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Chapter 9 : To the Barricades: the Molecular Revolution

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Abstract:

In 1981, two reports from the west and east coasts of the United States marked the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic by the lethal, immunosuppressant retrovirus, human immunodeficiency virus (HIV). Just four years later, in 1985, Kary Mullis and his colleagues described the polymerase chain reaction (PCR), which contributed to an explosion of research on HIV and AIDS. The story begins with an overview of the molecular genetics revolution, which was fundamental to what ultimately became molecular diagnostic virology. Key to management of infected individuals has been determination of viral load, detected by nucleic acid amplification techniques such as the PCR. Prior to the explosive commercial development of PCR and other nucleic acid amplification tests, certain molecular nucleic acid methods were explored for clinical diagnostic virology. Diagnostic virology played a central role in patient management, in pharmacotherapy, and in researching the epidemiology of circulating viral infections. Likewise, management of infections with viruses such as HIV, cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) has been significantly improved. The current trend is to devise user-friendly and walk-away molecular tests allowing more clinical laboratories to offer viral diagnostic services. From transmission studies of yellow fever with human volunteers to the application of high-throughput sequencing, diagnostic virology sits astride the confluence of advances in science and the challenges presented by human disease.

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9

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Nucleic Acid Amplification Techniques
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Central Nervous System Diseases
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Severe Acute Respiratory Syndrome
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Reverse Transcriptase PCR
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Figure 1

Oswald Avery. Working at the Rockefeller Institute in New York City, Avery demonstrated that transmission of a heritable characteristic was conveyed by DNA. Exacting studies published in 1944 with Colin MacLeod and Maclyn McCarty determined the nucleic acid basis of the transformation of pneumococcal colonies. It was a finding in advance of its time. (Courtesy of the Rockefeller Archive Center.) doi:10.1128/9781555818586.ch9.f1

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 2

Erwin Chargaff. A Vienna-educated biochemist working at the Columbia University College of Physicians and Surgeons, Chargaff had immediately understood the implications of Avery’s work. He determined that the purine and pyrimidine bases composing nucleic acids had reproducible ratios. These findings became known as Chargaff’s Rules, which defined base complementarity, a fundamental characteristic of heredity. (Courtesy of the Archives of Columbia University Medical Center and the National Library of Medicine.) doi:10.1128/9781555818586.ch9.f2

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 3

Rosalind Franklin. A brilliant X-ray crystallographer, Franklin took photographs of DNA which provided the crucial pieces of data to decipher its structure. They demonstrated that DNA was a two-chain helical structure with the chains oriented in opposite directions. (Courtesy of Vittorio Luzzati.) doi:10.1128/9781555818586.ch9.f3

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 4

Linus Pauling. Pauling’s work on chemical bonds, including his text (published in 1939), laid the basis for modern chemistry. For this work he won the Nobel Prize in 1954. His entry with Robert Corey in 1953 into the race to discover the structure of DNA, while flawed, accelerated Watson and Crick’s work to fit the pieces of evidence together. (Courtesy of Ava Helen and Linus Pauling Papers, Oregon State University Libraries.) doi:10.1128/9781555818586.ch9.f4

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 5

Francis Crick (left) and James D. Watson. Working at the Cavendish Laboratories at Cambridge University, Watson and Crick determined the structure of DNA. Published in an elegant, brief paper in in 1953, it provided the molecular structural basis to understand heredity. (Courtesy of the James D. Watson Collection, Cold Spring Harbor Laboratory Archives.) doi:10.1128/9781555818586.ch9.f5

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 6

DNA double helix. This drawing demonstrates the essential features of paired DNA strands: a backbone of sugars and phosphate groups, linked by bases pairing from opposite strands, and the strands coiled around each other oriented in opposite directions. Base pairing underlies the capacity to copy strands, that is, to reproduce genetic information. (Courtesy of the National Human Genome Research Institute.) doi:10.1128/9781555818586.ch9.f6

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 7

Poster about the AIDS epidemic. AIDS was first brought to public attention in June 1981 by unusual infections and cancers in young homosexual men. The underlying feature was found to be immunodeficiency; hence, the syndrome was termed the acquired immunodeficiency syndrome (AIDS). Risk factors included sex between men, intravenous drug abuse, commercial sex, unscreened blood transfusions, and birth to an infected mother. Public health campaigns were waged to warn of these risk factors, as in this poster of a harpy with needles and syringes in her wings. (Courtesy of Yale University, Harvey Cushing/John Hay Whitney Medical Library.) doi:10.1128/9781555818586.ch9.f7

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 8

Françoise Barré-Sinoussi (left) and Luc Montagnier (right). Working with clinicians who were attempting to find the cause of AIDS, Montagnier and Barré-Sinoussi at the Pasteur Institute in Paris found a retrovirus in a lymph node biopsy. Ultimately shown to be the cause of AIDS, the virus was to be called human immunodeficiency virus (HIV). Montagnier and Barré-Sinoussi were awarded the Nobel Prize in 2008 for their discovery. (Photo of Barré-Sinoussi courtesy of the Pasteur Institute; photo of Montagnier courtesy of Prolineserver.) doi:10.1128/9781555818586.ch9.f8

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 9

Harald zur Hausen. Suspected for years to be of viral origin, cervical cancer was demonstrated to be associated with HPV by zur Hausen. He had pioneered work with nucleic acid hybridization to detect viruses in clinical specimens of human tumors. He was awarded the Nobel Prize in 2008 for his discovery that HPVs cause human cervical cancer. (Courtesy of Harald zur Hausen, DKFZ, Heidelberg.) doi:10.1128/9781555818586.ch9.f9

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 10

Kary Mullis. The PCR takes advantage of the capacity of short lengths of nucleotides to find and hybridize with reciprocal pieces of nucleic acid. Once hybridized, multiple copies are made through repeating cycles of polymerase-assisted replication. PCR has transformed many fields in biology, including, notably, the capacity to discover minute amounts of viruses in clinical samples. Kary Mullis devised the process while driving one evening in 1983 and was awarded the Nobel Prize in 1993. (Photo by Mark Robert Halper.) doi:10.1128/9781555818586.ch9.f10

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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Figure 11

Emerging viral epidemics. The appearance of a viral epidemic produces fear and panic as well as sickness and death. Surveillance mechanisms and rapidly deployed diagnostic tools will be key to containing future emerging and reemerging epidemics. This political cartoon of 1919 by Charles Reese shows the panic of people rushing to get a “goode germ destroyer” in the context of the influenza pandemic. (Courtesy of the National Library of Medicine.) doi:10.1128/9781555818586.ch9.f11

Citation: Booss J, August M. 2013. To the Barricades: the Molecular Revolution, p 293-338. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch9
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