastly, this book is the story of a life well-lived, a success story in which careful thought and hard work culminate in a great achievement. In this regard the book is a lesson to others who work in biomedical research; often the quickest way to a goal is slow and steady accumulation of hard-won facts. Austrian's writing style reflects the
man: clear, precise, elegant, and dotted with wry humour. That the writing is the product of hard labour is obvious. Craft in prose is something of an anachronism these days, but then Robert Austrian is something of an anachro-
nism, as he himself would probably admit. He comes from that Oslerian tradition in which clinical medicine was an art to be practised with meticulous attention to detail. Here is Austrian's characteristic voice: 'It is easier to obtain an X-ray of the chest than to carry out and record the inspection, palpation, percussion, and auscultation thereof, but I have seen at least four instances in which an erroneous clinical diagnosis of pneumonia was concurred in by the radiologist when both the history and physical examination pointed clearly to the true nature of the illness, tuberculous pleurisy with effusion.' In the practice of his science, Austrian also reflects the tradition of careful, painstaking transfer of clinical data to the laboratory and of laboratory techniques to the bedside. See, for example, the chapters on 'The current status of bacteraemic pneumococcal pneumonia' or the one on 'The Quellung reaction: a neglected microbiologic technique'. Robert Austrian's career epitomizes the best qualities of American medicine during the last 100 years. To maintain those qualities, young physicians especially are encouraged to read this book.
Stanley A. Plotkin
Antigenic Variation in Infectious Diseases T.H. Birkbeck and C.W. Penn. IRL Press, Oxford, UK and McLean, USA, 1986, 176 pp., £20 or US$36 (soft) and £32 or US$58 (hard). ISBN 0-947946-99-3 (soft), 1-85221-000-1 (hard) This book is volume 19 in the series of special publications of the Society for General Microbiology. Although much of the material contained in this book was presented at a meeting which took place in 1985, the topicality of the issues discussed is a s relevant now as it was at that time. In producing the new generation of vaccines we have to come to terms with antigenic variation not only for those diseases which we are prepared to suffer (the common cold, influenza), but for diseases which are posing an ever increasing threat to our physical well being, (gonnorrhoea, AIDS). The collection of papers edited by Birkbeck and Penn represents a step forward in bringing together many, but unfortunately not all, the presently studied examples of antigenic variation in disease causing organisms as varied as the spirocheate Borrelia to the lentivirus that causes Visna-Maedi. In this slim volume there is much to read about the nature of the antibody response to the continuously changing immunodominant epitopes and in some of the cases there is a well worked out genetic model to account for such epitopic changes.
If there are conclusions to be drawn from the juxtapositioning of these various systems it is that those whose job it is to invent and develop new vaccines may have to acquire some new tricks for their inventory of approaches to the production of vaccines in those cases where antigenic variation is the norm rather than the exception. Such tricks will take full use of the knowledge which is emerging from the application of genetic engineering technology so that it will become increasingly possible to stabilize the moving antigenic target by looking for and finding the invariant or conserved regions of the proteins/glycoproteins which come into contact with the immunogenic system. The presentation of such conserved, immunorecessive regions of the organism to the immune system in such a way as to elicit a cross-reactive and neutralizing (in vivo) response is the challenge which the new vaccine makers are facing. There is little doubt in this reviewers mind that the compilation of papers as presented in this book can only serve to speed progress in this both important and fascinating area of man's conquest of nature.
R.E. Spier Vaccine, Vol. 5, September 1987 255
principles laid out here should enable the public health administrators to appreciate and implement a comprehensive control strategy and should also enable the worker in the field to appreciate the part they play in the overall eradication strategy. In conclusion I found the book a clear and concise account of the many diverse political and scientific procedures which must be implemented in order to control yellow fever. The book obviously has gained a great deal by combining the expertise and experience of a number of recognized experts in yellow fever, and the 'rapporteur' must be congratulated in integrating these diverse skills to produce a clear and precise final product. My only critisisms are first that I doubt if only 64 references are adequate to represent the large and diverse field of yellow fever research. Secondly, although the book is attractively produced and clearly printed, the relatively poor quality of paper and binding would be a disadvantage. This problem could be particularly enhanced as the book is clearly intended to be a frequently used handbook by workers in the field in tropical countries.
J.R. Stephenson
Vaccine Supply and Innovation Committee on Public-Private Sector Relations in Vaccine Innovation, Institute of Medicine, National Academy of Sciences National Academy Press, Washington, DC, 1985, 210 pp., ISBN 0-309035449 As stated by Dr J.P. Sanford (Chairman) in the preface, 'vaccines are an elegant solution to one of the perennial problems of the human race - infectious disease'. Though the potential savings in dollars and human misery are phenomenal, the ultimate possibilities have been far from realized. This is especially distressing at the dawn of a new era in biotechnology that provides approaches and solutions to problems that, until
recently, were considered intractable. The shortfall in development and utilization of vaccines is explicable in a maze of interrelating problems and circumstances that may only be resolved slowly and in stepwise progression. These problems are focused principally on a triumvirate of institutions and workers that include (a) basic research creators (usually academia and government but sometimes industry), (b)
Progress in Medical Virology, Vol. 33 Editor: J.L. Melnick, S. Karger AG, Basel, 1986, 182 pp., £58.50. ISBN 3-8055-4155-4 This series is consistent in providing high quality reviews covering all aspects of virology. Volume 33 is no exception and contains an interesting blend of subjects including human papillomaviruses, herpes simplex latency, cytomegalovirus, transmissable encephalopathy agents (e.g. scrapie and CreutzfeldtJakob disease) and persistent autonomous parvovirus infection (Aleutian disease). In addition there is an excellent review on virus vaccines which succinctly describes the present status and future developments of over 17 human vaccines. The section on future prospects for vaccination covers administr-
254 Vaccine,Vol. 5, September1987
ation routes, live (including genetically attenuated strains), inactivated, subunit, recombinant, synthetic and antiidiotype vaccines. This is both an interesting and readable summary and, aided by well tabulated data, a useful reference work. It is intended as a status report, thus the sections on individual vaccines are, of necessity, short and succinct summaries and not in depth studies. Papillomaviruses are DNA viruses and, except for bovine types, are species specific. They replicate in epidermal cells during keratinization. The human types are of interest because as well as
industrial research and development and production laboratories, and (c) health care providers including policy makers. The incentives, disincentives and motivations for this triple complex are multiple and include such matters as resource allocation for research, economic incentives for vaccine development and production, vaccine-caused injury and liability and compensation issues, marketability and extent of vaccine use, public information and public acceptance, and the lack of precedent and strong orientation in medical practice, aside from paediatrics, to disease prevention by vaccination. The committee's report is exemplary in its analysis of problems and proposals for solving this multifactorial complex of barriers to innovation in vaccine development and supply. The Committee recognized the difficulty of maintaining any coordinated and continuing activity in vaccine development and use and recommended, as did previous committees, that a non-governmental or quasi-governmental National Vaccine Commission be established. This commission would report to the President and the Congress, and the objectives would be '(1) to advance the control of infectious disease by promoting the continued innovation, production, and use of vaccines, and (2) to ensure that this goal is achieved in a socially responsible and just manner'. One aspect of report is, in a sense, outdated by the recent enactment of the omnibus health package (S. 1744) that contains vaccine injury compensation reforms. The committee may take credit, in part at least, for bringing about this favourable development. The report should be considered required reading for anyone engaged in development or delivery of vaccines. Dr Jay Sanford and his committee, and study director Dr Roy Widdus can be justifiably proud of what they have wrought.
Maurice R. Hilleman being responsible for warts, and benign tumours (papillomas), they are also associated with genital tumours. The review very thoroughly covers all aspects of their role in human disease, their interaction with the body's immune surveillance system, and therapeutic and prophylactic aspects. Aleutian disease is caused by an autonomous and persistent parvovirus infection of mink and has serious economic consequences. This chapter summarizes recent data on the postimmune response to the infection and its effect on initiating the disease. The chapter on herpes virus latency and recurrence addresses a problem that is still not fully understood and is of great importance to the development of safe herpes simplex virus vaccines. The
classical belief that recurrent disease arises from latent virus in the neuroganglia is now questionable with the discovery of other latent sites (e.g. footpad, genital skin, cervix). Whilst still admitting to many gaps in our knowledge of the mechanisms involved in latent and recurrent infections the author does put forward a full hypothesis of this phenomenon. The transmissable spongiform encephalopathy diseases, such as scrapie and Creutzfeldt-Jakob disease, are unconventional and poorly understood. The agents are filterable, have high resistance to inactivating agents such as heat, formalin and irradiation, and no virion-like particles or nucleic acids have been identified. This review de-
scribes recent biochemical and biological studies which have led to partial purification of the agents (protein component). The chapter on the structure of human cytomegalovirus and transcription data is very detailed and provides a full analysis of the genomic structure of the virus. It serves as a useful reference for studying genetic variation and for analysing the individual genes and their role in pathogenesis. In conclusion, a worthwhile addition to the series with new information on both well known and some not so well known diseases, with a high standard of presentation.
J.B. Griffiths
Life with the Pneumococcus. Notes from the Bedside, Laboratory and Library R. Austrian, University of Pennsylvania Press, Philadelphia, Pennsylvania, USA, 1985, 168 pp., US$25 This book can be viewed from several perspectives. It is a collection of essays by a physician and reputed medical scientist. The essays have all been previously published in journals, and therefore they vary in subject and literary intent, but they are sufficiently related to form a coherent picture. In these pages one finds clinical pearls, historical perspective and modern science on the subject of Streptococcus pneumoniae. For example, there are chapters concerning the discovery of pneumococcus and pneumococcal pneumonia; the syndrome of pneumococcal endocarditis, meningitis and rupture of the aortic valve; and the role of toxaemia in pneumococcal meningitis. The book is also a sort of autobiography of one who has built his career on the study of one microorganism. The autobiographical material has :o be gleaned from the facts presented, for with characteristic modesty Austrian has not added a curriculum vitae to the book. Nevertheless, by reading the essays one learns that he took up the study of the pneumococcus at an early age, when he was still at John Hopkins; that he continued these studies in New York from 1952 to 1962, where he showed that pneumococcal pneumonia was deadly despite the use of antibiotics; and that as Professor of Research Medicine at the University of Pennsylvania he designed pneumococcal vaccines to prevent bacteraemic disease. Lastly, this book is the story of a life well-lived, a success story in which careful thought and hard work culminate in a great achievement. In this regard the book is a lesson to others who work in biomedical research; often the quickest way to a goal is slow and steady accumulation of hard-won facts. Austrian's writing style reflects the
man: clear, precise, elegant, and dotted with wry humour. That the writing is the product of hard labour is obvious. Craft in prose is something of an anachronism these days, but then Robert Austrian is something of an anachro-
nism, as he himself would probably admit. He comes from that Oslerian tradition in which clinical medicine was an art to be practised with meticulous attention to detail. Here is Austrian's characteristic voice: 'It is easier to obtain an X-ray of the chest than to carry out and record the inspection, palpation, percussion, and auscultation thereof, but I have seen at least four instances in which an erroneous clinical diagnosis of pneumonia was concurred in by the radiologist when both the history and physical examination pointed clearly to the true nature of the illness, tuberculous pleurisy with effusion.' In the practice of his science, Austrian also reflects the tradition of careful, painstaking transfer of clinical data to the laboratory and of laboratory techniques to the bedside. See, for example, the chapters on 'The current status of bacteraemic pneumococcal pneumonia' or the one on 'The Quellung reaction: a neglected microbiologic technique'. Robert Austrian's career epitomizes the best qualities of American medicine during the last 100 years. To maintain those qualities, young physicians especially are encouraged to read this book.
Stanley A. Plotkin
Antigenic Variation in Infectious Diseases T.H. Birkbeck and C.W. Penn. IRL Press, Oxford, UK and McLean, USA, 1986, 176 pp., £20 or US$36 (soft) and £32 or US$58 (hard). ISBN 0-947946-99-3 (soft), 1-85221-000-1 (hard) This book is volume 19 in the series of special publications of the Society for General Microbiology. Although much of the material contained in this book was presented at a meeting which took place in 1985, the topicality of the issues discussed is a s relevant now as it was at that time. In producing the new generation of vaccines we have to come to terms with antigenic variation not only for those diseases which we are prepared to suffer (the common cold, influenza), but for diseases which are posing an ever increasing threat to our physical well being, (gonnorrhoea, AIDS). The collection of papers edited by Birkbeck and Penn represents a step forward in bringing together many, but unfortunately not all, the presently studied examples of antigenic variation in disease causing organisms as varied as the spirocheate Borrelia to the lentivirus that causes Visna-Maedi. In this slim volume there is much to read about the nature of the antibody response to the continuously changing immunodominant epitopes and in some of the cases there is a well worked out genetic model to account for such epitopic changes.
If there are conclusions to be drawn from the juxtapositioning of these various systems it is that those whose job it is to invent and develop new vaccines may have to acquire some new tricks for their inventory of approaches to the production of vaccines in those cases where antigenic variation is the norm rather than the exception. Such tricks will take full use of the knowledge which is emerging from the application of genetic engineering technology so that it will become increasingly possible to stabilize the moving antigenic target by looking for and finding the invariant or conserved regions of the proteins/glycoproteins which come into contact with the immunogenic system. The presentation of such conserved, immunorecessive regions of the organism to the immune system in such a way as to elicit a cross-reactive and neutralizing (in vivo) response is the challenge which the new vaccine makers are facing. There is little doubt in this reviewers mind that the compilation of papers as presented in this book can only serve to speed progress in this both important and fascinating area of man's conquest of nature.
R.E. Spier Vaccine, Vol. 5, September 1987 255