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, Philadelphia experienced an outbreak of yellow fever which shredded the fabric of civil society. While the Declaration of Independence and the Constitution have stood as blueprints for the philosophical and practical bases of representative government, the understanding of yellow fever at that time was still mired in the miasma of pre-germ theory speculation.

The first case of yellow fever in the Philadelphia 1793 outbreak was recognized in August by Benjamin Rush as the “bilious remitting yellow fever” (34). As the outbreak grew, there was no consensus on its origin. Rush attributed it to “putrid coffee” which “had emitted its noxious effluvia” after being dumped on a dock. The College of Physicians was “of the opinion that this disease was imported to Philadelphia by some of the vessels which were in the port after the middle of July.” The role of the mosquito as a vector for disease was not to be recognized until decades later. In the 1793 Philadelphia outbreak, “Fear or Terror was set on every countenance.” The effect on families was devastating. In reporting the horror of the desertion of sick wives by husbands, the desertion of sick husbands by wives, and the departure of parents from sick children, Mathew Carey, another contemporary observer, noted that those actions “. . . seemed to indicate a total dissolution of the bonds of society in the nearest and dearest connexions. . . .” He commented on “the extraordinary panic and the great law of self-preservation . . .” (6). Rush reported on the exodus, “The streets and roads leading from the city were crowded with families flying in every direction for safety in the country” (34). J. H. Powell, the modern-day chronicler of the 1793 Philadelphia epidemic, noted that business languished and public administration virtually halted. With widespread sickness, over 40,000 deaths, and diminished population, the economy of the city collapsed. It was not until November 1793 that the city began to rebound, “. . . a time of recovery—of moral, psychological, intellectual reconstruction” (28).

      Rush, who remained in the city, worked relentlessly, at times seeing upwards of 150 people in a day. At the end of his 1794 account of the epidemic, Rush tells of the effect on himself in a “Narrative of the state of the Author’s body and mind . . .” (34). Following the death of his sister, he wrote, “. . . my short and imperfect sleep was disturbed by distressing or frightful dreams. The scenes of these were derived altogether from sickrooms and graveyards.” This courageous, indefatigable physician embodied the paradox of latter 18th-century Philadelphia, which was the site of advanced social-governmental thinking but backward in scientific-medical thinking.

Beyond his medical pursuits, Rush was an advanced social thinker, a delegate to the Continental Congress, and a signer of the Declaration of Independence. He promoted improved conditions for mental patients and prisoners, promoted education, and promoted the abolition of slavery (35a). Yet Rush also reflected the confusion and ignorance of infectious diseases before the advent of laboratory methods. Ascribing yellow fever to the effluvia of putrefying coffee, he treated infected individuals with powerful purging and bloodletting and considered all diseases derived from one cause, comparing the “multiplication of diseases” to polytheism (34). Unrecognized at this time was the association of microbes with infectious diseases, which would come in the next century, along with the recognition that specific insect species could