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Title: The Foundations of Medical and Veterinary Virology: Discoverers and Discoveries Inventors and Inventions Developers and Technologies Frederick A. Murphy University of Texas Medical Branch


1
The Foundations of Medical and Veterinary
Virology Discoverers and Discoveries Inventors
and Inventions Developers and TechnologiesFrede
rick A. MurphyUniversity of Texas Medical Branch
m1956 - 1967
2
1956 J Morris, R Chanock, colleagues discovery of respiratory syncytial virus (the first pneumovirus)
3
Human rhinovirus 14
1956 W Mogabgab, W Pelon, W Price discovery of human rhinoviruses and development of the numerical nomenclature system
4
In 1956, Charlotte Friend isolated a virus which
caused erythroblastosis in mice she was able to
pass it serially in weanling mice. This virus,
which caused rapid enlargement of the spleen and
liver and led to progressive anemia, was
identified as a member of the retrovirus family.
1956 C Friend discovery of Friend murine erythroblastosis virus
5
Gierer A, Schramm G. Infectivity of ribonucleic
acid from tobacco mosaic virus. Nature. 1956 Apr
14177(4511)702703.
1956 A Gierer, G Schramm, H Fraenkel-Conrat, B Singer discovery of the infectivity of viral RNA (tobacco mosaic virus)
6
1956 A Gierer, G Schramm, H Fraenkel-Conrat, B Singer discovery of the infectivity of viral RNA (tobacco mosaic virus)
7
School of Veterinary Medicine, University of
California Davis, 1961
1956 S Madin, C York, D McKercher discovery of infectious bovine rhinotracheitis virus
8
ROSS RW. The Newala epidemic. III. The virus
isolation, pathogenic properties and relationship
to the epidemic. J Hyg (Lond). 1956. 54(2)177-91.
1956 R Ross discovery of chikungunya virus
9
1956 R Chanock discovery of human parainfluenza viruses
10
1956 M Smith, T Weller, W Rowe discovery of human cytomegalovirus
11
Walter Plowright, FRS, as a young veterinary
pathologist, left his native Great Britain to
carry out research in Kenya and Nigeria starting
in 1950. The East African Veterinary Research
Organization at Muguga in Kenya provided the base
for him and his colleagues to adopt the
cell-culture techniques used to develop the polio
vaccine to produce a live attenuated virus
vaccine. Unlike its predecessors, tissue culture
rinderpest vaccine (TCRV) could be used safely in
all types of cattle of any age or health status.
It could be produced very economically and
conferred lifelong immunity. Initial field use
from 1956 to 1963 showed that the vaccine was
genetically stable and produced no clinical side
effects. Plowright was recognized with the 1999
World Food Prize for this development, the key
element in the quest to eradicate rinderpest
worldwide.
1956gt W Plowright development of rinderpest vaccine
12
High Speed Automatic Cell Counter and Cell Size
Analyzer Wallace H. Coulter Coulter Electronics,
Chicago, Illinois 1956
1956 W Coulter development of first high-throughput flow cytometer
13
1956-1966 J Gorham, C Hartsough, J Henson, R Leader, G Padgett, F Dixon discovery of Aleutian disease of mink virus and its relationship to immunologically mediated glomerulonephritis and myeloma
14
Burnets diagram of clonal selection
1957 FM Burnet, D Talmadge discovery of clonal selection as the central mechanism in the immune response
15
1957 A Isaacs, J Lindenmann discovery of interferons
16
1957 A Isaacs, J Lindenmann discovery of interferons
17
Telford Hindley Work (1921-1995)
1957 T Work, F Rodriguez, P Bhatt discovery of Kyasanur Forest disease virus
18
Telford Work and Pushpa
1957 T Work, F Rodriguez, P Bhatt discovery of Kyasanur Forest disease virus
19
Left to rightJames PorterfieldPravin
BhattCarleton Gajdusek Telford
Work Bratislava 1960
1957 T Work, F Rodriguez, P Bhatt discovery of Kyasanur Forest disease virus
20
1957 E Doll, J Bryans, W McCollum discovery of equine arteritis virus (the first arterivirus)
21
Lee KM, Gillespie JH. Propagation of virus
diarrhea virus of cattle in tissue culture. Am J
Vet Res 195718952. Underdahl NR, Grace OD,
Hoerlein AB. Cultivation in tissue culture of
cytopathogenic agent from bovine mucosal disease.
Proc Soc Biol Med 195794795.
1957 K Lee, J Gillespie, N Underdahl, others discovery of bovine virus diarrhea virus (pestivirus)
22
1957gt J Enders, M Hilleman, A Gershon, S Katz, S Plotkin, M Takahashi, others development of vaccines against measles, mumps, rubella, Mareks disease, hepatitis A, hepatitis B, varicella-zoster, adenoviruses
23
1957gt J Enders, M Hilleman, A Gershon, S Katz, S Plotkin, M Takahashi, others development of vaccines against measles, mumps, rubella, Mareks disease, hepatitis A, hepatitis B, varicella-zoster, adenoviruses
24
1957gt J Enders, M Hilleman, A Gershon, S Katz, S Plotkin, M Takahashi, others development of vaccines against measles, mumps, rubella, Mareks disease, hepatitis A, hepatitis B, varicella-zoster, adenoviruses
25
Despite a widely-held perception that varicella
is a mostly benign disease, potential
complications exist, including secondary
bacterial infection, pneumonia, cerebellar
ataxia, encephalitis, Reye syndrome,
glomerulonephritis, arthritis, and, in the
immunocompromised host, disseminated
disease. Michiaki Takahashi and colleagues
carried out the first clinical trials with live
attenuated OKA strain varicella-zoster vaccine in
1973, using it first in children with underlying
malignancies and to halt the nosocomial spread of
the disease in hospitals. It soon became clear
that the vaccine was safe, efficacious and an
important addition to the pediatric vaccine
arsenal. It was soon used in several
countries. However, it was not until 1995 that
the U.S. FDA licensed the vaccine as produced by
a U.S. manufacturer. The American Academy of
Pediatrics and the Advisory Committee on
Immunization Practices (ACIP) immediately
recommended that the vaccine be added to the
childhood immunization schedule. The impact of
the varicella vaccine has been dramatic before
the introduction of the vaccine approximately
four million cases of varicella occurred annually
in the U.S., resulting in approximately 11,000
hospitalizations and 100 deaths. CDC reports
incidence reductions of approximately 85 from
1990 to 2001, with a 75 decrease in
varicella-related hospitalizations and a similar
decrease in the number of deaths. In 2006 the
FDA licensed a more highly immunogenic version of
the vaccine for use in older adults to prevent
zoster (shingles).
1957gt J Enders, M Hilleman, A Gershon, S Katz, S Plotkin, M Takahashi, others development of vaccines against measles, mumps, rubella, Mareks disease, hepatitis A, hepatitis B, varicella-zoster, adenoviruses
26
Matthew Meselson Franklin Stahl
1958 M Meselson, F Stahl discovery of the semi-conservative mode of replication of DNA
27
Meselson M, Stahl FW. 1958. The Replication of
DNA in Escherichia coli. PNAS 44 (7) 671-682.
original figure 4 analytic ultracentrifuge
Schlieren optics photographs Ultraviolet
absorption photographs showing DNA bands
resulting from density gradient centrifugation of
lysates of bacteria sampled at various times
after the addition of an excess of N14 substrates
to a growing N15-labeled culture. Each photograph
was taken after 20 hours of centrifugation at
44,770 rpm. The density of the CsCl solution
increases to the right. The degree of labeling of
a species of DNA corresponds to the relative
position of its band between the bands of fully
labeled and unlabeled DNA shown in the lowermost
frame, which serves as a density reference. The
DNA in the band of intermediate density is just
half-labeled proof is provided by the frame
showing the mixture of generations 0 and 1.9 --
the peak of intermediate density is centered at
50 (2) per cent of the distance between the N14
and N15 peaks.
1958 M Meselson, F Stahl discovery of the semi-conservative mode of replication of DNA
28
1958 R Kissling, R Goldwasser development of rabies immunofluorescence diagnostics
29
CDC Rabies Advisory Committee, 1949 Front (L to
R) W. G. Winkler, E. S. Tierkel, R. K. Sikes, H.
N. Johnson, T. F. Sellers. Back R. L. Parker,
R. E. Kissling, D. Dean, J. H. Steele, J. P. Fox,
K. Habel, R. Courter.
1958 R Kissling, R Goldwasser development of rabies immunofluorescence diagnostics
30
The viral etiology of Argentine hemorrhagic fever
was established in 1958 by two independent
groups. Each isolated the virus from the blood of
patients and organs obtained from necropsies at
the Junín Regional Hospital in the province of
Buenos Aires, Argentina. Parodi AS, Greenway DJ,
Rugiero HR, Frigerio M, De La Barrera JM, Mettler
N, Garzon F, Boxaca M, Guerrero L, Nota N. Sobre
la etiología del brote epidémico de Junín. Dia
Med. 30(62)2300-2301, 1958. Pirosky, I., J.
Zuccarini, E. A. Molinelli, A. Di Pietro, P.
Martini, B. Ferreyra, L. F. Gutman Frugone, and
T. Vazquez. 1959. Virosis hemorrágica del
noroeste bonaerense. Endemoepidémica, febril,
enantemática y leucopénica. I. La primera
inoculación experimental al hombre. Orientacion
Med. 8144148.
1958gt A Parodi, D Greenway, H Rugiero, I Pirosky, J Zuccarini, J Barrera Oro, J Maiztegui, others discovery of Junin virus, the etiologic agent of Argentine hemorrhagic fever, and development of attenuated live-virus vaccine
31
Ignacio Pirosky
  • In 1957, the first molecular biology laboratory
    in Argentina was established in the Malbrán
    National Institute of Microbiology (Instituto
    Nacional de Microbiología Dr. Carlos Malbrán).
    This institute had been founded in 1924, but in
    1957 underwent a major reorganization and
    revitalization, directed by Ignacio Pirosky, a
    distinguished bacteriologist, the interim
    director. After 1957, new departments were formed
    and researchers returned from positions abroad. A
    department of bacterial genetics was added,
    chaired by Cesar Milstein, a young chemist who
    won the Nobel Prize in 1983. In a short time,
    interesting papers were published in prestigious
    journals.
  • Earlier, the participation of Elie Wollman
    (Institut Pasteur) in the development of the
    Malbrán Institute had been crucial Wollman had
    visited in 1929, when his parents, Elizabeth and
    Eugène Wollman, were invited to establish a link
    between the Malbrán and the Institut Pasteur.
    Collaboration followed, and Pirosky was invited
    in 1936 and 1937 to the Institut Pasteur to work
    under Lwoff. According to Elie Wollman, when
    Pirosky became director of the Malbrán Institute,
    he went to the Pasteur Institute, and told Lwoff
    about his plans for innovation and, in
    particular, for the recruitment of young
    Argentinean scientists who wished to study
    bacterial genetics. Lwoff, who knew about my
    long-standing links with Latin America, urged me
    to help. So in August 1958, Wollman went to
    Buenos Aires and set up a new program in the
    Pasteur Pavilion of the Malbrán Institute.
  • The Malbrán Institute molecular biology
    laboratories were dismantled in 1962, when
    Pirosky was removed as director by the
    newly-appointed Minister of Public Health. This
    led to a breakdown in the successes that had come
    of age in the years between 1957 and 1962.
    Milstein resigned his post Sanger invited him
    back to Cambridge where he was appointed Medical
    Research Council Investigator. A number of
    measures completed the breakdown full-time posts
    were limited, and most of the staff were
    dismissed. This was done under the direction of a
    secretary of state who did not tolerate Jews. The
    firing of Ignacio Pirosky provoked the
    resignation and exile of most of the research
    personnel. In 1966, the military destroyed much
    of the Natural Sciences program of the University
    of Buenos Aires, beating and incarcerating
    researchers, and had the laboratories exorcised
    by a priest. In 1976, the undersecretary of
    science and technology, bought 40 crucifixes for
    the offices of the Institute.

32
Armando S. Parodi (1909-1969) spent 1939-40
working on respiratory viruses at the Rockefeller
Foundation laboratories under the direction of
Richard Moreland Taylor. Upon returning to
Argentina he worked at the Malbrán Institute on
Venezuelan equine encephalitis, influenza,
psittacosis, and Q fever (he was the first to
isolate Coxiella burnetti in Argentina). After
organizing the virology department in the
Ministry of Public Health in Uruguay, he became
professor in the Department of Microbiology,
University of Buenos Aires. He founded The
Virology Society of Argentina.
1958gt A Parodi, D Greenway, H Rugiero, I Pirosky, J Zuccarini, J Barrera Oro, J Maiztegui, others discovery of Junin virus, the etiologic agent of Argentine hemorrhagic fever, and development of attenuated live-virus vaccine
33
1958gt A Parodi, D Greenway, H Rugiero, I Pirosky, J Zuccarini, J Barrera Oro, J Maiztegui, others discovery of Junin virus, the etiologic agent of Argentine hemorrhagic fever, and development of attenuated live-virus vaccine
34
Candid 1 vaccine for Argentine hemorrhagic fever
was developed in 1985 by Julio Barrera Oro and
Julio Maiztegui, in collaboration with Gerald
Eddy and George French of USAMRIID. The vaccine
was shown to be very effective in preventing
disease in high risk farm workers in the endemic
region of Argentina. The vaccine was first
manufactured by the Salk Institute in the United
States and became available in Argentina in 1990.
In 2006, the Instituto Nacional de Enfermedades
Virales Humanas Dr. Julio I. Maiztegui started
production of the vaccine in Argentina, with a
goal of producing the 5 million doses required to
vaccinate the entire population of the endemic
area.
1958gt A Parodi, D Greenway, H Rugiero, I Pirosky, J Zuccarini, J Barrera Oro, J Maiztegui, others discovery of Junin virus, the etiologic agent of Argentine hemorrhagic fever, and development of attenuated live-virus vaccine
35
1958 D Burkitt description of Burkitts lymphoma in African children
36
Saul Krugman at the Willowbrook State School
1958gt S Krugman separation of two forms of hepatitis (HBV, HAV) in seminal studies of the natural history of viral hepatitis at the Willowbrook State School
37
1958 K Åström, E Richardson, J Cavanaugh, G Zu Rhein, B Padgett, D Walker discovery of progressive multifocal leukoencephalopathy and its etiologic agent, JC virus (polyomavirus)
38
1958gt K Åström, E Richardson, J Cavanaugh, G Zu Rhein, B Padgett, D Walker discovery of progressive multifocal leukoencephalopathy and its etiologic agent, JC virus (polyomavirus)
39
1959 J Gowans discovery of lymphocyte re-circulation
40
1959 A Sabin, H Cox, H Koprowski, others development of attenuated live-virus polio vaccine
41
Derivation of the three attenuated viruses used
in Sabin polio vaccine
42
People lined up for blocks to receive Sabin
attenuated live-virus polio vaccine San
Antonio, Texas 1962
1959 A Sabin, H Cox, H Koprowski, others development of attenuated live-virus polio vaccine
43
1959 L Kilham discovery of murine parvoviruses
44
A negative staining method for high resolution
electron microscopy of viruses. S. Brenner and R.
W. Horne Medical Research Council Unit for
Molecular Biology and Electron Microscopy Group,
Cavendish Laboratory, Cambridge, Great Britain
Biochimica et Biophysica Acta 34103-110, 1959
1959 S Brenner, R Horne invention of negative contrast electron microscopy
45
Horne RW, Wildy P. Virus Structure Revealed By
Negative Staining. Adv Virus Res. 196310101-70.
Horne RW. Special specimen preparation methods
for image processing in transmission electron
microscopy a review. J Microsc. 1978113241.
Horne RW, Wildy P. An historical account of the
development and applications of the negative
staining technique to the electron microscopy of
viruses. J Microsc. 1979 Sep117(1)103-22. Horne
RW. The formation of virus crystalline and
paracrystalline arrays for electron microscopy
and image analysis. Adv Virus Res. 197924173.
Robert W. Horne
1959 S Brenner, R Horne invention of negative contrast electron microscopy
46
1959 R Porter, G Edelman, A Nisonoff discovery of the structure and molecular function of antibodies
47
1959 R Porter, G Edelman, A Nisonoff discovery of the structure and molecular function of antibodies
48
1959 R Sinsheimer discovery that a virus may have a single stranded DNA genome (bacteriophage ?X174)
49
1959 R Yalow, S Berson development of radioimmunoassays (RIAs)
50
1959 A Kornberg, S Ochoa discovery of the mechanisms in the biological synthesis of DNA and RNA
51
The first successful minicomputer was Digital
Equipment Corporations 12-bit PDP-8, which cost
from US16,000 upwards when launched in the
1960s.
1960 Digital Equipment Corporation development of the first minicomputer
52
1960 B Sweet, M Hilleman discovery of simian virus 40 (SV40)
53
SV40 virusfrom minimum-exposure studyby Robley
Williams, 1974
1960 B Sweet, M Hilleman discovery of simian virus 40 (SV40)
54
Lactate dehydrogenase-elevating virus (LDH virus)
was discovered by Vernon Riley and colleagues,
including Edmund Rowson, in 1960 during work on
plasma enzyme levels in tumor-bearing mice. They
found that transplantable tumors of many types
caused a 5-10-fold increase in plasma lactate
dehydrogenase (LDH) activity within 3 days of
transplantation and before the tumors were
clinically obvious. To produce this dramatic
increase in plasma enzyme level it was not
necessary to transplant cells cell-free plasma
from tumor-bearing mice was equally effective.
The raised enzyme level could be serially
transmitted from mouse to mouse and proved to be
caused by a virus which replicated rapidly in
mouse macrophages. Very high titers of viral
infectivity (109 ID50/ml) are present in the
plasma 24 h after infection, and a stable viremia
at a lower level (104 ID50/ml) is established
after 7 to 10 days. This persists for the
remainder of the animal's life but does not cause
any obvious disease or reduction of life
expectancy. The persistent viremia clearly
provides a source of virus for transmission by
bloodsucking ectoparasites. It seems likely that
this is the method of cross-infection by which
the virus is maintained in feral mice, a number
of which have been found to be infected in
Europe, America and Australia. from Brian
Mahy The discovery of LDH virus had a profound
effect on our understanding of the subtleties of
the effects of some infections, especially on
immunological responses and tumor growth in
experimental animals, such that now we expect
experimental animals to be virus free (even if
this is not always the case).
1960 V Riley, K Rowson, colleagues discovery of lactate-dehydrogenase-elevating virus (arterivirus)
55
1960 W Thompson, B Kalfayan, R Anslow discovery of La Crosse virus
56
1960 W Thompson, B Kalfayan, R Anslow discovery of La Crosse virus
57
William Weigle
1960-1970s F Dixon, W Weigle, M Oldstone, J Feldman, J Vazquez, R Lerner, others founding of immunopathology, and the role of viruses in immune complex diseases
58
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
59
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
60
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
61
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
62
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
63
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
64
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
65
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
66
William Reisen
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
67
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
68
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
69
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
70
Thomas Monath
Roy Chamberlain
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
71
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
72
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
73
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
74
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
75
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
76
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
77
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
78
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
79
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
80
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
81
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
82
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
83
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
84
1960sgt R Taylor, W Downs, J Casals, D Clarke, many others discovery, characterization, classification, natural history, pathogenesis, and vector biology of many arboviruses and hemorrhagic fever viruses
85
Yale Epidemiology Faculty, 1959 First row J.T.
Riordan. Dr. F.L. Black, Dr. Dorothy M.
Horstmann, Dr. Richard M. Taylor, Dr. John R.
Paul (Chairman), Dr. R.H. Green, Dr. G.-D.
Hsiung. Second row Dr. B.H. Wilmer, Dr. James C.
Niederman, Dr. Robert W. McCollum, Dr. J.R.
Henderson, Dr. I. Yoshioka, Dr. M.G. Gudnadottir.
Third row Dr. S.R. Sheriden, Dr. W.H. Gaylord,
Dr. E.P. Isacson, Dr. H. Sunaga. Dr. Edward M.
Opton.
86
Yale School of Public Health, Infectious Diseases
Faculty, 1969
Front row (L to R) 1. 2. Ann Schluderberg 3. Walter Hierholzer4. Wilbur Downs 5. Robert McCollum 6. Max Theiler 7. Dorothy Horstmann 8. Jim Neiderman 9. Alfred Evans Middle row 1. 2. Robert Wallis 3. Frank Black 4. Ed Opton 5. Jordi Casals 6. Thomas Stim 7. 8. Back row 1. Bob Shope 2. 3. Wistar Meiggs 4. Charles Anderson 5. George Lebouvier6. John Riordan 7. Harvey Liebhaber 8. 9. Nick Karabatsos
87
Yale School of Public Health, Infectious Diseases
Faculty, 1989
88
Diane Griffin
1960s C Mims, R Johnson, N Nathanson, B Fields, R Blanden, M Oldstone, A Haase, D Griffin, others founding of the modern era of viral pathogenesis research
89
Volker ter Meulen
1960s C Mims, R Johnson, N Nathanson, B Fields, R Blanden, M Oldstone, A Haase, D Griffin, others founding of the modern era of viral pathogenesis research
90
1960s R Merrifield development of solid phase synthesis technology (polypeptides, oligonucleotides, etc.)
91
1961 F Jacob, J Monod, A Lwoff, S Brenner, F Gros, M Meselson discovery of messenger RNA, the operon theory, and genetic regulatory mechanisms for control of the synthesis of proteins
92
1961 J Miller discovery of the role of the thymus in cellular immunity
93
BHK-21 cells
MACPHERSON I, STOKER M. Polyoma transformation of
hamster cell clones--an investigation of genetic
factors affecting cell competence. Virology, 16,
147 (1962). 
1961 I Macpherson, M Stoker development of BHK-21 cell line
94
Crick and Brenner In a long series of complex
experiments, we induced mutations in the DNA of
bacteriophage T4. The mutations changed
individual bases in the DNA, knocking out the
function of a crucial phage gene (the B cistron
of the rII region of T4). When two or four
mutations were together, the gene was still
inactive, but when three mutations were put
together in the same gene, the gene started to
work again. We concluded that the genetic code is
a triplet code (three bases code for one
amino-acid), and that the code is degenerate (an
amino-acid may be coded by more than one triplet
of bases). Separately, we showed that the code is
non-overlapping.
1961 F Crick, S Brenner, J Griffith, L Orgel, L Barnett, R Watts-Tobin discovery of the triplet coding of DNA (bacteriophage)
95
1961. American and Russian virologists together
in Moscow. This was the first exchange visit with
Soviet virologists. Seated left to right Bela
Kaplan, interpreter R.J. Huebner, LID/NIAID/NIH
M.P. Chumakov, Director of the Soviet
Poliomyelitis Institute E.H. Lennette, Director
of the California State Health Laboratory W.McD.
Hammon, Dean of the University of Pittsburgh
School of Hygiene and Public Health. Standing
left to right R.M. Chanock, LID/NIAID/NIH F.
Davenport, University of Michigan S.G. Drozdov
A Avakian V.I. Agol unidentified scientist U.
Chumakova Ms. Lechinskaja A.I. Shelokov,
LID/NIAID/NIH unidentified scientist.
96
First issue MMWR 1961
1961 U.S. Communicable Disease Center publication of CDCs Morbidity and Mortality Weekly Report
97
1961-1966 M Nirenberg, H Khorana, R Holley, S Ochoa, J Matthaei, colleagues deciphering of the genetic code
98
The Vero cell line was derived from the kidney of
a normal, adult, African green monkey (Cercopithec
us aethiops) in 1962, by Y. Yasumura and Y.
Kawakita at Chiba University, Japan (Nippon
Rinsho 211209, 1963). In addition to its use as
a vaccine cell substrate, the cell line has been
used extensively for virus replication studies
and plaque assays. Vero cells are sensitive to
infection with SV-40 virus, SV-5 virus, measles
virus, many arboviruses, reoviruses, rubella
virus, simian adenoviruses, polioviruses,
influenza viruses, parainfluenza viruses,
respiratory syncytial viruses, vaccinia virus,
and many others.
1962 Y Yasumura, Y Kawakita establishment of the Vero cell line (African green monkey kidney epithelial cell, named from Verda Reno meaning green and truth in Esperanto)
99
Frontispiece 1 Cold Spring Harbor Symposium on
Quantitative Biology Basic Mechanisms in Animal
Virus Biology SOME SYMPOSIUM PARTICIPANTS Top
row I. Tamm, A. Lwoff, M. G.P. Stoker, R.
Dulbecco, A. Isaacs F. Fenner, R. Franklin, D.
Baltimore. Second row A. Granoff, L. Levintow,
B. Roizman D.L.D. Caspar, C. Hotchkiss F.L.
Schaffer, B.C. Backus. Third row A. lsaacs,
G.K. Hirst, H. Noll, P. Wildy G. Klein, F.
Fenner, L. Frisch B.R. Burmester, T. Hanafusa,
B.L. Seecof. Bottom row P. Tournier, R.W.
Simpson, W. Bernhard H. Rubin L. Sachs, B.
Ephrussi.
1962 A Chovnick, R Dulbecco, J Cairns, G Hirst, A Lwoff, H Rubin, M Stoker Cold Spring Harbor Symposium on Quantitative Biology Basic Mechanisms in Animal Virus Biology
100
Frontispiece 2 Cold Spring Harbor Symposium on
Quantitative Biology Basic Mechanisms in Animal
Virus Biology SOME SYMPOSIUM PARTICIPANTS Top
row G.K. Hirst, H. Koprowski, H. Noll Y. Ito
F.K. Sanders, C. Morgan, P. Cooper, R.W.
Schlesinger. Second row F.K. Sanders J.S.
Colter, T.S. Work E. Winocour. Third row J.E.
Hotchin H.M. Temin, B. Ephrussi, G. Attardi W.
Levinson, F. Fenner, A. Chovnick. Bottom row R.
Franklin, P.I. Marcus, B.S. Spendlove, E.
Wecker, D. Baltimore, A.F. Graham T. Hanafusa,
D. Baltimore, W.K. Joklik, N. Ledinko, J. Cairns.
1962 A Chovnick, R Dulbecco, J Cairns, G Hirst, A Lwoff, H Rubin, M Stoker Cold Spring Harbor Symposium on Quantitative Biology Basic Mechanisms in Animal Virus Biology
101
Annual Review of Microbiology 2045-74, 1966
In the early 1960s Lwoff became engaged in the
classification and nomenclature of viruses.
Together with Thomas Anderson and François Jacob,
he coined terms useful in classification such as
virion, capsid, capsomere, nucleocapsid,
peplomer, and envelope, which have become part of
the basic virologic vocabulary. In collaboration
with Robert Horne and Paul Tournier, he devised
the first modern virus classification system
based on virion characteristics.
1962 A Lwoff, R Horne, P Tournier first comprehensive classification of the viruses based on virion characteristics
102
1962 A Lwoff, R Horne, P Tournier first comprehensive classification of the viruses based on virion characteristics
103
1962 L Kraft discovery of mouse hepatitis virus (lethal intestinal virus of infant mice)
104
DLD Caspar presenting Kepler's solar systemin
Dürer's pentagonally illuminated sanctum
Aaron Klug 1982 Nobel Laureate in Chemistry,
for his development of crystallographic electron
microscopy and his structural elucidation of
biologically important nucleic acid-protein
complexes.
1962 D Caspar, A Klug discovery of the principles of icosahedral virus structure
105
Francis Crick Donald Caspar Aaron Klug Rosalind
Franklin 1965
1962 D Caspar, A Klug discovery of the principles of icosahedral virus structure
106
1962 P Gomatos, I Tamm discovery of double-stranded RNA in a virus (reovirus)
107
1962 A Cosgrove, H Lasher discovery of infectious bursal disease virus (the first birnavirus)
108
1962 F Rauscher discovery of the first virus-induced lymphoid leukemia in mice
109
1962 NCI Report The finding of John J. Trentin
that human adeno-virus-type 12 induces tumors in
hamsters (confirmed by Huebner and Rowe along
with the demonstration that adenovirus-type 18
also is oncogenic in hamsters), together with the
confirmation of the onco-genic nature of SV40
virus and the further characterization of its
properties in tissue culture (e.g., growth of
virus and transformation with chromosomal changes
in human cells in culture), and the delineation
of the nature of the papovaviruses (especially by
Melnick, Koprowski, and Hilleman) represent
important highlights of ongoing cancer virus
research.
1962 J Trentin, Y Yabe, G Taylor discovery of the induction of tumors in hamsters by human adenoviruses
110
Schneweis, K.E. Serologische Untersuchungen zur
Typendifferen zierung des Herpesvirus hominis.
Z. Immunitaetsforsch., 124 24, 1962. Dowdle.
W.R., Nahmias, A.J., Harwell, R.W., and Pauls.
F.P. Association of Antigenic Types of
Herpesvirus hominis with Site of Viral Recovery.
J. Immunol., 99 974, 1967.
1962- 1967 K Schneweis, W Dowdle, A Nahmias, R Harwell, F Pauls differentiation of herpes simplex viruses 1 and 2
111
1962gt R Webster, G Laver discovery of the link between avian and human influenza viruses and development of the concept that that pandemic virus strains arise via reassortment of genes of various human and non-human strains
112
1962gt2008 O Shimomura, M Chalfie, R Tsien discovery of green fluorescent protein and its eventual development as a tagging tool in viral disease research
113
Intact brain of mouse infected with recombinant
Semliki Forest virus (SFV) carrying  an EGFP
marker protein. John Fazakerley, Edinburgh
Neurons, mouse brain (cortex hippocampus)
fluorescing in many colors effect produced by
different amounts of three GFP-tagged proteins
that fluoresce yellow, cyan and red, thereby
allowing tracing of individual neuronal
processes. Jean Livet et al. Nature (2007)
1962gt O Shimomura, M Chalfie, R Tsien discovery of green fluorescent protein and its eventual development as a tagging tool in viral disease research
114
Rabies -- Widefield image of intrinsic EGFP
fluorescence in unstained tissue, 6d
post-infection. Deep-layer cortical pyramidal
cells infected after injection into thalamus.
From Retrograde neuronal tracing with a deletion
mutant rabies virus. IR Wickersham, S Finke, K-K
Conzelmann, EM Callaway. Nature Methods 447,
2007
115
1963 W Downs, C Anderson, L Spence, others discovery of Tacaribe virus (the first western hemisphere arenavirus)
116
Rabies virus, mouse neuron, thin section EM, 1961
Matsumoto, Seiichi. Electron Microscope Studies
of Rabies Virus in Mouse Brain. J. Cell Biol.
19565-591, 1963. Miyamoto, Kaneatsu and
Matsumoto, Seiichi. The Nature of the Negri
body.Journal of Cell Biology 27677-682,
1965 Miyamoto, Kaneatsu and Matsumoto, Seiichi.
Comparative Studies Between the Pathogenesis of
Street and Fixed Rabies Virus Infection. Journal
of Experimental Medicine 125447-456, 1967
1963 S Matsumoto, K Miyamoto discovery of the morphology and morphogenesis of rabies virus and the nature of the Negri body
117
Yvonne Barr, a PhD graduate of the University of
London in virology, assisted Michael Epstein in
the discovery of Epstein-Barr virus. Later, she
married and moved to Australia.
1964 M Epstein, B Achong, Y Barr discovery of Epstein-Barr virus and its association with Burkitts lymphoma
118
1964 W Jarrett discovery of feline leukemia virus
119
1964 K Johnson, N Wiebenga, R McKenzie, P Webb, others discovery of Machupo virus, etiologic agent of Bolivian hemorrhagic fever
120
U. S. Delegation on Hemorrhagic Fevers to the
U.S.S.R. under the terms of the U.S.-U.S.S.R.
agreement concerning exchanges in the scientific,
technical, educational, cultural and other
fields, 19641965. From left to right Ned
Wiebenga, Alexis Shelokov, B. Kaplan
(translator), Mikhail Chumakov, Karl Johnson,
E.V. Leshchinskaya, Marina Voroshilova, Jordi
Casals
1965 Mission to USSR A Current Appraisal of
Hemorrhagic Fevers in the U.S.S.R. Jordi Casals,
Harry Hoogstraal, Karl M. Johnson, Alexis
Shelokov, Ned H. Wiebenga and Telford H. Work.
Am. J. Trop. Med. Hyg., 15(5), 1966, pp. 751-764
1965 J Casals, H Hoogstraal, K Johnson, A Shelokov, N Wiebenga, T Work initial viral disease scientific exchange between U.S. and U.S.S.R. on hemorrhagic fevers in Eurasia
121

Commission on Viral Infections, 1965 (in the War
Room at the Walter Reed Army Institute of
Research) Front row L-R W. Sherer, W. Havens,
J. Enders, G. Sather, B. Gilbert, R. McCollum, W.
Hammon, D. McLean, E. Sulkin, G. Mirick, S.
Krugman, R. Murray, F. Robbins, W. Henle, R.
Green Back Row L-R G. Damin, W. Downs, T. Work,
R. Ward, F. Neva, S. Britten, W. Reeves, W.
Tiggert, J. Casals, R. Taylor, F. Bowling, F.
Bang
122
1965 D Tyrrell, M Bynoe, J Almeida, D Hamre, J Procknow discovery of human coronaviruses (B814 and 229E)
123
1965 M Bouteille, T Chen, L Horta-Barbosa, J Sever, others discovery of the etiology of subacute sclerosing panencephalitis (measles virus)
124
1965 R Atchison, J Melnick, colleagues discovery of adeno-associated viruses
125
Marguerite (Peggy) Helio Pereira (19181994)
Adenovirus 5, Robin Valentine, 1965
1965 R Valentine, H Pereria, E Norrby discovery of adenovirus structural / functional elements (penton fibers, etc)
126
1965gt B Roizman seminal studies of the molecular structure and replication and the cell biology of herpes simplex virus
127
Cell type Primary activities of IL-2
CD4 T cells Induces expansion of antigen-specific clones via proliferative anti-apoptotic mechanisms Augments production of other cytokines Required for differentiation to Th1 and Th2 subsets Induces apoptosis of activated T cells (activation-induced cell death) Involved in development of CD4CD25 T regulatory cells
CD8 T cells Induces expansion of antigen-specific clones Augments cytokine secretion Augments cytolytic activity Induces proliferation of memory CD8 cells
B cells Enhances antibody secretion Initiates immunoglobulin J chain transcription and synthesis Promotes proliferation
NK cells Promotes proliferation Augments cytokine production Enhances cytolytic activity
IL-2 S Kasakura, L Lowenstein (1965) lymphocyte
mitogenic activity J Gordon, LD Maclean (1965)
Blastogenic Factor K Smith (1977) T Cell Growth
Factor (TCGF) IL1 K Smith (1978) lymphocyte
activating factor (LAF)
1965-1978 S Kasakura, L Lowenstein, J Gordon, L Maclean, K Smith discovery and characterization of the first interleukin, IL-2
128
Hadlow WJ. Scrapie and kuru. Lancet 1959 ii
289-90. Gajdusek DC, Gibbs CJ Jr, Alpers M.
Experimental Transmission of a kuru-like
syndrome to chimpanzees. Nature 1966 209 794-6.
1966 C Gajdusek, C Gibbs, W Hadlow, M Alpers transmission of the etiologic agent of kuru (the kuru prion), to non-human primates
129
1966 C Gajdusek, C Gibbs, W Hadlow transmission of the etiologic agent of kuru (the kuru prion), to non-human primates
130
1966 National Library of Medicine development of Medline
131
1966 P Wildy, F Fenner, R Matthews, others founding of the International Committee on Nomenclature of Viruses (now the International Committee on Taxonomy of Viruses)
132
1966 P Wildy, F Fenner, R Matthews, others founding of the International Committee on Nomenclature of Viruses (now the International Committee on Taxonomy of Viruses)
133
1999 Executive Committee of the International
Committee on the Taxonomy of Viruses
(ICTV) Seated (L to R) C. Calisher, S.
Ghabrial, A. Jarvis, F. Murphy, C.
Fauquet. Standing M. van Regenmortel, R.
Goldbach, B. Mahy, C. Pringle, H. Pereira, L.
Berthiaume, G. Martelli, E. Carstens, J Maniloff,
J. Strauss, M. Summers, M. Mayo, A. Gibbs, H.
Ackermann, D. McGeoch, A. Della Porta, M.
Horzinek.
1966 P Wildy, F Fenner, R Matthews, others founding of the International Committee on Nomenclature of Viruses (now the International Committee on Taxonomy of Viruses)
134
1966 H Meyer, P Parkman development of rubella vaccine
135
Pravin Bhatt
? Pravin Bhatt, organizer of the Conference
and later organizer of the American Committee
on Laboratory Animal Diseases
1966gt P Bhatt, R Jacoby, H Morse, A New, others development of diagnostic virology of laboratory rodents
136
1966gt M Studdert seminal studies of equine viruses (herpesviruses, rhinoviruses, others)
137
1967 B Blumberg, H Alter, A Prince, others discovery of Australia antigen, hepatitis B virus and the etiology of post-transfusion hepatitis (the first hepadnavirus)
138
1967 J Kates, B McAuslan discovery of DNA-dependent RNA polymerase in a virion (vaccinia virus)
139
DNA-dependent RNA polymerase in a virion
(vaccinia virus)
  • Early on, enzymes required for viral DNA
    synthesis were found to be induced in vaccinia
    virus-infected cells. DNA polymerase activity was
    identified in 1962, and in the following year
    McAuslan and others reported the presence of
    thymidine kinase and deoxyribonuclease. These
    enzymes are present in uninfected cells but they
    are located in the nucleus. Because vaccinia
    virus DNA synthesis occurs in the cytoplasm, the
    question arose as to whether the virus-induced
    enzymes are different. McAuslan showed that the
    thymidine kinases in uninfected and infected
    cells are different. These observations were
    compatible with the idea that the enzymes
    required for viral DNA synthesis are encoded by
    the virus, but it was difficult at the time to
    see how their transcription from viral genes
    could take place in the cytoplasm of infected
    cells. In eukaryotic cells, synthesis of mRNA,
    which is transcribed from chromosomal DNA,
    requires RNA polymerase II and this enzyme is
    located in the nucleus. In a paper published in
    1967, Kates and McAuslan showed that
    virus-specific mRNA is not synthesized de novo
    and must be present at the time of infection. All
    available evidence pointed to the presence of RNA
    polymerase within the vaccinia virus virion.
    Thirty years ago this was difficult to conceive
    because virions were thought to be metabolically
    inert and no virion-associated enzyme had
    previously been described in any animal virus. It
    was at this stage that Kates and McAuslan
    published their study on the ability of vaccinia
    virus cores to synthesize virus-specific RNA.
    Poxvirus DNA-Dependent RNA Polymerase. J.R.
    Kates and B.R. Mcauslan. PNAS 58 134-141 (1967).
  • Kates and McAuslans discovery played a seminal
    role in studies which led to the detection of
    virion-associated enzyme activities in other
    viruses.
  • Attempts to infect cells with nucleic acid
    recovered from some RNA viruses proved
    unsuccessful and the possibility began to be
    considered that their genomes may be
    negative-sense. If so, a transcriptase would be
    required to act on the genomic RNA to produce a
    positive sense, complementary copy. Because a
    mammalian enzyme with such activity does not
    exist, it was considered that it must be brought
    into the host cell by the infecting virus, that
    is, the transcriptase would have to be a
    virion-associated enzyme. Such an RNA-dependent
    RNA transcriptase was found, in 1968, to be
    present in reovirus virions (by Kates, McAuslan,
    Shatkin and Sipe), and two years later in
    vesicular stomatitis virus virions (by Baltimore
    and Huang), and, in 1971, in influenza virions.
    of course, in 1970 an RNA-dependent DNA
    polymerase was found in retrovirus virions (by
    Temin and Baltimore)this enzyme, reverse
    transcriptase, became so famous that in some
    ways the other virion associated transcriptases
    were lost in time.

140
Staff, John Curtin School of Medical Research,
Department of Microbiology, Canberra, 1962 Back
row (from left to right) Mary McClain, Rob
Webster, William Murphy, Tom Grace, John Roberts,
Alfred Gottschalk, Betty Ermacora, Frank
Warburton, Ric Davern, Stephen Fazekas, Royle
Hawkes, Allan Logie. Front row Ron Weir, Rima
Greenland, Brian McAuslan, Bill Joklik, Cedric
Mims, Gwen Woodroofe, Frank Fenner, Fritz
Lehmann-Grube, John Cairns, Ian Marshall, Dennis
Lowther.
141
1967 W Siegert, R Slenczka, G Martini, R Kissling, R Robinson, F Murphy, others discovery of Marburg virus (the first filovirus)
142
1967 W Siegert, R Slenczka, G Martini, R Kissling, R Robinson, F Murphy, others discovery of Marburg virus (the first filovirus)
143
1967 W Siegert, R Slenczka, G Martini, R Kissling, R Robinson, F Murphy, others discovery of Marburg virus (the first filovirus)
144
Marburg virus, 1967
1967 W Siegert, R Slenczka, G Martini, R Kissling, R Robinson, F Murphy, others discovery of Marburg virus (the first filovirus)
145
1967 W Siegert, R Slenczka, G Martini, R Kissling, R Robinson, F Murphy, others discovery of Marburg virus (the first filovirus)
146
CDC Building 8, 1970s the latest in the design
of the maximum containment laboratory
James Lange and Herta Wulffworking through
glove-portsin CDC Building 8, 1970s
1967 U.S. Communicable Disease Center development of civilian high-containment virology laboratories
147
LuAnne Elliott in the first positive pressure
maximum containment suit, invented by Karl
Johnson CDC, 1977
positive pressure maximum containment suits,
2008
1967 U.S. Communicable Disease Center development of civilian high-containment virology laboratories
148
Bovine ephemeral fever virus
1967 B van der Westhuizen, Y Inaba, Y Tanaka, colleagues discovery of bovine ephemeral fever virus
149
The founding editors of the Journal of Virology,
at their first organizational meeting in
1966. From left to right, Lloyd Kozloff, Robert
Wagner, and Norman Salzman
1967 R Wagner, L Kozloff, N Salzman publication of the journal, Journal of Virology
150
Peter Wildy (1920-1987)
1967 C Kaplan, P Wildy publication of the journal, Journal of General Virology
151
1967 J Maizel, U Laemmli development of SDS polyacrylamide gel electrophoresis of proteins
152
Churchill, A. E. Biggs, P. M. Agent of Mareks
disease in tissue culture. Nature 215, 528530
(1967).
1967-1969 A Churchhill, P Biggs, B Burmester discovery of Mareks disease virus (herpesvirus) and development of vaccine
153
Pathogenesis of Mareks disease in fowl
József Marek (1868-1952) Marek first described
thedisease named for him in 1907
1967-1969 A Churchhill, P Biggs, B Bermester discovery of Mareks disease virus (herpesvirus) and development of vaccine
154
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