is, the technique would allow the identification of an offending virus. This methodology was applied by Phillip S. Gardner and Joyce McQuillin in pioneering efforts at Newcastle-upon-Tyne in the United Kingdom. They aimed to provide clinicians with a “rapid viral diagnosis,” particularly of acute respiratory disease in infants and children, within 24 hours.
Chapter 8 describes the evolution of our understanding of viral hepatitis and how innovative immunological techniques, developed by both serendipity and ingenuity, led to the identification of some of the culprits. In the case of radioimmunoassay (RIA), Rosalyn Yalow and Solomon Berson originally developed the highly sensitive and accurate technique to measure human insulin and other endocrine molecules. When applied to viral diseases, it allowed the screening of the blood supply for hepatitis viruses. Less complicated and nonradioactive assays, such as the enzyme-linked immunosorbent assay (ELISA) and the enzyme immunoassay (EIA), soon followed. They transformed many aspects of biology, including the diagnostic process in virology.
The final chapter, chapter 9, examines where we are today in diagnosing and managing viral diseases, and where we are going. It tracks HIV, AIDS, and the application of molecular methods for discovery and control. The syndrome first appeared in 1981 as a virtually inevitable death sentence, but that characterization was transformed by the use of an antiviral “cocktail,” including a protease inhibitor, in 1996. Its current status is as a managed chronic disease in those individuals fortunate to have access to molecular viral diagnostic assays and a wide spectrum of specifically targeted antiviral drugs. Tragically, that fortunate group represents only a small portion of the global population infected with HIV.
The molecular foundation for these developments started with the demonstration of DNA as the basis of heredity by Oswald Avery in the 1940s. The demonstration of the double helix by James D. Watson and Francis Crick, using X-ray crystallographic data of Rosalind Franklin, allowed the cracking of the genetic code and the molecular biological revolution which followed. Another key development was the demonstration of the enzyme reverse transcriptase, which transmits genetic information from RNA to DNA and facilitated the discovery of HIV. In another crucial development, exquisitely sensitive detection and quantitation assays were produced. They are based on nucleic acid amplification principles developed for PCR by Kary Mullis. PCR and other molecular techniques such as nucleic acid sequencing allow the measurement of the amount of HIV in plasma, i.e., “viral load,” and the determination of mutations of the virus, facilitating management of antiviral therapy.
The final section of chapter 9 takes a look into the future of viral diagnosis, which even now is becoming highly transformed. Molecular diagnostics have been streamlined so that the many individual steps of nucleic acid extraction, amplification, measurement, and reporting are done in closed systems in “real time.” Hence, the highly trained diagnostic virology specialists of the tissue culture era are being replaced by computer-savvy technologists. In the opinion of a number of experienced diagnostic virologists, the diagnostic virology lab as we have known it is becoming a thing of the past. Many of its functions are being and will be transferred to “point-of-care” locations such as clinics and other medical and public health locations. The process of viral discovery will make use of high-throughput nucleic acid sequencing and information comparisons in large biodatabases. These will be fundamentally important to identifying new viruses or old viruses in “new clothes” that will emerge to attack, frighten, and baffle.
We have sought illustrations from the general social context to illustrate perceptions of viral infections. Several other types of figures have also been chosen to support the text. In addition to photographic portraits of key historical figures, diagrams of diagnostic procedures and micrographs of virus-infected cells have been selected as examples of the kinds of work that diagnostic virologists have performed.
We hope that the book will appeal to a large audience, one concerned about the broader issues that our society faces. This audience includes the many types of professionals whose scientific interests have led them to work with viral diseases. There have always been a fascination, curiosity, and fear of viral epidemics that threaten the lives of individuals and the fabric of society. This was true for the yellow fever outbreak in 1793 in Philadelphia, as it was in the 1980s when AIDS first made its mysterious entrance, and as it is in the constant fear of a newly lethal influenza pandemic. Those emotions find some release in many popular films and books. It is to this broad audience that the book is directed, to demonstrate how science and technology have advanced to confront the virological threats to our well-being.
John Booss
Marilyn J. August
About the Authors
John Booss is Professor Emeritus of Neurology and Laboratory Medicine at the Yale University School of Medicine. For twelve years he was the National Program Director of Neurology for the U.S. Department of Veterans Affairs. Following residency in neurology, he trained in virology with G.-D. Hsiung, to whom this book is dedicated, and subsequently worked with E. F. Wheelock in viral immunology. He studied experimental models of viral infection of the brain, modulation of immune functions by murine cytomegalovirus, and T cells in multiple sclerosis with Margaret M. Esiri in Oxford and studied the host response to xenogenic brain cell transplantation with C. Jacque in Paris. Dr. Booss’ clinical interests have focused on viral encephalitis, multiple sclerosis, and the neurology of HIV/AIDS. He and Professor Esiri are coauthors of Viral Encephalitis in Humans, published by the ASM Press in 2003. (Republished with permission from the American Academy of Neurology Institute.)
Marilyn J. August was trained as a clinical virologist and microbiologist, completing her undergraduate work in microbiology at the University of Massachusetts, Amherst, and her PhD in virology with an emphasis on electron microscopy at Columbia University, College of Physicians and Surgeons. With training in both microbiology and virology, she became a postdoctoral fellow with G.-D. Hsiung at Yale University School of Medicine, which launched her career in clinical, diagnostic virology. Her professional activities progressed with positions as director of hospital and clinical diagnostic virology, microbiology, and infectious serology laboratories in southern California. Accepting a new challenge and returning to her roots in virology, Dr. August moved to the biotechnology industry in northern California and joined Aviron (now MedImmune/AstraZeneca) as director of the clinical testing laboratory, overseeing clinical trials testing to support pivotal studies that contributed to the approval of a live, intranasal influenza vaccine that was first licensed in 2003. Dr. August’s recent professional activities include consulting as a scientist and freelance medical writer-editor between wonderful trips, hiking adventures, and activities as a Let’s Look at Art docent for the San Jose Museum of Art. (Photo by Laurie Naiman.)
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Fear or Terror on Every Countenance: Yellow Fever
The production of yellow fever by the injection of blood-serum that had previously been through a filter capable of removing all test bacteria is, we think, a matter of extreme interest and importance.
Reed and Carroll, 1902 (33)
Introduction
In 1793, within two decades of the writing of the Constitution of the United States and the Declaration of Independence,
