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The Wiley Biotechnology Encyclopedias, composed of the Encyclopedia of Molecular Biology; the Encyclopedia of Bioprocess Technology: Fermentation, Biocatalysis, and Bioseparation; the Encyclopedia of Cell Technology; and the Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology cover very broadly four major contemporary themes in biotechnology. The series comes at a fascinating time in that, as we move into the twenty-first century, the discipline of biotechnology is undergoing striking paradigm changes. Biotechnology is now beginning to be viewed as an informational science. In a simplistic sense there are three types of biological information. First, there is the digital or linear information of our chromosomes and genes with the four-letter alphabet composed of G, C, A, and T (the bases guanine, cytosine, adenine, and thymine). Variation in the order of these letters in the digital strings of our chromosomes or our expressed genes (or mRNAs) generates information of several distinct types: genes, regulatory machinery, and information that enables chromosomes to carry out their tasks as informational organelles (e.g., centromeric and telomeric sequences). Second, there is the three-dimensional information of proteins, the molecular machines of life. Proteins are strings of amino acids employing a 20-letter alphabet. Proteins pose four technical challenges: (1) Proteins are synthesized as linear strings and fold into precise three-dimensional structures as dictated by the order of amino acid residues in the string. Can we formulate the rules for protein folding to predict three-dimensional structure from primary amino acid sequence? The identification and comparative analysis of all human and model organism (bacteria, yeast, nematode, fly, mouse, etc.) genes and proteins will eventually lead to a lexicon of motifs that are the building block components of genes and proteins. These motifs will greatly constrain the shape space that computational algorithms must search to successfully correlate primary amino acid sequence with the correct three-dimensional shapes. The protein-folding problem will probably be solved within the next 10-15 years. (2) Can we predict protein function from knowledge of the three-dimensional structure? Once again the lexicon of motifs with their functional as well as structural correlations will play a critical role in solving this problem. (3) How do the myriad of chemical modifications of proteins (e.g., phosphorylation, acetylation, etc.) alter their structures and modify their functions? The mass spectrometer will play a key role in identifying secondary modifications. (4) How do proteins interact with one another and/or with other macromolecules to form complex molecular machines (e.g., the ribosomal subunits)? If these functional complexes can be isolated, the mass spectrometer, coupled with a knowledge of all protein sequences that can be derived from the complete genomic sequence of the organism, will serve as a powerful tool for identifying all the components of complex molecular machines. The third type of biological information arises from complex biological systems and networks. Systems information is four dimensional because it varies with time. For example, the human brain has 1,012 neurons making approximately 1,015 connections. From this network arise systems properties such as memory, consciousness, and the ability to learn. The important point is that systems properties cannot be understood from studying the network elements (e.g., neurons) one at a time; rather the collective behavior of the elements needs to be studied. To study most biological systems, three issues need to be stressed. First, most biological systems are too complex to study directly, therefore they must be divided into tractable subsystems whose properties in part reflect those of the system. These subsystems must be sufficiently small to analyze all their elements and connections. Second, high-throughput analytic or global tools are required for studying many systems elements at one time (see later). Finally, the systems information needs to be modeled mathematically before systems properties can be predicted and ultimately understood. This will require recruiting computer scientists and applied mathematicians into biology--just as the attempts to decipher the information of complete genomes and the protein folding and structure/function problems have required the recruitment of computational scientists. I would be remiss not to point out that there are many other molecules that generate biological information: amino acids, carbohydrates, lipids, and so forth. These too must be studied in the context of their specific structures and specific functions. The deciphering and manipulation of these various types of biological information represent an enormous technical challenge for biotechnology. Yet major new and powerful tools for doing so are emerging. One class of tools for deciphering biological information is termed high-throughput analytic or global tools. These tools can be used to study many genes or chromosome features (genomics), many proteins (proteomics), or many cells rapidly: large-scale DNA sequencing, genomewide genetic mapping, cDNA or oligonucleotide arrays, two-dimensional gel electrophoresis and other global protein separation technologies, mass spectrometric analysis of proteins and protein fragments, multiparameter, high-throughput cell and chromosome sorting, and high-throughput phenotypic assays. A second approach to the deciphering and manipulation of biological information centers around combinatorial strategies. The basic idea is to synthesize an informational string (DNA fragments, RNA fragments, protein fragments, antibody combining sites, etc.) using all combinations of the basic letters of the corresponding alphabet, thus creating many different shapes that can be used to activate, inhibit, or complement the biological functions of designated three-dimensional shapes (e.g., a molecule in a signal transduction pathway). The power of combinational chemistry is just beginning to be appreciated. A critical approach to deciphering biological information will ultimately be the ability to visualize the functioning of genes, proteins, cells, and other informational elements within living organisms (in vivo informational imaging). Finally, there are the computational tools required to collect, store, analyze, model, and ultimately distribute the various types of biological information. The creation presents a challenge comparable to that of developing new instrumentation and new chemistries. Once again this means recruiting computer scientists and applied mathematicians to biology. The biggest challenge in this regard is the language barriers that separate different scientific disciplines. Teaching biology as an informational science has been a very effective means for breeching these barriers. The challenge is, of course, to decipher various types of biological information and then be able to use this information to manipulate genes, proteins, cells, and informational pathways in living organisms to eliminate or prevent disease, produce higher-yield crops, or increase the productivity of animals for meat and other foods. Biotechnology and its applications raise a host of social, ethical, and legal questions, for example, genetic privacy, germline genetic engineering, cloning of animals, genes that influence behavior, cost of therapeutic drugs generated by biotechnology, animal rights, and the nature and control of intellectual property. Clearly, the challenge is to educate society so that each citizen can thoughtfully and rationally deal with these issues, for ultimately society dictates the resources and regulations that circumscribe the development and practice of biotechnology. Ultimately, I feel enormous responsibility rests with scientists to inform and educate society about the challenges as well as the opportunities arising from biotechnology. These are critical issues for biotechnology that are developed in detail in the Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology. The view that biotechnology is an informational science pervades virtually every aspect of this science, including discovery, reduction to practice, and societal concerns. These Encyclopedias of Biotechnology reinforce the emerging informational paradigm change that is powerfully positioning science as we move into the twenty-first century to more effectively decipher and manipulate for humankind's benefit the biological information of relevant living organisms.
Leroy Hood
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