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."

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