This text provides a clear exposition of genetic principles and problems with comprehensive, up-to-date references. Specialists who have collaborated closely with industry give an inside authentic view of the genetics and breeding of industrial microorganisms such as yeasts, filamentous fungi, actinomycetes, pseudomonads, and other bacteria of major industrial significance. This book will be especially valuable to many professionals in the field of microbial genetics.

First multi-year cumulation covers six years: 1965-70.

The properties of continuous variation are basic to the theory of evolution and to the practice of plant and animal improvement. Yet the genetical study of continuous variation has lagged far behind that of discontinuous variation. The reason for this situation is basically methodological. Mendel gave us not merely his principles of heredity, but also a method of experiment by which these principles could be tested over a wider range ofliving species, and extended into the elaborate genetical theory of today. The power of this tool is well attested by the speed with which genetics has grown. In less than fifty years, it has not only developed a theoretical structure which is unique in the biological sciences, but has established a union with nuclear cytology so close that the two have become virtually a single science offering us a new approach to problems so diverse as those of evolution, development, disease, cellular chemistry and human welfare. Much of this progress would have been impossible and all would have been slower without the Mendelian method of recognizing and using unit differences in the genetic materials. These great achievements should not, however, blind us to the limitations inherent in the method itself. It depends for its success on the ability to assign the individuals to classes whose clear phenotypic distinctions reveal the underlying genetic differences.

The history of antibiotics may weIl have begun with the ancient Sudanese-Nubian civilization (see Chapter 1, "Historical Introduction"), but this volume reflects a more contemporary appraisal of the antibiotic era. We have compiled a comprehensive review of the tetracyclines which includes all the major sub divisions of these chemically important and clinically useful antibiotics. There can be little doubt about the contribution of antibiotics to both the increase in human life span and the alleviation of much human suffering. The tetracyclines are still playing an important role in these areas and will continue to do so in the foreseeable future. We hope this volume will be an important contribution to a better under standing of the chemistry, biochemistry, and medical aspects of tetracycline antibiotics. We are indebted to the individual authors who have given so much of their time and effort in the preparation of the chapters. Pearl River, NY J OSEPH J. HLA VKA Ocean Gate, NJ JAMES H. BOOTHE Contents CHAPTER 1 Historical Introduction. J. H. BOOTHE and J. J. HLAVKA References. 3 CHAPTER 2 Fermentation and Mutational Development of the Tetracyclines J. J. GOODMAN A. Introduction 5 B. The Producing Microorganisms . 6 I. Morphology and Ultrastructure 6 11. Mutation and Strain Selection 8 111. Cosynthesis. 13 The Fermentation Process 14 C. I. Inoculum 14 11. Contamination 16 Complex Media. 18 111. IV. Synthetic Media. 27 V. Stimulators and Inhibitors 30 Directed Fermentations 32 VI.

Economic Microbiology, Volume 2: Primary Products of Metabolism is part of a multi-volume series that aims to provide authoritative accounts of the many facets of exploitation and control of microbial activity. It discusses the production of industrially important chemicals by microbiological processes, specifically the production of primary products of metabolism. This volume includes accounts of the production of organic acids, nucleotides, and amino acids which form large and stable sectors of the microbiological industries. It also provides information on polysaccharide fermentations, which are currently undergoing extensive development. Further, there are discussions of the production of lipids and polyhydroxy alcohols, which have yet to be introduced on a commercial scale but could well become economically viable in the near future. Finally, there is also an account of the production of acetone and butanol by bacteria. This fermentation process featured significantly in the career of Chaim Weizmann, the first President of the State of Israel, and it is still operated in some countries.

Biotechnology of Filamentous Fungi: Technology and Products provides a comprehensive discussion of the molecular biology, genetics, and biochemistry of filamentous fungi. It also deals with general principles of biochemical engineering such as process design and scaleup. The book's main emphasis, however, is on the commercial significance of filamentous fungi. The book highlights the unique aspects of filamentous fungi along with those aspects common to most microorganisms studied in industries that use biotechnology. Filamentous fungi can generate a wide range of industrial products including primary metabolites such as organic acids, secondary metabolites such as ß-lactam antibiotics, nonantibiotic drugs, and enzymes for use in food production. Whole organisms such as mushrooms can be used as well as organisms used as insecticides and herbicides. Filamentous fungi also qualify as potential hosts for the secretion of certain heterogeneous proteins such as mammalian proteins. However, not all things related to fungi are beneficial. Mycotoxins products by fungi can be lethal to humans; there is also a need to develop antifungal agents to destroy fungi that can kill animals and plants. These topics are important aspects of the biotechnology of filamentous fungi and are dealt with in this text.

Allen I. Laskin Biosciences Research Exxon Research and Engineering Company Linden, New Jersey I was contacted in the Fall of 1981 by Professors Martin Dworkin and Palmer Rogers, of the University of Minnesota and asked to participate in the orgnization of the 1983 conference in the series, "Interface Between Biology and Medicine". They and the other members of the advisory committee had the vision to realize that this was a time to depart somewhat from the traditional theme, since one of the major areas of interest in the biological and related sciences these days is that of biotechnology in a broader sense than its impact on medicine alone. In designing the format of the Conference, we considered another factor. There has been a plethora of conferences, symposia, and meetings on biotechnology over the past few years, and the faces and topics have become rather familiar. There has been a strong emphasis on the development of the technology and the "biotechnology industry"; less attention has been paid to the science behind it. One might get the impression from some of these meetings and from the popular press that biotechnology has just recently sprung up, apparently full blown; the very fundamental scientific discoveries and the great body of 1 ALLEN I. LASKIN 2 continuing research that forms that basis for the technology is often obscured.

The Biology of ß-Lactam Antibiotics