Genetics is the core science of biology. Its ultimate subject matter is a class of chemical compounds, the hereditary determinants, which are the prime movers of cellular metabolism and, thereby, of the even more complex processes of development and evolution. Historically, genetics began with the demonstration of genes which behaved as unit factors in sexual transmission in higher plants and animals. Subsequently, in a great burst of fruitful research, genetics became established as a predictive science dealing with the organization and behavior of hereditary material at the biological level. Genetics is unique in biology for its broad and fundamental theory, and for methods which provide approximate solutions of the problems posed. In the 1930,s it was already possible to build upon the theory of genetics, for example, in the experimental study of evolution, in the analysis of genetic effects upon physiology and development, and in application to plant and animal breeding.

Today, the science of genetics is coming to grips with the analysis of heredity at the molecular level in studies of the hereditary determinants: their chemistry, the molecular basis of their replication, mutation, and transmission, and the translation systems by means of which they exert their control over all cellular processes.

Progress in molecular genetics began to accelerate following the introduction of microorganisms into genetic research, a development which has been gaining momentum steadily since about 1940. In the last 20 years, there have been tremendous advances in this field, and in its impact upon other areas of biology. With microorganisms it has been possible to perform certain decisive experiments, technically infeasible with higher organisms, which have clarified and solidified points of genetic theory previously the subject of speculation. At the same time, some wholly unexpected new findings have emerged which are forcing a revaluation and broadening of concepts in the entire science:

It has seemed timely, therefore, to attempt a summary statement, in the form of a modern textbook, of what appear to us the essential features of our science, and the principal directions of current inquiry. Such a statement must be understood to be tentative, with many areas of uncertainty, as befits a science in a fluid state. When they seemed important, we have included concepts about which there is considerable doubt, always indicating where this is the case. After all, the testing of concepts, and not their certainty, is the heart of science. The basic tenets of genetics are presented in terms of key illustrative experiments, and we have tried to capture the critical mood of the scientist and the controversial aspects of the findings as well as the facts.

In this book we have abandoned the chronological approach and have attempted a synthetic presentation, organizing the knowledge in a logically sequential pattern wherever possible. Thus we begin not with Mendel's pea crosses of 1866, but with the transformation experiment of 1943, which provided the first direct evidence of the chemical composition of hereditary material. In all fields of cell biology, the direction of progress has been towards a more mechanistic analysis of events on a physicochemical basis. In genetics, the largest stride in this direction occurred with the chemical indentification of nucleic acids as carriers of hereditary information. Nucleic acids may not be the sole hereditary determinants in the cell, but at least they represent one class, the only class yet detected; as such they provide the best frame of reference for a review of the facts and fancies of genetics, as they appear in 1960.

Although this is not a textbook of microbial genetics, experiments with microorganisms are heavily cited because they have provided material for many incisive experiments. We have limited ourselves to the discussion of genetics at the cellular level, and have omitted the application of genetic principles to scientiflc agriculture, to the experimental analysis of evolution, and to related fields. Although in the past, cell genetics and population genetics have been presented side by side, these fields have become so divergent in methodology and frame of reference that it seems preferable to treat them independently.

Genetics lends itself well to a formal presentation, largely abstracted from descriptive details and, therefore, it can be understood by persons who lack a background in biology. Until recently, even a lack of knowledge of physics and chemistry was no barrier, but as new experiments explore the molecular behavior of hereditary determinants, an elementary knowledge in the physical sciences becomes essential.

This book is addressed to the curious-minded of all ages from college students to mature scholars in disciplines other than genetics. It is written out of an awareness that genetics is rapidly becoming of keener interest to scientists in other fields, as the impact of genetic determinants is felt in their experiments, and to students in search of challenging research problems. It is written especially in the hope that for some readers the acquisition of a broader understanding about a particular branch of science may be an exhilarating intellectual experience.

In preparing this book, we were aided by many friends and colleagues who provided us generously with information, illustrations, and criticism. We wish to acknowledge our deep appreciation to the following persons:

C. B. Anfinson, R. Appleyard, K. C. Atwood, H. Crouse, M. Demerec, M. Fischberg, S. Fogel, P. E. Hartman, N. W. Horowitz, R. D. Hotchkiss, J. Iino, F. Gros, K. Kimura, J. Lederberg, E. B. Lewis, O. Maaloe, B. McClintock, G. E. Palade, D. D. Perkins, M. M. Rhoades, F. Stahl, J. H. Taylor, M. Tsujita, H. Vogel, M. Westergaard. We are particularly indebted to S. Fogel, B. N. Jamin, and D. D. Perkins for their detailed criticisms of the entire manuscript, and to G. E. Palade for the electron micrographs.

New York, April 1961
RUTH SAGER
FRANCIS J. RYAN