The editorial staff at ASM Press has provided insight and creative encouragement throughout the long gestation of the book. Jeff J. Holtmeier, the Editor-in-Chief at the book’s inception, guided the development of the concept and provided patient encouragement. Christine Charlip, his successor, encouraged us to enlarge the audience from one that was primarily technical in orientation to one with broad interests in science and medicine. Thus encouraged, we sought illustrations to complement the text and to provide appeal to a broader readership. John Bell, our production editor, has facilitated that shift by creative suggestions, sound editing, and good humor. We also thank artist Debra Naylor for her creativity in collaborating on the book cover design.
Conversations, face to face, by emails, or by letter, with virologists and others whose work has a bearing on virological infections have played a major role in shaping our understanding of how the field of diagnostic virology evolved. These individuals included Warren Andiman, Jangu Banatvala, Edward A. Beeman, Leonard N. Binn, F. Marilyn Bozeman, Irwin Braverman, Charlie Calisher, Dave Cavanagh, Gustave Davis, Walter Dowdle, Bennett L. Elisberg, Margaret M. Esiri, Durland Fish, Bagher Forghani, Harvey Friedman, D. Carleton Gajdusek, J. Robin Harris, David L. Hirschberg, Richard L. Hodinka, Robert Horne, Albert Z. Kapikian, Robert J. T. Joy, Edwin D. Kilbourne, Jung H. Kim, Diane S. Leland, W. Ian Lipkin, Dick Madeley, Kenneth McIntosh, Michael B. A. Oldstone, Stanley Plotkin, Morris Pollard, Philip K. Russell, Karen-Beth G. Scholthof, Gregory Tignor, and Alex Tselis.
Historians and curators are the guardians of the traces of our past, and several have provided indispensable help. At Yale, Toby Appel, Melissa Grafe, Frank Snowden, and Susan Wheeler were expert and gracious. Elsewhere, Steven Greenberg, Col. Richard C. V. Gunn, Sally Smith Hughes, and Sarah Wilmot provided invaluable guidance.
Because of their associations with virologists, by birth or profession, certain other individuals provided important pieces of information. These included Mary Emma Armstrong, Jean Saperstein Beeman, Kevin Breen, James A. Poupard, James W. Reagan, David R. Scholl, and Kenneth Wertman.
We are not the first to note this, but there must be a special place in heaven for archivists and specialist librarians. Several of the staff at the Yale Medical and Historical Libraries were particularly helpful. Mary Angelotti was exceptionally resourceful in locating documents at Yale and elsewhere and generous in explaining the means of access. Florence Gillich effortlessly facilitated access to the riches of the Historical Library holdings. At other institutions, Barbara Faye Harkins, Leigh Mantle, Barbara J. Niss, Stephen Novak, and Alycia J. Vivona responded to repeated pleas for help, providing answers, documents, and guidance.
Mary Ann Booss and Brigitte Griffith offered expert advice in translating scientific publications in French, while Carolin I. Dohle provided expert translations of scientific publications in German.
A number of individuals provided help above and beyond the call of duty to secure especially difficult-to-find figures or provided critical help in developing the manuscript. Zhe Zhao, Dr. Hsiung’s grandniece, was kind enough to provide the portrait used with the dedication. Special thanks are extended to Paul Theerman and Ginny A. Roth at the National Library of Medicine for providing many high-resolution images from the library collection. Others included Joyce Almeida, Debbie Beauvais, Claire Booss, Robert B. Daroff, John and Donna Jean Donaldson, Will Fleeson, Emma Gilgunn-Jones, Tina Henle, Albert Z. Kapikian, David Keegan, Edwin Paul Lennette, Rich McManus, Venita Paul, Thomas Ruska, and Irving Seidman.
It seemed particularly important to gain an understanding of the first diagnostic virology and rickettsiology labs established anywhere. The first was established in January 1941 at the Walter Reed Army Medical Center. In investigating the establishment and operation of that laboratory, we had exceptional support from committed and knowledgeable personnel. We extend special thanks to Michael P. Fiedler, research librarian, Andrew H. Rogalsky, archivist, and Leonard N. Binn, whose career in virology at Walter Reed spans over five decades. The first diagnostic virology and rickettsial lab in the U.S. civilian sector was at the State of California Public Health Labs. We are grateful to Bagher Forghani for generously and graciously providing a full understanding of that very important lab and its leaders.
Finally, the book could not have been written without the support of J.B.’s family. Months turned into years, and stacks of books and reprints turned into multiple file cases. Yet patience and encouragement were constant. Mary Ann offered insights from her public health work, Dave recurrently provided much-needed computer support, and Christine provided a West Coast haven when the research moved west. J.B. is humbled and grateful for their support. M.J.A. was continually cheered by her dear father, Ralph August, by friends near and far away, and by her Let’s Look at Art docent colleagues at the San Jose Museum of Art.
Foreword
This book traces the growth of diagnostic virology from its beginnings over a century ago to the present: the scientific discoveries, the blind alleys, the missteps, the epidemics that gave urgency to the quest, the technological advances, and the unique individuals whose commitment and hard work were the keys to progress.
The idea for this book first arose at a memorial service for Dr. Gueh-Djen (Edith) Hsiung, a leader in clinical and diagnostic virology who died in 2006 and in whose laboratory the authors and I had all trained. To us, Edith Hsiung embodied the enthusiasm, dedication, and perseverance of an older generation who, sadly, had died or were dying and whose stories were being lost. John Booss, to his great credit, has been the driving force behind this project, traveling the country to research historical archives and interview key people. He was fortunate to enlist Marilyn August, a diagnostic expert and science writer who is a key contributor to this important endeavor. Although a diagnostic virologist myself, I knew little of the history of the field and thus have learned a tremendous amount reading the material they have unearthed and presented in this fascinating book.
When I first entered Dr. Hsiung’s laboratory in 1979, virus isolation involved inoculating litters of newborn mice or embryonated hens’ eggs, or preparing cell cultures by harvesting rabbit kidneys and chicken and guinea pig embryos—i.e., working with a virtual menagerie—as well as recovering discarded human foreskins from the obstetrics ward. Time to result was slow, and it was often said that the patient was dead or better by the time the result was received. Over the intervening years, diagnostic advances have transformed the field by allowing accurate results in a clinically useful time frame. Today, with molecular methods and rapid diagnostic tests, most results are reported within minutes to hours to 1 to 2 days. Providing sophisticated molecular tests that require minimal skill is now a reality.
With these advances have come new challenges. As tests become more sensitive, low levels of clinically irrelevant or nonviable viruses may be detected and can be misleading to clinicians. Similarly, interpreting the clinical relevance of multiple viral pathogens in the same sample is problematic. Furthermore, with numerous commercial virus detection kits now becoming available, laboratories can find it hard to decide which technologies to invest in. As diagnostic virology enters a new phase in the clinical mainstream, it is highly fitting and fortunate that this book is available to mark the first century of progress and to recount the many stories and contributions that have led us to where we are today.
Marie Louise Landry, MD
Yale University School of Medicine
Preface
With a nod to To Catch a Thief, Alfred Hitchcock’s 1955 classic mystery film, this book tells the story of the ways in which viruses are captured and identified. It is a chronicle of discovery and diagnosis, a history of diagnostic virology. It begins with yellow fever, the first human disease shown to be viral in nature. That happened in Cuba at the turn of the 20th century, when Walter Reed and the Yellow Fever Commission demonstrated that the disease was transmitted by mosquitoes. They then showed that the agent passed through a filter designed to hold back bacteria, a defining characteristic of viruses. The chronicle has continued through more than a century of historical developments, epidemics, and discoveries, coming