To obey the precepts of therapeutic rationality, we should avoid treating the "effect" when there is a way to attack the cause. But what is the cause of diabetes? Diabetes is a molecular disease, that is, a disease in which important cellular components are seriously impaired. Eventually, the activities or the products arising from the impairment find expression in various ways, finally culminating in the abnormalities of diabetes. How early is early enough to attempt to delay this sequence of events? What will provide us with the basis to explore ways and means of halting the progression of the pathological process? What are the new approaches for the treatment of early diabetes? The Fourth International Symposium on Early Diabetes, sponsored by the Diabetes Center of the New York Medical College, held in Algarve, Portugal in November 1978, from which this book evolved, attempted to answer some of these questions. A list of the participants, including their affiliations, will be found preceding the index. Rafael A. Camerini-Davalos v Acknowledgments To our sponsors, U.S.V. Pharmaceutical Corp., Pfizer Pharmaceuticals, Ames Company, Hoechst, Frankfurt; supporters, Boehringer, Manheim, Laboratoires Servier, Nordisk Laboratory, The Upjohn Company, Eli Lilly and Company, F. Hoffman La Roche; and contributors, Bayer A. G. Leverkusen, McNeil, Novo Research Institute, ICI Belgium, Hope for Diabetics Foundation, New York, we express our appreciation for the financial support which made possible the Fourth International Symposium on Early Diabetes. THE ORGANIZING COMMITTEE Rafael A. Camerini-Davalos, M.D.

The subject of this book is neuroendocrinology, that branch of biological science devoted to the interactions between the two major integrative organ systems of animals-the endocrine and nervous systems. Although this science today reflects a fusion of endocrinology and neurobiology, this synthetic ap proach is relatively recent. At the beginning of the 20th century, when the British physiologists, Bayliss and Starling, first proposed endocrinology to be an independent field of inquiry, they went to great lengths to establish the autonomy of chemical secretions in general and their independence from nervous control in particular (Bayliss, W. M. , and Starling, E. H. , 1902, The mechanism of pancreatic secretion,]. Physiol. 28:325). They argued with Pav lov, who said that there was a strong influence of the nervous system on the gastrointestinal phenomena the endocrinologists were studying. For several decades, the English physiologists prevailed, at least in the West; and Pavlov's critique was not taken to heart by the practitioners of the newly emerging discipline of endocrinology. Through the work of Harris, the Scharrers, Sawyer, Everett, and others, there has been something of a scientific detente in the latter half of this century; the hybrid field of neuroendocrinology is now regarded as one of the corner stones of modern neural science and is of fundamental importance in basic and clinical endocrinology.

This has been a year of substantial change for The Year in Endocrinology. The first change, though perhaps only a semantic one, nevertheless represents a landmark. Although last year's volume was designated as the first of an annual series, that seemed to me at the time merely a hope-a realistic hope, perhaps, but a hope, nevertheless. With the publication of this year's volume, however, this can accurately be said to be an annual series, one that we trust will fulfill a need and will therefore continue for years to come. Among other changes from last year's volume are some that were originally intended and others that were unintended. In the former category is the substitution of a chapter on water metabolism and vaso pressin, excellently prepared by Dr. Gary L. Robertson, for the chapter on paraendocrine syndromes that appeared last year. Chapters on these two topics will continue to appear on alternate years. Obviously, the non recurring chapter on a topic of special interest has also changed, and this year's comprises a comprehensive review of autoimmune endocrine dis ease by Drs. Jay Silverberg and Robert Volpe. The unexpected change results from the inability of Dr. Louis Avioli to continue as a member of the Editorial Board. Most fortunately, however, we have persuaded Dr. Charles R. Kleeman to join the Board and to be responsible for the chapter on the parathyroid gland and mineral metabolism. Dr. Kleeman has been assisted on the preparation of this chapter by his daughter, Dr."

The German land of Hesse (Bundesland Hessen) is well known for its excellent wines (Rheinhessen), for its financial centre and for its airport (FrankfurtlMain). It is, unjustifiably, far less well known for its importance to thennoregulation. Within the small area of Bad Nauheim, Giessen and Marburg (in alphabetical order) a greater concentration of students of thenno regulation has been trained or worked or is working than probably in any other single area of Europe, if not the world. It is thus most appropriate to hold the Ninth International Symposium on the Pharmacology of Thennoregulation in Giessen, from August 7 to 12, 1994. The community of students of thennoregulation was extremely grateful that Professor Kurt Bruck and the lustus-Liebig-University of Giessen had extended this invitation. The same community was even more saddened that Kurt Bruck died on April 27, 1992 and thus could not participate in this event that had been planned to honour his achievements. As a small token of friendship and affection, the many friends of Kurt Bruck from all over the world who will participate in this event dedicate this symposium to the memory of Kurt Bruck. Another staunch friend, researcher of temperature regulation and supporter of this series of symposia died in October 1993: Professor Wilhelm Siegmund Feldberg. We feel fortunate to be able to start this volume with two brief infonnal and personal accounts of professors Bruck and Feldberg."

Physical activity exerts an important influence on the endocrine system, modulating synthesis and secretion of several hormones. Almost every organ and system in the body is affected by physical activity and exercise, mainly through the endocrine and neuroendocrine system. Mode, intensity, and duration of the exercise bout, age, gender and fitness level of the individual as well as environmental and psychological factors may affect the endocrine response to physical activity.

On the other hand, several hormones are able to influence physical performance and body composition. Thus, a bi-univocal interrelationship between exercise and hormones exists.

In this book new developments on metabolic and endocrine response to exercise are revised and introduce the "hot topic" of hormonal doping in sports. In the past decades, hormone abuse has become a widespread habit among professional and most of all and more frequently recreational athletes. A substantial part of this volume is devoted to the effects of exogenous hormones on performance. Anabolic steroids, growth hormone and erythropoietin properties, use and misuse in sports are widely described. Specific methods to detect hormone abuse are presented and discussed.

The contributors to this volume are well-known experts and dedicated researchers in the fields of sports medicine and endocrinology, endocrine physiology, pharmacology, and doping detection.

The purpose of this volume is to provide all professionals involved in sports medicine and endocrinology a state-of-the-art overview of the complex interactions between physical activity and the endocrine system and to focus on hormone abuse in sports at competitive and recreational level highlighting its negative consequences for long-term health."

From our current knowledge, it is obvious that estrogen action in volves more than reproduction and fertility. Rather, estrogens affect and influence a number of other organ systems such as the immune, cardiovascular and central nervous system as well as the gastrointes tinal tract, urinary tract and skeleton. The importance of estrogens and estrogen receptor activity is appreciated from the spectrum of significant physiological dysfunctions that occur when there is a loss The participants of the workshop VI Preface of the hormone or the receptor activity. Loss of estrogen, however (for instance during menopause), occurs with time and results in a variety of clinical conditions. We know that the developmental loss of estrogen, as seen in clinical cases of aromatase gene mutations and experimental models, has dramatic effects in both men and women alike. The evidence that these effects are mediated through the estrogen receptor(s) is based on similar but not always identical phenotypes as observed in experimental animal models of estrogen receptor mutations as well as the single clinical case of an estrogen receptor alpha mutant patient. Developing an understanding of the spectrum of estrogen in a variety of tissues related to the condition of estrogen loss is a major and highly active clinical as well as basic scientific research area. Following the discovery of a second estrogen receptor and possible receptor ligand-independent activity as well as the genomic and non genomic actions of estrogen, it is clear that the mechanisms of the effects of estrogen are multifaceted.

The Hypothalamus is an important area of the brain for understanding a variety of neurological disorders. This volume summarizes for readers the anatomy and physiology of the middle and posterior hypothalamus, to better understand pathology and treatment of hypothalamus related disorders. In addition to anatomy and physiology in humans, cytoarchitecture and chemoarchitecture in rodents is provided. The volume explores the role of the hypothalamus in disorders of eating, sleeping, anxiety, and mood, as well as its role in sexual behavior and gender identity. Coverage includes how Parkinson's, Alzheimer's and other neurological disorders relate to the hypothalamus.

Cell biology has made an appreciable impact on the evaluation of physiological and pathophysiological processes leading to a more detailed understanding of the signaling mechanisms by which cells communicate in vivo and in vitro and modify adaptively. By using cell culture models in addition to animal experiments we are now able to better define the overall and the selective potential of drugs. This book is designed to give information on the advantages and limitations and on new aspects and the meaning of cell culture models in pharmaceutical research.

The Center for Population Research of the National Institute of Child Health and Human Development began operations in August 1968 and is engaged in research dealing with health-related popula tion problems. We organize and support projects for the develop ment of new contraceptives and in the broad field of population research in the social sciences o The Center also supports a variety of projects dealing with the mechanism of action and medical effects of contraceptives now in use, particularly oral contraceptives and intrauterine devices. These studies were initiated several years ago at the specific direction of Congresso We were pleased, therefore, with the opportunity to help organize and support this important and timely conference on the "Metabolic Effects of Gonadal Hormones and Contraceptive Steroids," the subject of which forms an integral part of the Center's research program. April, 1969 Philip Ao Corfman Director Center for Population Research National Institute of Child Health and Human Development v PREFACE Progress in science is often associated with either a "sixth sense" or an inevitable timeliness. Both factors, perhaps, led the members of the Endocrinology Study Section of the National Institutes of Health to propose, in 1966, that an expanded view of the effects of gonadal hormones, in general, and the contra ceptive steroids, in particular. was needed. There had been ample evaluations of the clinical symptomatology, contraceptive efficacy, and effects on the reproductive system, but there was a dearth of information on their multiple systemic'metabolic effects."

In the summer of 1969, the first Workshop on Control of Renin Secretion was held at Stanford University. At its completion, it was suggested by many of those who attended that a second Workshop be planned in about two years time. Thus the second Workshop on Control of Renin Secretion took place and from this event the chapters in this book had their origin. The setting of this Work shop was the beautiful J & R Double Arch Ranch in Santa Ynez, California which houses the Kroc Foundation. The Foundation, through the kindness of its President, Dr. Robert L. Kroc, provided us with luxurious accommodations, excellent meeting facilities and an atmosphere extremely conducive to the exchange of scientific knowledge, both formally and informally. In addition, the Founda tion assisted financially in the travel expenses of three of our foreign guests and in the preparation of the manuscripts for this book. I know I speak for all of us who attended the Workshop in expressing our sincere gratitude to the Foundation and to Dr. and Mrs. Kroc and their staff. In addition, I personally, as organizer of the meeting and editor, wish to acknowledge the help of many others who made my job much easier. Drs. Davis, Ganong, Luetscher and Tobian kindly took on the jobs of chairing the four sessions and directing the lively discussions which followed each presentation."

Perinatal problems in thyroid gland physiology are common but complicated and present a diagnostic dilemma for the primary clinician. In December 1990, an international group of basic and clinical investigators gathered in Longboat Key, Florida to address these issues. The participants included internists, obstetricians, pedia tricians, neurologists, pathologists and basic scientists in cellular metabolism, endocrine physiology, and molecular biology. The presentations contained within this book bring together their most current and vital research related to the field of perinatal thyroidology. This book is based on the dynamic and fruitful exchange of the participants at the symposium. We are indebted to these individuals whose valuable insights and efforts are contained within this text. Barry B. Bercu Dorothy I. Shulman vii CONTENTS Session I Mechanism of Thyroid Hormone Action 1 Leslie J. DeGroot Thyroid System Ontogeny in the Sheep: A Model for Precocial Mammalian Species * . . * * 11 Delbert A. Fisher Pathologic Studies of Fetal Thyroid 27 Development * * * * * * * Douglas R. Shanklin Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, 47 and Behavioral Studies * * * * * * * S. A. Stein, P. M. Adams, D. R. Shanklin, G. A. Mihailoff, and M. B. Palnitkar The Thyroidectomized Pregnant Rat: An Animal Model to Study Fetal Effects of Maternal Hypothyroidism 107 Susan P. Porterfield and Chester E.

This volume describes the proceedings of the Workshop Conference on The Human Testis which was held at Positano, Italy, April 23-25, 1970. The format of the book has been arranged according to topics discussed during the Conference. Each chapter includes individual contributions followed by discussion. Thus, this volume provides a current critical evaluation of the subjects discussed. The Editors assume responsibility for any shortcomings and wish to thank all par~ ticipants for their unprecedented cooperation in making this publi cation possible. The Editors are indebted to Miss Barbara Martin for her able secretarial and administrative assistance and to Mrs. Griff T. Ross who supervised the secretarial staff during the conference. Rec ognition is also due to Mrs. M. Flack for editorial assistance. The Workshop Conference could not have taken place but for the Serono Foundation, which supported this Meeting as well as the pub lication of the Proceedings of this Workshop. The physical as well as the technical arrangements were under the careful direction of Mr. Cesare Florimonte of the Serono Foundation. The support pro vided by the Serono Foundation is another proof of its generosity in stimulating scientific exchanges and a demonstration of its con tinuous efforts to support basic and applied studies in the field of human reproduction. We express our thanks to our Publisher, Plenum Press, for their fine cooperation and for ensuring the rapid publication of this vol ume.

This volume is an outgrowth of a symposium held at the University of Michigan, Ann Arbor, Michigan, October 27-29, 1975. This symposium was organized to bring together basic scientists and clinicians for the purpose of exchanging new ideas and the latest information in the area of Steroid Hormone Action and Cancer. The design of the symposium included both formal plenary sessions and informal roundtable discussion groups, the chapters of this volume being drawn primarily from these proceedings. During the last quarter of a century considerable progress has been made toward understanding the molecular mechanisms in volved in steroid hormone action. It now appears that the mechan sim of action of the four major classes of steroid hormones is qualitatively similar. Research during the past decade has demonstrated steroid hormone receptors in a variety of normal and neoplastic tissues. Receptor-containing neoplasms have been shown to be hormone-dependent and undergo regression when treated with hormone antagonists. Natural and synthetic steroids also have been employed for many years to successfully treat various types of cancer, for example: estrogens, androgens and progestagens for breast cancer; estrogens and progestagens for prostatic carcinoma; progestagens for endometrial carcinoma; and corticoids for leu kemias. All of these neoplasms have now been found to possess receptors for the steroids empirically used in their treatment."

This fifth edition of Autonomic Failure covers the many recent advances made in our understanding of the autonomic nervous system. There are numerous new chapters and extensive revisions of all other contributions. This book makes diagnosis increasingly precise by fully evaluating the underlying anatomical and functional deficits, thereby allowing more effective treatment. This new edition continues to provide a rational guide to aid in the recognition and management of autonomic disorders for practitioners from a variety of fields, including neurology, cardiology, geriatric medicine, diabetology and internal medicine.

As humans ventured into the twentieth century, the industrialized countries were confronted with the scourge of rickets. Although solariums were becoming common in the early 1900s and phototherapy was gaining popularity as a result of the awarding of a Nobel Prize to Finsen in 1903, it wasn't until 1921 when Hess and Unger demonstrated that rickets could be cured by exposure to sunlight that the healthful benefit of sun exposure appreciated. In 1941, Apperly (Cancer Research; 1: 191-195, 1941) noted that the occasional increased risk of skin cancer was associated with a decreased risk of many other more common and serious cancers. The alarming increase in the number of cases of skin cancer, especially melanoma, has caused great concern about the negative role of sunlight in health. The Sixth International Arnold Rikli Symposium on the Biologic Effects of Light was held in Boston, Massachusetts from June 16th - 18th, 2001. The goal of this Symposium was to focus on the very popular practice of tanning either by sunlight or by artificial light sources and the overall impact this practice has on health and disease. The program was organized by members of the Scientific Advisory Committee and my co-chair emeritus, Professor Ernst G. Jung. The Program Committee organized an outstanding state-of-the-art program that was enthusiastically received by the participants.

Evidence accumulated over the past decade show that gonadal steroid hormones participate in an important way in the physiological and pa thophysiological regulation of the cardiovascular system. The hor monal profile appears to put males at a disadvantage biologically in terms of cardiovascular diseases. The incidence of hypertension is higher in men than in pre-monopausal women indicating an influence of gender on the hypertensive disease process. Males and females have equivalent cholesterol levels until puberty but males suffer an ex ponential increase in heart disease in their forties, while the female rise does not start until a decade later, after menopause. Animal and human studies provided ample evidence, that estrogens lower the levels of low density lipoproteins and keep high density lipoproteins elevated. These changes may be advantageous in the prevention of heart diesease. Co ronary artery atherosclerosis has been shown to be more pronounced in ovarectomized female monkeys as in intact females. Androgen, con versely, lowers the high density lipoproteins and elevates low density lipoproteins. Regarding blood pressure, it is well established that hypertension is more severe or develops more rapidly in male than fe male rats in several genetic forms of hypertension, and that gonadal steroid hormones are probably playing an important role in explaining this observation. Risk factors of human hypertension and coronary heart dies ease include menopause and ovarectomy."

Endocrinology of Cardiovascular Function is a fitting inauguration to the Endocrine Update Series. The aim of these publications is to provide the clinician with cutting edge, yet succinct, access to the latest advances in endocrinology. Historically, our understanding of hormonal disturbances was restricted to the classical secretory glands and their targets. As Endocrinology of Cardiovascular Function so aptly indicates, endocrinology is no longer constrained by our early physiologic understanding of glandular disorder. Endocrinology of Cardiovascular Function has set the standard of excellence for the future volumes in this series. Shlomo Melmed, M.D. Series Editor, Endocrine Update Growth factors such as IGF-1 play important roles in cardiovascular cell hypertrophy and the response to acute vascular injury. From another perspective, traditional endocrine hormones, such as estrogen, have been found to participate in preventing the development of atherosclerosis in women, acting through novel mechanisms on target vascular cells. Other `endocrine' hormones, such as PTHRP and adrenomedullin, also modulate cardiovascular and renovascular dynamic states, suggesting new roles for these peptides as vasodilators. This multi-authored text is dedicated to highlighting emerging and important new information regarding the endocrinology of the cardiovascular system. Ellis R. Levin, M.D.

Amenorrhea: A Case-Based Clinical Guide is a comprehensive review of the current knowledge regarding normal female reproductive physiology. Replete with interesting case vignettes and providing diagnostic algorithms and therapeutic strategies for amenorrhea, Amenorrhea: A Case-Based Clinical Guide is divided into three sections. The first section is composed of two chapters that provide a thorough review of basic science and clinical knowledge about the organ systems responsible for normal physiology of the menstrual cycle. The second section includes discussion about menstrual cycle disruption as it relates to hypothalamic-pituitary dysfunction, surgical and natural menopause, genetic defects, premature ovarian failure/insufficiency and the effects of caloric excess and restriction. The third section offers an update on the physiological effects of prolonged amenorrhea induced surgically or by hypothalamic dysfunction and also includes an original chapter that focuses solely on the impact of race and ethnicity on the prevalence and diagnosis of amenorrhea. Amenorrhea: A Case-Based Clinical Guide brings together chapters from renowned experts who offer state-of-the-art, clinically useful information in a case-based, reader-friendly fashion. This title will be a welcome addition to the bookshelves of all clinicians who practice in women's health settings.

The human pancreas consists of two organs in one: the exocrine gland made up of pancreatic acinar cells and duct cells that produce digestive enzymes and sodium bicarbonate, respectively; the endocrine gland made up of four islet cells, namely alpha-, beta-, delta- and PP-cells that produce glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. While the physiological role of exocrine p- creas is to secrete digestive enzyme responsible for our normal digestion, absorption and assimilation of nutrients, the endocrine pancreas is to secrete islet peptide h- mones maintaining our glucose homeostasis. The pancreatic functions are nely regulated by neurocrine, endocrine, paracrine and/or intracrine mechanisms. Thus, dysregulation of these pathways should have signi cant impacts on our health and disease. Nevertheless, the underlying mechanisms by which pancreatic functions are regulated remain poorly understood. Recent basic science and clinical studies con rm myriad physiological and pathophysiological roles of the tissue renin-angiotensin systems (RAS). Of parti- lar interest is the recent identi cation of a local and functional RAS in the pancreas, which in uences both its exocrine and endocrine function. Its role in the pat- genesis of pancreatic diseases including diabetes and pancreatitis is increasingly recognized, as is the therapeutic potential of RAS antagonism: RAS blockade l- its disease progression of type 2 diabetes mellitus and impaired glucose tolerance, and may also protect against pancreatic in ammation.

This book includes the most significant contributions of the 3rd International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE held in Florence, Italy, July 6-9, 1994. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological evidence that individuals from industrialized countries often possess two or more risk factors which synergistically increase the global risk profile. This has become more evident in recent years with the increase in life expectancy of the general population. The evidence that in high risk patients, a combination of risk factors often is detected, is highlighted in these Proceedings. Many recent epidemiological data identifYing the intrinsic and environmental factors contributing to the development of atherosclerosis are discussed. These results, in parallel with basic and clinical research, underline how atherosclerosis is a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure, rheologic forces, carbohydrate tolerance, and thrombogenic factors. Furthermore, the risk associated with anyone of these risk factors varies widely depending on level of the associated atherogenic risk factors.

A panel of expert clinical and basic investigators summarize the state-of-the-art in the use of transgenic technology in a broad range of endocrinological applications. Up-to-date and comprehensive, Transgenics in Endocrinology reviews the most recent developments in the analysis of endocrine physiology and its pathologies through mouse models, and provides a host of creative approaches to understand better the complex processes that are characteristic of hormonal systems.

Leading researchers comprehensively translate all the latest scientific information regarding endocrine physiology and development into an understanding of the clinical pathogenesis, diagnosis, and treatment of endocrine disease. Organized by endocrine system, each section of the book concisely describes the chronological development of the human organism, from the fetal/prenatal period through childhood, adolescence, and in some cases, into adulthood. The prenatal sections review recent discoveries concerning transcription factors, homeobox genes, and human molecular mutations-the basic processes governing prenatal development of the individual endocrine organs-and detail the pathophysiology, clinical characteristics, and treatment of pediatric endocrine disorders.

Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.

THIS BOOK collects together papers given at a NATO Advanced Research Workshop held at Il Ciocco (Lucca), Italy, from the 9th to the 15th April, 1989. It sets out to present the current state of understanding of the principles governing the way fluxes and concentrations are maintained and controlled in metabolic systems. Although this is a topic that has held the interest of biochemists for many years, it is only quite recently that the methods of analysing the kinetics of multi-enzyme pathways developed over the past two decades have come to be widely discussed or applied experimentally. Many biochemists remain sceptical that the new methods offer a real advance (except in complexity) over the landmark discoveries of the 1950s and 1960s relating to inhibition of enzymes at branch-points by the end products of metabolic pathways, and the interpretation of allosteric effects and cooperativity. Even those who have become convinced that the classical ideas provide only the starting point for understanding metabolic control have been by no means unanimous in their assess ment of the direction in which one should advance. In this book we have tried to include all of the current points of view, including the view that the classical theories tell us all that we need to know. We have not seen it as our role as editors to paper over the cracks that exist and to pretend that we can speak to the world with one voice."

The eleventh monograph and meeting of the Foundation on "Hormon al Control of the Hypothalamo-Pituitary-Gonadal Axis" was held in October 1983 at the Weizmann Institute of Science. This monograph honors the memory of Professor Hans R. Lindner, a productive and innovative scientist greatly respected and admired by his col leagues. When addressing the opening session I remarked that my impres sion of the Weizmann Institute was one or two large buildings hous ing the various departments. This was my first visit to Israel and I was overwhelmed by the beautiful semi-tropical gardens of the in stitute, in a setting of shrubs and trees, orange groves and flow ers. Sited among this seventy-five acres are over fifty buildings and residential areas for the staff and visiting scientists. I saw pictures of this area when Dr. Chaim Weizmann founded in 1934, the Daniel Sieff Research Institute, the forerunner of the Weizmann In stitute. The site was sand dunes without a blade of grass. That the desert shall bloom is illustrative of the progress made in Is rael. The topics of the monograph are grouped into twelve sections.