Claudio Nicolini - Böcker

This volume represents the fIrst of a series of proceedings of the EL.B.A. Forum on Bioelectronics, a scientifIc discipline at the frontiers of Advanced Electronics and Biotechnology. The name for these forums derives not only from the place (the Isle of Elba in Italy), where the conferences have been held every 6 months since 1991, but also from an acronym: Electronics and Biotechnology Advanced. Bioelectronics is intended as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level" and focuses its attention on three major areas: I New hardware architectures borrowed from the thorough study of brain and sensory systems down to the molecular level, utilizing existing semiconductor inorganic materials (both GaAs and Si) and giga-scale integration; II Protein Engineering, especially of systems involved in electron transfer and molecular recognition, integrated with Metabolism and Chemical Engineering, to develop new biomaterials by learning basic rules of macromolecular folding and self-assembly; m Sensors, thin film and electronic devices utilizing organic compounds and biopolymers, and by implementing nanotechnology bottom up through manufacturing and characterization at the atomic level.

The present volume is a continuation of the EL.B.A. Forum Series, which was initiated in the spring of 1995 with the first volume, entitled From Neural Network and Biomolecular Engineering to Bioelectronics, in which a brief outline of modem bioelectron­ ics given as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level. " The present volume highlights the aspects of advanced biotechnology and electronics originating from molecular manufacturing, which has been emerging as an independent branch of research. This volume appears in a crucial moment, when significant progress has already been made in this strategic field and when technologies derived from it are recognized as critical for the welfare of our society. In addition, acknowledging to the Italian Ministry of University and Scientific and Technological Research for launching the National Research Program "Technologies for Bioelectronics" in 1992 and for continuation of support of this advanced multidisciplinary research, we would like to acknowledge the support of the National Research Council of Italy through the "Molecular Manufacturing" CNR Strategic Project since 1994. The significant unique role of Technobiochip in the organization of the EL.B.A. Forums and in bringing to light the enormous industrial potential of bioelectronics is duly acknowledged, as well as its attraction and support of top level scientists to the series of EL.B.A. Forums of which this volume is part. Dr. Sergey Vakula of the EL.B.A.

Many areas of today's scientific inquiry, as well as many technological developments, depend on the collaboration of physicists, chemists, mathematicians, engineers, biologists, and physicians. This volume demonstrates the value of pooling together the resources of these disciplines and provides a synthesis of theoretical and empirical knowledge, encouraging interaction between traditional "soft" and "hard" sciences.

Since early Greek and Roman times, atoms were assumed-after un­ dergoing their various interactions-to take on the stable configurations of either the living or the inanimate world. This simple and unitary theory has evolved markedly, even while maintaining its validity over several centuries of vicissitudes, and in essence constitutes the first ex­ ample of a synthesis between the physical and the life sciences. In modern times, a similar relationship between the structure of various macromolecules and the function of living cells has also emerged as one of the most striking findings of those scientists active at the con­ vergence of the physical and life sciences. This fundamental result is re­ ported in the first two sections of the present work, namely those on "Oncogenes and Cancer" and "Lower-to-Higher-Order DNA Struc­ ture," in many cases by those recent Nobelists who themselves have been major contributors to work at the intersection of these fields. Many other significant areas of forefront scientific inquiry today (for example, research on the brain and vision), as well as some of the most exciting technological developments (e.g., work on renewable fuels and materials, biotechnology, and NMR and X-ray tomography) and method­ ological advances (e.g., studies in the fields of statistical mechanics and cancer chemotherapy) depend on the complex but harmonious collabora­ tions of physicists, chemists, mathematicians, engineers, biologists, and physicians.

Since the early times of the Greek philosophers Leucippus and Democritus, and later of the Roman philosopher Lucretius, a simple, fundamental idea emerged that brought the life sciences into the realm of the physical sciences. Atoms, after various interactions, were assumed to acquire stable configurations that corresponded either to the living or to the inanimate world. This simple and unitary theory, which has evolved in successive steps to our present time, remarkably maintained its validity despite several centuries of alternative vicissitudes, and is the foundation of modern biophysics. Some of the recent developments of this ancient idea are the discovery of the direct relationship between spatial structures and chemical activity of such molecules as methane and benzene, and the later discovery of the three-dimensional structure of double-helical DNA, and of its relationship with biological activity. The relationship between the structure of various macromolecules and the function of living cells was one of the most striking advancements of modern science, obtained by the cooperation of physicists, chemists, mathematicians, engineers, biologists, and physicians. This crossing of the life and physical sciences has given rise to new and exciting frontiers, and to a new synthesis where there is a frequent interconnection of expertise, and where there is an exchange of roles among traditionally separated soft and hard sciences. Even if knowledge is still transmitted to new generations within univer­ sities as separate disciplines, new knowledge is acquired today in the laboratory by truly interdisciplinary teams.

This volume is the second part of the book on "Chromatin Structure and Function", which resulted from a NATO-Advanced Study Institute held at Erice during April 1978. In addition to giving an updated and detailed description of various levels of chromatin organization, i. e. octamers, nucleosomes, multimers, solenoid and higher order fibers (including the most recent, yet unpublished, findings), it focuses, in a tutorial and organic format, on the possible mechanisms controlling transcription and on the basic biological phenomena (either genetic or epigenetic) related to cell aging, cell cycle, differentiation, transformation and chemical carcinogenesis. The most significant (sometime spirite~ discussion sessions have been included at the end of every section. Their clarifying nature is further supported by the final section (V), which summarizes and reviews the current state of the art on the genetic apparatus and its constituents. All chapters have selected up-to-date references; quite a few have an extensive bibliography both in terms of basic reference books and most recent findings. A few chapters, dealing at the level of intact cell and/or in classical genetic terms, with aging, differentiation and neoplastic transformation, have been included to furnish a more comprehensive view of fundamental cell functions directly and indirectly related to the structure and function of the genetic apparatus. At the same time it is hoped that interested students and investigators will find in the chapters of this volume the necessary and stimulating introduction to the wide variety of fundamental mechanism and phenomena occurring in higher eukaryotes.

During October 18-31, 1980, the first course of the Inter- national School of Pure and Applied Biostructure, a NATO Advanced Study Institute was held at the "Et tore Majorana Center for Scien- tific Culture" in Erice, Sicily, co-sponsored by national and international agencies. The subject of the course was "Cell Growth", with participants (from 16 different countries) selected worldwide. The study of cell growth has been one of humanity's most challenging problems and it has been approached from many differ- ent points of view, such as biochemistry, genetic engineering, cell biology, zoology, oncology, immunology, biophysics and a few other fields. It has been very difficult to keep such varied points of view all in one room and in one audience, because of the heterogeneity of background and inherent difficulty of communica- tion, with occasional nominalistic rather than factual debates.This Institute aimed to bypass those limitations by approaching in a structured and tutorial fashion the problem of cell growth in three dimensions: (1) in terms of the various disciplines involv- ed, from molecular to cellular biology, from genetic engineering to clinical oncology, from biophysics to immunology; (2) in terms of the system studied, from prokaryotes to eukaryotes and cancer cells; (3) in terms of the various levels of macromolecular orga- nization, from membrane to cytoskeleton and chromatin.

During October 18-30, 1981, the second course of the International School of Pure and Applied Biostructure, a NATO Advanced Study Institute, was held at the Ettore Majorana Center for Scientific Culture in Erice, Italy, co-sponsored by the International Union Against Cancer, the Italian League Against Cancer, the Italian Ministry of Public Education, the Italian Ministry of Scientific and Technological Research, the North Atlantic Treaty Organization, the Italian National Research Council, the Sicilian Regional Government and two pharmaceutical Companies (Zambeletti and Farmitalia). The subject of the course was "Chemical Carcino­ genesis" with participants selected world-wide from 18 different countries. It is now eminently clear that.the bulk of human cancers are related to one of several types of environmental exposure. Of the environmental hazards, chemicals are among the best characterized carcinogens. However, how chemicals induce cancer is still poorly understood. Because of the magnitude of the problem and the ob­ vious need for a much more critical scientific analysis of the process by which cancer is induced (carcinogenesis), it was highly desirable to expose a greater number of scientists with varying background to some of the latest thinking in chemical carcino­ genesis. The course had this as its major objective and the re­ sulting book does reflect it.

The Fourth Course of the International School of Pure and Applied Biostructure, a NATO Advanced Study Institute, was held September 18-31, 1983 at the Ettore Majorana Center for Scientific Culture in Erice, Sicily. The subject of the Fourth Course, which was co-sponsored by national and international agencies, was "Structure and Function of the Genetic "Appara­ tus. " Participants from 15 countries around the world attended the course. The study of the genetic apparatus is one of humanity's most challeng­ ing problems, and it has been approached in the tradition of the School from many different points of view, among them biochemistry, genetic eng­ ineering, cell biology, oncology, biophysics and other fields. It has been most difficult to confine such diverse points of view, as well as their pro­ ponents, within the four walls of one room, in front of one audience - es­ pecially since the heterogeneity of background and the inherent difficul­ ties encountered in communication could overshadow the true spirit of sci­ entific exchange. We are once again pleased to say the outcome of the 1983 Course has matched the success of the previous course held in Erice on the same subject five years ago. This book is the result of the 1983 Advanced Study Institute, and aims to present a cohesive, interdisciplinary view of the current knowledge on the structure and fuction of the genetic apparatus.

This NATO Double Jump Program, held at Erice, Italy, on NMR in the Life Sciences was supported in part by contributions from Oxford Research Sys- tems, Philips International, Technicare Corporation, Varian Instruments, Sciemens Medical, and ESA Control. This program brought together three major research activities in biomedical applications of NMR: high resolu- tion NMR studies of proteins and nucleic acids, in vivo studies of animals, and NMR imaging. Whereas in the development of in vivo NMR and NMR imaging the major technological advances came initially from high resolution NMR spectroscopy, this is no longer the situation. The importance of in vivo NMR and NMR imaging in biomedical science and medical diagnosis haS-resulted in an explosion of growth in these areas involving schools of medicine, hos- pitals and instrument manufacturers. Major advances in NMR technology now come from biomedical applications of NMR as well as from high resolution NMR. Applications of high resolution NMR to the solutions structures of pro- teins and nucleic acids have been revolutionized by the development of two dimensional NMR Fourier transform techniques and the techniques of biotech- nology.Now it is possible, with small proteins up to 10,000-12,000 daltons, by 2D FT NMR techniques to follow the path of the polypeptide back- bone through the molecule. The combination of 2D FT NMR techniques with genetically engineered proteins provides one of the most powerful approaches to understanding the principles of protein folding, protein stucture and enzyme catalysis.

Molecular bioelectronics is a field in strong evolution at the frontier of life and materials sciences. The term is utilized in a broad context to emphasize a unique blend of electronics and biotechnology which is seen as the best way to achieve many objectives of industrial and scientific relevance, including biomolecular engineering, bioelectronic devices, materials and sensors capable of optimal hardware efficiency and intelligence and molecular miniaturization.

This volume introduces, in a coherent and comprehensive fashion, the Pan Stanford Series on Nanobiotechnology by defining and reviewing the major sectors of nanobiotechnology and nanobiosciences with respect to the most recent developments. It covers the basic principles and main applications of nanobiotechnology as an emerging field at the frontiers of biotechnology and nanotechnology, with contributions from leading scientists active in their respective specialties.

This volume introduces in a coherent and comprehensive fashion the Pan Stanford Series on Nanobiobiotechnology by defining and reviewing the major sectors of Nanobiotechnology and Nanobiosciences with respect to the most recent developments. Nanobiotechnology indeed appears capable of yielding a scientific and industrial revolution along the routes correctly foreseen by the numerous programs on Nanotechnology launched over the last decade by numerous Councils and Governments worldwide, beginning in the late 1995 by the Science and Technology Council in Italy and by the President Clinton in USA and ending this year with President Putin in Russian Federation.

This book presents an overview of the current state of research in the field of nanotechnologies and biotechnologies for energy, environment, electronics, and health, as emerging from leading laboratories worldwide. It presents and describes in detail the recent research results in the most advanced nanobiotechnology-based methods and their possible applications to energy, environment, electronics, and public health. The methods discussed in the book include anodic porous alumina, nanotubes, conductive polymers, molecular dynamics, innovative software, nanomembranes, lipases, octopus rhodopsin, chromosome translocation, pulsed power, nanotechnology, megatechnologies, mass spectrometry, and protein array. The applications discussed include nanobioelectronics, nanosensors, nanodevices, gas, environment, energy, industrial biofermentation, health, vaccinology, biodiesel production, Earth’s interior, and metals. The book focuses on an array of applications to highlight important aspects of this interdisciplinary approach, underpinning the present challenges and showing the future potential solutions.