but also the possibility of intervention in specific stages. In Human behavior, including stress and other factors, plays an important role in neoplasia, although too little is known addition, variables which affect cancer development as well on the reasons for such development. Carcinogens, which as some endogenous factors can be better delineated help initiate the neoplastic process, may be either synthetic through such investigations. The topics of this volume encompass premalignant non or naturally-occurring. Cancer causation may be ascribed to invasive lesions, species-specific aspects of carcinogenicity, certain chemicals, physical agents, radioactive materials, viruses, parasites, the genetic make-up of the organism, and radiation, viruses, a quantum theory of carinogenesis, onco bacteria. Humans, eumetazoan animals and vascular plants genes, and selected environmental carcinogens. are susceptible to the first six groups of cancer causes, whe reas the last group, bacteria, seems to affect only vascular plants. Neoplastic development may begin with impairment ofJmdy defenses by a toxic material (carcinogen) which acts as an initiator, followed by promotion and progression to an overt neoplastic state. Investigation of these processes Series Editor Volume Editor allows not only a better insight into the mechanism of action Hans E. Kaiser Elizabeth K. Weisburger vii ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E. H. Krokowski.

The scientific basis, inference assumptions, regulatory uses, and research needs in risk assessment are considered in this two-part volume. The first part, Use of Maximum Tolerated Dose in Animal Bioassays for Carcinogenicity, focuses on whether the maximum tolerated dose should continue to be used in carcinogenesis bioassays. The committee considers several options for modifying current bioassay procedures. The second part, Two-Stage Models of Carcinogenesis, stems from efforts to identify improved means of cancer risk assessment that have resulted in the development of a mathematical dose-response model based on a paradigm for the biologic phenomena thought to be associated with carcinogenesis.

A Nobel Prize–winning cancer biologist, leader of major scientific institutions, and scientific adviser to President Obama reflects on his remarkable career. A PhD candidate in English literature at Harvard University, Harold Varmus discovered he was drawn instead to medicine and eventually found himself at the forefront of cancer research at the University of California, San Francisco. In this “timely memoir of a remarkable career” (American Scientist), Varmus considers a life’s work that thus far includes not only the groundbreaking research that won him a Nobel Prize but also six years as the director of the National Institutes of Health; his current position as the president of the Memorial Sloan-Kettering Cancer Center; and his important, continuing work as scientific adviser to President Obama. From this truly unique perspective, Varmus shares his experiences from the trenches of politicized battlegrounds ranging from budget fights to stem cell research, global health to science publishing.

It has been recognized for almost 200 years that certain families seem to inherit cancer. It is only in the past decade, however, that molecular genetics and epidemiology have combined to define the role of inheritance in cancer more clearly, and to identify some of the genes involved. The causative genes can be tracked through cancer-prone families via genetic linkage and positional cloning. Several of the genes discovered have subsequently been proved to play critical roles in normal growth and development. There are also implications for the families themselves in terms of genetic testing with its attendant dilemmas, if it is not clear that useful action will result. The chapters in The Genetics of Cancer illustrate what has already been achieved and take a critical look at the future directions of this research and its potential clinical applications.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.