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Chapter 5 : The Turning Point: Cytopathic Effect in Tissue Culture

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Abstract:

This chapter focuses on the cytopathic effect (CPE), which refers to degenerative changes in tissue cultures that were specifically associated with viral infection and visible on microscopic examination. Tissue culture was used for viral cultivation, particularly vaccinia virus, the smallpox vaccine virus, well before its diagnostic use. The study of vaccinia virus in culture remained an important focus for virologists in the first four decades of the 20th century. Tissue culture was adapted to grow poliovirus, allowing the production of the vaccine. Tissue culture facilitated viral diagnosis, not requiring assay in animals or in embryonated eggs. That ability to grow virus in tissue culture and to simultaneously measure its amount was the pivotal event, the turning point, after which the study of diagnostic virology accelerated immeasurably. The crucial contribution to diagnostic virology by the Enders group was the recognition of CPE as a visual aid in the detection and assay of virus infections in tissue culture. The findings of Enders, Weller, and Robbins, in addition to providing the means to create the polio vaccine and to merit recognition with the 1954 Nobel Prize in Physiology or Medicine, opened the floodgates for the isolation of viral agents in the 1950s and beyond. Their work transformed diagnostic virology from a largely serologically based enterprise to one in which virus isolation became feasible for laboratories attached to public health departments and academic hospitals.

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5

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Figure 1

Ross Granville Harrison. In 1907, Harrison reported the outgrowth of nerve fibers from embryonic tissue . While Harrison did no further work with the technique, tissue culture was to transform many areas of biology. In years to come, tissue culture became the standard technique for virus isolation and identification. (Courtesy of the National Library of Medicine.) doi:10.1128/9781555818586.ch5.f1

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Thomas Rivers. Rivers established laboratory studies of virological diseases at the Rockefeller Institute in New York City. He edited the first comprehensive textbook of clinical virology and rickettsiology in the United States. (Courtesy of Rockefeller Archive Center.) doi:10.1128/9781555818586.ch5.f2

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 3

FDR at Hill Top Cottage on his family’s estate in Hyde Park, NY. FDR, who experienced polio as an adult, is shown with his dog, Fala, and Ruthie Bie. The National Foundation for Infantile Paralysis, which FDR founded with his partner, Basil O’Connor, underwrote the costs of developing the Salk polio vaccine. Less well-known is that the Foundation supported important investigations in basic science. (Courtesy of the Franklin D. Roosevelt Presidential Library and Museum, Hyde Park, NY.) doi:10.1128/9781555818586.ch5.f3

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 4

Polio poster. This fund-raising poster shows a vigorous and fully intact, young boy striding toward the viewer. He is shown on a background featuring the same boy exhibiting polio, with a weak right leg, unable to hold his head upright, and with his left hand in a brace; footsteps lead from illness to health. (Courtesy of Yale University, Harvey Cushing/John Hay Whitney Medical Library.) doi:10.1128/9781555818586.ch5.f4

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 5

Frederick Robbins. John Enders, Thomas Weller, and Robbins received the Nobel Prize in 1954 for the discovery of the capacity to grow poliovirus in tissue culture of nonneural origin. With Enders and Weller, Robbins demonstrated that CPE in tissue culture could be used to detect the growth of virus for isolation from clinical specimens, to measure the amount of virus present, and to determine the presence of antibodies. These crucial discoveries led to the rapid and widespread development of diagnostic virology laboratories. (Image 00716, property of Case Western Reserve University Archives.) doi:10.1128/9781555818586.ch5.f5

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 6

CPE. The upper panel shows a monolayer of uninfected, human diploid fibroblasts. The lower panel shows a focus of viral infection, described as CPE, marked by enlarged, rounded cells seen in the center of the photograph surrounded by normal, uninfected cells. CPE resulted from cytomegalovirus replication in the monolayer. (Courtesy of Diane S. Leland and Indiana Pathology Images.) doi:10.1128/9781555818586.ch5.f6

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 7

Harry Plotz. Colonel Harry Plotz (left) is shown receiving a World War II medal from Brigadier General George Callender. Plotz was the founding chief of the first virus and rickettsia lab set up primarily for diagnosis. It was established in January 1941 at the Walter Reed Army Medical Center. (From . Courtesy of the Borden Institute, Fort Detrick, MD.) doi:10.1128/9781555818586.ch5.f7

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 8

Joseph Edwin Smadel. One of America’s premier medical virologists, Smadel directed the ETO virus and rickettsial diagnostic lab for the Army during World War II. On returning to the United States, he succeeded Harry Plotz as chief of the diagnostic lab at the Walter Reed Army Medical Center. (Courtesy of the Albert and Mary Lasker Foundation.) doi:10.1128/9781555818586.ch5.f8

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 9

Maurice Hilleman. America’s premier vaccinologist, Hilleman was at the Walter Reed Army Medical Center from 1948 until 1957. Among his accomplishments at Walter Reed, Hilleman described shifts in the antigenic nature of influenza viruses resulting in worldwide pandemics, and he isolated adenovirus from military troops. At the time of his death, he had created 8 of the 14 vaccines recommended for use in the United States. (Courtesy of the National Library of Medicine.) doi:10.1128/9781555818586.ch5.f9

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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Figure 10

Edwin Herman Lennette. With an extensive background in the study of numerous viruses, Lennette was designated the chief of the first state public health laboratory in the United States for viral and rickettsial diagnosis. He held the position in California from 1947 until retiring in 1978. With Nathalie J. Schmidt, he had a major role in establishing the field of diagnostic virology; he has been called “the father of diagnostic virology.” (Courtesy of Edwin Paul Lennette.) doi:10.1128/9781555818586.ch5.f10

Citation: Booss J, August M. 2013. The Turning Point: Cytopathic Effect in Tissue Culture, p 113-156. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch5
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