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Life Science

 

Review Essays of Academic, Professional & Technical Books in the Humanities & Sciences

 

Biotechnology Research in an Age of Terrorism: Confronting the "Fual Use" Dilemma (National Academy Press) The fact that the anthrax used in the October 2001 terrorist attacks in the United States was genetically identical to that developed by the U.S. government is evidence that almost all biotechnology can be subverted for hostile use. This report by the National Research Council considers ways to balance national security and scientific openness in the development of biotechnologies. The report reviews current rules and regulations related to oversight of dangerous pathogens and potentially dangerous research in the U.S., assesses their efficacy, and recommends changes. The authors propose a system for research oversight based on the earlier National Institutes of Health Guidelines for Research Involving rDNA Molecules. 

This report reflects the increasing attention being paid by scientists and policymakers to the potential for misuse of biotechnology by hostile individuals or nations and to the policy proposals that could be applied to minimize or mitigate those threats. The term "misuse of biotechnology" is a phrase that captures a wide spectrum of potentially dangerous activities from spreading common pathogens (e.g., spraying Salmonella on salad bars) to sci-fi plots of transforming pathogens into the next "Andromeda strain." The Committee addressed one important part of this spectrum of risks: the capacity for advanced biological research activities to cause disruption or harm, potentially on a catastrophic scale. Broadly stated, that capacity consists of two elements: (1) the risk that dangerous agents that are the subject of research will be stolen or diverted for malevolent purposes; and (2) the risk that the research results, knowledge, or techniques could facilitate the creation of "novel" pathogens with unique properties or create entirely new classes of threat agents.

Throughout the Committee's deliberations there was a concern that policies to counter biological threats should not be so broad as to impinge upon the ability of the life sciences community to continue its role of contributing to the betterment of life and improving defenses against biological threats. Caution must be exercised in adopting policy measures to respond to this threat so that the intended ends will be achieved without creating "unintended consequences." On the other hand, the potential threat from the misuse of current and future biological research is a challenge to which policymakers and the scientific community must respond. The system proposed in this report is intended as a first step in what will be a long and continuously evolving process to maintain an optimal balance of risks and rewards. The Committee believes that building upon processes that are already known and trusted and relying on the capacity of life scientists to develop appropriate mechanisms for self-governance, while greatly expanding the consultation and dialogue between the science and national security communities, offers the greatest potential to find the right balance. This system may provide a model for the development of policies in other countries. Only a system of international guidelines and review will ultimately minimize the potential for the misuse of biotechnology. 

Biomedia by Eugene Thacker (Electronic Mediations, V. 11: University of Minnesota Press) As biotechnology defines the new millennium, genetic codes and computer codes increasingly merge—life understood as data, flesh rendered programmable. Where this trend will take us, and what it might mean, is what concerns Eugene Thacker in this timely book, a penetrating look into the intersection of molecular biology and computer science in our day and its likely ramifications for the future.

Integrating approaches from science and media studies, Biomedia is a critical analysis of research fields that explore relationships between biologies and technologies, between genetic and computer "codes." In doing so, the book looks beyond the familiar examples of cloning, genetic engineering, and gene therapy—fields based on the centrality of DNA or genes—to emerging fields in which "life" is often understood as "information." Focusing especially on interactions between genetic and computer codes, or between "life" and "information," Thacker shows how each kind of "body" produced—from biochip to DNA computer—demonstrates how molecular biology and computer science are interwoven to provide unique means of understanding and controlling living matter.

Throughout, Thacker provides in-depth accounts of theoretical issues implicit in biotechnical artifacts—issues that arise in the fields of bioinformatics, proteomics, systems biology, and biocomputing. Research in biotechnology, Biomedia suggests, flouts our assumptions about the division between biological and technological systems. New ways of thinking about this division are needed if we are to understand the cultural, social, and philosophical dimensions of such research, and this book marks a significant advance in the coming intellectual revolution.

At this point, it will be useful to consider some of the basic assumptions in bio­media, as it is manifested in biotech research fields such as genomics, bioinformatics, proteomics, and medical genetics.

There is, in biomedia, a general devaluation of material substrates (the materiality of the medium) as being constitutive of patterns of relationships (or essential data). Although biomedia do take into account the role of material substrates, they exist, as we have seen, in the backdrop, as support for "what the body can do" (or, more accu­rately, what patterns of relationships can do). Again, biomedia generally and biotech­nology specifically are not dematerializing technologies, at least in the posthumanist or Extropian senses of the term. Biomedia is constantly working toward the body, always coming around via a spiral, and enframing this movement as a return to the body. The difference within this spiral movement, the difference that makes it a spiral and not a loop, is the tension between abstract essential data (patterns of relation-ships) and the media (material substrate) in which that data inheres. However, as we have seen in the examples of bioinformatics, biocomputing, microarrays, protein pre-diction, and rational drug design, the materiality of the medium literally matters, a difference that makes a difference. Biomedia is not only predicated on the ability to separate patterns of relationships from material substrates, but, in never completely doing away with the material orders, it often relegates the constitutive qualities of ma­terial substrates to the role of delivery, of a vehicle for data, of transparent mediation.

Biomedia is defined as neither a technological instrument nor an essence of technology, but a phenomenon in which a technical recontextualization of biological components and processes enables the biomolecular body to demonstrate itself, in applications that may be biological or nonbiological. In its informatic proto­col of encoding, recoding, and decoding, biomedia bears within itself a fundamental tension. On the one hand, there is the ability to isolate and abstract certain types of essential data, or patterns of relationships, which are independent of and mobile across varying media, or material substrates. On the other hand, something is implicitly added through these varying media, such that the essential data never remains com­pletely untouched, but is itself becoming infused and in-formed by the integration with the medium. This is further complicated by the fact that, with biomedia, the aim or application is not to move beyond the material substrate, but to constantly appear to return to it, in a self-fulfilling, technical optimization of the biological, such that the biological will continue to remain biological (and not "technological").

As contemporary biotechnology research pursues the integration of bio-science and computer science, it might be worth continuing to think through the philosophical-technical implications that arise from the biomedia that are generated (such as protein prediction software and DNA computers).

The gap between emerging biotechnolo­gies and the bioethical discourses that attempt to address their impact—seems to be a clear sign that alternative ways of viewing the body, biological life, and the relation-ship between human subjects and technologies are needed. This book is an attempt to address this gap, through a focus on the philosophical-technical aspects of emerging fields in biotechnology. Although this does not imply that the analyses are without any relation to cultural and political aspects of biotech, what has been foregrounded here are the ways in which our varying notions of "the human," biological "life," and the boundary between the body and technology are being transformed within biotech re-search. It should be stressed that this study is not explicitly a critique of globalization, capital, and biotech; other individuals and groups are approaching this issue in sophisti­cated and politically engaged ways. Nor is it concerned with the broader dissemina­tion of biotechnology as a "cultural icon," for instance, in popular culture, mainstream media, or in instances of the everyday. It is, however, an inquiry into the difficult questions that biotech inadvertently puts forth in its techniques, technologies, and concepts, and in this sense the main methodological focus here is simultaneously philo­sophical and technical.

In this concern, the individual essays intentionally take up "emerging" research fields as case studies—bioinformatics, biocomputing, MEMS (microelectromechanical sys­tems) research, nanomedicine, and systems biology. These are fields that may be inter-disciplinary, involved in research that is as much theoretical as empirical, and that, in some cases, have no definite area of projected application. They are also situated as "future sciences" or "fiction sciences" through their rhetoric (e.g., articles in magazines such as the MIT Technology Review and Wired), and as components of a biotech industry (start-up companies, new job markets, new degree programs). The primary reason for considering such fields is to ask how these questions concerning the body, biological life, and the body–technology boundary are addressed and resolved in explicitly technical ways.

The focus on these fiction sciences is also not without a strong link to science fiction (or, SF). Certainly, the implication is not that science is "fictional," if by this we mean nonexistent, ineffectual, or a pure construction of cultural, social, or economic forces. However, as emerging fields, such areas as biocomputing and nanomedicine do partic­ipate in a particular type of discourse, a talking and doing, in which projected applica­tions, development in knowledge, and relationship to other disciplines and industries are all employed in a speculative fashion. Any field, in attempting to distinguish itself

as a field, will by necessity look around itself, to state what it is not, or which fields it combines in an interdisciplinary manner. Involved in this gesture is a speculation of what the field could be, in the same way that it is standard for research articles to specu­late, in either their opening or closing remarks, the future directions and significance of their empirical data. For this reason, each chapter begins with an anecdote from selected works of contemporary science fiction. The goal of this is not to derealize technoscientific practice, but in fact to render it all the more "real."

The informatic protocols of encoding are the focus of chapters 3 (on biochips) and 4 (on biocomputing). Both biochips, such as DNA microarrays, and biocomputers, such as DNA computers, involve the construction of literal hybrids between living and nonliving components and processes. Both are also examples of encoding practices, which highlight patterns of relationships and transport them into novel contexts. How-ever, their overall aims are significantly different, roughly being divided between med­ical and computational application.

Likewise, the practices of recoding are foregrounded in chapter 2, which deals with bioinformatics, as well as chapter 6, which examines alternative approaches in biotech research broadly known as "systems biology." The central question in these examina­tions of encoding is whether systems-based approaches (focusing on "biopathways" and studies of "systemic perturbations") might transform the very assumptions in biomedia's informatic protocol—the notion of equivalency between genetic and com­puter codes.

Finally, the practices of decoding are the focus of chapter 5, on nanotechnology and nanomedicine. Whereas a number of these biotechnology fields reconfigure the relationships between bodies and technologies, nanotech has for some time implied that, at the atomic level of matter, the distinction is itself irrelevant. Specialized med­ical applications in nanotech research are materializing such claims, in the design of in vivo biosensors and nano-scale devices for medical diagnostics. As a practice of de-coding, nanomedicine demonstrates how patterns of relationships and material sub­strates are one and the same.

This study closes with a final chapter on the relations between notions of "design" and bioethical issues raised by biotechnologies. However, bioethics in this sense is taken to be a practice fundamental to research in progress and research as process, rather than post hoc responses to finished research. This chapter examines the ways in which the question of design suddenly takes on contentious moral and ethical reso­nances when design is imbricated in the biological domain, and especially the human body. The questions we close with have to do with the possibility for a technically sophisticated "actant bioethics" that places as much emphasis on the "affect" of design as it does on the design of embodied practice, or "enaction."

Finally, it should be stated that two general, open-ended, "impossible" questions run throughout this study:

First, what is "biomolecular affect"? We are used to thinking of affect and phenom­enological experience generally in anthropomorphic terms. Is there a phenomenology of molecular biology? Are there zones of affect specific to the molecular domain and irreducible to "molar" aggregations or anthropomorphisms? What would such an analy­sis say concerning our common notions of embodied subjectivity?

Second, is the body a network? Although work in immunology and certainly neu­rology has answered this in the affirmative, the work from molecular genetics is more ambivalent. Is the biomolecular body a distributed relation? If so, what does this say concerning more traditional, centralized notions of consciousness, "mind," and the normative anatomical-medical enframing of the body?

Whereas the Extropian and posthumanist dreams of "uploading" continue a move away from the body and embodiment, there is, perhaps, another type of posthuman, even inhuman, body within these two questions.

Applying Genomic and Proteomic Microarray Technology in Drug Discovery by Robert S. Matson (CRC Press) Microarray technology, more commonly known as small spots, has proved a success when employed in DNA array-based genomic analysis. It is now beginning to be employed in protein tissue array analysis; and as microarray continues to be adopted it is important that researchers grasp the fundamental principles behind it, as well as, the strengths and limitations. This highly informative book written by an leader in the field introduces the fundamentals of microarray technology, it then goes on to describe and evaluate the use of microarray technology in genomic and proteomic applications, and provide practical tips on how to employ the technology in drug discovery and development.

This book details the commercial array landscape, covering the many issues surrounding the future adoption of gene expression and protein microarrays for pharmacogenomic and pharmacoproteomic applications. The author critically assesses those studies that have helped define applications in genomics and proteomics, explains gene expression microarray applications, and examines the utility of the protein microarray.

An understanding of the process used in making microarrays is fundamentally important to those interested in producing "spotted" arrays and using them properly. As this technology expands in popularity and application, industry experts must grasp the fundamental principles behind it, its strengths, and its limitations. A basic reference on the benefits of microarray technology in drug discovery, this publication offers a detailed perspective and insight into the present and future uses of this technology.

Features

Includes an extensive literature survey and comparison of microarray technology formats

Discusses the relevance and general utility of microarray technologies in the drug discovery process

Provides an in-depth discussion of important factors for successful array printing Contains protocols for printing nucleic acids and proteins and a selection of substrates and preparation of surface chemistries

Supplies an extensive review and assessment of key studies demonstrating the utility of gene expression and protein microarrays

Array technology, much like polymerase chain reaction (PCR) technique, was created to satisfy an existing need in molecular biology. PCR provided a means to amplify enough DNA to sequence genes. The first applications for arrays involved gene sequencing by hybridization (SBH) and genotyping. However, gel-based sequencing quickly supplanted the emerging SBH approach, while genotyping and mutation analysis have been slow in development. The challenge for those involved in array technology then became finding that elusive application niche, one that would demonstrate a clear, unmitigated, and thereby sustained need for the technology.

This book picks up the array technology journey from the mid-1990s with the introduction of microarray-based gene expression analysis. The global analysis of genes by microarrays has provided a fresh and exciting view of the cellular process. More importantly, it enabled others to consider similar utility in various "omic" fields. Hence, we have witnessed the emergence of protein arrays to address proteomics.

In writing this book, my aim was first to provide a detailed description and offer insight into present and future utilities for microarray technology. While arguably array-based technologies are now being adopted in diverse fields, I have placed emphasis on applications related to drug discovery. Microarrays continue to play significant and increasingly important roles in the drug discovery process.

Chapter 1 considers the respective roles as well as the many issues surrounding the future adoption of gene expression and protein microarrays for pharmacogenomic and pharmacoproteomic applications. For acceptance by the pharmaceutical and diagnostic industries, commercially validated array technology is required. Chapter 2 details the commercial microarray landscape. Chapter 3 describes alternative substrates and the preparation of various surface chemistries along with their suitability for immobilization of nucleic acids and proteins. In Chapter 4, the mechanics of microarraying are described in detail including environmental conditions, printer and pin performance, and instructions for setting up a print run. Protocols for printing nucleic acids and proteins are provided along with in-depth discussion of other important parameters such as print buffers (inks) and factors influencing print quality. I also set out to discuss the importance and provide a critical assessment of studies that helped to define applications in genomics and proteomics. In Chapter 5, gene expression microarray applications are described; Chapter 6 examines the utility of protein microarrays.

Finally, an understanding of the making of a microarray is fundamentally important to those interested in producing "spotted" arrays and properly using them. While complementary (cDNA) microarray fabrication on glass slides has been well studied, we have less experience with the attachment of oligonucleotides and the preparation of protein arrays. Moreover, additional substrates and surface chemistries that may be better suited for printing proteins are now available.

Robert (Bob) Matson, Ph.D., is a senior staff scientist in the Advanced Technology Center at Beckman Coulter, Inc., Fullerton, California. He has been involved in the development of both nucleic acid and protein array-based technology for the past 13 years. His initial introduction to array technology began in collaboration with Sir Edwin Southern in developing an in situ oligonucleotide array synthesis platform for the corporation. Later work by Dr. Matson and his research team produced some of the

first plastic microplate-based microarrays. Beckman Coulter recently launched the A2TM plate based upon the microplate "array of arrays" concept.

Prior to joining Beckman Coulter, he served in several technical management roles including: R&D director at BioProbe International, R&D director at Costar-Nuclepore, and R&D group leader, chemistry, at BioRad Lab-oratories.

Dr. Matson currently holds seven United States patents and has contributed numerous papers in peer-reviewed journals as well as chapters in several books on microarrays. He has also made many presentations in the United States and abroad on the development of microarray technology. His current interest is in automated approaches to multiplexed assay development.

Dr. Matson grew up in the San Juan Islands of Washington State and attended Western Washington University, Bellingham, where he earned his B.A. and M.S. in chemistry. He received his Ph.D. in biochemistry from Wayne State University. Following postdoctoral studies at the medical school of the University of California at Los Angeles, he served as a principal investigator with the Veterans Administration Medical Center and as an adjunct professor of biological chemistry at the medical school of the University of California at Davis. Dr. Matson also held a faculty lectureship in the department of chemistry at University of Southern California and was an assistant professor of chemistry at the University of Southern Maine, Portland. He served on the editorial boards of Applied Biochemistry and Biotechnology and the Journal of Preparative Chromatography, and is a member of the Scientific Advisory and Organizing Board of International Business Compunications' "Chips to Hits" conferences.

 

Genomes, second edition edited by Terence A. Brown (Wiley) In the belief that courses on molecular biology should reflect the major research issues on the millennial horizon rather than those of the past decades, Brown offers an undergraduate textbook that focuses on the genome as a whole rather than individual genes. He recognizes that it is not yet possible to describe the events leading from DNA to protein entirely in terms of genome to proteome, but does attempt to explore the expression of individual genes in the context of the activity and function of the genome as a whole. Cell biology is described very well in terms of Genomics language. So it is certainly an excellent book to learn cell biology and to understand the genomes. Each chapter is well written and covered with important references. Responding to the immense changes due to recent development in research, Genomes is the first in a generation of molecular genetics books which combine standard molecular biology with more contemporary genomics. This book focuses on genome organization, expression, replication, and evolution, and includes a description of applications for molecular ecology and anthropology, reflecting the impact of genome biology on other fields of study. Brown includes a glossary without pronunciation guides and a list of journals, Internet cites, and other resources for keeping up with current research. The second edition continues to include this useful holistic approach to molecular biology and is a thorough update.

The Seven Daughters of Eve: The Science That Reveals Our Genetic Ancestry by Bryan Sykes (W.W. Norton) broadens the view of human evolution, tracing migrations through time and around the globe. Sykes comes close to explaining in lay terms the complexity genetics. His descriptions of the discovery and defense of the paradigm shift of using mitochondrial DNA in anthropology are clear and easy to understand. While some might think that the academic controversy raised by Dr. Sykes' findings does not add to the book, I found it fascinating in getting a look at some of the infighting for bragging rights in this field.

One of the most dramatic stories of genetic discovery since James Watson's The Double Helix-a work whose scientific and cultural reverberations will be discussed for years to come. n 1994 Professor Bryan Sykes, a leading world authority Ion DNA and human evolution, was called in to examine the frozen remains ofa man trapped in glacial ice in northern Italy. News of both the Ice Man's discovery and his age, which was put at over five thousand years, fascinated scien­tists and newspapers throughout the world. But what made Sykes's story particularly revelatory was his successful iden­tification ofagenetic descendent ofthe Ice Man, a woman liv­ing in Great Britain today.

How was Sykes able to locate a living relative of a man who died thousands of years ago? In The Seven Daughters of Eve, he gives us a firsthand account of his research into a remark­able gene, which passes undiluted from generation to gener­ation through the maternal line. After plotting thousands of DNA sequences from all over the world, Sykes found that they clustered around a handful of distinct groups. Among Europeans and North American Caucasians, there are, in fact, only seven.

This conclusion was staggering: almost all people of native European descent, wherever they may live throughout the world, can trace their ancestry back to one of seven women, hence, the Seven Daughters of Eve. Naming them Ursula, Xenia, Helena, Velda, Tara, Katrine, and .Jasmine, Sykes has created portraits of their disparate worlds by mapping the migratory patterns followed by millions oftheir ancestors. In reading the stories of these seven women, we learn exactly how our origins can be traced, how and where our ancient genetic ancestors lived, and how we are each living proof of the almost indestructible strands of DNA, which have survived over so many thousands of years. Indeed, The Seven Daughters of Eve is filled with dramatic stories: from Sykes's identification, using DNA samples from two living relatives, of the remains of Tsar Nicholas and Tsaress Alexandra, to the Caribbean woman whose family had been sold into slavery centuries before and whose ancestry Sykes was able to trace back to the Eastern coast of central Africa.

The Seven Daughters of Eve is a compelling work of science that reveals how biological research can enrich ourtan­gled lives. It is a book that chronicles many of the most exciting developments in genetics over the past decade by a man who is not only a brilliant scientist but also a gifted and thoroughly engaging writer. It ultimately demonstrates how much more we still have to discover about the absorb­ing story of human evolution.

The heart of the book is the fictionalized reconstruction of the lives of the seven European "clan mothers" discovered by mitochondrial DNA analysis. Mr. Sykes weaves stories of the day-to-day struggle for survival of women at different points in human history. The stories are evocative, and connected me with the actual women more than simply reading "25,000 B.C." would have done. I enjoyed the stories very much. I only wish that Mr. Sykes had footnoted which of the objects mentioned in the stories had actually been found by archaeologists