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No author has gone as far as Doerfler in covering methods of mental
calculation beyond simple arithmetic. Even if you have no interest
in competing with computers you'll learn a great deal about number
theory and the art of efficient computer programming. --Martin
Gardner
The data summarized in this chapter show that morphological
transformation and oncogenesis by adenoviruses are brought about by
the coordinated activity of regions E1A and E1B. Gene products of
each of these subregions appear to fulfill distinct roles in
oncogenic transformation, with the possible exception of the
product(s) encoded by the O. 9-kb E1A mRNA. Also unclear is the
func- tion of the 20-kd E1B protein, which has a small role, if
any, in morphological transformation, but appears to be essential
for the development of the oncogenic phenotype, as defined by the
ability of transformed cells to grow in immuno- deficient nude
mice. The differences in biological properties of oncogenic and
nononcogenic adenoviruses must be attributed to differences in the
primary structure of the respective E1A and E1B gene products, in
particular of the product(s) of the 1. 0-kb E1A mRNA and of the
55-kd protein encoded by the 2. 2-kb EiB mRNA. The availability of
cold-sensitive adenovirus mutants has enabled us to conclude that
the transformed phenotype is maintained as a result of continuous
expression of at least region E1A gene products, and is therefore
not the result of a hit-and-run mechanism. Despite the progress in
our understanding of adenovirus transformation and oncogenesis,
virtually nothing is known about the precise mechanism by which the
viral gene products bring about the neoplastic changes in cells.
The only exception is the demonstration that Ad12 region E1A (1.
A puzzling epidemiological problem was the driving force behind the
discovery of human adenoviruses by Wallace Rowe and his colleagues
30 years ago. The de velopment of a plaque assay for poliomyelitis
virus in 1953 led us to the threshold of quantitative virology, and
in the same year the double-helical structure of DNA was discovered
and became a cornerstone of mo lecular biology. The potential of
adenoviruses as research tools in the molecular and cellular
biology of eukaryotic cells was recognized as early as the late
1950s and early 1960s by several investigators. Structural and
biochemical stu dies dominated the early years. In 1962, some of
the adenoviruses were the first human viruses shown to be oncogenic
in experimental animals. Thus adenovirology offered the
investigator the entire gamut of host cell interactions, productive
and abortive, as well as trans formed and tumor cell systems. The
possibilities that adenoviruses afforded for the study of the
molecular biology and genetics of eukaryotic cells were fully rea
lized in the late 1960s and the 1970s."
During the past few decades we have witnessed an era of remarkable
growth in the field of molecular biology. In 1950 very little was
known of the chemical constitution of biological systems, the
manner in which information was trans mitted from one organism to
another, or the extent to which the chemical basis of life is
unified. The picture today is dramatically different. We have an
almost bewildering variety of information detailing many different
aspects of life at the molecular level. These great advances have
brought with them some breath-taking insights into the molecular
mechanisms used by nature for rep licating, distributing and
modifying biological information. We have learned a great deal
about the chemical and physical nature of the macromolecular
nucleic acids and proteins, and the manner in which carbohydrates,
lipids and smaller molecules work together to provide the molecular
setting of living sys tems. It might be said that these few decades
have replaced a near vacuum of information with a very large
surplus. It is in the context of this flood of information that
this series of monographs on molecular biology has been organized.
The idea is to bring together in one place, between the covers of
one book, a concise assessment of the state of the subject in a
well-defined field. This will enable the reader to get a sense of
historical perspective-what is known about the field today-and a
description of the frontiers of research where our knowledge is
increasing steadily."
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